Search

Since the reports of the first cases of COVID-19, in less than 5 years, a huge number of documents regarding that disease and the coronavirus (SARS-CoV-2), responsible for the infection, have been published. The tremendous number of scientific documents covers many topics on different issues directly related to COVID-19/SARS-CoV-2. The number of articles—including reviews—reporting adverse/side effects of the approved COVID-19 vaccines is considerable. A wide range of adverse/side effects have been reported in humans after COVID-19 vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, and other miscellaneous adverse effects. In contrast, information on nonclinical studies conducted to assess the potential toxicity/adverse effects of the COVID-19 vaccines in laboratory animals, is comparatively very scarce. The present review was aimed at revising the scientific literature regarding the studies in laboratory animals on the toxic/adverse effects of COVID-19 vaccines. In addition, the investigations reported in those specific toxicology journals with the highest impact factors have been examined one by one. The results of the present review indicate that most nonclinical/experimental studies on the adverse/toxic effects of the COVID-19 vaccines and/or potential candidates showed—in general terms—a good safety profile. Only in some animal studies were certain adverse effects found. However, a rather surprising result has been the limited number of available (in the databases PubMed and Scopus) nonclinical studies performed by the companies that have been the largest manufacturers of mRNA vaccines in the world. It is assumed that these studies have been conducted. However, they have not been published in scientific journals, which does not allow the judgment of the international scientific community, including toxicologists. [ABSTRACT FROM AUTHOR]

Background and objective: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. Methods: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. Results: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. Conclusion: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations. [ABSTRACT FROM AUTHOR]

Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid. [ABSTRACT FROM AUTHOR]

Objectives: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. Methods: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. Results: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. Conclusions: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. Clinical relevance statement: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. Key Points: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the psychometric properties of the Spanish-language version of the HIV-Symptom Index (HIV-SI) questionnaire in Spanish patients undergoing antiretroviral therapy. Methods: Between 2014 and 2016, an observational, multicenter, prospective cohort study was conducted in seventeen Spanish hospitals to validate HIV-SI questionnaire in terms of: construct validity (confirmatory factor analysis), internal consistency (Cronbach's alpha), convergent validity (Pearson's correlation coefficient) and Known-group validity. In addition, a sensitivity to change analysis was also performed. Results: A total of 232 patients were included in the study. They had a mean age of 46.17 (SD9.82) and were 75% male. The median overall score for the HIV-SI was 10 (IQR 4– 19.5) and the most common symptoms reported were feelings of nervousness or anxiety, fatigue or energy loss, feeling sad or depressed, stomach pain or bloating, and difficulty sleeping. In the current study, the Spanish HIV-SI questionnaire showed a high internal consistency (α = 0.89) and adequate construct validity (CFI and TLI > 0.90). When contrasted with the MOS-HIV questionnaire, an inverse correlation was found. It showed a good association with the mental (r=-0.61; P < 0.0001) and physical score (r=-0.60; P < 0.0001). In a multivariate analysis, the age of the patient, female condition, hepatitis C coinfection, concomitant treatment and non-adherence resulted in a higher HIV-SI score. Conclusions: Our study has shown that the Spanish HIV-SI is a valid and reliable self-administered PROM for routine measurement of patient- reported symptoms among Spanish patients on antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Background: Aesthetic injections have become increasingly popular for maintaining a youthful appearance. However, with the rise of SARS-CoV-2, there have been concerns about potential complications. This study aims to summarize and understand the complications that occur in individuals who have received cosmetic injections after SARS-CoV-2 infection or vaccination. By doing so, we hope to provide recommendations to minimize these complications and ensure the safety of aesthetic treatments in the current COVID-19 era. Methods: The PRISMA guidelines, the Preferred Reporting Program for Systematic Reviews and Meta-Analyses, were used for this review. Databases including PubMed, EMBASE, Medline, Web of Science and ScienceDirect were searched. The last search time of each database was May 10, 2023. In addition, relevant references were manually searched. Results: A total of 26 studies containing 139 patients were searched. The complication with the highest percentage of reported patients was delayed inflammatory response (DIR) (n = 68; 48.92%), followed by diminished efficacy (n = 45; 32.37%) and filler reaction (n = 12; 8.63%). The remaining complications include hypersensitivity reactions, symptomatic hypercalcemia, sub-acute hypersensitive reactions, hyperalgesia, infection, fat necrosis and granulomatous reaction. Conclusions: Cosmetic injectable procedures are generally safe but may have adverse effects, particularly during the pandemic. It is important for individuals to fully understand these risks beforehand. Clinicians should be knowledgeable about adverse event mechanisms and management to prevent issues. Industry leaders should strengthen risk management efforts to ensure safe and steady development of cosmetic injections. Overall, a comprehensive understanding, effective communication and risk management are crucial for the safe use of cosmetic injectable procedures. Level of Evidence III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. Methods: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. Results: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. Conclusions: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary. [ABSTRACT FROM AUTHOR]

