Search

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: This study aimed to evaluate the therapeutic efficacy and safety of injecting Type III collagen lyophilized fibers into the mid-to-deep layers of the facial dermis to ameliorate dynamic facial wrinkles. Methods: In this retrospective analysis, clinical data were collected from patients exhibiting dynamic facial wrinkles (encompassing frown lines, forehead lines, and crow's feet) with a wrinkle severity rating scale (WSRS) score of 3 or higher. In the control group, 75 participants received collagen implant injections into the mid-to-deep facial dermal layers, whereas 76 participants in the experimental group received injections of Type III collagen lyophilized fibers in similar layers. The study analyzed and compared clinical efficacy, WSRS score alterations, patient satisfaction, and safety profiles between the groups over the 30-day and 90-day treatment periods. Results: At the 30-day mark, the therapeutic efficacy was not significantly different between the two groups (P > 0.05). However, at 90 days, the treatment efficacy in the experimental group surpassed that in the control group, showing a statistically significant difference (P < 0.05). After 30 days of treatment, the WSRS score improvement in the experimental group was significantly superior to that in the control group (P < 0.05). Conversely, at the 90-day mark, the results revealed no significant variation in WSRS score improvements between the two groups (P > 0.05). Regarding treatment satisfaction among researchers and participants post-30 and 90-day treatment in both groups, no statistically significant differences were observed (P > 0.05). Similarly, the incidence of adverse reactions between the groups was not statistically significant (P > 0.05). Conclusions: Injections of lyophilized type III collagen fibers into the mid-to-deep layers of the facial dermis have a definitive therapeutic effect on dynamic facial wrinkles. This treatment not only substantially diminishes wrinkle severity but also has a commendable safety profile. Level of Evidence I: 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]

This review paper explores the history, cultural significance, and functional characteristics of soybean paste (doenjang) in Korean cuisine. In particular, it covers its origins, cultural importance, production methods, functionalities, and associated risks. This review delves into the nutritional and functional aspects of fermented soybean products, focusing on compounds in soybean paste linked to health benefits, such as anticancer, anti-obesity, anti-diabetic, and antithrombotic properties. The key bioactive compounds identified in soybean paste include total phenols, total flavonoids, γ-Aminobutyric acid, vitamin B group, and vitamin E. These compounds are primarily produced through microbial fermentation, which enhances their biological activity. Additionally, the review addresses potential risks such as biogenic amines, aflatoxins, Bacillus cereus contamination, and high sodium levels, and suggests methods for mitigating these risks. By synthesizing current research, this paper aims to provide a comprehensive understanding of the physiological compounds in soybean paste and their health benefits. It also highlights the need for strategies to reduce associated risks. [ABSTRACT FROM AUTHOR]

There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a "classic" serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin's potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders. [ABSTRACT FROM AUTHOR]

This article presents a comprehensive study on the formulation and physicochemical characterization of a novel terpenocannabinoid-functionalized hemp oil emulsifier (AMCana-Oil) for potential applications in topical anti-inflammatory, antinociceptive, and wound healing treatments. The emulsifier exhibits interesting properties, meets international acidity index requirements, and has a room temperature density comparable to liquid oils. The prepared emulsifier (AMCana-Oil), AMCana-Oil (10% TC) and AMCana-Oil (20% TC), contains a diverse array of cannabinoids, including cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), alongside bioactive compounds such as benzenepropanoic acid and oleamide. Physicochemical properties of AMCana-Oil and MCana-Oil (20% TC) were found, respectively, as follows: density value of 0.9872 ± 0.001 mg/mL: g/cm³ and 0.9882 ± 0.002 mg/mL: g/cm³; an acidity index of 1.599 ± 0.002 mgKOH/g and 1.605 ± 0.001 mgKOH/g; an average peroxide value encompassing a range from 12.982 ± 0.351 to 23.320 ± 0.681 (mEq O2/kg), and a K of 1.575 ± 0.004 and 1.535 ± 0.0039, which underscore the fluidity, stability, and quality of emulsifiers studied. Preliminary pharmacological examinations reveal significant antioxidant, anti-inflammatory, antinociceptive, and wound healing potentials. Moreover, in silico predictions confirm the safety profile of the prepared emulsifiers. These findings emphasize the multifaceted nature of the terpenocannabinoid-functionalized emulsifier, paving the way for its potential applications in topical formulations. [ABSTRACT FROM AUTHOR]

