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Background: The most effective injective treatment approach for sacroiliac joint (SIJ) pain remains unclear. Aim of this study was to quantify the safety and effectiveness of the available injective strategies to address SIJ pain. Methods: A systematic review and meta-analysis of the literature was conducted on PubMed, Scopus, and Embase databases from inception until January 2023. Inclusion criteria were studies written in English, comparative and non-comparative studies regardless of the minimum follow-up, and case series on SIJ injections. Safety and efficacy of the different injection therapies for the SIJ were quantified. A meta-analysis was conducted on the available data of the documented injective therapies. The "Checklist for Measuring Quality" by Downs and Black was used to assess the risk of bias and the quality of papers. Results: The literature search retrieved 43 papers (2431 patients): 16 retrospective case series, 2 retrospective comparative studies, 17 prospective case series, 3 prospective comparative studies, and 5 randomized controlled trials. Of the selected studies, 63% examined the effect of steroid injections, 16% of PRP injections, while 21% reported other heterogeneous treatments. The failure rate was 26% in steroid injections and 14% in PRP injections. The meta-analysis showed a statistically significant reduction in pain with the VAS score for both steroids and PRP: steroids improvement at mid-term 3.4 points (p < 0.05), at long-term 3.0 (p < 0.05), PRP improvement at mid-term 2.2 (p = 0.007), at long-term 2.3 points of the VAS pain scale (p = 0.02). Conclusions: Steroids are the most documented injective approach, with studies showing an overall safety and effectiveness. Still, the high number of failures underlined by some studies suggest the need for alternative procedures. Early PRP data showed promise, but the limitations of the current literature do not allow to clearly define the most suitable injective approach, and further studies are needed to identify the best injective treatment for SIJ patients. [ABSTRACT FROM AUTHOR]

Background: One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3–5.5% of cases and affects 0.5–7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems. Methods: The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme. Results: Meta-analysis finally contained 6 papers. In six investigations, the test & control group's VAS scores improved, with the test team's score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P < 0.01], shoulder pain and disability index (SPADI) score (SMD:8.13; 95% Cl: 5.34,10.91; P < 0.01), Flexion (SMD:5.73; 95% Cl: 0.99,10.47; P < 0.05), Abduction (SMD:6.49; 95% Cl: 0.66,12.31; P < 0.05), Internal rotation (SMD:-1.74; 95% Cl: -4.25,0.78; P = 0.176) and External rotation (SMD:2.78; 95% Cl: -0.13,5.69; P = 0.062). Conclusion: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation treatment based on the visual analogue scale (VAS) score, the Shoulder Pain and Disability Index (SPADI) score, Flexion, & Abduction. These results must, nevertheless, be supported by high-caliber follow-up research. [ABSTRACT FROM AUTHOR]

Background: The number of non-intubated general anesthesia outside the operating room is growing as the increasing demand for comfort treatment. Non-intubated general anesthesia outside the operating room requires rapid onset of anesthesia, smoothness, quick recovery, and few postoperative complications. Traditional anesthetic regimens (propofol alone or propofol and opioids/dezocine/midazolam, etc.) have severe respiratory and circulatory depression and many systemic adverse effects. In this paper, we compare the effectiveness and safety of propofol and subclinical doses of esketamine with other traditional regimens applied to non-intubated general anesthesia through a systematic review and meta-analysis. Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Sinomed databases for the period from January 2000 to October 2022. We rigorously screened the literature according to predefined inclusion and exclusion criteria, while risk assessment of the studies was performed using The Cochrane Collaboration's tool, and statistical analysis of the data was performed using RevMan 5.4 software. The main outcome indicators we evaluated were the various hemodynamic parameters and incidence of various adverse effects between the experimental and control groups after induction of anesthesia. Results: After a rigorous screening process, a total of 14 papers were included in the final meta-analysis. After risk bias assessment, three of the papers were judged as low risk and the others were judged as having moderate to high risk. Forest plots were drawn for a total of 16 indicators. Meta-analysis showed statistically significant differences in HR' WMD 3.27 (0.66, 5.87), MAP' WMD 9.68 (6.13, 13.24), SBP' WMD 5.42 (2.11, 8.73), DBP' WMD 4.02 (1.15, 6.88), propofol dose' SMD -1.39 (-2.45, -0.33), hypotension' RR 0.30 (0.20, 0.45), bradycardia' RR 0.33 (0.14, 0.77), hypoxemia or apnea' RR 0.45 (0.23, 0.89), injection pain' RR 0.28 (0.13, 0.60), intraoperative choking' RR 0.62 (0.50, 0.77), intraoperative body movements' RR 0.48 (0.29, 0.81) and overall incidence of adverse reactions' RR 0.52 (0.39, 0.70).The indicators that were not statistically different were time to wake up' WMD − 0.55 (-1.29, 0.19), nausea and vomiting 0.84' RR (0.43, 1.67), headache and dizziness' RR 1.57 (0.98, 2.50) and neuropsychiatric reaction' RR 1.05 (0.28, 3.93). The funnel plot showed that the vast majority of studies fell within the funnel interval, but the symmetry was relatively poor. Conclusion: In non-intubated general anesthesia, the combination of subclinical doses of esketamine and propofol did reduce circulatory and respiratory depression, injection pain, and other adverse effects, while the incidence of esketamine's own side effects such as neuropsychiatric reactions did not increase, and the combination of the two did not cause the occurrence of new and more serious adverse reactions, and the combination of the two was safe and effective. Trial registration: PROSPREO registration number: CRD 42022368966. [ABSTRACT FROM AUTHOR]

Objective. To analyze and evaluate the effectiveness of traditional Chinese medicine decoction (TCMD) in the treatment of cardiac neurosis (CN) complicated with depression and anxiety. Methods. Relevant literature on TCMD in the treatment of CN complicated with depression and anxiety was retrieved from Chinese and English databases, and the retrieved literature was included and excluded. The quality of the retrieved literature was evaluated according to the Cochrane system, and the meta-analysis was undertaken with RevMan5.3 software. Results. A total of 10 papers were included, including 686 patients and 349 patients in the treatment group (131 males and 218 females), and there were 337 cases in the control group (131 males and 206 females). The results of the meta-analysis showed that compared with the control group, TCMD could significantly improve palpitation (MD = 0.78, 95% CI = 0.55–1.01, P < 0.00001), chest tightness/chest pain (MD = 0.53, 95% CI = 0.10–0.97, P < 0.05), shortness of breath (MD = 0.60, 95% CI = 0.26–0.93, P = 0.0005), and TCM syndrome score (MD = 5.91, 95% CI = 4.32–7.49, P < 0.00001), reduce resting heart rate (MD = 13.21, 95% CI = 9.01–17.40, P < 0.00001), and could reduce psychological scale scores, such as Zung's self-rating Depression Scale (MD = 7.90, 95% CI = 4.98–10.83, P < 0.00001), Zung's self-rating Anxiety Scale (MD = 6.55, 95% CI = 4.25–8.86, P < 0.00001), Hamilton Depression Scale (MD = 4.46, 95% CI = 3.00–5.92, P < 0.00001), and Hamilton Anxiety Scale (MD = 3.35, 95% CI = 1.85–4.85, P < 0.0001). The differences were statistically significant. Tonic drugs were commonly used; Angelica sinensis, Poria cocos, Polygala tenuifolia, Wild jujube kernel, and Bupleurum were the most frequently used traditional Chinese medicines. Conclusion. TCMD mainly composed of tonic and tranquilizing herbs could significantly improve the clinical symptoms of patients with CN and reduce heart rate, anxiety, and depression scores. However, the evidence grade of the clinical research was limited by the quality of the included literature, and more high-quality clinical trials are still needed for further verification. This trial was registered with PROSPERO: CRD42022312164 [ABSTRACT FROM AUTHOR]