Purpose: Hydroxychloroquine is currently recommended for the treatment of systemic lupus erythematosus (SLE), but it can cause irreversible retinal toxicity. This study aimed to identify factors associated with early hydroxychloroquine-induced retinal toxicity in patients with SLE from a single centre for 20 years. Methods: SLE patients diagnosed between 1998 and 2017 and followed up for at least 1 year were included. Demographic, clinical, laboratory and therapeutic data were collected from the electronic medical records and retrospectively analysed. Early hydroxychloroquine-induced retinal toxicity was defined as the development of macular toxicity within the first 5 years of hydroxychloroquine treatment. Results: A total of 345 patients followed for a median of 15 years were analysed; 337 (97.7%) patients received hydroxychloroquine, 38 (11.3%) of them presented with retinal toxicity, and 10 (3%) developed early retinal toxicity. These patients had a mean treatment duration of 3.3 years with a mean cumulative dose of 241 g. Patients were diagnosed by visual field (VF) and fundoscopy, and two were also assessed using spectral domain optical coherence tomography (SD-OCT). The median (IQR) age of patients with early toxicity was 56 (51–66) years, and 80% were female. Factors independently associated with early hydroxychloroquine-induced retinal toxicity were lupus anticoagulant positivity (OR 4.2; 95% CI 1.2–15.5) and hypercholesterolaemia (OR 5.6; 95% CI 1.5–21.5). Conclusion: Our results suggest that lupus anticoagulant positivity and hypercholesterolaemia among SLE patients may be risk factors for early hydroxychloroquine-induced retinal toxicity, regardless of the dose or duration of treatment. [ABSTRACT FROM AUTHOR]

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44–80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4–16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance. [ABSTRACT FROM AUTHOR]

Purpose of review: This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels. Recent findings: A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. Summary: While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals. [ABSTRACT FROM AUTHOR]

Immune-mediated inflammatory disease (IMID) prevalence is estimated at 3–7% for Westernised populations, with annual incidence reported at almost 1 in 100 people globally. More recently, drug discovery approaches have been evolving towards more targeted therapies with an improved long-term safety profile, while the requirement for individualisation of medicine in complex conditions such as IMIDs, is acknowledged. However, existing preclinical models—such as cellular and in vivo mammalian models—are not ideal for modern drug discovery model requirements, such as real-time in vivo visualisation of drug effects, logistically feasible safety assessment over the course of a lifetime, or dynamic assessment of physiological changes during disease development. Zebrafish share high homology with humans in terms of proteins and disease-causing genes, with high conservation of physiological processes at organ, tissue, cellular and molecular level. These and other unique attributes, such as high fecundity, relative transparency and ease of genetic manipulation, positions zebrafish as the next major role player in IMID drug discovery. This review provides a brief overview of the suitability of this organism as model for human inflammatory disease and summarises the range of approaches used in zebrafish-based drug discovery research. Strengths and limitations of zebrafish as model organism, as well as important considerations in research study design, are discussed. Finally, under-utilised avenues for investigation in the IMID context are highlighted. [ABSTRACT FROM AUTHOR]

Background: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. Results: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. Conclusion: This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?" for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology. Methods: A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain. Results: Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review. Conclusion: The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: "The benefit of primary G-CSF prophylaxis is not clear in NRC-STS" and "The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs." G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Background: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. Methods: We conducted a retrospective analysis of 308 patients with stage 0–III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local–regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. Results: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1–2 skin reactions (91.6%). The most common late toxicity was grade 0–1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1–2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. Conclusions: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery. Highlights: This study evaluated clinical outcomes, side effects and cosmetic results after SIB-IMRT. The three-year OS, LRC, and DMFS were 100%, 99.6%, and 99.2%, respectively. 96.9% of 262 patients achieved good cosmetic results after 2 year radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Since the onset of the coronavirus (COVID-19) pandemic crisis, the supplement market has consistently grown. Therefore, we conducted this survey during the fourth wave of the COVID-19 pandemic to study the frequency and context of dietary supplement (DS) consumption (vitamins and mineral intake) and explore the consumer's pharmaceutical buying behaviour; and (3) to study its determinants as regards the demographics, Fatigue Severity Scale (FSS), and healthy eating pyramids. Methods: We conducted a cross-sectional web-based survey on 1333 Arabic adults aged 18 years or more residing in six Arabic-speaking countries in May 2022, using a validated self-administrated questionnaire. The survey-involved questions about sociodemographic characteristics, physical activity, FSS, healthy eating pyramid, DS consumption, and consumers' pharmaceutical purchasing behaviour. Results: Most participants were aged 20 to less than 35 years, and 64.6% used dietary supplements. There was a statistically significant difference between supplement users and nonusers as regards consumers' pharmaceutical buying behaviour in terms of advertising quality, safety rules, pharmaceutical forms, and packet quality. Arabic adults consumed the following dietary supplements: 63.5% vitamin C, 60.1% vitamin D, 47.1% iron, and 44.4% zinc. Authorised products (76.0%), natural contents (75.0%), and safety rules (68%), were the most common factors influencing Arabic consumers' pharmaceutical purchasing behavior. Multi-logistic regression analysis showed that being female, having a history of COVID-19, having a positive attitude about the benefits, and being recommended for supplement use were predictors of dietary supplement use. Conclusion: The dietary consumption of supplements is prevalent, mainly including vitamin C, vitamin D, iron, zinc, vitamin B, and magnesium. In addition, Arabic adults are poorly adherent to healthy eating pyramids. Given the ongoing COVID-19 pandemic, Arabic health authorities should prioritize this issue to minimize the potential for misusing dietary supplements. [ABSTRACT FROM AUTHOR]