Background: The global surge in non-communicable diseases, like cancer, strains health systems financially and restricts patient access to treatment. Generic drugs offer comparable efficacy, safety, and quality to innovator drugs, improving patient access and well-being. To aid healthcare workers in selecting the best generic drugs, Generic drug Adoption Framework (GRAF) was developed as an evaluation tool. This paper aims to adapt the tool to Colombia for healthcare professional's daily use. Methods: Adapting the tool involved two phases: surveying healthcare workers (oncologists' specialists and pharmacists) to gauge their readiness for adopting generic drugs, additionally and expert consensus was developed to adapt the tool to the Colombian context. Results: Of 62 surveyed healthcare workers, 38.7% were early adopters and 32.3% were late adopters. Pharmacists showed higher early adoption rates (47%) than physicians (33%). In the second phase, experts identified 12 relevant attributes for the Colombian scenario, refining descriptions and scoring scales. Conclusion: The study revealed Colombian healthcare workers' perceptions of generic drugs and differences in adoption rates. The adapted tool to the Colombian healthcare context could clarify misconceptions that require diverse strategies to increase the use of generic drugs, aiding in better patient care. [ABSTRACT FROM AUTHOR]

Background: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring the safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. Methods: Randomized controlled trials assessing the safety of semaglutide vs. placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia, and new-onset neoplasm. Results: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. Conclusion: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Aim: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum‐resistant ovarian cancer (RPR‐OC) patients. Methods: This study retrieved 67 RPR‐OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. Results: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression‐free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5–6.3) months in apatinib + chemo group and 3.8 (2.0–5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5–24.5) months in apatinib + chemo group and 13.6 (8.6–18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). Conclusion: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR‐OC patients. [ABSTRACT FROM AUTHOR]

• The meta -analysis included 11 studies (7 RCTs and 4 cohort studies) with varied geographical representation and patient demographics. Most studies were rated as having low to moderate risk of bias. However, some outcomes displayed heterogeneity, which was addressed through sensitivity analyses to ensure robust results. • Clazosentan significantly reduces the incidence of vasospasm, including moderate to severe vasospasm, and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The risk ratios for vasospasm, moderate to severe vasospasm, and DCI were 0.49, 0.53, and 0.70 respectively, indicating a substantial reduction compared to placebo. • The use of clazosentan significantly lowers the need for rescue therapy among aSAH patients. The pooled analysis showed a risk ratio of 0.65, suggesting a 35 % reduction in the requirement for additional interventions. • Clazosentan is associated with increased rates of specific adverse events such as pulmonary complications (RR = 1.89), hypotension (RR = 2.47), and anemia (RR = 1.49). However, it does not increase the risk of hepatobiliary adverse events or cerebral hemorrhage. • Despite its efficacy in reducing vasospasm and DCI, clazosentan does not show a significant improvement in functional outcomes (measured by GOSE and mRS) or mortality rates. This suggests that while it mitigates certain complications, it does not necessarily enhance overall survival or recovery quality. Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality. We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software. A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta -analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34–0.70), moderate to severe vasospasm (R/R = 0.53: 0.46–0.61), DCI (R/R = 0.70: 0.59–0.82), and the need for rescue therapy (R/R = 0.65: 0.52–0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64–2.18), hypotension (R/R = 2.47: 1.79–3.42), and anemia (R/R = 1.49: 1.23–1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage. Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm. [ABSTRACT FROM AUTHOR]

Abstract This review paper explores the history, cultural significance, and functional characteristics of soybean paste (doenjang) in Korean cuisine. In particular, it covers its origins, cultural importance, production methods, functionalities, and associated risks. This review delves into the nutritional and functional aspects of fermented soybean products, focusing on compounds in soybean paste linked to health benefits, such as anticancer, anti-obesity, anti-diabetic, and antithrombotic properties. The key bioactive compounds identified in soybean paste include total phenols, total flavonoids, γ-Aminobutyric acid, vitamin B group, and vitamin E. These compounds are primarily produced through microbial fermentation, which enhances their biological activity. Additionally, the review addresses potential risks such as biogenic amines, aflatoxins, Bacillus cereus contamination, and high sodium levels, and suggests methods for mitigating these risks. By synthesizing current research, this paper aims to provide a comprehensive understanding of the physiological compounds in soybean paste and their health benefits. It also highlights the need for strategies to reduce associated risks.