Background: Dysgeusia is a relatively early symptom of zinc deficiency, and zinc replacement is effective in treating dysgeusia. The administration of zinc acetate hydrate (ZAH) was approved in 2017 for patients with hypozincemia in Japan. This retrospective study was conducted to explore the efficacy and safety of ZAH administration in patients with hypozincemia-induced dysgeusia. Methods: Patients with hypozincemia-induced dysgeusia who visited our hospital from May 2013 to December 2019 were included in this study. ZAH (zinc content; 50 mg/day) was administered to 42 patients for 24 weeks. The taste test was performed using the filter paper disk method, and the total cognitive thresholds of the left and right chorda tympani regions were used. Changes in taste function, serum zinc and copper levels, and copper/zinc ratio were analyzed. A total of 28 patients who received polaprezinc (PPZ, zinc content; 34 mg/day) for 24 weeks, who were prescribed until ZAH was approved, were registered as controls. Results: Serum zinc levels at 12 and 24 weeks after ZAH or PPZ administration were higher than those before administration. These levels were significantly higher in the ZAH-treated group than in the PPZ-treated group. However, serum copper levels did not significantly change before and after administration. In the taste test, the taste thresholds for the acidity and salty at 12 and 24 weeks after ZAH administration were significantly decreased compared to before administration. In contrast, in the PPZ group, the taste thresholds for the acidity and salty were significantly decreased 24 weeks after administration. Conclusions: ZAH (50 mg/day) administration was effective in improving the gustatory sensitivity of patients with dysgeusia and hypozincemia 12 weeks after administration without affecting the serum copper level. ZAH was also more effective than PPZ. [ABSTRACT FROM AUTHOR]

INTRODUCTION Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. METHODS Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI75) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. RESULTS A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9-16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91-18.89), 14.14 (95% CI: 8.27-24.20), and 3.05 (95% CI: 1.20-7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI75 achievement. CONCLUSIONS Tobacco smoking was negatively associated with PASI75 achievement both in current and former smokers, and former smokers had higher PASI75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has revolutionized the therapeutic options for patients living with non-small-cell lung cancer (NSCLC). Despite the unprecedented results achieved through immunotherapy, a low body mass index, which is referred to as cachexia, and the bacterial composition of the gut microbiota are known factors associated with resistance. In this paper, we enrolled 113 Japanese patients with NSCLC and demonstrated that cachexia was associated with poor outcomes. Moreover, microbiota sequencing revealed that patients without cachexia had abundant bacteria that correlated with a beneficial outcome. Altogether, our results demonstrated an association between the gut microbiota and cachexia. This study provides a rationale to launch clinical trials on the outcome of shifting the microbiota composition of patients with cachexia that are receiving immunotherapy. Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer‐related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are effective for advanced non‐small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation‐related score based on C‐reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR‐TKIs. Methods: This retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR‐TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR‐TKIs. The Kaplan‐Meier method and Cox proportional hazard models were used to evaluate progression‐free survival (PFS) and overall survival (OS). Results: In 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR‐TKIs; good GPS (0–1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38–0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33–0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0–1) independently predicted good PFS and OS among patients who had PS of 0–1. Good GPS (0–1) independently predicted good OS among patients receiving treatment in first‐line settings. Conclusions: The GPS independently predicted the efficacy of EGFR‐TKIs for EGFR‐mutated NSCLC; however, further studies are needed to validate our findings. Key points: Significant findings of the study: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment for EGFR‐mutated NSCLC. What this study adds: The findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR‐TKI treatment by using GPS. [ABSTRACT FROM AUTHOR]

Background: Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism. Methods: The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment I / R group (12.5, 25, 50 mg / kg). After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins. Results: Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression. Conclusion: The antioxidant properties of astragalin may play an important role in improving cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Background and Aims: Several methods have been used in plastic and reconstructive surgery to reduce post-surgical complications, such as partial or complete flap loss due to ischemia and necrosis. Nitroglycerine application has been introduced as a viable alternative to papaverine to act as a local vasodilator to improve perfusion and reduce vasospasm. However, the literature has not thoroughly studied its efficacy and administration dose. This systematic review and meta-analysis study has been designed to assess the efficacy of topical nitroglycerine applications in reducing post-surgical flap necrosis and complications. Methods and Materials: A systematic literature search was performed on PubMed, Scopus, and Web of Science from inception to January 2023 with relevant keywords and terms. Case reports, review articles, letters, articles in any language other than English, and animal studies were excluded. The Newcastle-Ottawa and Jadad scales were used to assess the quality of the included studies. The pooled effect sizes were calculated using the random effect model with the Mantel-Haenszel method. Results: Overall, 2031 studies were obtained, among which 454 articles were duplicated and removed. Of the remaining 1577 articles, based on the eligibility and exclusion criteria, 20 articles were retrieved for full-text review. Finally, eight articles were included in our study. Three thousand nine hundred six patients had undergone reconstructive microsurgery and received topical nitroglycerin for the prevention of possible complications. The pooled rate of flap complication was 15% (95% CI: 8% to 25%, I2 = 96%, p-value < 0.01), and the pooled odds ratio of flap complication was 0.35 (95% CI: 0.15 to 0.83, I2 = 91%, p-value = 0.02). The heterogeneity of the included studies was significantly high. The dose and regimen of application significantly differed between each study. Conclusion: Topical administration of nitroglycerin compounds post reconstructive microsurgery can reduce the risk of flap necrosis. However, the precise dosage, duration of application, and possible underlying factors affecting drug efficacy are yet to be discovered. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the anti-leishmanial effects of curcumin nanoemulsion (CUR-NE) against Leishmania major (MRHO/IR/75/ER) in both in vitro and in vivo experiments. CUR-NE was successfully prepared via the spontaneous emulsification method. The in vitro effect of various concentrations of CUR-NE against L. major promastigotes was assessed using the flow cytometry method. In vivo experiments were carried out in BALB/c mice inoculated subcutaneously with 2 × 106 L. major promastigotes. Mice were treated with topical CUR-NE (2.5 mg/ml), intra-lesion injection of CUR-NE (2.5 mg/ml), topical CUR suspension (CUR-S, 2.5 mg/ml), topical NE without CUR (NE-no CUR), amphotericin B as the positive control group, and infected untreated mice as the negative control group. In vitro exposure of promastigotes to CUR-NE showed a dose-dependent anti-leishmanial effect, with a 67.52 ± 0.35% mortality rate at a concentration of 1250 µg/ml and an IC50 of 643.56 µg/ml. In vivo experiments showed that topical CUR-NE and CUR-S significantly decreased the mean lesion size in mice after four weeks from 4.73 ± 1.28 to 2.78 ± 1.28 mm and 4.45 ± 0.88 to 3.23 ± 0.59 mm, respectively (p = 0.001). Furthermore, CUR-NE significantly decreased the parasite load in treated mice compared with the negative control group (p = 0.001). Results from the current study demonstrated the promising activity of CUR-NE against L. major in both in vitro and in vivo experiments. Moreover, CUR-NE was more efficient than CUR-S in healing and reducing parasite burden in mouse models. Future studies should aim to identify molecular mechanisms as well as the pharmacologic and pharmacokinetic aspects of CUR-NE. [ABSTRACT FROM AUTHOR]

Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually (SLIT). The aim of the current study was to evaluate and compare the efficacy of SCIT and SLIT for the treatment of allergic asthma in children. Our study included 69 children with allergic asthma who underwent immunotherapy for house dust mites or pollen for at least 3 consecutive years. After 3 years of SCIT and SLIT, the median number of asthma exacerbations in the last three months decreased from 2 to 0 (p < 0.01) and from 1 to 0 (p < 0.01), respectively. When comparing the efficacy of SCIT and SLIT, our study revealed a significantly better efficacy of SCIT only in terms of increasing lung function. The median increase in forced expiratory volume in one second (FEV1) after 3 years was 8% with SCIT and −1% with SLIT (p < 0.01). Daily controller therapy could be withdrawn or reduced in 9 out of 16 (56.3%) children who received it before SCIT (p < 0.01) and in 19 of 29 (65.6%) children who received it before SLIT (p < 0.01), but the difference in efficacy was not significant (p = 0.88). Both SCIT and SLIT are effective treatments for allergic asthma in children. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore the therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its related mechanism. The Span-PEG microbubbles loaded with schisandrin A were prepared using Span60, NaCl, PEG-1500, and schisandrin A. The loading rate of schisandrin A in Span-PEG composite microbubbles was determined by ultraviolet spectrophotometry method. The Walker-256 cell survival rate of schisandrin A was determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The content of schisandrin A in the cells was determined by high performance liquid chromatography. Ultrasound imaging was used to evaluate the therapeutic effect in situ. Enzyme linked immunosorbent assay (ELISA) was used to measure the content of inflammatory factors in serum. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of experimental animals in each group. Immunohistochemistry was used to detect the expression of hypoxia inducible factor-1α (HIF-1α), vascular endothlial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) in tumor tissues, and western blot was used to detect the protein expression of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues. The composite microbubbles were uniform in size, and the particle size distribution was unimodal and stable, which met the requirements of ultrasound contrast agents. The loading rate of schisandrin A in Span-PEG microbubbles was 8.84 ± 0.14%, the encapsulation efficiency was 82.24±1.21%. The IC50 value of schisandrin A was 2.87 μg/mL. The drug + microbubbles + ultrasound (D+M+U) group had the most obvious inhibitory effect on Walker-256 cancer cells, the highest intracellular drug concentration, the largest reduction in tumor volume, the most obvious reduction in serum inflammatory factors, and the most obvious improvement in pathological results. The results of immunohistochemistry showed that HIF-1α, VEGF and VEGFR-2 protein decreased most significantly in D+M+U group (P < 0.01). WB results showed that D+M+U group inhibited the PI3K/AKT/mTOR signaling pathway most significantly (P < 0.01). Schisandrin A had an anti-tumor effect, and its mechanism might be related to the inhibition of the PI3K/AKT/mTOR signaling pathway. The schisandrin A microbubbles could promote the intake of schisandrin A in tumor cells after being destroyed at the site of tumor under ultrasound irradiation, thus playing the best anti-tumor effect. [ABSTRACT FROM AUTHOR]

Background Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. Methods Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. Results The tpCR rate in the PLR− group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P  = .032). The tpCR rate in the NLR− group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P  = .024). The tpCR rate of the PLR−NLR− (PLR− and NLR−) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P  = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR− group (P  = .028 for EFS; P  = .047 for OS). Patients in the PLR−NLR− group had a longer EFS than those in the PLR+/NLR+ group (P  = .002). Conclusion PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. Methods: A total of 188 patients aged 3–12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. Results: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. Conclusions: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. Trial registration: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006). [ABSTRACT FROM AUTHOR]

Simple Summary: Nabpaclitaxel plus gemcitabine is the standard of care treatment for advanced pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer-related deaths worldwide. This therapy reported improved overall survival in metastatic PDAC. Despite the efficacy of available treatments, the poor outcome for patients with PDAC necessitates the need for novel therapies. In a preclinical study, a neutralizing monoclonal antibody specific to human platelet-derived growth factor receptor alpha (PDGFRα) has proven its efficacy in advanced PDAC. Further, a PDGFRα monoclonal antibody, olaratumab, in combination with chemotherapy demonstrated clinical benefit in patients with soft tissue sarcoma. In light of the above findings, the current trial evaluates the efficacy and safety of olaratumab and nabpaclitaxel plus gemcitabine combination therapy in treatment-naïve patients with metastatic PDAC. However, the combination therapy failed to improve survival outcomes compared with chemotherapy alone. Nevertheless, the safety profile of olaratumab was consistent with the previous studies. The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527; p = 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764; p = 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals. [ABSTRACT FROM AUTHOR]

Background: To prevent occupational skin diseases, employees are instructed to periodically apply hand protection products as a barrier to protect their hands from water, cleaning agents or other irritants. The aim of this work was to investigate whether bacteria present on the skin at the time of protection product application are enclosed underneath this protective layer, if they can be transferred to other surfaces and if a standard isopropanol-based skin disinfectant can nonetheless reduce the bacterial burden. Methods: This prospective study was conducted in human volunteers based on the European Standard (EN 1500) to assess the burden of microorganisms before and after the application of various protection product formulations and subsequent hand disinfection. Results: All protection products, with the exception of alcohol-based gels, enclosed bacteria underneath a lipid layer which could be transferred onto other surfaces. Still, the hand disinfectant efficiently reduced the bacteria burden. Discussion: In occupations where proper hand hygiene is vital, alcohol-based gels might be the best option for the protection of the skin barrier as well as for reducing the contamination risk. Conclusion: An alcohol-based disinfection agent can dissolve the lipid film of protection products following the standard protocol for hygienic hand disinfection. [ABSTRACT FROM AUTHOR]

Purpose: There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. Methods: As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. Results: Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = − 0.50, 95% confidence intervals [CI]: −0.70 to − 0.31, P < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I2 = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I2 = 0%). Conclusion: Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA. [ABSTRACT FROM AUTHOR]

