Median Onset Research Articles

Ocular adverse events associated with antibody-drug conjugates: a comprehensive pharmacovigilance analysis

IntroductionAntibody-drug conjugates (ADCs) are increasingly utilized in patients with solid tumors and hematologic malignancies. However, the adverse ocular toxicity induced by ADCs has not been comprehensively evaluated in real-world clinical settings.MethodsData from April 2019 to March 2024 based on the FDA Adverse Event Reporting System (FAERS) were extracted and analyzed. Disproportionality analysis was used to evaluate the association between ADCs and ocular adverse events (AEs). The median time to onset (TTO) of various ADCs was compared.ResultsA comprehensive analysis identified 2,686 ocular AEs associated with ADCs. Among these, Tisotumab vedotin had the most positive signals at the preferred terms (PTs) level, followed by trastuzumab emtansine and enfortumab vedotin. In contrast, gemtuzumab ozogamicin demonstrated minimal ocular toxicity signals. Cluster analysis revealed that ADC-related ocular toxicities predominantly manifested as corneal disorders or ocular neuromuscular disorders. The median onset of ocular toxicity varied considerably, with enfortumab vedotin showing the earliest median onset at 12.5 days.ConclusionsOur study demonstrates the association between ADCs and ocular AEs based on real-world data, providing valuable guidance for clinicians when prescribing ADCs. And we found some important safety signals that have not been mentioned in the label or previous studies.

Evaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) and are now used in both early-stage and metastatic disease. Recent case reports suggest that pseudo-serum creatinine (Scr) elevations are likely a class effect of CDK4/6i. This single-center retrospective analysis included patients aged ≥18 years who received at least one dose of palbociclib, ribociclib, or abemaciclib for the treatment of HR+/HER2- BC in the early or advanced setting. The primary objective was the incidence of pseudo-Scr elevation for each of the three agents. CDK4/6i-induced pseudo-Scr elevation was suspected when the Scr elevation could not be fully attributed to other causes. Secondary endpoints included the grade, onset, duration, and clinical consequences of pseudo-Scr elevation. 143 patients were included. Pseudo-Scr elevation was suspected in patients treated with palbociclib, ribociclib, or abemaciclib, with incidences of 16% (8/50), 14% (6/43), and 20% (10/50), respectively. Rates did not significantly differ between agents (p = 0.727). Among patients with CDK4/6i-induced pseudo-Scr elevation, all events were grade 1 (8.3%) or 2 (91.7%). The median onset from treatment initiation to first Scr elevation was 33.5, 42, and 21.5 days, for palbociclib, ribociclib, or abemaciclib, respectively. Pseudo-Scr elevation appears to be a class effect of CDK4/6i, with similar rates of Scr elevation observed across the three agents currently FDA approved.

MOGAD and NMOSD: insights on patients’ radiological and laboratory findings from a single UAE center

IntroductionAlthough neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are rare diseases, they pose a significant burden on both society and the healthcare system. This study aims to discuss the demographics and patient characteristics of these diseases in a single center in the United Arab Emirates (UAE).MethodsThis is a retrospective, descriptive study that included patients with either NMOSD or MOGAD treated at Rashid Hospital, UAE during the period between January 2019 and January 2024. Patients were selected and categorized according to NMOSD criteria, aquaporin-4 antibodies, and MOG antibodies. Patient demographics, clinical characteristics, and medical history were retrieved from their medical records and descriptively analyzed in the light of patients’ serological data.ResultsWe identified 34 patients with non-multiple sclerosis atypical CNS inflammatory/demyelinating syndromes. Twenty-seven patients (79.4%) fulfilled the criteria for NMOSD, while seven (20.6%) tested positive for MOG antibodies, fulfilling the criteria for MOGAD. In the NMOSD cohort, 19% (n = 5) were AQP4-antibody negative. Seventy-four percent of the NMOSD cohort and 43% of the MOGAD cohort were female. For MOGAD patients, disease onset was at a younger age (median onset age of 25 years) compared to the overall study population (mean onset age of 28.94 years). Long segment transverse myelitis was only detected in NMOSD patients (33.3%), and brainstem syndrome with area postrema syndrome was more common in the MOGAD cohort (29% vs. 4%). The rate of positive response to intravenous methylprednisolone as initial therapy was comparable across both cohorts (74% in case of NMOSD and 71% in case of MOGAD).ConclusionThis study provides valuable insights into the status of NMOSD and MOGAD in the UAE, highlighting the need for larger, prospective studies to further characterize these diseases in the local population, as well as the need for improved understanding of the epidemiology and management of these rare but debilitating conditions.