Background. Small cell lung cancer (SCLC), predominantly due to smoking, is a highly differentiated, rapidly growing epithelial cell carcinoma of high malignancy originating from bronchial neuroendocrine cells. Almost 70% of SCLC patients have metastases at the time of diagnosis, which requires the use of drug therapies, including immunotherapy. Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with small cell lung cancer. Materials and methods. One hundred and twenty one patients (90 men and 31 women) aged 44 to 84 years were included in the retrospective multicentre non-randomised study. The majority (90.9%) of patients were treated in the 1st line of therapy. IT were administered in the 2nd line and subsequent lines of treatment in 9.1% of patients. Weakened (ECOG 2–3) state at the time of treatment initiation was noted in 30 (24.8%) patients. Results. Progression-free survival in patients with SCLC receiving 1st-line treatment was 5.82 (95% CI 3.92–7.72) months, and 2nd-line and beyond was 6.21 (95% CI 0.76–11.66) months. Survival in patients with small-cell lung cancer receiving 1st-line IT was 8.0 (95% CI 6.18–9.81) months, and 2nd-line or longer was 11.3 months (95% CI 4.31–18.29) months (p=0.108). Objective response was achieved in 43 (35.5%) patients, of whom 38 (34.5%) were on first-line IT and 5 (45.5%) patients were on 2nd or more. iAEs grade 3–4 was observed in only 18 (14.9%) patients. Conclusion. Immunotherapy for SCLC allows achieving high rates of objective response and disease control. This method of treatment is characterized by insignificant number of grade 3–4 immune-mediated adverse events, which indicates an acceptable safety profile.

Honggang Zhang,1 Huiling Li,1 Shuangjun Zhao,2 Fangping Bao1,2 1Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fangping Bao, Email baofp@zju.edu.cnAbstract: Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam’s applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.Keywords: remimazolam, clinical efficacy, general anesthesia, safety profile, respiratory depression

Abstract Background Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. Methods ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. Conclusions This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. Trial registration EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016.

Adoptive cell therapy represents a modern immunotherapeutic approach utilizing immune cells as dynamic agents against cancer cells, often called "living drugs". In recent times, chimeric receptor antigen T cell (CAR-T cell) therapy has shown efficacy and promise in the immunotherapy of cancers, presenting a significant advancement in blood cancer treatment. However, despite its effectiveness in treating B-cell lymphoma, challenges persist with response variability, resistance, and adverse effects. This review focuses on recent advances and current challenges, limitations, and the related preclinical and clinical findings of cancer immunotherapy as well as solutions for increasing the safety and effectiveness of CAR-T cell therapy. Ongoing research focuses on exploring molecular and cellular processes post-infusion, developing "universal CAR-T lymphocytes" sourced from healthy donors as well as exploring alternative candidates like CAR-armored NK cells and CAR-NKT cells, which show promise due to their potent anti-tumour properties and diverse cytotoxic capabilities. The interplay of genetics with the immune system undoubtedly holds the potential for developing innovative treatments that could revolutionize cancer therapy in the future.

Michael W Jung Wisconsin Spine and Pain, Sheboygan, WI, 53081, USACorrespondence: Michael W Jung, Wisconsin Spine and Pain, 2124 Kohler Memorial Drive Suite 110, Sheboygan, WI, 53081, USA, Email mjungmd@wispineandpain.comIntroduction: Minimally invasive sacroiliac (SI) joint fusion has become the mainstay treatment for chronic refractory sacroiliac joint dysfunction. Multiple procedures are now available including transfixing procedures with implants placed in the lateral or posterolateral transiliac trajectories, and intra-articular procedures with devices and/or allograft placed via a dorsal approach. To date, the published literature on the lateral approach has been primarily by surgeons. This retrospective chart review aims to evaluate the safety and preliminary effectiveness when the procedure is performed by physicians trained in interventional pain management.Methods: Retrospective analysis of patients who underwent lateral SI joint fusion using a lateral transiliac approach between December 2022 and September 2023 by a single physician. Data on demographics, perioperative details, complications, and postoperative outcomes were collected and analyzed. The study was reviewed by WCG IRB and received an exemption authorization.Results: Medical charts were reviewed for the first 49 consecutive cases performed. Mean (SD, range) age was 64 (11, 34– 83), BMI was 32.5 (8.4), 59% were female, 35% were smokers, and 82% were on opioids at baseline. Mean (SD) operative time was 40 (11) minutes and all procedures were performed at an ambulatory surgery center under monitored anesthesia care. No device- or procedure-related complications occurred. Mean follow up was 175 days; Mean (SD) baseline reported pain was 9 (1.5) on a 0– 10 numerical rating scale. At follow up, 88% of the patients reported ≥ 50% pain relief. Six patients who reported 0% relief suffer from multiple pain generators and are on long term opioids.Conclusion: Results of this single center experience support the safety of lateral SI joint fusion using a threaded implant when performed by interventional pain management physicians. However, further prospective studies with larger sample sizes and longer follow-ups are warranted to validate these findings.Keywords: sacroiliac joint fusion, safety profile, perioperative complications, postoperative outcomes

Abstract Background Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). Methods Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. Results 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events—CTCAE version 5.0) (RR: 1.61, 95% CI 1.19–2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004–2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416–0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. Conclusions Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings.