A meta‐analysis was conducted to comprehensively evaluate the prophylactic and therapeutic efficacy of botulinum toxin type A (BTX‐A) in the treatment of facial hypertrophic scars. Computerised searches were performed in databases, from their inception to November 2023, including Embase, Google Scholar, Cochrane Library, Wanfang, PubMed and China National Knowledge Infrastructure databases, focusing on randomised controlled trials (RCTs) that investigated the use of BTX‐A for treating facial hypertrophic scars. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Seventeen RCTs were ultimately included, involving 1605 patients who underwent facial cosmetic surgery. The analysis revealed that compared with conventional treatments, BTX‐A significantly reduced visual analogue scale (VAS) scores (standardized mean difference [SMD]: −3.50, 95% confidence interval [CI]: −5.16 to −1.84, p < 0.001) and Vancouver scar scale (VSS) scores (SMD: −2.86, 95% CI: −4.03 to −1.68, p < 0.001), and narrowed scar width (SMD: −1.80, 95% CI: −2.48 to −1.13, p < 0.001), while also enhancing the overall effectiveness of the treatment. This study indicates that BTX‐A is an effective modality in the prophylaxis and treatment of facial hypertrophic scars, significantly alleviating scar‐related pain and preventing scar widening, and is thus worthy of broader clinical application. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of topical nasal Pomegranate Fruit Extract (PFE) for Chronic Rhinitis (CR), Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP), and Chronic Rhinosinusitis without Nasal Polyposis (CRSsNP). Methods: Prospective, double-blinded, randomized study including 111 consecutive patients, between April 2012 and January 2017, afflicted by CRSwNP, CRSsNP, and CR. Patients from each group were randomly assigned to either PFE treatment or placebo twice daily for 30 days. Therapeutic efficacy was assessed by Ear Nose and Throat, blood and tomographic examinations, and the SNOT-20 questionnaire. Results: CR patients treated with PFE suffered significantly less from thick nasal discharge, difficulty falling asleep, reduced productivity, reduced concentration, and sadness (P =.004, P =.02, P =.03, P =.007 and P =.02, respectively). Conclusions: Topical nasal PFE was found to have some benefits for CR patients, however, not for CRS with or without Nasal Polyposis. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19. Methods: We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy. Results: A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis. Conclusion: Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities. [ABSTRACT FROM AUTHOR]

Background: Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC. Materials and Methods: We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle-Ottawa-Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Results: Seventeen articles were finally selected, involving 5182 patients. Meta-analysis results showed that PD1/PD-L1 combined with AAs therapy significantly improved progression-free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50-0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71-0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81-0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS. Conclusion: The combination of PD-1/PD-L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD-1/PD-L1 inhibitors in conjunction with AAs, or sequential treatment involving PD-1/PD-L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients. Methods: PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure were used to find concerned studies for meta-analysis. The main outcome was the incidence of postoperative delirium, and the secondary outcomes were side effects of haloperidol and the length of hospital stay. The meta-analyses were conducted using the Review Manager Version 5.1. This study was conducted based on the PRISMA statement. Results: Eight RCTs (1569 patients) were included in the meta-analysis. There was a significant difference in the incidence of postoperative delirium between haloperidol and control groups (OR = 0.62, 95%CI 0.48–0.80, P = 0.0002, I2 = 20%). In addition, side effects of haloperidol and the duration of hospitalization were comparable (OR = 0.58, 95%CI 0.25–1.35, P = 0.21, I2 = 0%; MD =-0.01, 95%CI -0.16-0.15, P = 0.92, I2 = 28%). Subgroup analysis implied the effect of haloperidol on postoperative delirium might vary with the dose (5 mg daily: OR = 0.40, 95%CI 0.22–0.71, P = 0.002, I2 = 0%; <5 mg daily: OR = 0.72, 95%CI 0.42–1.23, P = 0.23, I2 = 0%). Conclusions: The meta-analysis revealed perioperative application of haloperidol could decrease the occurrence of postoperative delirium without obvious side effects in elderly people, and high-dose haloperidol (5 mg daily) possessed a greater positive effect. [ABSTRACT FROM AUTHOR]

Surgical site infections (SSIs) post‐surgery impact patient health and raise healthcare costs. This meta‐analysis examines the efficacy of antiseptics, chlorhexidine and povidone–iodine, in reducing SSIs, including various types, to settle ongoing debates on their comparative effectiveness. A systematic literature search conforming to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines was executed on four established databases without temporal restrictions. Only randomized controlled trials (RCTs) including patients aged 18 years or older undergoing clean or potentially contaminated surgeries were included. Two independent evaluators carried out study selection, data extraction and quality assessment, adhering to Cochrane Collaboration's risk of bias tool. Statistical analyses were performed using chi‐square tests and the I2 index to evaluate heterogeneity, and meta‐analyses were conducted employing either fixed‐effects or random‐effects models as warranted by the heterogeneity assessments. A total of 16 RCTs were included after rigorous selection from an initial pool of 1742 articles. The studies demonstrated low levels of heterogeneity, supporting the use of a fixed‐effects model. Chlorhexidine exhibited statistically lower rates of overall SSIs (RR 0.75; 95% CI 0.64–0.88; p < 0.001), superficial SSIs (RR 0.62; 95% CI 0.47–0.82; p < 0.001) and deep SSIs compared to povidone–iodine. The study furnishes compelling evidence in favour of chlorhexidine as a more efficacious antiseptic agent over povidone–iodine in minimizing the risk of various types of SSIs. [ABSTRACT FROM AUTHOR]

Background: Triple antibiotic paste (TAP) is the commonly used intracanal medicament against Enterococcus faecalis. Amoxicillin clavulanate paste (ACP) is recommended as a "fall-back" antibiotic when traditional dental antibiotics fail. Literature comparing the antimicrobial efficacy of TAP and ACP in eradicating E. faecalis from the root canal system is sparse; hence, this in vitro study was conducted to evaluate and compare the antimicrobial efficacy of TAP and ACP as an intracanal medicament for endodontic treatment of single-rooted permanent teeth against E. faecalis. Materials and Methods: This in vitro, experimental study evaluated 60 root samples obtained from extracted single-rooted human permanent teeth. The canal diameter was enlarged and subsequently infected with E. faecalis for 21 days. Four groups of the contaminated samples were treated with TAP, ACP, calcium hydroxide (positive control), and saline (negative control), respectively. Dentinal shavings were collected at the end of the 1st, 7th, and 10th day and inoculated in agar plates. The number of colony-forming units was determined, and the data were statistically analyzed using the Kolmogorov-Smirnov and Shapiro-Wilks test. P <0.05 was considered statistically significant. Results: The mean number of E. faecalis colony counts across all 3 test days demonstrated that TAP exhibited the highest inhibition of bacterial growth, followed by ACP which is not statistically significant (P = 1.00). Conclusion: Considering the limitations of this in vitro study, the findings suggest that ACP could be an effective alternative intracanal medicament to TAP for endodontic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of abiraterone plus prednisolone (ABI) against nonmetastatic castration-resistant prostate cancer (CRPC) remains unclear. To evaluate enzalutamide and ABI as the first-line treatment for CRPC, we conducted the randomized controlled trial including both metastatic and nonmetastatic CRPC. As a sub-analysis, we focused on nonmetastatic CRPC in this study. ABI and enzalutamide had similar efficacy and safety profiles in patients with nonmetastatic CRPC. Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22–2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35–1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19–2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC. [ABSTRACT FROM AUTHOR]