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)

ABSTRACT Objective Given the extensive use of atorvastatin in managing cardiovascular conditions and the surge in reported adverse drug reactions (ADRs), this study leverages the FAERS database to comprehensively evaluate atorvastatin-associated adverse events, thereby enhancing our understanding of its safety profile in real-world settings. Methods A retrospective observational pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q1 2024. Four algorithms – ROR, PRR, BCPNN, and EBGM – were employed to detect signals of adverse events (AEs) linked to atorvastatin through disproportionality analysis. Results Out of 17,627,340 reports in the FAERS database 81,955 involved atorvastatin. Consistently identified AEs across all four algorithms included musculoskeletal and connective tissue disorders, metabolic and nutritional disorders, and hepatobiliary disorders at the system organ class (SOC) level. A total of 4,575 significant disproportionate preferred terms (PTs) were observed across 23 SOCs, with key PTs being ‘immune-mediated myositis,’ ‘type 2 diabetes mellitus,’ ‘necrotizing myositis,’ ‘autoimmune myositis,’ and ‘myopathy.’ Additionally, unexpected AEs such as erectile dysfunction were identified. The median onset time for these AEs was 60 days, with most occurring within the first 30 days of treatment. Conclusion This study identified both expected and unexpected AEs associated with atorvastatin, highlighting the need for continued surveillance and providing valuable insights for clinicians to optimize atorvastatin use and address safety concerns.

Understanding paralogous epilepsy–associated GABAA receptor variants: Clinical implications, mechanisms, and potential pitfalls

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABAA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABAA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in GABRA1, GABRB2, GABRB3, and GABRG2. Seven mutations (α1P260L, α1P260S, β2P252L, β3P253L, β3P253S, γ2P282A, and γ2P282S) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations. All individuals in the cohort were diagnosed with developmental and epileptic encephalopathy, with a median seizure onset age of 3.5 mo, and all exhibited global developmental delay. The clinical data for this cohort aligned with established GABAA receptor GOF but not LOF cohorts. Electrophysiological assessments revealed that all variants caused GOF by increasing GABA sensitivity by 3- to 23-fold. In some cases, this was accompanied by LOF traits such as reduced maximal current amplitude and enhanced receptor desensitization. The specific subunit mutated and whether the mutation occurred in one or two subunits within the pentamer influenced the overall effects. Molecular dynamics simulations confirmed similar structural changes from all mutations, but with position-dependent asymmetry. These findings establish that paralogous variants affecting the 100% conserved proline residue in the M1 transmembrane helix of GABAAR subunits all lead to overall GOF traits. The unexpected asymmetric and mixed effects on receptor function have broader implications for interpreting functional analyses for multimeric ion-channel proteins.

Clinical and Genetic Analysis of 8 Children With Ornithine Transcarbamylase Deficiency: Two Novel Mutations.