Background: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. Aims: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. Methods: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. Results: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. Conclusions: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails. A retrospective cohort study was conducted to compare the safety and efficacy of the 33 sequential DGW-TPS and 84 primary TPS techniques. No significant differences were found in PEP, cannulation success, or other AEs. Multivariable regression analysis reaffirmed these findings. The sequential DGW-TPS technique showed a comparable safety and efficacy to primary TPS, supporting its use if inadvertent pancreatic access occurs. [ABSTRACT FROM AUTHOR]

Objectives: Meditation is increasingly popular, and yet studies of meditation-related adverse effects, or experiences of unusual psychological states, have mostly focused on those of extremely unpleasant or pleasant nature, respectively, despite the wide range of possible experiences. We aimed to create an instrument to capture meditation-related experiences of varied intensity and subjective valence. Method: We collected detailed data from 886 US meditators after screening over 3000 individuals to generate a sample representative of major types of meditation practices and experience levels. Participants answered questions about meditation history, mental health, and 103 meditation-related experiences identified for the development of the Inventory of Meditation Experiences (IME). Results: Parallel analysis guided the eventual determination of factors; exploratory and confirmatory factor analysis yielded good model-to-data fit on a 30-item, 3-factor version of the scale. The total scale and subscales showed expected correlations with measures of adverse effects, meditation characteristics, and mental health symptoms. Analysis indicated utility in examining experience intensity and valence as potentially distinct or combined features of experiences. Conclusions: The IME is a psychometrically valid tool that may prove useful to assess a variety of meditation-related experiences that account for both the intensity and subjective valence of those experiences. Preregistration: While several hypotheses were preregistered (https://osf.io/r8beh/), the present study pertains only to the development and validation of the instrument. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis aimed to determine the effectiveness of psychologically informed practice (PIP) with behavioural graded activity (BGA) compared to (1) waitlist controls (WLC), (2) other interventions (OI), (3) PIP alone or (4) BGA alone in cancer patients and survivors (CPaS). Methods: PubMed, Web of Science and Embase were screened for randomised controlled trials encompassing BGA + PIP in CPaS. Effect sizes were inventoried for outcomes regarding physical activity (PA), quality of life (QoL) and debilitating symptoms (DS), which were assessed at four time points: post-intervention (PI), follow-up F1 (1 to 3 months), F2 (4 to 6 months) and F3 (> 6 months). The quality of the evidence was classified by the GRADE approach. Results: Thirty-three studies were found eligible, comprising 4330 participants. Significant effects with low heterogeneity of PIP + BGA comparing to WLC were found for anxiety (SMD − 1.29 [−1.71; − 0.86]), depression (SMD − 0.79 [− 1.10; − 0.48]), functional impairment (SMD − 0.72 [− 0.95; − 0.50]), PA (self-reported: (SMD − 0.58 [− 0.84; − 0.32]) and objectively measured: (SMD − 0.51 [− 0.90; − 0.13])) and social impairment (SMD − 0.33 [− 0.58; − 0.08]). When comparing PIP + BGA to OI, fatigue (SMD − 0.35 [− 0.51; − 0.20]) and PA (SMD − 0.26 [− 0.41; − 0.11]) at PI, and fatigue (SMD − 0.34 [− 0.58; − 0.10]) at F1 were found significant with low heterogeneity. No significant effects were observed in the meta-analyses of studies comparing PIP + BGA to BGA or PIP alone. Conclusions: PIP with BGA has a favourable effect on DS, PA and QoL in CPaS when compared to non-behavioural interventions such as WLC, usual care and education. However, further research is needed on 'how' and 'when' PIP + BGA should be provided in cancer rehabilitation. Implications for Cancer Survivors: PIP + BGA has the potential to facilitate CPaS to reach the recommended amount of PA and reduce DS. [ABSTRACT FROM AUTHOR]