Background: The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy. Methods: We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events. Results: Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant. Conclusions: Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) has been recently proposed as a promising alternative therapy for Denture Stomatitis (DS). The present systematic review and meta-analysis investigated the current available evidence regarding the efficacy of PDT in the management of DS. Materials and methods: PubMed, Scopus, Web of Science, Google Scholar, and ProQuest were searched up to June 7, 2023. All relevant clinical trials were included. RevMan software was used for the statistical analyses. Results: Elven randomized clinical trials (460 DS patients) were included. Eight studies assessed the efficacy of PDT vs. topical antifungal therapy, while three studies assessed the adjunctive use of PDT (PDT + antifungal therapy) vs. topical antifungal therapy alone. The results revealed comparable efficacy of PDT and conventional antifungal therapy on candida colonization at 15 days (MD: 0.95, 95% CI: -0.28, 2.19, p = 0.13) and at the end of follow-up (MD: -0.17, 95% CI: -1.33, 0.98, p = 0.77). The pooled two studies revealed relatively better efficacy of adjunctive use of PDT with antifungal therapy on candida colonization compared to antifungal therapy alone at 15 days (MD: -6.67, 95% CI: -15.15, 1.82, p = 0.12), and at the end of follow-up (MD: -7.14, 95% CI: -19.78, 5.50, p = 0.27). Additionally, the results revealed comparable efficacy of PDT and topical antifungal therapy on the clinical outcomes. Conclusions: PDT might be considered a viable option for DS either as an adjunct or as an alternative to the topical antifungal medications. Further studies with adequate sample sizes and standardized PDT parameters are warranted. [ABSTRACT FROM AUTHOR]

Background. Post-dural puncture headache (PDPH) as an annoying complication after spinal anaesthesia and is of great importance in patients undergoing caesarean section. Objectives. This study aimed to evaluate the effect of nasal oxytocin on the incidence and severity of PDPH after caesarean section. Material and methods. This double-blinded randomised clinical trial was carried out on 170 patients undergoing elective caesarean section in Kamali Hospital, Karaj, Iran, from May 2021 to September 2021. Participants were randomly assigned to receive three puffs of intranasal oxytocin (30 IU) (intervention group) or intranasal normal saline (0.3 ml of 0.09% saline solution) (control group) as a placebo right after delivery. The occurrence of PDPH was the primary outcome, and participants were also asked about the use of analgesics and associated symptoms. Results. The results showed that the rate of PDPH was not significantly different between the two groups at 12 (p = 0.108) and 72 (p = 0.245) hours after surgery, but it significantly reduced the incidence of PDPH at 24 (p = 0.022) and 48 hours (p = 0.042). Oxytocin did not reduce the analgesic requirement compared to the control group (p > 0.05). Oxytocin did not significantly mitigate PDPH associated symptoms, including tinnitus, vertigo, nausea and double vision (p > 0.05). Conclusions. Administration of intranasal oxytocin in combination with routine analgesic for post-dural puncture headache after caesarean section is beneficial and reduces the incidence of headache after 24 and 48 hours of surgery. Use of nasal oxytocin has no effect on the need for sedation and reduction of associated symptoms (dizziness, diplopia, nausea, tinnitus). [ABSTRACT FROM AUTHOR]

Chronic prostatitis, which frequently manifests with perineal or urethral ulcers, can have substantial impact on the quality of life experienced by affected individuals. Present treatment approaches primarily target the alleviation of symptoms and control of complications. In patients with chronic prostatitis, this investigation examined the potential synergistic effects of tamsulosin and levofloxacin on urinary function and urethral and perineal wounds healing. This cross‐sectional observational study was carried out at Chongqing Western Hospital, China, from February to November 2023. The participants comprised 88 males aged 40–75 years who had been clinically diagnosed with chronic prostatitis and complications that accompany the wound healing process. The participants were equally distributed into two groups: one assigned to the treatment group, which received a daily combination of levofloxacin (500 mg) and tamsulosin (0.4 mg) and other to receive conventional care. The wound healing rate and improvement in urinary function were the primary outcomes evaluated monthly for 9 months. Patient satisfaction and symptom amelioration were secondary outcomes, in addition to the surveillance of adverse effects. In comparison to the control, treatment group exhibited significantly higher rate of wound closure (78.08% at 1 month and 79.38% at 9 months) and urinary function improvement (66.69% at 1 month and 67.95% at 9 months). In addition, the treatment group exhibited a greater degree of symptom amelioration; however, a rise in adverse effects was observed. In every domain, patient satisfaction scores were significantly higher in the treatment group. Thus the combination of tamsulosin and levofloxacin improved urinary function and wound repair in patients with chronic prostatitis, while also exhibiting tolerable profile of adverse effects. [ABSTRACT FROM AUTHOR]

Facial soft tissue injuries, often resulting in scarring, pose a challenge in reconstructive and aesthetic surgery due to the need for functional and aesthetic restoration. This study evaluates the efficacy of recombinant human growth factors (rhGFs) in scar remodelling for such injuries. A retrospective evaluation was conducted from January 2020 to January 2023, involving 100 patients with facial soft tissue injuries. Participants were divided equally into a control group, receiving standard cosmetic surgical repair, and an observation group, treated with rhGFs supplemented cosmetic surgery. The study assessed scar characteristics (pigmentation, pliability, vascularity, height), hospital stay duration, tissue healing time, complication rates and patient satisfaction. The observation group demonstrated significant improvements in all scar characteristics, with notably better pigmentation, pliability, vascularity and height compared with the control group. The rhGF treatment also resulted in reduced hospital stay duration and faster tissue healing. Notably, the total complication rate was significantly lower in the observation group (10%) compared with the control group (34%). Additionally, patient satisfaction levels were higher in the observation group, with 98% combined satisfaction compared with 76% in the control group. The application of rhGFs in treating facial soft tissue injuries significantly enhances scar remodelling, expedites healing, reduces complications and improves patient satisfaction. These findings establish rhGFs as a valuable tool in the management of facial soft tissue injuries, highlighting their potential in improving both functional and aesthetic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Pazopanib is an oral drug for metastatic pretreated uterine leiomyosarcoma that received approval in 2012, but poor data have been reported on its activity in real life since the disease is very rare. Uterine leiomyosarcoma has a poor objective response rate to other agents. We assessed the effectiveness and safety of pazopanib in everyday clinical practice, showing its activity and tolerability in patients. Background: Uterine leiomyosarcoma (uLMS) is characterized by aggressive behavior associated with a high risk of relapse and mortality. Several therapeutic agents have been employed in the treatment of metastatic disease, with a poor objective response rate. Pazopanib, approved in 2012, is a multi-targeted, orally active small molecule that exerts its effects by inhibiting several tyrosine kinases. To date, poor research on real-life data has been conducted. We aimed to assess the effectiveness and safety of the drug in everyday clinical practice. Methods: We present results of multicenter retrospective data on 38 patients with heavily pretreated metastatic uLMS who underwent oral pazopanib during their therapeutic journey. Results: At a median follow-up of 8.6 months, the disease control rate was 55.2%, with 17% partial responses and 15 patients (39.5%) with stable disease. At a median follow-up of 8.6 months, median progression-free survival was 4 months, and median overall survival was 19.8 months. The most common grade 3 adverse events (AEs) drug-related were hepatic toxicities, diarrhea, hypertension, nausea, and vomiting (all of them with an incidence of 5% considering the whole study cohort). No grade 4 AEs occurred. Conclusions: Pazopanib in everyday clinical practice is safe and shows a good disease control rate with prolonged survival. [ABSTRACT FROM AUTHOR]