Cases and studies of neurologic symptoms in children caused by genetic metabolic diseases have been widely reported. Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, which is due to mutations in the OTC gene located on chromosome Xp21.1. In this study, we analyzed the clinical and genetic characteristics of 8 Chinese children diagnosed with OTCD. A total of 8 patients (5 male and 3 female) were diagnosed with OTCD by biochemical and molecular analysis between 2015 and 2023. Clinical manifestations, biochemical features, and OTC gene sequencing analysis were reviewed retrospectively. The effect of c.664-1G>C on OTC mRNA synthesis was confirmed by a minigene splicing assay. All children were late-onset patients, with a median onset age of 3.6 years (range 1.8-17 years). Neurologic symptoms caused by hyperammonemia include vomiting, coma, dyssomnia, and seizures. The peak plasma ammonia levels ranged from 149 to 4,490 μmol/L, and alanine transaminase levels ranged from 20 to 1316 U/L. Four of them had received CRRT, and only 1 patient was admitted for liver transplantation. By December 2023, 4 patients had survived and 4 were deceased. Blood amino acids or urinary organic acids were detected in 7 cases. All patients underwent whole-exome sequencing, and 2 novel mutations were revealed (P1, c.617dupT and P2, c.664-1G>C). The alteration (c.664-1G>C) leads to the deletion of a 54-bp sequence in the exon 7 of the OTC gene (NM_000531.6: c.664_717del). Two novel pathogenic variants in the OTC gene were confirmed in 8 Chinese children by biochemical findings and genetic analysis. These findings will provide a better understanding of the diagnosis and treatment of pediatric patients with OTCD.

Disproportionality analysis of adverse events associated with asfotase alfa: a post-marketing study using the FDA Adverse Event Reporting System

ABSTRACT Background Asfotase alfa (AA) is an FDA-approved enzyme replacement therapy for hypophosphatasia (HPP). Limited real-world data on its adverse events (AEs) exist. This study evaluates AA-related AEs using the U.S. FDA’s Adverse Event Reporting System (FAERS) database. Methods Reports for AA were extracted from FAERS and analyzed per FDA guidelines. AEs were categorized using MedDRA version 26.1. Disproportionality analysis was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) algorithms. Time-to-onset (TTO) was calculated, with a Weibull shape parameter test to assess risk over time. Results Out of 13,702,373 reports, 5,040 AA-related AEs were identified, with 198 significant preferred terms (PTs). Common AEs included injection site reactions and pain, with additional PTs for ear/labyrinth disorders and infections. The median onset for 234 AEs with reported times was 170 days (IQR 18–390 days). No significant differences in AEs were found across gender or age groups. Conclusion Most AEs align with known data, but newly identified ear/labyrinth disorders and infections require further investigation to enhance AA’s safety profile.

Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke Following Cardiac Interventions: A Systematic Review and Meta-Analysis.

The purpose of this study isto pool the evidence on the safety and efficacy of mechanical thrombectomy (MT) in patients who develop acute ischemic stroke (AIS) due to large vessel occlusion (LVO) following recent cardiac interventions. PubMed, Embase and Scopus were searched from inception up to February 2024 using a combination of "cardiac interventions" and "mechanical thrombectomy" as keywords. Studies that evaluated AIS within 30days of a recent cardiac intervention who underwent MT were included. The proportion of mortality, favorable functional outcome (modified Rankin Scale (mRS) 0-2), successful reperfusion (TICI ≥ 2b or TIMI ≥ 2) and symptomatic intracranial hemorrhage (sICH) were pooled using generalized linear mixed model. Thirty-one case reports/series and 11 observational studies including 195 MT procedures were included. The patients' mean age was 72years. The most common cardiac intervention associated with AIS was transcatheter aortic valve replacement/implantation in 96/192 cases (50%). The median onset of stoke was 0 (IQR 0-3) days after cardiac intervention. Rate of successful reperfusion was 79.4% [95%confidence interval (CI) 66.7-88.1%], rate of mRS 0-2 after 90 days was 42.7% [95%CI 32.5-53.6%], and rate of mortality at 90 days was 30.3% [95%CI 21.7-40.6%]. The rate of sICH was 11.6% [95%CI 5.9-21.5%]. MT to treat AIS due to LVO after cardiac interventions may result in good rates of functional recovery, though mortality and sICH may be higher. Regular and repeated neurological examinations should be performed following cardiac interventions, with special attention to stroke. If stroke is detected, MT should be considered as a viable option.

