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Objective: The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI)., Methods: We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI., Results: There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282-0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346-0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445-0.975; P = 0.037)., Conclusion: The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function. Please cite this article as: Gong ZT, Yang HX, Zhu BB, Liu HH, Siri GL. Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study. J Integr Med. 2024; 22(6): 645-651., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Linezolid-induced anemia (LI-AN) is a severe adverse reaction, but risk factors of the LI-AN for elderly patients have not been established., Objectives: The objective of this study was to develop a nomogram capable of predicting LI-AN in elderly patients., Design: This is a retrospective study to develop and validate a nomogram for anemia prediction in elderly patients treated with linezolid., Methods: We retrospectively screened elderly patients treated with linezolid at Inner Mongolia People's Hospital from January 2020 to December 2023 and validated our findings using the MIMIC-IV 2.2 database. Anemia was defined as hemoglobin reduction to 75% of baseline value. Univariate and multivariable logistic regression models were used to identify predictors and construct the nomogram, which was evaluated using receiver operating characteristic (ROC) curve analysis, calibration plot, and decision curve analysis., Results: A total of 231 patients were enrolled in this study. The training set comprised 151 individuals, and anemia occurred in 28 cases (18.54%). In the external validation set of 80 individuals, 26 (32.5%) were diagnosed with anemia. The predictors included duration of linezolid therapy, patient estimated glomerular filtration rate value, and sequential organ failure assessment score ⩾2. The ROC curve for the training set was 0.830 (95% CI: 0.750-0.910), while a similar ROC curve of 0.743 (95% CI: 0.621-0.865) was obtained for the validation set. The calibration curve demonstrated good correlation between predicted and observed results, indicating that this study effectively predicts risk factors associated with LI-AN in elderly patients., Conclusion: The developed prediction model can provide valuable guidance for clinicians to prevent anemia and facilitate rational linezolid use in elderly patients., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Gastric cancer (GC) is a prominent cause of cancer-related mortality worldwide. Long noncoding RNA (lncRNA) maternal expression gene3 (MEG3) participates in numerous signaling pathways by targeting the miRNA-mRNA axis. Studies on human tumors have demonstrated that the antibiotic Ciprofloxacin induces cell cycle changes, programmed cell death, and growth suppression. In this study, we transfected MEG3 lncRNA and Ciprofloxacin into the MKN-45 GC cell line. qRT-PCR was employed to evaluate the effects on the specific microRNA and mRNA. The wound healing test, MTT assay, and flow cytometry were used to assess the impact of their administration on cell migration, viability, and apoptosis, respectively. Research showed that miR-147 expression fell even more after MEG3 lncRNA transfection, leading to an increase in B-cell lymphoma 2 (BCL-2) levels. Ciprofloxacin transfection did not significantly affect the axis, except for MEG3, which led to its slight upregulation. MEG3 lncRNA inhibited the migration of MKN-45 cells compared to the control group. When MEG3 lncRNA was coupled with Ciprofloxacin, there was a significant reduction in cell migration compared to untreated groups and controls. MTT assay and flow cytometry demonstrated that MEG3 lncRNA decreased cell viability and triggered apoptosis. Simultaneous administration of MEG3 lncRNA and Ciprofloxacin revealed a significant reduction in cell viability caused by increased apoptosis obtained from MTT or flow cytometry assays. Modulating the miR-147-BCL-2 axis decreases cell migration and survival while promoting cell death. In conclusion, combining MEG3 lncRNA with Ciprofloxacin may be an effective therapeutic approach for GC treatment by influencing the miR-14-BCl-2 axis, resulting in reduced cell viability, migration, and increased apoptosis., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period., Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data., Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer ( p -interaction event*time = 0.08), systolic ( p = 0.07) and diastolic ( p = 0.05) blood pressure and a decrease of left ventricular ejection fraction ( p = 0.15) for subjects who experienced a CV event., Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: This study aimed to gather data on physical activity (PA), bleeding, health-related quality of life, and health status, using a wearable device and an electronic patient-reported outcome (ePRO) app, in individuals with moderate or severe hemophilia A (HA) without inhibitors receiving treatment according to the clinical practice. Methods: This is a 12-month multicenter cohort study conducted in Italy. The primary outcomes included the description of PA by type and intensity, adherence to World Health Organization guidelines, bleeding, and health-related quality of life by EQ-5D questionnaire. PA data were collected continuously through a fitness tracker worn by the patient; all the other variables were collected through ePRO questionnaires. Results: Only 54 of the 103 enrolled subjects (52.4%) used their fitness tracker for the defined valid period; adolescents were the least compliant age group. PA was performed at low rates and intensity. Approximately 52% of the subjects had sedentary behavior. The mean EQ-5D values did not change over time. At least one bleeding was reported in 43.7% of the subjects, mostly with sedentary behavior. The PA in the 2 days preceding the bleeding was comparable to the one observed in the overall observational period. Conclusions: The systematic recording of data through a fitness tracker and ePRO app shows that subjects with HA without inhibitors have lower-than-expected PA and that they still experience issues related to bleeding.