Background: Antibody-drug conjugates have revolutionized cancer therapy due to their selectivity and efficacy. However, concerns have been raised regarding the potential effects of trastuzumab deruxtecan in interstitial lung diseases. Aim: This study aimed to investigate the safety signals and time to onset of antibody-drug conjugates induced interstitial lung disease. Method: We utilized the FDA Adverse Event Reporting System database (2004–2022) to identify interstitial lung disease safety signals in 13 FDA-approved antibody-drug conjugates. Disproportionality analysis was conducted to estimate the reporting odds ratios for interstitial lung disease. Results: Seven antibody-drug conjugates exhibited safety signals of interstitial lung disease: trastuzumab deruxtecan [reporting odds ratio, ROR (95% confidence intervals, CI) = 64.15 (57.07–72.10)], enfortumab vedotin [ROR (95% CI) = 5.24 (3.25–8.43)], trastuzumab emtansine [ROR (95% CI) = 3.62 (2.90–4.53)], brentuximab vedotin [ROR (95% CI) = 3.22 (2.49–4.17)], polatuzumab vedotin [ROR (95% CI) = 2.56 (1.59–4.12)], gemtuzumab ozogamicin [ROR (95% CI) = 2.53 (1.70–3.78)], and inotuzumab ozogamicin [ROR (95% CI) = 2.33 (1.21–4.49)]. Five antibody-drug conjugates with limited reports were excluded from further analysis: belantamab mafodotin, loncastuximab tesirine, mirvetuximab sorafenib, tisotumab vedotin, and moxetumomab pasudotox. Japan and the United States were the primary reporting countries. Conclusion: This real-world study highlights high safety signals of interstitial lung disease associated with antibody-drug conjugates. Clinicians should be aware of these safety concerns and risk factors and implement early identification measures for their patients. Future research should prioritize comprehensively exploring the relationship between antibody-drug conjugates and lung diseases. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and safety of perioperative parenteral administration or submucosal infiltration of tramadol for perioperative pain control on the basis of pain intensity or analgesics consumption and perioperative outcomes in mandibular third molar surgery. Material-methods: An electronic database search was conducted up to 10 November 2022 to retrieve all randomized controlled trials (RCTs), assessing the analgesic efficacy of parenteral use of tramadol implemented as an adjunct to local anesthesia or intraoperative sedation/general anesthesia, in surgical extraction of mandibular third molars. Modified Jadad scale and Cochrane bias tool were used for the qualitative appraisal. Results: Nineteen RCTs were selected for qualitative analysis. Nine studies involved intravenous, and 5 intramuscular administration of tramadol, while 5 evaluated submucosal infiltration with tramadol. Intravenous or intramuscular tramadol provided a weaker analgesic effect compared with non-steroidal anti-inflammatory drugs (NSAIDs), while intravenous tramadol induced an enhanced analgesic effect than oral tramadol. Parenteral administration of tramadol improved the quality of postoperative analgesia versus placebo. No notable adverse effects were recorded. Conclusions: Parenteral or submucosal infiltration of tramadol constitutes an effective and safe alternative analgesic approach in surgical extraction of mandibular third molars, yet the nociceptive effect of this analgesic modality could not supersede that of NSAIDs. Trial registration: PROSPERO No CRD42021227574. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis was performed to investigate if there was a significant association between the number of cigarettes smoked per day and the results of root coverage procedures. Methods: Electronic search was performed through PubMed, Web of Science, Embase, and Scopus until January 2023. Studies were included if evaluated the outcomes of periodontal plastic surgery procedures for the treatment of gingival recession in smokers. Statistical evaluation was conducted using random-effects method to analyze the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CI). Results: From a total of 4494 references, 15 studies were considered relevant to be included in this study. The results showed that 44.39% sites had complete root coverage (CRC) at 6 months (non-smokers: 54.06%, < 10 cigarettes/day: 48%, 10–20 cigarettes/day: 19.56%, ≥ 20 cigarettes/day: 50%). Mean root coverage at 6 months were as follows: non-smokers: 74.94% ± 16.71%, < 10 cigarettes/day: 84.20% ± 2.24%, 10–20 cigarettes/day: 75.30% ± 14.69%, ≥ 20 cigarettes/day: 68.75% ± 26.51%. A significant difference was revealed between non-smokers and individuals who smoked 10–20 cigarettes/day in terms of CRC at 6 months: OR = 0.15 (95% CI = 0.03 to 0.71; P =.017). However, no significant difference was detected comparing 10–20 and ≥ 20 cigarettes/day. Conclusion: As there was not enough data available, any definitive conclusions about the connection between an increase in the amount of cigarettes consumed per day and the results of root coverage procedures could not be reached. Further research is required with comparative studies involving individuals who smoke varying numbers of cigarettes. [ABSTRACT FROM AUTHOR]

Background: It has been reported that botulinum toxin type A (BoNT-A) produces structural changes in masticatory muscles. However, not all histomorphometric parameters affected by BoNT-A parameters have been assessed. This study investigated the histomorphometric changes in the masseter muscle of rats after a single injection of BoNT-A. Methods: Forty-four adult animals were randomly divided into control group (n = 22) and BoNT-A group (n = 22). Controls received a single dose of 0.14 mL/kg of saline in masseter muscles, and the BoNT-A group received a 7 U/Kg of BoNT-A. The groups received the same volume of injected substances. Animals were sacrificed on 7th (n = 5), 14th (n = 5), 21st (n = 5), 28th (n = 4) and 90th (n = 3) days post-treatment. Histological masseter tissue slides were obtained from hematoxylin–eosin treatment and analyzed in optical microscopy regarding muscle cross-sectional area, amount of connective tissue and quantity and diameter of myocytes. For statistical analysis, generalized linear models were used to compare the data (ANOVA). In all test, the significance level of 5% was set. Results: BoNT-A values of cross-sectional area of the masseter muscle were significantly lower than controls (p < 0.01) throughout the study. Regarding myocytes quantity, BoNT-A subgroups presented higher values than controls (p < 0.0001) since the 14th day until the end of the study; however, the diameter of myocytes was smaller in all BoNT-A subgroups (p < 0.0001) in all assessment points. The amount of connective tissue was higher in BoNT-A subgroups (p < 0.0001) throughout the study. Conclusion: A single injection of BoNT-A altered the structure of masseter muscle of rats, regarding its histomorphometric parameters. No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: External apical root resorption (EARR) is a frequently observed adverse event in patients undergoing fixed appliance therapy. Assessing the patients' risk during treatment is important, as certain factors are assumed to be associated with an increased likelihood of occurrence. However, their predictive value remains limited, making evidence-based clinical decision-making challenging for orthodontists. To address this issue, the Dutch Association of Orthodontists (NvVO) developed a clinical practice guideline (CPG) for EARR in accordance with the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation II) in 2018. The aim of this study is to get insight into the actual utilization and the practical implementation of the guideline among orthodontists. The hypothesis to be tested was that after its introduction, clinical practice for EARR has changed towards the recommendations in the CPG. Objective: To investigate the use of the 2018 clinical practice guidelines for EARR among orthodontists 3 years after its introduction. Methods: A questionnaire using a 7-point Likert scale was developed concerning four domains of EARR described in the guideline. The questionnaire was piloted, finalised, and then distributed digitally among Dutch orthodontists. REDCap was used for data collection, starting with an invitation email in June 2021, followed by two reminders. Effect was tested by the Mann–Whitney U test, and the influence of demographic variables was analysed. Results: Questionnaires were sent out to all 275 and completed by 133 (response rate 48%); N = 59 females and N = 73 males were included; 81% had their training in the Netherlands, 89% had ≥ 6 years of work experience, and 89% worked in private orthodontic practice. One hundred thirty orthodontists (98.5%) reported changes in clinical practice. The biggest positive change in clinical behaviour regarding EARR occurred if EARR was diagnosed during treatment. Sex, clinical experience, country of specialist training, and working environment of the respondents did not affect clinical practices regarding EARR. Conclusions: This questionnaire demonstrated that, 3 years after introduction of the guideline, orthodontists improved their self-reported clinical practices to a more standardised management of root resorption. None of the demographic predictors had a significant effect on the results. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. Methods: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Results: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. Conclusions: The results of this paper show that the occurrence of irAEs is associated with patients’ OS. irAEs occurrence can prolong patients’ OS. irAEs occurrence may serve as a surrogate marker for ICIs. [ABSTRACT FROM AUTHOR]