Abstract Objective This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. Methods This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. Results The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). Conclusion Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Background: Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. Methods: ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. Conclusions: This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. Trial registration: EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016. Highlights: ABTL0812 is a novel drug in clinical development that kills tumor cells by cytotoxic autophagy. The recommended phase 1/2 dose of ABTL0812 in combination with paclitaxel/carboplatin is 1300 mg three times a day (tid) by the oral route. The combination of ABTL0812 plus carboplatin and paclitaxel (CP) in patients with advanced/recurrent EC suggests an improved benefit-to-risk ratio vs. CP alone and warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

Chimeric marker vaccine candidates, vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, have been generated and their efficacy and capability to differentiate infected from vaccinated animals were confirmed in previous studies. The safety profile of the two chimeric marker vaccine candidates, particularly in the potential reversion to virulence, was evaluated. Each virus was administered to pigs with a dose equivalent to the vaccination dose, and pooled tonsil homogenates were subsequently inoculated into further pigs. Chimeric virus vGPE−/PAPeV Erns displayed the most substantial attenuation, achieving this within only two passages, whereas vGPE−/PhoPeV Erns was detectable until the third passage and disappeared entirely by the fourth passage. The vGPE− strain, assessed alongside, consistently exhibited stable virus recovery across each passage without any signs of increased virulence in pigs. In vitro assays revealed that the type I interferon-inducing capacity of vGPE−/PAPeV Erns was significantly higher than that of vGPE−/PhoPeV Erns and vGPE−. In conclusion, the safety profile of the two chimeric marker vaccine candidates was affirmed. Further research is essential to ensure the stability of their attenuation and safety in diverse pig populations. [ABSTRACT FROM AUTHOR]

Alopecia, a condition characterized by hair loss, affects a significant portion of the population and has various psychological and physical impacts. This review article explores the efficacy and safety of herbal treatments for alopecia, integrating traditional knowledge with contemporary scientific research. The article examines various herbal remedies used across cultures, such as Saw Palmetto, Ginseng, Green Tea, and Phyllanthus Emblica, delving into their bioactive compounds and mechanisms of action. Studies and case reports, adhering to APA citation style, highlight the potential of these natural remedies in promoting hair growth and managing different types of alopecia. The review also addresses the safety profile and toxicological considerations of these herbal treatments, underscoring the importance of comprehensive evaluations and standardized dosages. The integration of herbal treatments with conventional therapies is discussed as a promising avenue for enhancing treatment outcomes. The article concludes by emphasizing the need for more rigorous clinical trials, exploration of new herbal compounds, and the development of standardized, safe herbal formulations for alopecia treatment. [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium (POD) and cognitive dysfunction (POCD) are common complications following thoracic surgery, particularly in patients aged 65 years and above. These complications can significantly affect recovery and increase healthcare costs. This study investigates the effects of low-dose S-ketamine on reducing POD and POCD in this patient demographic. Methods: In this retrospective cohort study, medical records of patients aged ≥ 65 years who underwent elective thoracic surgery from January 2019 to August 2023 were reviewed. Patients were categorized into S-ketamine and Control groups based on intraoperative S-ketamine exposure. POD was assessed using the Confusion Assessment Method (CAM), while cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline, 1 week, 1 month, and 6 months post-surgery. Intraoperative and postoperative parameters, including hemodynamic stability, blood loss, pain scores, and ICU stay length, were also recorded. Results: The study comprised 140 participants, with 70 in each group. The S-ketamine group demonstrated a significantly lower incidence of POD at 7 days post-surgery (12.0% vs. 26.7%, P < 0.001), and reduced POCD at 1 month (18.7% vs. 36.0%, P < 0.05) and 6 months (10.7% vs. 21.3%, P < 0.05). The Ketamine group had a significantly higher median MoCA score compared to the Control group both at 1 month (P = 0.021) and 6 months (P = 0.007). Adverse events, such as infection, bleeding, and respiratory failure, showed no significant differences between the groups, suggesting a safe profile for S-ketamine. Conclusion: Administering low-dose S-ketamine during thoracic surgery in patients aged 65 years and above significantly reduces the incidence of POD and POCD, highlighting its neuroprotective potential. These findings advocate for the inclusion of S-ketamine in anesthetic protocols to improve postoperative outcomes and reduce healthcare costs in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted. Methods: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study. Results: For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4–50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1–25.0% and 30.8%). Serious AEs were reported for 2.8–8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue. Conclusions: Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications. Trial Registration: ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896. Plain Language Summary: Unintended movements are often the first sign of Huntington disease. This type of unintended movement is called chorea in Huntington disease. Tardive dyskinesia causes unintended body movements. Deutetrabenazine is a medicine used to treat both types of movements. This report summarizes deutetrabenazine safety across five clinical studies. Safety was assessed via adverse events (side effects). Adverse events were compared between deutetrabenazine and inactive treatment (placebo). Serious adverse events were also compared. Serious adverse events cause substantial impairment or disruption. In tardive dyskinesia and chorea in Huntington disease studies, most patients kept taking deutetrabenazine. Adverse events were not a common reason to stop treatment. For tardive dyskinesia, adverse event rates were similar between deutetrabenazine (≤ 60%) and placebo (54%). Serious adverse event rates were also similar for deutetrabenazine (≤ 8%) and placebo (7%). Adverse events tended to be reported earlier in treatment. Common adverse events were headache, sleepiness, nausea, anxiety, fatigue, dry mouth, and diarrhea. For chorea in Huntington disease, adverse event rates were similar for deutetrabenazine (64%) and placebo (60%). Serious adverse event rates were also similar for deutetrabenazine (2%) and placebo (2%). Irritability, fall, depression, dry mouth, and fatigue were common adverse events. Adverse events were similar between deutetrabenazine and placebo in both conditions. Deutetrabenazine was well tolerated for patients with either tardive dyskinesia or chorea in Huntington disease. [ABSTRACT FROM AUTHOR]