Context: The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency., Objective: This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU)., Data Sources: Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022., Study Selection: Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected., Data Extraction: After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process., Results: Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P = .03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P = .26). Thiamine supplementation did not decrease the risk of all-cause mortality (P = .71) or the need for renal replacement therapy (P = .14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P = .39)., Conclusion: This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients., Systematic Review Registration: PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=399710)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study was to investigate the clinical efficacy and safety of conducting therapeutic drug monitoring (TDM) of vancomycin in patients with postoperative intracerebral haemorrhage., Methods: We conducted a retrospective analysis of 435 patients who experienced postoperative cerebral haemorrhage and were treated with vancomycin in the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2017 to December 2021. Patients were then matched using the propensity score matching method in a ratio of 1:1. Ninety-two pairs of cases were successfully matched, and the data before and after performing vancomycin TDM were analysed., Results: After PSM, the baseline data of the two groups were balanced. There were no significant differences in the 14-day mortality and length of hospital stay (p>0.05) between the two groups. Compared with the non-TDM group, the TDM group had a higher proportion of patients with normal white blood cells (83.7% vs 56.5%, p=0.000), neutrophil count (57.6% vs 25.0%, p=0.000) and attaining desirable reductions of 80% in procalcitonin (65.2% vs 10.9%, p=0.000) and C-reactive protein (78.3% vs 41.3%, p=0.000) levels. At US$15.82 per additional TDM, TDM significantly promoted patient outcomes, as seen in improvements in the proportion of patients attaining desirable levels of white blood cells, neutrophil count, procalcitonin and C-reactive protein., Conclusions: Vancomycin TDM is a safe and effective approach for the treatment of patients with postoperative intracerebral haemorrhage. The empirical use of TDM of vancomycin significantly improved normal values of white blood cells and neutrophil count, achieved desirable reductions of 80% in procalcitonin and C-reactive protein, and reduced nephrotoxicity in patients with postoperative intracerebral haemorrhage., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV., Objective: Evaluation of EBV, CMV, HHV-6 ,and JCV, BKV frequency among gastric cancer patients., Methods: In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency., Results and Conclusion: The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objectives: Previous reports have indicated that the methylation profile in peripheral blood mononuclear cells (PBMCs) in different genes and loci is altered in colorectal cancer (CRC). Regarding the high mortality rate and silent nature of CRC, screening and early detection can meaningfully reduce disease-related deaths. Therefore, for the first time, we aimed to evaluate the early non-invasive diagnosis of CRC via quantitative promoter methylation analysis of RUNX3 and RASSF1A genes in PBMCs., Materials and Methods: In the present study, we analyzed the methylation status of two important tumor suppressor genes including RUNX3 and RASSF1A in 70 CRC patients and 70 non-malignant subjects using methylation-quantification of endonuclease-resistant DNA (MethyQESD), and a bisulfite conversion-independent method., Results: RUNX3 was significantly hypermethylated in PBMCs of CRC patients compared to healthy controls (P < 0.001). By determining the efficient cutoff value, the sensitivity, and specificity of RUNX3 promoter methylation for CRC diagnosis reached 84.28% and 77.14%, respectively. The receiver operating characteristic (ROC) curve analyses demonstrated that RUNX3 promoter methylation has high accuracy (areas under the curve [AUC] = 0.840, P < 0.001) for discriminating CRC subjects from healthy individuals. Moreover, RUNX3 methylation levels in PBMCs progressively increased with the stage of the disease (P < 0.001). Although the amount of RASSF1A promoter methylation was not significantly different between CRC patients and controls as well as in different stages of the disease (P > 0.05)., Conclusion: Our findings confirmed that PBMCs are reliable sources of methylation analysis for CRC screening, and RUNX3 promoter methylation can be used as a promising biomarker for early diagnosis of CRC., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: Studies indicate a higher level of distress in women than men with cancer, but whether this difference is retained over time is unknown. We studied the frequency and level of distress and fatigue during time according to gender in a cohort of cancer survivors., Patients and Methods: In this prospective study, cancer survivors were invited to undergo a psychological session immediately before the medical visit. Distress was assessed by the distress thermometer, and fatigue was assessed by the ESAS-r scale. Patients underwent follow-up visits to assess changes over time., Results: A total of 305 patients and 568 visits were performed with a median follow-up of 15.8 months. At baseline, females, young age, and breast cancer patients had significantly higher distress. However, there was an increase in distress of 0.29 points every 6 months in males (95% CI, 0.09-0.50) versus no change in females (0.03 points, 95% CI, - 0.09-0.15; p-interaction = 0.01). The different behavior of cancer distress during time according to gender was more evident in subjects aged 68 or older due to increasing physical problems in men (p-interaction = 0.005). There was no change in fatigue with time according to sex., Conclusions: Women, younger age, and breast cancer patients had increased cancer distress at the initial visit. However, women tend to stabilize during follow-up, whereas men tend to worsen their distress, especially because of physical and emotional problems, suggesting different coping capabilities., Trial Registration: The study is registered at ClinicalTrials.gov NCT05122052., Implications for Cancer Survivors: Interventions aimed at improving recognition of emotions related to disease experience in male cancer survivors appear necessary., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastric cancer (GC) remains one of the deadliest malignancies worldwide, demanding new targets to improve its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are dysregulated through gastric tumorigenesis and play a significant role in GC progression and development. Recent studies have revealed that lncRNAs can interact with histone-modifying polycomb protein, enhance Zeste Homolog 2 (EZH2), and mediate its site-specific functioning. EZH2, which functions as an oncogene in GC, is the catalytic subunit of the PRC2 complex that induces H3K27 trimethylation and epigenetically represses gene expression. EZH2-interacting lncRNAs can recruit EZH2 to the promoter regions of various tumor suppressor genes and cause their transcriptional deactivation via histone methylation. The interactions between EZH2 and this lncRNA modulate different processes, such as cell cycle, cell proliferation and growth, migration, invasion, metastasis, and drug resistance, in vitro and in vivo GC models. Therefore, EZH2-interacting lncRNAs are exciting targets for developing novel targeted therapies for GC. Subsequently, this review aims to focus on the roles of these interactions in GC progression to understand the therapeutic value of EZH2-interacting lncRNAs further., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To tackle the environmental unfriendly issue in existing synthesis strategies for 6-substitued thiopurine derivatives, such as poor step economy, frequent use of malodorous organic sulfur starting materials, toxic organic solvents, and equivalent dosage of base, we have developed a CuI-catalyzed base-free three-component Ullmann C-S coupling synthetic strategy, featured using inorganic salt Na 2 S as the sulfur source and nontoxic PEG-600 as the solvent. The newly developed strategy is particularly effective for the synthesis of 6-arylthiopurines. The high catalytic efficiency in PEG-600 can be rationalized by the high soluble ability of CuI catalyst, likely due to the presence of multiple oxygen coordination sites in PEG.

Background: Early colorectal cancer (CRC) diagnosis can drastically reduce CRC-related morbidity and mortality. In this regard, increasing attention is now being directed to DNA-based tests, especially the evaluation of methylation levels, to prioritize high-risk suspected persons for colonoscopy examination. Therefore, we aimed to assess the accuracy of MGMT gene promoter methylation levels in peripheral blood mononuclear cells (PBMCs) for distinguishing CRC patients from healthy people., Materials and Methods: For this study, a total of seventy individuals with CRC and 75 healthy individuals from Iran were included. The methylation level of MGMT in the DNA isolated from PBMCs was evaluated using the methylation quantification endonuclease-resistant DNA technique. To assess the diagnostic capability of the MGMT promoter methylation level, a receiver operating characteristic (ROC) curve was generated., Results: The mean promoter methylation level of MGMT in the CRC and control groups was, respectively, 27.83 ± 22.80 vs. 12.36 ± 14.48. The average percentage of methylation of the MGMT promoter between the CRC and control groups was significantly different ( P < 0.001). Also, the MGMT promoter was more hypermethylated in female patients than in males. ROC analyses indicated that the diagnostic power of the MGMT promoter methylation level for CRC was 0.754, with a sensitivity of 81.43% and a specificity of 75.71%, indicating a good biomarker for CRC diagnosis., Conclusion: Methylation evaluation of MGMT in PBMCs could be utilized as a diagnostic biomarker with high accuracy for prioritizing suspected CRC patients before colonoscopy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Background: Diaphragmatic ultrasound is increasingly used to assess patients with Chronic Obstructive Pulmonary Disease (COPD). The present study aims to investigate diaphragmatic dysfunction in COPD patients through a systematic review and meta-analysis., Methods: In December 2022,The researchers studied four international databases such as Medline/PubMed, ProQuest, ISI/WOS, and Scopus. Joanna Briggs Institute (JBI) checklist was used to review and control the quality of articles., Results: Finally, 6 articles were included in the analysis. Based on the meta-analysis results, forced expiratory volume (FEV1) was significantly lower in COPD patients compared to the control group (Hedges's g= -2.99, 95 % CI -4.78, -1.19; P =0.001). Forced vital capacity (FVC) was significantly lower in COPD patients compared to the control group (Hedges's g= -1.12, 95 % CI -1.91, - 0.33; P =0.005). COPD patients had significantly lower FEV1/FVC than the control group (Hedges's g= -1.57, 95 % CI -2.33, -0.81; P <0.001)., Conclusion: The present study showed that the diaphragm ultrasound (DUS) method could identify the difference in FEV1, FVC, and FEV1/FVC indices in two groups of COPD patients and healthy people., (© 2023 Hadi E.S.K., et al.)