Simple Summary: There are limited studies comparing selpercatinib to standard treatments in previously treated patients with certain solid cancers that have alterations in the RET receptor. The aim of this post hoc comparative effectiveness analysis study was to compare investigator-assessed outcomes among patients with RET-altered solid tumors who were treated with selpercatinib but naïve to standard therapies versus those previously treated with only standard therapies. This study showed that selpercatinib use as frontline therapy is associated with improved outcomes versus standard therapies in patients with RET-altered cancers in the lung, thyroid, and other non-lung, non-thyroid organs in the body. Selpercatinib use was associated with a significantly lower risk of treatment discontinuation, starting a new systemic treatment (or death), or disease progression compared to standard therapies. Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers. [ABSTRACT FROM AUTHOR]

Introduction: Liver X Receptor (LXR) agonists could attenuate the development of atherosclerosis but bring excess lipid accumulation in the liver. Danlou Recipe was believed to be a benefit for improving the lipid profile. Thus, it is unclear whether Danlou Recipe could attenuate hyperlipidemia without excess lipid accumulated in the liver of mice. This study aimed to clarify if Danlou Recipe could alleviate the progression of hyperlipidemia in mice without extra lipids accumulated in the liver. Methods: Male murine macrophage RAW264.7 cells and murine peritoneal macrophages were used for the in vitro experiments. Cellular cholesterol efflux was determined using the fluorescent cholesterol labeling method. Those genes involved in lipid metabolism were evaluated by qRT‐PCR and western blotting respectively. In vivo, a mouse model of hyperlipidemia induced by P407 was used to figure out the effect of Danlou Recipe on reverse cholesterol transport (RCT) and hyperlipidemia. Ethanol extract of Danlou tablet (EEDL) was prepared by extracting the whole powder of Danlou Prescription from ethanol, and the chemical composition was analyzed by ultra-performance liquid chromatography (UPLC). Results: EEDL inhibits the formation of RAW264.7 macrophage-derived foam cells, and promotes ABCA1/apoA1 conducted cholesterol efflux in RAW264.7 macrophages and mouse peritoneal macrophages. In the P407-induced hyperlipidemia mouse model, oral administration of EEDL can promote RCT in vivo and improve fatty liver induced by a high-fat diet. Consistent with the findings in vitro, EEDL promotes RCT by upregulating the LXR activities. Conclusion: Our results demonstrate that EEDL has the potential for targeting RCT/LXR in the treatment of lipid metabolism disorders to be developed as a safe and effective therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Although body composition-related biomarkers are associated with the prognosis of patients with cancer, whether they are associated with the therapeutic effects of immune checkpoint inhibitors remains unclear. We found that among body composition-related biomarkers, sarcopenia based on skeletal muscle mass was strongly associated with the treatment efficacy of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. However, body composition-related biomarkers based on subcutaneous or visceral fat were not associated with treatment efficacy. The skeletal muscle releases myokines to activate the immune system. Therapeutic interventions for sarcopenia may not only improve patients' quality of life but also improve the therapeutic effects of immune checkpoint inhibitors and prolong the prognosis of patients. Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. Patients and Methods: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65–14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83–23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. Conclusions: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant enterobacteriaceae (CRE) is associated with high mortality in critically ill patients, with limited treatment options. This study aims to compare clinical response, microbiological response, and mortality in patients treated with ceftazidime--avibactam with or without aztreonam (CAZ-AVI + AZT) and colistin or polymyxin B (polymyxins) in CRE infections. Materials and methods: This single-center prospective observational study included adult patients with CRE infections treated with CAZ-AVI+AZT or polymyxins between January 2022 and December 2022 at a Tertiary Care Medical Center in India. The clinical response, microbiological response, and mortality were compared between the two groups using a Cox multivariate regression model adjusted for the baseline SOFA score and comorbidities. Results: A total of 89 patients were enrolled, with 59 (66%) patients receiving CAZ-AVI + AZT and 30 receiving polymyxins. Baseline demographics and clinical characteristics were similar between the two groups. The Cox multivariate regression analysis showed a statistically significant difference in clinical failure on day 14 with the CAZ-AVI + AZT group vs polymyxins (HR = 0.78, 95% CI 0.63-0.95, p = 0.018). There was no difference in microbiological failure (HR = 1.08, 95% CI 0.66-1.77, p = 0.76), microbiological relapse (HR = 0.75, 95% CI 0.36-3.02, p = 0.62), and hospital mortality (HR = 1.04, 95% CI 0.75-1.43, p = 0.796) between the two groups. Conclusion: Treatment with ceftazidime--avibactam with or without aztreonam for CRE infections associated with a better clinical response compared with polymyxins monotherapy but without any difference in microbiological response or mortality. [ABSTRACT FROM AUTHOR]

Background: Herein, the effect of pre-use of Dexmedetomidine(Dex) on the half-effective dose (ED50) and 95%-effective dose (ED95) of Remimazolam tosilate(RT) in inhibiting the positive cardiovascular response(CR) which means blood pressure or heart rate rises above a critical threshold induced by double-lumen bronchial intubation was evaluated. Methods: Patients who underwent video-assisted thoracic surgery were divided into groups A (0), B (0.5 µg/kg), and C (1 µg/kg) based on different Dex doses. Group A included subgroups comprising young (A-Y) and elderly (A-O) patients. Neither groups B nor C included elderly patients due of the sedative effect of Dex. Based on the previous subject's CR, the dose of RT was increased or decreased in the next patient using the sequential method. This trial would be terminated when the seventh crossover occurred, at which point the sample size met the stable estimate of the target dose. Heart rate (HR) and mean arterial pressure (MAP) were monitored throughout the trial, and sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. HR and MAP were recorded at baseline (T1), the end of Dex (T2), and the end of RT (T3), the maximum HR and MAP were recorded within 3 min of intubation from beginning to end (T4). There was a positive CR when the T4 levels rose above 15% of the baseline. The ED50/ED95 and corresponding confidence interval were calculated using probability regression. Results: In total, 114 patients completed the trial. Without the use of Dex, the ED50/ED95 of TR inhibiting the positive CR caused by double-lumen bronchial intubation was 0.198/0.227 and 0.155/0.181 mg/kg in groups A-Y and A-O, respectively. The changes in vital signs from T1 to T3 were similar in the subgroups, indicating that the elderly patients were more sensitive to the dose of RT. The ED50/ED95 of RT inhibiting the positive CR caused by double-lumen endobronchial intubation was 0.122/0.150 and 0.068/0.084 mg/kg in groups B and C, respectively. And, the fluctuation of blood pressure from T3 to T4 was reduced by using Dex. RT was 100% effective in sedation with no significant inhibition of circulation. Apart from one case of hypotension occurred in group A-Y, two cases of low HR in group B, and one case of low HR in group C, no other adverse events were noted. Conclusions: The optimal dose of RT to inhibit positive CR induced by double-lumen bronchial intubation in elderly patients was 0.18 mg/kg and 0.23 mg/kg in younger patients. When the pre-use dose of Dex was 0.5 µg/kg, the optimal dose to inhibit positive CR of RT was 0.15 mg/kg. And, when the pre-use dose of Dex was 1 µg/kg, the optimal dose of RT was 0.9 mg/kg. Clinical trial registration: NCT05631028. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS. Methods: RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4. Results: Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant. Conclusions: Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS. Trial registration: INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055. [ABSTRACT FROM AUTHOR]