Background: Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs). Methods: Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed. Results: 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events—CTCAE version 5.0) (RR: 1.61, 95% CI 1.19–2.19, I2 = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004–2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416–0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate. Conclusions: Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. Methods: This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. Results: The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). Conclusion: Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians. [ABSTRACT FROM AUTHOR]

Background: Suction blister epidermal grafting (SBEG) is currently one of the most prevalent surgical methods for stable vitiligo. Objective: To investigate the long-term outcomes of vitiligo patients who underwent SBEG and to explore risk factors associated with postoperative relapse. Methods: A retrospective cohort study was conducted in patients who underwent SBEG in our department between January 2016 and December 2022. Treatment outcomes, including repigmentation rate, adverse events, and postoperative relapse, were surveyed via telephone interview or out-=patient visit. Multivariate logistic regression models were used to assess the potential risk factors for postoperative relapse. Statistical significance was assumed at P <.05. Results: A total of 253 patients were included with a repigmentation rate of 96% (243/253) after grafting. Common adverse events included cobblestone-like appearance (73.1%, 185/253) in the donor site, perigraft halo (46.2%, 117/253), and cobblestone-like appearance (26.1%, 66/253) in the recipient site. Postoperative relapse occurred in 20.1% of patients over a mean time of 29.7 months after grafting. Nonsegmental type of vitiligo and coexistence of autoimmune diseases were risk factors for postoperative relapse. Conclusion: SBEG is an effective surgical treatment for vitiligo with high repigmentation rate and good safety profile. Nonsegmental vitiligo and comorbid autoimmune diseases may increase the risk of postoperative relapse. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Introduction Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted. Methods For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study. Results For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4–50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1–25.0% and 30.8%). Serious AEs were reported for 2.8–8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue. Conclusions Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications. Trial Registration ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896.

Abstract The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = − 22.07 mg/dl (95% CI − 27.17, − 16.97), HbA1c [MD = − 0.53% (95% CI − 0.67, − 0.38)], HOMA-IR [MD = − 1.26 (95% CI − 2.16, − 0.37)], and fasting insulin [MD = − 19.83 pmol/L (95% CI − 29.54, − 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D. PROSPERO registration no. CRD42023412603.

Central Illustration. Abbreviation: RSV – Respiratory Syncytial Virus. [Display omitted] • Simultaneous vaccination against RSV and Influenza virus among high-risk heart failure patients is safe. • Only small percentage of patients experienced reactions severe enough to prevent daily activities. • Simultaneous vaccination reduces patients contact with healthcare. The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events. [ABSTRACT FROM AUTHOR]