Background: Several case-control studies have suggested that global and loci-specific deoxyribonucleic acid (DNA) methylation in peripheral blood mononuclear cells (PBMCs) of DNA might be potential biomarkers of cancer diagnosis and prognosis. In this study, for the first time, we intended to assess the diagnostic power of the methylation level of tumor suppressor candidate 3 ( TUSC3 ) gene promoter in patients with colorectal cancer (CRC)., Materials and Methods: In the current study, we quantitatively assessed the promoter methylation level of TUSC3 in PBMCs of 70 CRC cases and 75 non-cancerous subjects via methylation quantification of endonuclease-resistant DNA (MethyQESD) method., Results: The methylation level of the TUSC3 was meaningfully higher in CRC cases than in non-CRC subjects (43.55 ± 21.80% vs. 16.07 ± 13.63%, respectively; P < 0.001). The sensitivity and specificity of this gene for the detection of CRC were 88.6% and 76.0%, respectively. The receiver operating characteristic (ROC) curve examination discovered an area under the curve (AUC) of 0.880, representing a very high accuracy of the TUSC3 methylation marker in distinguishing CRC subjects from healthy individuals. However, there was no substantial diversity in methylation level between various CRC stages ( P : 0.088)., Conclusion: For CRC screening, PBMCs are a reliable source for DNA methylation analysis and TUSC3 promoter methylation can be utilized as a hopeful biomarker for early and non-invasive diagnosis of CRC., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

During the past decades, gastric cancer (GC) has emerged as one of the most frequent malignancies with a growing rate of prevalence around the world. Despite considerable advances in therapeutic methods, the prognosis and management of patients with gastric cancer (GC) continue to be poor. As one of the candidate molecular targets in the treatment of many types of cancer, the Wnt/β-catenin pathway includes a family of proteins that have important functions in adult tissue homeostasis and embryonic development. The aberrant regulation of Wnt/β-catenin signaling is strongly correlated with the initiation and development of numerous cancers, including GC. Therefore, Wnt/β-catenin signaling has been identified as one of the main targets for extending therapeutic approaches for GC patients. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, are important components of epigenetic mechanisms in gene regulation. They play vital roles in various molecular and cellular processes and regulate many signaling pathways, such as Wnt/β-catenin pathways. Insights into these regulatory molecules involved in GC development may lead to the identification of potential targets for overcoming the limitations of current therapeutic approaches. Consequently, this review aimed to provide a comprehensive overview of ncRNAs interactions involved in Wnt/β-catenin pathway function in GC with diagnostic and therapeutic perspectives. Video Abstract., (© 2023. The Author(s).)

During 2019, the SARS-CoV-2 emerged from China, and during months, COVID-19 spread in many countries around the world. The expanding data about pathogenesis of this virus could elucidate the exact mechanism by which COVID-19 caused death in humans. One of the pathogenic mechanisms of this disease is coagulation. Coagulation disorders that affect both venous and arterial systems occur in patients with COVID-19. The possible mechanism involved in the coagulation could be excessive inflammation induced by SARS-CoV-2. However, it is not yet clear well how SARS-CoV-2 promotes coagulopathy. However, some factors, such as pulmonary endothelial cell damage and some anticoagulant system disorders, are assumed to have an important role. In this study, we assessed conducted studies about COVID-19-induced coagulopathy to obtain clearer vision of the wide range of manifestations and possible pathogenesis mechanisms., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: There have been debates about the human appendix function, and while previous research suggested it might be a vestigial organ with no functional significance, recent studies have pointed out that it might have an important role in the immune system. Acute appendicitis (AA) is a common cause of emergency abdominal surgery in the world. Some epidemiologic investigations have found an association between appendicitis and viral infections. In this study, we have reviewed systematically articles to discover viral infections that cause appendicitis and find any possible correlations between the two., Methods: This systematic review was performed by searching among electronic databases including Web of Science, PubMed, Scopus, and EMBASE on viruses and appendicitis topics., Results: Conducted search leads to 983 results in all databases after the duplicate removal and screening by title, abstract, and full-text based on inclusion criteria lead to 19 studies. There were several assays to detect the viruses, which are thought to be AA causative agents. RT-PCR and immunoassays were the mainstay methods to detect the probable cause., Conclusion: Investigations suggested that some viruses including measles virus (MV), influenza virus, dengue fever virus (DFV), human immunodeficiency virus (HIV), human herpesviruses, rotavirus, and adenovirus are associated with acute appendicitis. Despite the available reports, the specific mechanisms behind the relationship between acute appendicitis and viral infections are yet to be understood. Therefore, further investigations are necessary to find out the pathogenesis and pathophysiology of viral complications in appendicitis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In May 2022, a re-emerging viral pathogen belonging to the Poxviridae was first reported from the UK, and WHO confirmed the outbreak after the prevalence of the disease increased. As of February 15, 2023, more than 85,000 confirmed cases have been recorded in 110 countries. Due to the spread of the virus across multiple countries, WHO declared the mpox outbreak as a public health emergency. Human mpox virus is an enveloped virus with a linear double-stranded DNA that can cause encephalitis with neurological complications such as pharyngitis, fever, anorexia, adenopathy, vesiculopapular rash, and headache. Dysregulation of microRNAs in viral encephalitis has been reported in a variety of documents. In this mini-review, we aim to discuss the possibility of CNS-related microRNA dysregulation in mpox-related encephalitis., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Abstract: Spark's nevus is a particular type of melanocytic nevus, with histology that shows features of both Spitz and Clark nevus. Detailed dermoscopic features in a series of Spark nevi have not been described yet. We performed a monocentric retrospective observational study on 20 lesions of Spark nevus excised from 19 patients (M:F = 10:9; mean age: 37,6 years), reviewed by 5 experts in dermoscopy and 2 dermatopathologists. A histologic review confirmed that Spark nevi were mostly symmetric (80%), well circumscribed (100%), mainly compound (65%) melanocytic lesions with either epithelioid (55%) or spitzoid (45%) cell morphology and bridging of the nests (100%). Spark nevi were more frequently found on the trunk (85%) in patients with a history of sunburns in childhood (84%), with skin phototype III (79%), and with high nevus count (>100 nevi, 7 patients (36%)). On dermoscopy, we observed different general patterns: multicomponent (40%), reticular-globular-homogeneous (15%), globular homogeneous (15%), reticular (15%), reticular-globular (5%), homogeneous (5%), and globular (5%). Spark nevi showed frequently dermoscopic asymmetry (63%), brown color (90%) with areas of central hyperpigmentation (41%) and peripheral hypopigmentation (28%), atypical pigment network (48%), irregular globules (42%), irregular dots (31%), irregular blotches (16%), blue-whitish veil (13%), peripheral island (25%), irregular hyperpigmented areas (12%), and regression (33%). BRAF mutation was present in 7 of the 10 analyzed cases (70%); all these cases presented a history of evolution. In conclusion, Spark nevi occur on the trunk of young adults with high nevus count and history of sunburns; dermoscopic features are protean, often atypical and suspicious of melanoma., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dietary indices and scores are valuable predictive markers against chronic diseases. Several previous studies have revealed the beneficial effects of diabetes risk reduction score (DRRS) against diabetes and cancer incidence. However, its association with metabolic abnormalities among obese individuals have not been revealed before. In the current study, we aimed to investigate the association between DRRS and metabolic risk factors among obese individuals., Methods: In the current cross-sectional study, 342 obese individuals [Body mass index (BMI) ≥ 30 kg/m 2 ] aged 20-50 years were included. Dietary intake was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) of 168 food items and DRRS was calculated. Metabolic syndrome (MetS) was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Enzymatic methods were used to assess serum lipids, glucose, and insulin concentrations. Blood pressure was measured by a sphygmomanometer and body composition with bioelectrical impedance analysis (BIA)., Results: Those with a higher adherence to DRRS had a significantly higher intake of energy, fiber, and lower protein compared with those in the lower quartiles. Moreover, lower intakes of trans fats, meat, sugar sweetened beverages (SSB), and glycemic index (GI) with higher intakes of fruits, cereal fiber, polyunsaturated fatty acids/ saturated fatty acids (PUFA/ SFA) ratio, coffee, and nuts were observed in the highest versus lowest DRRS categories. Lower systolic blood pressure, diastolic blood pressure, triglyceride and, higher high-density lipoprotein values were observed in higher DRRS categories. Logistic regression analysis showed that hypertension was significantly associated with adherence to DRRS among obese individuals, the odds ratio (OR) was 0.686 (95% confidence interval [CI], 0.26-0.84) after adjustment for potential confounders. But the risk of other components of MetS was not significantly associated with higher quartiles of adherence to DRRS. Also, a non-significantly lower prevalence of MetS was observed in the higher quartile of DRRS., Conclusions: According to the results of the current study, higher DRRS was associated with lower blood pressure, modified serum lipids, and lower Mets prevalence. Further studies in different populations are warranted for better generalization of the obtained findings., (© 2023. The Author(s).)