Objective: With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty. Methods: PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging. Results: Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = − 65.60, 95% confidence interval (CI) [− 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [− 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [− 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = − 0.13), 95% CI [− 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [− 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [− 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study. Conclusion: 1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the main challenges faced by cancer immunotherapy is the emergence of resistance against monotherapies, mediated by several immune escape mechanisms, which are able to impair therapy outcomes. Here, we investigated the biological properties of two novel bispecific constructs, known as tribodies, previously generated in our laboratory. These two bispecific molecules, named TR0304 and TR0506, are able to bind simultaneously to two immune checkpoints, i.e., LAG-3 and PD-L1 or LAG-3 and PD-1, respectively. After testing their effects on lymphocytes and on co-cultures of immune and tumor cells by comparing them to the monoclonal antibodies currently approved for clinical use, we found that these new constructs were able to activate the hPBMCs more efficiently than clinically validated mAbs, leading to stronger tumor cell lysis and, thus, showing their therapeutic potential for monotherapy-resistant tumors. Many advances in antitumor therapies have been achieved with antagonistic antibodies targeting the programmed cell death protein 1 (PD-1) or its ligand (PD-L1); however, many cancer patients still develop resistance to anti–PD-1/PD-L1 treatments often associated with the upregulation of other immune checkpoints such as Lymphocyte Activation Gene-3 (LAG-3). In order to verify whether it is possible to overcome these limits, we analyzed and compared the effects of combinations of the clinically validated anti-LAG-3 mAb (Relatlimab) with anti-PD-1 (Pembrolizumab) or anti-PD-L1 (Atezolizumab) monoclonal antibodies (mAbs) with those of novel bispecific tribodies (TRs), called TR0304 and TR0506, previously generated in our lab by combining the binding moieties of novel human antibodies targeting the same ICs of the mentioned mAbs. In particular, TR0304, made up of a Fab derived from an anti-PD-L1 mAb and two single-chain variable fragments (scFvs) derived from an anti-LAG-3 mAb, was tested in comparison with Relatlimab plus Atezolizumab, and TR0506, made up of an antigen-binding fragment (Fab) derived from the same anti-LAG-3 mAb and two scFvs derived from an anti-PD-1 mAb, was tested in comparison with Relatlimab and Pembrolizumab. We found that the two novel TRs showed similar binding affinity to the targets with respect to validated mAbs, even though they recognized distinct or only partially overlapping epitopes. When tested for their functional properties, they showed an increased ability to induce lymphocyte activation and stronger in vitro cytotoxicity against tumor cells compared to combinatorial treatments of clinically validated mAbs. Considering that tribodies also have other advantages with respect to combinatorial treatments, such as reduced production costs and lower dose requirements, we think that these novel immunomodulatory TRs could be used for therapeutic applications, particularly in monotherapy-resistant cancer patients. [ABSTRACT FROM AUTHOR]

Background: The study aims to compare the synergistic antibacterial efficacy of different combinations of calcium hydroxide as an intracanal medicament against E. faecalis. Material and methods: The current study included four hundred extracted human permanent mandibular premolar teeth. After complete chemo-mechanical preparation, the middle third of the root was sectioned using a rotary diamond disc and a total of 400 samples were obtained. The specimens were inoculated with E. faecalis for 21 days. After that, specimens were divided into five groups (n = 80) based on materials used for the disinfection of samples: Group I, calcium hydroxide alone; Group II, calcium hydroxide + 2% chlorhexidine gel; Group III, calcium hydroxide + 2% chitosan gel; Group IV, calcium hydroxide + 0.02% silver nanoparticle gel; Group V, calcium hydroxide + Bioactive glass S53P4. Dentin shavings from the apical third were obtained from the inner third of dentin were obtained using gates glidden no.1 to the apical depth, followed by no.2, 3, 4 and 5 analyzed for E. faecalis using the culture method. One-way analysis of variance (ANOVA) was used for data analysis, followed by post-hoc Tukey's test for multiple comparisons of means to check the difference in bacterial inhibition between the groups. Results: ANOVA results revealed a significant reduction of bacterial counts in all the groups compared (p < 0.001). Intergroup comparison showed maximum bacterial reduction (p < 0.001) with calcium hydroxide + bioactive glass S53P4 compared with other groups. Conclusion: Synergistic effect of calcium hydroxide showed better bacterial reduction compared to calcium hydroxide alone. Among the combinations evaluated, calcium hydroxide with bioactive glass, found to be most effective compared to other groups. [ABSTRACT FROM AUTHOR]

Background: Although second-generation antihistamines (SGAHs) are recommended as first-line drugs in chronic spontaneous urticaria (CSU), symptom relief has been reported in <50% of patients at licensed doses and up to fourfold dosing is recommended for these patients. Bilastine (SGAH), at licensed doses and higher doses, is efficacious in CSU. However, large-scale real-world data is scarce. Objectives: To report the real-world evidence of the safety and effectiveness of bilastine at a double dose (40-mg per day) in CSU management. Materials and Methods: In this retrospective questionnaire-based study carried out from February 2022 to July 2022, a pre-validated questionnaire was used to gather data on patients with CSU in dermatology practice from 62 centres across India. Adult patients of either gender diagnosed with CSU and switched over to bilastine 40 mg/day due to a non-satisfactory response (UCT score <12) to other antihistamines at double dose were considered for analysis. Based on UCT scores, patients were classified as responders (UCT ≥12) and non-responders at follow-up assessment at 2 weeks as compared to baseline. Results: 177 patients with a mean disease duration of 2.11 ± 1.48 years were included in the final analysis, with 53% females and 47% males. At the end of two weeks, 74/177 (42%) patients were classified as responders, and 103/177 (58%) were non-responders to Bilastine 40 mg/day. The mean change of UCT score from 5.0 ± 2.2 at baseline to 8.08 ± 5.41 (62% improvement) was significant (P < 0.001). Sedation was reported by ten patients without any discontinuation of treatment. Conclusion: Bilastine 40 mg/day was effective and well-tolerated in controlling CSU symptoms refractory to antihistamines at double doses. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment. Materials and Methods: This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model. Results: A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, P<0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (P>0.05). Baseline pain score was a predictive factor for the success of analgesics (P<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (P<0.05). Gender and age of patients had no significant effect on success of analgesics (P>0.05). Conclusion: Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed. [ABSTRACT FROM AUTHOR]