Epidemiology of healthcare-associated bloodstream infection in South African neonatal units

BackgroundReports of healthcare-associated bloodstream infection (HA-BSI) epidemiology in African neonatal units are limited.MethodsWe conducted a cross-sectional study (2017–2018) in nine neonatal units in the Western Cape Province, South Africa, including central, regional and district hospitals (416 beds) using laboratory and clinical records. Patient demographics, HA-BSI rates, pathogen spectrum, and hospital outcomes and empiric antibiotic coverage rates were determined.ResultsOver two years, 23,748 neonates were admitted with unit occupancy rates ranging from 79 to 93%. 485 HA-BSI episodes occurred, with median onset at 11 (IQR 7–24) days of life. Most HA-BSI episodes (348; 72%) affected very low birth weight neonates (< 1500 g). The overall HA-BSI rate was 2.0/1000 patient days. The highest HA-BSI rate was observed at the central unit with onsite surgery (3.8/1000 patient days). Crude HA-BSI mortality was 31.8% (154/485) with two-thirds of deaths occurring within three days of BSI onset. Higher mortality was observed for Gram-negative/fungal BSI compared to Gram-positive BSI (RR 1.5; 95%CI 1.1-2.0; p = 0.01) and very preterm neonates (gestation < 32 weeks) versus ≥ 32 weeks (RR 1.5; 95%CI 1.1–2.1; p = 0.01). Mean estimated empiric antibiotic coverage rates varied by unit type: 66–79% for piperacillin-tazobactam plus amikacin, 60–76% for meropenem and 84–92% for meropenem plus vancomycin.ConclusionMost HA-BSI events affected preterm neonates at the central hospital with onsite surgery. One-third of patients with HA-BSI died, with highest mortality in preterm infants and Gram-negative/fungal BSI. Empiric antibiotic regimens provide moderate coverage of circulating pathogens but require annual review given increasing carbapenem resistance rates.

Sustained Drug-Free Remission in Giant Cell Arteritis.

To evaluate the frequency and timing of sustained drug-free remission (SDFR) in patients with giant cell arteritis (GCA) and to identify potential predictive factors of this outcome. Retrospective review of all patients included in the large Spanish multicentre registry for GCA (ARTESER) with at least two years of follow-up. SDFR was defined as the absence of typical signs, symptoms, or other features of active GCA for ≥12 months after discontinuation of treatment. We included 872 patients. Forty-seven percent had received concomitant treatment with tocilizumab and/or immunosuppressants, mainly methotrexate.SDFR was achieved in 21.2% (185/872) of the patients. The cumulative rates of patients achieving SDFR at 2, 3, and 4 years were 6.3%, 20.5%, and 25.3%, respectively.Patients who achieved SDFR could reduce their prednisone dosage to 10 mg/day (p = 0.090) and 5 mg/day (p = 0.002) more quickly than those who did not. Relapses were less frequent in patients with SDFR (p = 0.006).The presence of relapses (incident rate ratio: 0.492, p < 0.001) and the need for intravenous methylprednisolone boluses at diagnosis (IRR: 0.575, p = 0.003) were significantly associated with a decreased likelihood of achieving SDFR.Only 5 patients (2.7%) experienced a recurrence, with a median onset of 19 months after achieving SDFR (IQR 25th-75th: 14-35 months). Within 3-4 years of diagnosis, only one-quarter of patients with GCA successfully reached the SDFR. Once the SDFR was achieved, the likelihood of experiencing recurrence was low. Relapses and the need for glucocorticoid boluses appear to be predictors of long-term GC need.