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. Although numerous studies have been conducted on advanced GC, the molecular mechanisms behind it remain obscure. Long non-coding RNAs (lncRNAs) are a family of RNA transcripts capable of regulating target genes at transcriptional, post-transcriptional, and translational stages. They do this by modifying mRNAs, miRNAs, and proteins. These RNAs are critical regulators of many biological processes, including gene epigenetics, transcription, and post-transcriptional levels. This article highlights recent results on lncRNAs involved in drug resistance, proliferation, migration, angiogenesis, apoptosis, autophagy, and immune response in GC. The potential clinical implications of lncRNAs as biomarkers and therapeutic targets in GC are also discussed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Timely access to medical assistance is the first crucial step to improving clinical outcomes of stroke patients. Many educational campaigns have been organized with the purpose of making people aware of what a stroke is and what is necessary to do after its clinical onset. The PRESTO campaign was organized in Genoa (Italy) to spread easy messages regarding the management of the acute phase of stroke. Educational material was disseminated to educate people to call the emergency medical services as soon as symptoms appear. Data collected were analyzed in three different phases of the campaign: before the beginning, during, and after the end. We enrolled 1,132 patients with ischemic stroke admitted to hospital within 24 hours of symptoms onset. Our data showed a mild reduction in onset-to-door time (24 minutes) during the months following the end of the campaign and a slight increase in number of patients who arrived at hospitals, in particular with milder symptoms and transient ischemic attack, as opposed to the same period before the campaign. Interestingly, in the months after the end of the campaign, we observed a slight reduction of the percentage of patients who accessed hospitals after 4.5 hours from symptoms onset. In conclusion, our results may suggest that an informative campaign can be successful in making people rapidly aware of stroke onset, with the consequent rapid access to hospitals. Considering the changing of way of access to information, we think that an extensive multimedia campaign should be evaluated in the next future., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: IL-23 receptor (IL-23R) dysregulation has been shown to have critical roles in pathogenesis of different autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) via suppression of regulatory T cells (Tregs) as well as differentiation, expansion, and survival of T helper 17 (Th17) cells, followed by upregulation of interleukin 17 (IL-17). Here, we assessed the association of a functional microRNAs (miRNAs)-related single nucleotide polymorphism (miR-SNPs: rs10889677) in IL-23R, which was correlated with its overexpression and increased risk for SLE and RA in the Iranian population., Methods: Genotype and allele distribution of rs10889677 variant were investigated in 105 RA patients, 100 SLE cases and 105 healthy controls via polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method., Results: Our findings suggested that AA genotype, but not AC genotype, was associated with increased risk of RA (AA vs. CC; OR: 3.27; 95%CI [1.467-7.551]). The allele A was more frequent in RA group compared to controls (A allele vs. C allele; OR: 1.92; 95%CI [1.282-2.894]). This common variant was not significantly correlated with SLE risk in our population (P > 0.05). However, stratification analysis indicated that RA patients with AA genotype show higher serum concentration levels of C-reactive protein (CRP) (P: 0.008). No obvious correlation was noticed between different genotypes in SLE cases, except for a slight difference in terms of oral ulcer manifestation incidence (P: 0.038)., Conclusion: This study suggests a significant relationship between rs10889677 variant in IL-23R with increased risk of RA and some clinical features in RA and SLE patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Considering the limitations of the current approaches to colorectal cancer (CRC) screening, scientists strived to find noninvasive and more powerful biomarkers for the early diagnosis of CRC. Nowadays, there are different sources of biomarkers for CRC diagnosis. Blood-based samples including circulating cell-free tumor DNA (ctDNA) and DNA extracted from leukocytes in peripheral blood might be promising sources of noninvasive cancer biomarkers such as cancer-specific methylation patterns. In this study, we aimed to evaluate the noninvasive early diagnosis of CRC via quantitative promotor methylation analysis of SDC2 gene in whole blood., Materials and Methods: Sixty-five CRC patients and 65 healthy participants were enrolled to assess promoter methylation of SDC2 gene in whole blood using the methylation quantification endonuclease-resistant DNA (MethyQESD) technique., Results: Our findings demonstrated drastic hypermethylation of SDC2 in blood samples from CRC subjects (37.91%) compared with non-malignant individuals (17.02%) (P < 0.001). The sensitivity for detection of CRC by methylation of SDC2 was 81.54%, with a specificity of 69.23%. The ROC curve analysis demonstrated that the AUC was 0.847 (P < 0.001), indicating that the status of SDC2 promoter methylation in whole blood is an excellent biomarker of CRC diagnosis. Furthermore, our results showed that methylation level in CRC patients significantly increased in higher tumor stages, demonstrating that an increased percentage of methylation is correlated with tumor progression (P < 0.001)., Conclusion: SDC2 promoter methylation status in blood samples is a valuable cancer biomarker and holds high power and accuracy in distinguishing CRC patients from healthy subjects in the early stages of the disease., Competing Interests: None