Background: Ureteric stones, characterized by the crystallization of mineral particles in stagnant urine, cause considerable discomfort and pain. Alpha-blockers are employed in the management of ureteric stones to alleviate symptoms by dilating the ureter and facilitating stone passage. Alpha-blockers have proven to be effective in improving the clinical outcomes of patients with ureteric stones, with Silodosin, Alfuzosin, and Tamsulosin emerging as promising options. Aim and Objectives: This study aims to evaluate the effectiveness and safety of Silodosin, Alfuzosin, and Tamsulosin in treating ureteric stones. It assesses their performance in patients at a Tertiary Care Hospital, aiming to identify the most suitable alpha-blocker for optimum outcomes. Materials and Methods: The study involved 60 patients with ureteral stones treated at the Urology Department of Dhiraj Hospital. Patients' responses to a structured questionnaire assessing variables related to ureteric stone development were collected. Physical examinations, along with radiological confirmation through X-ray, Ultrasound (USG), and CT-scan, were conducted. A 15-day follow-up assessed the efficacy of alpha-blockers. Statistical analysis and paired t-tests were employed to compare the drugs' effectiveness. Results: Silodosin demonstrated the highest stone expulsion rate at 95%, whereas Tamsulosin exhibited a 50% rate, and Alfuzosin recorded a 10% rate. Minimal side effects were observed, such as nausea, vomiting, and diarrhea, which were typical for patients with ureteric stones. Conclusion: Silodosin emerged as the most effective alpha blocker for promoting stone expulsion and ameliorating ureteric stone symptoms when compared to Tamsulosin and Alfuzosin. It is considered a pharmacologically superior choice for patients with ureteric stones, making it a valuable option in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. Materials and Methods: We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Results: Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. Conclusions: The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice—lovastatin—is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bebtelovimab (BEB), Tixagevimab/Cilgavimab (TIX/CIL), and Sotrovimab (SOT) are important agents against the severe acute respiratory syndrome coronavirus 2-Omicron strain. However, due to their short duration of application, little is known about their safety profiles. This research aimed to explore the safety profile of these monoclonal antibodies (mAbs) via real-world evidence databases and data mining tools. MATERIALS AND METHODS: Safety reports were retrieved from the database of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System from April 2022 to March 2023. To detect the safety signal, the disproportionality analysis was performed using the reporting odds ratio method. RESULTS: SOT had the greatest proportion of "skin and subcutaneous tissue disorders" and "disorders of investigations"; BEB showed significant associations with "gastrointestinal disorders" and "nervous system disorders"; TIX/CIL had the weakest correlation with "skin and subcutaneous tissue disorders" and "general disorders and administration site conditions". Furthermore, there were still other signals related to nervous system disorders, gastrointestinal disorders only caused by BEB. TIX/CIL has been reported solely to be associated with multiple types of cardiovascular disorders. As for SOT alone, signals were strongly related to infusion reactions and hypersensitivity. CONCLUSIONS: In summary, SOT may be unsuitable for allergic patients and may lead to abnormal test results. BEB showed the highest correlations with gastrointestinal and neuropsychiatric events. In addition, its infusion reactions should also be noted. TIX/CIL can lead to a variety of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Despite the approval of tremelimumab in 2022, there is a lack of pharmacovigilance studies investigating its safety profile in real-world settings using the FDA Adverse Event Reporting System (FAERS) database. Aim: This pharmacovigilance study aimed to comprehensively explore the adverse events (AEs) associated with tremelimumab using data mining techniques on the FAERS database. Method: The study utilized data from the FAERS database, covering the period from the first quarter of 2004 to the third quarter of 2022. Disproportionality analysis, the Benjamini Hochberg adjustment method and volcano plots were used to identify and evaluate AE signals associated with tremelimumab. Results: The study uncovered 233 AE cases associated with tremelimumab. Among these cases, pyrexia (n = 39), biliary tract infection (n = 23), and sepsis (n = 21) were the three main AEs associated with tremelimumab use. The study also investigated the system organ classes associated with tremelimumab-related AEs. The top three classes were gastrointestinal disorders (17.9%), infections and infestations (16.6%), and general disorders and administration site infections (11.2%). Several AEs were identified that were not listed on the drug label of tremelimumab. These AEs included pyrexia, biliary tract infection, sepsis, dyspnea, infusion site infection, hiccup, appendicitis, hypotension, dehydration, localised oedema, presyncope, superficial thrombophlebitis and thrombotic microangiopathy. Conclusion: This pharmacovigilance study identified several potential adverse events signals related to tremelimumab including some adverse events not listed on the drug label. However, further basic and clinical research studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Objectives and Aim: The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures. Materials and Methods: This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro–Wilk, independent t-test, Mann–Whitney U test, and chi-square test, with a significance threshold of p < 0.05. Results: Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups (p = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group (p < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; p = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; p = 0.045). Conclusion: This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile. [ABSTRACT FROM AUTHOR]