Purpose: Owing to the pharmacological mechanism, sodium–glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects. Results: Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was − 141.34 mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo. Conclusion: For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits. [ABSTRACT FROM AUTHOR]

The recreational use of cannabis products has risen considerably worldwide over the past decade. As the cannabis legal market grows, a critical challenge has been to make substantiated claims about the benefits and adverse health problems triggered by cannabis exposure. Despite accumulating evidence from animal studies demonstrating the role of cannabinoids on bone metabolism, there are conflicting results in clinical literature regarding their effects on bone health outcomes. We undertook a systematic review to assess the evidence for the safety of cannabis use on bone health. We searched the databases MEDLINE, EMBASE, Cochrane Library, and Web of Science up to March 2023 for studies evaluating the effect of the recreational use of cannabis on the bone mineral density (BMD) of adults. Among the 2620 studies reviewed, three cross-sectional studies and one randomized controlled trial comprised 4032 participants from 18 to 60 years who met the inclusion criteria. Two studies showed that cannabis exposure decreased BMD, while the other 2 indicated no alteration. Despite the different study designs, the included studies showed a low risk of bias according to the Joanna Briggs Institute tool. Eligible studies present differences in cannabis products, administration routes, and exposure determination. Further longitudinal research is needed to establish multiple clinical predictors associated with potentially negative consequences of cannabis exposure, especially in vulnerable populations such as elderly individuals. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by a comprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. Methods: A total of 314 prostate cancer patients (age ≥ 65 years) undergoing definitive radiotherapy at a tertiary academic center were included. Prior to treatment, patients underwent a GA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. Results: A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37 patients (11.8%) and rectal toxicity in 8 patients (2.5%), respectively. Multivariable analysis revealed a significant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260–5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017–4.625; p = 0.045 and OR 7.220, 95%CI 1.227–42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004–0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028–0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045–20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. Conclusion: Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has been a major challenge worldwide for the past years with high morbidity and mortality rates. While vaccination was the cornerstone to control the pandemic and disease spread, concerns regarding safety and adverse events (AEs) have been raised lately. A cross-sectional study was conducted between January 1st and January 22nd, 2022, in six Arabic countries namely Saudi Arabia, Egypt, Syria, Libya, Iraq, and Algeria. We utilized a self-administered questionnaire validated in Arabic which encompassed two main parts. The first was regarding sociodemographic data while the second was about COVID-19 vaccination history, types, doses, and experienced AEs. A multistage sampling was employed in each country, involving the random selection of three governorates from each country, followed by the selection of one urban area and one rural area from each governorate. We included the responses of 1564 participants. The most common AEs after the first and second doses were local AEs (67.9% and 46.6%, respectively) followed by bone pain and myalgia (37.6% and 31.8%, respectively). After the third dose, the most common AEs were local AEs (45.7%) and fever (32.4%). Johnson and Johnson, Sputnik Light, and Moderna vaccines showed the highest frequency of AEs. Factors associated with AEs after the first dose included an increase in age (aOR of 61–75 years compared to the 12–18 years group: 2.60, 95% CI: 1.59–4.25, p = 0.001) and male gender (OR: 0.72, 95% CI: 0.63–0.82, p < 0.001). The cumulative post-vaccination COVID-19 disease was reported with Sinovac (16.1%), Sinopharm (15.8%), and Johnson and Johnson (14.9) vaccines. History of pre-vaccination SARS-CoV-2 infection significantly increases the risk of post-vaccination COVID-19 after the first, second, and booster doses (OR: 3.09, CI: 1.9–5.07, p < 0.0001; OR: 2.56, CI: 1.89–3.47, p < 0.0001; and OR: 2.94, CI: 1.6–5.39, p = 0.0005 respectively). In conclusion, AEs were common among our participants, especially local AEs. Further extensive studies are needed to generate more generalizable data regarding the safety of different vaccines. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them. Materials and methods: This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded. Results: Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day. Conclusions: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly. Critical relevance statement: Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice. Key points: • The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%. • Patients were more likely to have AEs in abdominal applications than superficial ones. • Severe AEs are life-threatening and need prompt identification and treatment. • We summarized some detailed suggestions for clinical prevention and treatment of AEs. [ABSTRACT FROM AUTHOR]