Background and Aims: Immunosuppressive therapy has a key role in developing coronavirus disease-2019 (COVID-19)-associated mucormycosis. In this study, we investigated the effect of the type and cumulative dose of immunosuppressive agents on COVID-19-associated mucormycosis., Methods: We designed a descriptive cross-sectional study involving three COVID-19 hospitals in Iran. Clinical and demographic data were gathered from the medical records and checked by two independent researchers to minimize errors in data collection., Results: Seventy-three patients were included in the study. The mean age of cases was 57.41 (SD = 12.64) and 43.8% were female. Among patients, 20.5% were admitted to the intensive care unit (ICU) during COVID-19. Furthermore, 17 patients (23.29%) had a history of diabetes mellitus. Sixty-nine patients (94.52%) had a history of receiving corticosteroids (dexamethasone) during treatment of COVID-19, and of those, five patients (6.85%) received Tocilizumab beside. The mean cumulative dose of corticosteroids prescribed was 185.22 mg (SD = 114.738). The average cumulative dosage of tocilizumab was 720 mg (SD = 178.89). All of the included patients received amphotericin B for mucormycosis treatment, and 42 survived (57.53%). Also, there was a significant relationship between hospitalization in ICU for COVID-19 and the mucormycosis outcome ( p  = 0.007). However, there weren't any significant associations between cumulative doses of immunosuppressive drugs and mucormycosis outcome ( p  = 0.52)., Conclusion: The prevalence of COVID-19-associated mucormycosis is increasing and should be considered in the treatment protocols of COVID-19. Controlling risk factors such as diabetes, malignancy and the administration of immunosuppressive agents based on recommended dosage in validated guidelines are ways to prevent mucormycosis., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Introduction: The importance of genetic and dietary factors in occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has been established. However, complex interrelationships, including direct and indirect effects of these variables are yet to be clarified. So, our aim was to investigate the mediating role of glycemic indices in the relationship between CARTPT rs2239670 polymorphism, socio-demographic and psychological factors and metabolic risk factors and the presence of MetS in adults with obesity., Methods: In a cross-sectional study of 288 apparently healthy adults with obesity aged 20-50 years, dietary glycemic index (GI) and glycemic load (GL) were measured using a validated semi-quantitative food frequency questionnaire (FFQ). Biochemical parameters, blood pressure and anthropometric indicators were assayed by standard methods. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Structural equation modeling (SEM) was used in the statistical analysis., Results: CARTPT rs2239670 had a positive direct effect on MetS (B = 0.037 ± 0.022; P = 0.043) and, on the other hand, this variant was found to be indirectly associated with MetS presence through mediation of GI (B = 0.039 ± 0.017; P = 0.009). CARTPT was a significant predictor of both dietary GI and GL (B = 1.647 ± 0.080 and B = 3.339 ± 0.242, respectively). Additionally, glycemic indicators appeared to mediate the association of age and gender with LDL-C (B = 0.917 ± 0.332; P = 0.006) and HDL (B = 1.047 ± 0.484; P = 0.031), respectively. GI showed a positive relationship with LDL-C (P = 0.024) in men and similar relationships were found between GL and LDL-C (P = 0.050) and cholesterol (P = 0.022) levels in women., Conclusion: The SEM findings suggest a hypothesis of the mediating effect of glycemic indices in the relationship between genetic susceptibility to obesity and MetS presence. Our findings need to be confirmed with large prospective studies., (© 2022. The Author(s).)

Background: The association of genetic and dietary factors with occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has long been addressed but there is a lack of evidence for complex interrelationships, including direct and indirect effects of these variables. Hence, this study is aimed at evaluating the mediating role of glycemic indices in the association of melanocortin-4 receptor (MC4R) rs17782313 polymorphism, sociodemographic, and psychological factors with the risk of MetS in obese adults using structural equation modeling., Methods: We performed a cross-sectional analysis of data from 287 apparently healthy adults. Dietary glycemic index (GI) and glycemic load (GL) were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Structural equation modeling was used to explore direct and indirect effects of genetic and nongenetic factors on MetS., Results: MC4R gene variant was directly associated with the risk of MetS ( B = 0.010; P = 0.023). On the other hand, this variant was found to be indirectly and positively associated with LDL-C ( B = 6.589; P = 0.042) through mediatory effects of GI and GL. Moreover, GI and GL also mediated indirect positive effects of sex and age on LDL-C ( B = 3.970; P ≤ 0.01; B = 0.878; P ≤ 0.01, respectively) and HDL ( B = 2.203; P ≤ 0.01; B = 0.129; P ≤ 0.01, respectively). MC4R rs17782313 polymorphism had positive effects on GI ( B = 1.577; P ≤ 0.01) and GL ( B = 1.235; P ≤ 0.01)., Conclusion: Our data may state a hypothesis of the mediating effect of quantity and quality of carbohydrates consumed in relationship between genetic susceptibility to obesity and cardiometabolic risk factors. Further analyses should be carried out in high-quality cohort studies in order to confirm the findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022 Mahdieh Khodarahmi et al.)

Background: Endothelin-1 (ET-1) is a peptide overexpressed in gastric cancer (GC) and linked to carcinogenesis and resistance to chemotherapy. Applying microRNAs (miRNAs/miRs) to downregulate ET-1 and reverse resistance to commonly used chemotherapy drugs such as 5-fluorouracil (5-FU) is practical., Methods: The current study sought to evaluate the miR-648 expression in GC and any plausibility of its replacement, either with or without the combination of chemo agents to downregulate ET-1 expression through interaction with its target gene. To this end, miR-648 and ET-1 expression levels were assessed in GC tissues and adjacent non-tumor tissues driven from 65 patients who had already undergone surgery, fifteen of which had received 5-FU before surgery. The impact of miR-648 and chemo agents on ET-1 expression was measured using qPCR and Western blotting. Further, an MTT assay was conducted to assess its association with cell viability. Ultimately, the association of miR-648 and ET-1 with clinicopathological characteristics was evaluated., Results: The current study revealed that miR-648 was considerably down-regulated, while ET-1 was substantially up-regulated in patients with GC. The 5-FU caused a significant increase in miR-648 and reduced ET-1 expression. It was also determined that overexpression of miR-648 suppressed ET-1 production, notably when combined with 5-FU, leading to survival reduction. These results further showed that miR-648 replacement could sensitize chemoresistant GC cells. Besides, a significant association between ET-1 and miR-648 with clinicopathological features was discovered CONCLUSIONS: miR-648 replacement may serve as a potential oncosuppressive therapeutic approach that warrants further investigation to translate into an effective GC treatment., Competing Interests: Competing interests None., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Purpose: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography ( 18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL)., Methods: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS)., Results: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUV mean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM&#95;Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM&#95;Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both., Conclusions: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival., (© 2022 Wiley Periodicals LLC.)

Background: The dietary glycemic index (GI) has been introduced as a novel index to elucidate the potential of foods to increase postprandial glucose. According to the limited available data about the association of GI with cardio-metabolic risk factors such as lipid profile, blood glucose markers, and blood pressure in developing countries, the current study was conducted to investigate this association in apparently obese individuals., Method and Material: Three hundred forty-seven obese adults were recruited in the present cross-sectional study. A validated 147-food item semi-quantitative food frequency questionnaire (FFQ) was used to evaluate the usual dietary intake of study participants. Dietary GI was calculated using the international GI database. Fatty acid desaturase (FADs)2 gene variants were determined according to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ANOVA was used to compare study variables across different tertile of GI., Results: We found significant differences in terms of anthropometric parameters [weight (P = 0.038), waist circumference (WC) (P = 0.023), weight to hip ratio (WHR) (P = 0.007), and fat-free mass (FFM) (P < 0.001)] between different tertiles of GI. Similarly, energy and macronutrient intakes had a significant difference across dietary GI, and subjects with a higher dietary intake of energy and macronutrients (carbohydrate, protein, and total fat) were assigned to the third tertile of dietary GI (P < 0.001). While there was no significant difference in terms of cardio-metabolic risk factors in different dietary GI tertiles. Moreover, the total GI score was non-significantly higher in the TT genotype of FADS2 gene polymorphism compared with other genotypes. While no significant difference was observed between FADS2 genotype frequencies in different GI tertiles., Conclusion: Calculated dietary GI was associated with several cardio-metabolic risk factors in obese individuals. However, further prospective studies and clinical trials are needed to confirm our findings., (© 2022. The Author(s).)