Safety concerns of aztreonam: a real-world disproportionality analysis based on FDA Adverse Event Reporting System

ABSTRACT Background Aztreonam was approved by the FDA for treating Gram-negative infections, including metallo-β-lactamase producers. This study extensively evaluated aztreonam-related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) database for a better understanding of toxicities. Methods The signals of aztreonam-related AEs were quantified using disproportionality analyses, like reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker algorithms. Results Among the 18,182,912 records retrieved from the FAERS 11,627 cases were identified where aztreonam was the primary suspect drug. A total of 127 preferred terms with significant disproportionality that simultaneously met the criteria of all algorithms were retained. Unexpected safety signals such as cholestatic liver injury, hypoprothrombinemia, hemoptysis, pulmonary hemorrhage, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis and so on may also manifest in adults, particularly in elderly patients. The median onset time for AEs related to intravenous aztreonam was 4 days, compared to a year after the initiation of inhaled aztreonam. Conclusions Our study identified potential new adverse event signals and offered a thorough understanding of aztreonam’s safety profiles. This information is crucial for enhanced cliggnical monitoring and risk assessment, aiding healthcare professionals in tailoring their approach.

Dexmedetomidine for electroencephalogram in children with behavioural disorders: a comparative study between intranasal and intravenous administration

ObjectiveThe aim of the project was to compare the efficacy and safety of intranasal (IN) and intravenous (IV) dexmedetomidine (DEX) in procedural sedation for electroencephalogram (EEG) in paediatric patients with behavioural disorders.MethodsSingle-centre comparative observational study in the tertiary care centre of Padua, regarding all consecutive patients < 18 years old affected by behavioural disorders, who needed sedation for EEG recording. From 2018 to 2019 a group of children received IV administration of DEX, from 2020 to 2021 a second group of children received IN administration of the same drug. In both groups, the target of sedation was level 2, in accordance with the Paediatric Sedation State Scale (PSSS). Heart rate (HR), pulse oxygen saturation and blood pressure (BP) were registered. The quality of the EEG recordings and the satisfaction of caregivers were collected.ResultsDEX was used in 48 patients (IV = 24; IN = 24) with total sedation success rate of 98%. Only one patient failed with IN DEX. IN DEX showed longer median onset time (p < 0.01), but shorter offset (p = 0.01) than IV route. All adverse effects were self-resolved. The IN group reported 9 cases of bradycardia, while hypotension and hypertension occurred in the IV group. EEG recording quality and level of satisfaction among caregivers and EEG technicians were high in both groups.ConclusionsIN DEX is an effective sedative; its recovery time shorter than IV DEX and its favourable adverse events profile make this route a reasonable alternative, especially in paediatric patients with a low compliance to procedures.

Mortality Risk in Patients With Cardiac Complications Following Ischemic Stroke: A Report From the Virtual International Stroke Trials Archive.

Cardiac complications may occur in patients following ischemic stroke (stroke-heart syndrome [SHS]). We investigated the mortality risk in patients with SHS and across the SHS manifestations. Data were sought from the VISTA (Virtual International Stroke Trials Archive), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into 2 cohorts based on the incidence of SHS. The SHS was defined as developing any cardiac complications within 30 days following stroke. Using Cox proportional hazards models, we evaluated the temporal risk dynamics of 90-day death associated with the day of SHS onset. We also compared the risk of 90-day death across SHS manifestations, using multivariate analysis. Among 15 054 patients with ischemic stroke (mean age, 69±12 years; 55% men), 1787 (11.8% [95% CI, 11.3-12.3]) developed SHS. The median onset time for SHS was 2 (interquartile range, 1-4) days. The most prevalent manifestation was other arrhythmia/ECG abnormalities, with the incidence rate of 6.5% (95% CI, 6.1-6.9). Patients who developed SHS between 10 and 30 days following stroke had significantly higher risks of death compared with those with SHS within the first 0 to 3 days (adjusted hazard ratio, 1.84 [95% CI, 1.36-2.49]). In the multivariate-adjusted analysis, SHS manifested as acute myocardial injury/myocardial injury, heart failure/left ventricular dysfunction, and atrial fibrillation/flutter were associated with the highest risk of death within 90 days after stroke across SHS manifestations excluding cardiorespiratory arrest. SHS is associated with a high risk of death, with a greater risk observed with delayed SHS onset.

Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US Food and Drug Administration adverse event reporting system

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) potentially increase the risk of pulmonary aspiration resulting from impaired gastric emptying (IGE). We evaluated the association between GLP-1RAs and IGE using the US Food and Drug Administration Adverse Event Reporting System (FAERS). MethodsWe analysed FAERS data from 2004 Q1 to 2024 Q1, identifying the top 10 drugs linked to IGE and determining the proportion of GLP-1RA use. Disproportionality analysis using the reporting odds ratio was conducted to assess the relative IGE risk for each drug. Logistic regression analysed the impact of age, weight, and sex on IGE risk. Cumulative incidence and time to onset of IGE events were examined using Kaplan–Meier and Weibull shape parameter tests. ResultsAmong the top 10 drugs associated with IGE reports, five were GLP-1RAs, accounting for 49.5% (982/1982) of cases. Dulaglutide (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.94–1.00, P=0.033) and semaglutide (OR 0.96, 95% CI 0.94–0.97, P=0.001) showed lower IGE risk with older age. For exenatide, higher weight (OR 0.99, 95% CI 0.98–1.00, P=0.033) and male sex (OR 0.39, 95% CI 0.20–0.68, P=0.033) were associated with lower IGE risk. Median onset times ranged from 40.5 days (semaglutide) to 107.5 days (tirzepatide) from intitiation of therapy. The Weibull shape parameter β was <1 for all GLP-1RAs, indicating a higher IGE risk early in treatment. ConclusionsGLP-1RAs were notably associated with reports of impaired gastric emptying in the FAERS. Age, weight, and sex were significantly associated with impaired gastric emptying risk for certain GLP-1RAs. IGE events tended to occur early in treatment, with risk diminishing over time. These findings provide valuable references for future research on perioperative safety with GLP-1RAs.

A real-world pharmacovigilance analysis of adverse events associated with irbesartan using the FAERS and JADER databases.

Hypertension is a leading global risk factor for disability and death. Irbesartan, a potent angiotensin II receptor blocker, requires continuous safety monitoring. We conducted a disproportionality analysis of irbesartan-related adverse drug events (ADEs) using the FDA's FAERS and Japan's JADER databases. We extracted irbesartan-related ADE reports from FAERS (Q1 2004 to Q1 2024) and JADER (Q2 2008 to Q4 2023). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) for signal detection. Sensitivity analyses were conducted to exclude comorbid medications, and subgroup analyses by age and gender were performed to explore ADE occurrence in specific populations. Th time to onset (TTO) of ADEs was assessed using Weibull distribution test and Kaplan-Meier curves. A total of 5,816 (FAERS) and 366 (JADER) reports were analyzed, with irbesartan-related preferred terms (PTs) involving 27 System Organ Classes (SOCs) in FAERS and 22 in JADER. Three SOCs met detection thresholds in both databases: "metabolism and nutrition disorders," "cardiac disorders," and "renal and urinary disorders." We identified 219 positive signals in FAERS and 20 in JADER, including known signals like hyperkalemia, hypotension, and acute kidney injury. Notably, newly identified signals such as acute pancreatitis (n = 50, ROR: 7.76 [5.88-10.25]) and rhabdomyolysis (n = 50, ROR: 7.76 [5.88-10.25]) in FAERS and respiratory failure (n = 7, ROR: 6.76 [3.20-14.26]) in JADER could have significant clinical implications, as they may lead to severe outcomes if not recognized and managed promptly. Subgroup analyses revealed both similarities and differences in signal detection across gender and age groups. Sensitivity analyses, excluding concomitant medications, confirmed the persistence of key positive signals, including hyperkalemia, angioedema, acute pancreatitis, and agranulocytosis. ADEs mainly occurred within 1month (34.14%) and after 1year (32.32%) after dosing, with a median onset of 107days. This study provides valuable real-world evidence on the safety profile of irbesartan. The identification of new safety signals underscores the necessity of updating drug labels, particularly for assessing and managing high-risk patients. Additionally, the TTO analysis emphasizes the importance of sustained vigilance for adverse events over time. In conclusion, our findings contribute to a more comprehensive understanding of irbesartan's safety, aiding healthcare professionals in optimizing its use in clinical practice.