Background: Although the severity of coronavirus disease 2019 (COVID-19) tends to be lower in children, it can still lead to severe illness, particularly among those with chronic medical conditions. While remdesivir (RDV) is one of the few approved antiviral treatments for COVID-19 in children in many countries, the available data on the safety of RDV in this population is limited. Methods: To address this knowledge gap, a multicenter study involving 65 patients retrospectively analyzed the clinical data from individuals aged <18 who were hospitalized due to severe COVID-19 (defined as SpO2 < 94% or requiring supplemental oxygen) and received at least one dose of RDV. Additionally, the study encompassed 22 patients with mild-moderate COVID-19 who were considered at high risk of developing severe disease. Results: Nineteen children (29%) experienced mild-to-moderate adverse events (AEs) attributed to RDV, including transaminitis in 20% of children, bradycardia in 8%, and hypotension in 5%. AEs did not require discontinuation of RDV, except in one patient who developed premature ventricular contractions. The rate of AEs did not differ between patients with severe COVID-19 and those with mild-moderate COVID-19 but at high risk for severe disease. All but one patient were discharged within 23 days of admission, and no fatalities were recorded. Among high-risk patients with mild-moderate disease, only 2 (9%) progressed to the point of needing supplemental oxygen. Conclusions: Our data suggests that RDV is safe in children, with no reported serious AEs. However, the absence of a control group limits the extent to which conclusions can be drawn. RDV may contribute to clinical improvement, particularly in high-risk patients. [ABSTRACT FROM AUTHOR]

Purpose: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. Methods: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). Results: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2–3.2)) and distal occlusion locations (aOR 2.2 (95% CI 1.3–3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23–0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. Conclusion: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk. [ABSTRACT FROM AUTHOR]

Adverse conditions in weather, economy and diseases are perceived universally leading to the global food-insecurity. Homegardens could play a crucial role in building resilience at the household level to cope with these extremities to minimize food-insecurity. Since homegardens in the existing forms are not efficiently utilized in this regard, identify hindering factors and overcome them are vital. In this context, two administrative districts in Sri Lanka, Matale and Jaffna were selected as cases having diversified and unique homegardens, respectively, and K-means cluster analyses were performed to group homegardens. The variables important for grouping homegardens were identified through discriminant function analysis. The characteristics of the identified variables were used to differentiate groups of homegardens, where those groups in the two districts could be described by socio-economic and ecological variables. The mean annual income of better groups of homegardens in Matale and Jaffna was 39,341 LKR and 31,609 LKR, respectively. Results revealed that the common factors that hinder efficient utilization of homegardens in two districts were insufficient amounts of food sources, lack of productive and income-generating trees species, inability to incorporate annual and perennial crops without altering existing environment, absence of poultry or livestock, labor shortage, low investment and insufficient technical knowledge on farming. Accordingly, households interacted with homegardens at varying levels of absorptive and adaptive capacities in building resilience. Therefore, consideration of correct blend of floral and faunal components and the variables that strengthen the capacity and efficiency of homegardens to cope with extreme situations is a key to minimize food-insecurity. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. Subsequently, understanding the underlying mechanisms that lead to the development of CIPN is essential for finding better pharmacological therapy. Therapy-induced senescence (TIS) is a form of senescence that is triggered in malignant and non-malignant cells in response to the exposure to chemotherapy. Recent evidence has also suggested that TIS develops in the dorsal root ganglia of rodent models of CIPN. Interestingly, several components of the senescent phenotype are commensurate with the currently established primary processes implicated in the pathogenesis of CIPN including mitochondrial dysfunction, oxidative stress, and neuroinflammation. In this article, we review the literature that supports the hypothesis that TIS could serve as a holistic mechanism leading to CIPN, and we propose the potential for investigating senotherapeutics as means to mitigate CIPN in cancer survivors. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33–0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83–1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55–1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82–3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17–3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88–4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00–1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02–1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81–1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75–1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Purpose: Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. Methods: We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. Results: We identified 103 patients meeting eligibility criteria with median follow-up of 92 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46 mg/dL (95% CI − 77 to − 15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22). Conclusions: SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) have attracted global interest because they have been recognized as emerging pollutants that require urgent attention. MPs are plastic particles with a size between 1 micron and 5 mm (1 µm-5mm); those measuring less than 1 µm are known as nanoplastics (NPs). MP is distributed in the environment in various physical forms that depend on the degradation process, the erosion factors to which it was subjected, or the original form in which it was intentionally manufactured. Humans may be exposed to these pollutants mainly by ingestion or inhalation, which could adversely affect human health with effects that are still unknown due to limitations that are often dependent on their analytical determination and lack of studies over time, as it is a relatively new topic. Therefore, this review focuses on the challenges currently faced by laboratories for determining MPs in different matrices. We highlight the application of methods and techniques to assess the precise levels of exposure to MPs in biological samples. In addition, exposure pathways, sources, and evidence of adverse effects reported in vitro and in vivo studies are described to generate knowledge about their potential threat to human health. [ABSTRACT FROM AUTHOR]