When we read fiction, we encounter characters that interact in the story. As such, we encode that information and comprehend the stories. Prior studies suggest that this comprehension process is facilitated by taking the perspective of characters during reading. Thus, two questions of interest are whether people take the perspective of characters that are not perceived as capable of experiencing perspectives (e.g., robots), and whether current models of language comprehension can explain these differences between human and nonhuman protagonists (or lack thereof) during reading. The study aims to (1) compare the situation model (i.e., a model that factors in a protagonist's perspective) and the RI-VAL model (which relies more on comparisons of newly acquired information with information stored in long term memory) and (2) investigate whether differences in accessibility of information differ based on adopting the intentional stance towards a robot. To address the aims of our study, we designed a preregistered experiment in which participants read stories about one of three protagonists (an intentional robot, a mechanistic robot and a human) and answered questions about objects that were either occluded or not occluded from the protagonist's view. Based on the situation model, we expected faster responses to items that were not occluded compared to those that were occluded (i.e., the occlusion effect). However, based on the RI-VAL model, we expected overall differences between the protagonists would arise due to inconsistency with general world knowledge. The results of the pre-registered analysis showed no differences between the protagonists, nor differences in occlusion. However, a post-hoc analysis showed that the occlusion effect was shown only for the intentional robot but not for the human, nor mechanistic robot. Results also showed that depending on the age of the readers, the RI-VAL or the situation model is able to explain the results such that older participants "simulated" the situation about which they read (situation model), while younger adults compared new information with information stored in long-term memory (RI-VAL model). This suggests that comparing to information in long term memory is cognitively more costly. Therefore, with older adults used less cognitively demanding strategy of simulation., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Adolescence is a critical period in human life, associated with reduced physical activity and increased sedentary behaviors. In this systematic review and dose-response meta-analysis, we evaluated the association between screen time and risk of overweight/obesity among adolescents., Methods: A systematic search in electronic databases, including PubMed, Embase, and Scopus was performed up to September 2021. All published studies evaluating the association between screen time and risk of overweight/obesity among adolescents were retrieved. Finally, a total of 44 eligible studies were included in the meta-analysis., Results: The results of the two-class meta-analysis showed that adolescents at the highest category of screen time were 1.27 times more likely to develop overweight/obesity (OR = 1.273; 95% CI = 1.166-1.390; P < 0.001; I-squared (variation in ES attributable to heterogeneity) = 82.1%). The results of subgrouping showed that continent and setting were the possible sources of heterogeneity. Moreover, no evidence of non-linear association between increased screen time and risk of overweight/obesity among adolescents was observed (P-nonlinearity = 0.311)., Conclusion: For the first time, the current systematic review and meta-analysis revealed a positive association between screen time and overweight/obesity among adolescents without any dose-response evidence., Trial Registration: The protocol of the current work has been registered in the PROSPERO system (Registration number: CRD42021233899 )., (© 2022. The Author(s).)

Eosinophilic esophagitis (EoE) is an emerging antigen-mediated, inflammatory disease of unknown etiology. EoE affects about 1/2,000 patients in the United States (US), with a higher prevalence rate in adults (43.4/100,000) than in children (29.5/100,000), prevailing in Caucasians and male sex. EoE is a multifactorial disease typically characterized by type 2 inflammation. Pathogenesis is not entirely understood and is likely non-IgE mediated. Food allergens trigger EoE, stimulating the dysregulated immune cells through an impaired esophageal epithelial barrier. Clinical presentation of EoE depends on age and mainly includes food refusal, vomiting, abdominal or chest pain, dysphagia, and food impaction. Endoscopy is the gold standard to diagnose EoE. The goal of EoE therapy is to achieve clinical and histological remission to prevent esophageal fibrosis and improve patients' quality of life (QoL). Cornerstones of therapy are PPIs, topical steroids, and elimination diets. Over recent decades, research progress has been made in terms of a greater understanding of the EoE pathogenesis and new therapeutic approaches. However, there are still several unmet needs, such as non-invasive tools and biomarkers for monitoring the disease.

The goal of this study was to conduct a systematic review of the literature on the relationship between peripheral blood platelet to lymphocyte ratio (PLR) and mortality in sepsis and to integrate the findings in a meta-analysis. An electronic search of three main databases was performed: PubMed, Embase, and Scopus on 19 December 2021. Finally, 16 studies comprising 2403 septic patients, including 1249 survivors and 1154 nonsurvivors, were included in this meta-analysis. We found that PLR levels were significantly higher in nonsurvivors than in survivors (random effect model: SMD = 0.72, 95% CI; 0.35-1.10, p < 0.001). However, significant heterogeneity was observed across the studies ( I 2 = 94.1%, p < 0.01). So, we used random effect model in our meta-analysis. In the subgroup analysis, according to mortality time, patients deceased during one month after sepsis had elevated levels of PLR compared to survivors (SMD = 1.03, 95% CI = 0.15-1.92, p = 0.22). However, in-hospital mortality was not associated with PLR level (SMD = 0.41, 95% CI = -0.18-0.99, p = 0.175). Our findings support PLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of sepsis mortality., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Gancheng Wang et al.)

Background: In 2007, POLYTECH Health & Aesthetics (POLYTECH, Dieburg, Germany) established an ongoing patient survey to improve the post-market surveillance of silicone gel-filled breast implants based on patient-reported outcomes in the context of the pioneering "Implants of Excellence" (IoE) program., Objectives: To disclose an update on safety and performance outcomes at 5 years for Mesmo breast implants., Methods: Between January 2014 and October 2019, 919 patients (for a total of 1816 implants) who underwent breast augmentation and reconstruction with Mesmo implants were asked to participate in the IoE program. Data were collected by mean of 1320 questionnaires received. A survival analysis assessed the onset of different complications., Results: Eight patients (0.9%) experienced capsular contracture Baker grade III or IV with a cumulative rate at 5 years of 1.2% (95% CI = 0.6-2.4). The proportion of revisional surgery was 0.5% with a 5-year rate of 0.6% (95% CI = 0.2-1.5). Additional adverse events such as hematoma, seroma, malposition, open wounds, and other complications were carefully monitored. Questionnaires showed that 93.9% (95% CI = 92.2-95.4) of the patients were satisfied or very satisfied with their aesthetic results with Mesmo implants., Conclusions: Post-market clinical follow-up revealed that the overall complications rate reported was low. Data demonstrated an excellent safety property on a large cohort of patients. This result allows the rating of Mesmo breast implants as highly competitive and a very safe choice for both surgeons and patients., (© 2022 The Aesthetic Society.)