Objectives. Oral sulfate solution (OSS) is used for bowel preparation (BP) during colonoscopy. The way of taking this agent can be used a same-day regimen (only on the day of colonoscopy) and split regimen (the day before and on the day of colonoscopy) for receiving it. In this study, we analyzed the efficacy of a same-day regimen of 480 ml OSS for insufficient bowel preparation (BP) with high-concentrated polyethylene glycol (H-PEG). Materials and Methods. This multicenter retrospective study was conducted from December 2021 to December 2022 at three related institutions on patients aged ≥ 20 years with a fair or poor Aronchick score of BP with 1 l H-PEG in previous colonoscopy. All patients received a low-residual diet and 10 ml of 0.75% picosulfate sodium a day before the colonoscopy and 480 ml of OSS and ≥1 l of water 3 hours before the colonoscopy. We analyzed the rate of improvement with OSS compared to H-PEG and other efficacies, and adverse events (AE). Results. We evaluated 125 cases (77 males) with an average age of 72.1 ± 8.8 years. The completion rate of 480 ml of OSS was 97.6% (122/125). The improvement rate of BP showing good or excellent score with OSS was 70.4% (88/125). Compared OSS with previous H-PEG, the insertion time (min) was 7.0 ± 4.8 vs. 8.1 ± 6.0 (p = 0.01), and the adenoma detection rates were 67.2% vs. 63.2% (p = 0.05). The cleansing time (min) was 131 ± 46 vs. 165 ± 53 (p < 0.01). The rate of AE with OSS was 10.4% (13/125). There were no significant differences about AE in age and gender. The tolerance of OSS compared with H-PEG (good/similar/bad) was 72.0%/24.8%/3.2% (amounts), 26.4%/39.2%/34.4% (taste), and 76.8%/10.4%/12.8% (overall preference), respectively. Conclusions. The same-day regimen of 480 ml OSS effectively improved the insufficient BP of 1 l H-PEG. [ABSTRACT FROM AUTHOR]

Background: Cerebral malaria is one of the most serious complications of Plasmodium infection and causes behavioral changes. However, current antimalarial drugs have shown poor outcomes. Therefore, new antimalarials with neuroprotective effects are urgently needed. This study aimed to evaluate the effects of selected extracts as monotherapy or adjunctive therapy with artesunate on antimalarial, anti-inflammatory, antioxidant, and neuroprotective properties in experimental cerebral malaria (ECM). Methods: ECM was induced in male C57BL/6 mice by infection with Plasmodium berghei ANKA (PbA). Ethanolic extracts of Atractylodes lancea (a dose of 400 mg/kg) and Prabchompoothaweep remedy (a dose of 600 mg/kg) were evaluated as monotherapy and adjunctive therapy combined with artesunate at the onset of signs of cerebral malaria and continued for 7 consecutive days. Parasitemia, clinical scores, and body weight were recorded throughout the study. At day 13 post-infection, mouse brains were dissected and processed for the study of the inflammatory response, oxidative stress, blood–brain barrier (BBB) integrity, histopathological changes, and neurocognitive impairments. Results: Ethanolic extracts of A. lancea and Prabchompoothaweep remedy alone improved cerebral malaria outcome in ECM, whereas artesunate combined with extracts of A. lancea or Prabchompoothaweep remedy significantly improved the outcome of artesunate and crude extracts alone. Using real-time PCR, PbA-infected mice that had received the combination treatment showed significantly reduced gene expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10), chemokines (CXCL4 and CXCL10), and adhesion molecules (ICAM-1, VCAM1, and CD36). The PbA-infected mice that received the combination treatment showed a significantly decreased malondialdehyde level compared to the untreated group. Similarly, the Evans blue dye assay revealed significantly less dye extravasation in the brains of infected mice administered the combination treatment, indicating improved BBB integrity. Combination treatment improved survival and reduced pathology in the PbA-infected group. Additionally, combination treatment resulted in a significantly reduced level of cognitive impairment, which was analyzed using a novel object recognition test. Conclusions: This study demonstrated that artesunate combined with A. lancea or Prabchompoothaweep remedy extracts as adjunctive therapy reduced mortality, neuroinflammation, oxidative stress, BBB integrity protection, and neurocognitive impairment in the ECM. [ABSTRACT FROM AUTHOR]

Background: Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients. Methods: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model. Conclusions: Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the lack of progress in OsA's treatment and survival, there is a need to develop new therapeutic approaches for this tumor. OsA is a complex tumor for which the immune microenvironment appears as a potential therapeutic option. This study explores the antitumor effect of a chemically detoxified TLR4 agonist MP-LPS, under liposomal formulation called Lipo-MP-LPS. The agent induces a significant antitumor response and inhibition of tumor growth in an immunocompetent OsA model. Lipo-MP-LPS acts by favoring the switch of M2 macrophages to M1, and promotes T-cell recruitment. The study suggests that Lipo-MP-LPS could be used alone or in combination with other therapies for refractory tumors like OsA. Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA's immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC) patients (IB-IIIA) with no targetable driver mutations. Although genetic and physiological factors could suggest a priori differences in response to ICIs regarding sex, there are few works addressing it, and the available results are confusing. It is well established that women have a more proficient immune system; thus, a higher immune editing level is needed to develop metastatic disease, which could explain their better responses in the early phases of disease. Furthermore, the encouraging results observed for metastatic disease have promoted the use of ICIs as neoadjuvant treatments. Here, we aimed to first review the landscape of current neoadjuvant settings used in resectable NSCLC patients, before analyzing whether sex may be a factor that modulates responses to ICIs. To this end, we have carried out a meta-analysis of the available data. Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13–2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97–2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). Objectives: The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients. Methods: We retrospectively analyzed the survival data of ICI-treated 104 patients with stage III–IV NSCLC, who either received COVID-19 vaccination (n = 25) or no vaccination (n = 79). The potential risk factors, in particular roles of COVID-19 vaccination in the efficacy of ICIs in these patients, were evaluated. Results: Our results showed significantly improved ORR (28.0% vs. 11.39%, p = 0.05) and DCR (88.0% vs. 54.43%, p = 0.005) in the COVID-19 vaccinated group compared with the non-vaccinated group. Regarding the long-term survival benefits, COVID-19 vaccine showed profound influence both on the PFS (HR = 0.16, p = 0.021) and OS (HR = 0.168, p = 0.019) in patients with NSCLC under ICIs treatment. The PFS (p < 0.001) or OS (p < 0.001) was significantly improved in the COVID-19 vaccinated group, compared with the non-vaccinated group. Moreover, CD4 T cell (p = 0.047) level was higher in the COVID-19 vaccinated group than in the non-vaccinated group. Conclusions: COVID-19 vaccination enhances anti-PD-1 immunotherapy efficacy in patients with stage III–IV NSCLC, suggesting that COVID-19 vaccination may provide additional benefit to NSCLC patients. [ABSTRACT FROM AUTHOR]