Use of glucocorticoid in various diseases including rheumatology and respiratory diseases is on the rise because of its prompt beneficial effects. This culminates in osteoporosis and fragility fractures. Judicious use of glucocorticoid hence calls for attention with regard to the dose schedule, route of administration and accompanying enhancing factors. Institution of proper therapeutic management as per WHO risk stratification with anabolic and/or resorptive drugs like bisphosphonates, teriparatide or denosumab is necessary to prevent the eventuality of fragility fractures. Even otherwise, knowledge of glucocorticoid, its metabolism, various dose schedules, adverse effects are areas worth discussing. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the safety and effectiveness of high-dose-rate brachytherapy as a treatment modality for recurrent or residual neck metastatic lymph nodes following external radiotherapy. Methods: 38 patients with 52 metastatic lymph nodes recurring or residual after previous external radiotherapy was completed to metastatic lymph nodes in the neck were collected from January 2019 to February 2022. High-dose-rate brachytherapy with 192Ir was performed with a prescribed dose of 20–30 Gy/1f (effective biological dose of 60–120 Gy), and imaging was performed at 1, 3, and 6 months after treatment to assess the local control rate and adverse effects of treatment. Results: All 38 patients received completed treatment, and they were followed up for 6 months. 52 patients with neck lymph node metastases had an objective response rate. (Complete response, CR + Partial response, PR) of 76.9%, which comprised 89.5% (34/38) for lymph nodes ≤ 3 cm and 42.9% (4/14) for > 3 cm, P = 0.028. P > 0.05 for CR + PR versus stable disease, SD + progressive disease, PD for lymph nodes between different subdivisions of the neck. Using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scoring System, there were 6 cases of acute radioskin injuries of degree I and 4 cases of degree II with a 60% symptomatic relief rate. Conclusions: High-dose-rate brachytherapy serves as a safe and effective method in treating recurrent residual neck metastatic lymph nodes in the field after external radiotherapy, exerting tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Public concerns about cyanotoxins production in water and its detrimental impacts on human and animal health are growing primarily due to the widespread eutrophication observed in aquatic ecosystems. A review of relevant literature was done to determine the degree of cyanotoxin occurrence and its harmful effects in African waterbodies. Data were extracted from 64 published studies from 1990 to 2022 that quantified the concentration of cyanotoxins in African aquatic ecosystems. Cyanotoxins have been reported in 95 waterbodies (29 lakes, 41 reservoirs, 10 ponds, 9 rivers, 5 coastal waters, and 1 irrigation canal) from 15 African countries. Cyanotoxins were documented in all the regions of Africa except the central region. Microcystins have been reported in nearly all waterbodies (98.9%), but anatoxin-a (5.3%), cylindrospermopsin (2.1%), nodularins (2.1%), homoanatoxin-a (1.1%), and β-N-methylamino-l-alanine (1.1%) were encountered in a small number of water ecosystems, homoanatoxin-a and β-N-methylamino-l-alanine each occurred in one waterbody. The largest concentrations of microcystins and nodularins were reported in South African Lakes Nhlanganzwani (49,410 μg L−1) and Zeekoevlei (347,000 μg g−1). Microcystin concentrations exceeding the WHO guideline for lifetime drinking water (1 μg L−1) were reported in 63% of the aquatic ecosystems surveyed. The most frequently reported toxin-producing cyanobacteria genus is Microcystis spp. (73.7%), followed by Oscillatoria spp. (35.8%) and Dolichospermum spp. (33.7%). Cyanotoxin-related animal mortality and human illness were reported in the continent. Consequently, it is necessary to regularly monitor the level of nutrients, cyanobacteria, and cyanotoxins in African waterbodies in an integrated manner to devise a sustainable water resources management. [ABSTRACT FROM AUTHOR]

Objective: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. Methods: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. Results: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months—p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months—p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. Conclusion: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP). Methods: This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician's Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed. Results: 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from − 14.6% (95% confidence interval [CI]: − 31.5%, 2.2%) to − 5.3% (95% CI: − 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference − 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo. Conclusion: The primary objective to demonstrate a non-flat dose–response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518). Plain Language Summary: A clinical trial of spesolimab for patients with palmoplantar pustulosis. Palmoplantar pustulosis (PPP) is a painful, difficult-to-treat skin disease that is found on patients' palms and the soles of their feet. In this clinical trial, we studied an injected medicine called spesolimab for treating patients with PPP. Patients were split into five groups; four groups received different doses of spesolimab and one received placebo (an injection without spesolimab). After 16 weeks, patients receiving placebo switched to spesolimab. We measured the body area affected by PPP and how severe PPP was at week 16. Patients' doctors also assessed skin affected by PPP. At 16 weeks of treatment, there was no significant difference between spesolimab and placebo in terms of the PPP-affected area and severity. However, more patients had clear or almost clear skin with spesolimab than placebo. Among non-Asian patients, more showed an improvement in their PPP with spesolimab than with placebo; this was not the case with Asian patients. Patients taking spesolimab or placebo reported side effects, of which the most common were colds, aches and headaches. More patients receiving spesolimab reported a reaction at the injection site compared with placebo. We monitored patients for up to 1 year, and results remained similar. We showed that spesolimab may have a modest effect on the body area affected by PPP, as well as the severity of PPP, and did not seem to cause more side effects than placebo, except for reactions at the injection site. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship. [ABSTRACT FROM AUTHOR]