The acute toxicity study is a crucial component of preclinical toxicology assessments conducted to evaluate the potential adverse effects of a substance or compound on albino rabbits. This study provides key findings and implications of an acute toxicity study of natural and synthetic polymers that are used in the preparation of transdermal microneedle patches (TMNPs) for sustained delivery of doxazocin mesylate. In this study, we divided the albino rabbits into three equal groups (n = 6). Group-I was labeled as a control group and group-II was treated with TMNPs-1 (HPMC, maltose) and group-III was treated with TMNPs-2 (PLGA, polyvinyl acetate). The results obtained from feed consumption, hematology profile, biochemical studies, vital organ weight, and histopathological changes in vital organs were compared with the control group, and proved the safety profile of the polymers involved in the fabrication of microneedle patches. Mechanical strength and dermal safety study established the facts about the safety of microneedle patches and potential risks to health as a carrier system for the delivery of drugs into the systemic circulation directly. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Adoptive cell therapy represents a modern immunotherapeutic approach utilizing immune cells as dynamic agents against cancer cells, often called “living drugs”. In recent times, chimeric receptor antigen T cell (CAR-T cell) therapy has shown efficacy and promise in the immunotherapy of cancers, presenting a significant advancement in blood cancer treatment. However, despite its effectiveness in treating B-cell lymphoma, challenges persist with response variability, resistance, and adverse effects. This review focuses on recent advances and current challenges, limitations, and the related preclinical and clinical findings of cancer immunotherapy as well as solutions for increasing the safety and effectiveness of CAR-T cell therapy. Ongoing research focuses on exploring molecular and cellular processes postinfusion, developing “universal CAR-T lymphocytes” sourced from healthy donors as well as exploring alternative candidates like CAR-armored NK cells and CAR-NKT cells, which show promise due to their potent antitumor properties and diverse cytotoxic capabilities. The interplay of genetics with the immune system undoubtedly holds the potential for developing innovative treatments that could revolutionize cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Until now, research has been performed mainly in men, with a low recruitment of women; consequentially, biological, physiological, and physio-pathological mechanisms are less understood in women. Obviously, without data obtained on women, it is impossible to apply the results of research appropriately to women. This issue also applies to medical devices (MDs), and numerous problems linked to scarce pre-market research and clinical trials on MDs were evidenced after their introduction to the market. Globally, some MDs are less efficient in women than in men and sometimes MDs are less safe for women than men, although recently there has been a small but significant decrease in the sex and gender gap. As an example, cardiac resynchronization defibrillators seem to produce more beneficial effects in women than in men. It is also important to remember that MDs can impact the health of healthcare providers and this could occur in a sex- and gender-dependent manner. Recently, MDs' complexity is rising, and to ensure their appropriate use they must have a sex–gender-sensitive approach. Unfortunately, the majority of physicians, healthcare providers, and developers of MDs still believe that the human population is only constituted by men. Therefore, to overcome the gender gap, a real collaboration between the inventors of MDs, health researchers, and health providers should be established to test MDs in female and male tissues, animals, and women. [ABSTRACT FROM AUTHOR]

Copyright of Remedia is the property of Medical Tribune CZ, s.r.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pregnant women manifest an increased risk of developing coagulation disorders. Unfractionated heparin (HEP) and low-molecular-weight heparin (LMWHep) are considered as selective medication in the case of pregnancy which needs anticoagulant treatment. In addition to anticoagulant properties, HEP and its derivatives manifest other properties including anti-cancer potential. According to Globocan’s latest data, colorectal cancer (CRC) is the second most encountered form of malignancy in the case of women, manifesting some special particularities, as confusion of symptoms from cancer with symptoms encountered normally in pregnant women (such as constipation or rectal bleeding), delayed diagnosis because of limitations imposed both for the fetus and for the mother, and the need for special treatment.

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to compare the safety and efficacy of treatment using simple prostatectomy (SP) and using photoselective vaporization of the prostate (PVP) with a 180W GreenLight XPS laser in patients with high-volume prostate hypertrophy. Material and methods The study included 120 patients with LUTS symptoms caused by prostatic enlargement of more than 80 ml; 79 patients were treated with SP, while 41 were treated with PVP. The analysis included subjective the International Prostate Symptom Score (IPSS) and Quality of Life (QoL), and objective (Qmax), (Qave), and post-void residual volume (PVR) parameters before treatment and at an average of 38 months after surgical treatment. Early and late adverse effects and length of hospitalisation were assessed. Complication reports were performed according to the modified Clavien-Dindo system. Results The analysis independently showed the effectiveness of both methods. Subjective parameters (IPSS, QoL), showed no significant differences. Patients treated with SP scored slightly better on objective parameters (Qmax, Qave, and PVR). Analysis of adverse effects and hospitalisation time were more favourable after PVP. Conclusions SP and PVP were found to be comparable and highly effective in treating benign prostatic hyperplasia in terms of IPSS and QoL. Patients treated with the SP method obtained slightly better results of objective parameters such as Qmax, Qave, and PVR. Compared with SP, PVP has a more favourable safety profile. [ABSTRACT FROM AUTHOR]