Introduction: Vascular Eagle syndrome, due to impingement of the extracranial internal carotid artery (ICA) by the styloid process (SP), is an uncommon and not yet widely recognized cause of ICA dissection. Up to now, this diagnosis is still presumptive, based mainly on the length of the SP. However, given the discrepancy between the much higher prevalence of an elongated SP in the population compared to the reported rate of Eagle syndrome, other anatomical factors beyond the length itself of this bony structure seem to be involved., Material and Methods: We performed a retrospective single center case-control study of ICA dissection related to abnormalities of styloid process and age- and sex-matched controls affected by ICA dissection not related to abnormal relationship with the styloid process. In our work instead of considering SP length as the main criteria to differentiate the two groups, we decided to consider styloid process-internal carotid artery distance (at the dissection point) as the main factor to define a styloid process related dissection (SPRD). In fact in some patients, the distance between the dissected artery and the bony prominence was virtual., Results: Our study showed that in patients with SPRD the styloid process angulation on the coronal plane tends to be more acute and that styloid process-C1 distance is significantly shorter at the side of the dissection. This data reinforces the idea that ICA dissection risk in the vascular Eagle syndrome has probably a multifactorial pathogenesis., (© 2021. Fondazione Società Italiana di Neurologia.)

Background: The association between cocaine- and amphetamine-regulated transcript prepropeptide gene (CARTPT) and obesity-related outcomes has shown in the epidemiological studies. Nevertheless, there is lack of data regarding the CARTPT gene-diet interactions in terms of antioxidant potential of diet. So, this study aimed to test CARTPT gene-dietary non-enzymatic antioxidant capacity (NEAC) interactions on cardio-metabolic risk factors in obese individuals., Methods and Material: The present cross-sectional study was carried out among 288 apparently healthy obese adults within age range of 20-50 years. Antioxidant capacity of diet was estimated by calculating the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC) using a semiquantitative food frequency questionnaire (FFQ). Genotyping for CARTPT rs2239670 polymorphism was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: A significant interaction was revealed between CARTPT rs2239670 and dietary ORAC on BMI ( P Interaction  = 0.048) and fat mass percent (FM%) ( P Interaction  = 0.008); in A allele carriers, higher adherence to the dietary ORAC was related to lower level of BMI and FM%. And, the significant interactions were observed between FRAP index and rs2239670 in relation to HOMA ( P Interaction  = 0.049) and QUICKI ( P Interaction  = 0.048). Moreover, there were significant interactions of rs2239670 with TRAP ( P Interaction  = 0.029) and TEAC ( P Interaction  = 0.034) on the serum glucose level; individuals with AG genotype were more respondent to higher intake of TRAP., Conclusion: The present study indicated that the relationships between CARTPT rs2239670 and obesity and its-related metabolic parameters depend on adherence to the dietary NEAC. Large prospective studies are needed to confirm our findings., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Introduction: Our retrospective study evaluates head CTs performed in our Hospital in the last 11 years (2009-2019) in centenarian patients., Objectives: To estimate the correlation between reasons for examination and CT findings in emergency and to evaluate if there was the expected involution of the brain by analyzing some non-emergency neuroradiological parameters (NENP)., Material and Methods: 62 Head CTs performed on patients aged 100 and over were reviewed. They were evaluated emergency CT findings and NENP (leukoencephalopathy, enlargement of the ventricular volume, presence of vascular calcifications). For comparison, NENP were also assessed in two relatively younger populations of 62 patients aged between 65-70 (called "65-70") and 85-90 ("85-90")., Results: In cases of suspected traumatic brain lesions, 11.9% (n = 5/42) of centenarians showed a cerebral bleeding; as concerns suspected stroke we found a higher concordance between clinical suspicion and CT features, 46.6% (n = 7/15). As regards NENP, no significant differences were found with respect to the "85-90" population in terms of severity of leukoencephalopathy, enlargement of the ventricular volume and presence of vascular calcifications., Conclusions: In emergency, CT plays a pivotal role in defining an immediate diagnosis and from a medico-legal point of view, resulting together with clinical observation the main strategy in the management of centenarians. By the analysis of NENP we may support that centenarians' brains on CT are similar to those of "85-90"., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment., Patients and Methods: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose., Results: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 10 9 /L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009)., Conclusion: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 10 9 /L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS., Gov Identifier: NCT04932863., Competing Interests: Conflict of interest statement We declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Frailty is a common syndrome in older people that carries an increased risk of mortality. Two main models describe frailty, either as a loss of physical functions or as an accumulation of multiple deficits. The aim of our study was to compare the physical frailty index developed in the Cardiovascular Health Study (CHS) with a multidimensional frailty tool, the Multidimensional Prognostic Index (MPI), in predicting death in community-dwelling older subjects. Four hundred and seven community-dwelling older subjects were enrolled. Each subject underwent a comprehensive geriatric assessment (CGA) with calculation of the MPI and CHS index. Mortality was recorded over the following 5 years. In the overall sample (mean age of 77.9 ± 4.5 years; 51.6% female), 53 subjects (13%) died during the 5-year follow-up period. Both the MPI and CHS index were able to predict mortality; however, the MPI was significantly more accurate than the CHS index in predicting mortality (C-index = 0.69 and 0.59, respectively; p < 0.001), with a statistically significant difference of 10%. In conclusion, multidimensional frailty, assessed by the MPI, predicts five-year mortality in community-dwelling older people better than physical frailty, as assessed by the CHS index. These findings suggest the usefulness of assessing frailty by means of CGA-based tools to predict relevant health-negative outcomes in older people.

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p -value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p -value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

Purpose: the validation of a new scoring model considering the principal risk factors of differentiated thyroid cancer (DTC) relapse., Methods: we evaluated all DTC patients treated with thyroidectomy and radioactive iodine (RAI) therapy. Three domains were considered: the demographic domain (age and gender), the surgical domain (histology and the American Thyroid Association risk categories), and the RAI-related domain (pre-RAI thyroglobulin and post-therapeutic 131 I whole-body scan). The progression-free survival was assessed. The patients' sample was randomly split into a training and validation set. The three-domain score was calculated as the weighted sum of the levels of each significant factor, then scaled to an integer range (0-100) and, finally, stratified into terciles: mild risk 0-33, moderate risk 34-66, and severe risk 67-100., Results: 907 DTC patients were included. The RAI-related domain was the most relevant factor in the score calculation. The tercile stratification identified significantly different survival curves: patients within the two upper terciles showed approximately 6 to 30 times more progressive risk than patients at mild risk., Conclusion: we have validated a three-domain scoring system and the principal impact on this score is provided by the peri-RAI findings, whose prognostic role seems to be essential in risk identification.