Opinion statement: Opioid-induced neurotoxicity (OINT) is a neuropsychiatric syndrome observed with opioid therapy. The mechanism of OINT is thought to be multifactorial, and many risk factors may facilitate its development. If symptoms of OINT are seen, the prescriber should consider hydration, discontinuation of the offending opioid drug, or switching of opioid medication, or the use of some adjuvants. Multiple factors like inter- and intraindividual differences in opioid pharmacology may influence the accuracy of dose calculations for opioid switching. Experience and clinical judgment in a specialistic palliative care setting should be used and individual patient characteristics considered when applying any conversion table. [ABSTRACT FROM AUTHOR]

Background: Effective delirium prevention could benefit from automatic risk stratification of older inpatients using routinely collected clinical data. Aim: Primary aim was to develop and validate a delirium prediction model (DELIKT) suitable for implementation in hospitals. Secondary aim was to select an anticholinergic burden scale as a predictor. Method: We used one cohort for model development and another for validation with electronically available data collected within the first 24 h of admission. Included were patients aged ≥ 65, hospitalised ≥ 48 h with no stay > 24 h in an intensive care unit. Predictors, such as administrative and laboratory variables or an anticholinergic burden scale, were selected using a combination of feature selection filter method and forward/backward selection. The final model was based on logistic regression and the DELIKT was derived from the β-coefficients. We report the following performance measures: area under the curve, sensitivity, specificity and odds ratio. Results: Both cohorts were similar and included over 10,000 patients each (mean age 77.6 ± 7.6 years) with 11% experiencing delirium. The model included nine variables: age, medical department, dementia, hemi-/paraplegia, catheterisation, potassium, creatinine, polypharmacy and the anticholinergic burden measured with the Clinician-rated Anticholinergic Scale (CrAS). The external validation yielded an AUC of 0.795. With a cut-off at 20 points in the DELIKT, we received a sensitivity of 79.7%, specificity of 62.3% and an odds ratio of 5.9 (95% CI 5.2, 6.7). Conclusion: The DELIKT is a potentially automatic tool with predictors from standard care including the CrAS to identify patients at high risk for delirium. [ABSTRACT FROM AUTHOR]

Objectives : Examination of patients claiming adverse effects from dental materials can be very challenging. Particularly, systemic aspects must be considered besides dental and orofacial diseases and allergies. Therefore, the aim of this study was to investigate a cohort of 687 patients reporting on adverse effects from dental materials focusing on findings related to known general diseases or conditions or medication-related findings with relevance to their subjective complaints. Methods: Six hundred eighty-seven patients visiting a specialized consultation on claimed adverse effects from dental materials were retrospectively investigated for their subjective complaints, findings related to known general diseases or conditions, medication-related findings, dental and orofacial findings, or allergies with relevance to their subjective complaints. Results: The most frequent subjective complaints were burning mouth (44.1%), taste disorders (28.5%), and dry mouth (23.7%). In 58.4% of the patients, dental and orofacial findings relevant to their complaints could be found. Findings related to known general diseases or conditions or medication-related findings were found in 28.7% or 21.0% of the patients, respectively. Regarding medications, findings related to antihypertensives (10.0%) and psychotropic drugs (5.7%) were found most frequently. Relevant diagnosed allergies toward dental materials were found in 11.9%, hyposalivation in 9.6% of the patients. In 15.1% of the patients, no objectifiable causes for the expressed complaints could be found. Conclusions: For patients complaining of adverse effects from dental materials, findings related to known general diseases or conditions and medications should be given particular consideration, while still in some patients, no objectifiable causes for their complaints can be found. Clinical relevance: For patients complaining about adverse effects from dental materials, specialized consultations and close collaboration with experts from other medical fields are eligible. [ABSTRACT FROM AUTHOR]

Purpose of Review: Long-term outcomes have significantly improved with treatment of chronic myeloid leukemia. With proper treatment, most patients will achieve similar survival rates compared to an age-matched population. Treatment-free remission is not attainable for over half of patients and chronic treatment carries with it unique challenges. We provide a pragmatic approach to the monitoring and management of chronic adverse effects (AEs). Recent Findings: In the presence of severe or intolerable AEs, switching tyrosine kinase inhibitors (TKIs) is reasonable but is not without risk. Dose reductions can be attempted when response is stable to reduce AE intensity. More frequent molecular monitoring with any change is essential. Summary: Treatment strategies must adapt to the personalized treatment goal of each patient. Long-term survival remains good even when response is less than a complete molecular response. Consider risks of new AEs when changing therapy and evaluate for dose reductions when appropriate. [ABSTRACT FROM AUTHOR]

Background: The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. Materials and methods: A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. Results: The median follow-up was 49.5 months (26–67). Median age was 57 years (36–82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. Conclusions: Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control. [ABSTRACT FROM AUTHOR]