Background: Neonatal hyperbilirubinemia remains a common clinical challenge. Phototherapy is a primary intervention, but its impact on bilirubin and electrolyte levels, as well as its safety profile, needs ongoing evaluation. Objective: To assess the changes in bilirubin and electrolyte levels in neonates undergoing phototherapy and to evaluate its safety profile. Methods: A prospective study involving 100 term neonates subjected to phototherapy. Bilirubin and electrolyte levels were measured at various durations, and adverse effects were monitored. Results: A significant reduction in total bilirubin was observed, especially beyond 48 hours of phototherapy, from a baseline of 17.5 ± 2.1 mg/dl to 11.0 ± 2.1 mg/dl. Electrolyte assessments post-phototherapy indicated subtle declines, with sodium decreasing from 140 ± 3 mEq/L to 135 ± 4.5 mEq/L after >48 hours. The adverse effect profile was reassuring, with 90% of neonates displaying no negative outcomes, though dehydration was observed in 5% of the cohort. Conclusion: Phototherapy effectively reduced bilirubin levels in neonates. Concurrently, changes in electrolyte levels and a low incidence of dehydration highlight the need for vigilant monitoring. These insights stress the importance of individualized therapeutic strategies in neonatal hyperbilirubinemia management. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis is a common and potentially serious complication following endoscopic retrograde cholangiopancreatography (ERCP). There is an unmet need for effective prophylactic therapies. The aims of this work evaluate the efficacy and safety of intravenous diclofenac sodium in reducing the incidence of post-ERCP acute pancreatitis. A prospective, randomized, double-blind, placebo-controlled trial was conducted. 300 patients undergoing ERCP were randomized to receive either 100mg diclofenac sodium or saline placebo intravenously immediately after the procedure. The primary outcome was development of acute pancreatitis within 72 hours as defined by revised Atlanta criteria. Secondary outcomes included adverse events, hospital stay and need for intervention. Diclofenac sodium resulted in a 58% relative risk reduction in acute pancreatitis compared to control (5.3% vs 12.7%, p<0.05). Exploratory analyses found it effective across all age groups and risk factor statuses. Incidence of adverse events and serious adverse events was comparable between groups. In conclusion, A single intravenous dose of diclofenac sodium following ERCP significantly reduces the incidence of postprocedural acute pancreatitis, with an excellent safety profile. This intervention holds promise for revolutionizing prevention of this debilitating complication. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors have heralded a paradigm shift in the management of immune-mediated diseases. While their efficacy is well-established, the safety concerns associated with these agents, particularly regarding thromboembolic events (TE), remain a focus of extensive research and clinical scrutiny. This comprehensive literature review embarks on an exploration of the multifaceted landscape of JAK inhibitors, providing insights into their safety profiles across diverse immune-mediated diseases. The introduction highlights the transformative influence of JAK inhibitors in the treatment of immune-mediated diseases. Historically, the therapeutic arsenal for these conditions included corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics. The advent of JAK inhibitors has revolutionized this landscape, although concerns about their safety persist. This review strives to comprehensively evaluate their safety, amalgamating knowledge from multiple studies and trials. The subsequent sections delve into the safety of specific JAK inhibitors in the context of rheumatoid arthritis, inflammatory bowel diseases, and dermatologic conditions and their associations with venous thromboembolism. The evolving understanding of TE risk, particularly the intricate relationship between these agents and immune-mediated diseases, is meticulously unravelled. The concluding remarks underscore the dynamic nature of TE risk assessment with regard to immune-mediated diseases involving JAK inhibitors. It underscores that risk assessment is multifactorial, influenced not only by the choice of JAK inhibitor but also by the nuances of the underlying immune-mediated disease and the unique patient characteristics. This review offers a holistic perspective on TE risks associated with JAK inhibitors and contributes to the ongoing dialogue regarding their safety in the realm of immune-mediated diseases. [ABSTRACT FROM AUTHOR]

The medicinal characteristics of garlic's (Allium sativum L.) dynamically bioactive constituents such as alliin, allicin, ajoene, S-allyl-cysteine, S-trityl-L-cysteine, diallyl sulfide, and S-allylmercaptocysteine, have gained a lot of scientific attention from a large number of investigators who have occupied the related pre-clinical and clinical studies, as well as in the industrial sector. The outcomes from basic investigations demonstrated that, depending on the type of food processing, the presence of bioactive compounds in the matrix of garlic have a coherent and direct relation with the appearance/development of health-promoting effects in the host. Besides, it can be acknowledged that at present spectroscopic and chemometric techniques are powerful tools to detect fraud, prevent criminal activities of fraudsters, and ensure food chain safety, and future studies should lead to further progress, such as portable and hand-held spectroscopy devices for rapid on-site analysis, in this field. There have been also many issues on the effects of processing on garlic's bioactive compounds, potential toxicities, pharmacokinetics, and safety profile of these elements that should be studied to validate the health advantages of garlic in humans. In this review, the outcomes of recent experimental and clinical reports are reviewed and metabolism pathway, bioavailability, biological/therapeutically effects, food-related applicability, methods of adulteration detection, potential toxicities, and safety profile of garlic's derived bio-compounds are discussed. [ABSTRACT FROM AUTHOR]