Background: Multidimensional Prognostic Index (MPI) is recognized as a prognostic tool in hospitalized patients, but data on the value of MPI in community-dwelling older persons are limited. Using data from a representative cohort of community-dwelling persons, we tested the hypothesis that MPI explains mortality during 15 years of follow-up., Methods: A standardized comprehensive geriatric assessment was used to calculate the MPI and to categorize participants in low-, moderate-, and high-risk classes. The results were reported as hazard ratios (HRs) and the accuracy was evaluated with the area under the curve (AUC), with 95% confidence intervals (CIs) and the C-index. We also reported the median survival time by standard age groups., Results: All 1453 participants (mean age 68.9 years, women = 55.8%) enrolled in the InCHIANTI study at baseline were included. Compared to low-risk group, participants in moderate (HR = 2.10; 95% CI: 1.73-2.55) and high-risk MPI group (HR = 4.94; 95% CI: 3.91-6.24) had significantly higher mortality risk. The C-index of the model containing age, sex, and MPI was 82.1, indicating a very good accuracy of this model in explaining mortality. Additionally, the time-dependent AUC indicated that the accuracy of the model incorporating MPI to age and sex was excellent (>85.0) during the whole follow-up period. Compared to participants in the low-risk MPI group across different age groups, those in moderate- and high-risk groups survived 2.9-7.0 years less and 4.3-8.9 years less, respectively., Conclusions: In community-dwelling individuals, higher MPI values are associated with higher risk of all-cause mortality with a dose-response effect., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess the prognostic role of different inter and intralesional expression (heterogeneity) of oestrogen receptor (ER) in bone metastases, as identified by the combined use of [18F]FES PET/CT and [18F]FDG PET/CT in patients with oestrogen receptor-positive (ER+) metastatic breast cancer (BC)., Methods: We analysed patients with a new diagnosis of bone metastases who were candidates for first-line systemic endocrine therapy. Before starting therapy, patients underwent baseline [18F]FES PET/CT and [18]FDG PET/CT. Semi-quantitative evaluation of whole-body bone metabolic burden (WB-B-MB) was performed on [18F]FES and [18F]FDG PET/CT in order to evaluate disease extent, tumour metabolism and ER heterogeneity. We used time-to-event analyses (Kaplan-Meier and Cox proportional-hazards methods) to estimate progression-free (PFS) and overall survival (OS), in order to assess the independent prognostic value of [18F]FES PET/CT and [18F]FDG PET/CT, alone and in combination., Results: According to our criteria, we enrolled 49 patients. Over a median follow-up of 44.7 months, 35 patients suffered disease progression (71.4 %) and 15 died of disease (30.6 %). When the risk of disease progression was calculated by means of the Cox model, only [18F]FDG WB-B-MB was independently and directly associated to PFS (p = 0.02). On analysing the association between all prognostic parameters and survival, the Cox model showed that the only parameter associated with OS was the WB-B-MB FES/FDG ratio (p = 0.01)., Conclusion: The combined use of [18F]FES-PET/CT and [18F]FDG-PET/CT can identify ER heterogeneity in BC bone metastases. This heterogeneity is significantly associated with survival. Moreover, the extension of the FDG-avid component correlates with the risk of disease progression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine., Results: In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone., Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023., (© 2021. The Author(s).)

Aim: The economic recognition of disability is of importance in daily practice, but the tools used in older people are still limited. Therefore, we aimed to investigate the effectiveness of the multidimensional prognostic index (MPI) to identify frail older subjects to be submitted to civil invalidity application for disability benefits including Attendance Allowance (AA) indemnity, Carer's Leave (Law 104) and/or Parking Card for people with disabilities., Methods: From March 2018 to January 2019, 80 older people were included. The MPI was calculated from comprehensive geriatric assessment information including eight different domains. Civil benefits included attendance allowance (AA) indemnity by the Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (INPS), Carer's Leave (Law 104), and Parking Card for people with disabilities., Results: MPI values were associated with an increased probability to obtain a 100% civil disability, AA indemnity, Carer's Leave and a parking card for people with disabilities. MPI score showed a very good accuracy in predicting the civil invalidity benefits with a area-under-curve (AUC) of 87.3 (95% CI 80.6-97.4) to predict the release of AA indemnity, 81.3 (95% CI 68.5-91.1) to predict Care's leave and 70.7 (95% CI 59.4-84.7) to predict the Parking Card release. Moreover, data showed that a cut-off score of MPI ≥ 0.75 could identify the 100% of older subjects who successfully obtained the indemnity release., Conclusion: MPI is an excellent predictor of social benefits' release by local and national agencies.

Purpose: There is clear evidence for an association between oral health and systemic illnesses, geriatric syndromes, and mortality. Frail and multimorbid older people often suffer from insufficient oral health care, but standardized dental examinations are not routinely performed in clinical settings. The aim of this study was to verify the practicability of in-hospital oral health examinations and to identify their association with patients' prognosis as assessed by means of the Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI)., Methods: One hundred hospitalized patients aged 65 years and older (mean age 76.9 years (SD 6.4); 58.2% male, 41.8% female) underwent a CGA-based MPI calculation at discharge with subdivision into three mortality risk groups (MPI-1, low risk, score 0-0.33; MPI-2, moderate risk, score 0.34-0.66; MPI-3, high risk, score 0.67-1). To identify the current oral health status and the Oral Health-related Quality of Life (OHRQoL), three oral health examinations were performed. Information on survival, the incidence of oral diseases, dental appointments, and treatments up to 6 months after discharge were collected., Results: All oral health examinations were feasible during hospitalization and were associated with MPI prognosis, even though they were not associated with 6-month mortality. The MPI could not predict the use of dental health care or treatment, as, irrespective of MPI and oral health examinations, dental services were underutilized during follow up., Conclusion: Besides MPI evaluation, oral health examinations should be implemented into an inhospital course to improve clinical decision-making as well as secondary and tertiary prevention of oral health- and related systemic diseases., Trial Registration Number: German Clinical Trials Register: DRKS00013607 (07.02.2019, retrospectively registered).

Purpose: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender., Methods: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131 I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed., Results: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (Δ C-index  = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (Δ C-index  = + 5.1%, P < .001)., Conclusions: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

Background: Capsular contracture (CC) is the most common complication following Immediate Breast Reconstruction (IBR) with breast implants. Different implant surfaces were developed aiming to reduce the incidence of CC. We evaluated the incidence and degree of CC after Direct-to-Implant (DTI) IBR with insertion of textured (TE) or polyurethane (PU) covered implants., Methods: A retrospective review of consecutive patients treated at our Institution with mastectomy and one-stage IBR and implant reconstruction between 2013 and 2018, with or without post mastectomy radiation therapy (PMRT), was conducted. Immediate breast reconstruction was performed by implanting 186 PU covered implants and 172 TE implants., Results: Three-hundred-twelve women underwent 358 DTI IBR with PU or TE implants, were analyzed with a median follow-up time of 2.3 years (range 1.0-3.0). The overall rate of CC Baker grade III and IV was 11.8% (95%CI: 8.4-16.3), while, after PU and TE implant placement it was 8.1% (95% CI: 4.1-15.7) and 15.8% (95% CI: 4.1-15.7) [p = 0.009]), respectively. Irradiated breasts developed CC more frequently rather than non-irradiated breasts (HR = 12.5, p < 0.001), and the relative risk was higher in the TE group compared with the PU group (HR = 0.3, p = 0.003)., Conclusions: After mastectomy and one-stage IBR, the use of PU covered implants is associated with a lower incidence of CC compared to TE implants. This advantage is amplified several folds for patients who necessitate PMRT. Footnote: Capsular contracture (CC); Immediate Breast Reconstruction (IBR); Directto- Implant (DTI); Textured (TE); Polyurethane (PU); Post mastectomy radiation therapy (PMRT); Nipple Sparing mastectomy (NSM)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)