Impact of Antipsychotic Medications on Weight Gain and Eating Disorder-Related Psychopathology in Adult Inpatients with Anorexia Nervosa.

The impact of antipsychotic use on weight gain and eating disorder-related psychopathology in adult inpatients with anorexia nervosa (AN) is unclear. Consecutively hospitalized adults with AN were retrospectively analyzed. Co-primary outcomes were body mass index (BMI) and weekly weight change. Secondary outcomes were Eating Disorder Inventory-2 (EDI-2) subscale scores 'drive for thinness' and 'body dissatisfaction'. Admission-to-discharge changes were compared in patients continuing pre-admission antipsychotics (APcont), starting antipsychotics (APnew) and patients without psychopharmacotherapy (noMed) using linear mixed models. Sensitivity analyses were conducted in subgroups matched for age, length of stay, baseline BMI and baseline EDI-2 scores. Subgroups were also compared regarding BMI trajectories, using non-linear growth curve models. Within-group analyses compared weight gain before vs. after the median antipsychotic onset week. Of 775 adult inpatients (mean length of stay =103.5±48.0 days), 21.7% received antipsychotics (APcont =7.7%; APnew=13.9%), i. e., olanzapine (n=127, dose =5.5±3.1 mg/day) or quetiapine (n=41, dose=100.0±97.7 mg/day), while 78.3% did not receive any medication. Comparing all three groups, a significant time×group interaction was found for noMed and APnew vs. APcont (p=0.011), but this effect disappeared when comparing matched subgroups. However, in matched subgroups (n=54 each) APnew showed steeper weight gain vs. APcont both overall (p=0.011) and after median antipsychotic initiation (5.8±5.0 weeks) (p≤0.001). No significant group differences emerged in EDI-2 subscale scores. In this naturalistic study, 22% of adult inpatients received antipsychotics. However, neither weight gain nor AN-related psychopathology changed differently in patients treated with vs. without antipsychotics. Newly initiated antipsychotic treatment vs. continuation from pre-admission had better weight gain outcomes.

Early Postoperative Serum Lactate Levels Predict Anastomotic Leakage After Minimally Invasive Esophagectomy.

Anastomotic leakage (AL) is a major complication after esophagectomy for esophageal cancer, and the significance of elevated postoperative lactate levels in the occurrence of AL is unclear. We evaluated 583 patients who underwent minimally invasive esophagectomy for esophageal cancer. Serum lactate levels were measured immediately after esophagectomy and in the morning on postoperative days (POD) 1, 2, 3, and 4. We also evaluated the factors associated with AL using multivariable logistic regression analysis. AL occurred in 8.9% (n = 52) of patients, and the median onset of AL was POD10 (interquartile range: 7-13). The lactate levels immediately after esophagectomy through POD3 were significantly higher in patients with AL than in those without AL. A further multivariable logistic regression analysis showed that elevated lactate level on POD2 was an independent predictor of the occurrence of AL (odds ratio 11.9; 95% confidence interval: 4.04-17.3; P < 0.001). Severe AL was significantly more frequent in the higher lactate patients (P < 0.001). Furthermore, in patients with AL with higher lactate, the onset tended to be earlier (P = 0.054), and the treatment duration of AL was significantly longer compared with those with lower lactate (P = 0.037). AL was significantly associated with elevated postoperative lactate levels. Elevated lactate levels on POD2 could be significant predictor of AL development after esophagectomy.

Why do patients with pheochromocytomas/paragangliomas exhibit significantly inconsistent elevation of catecholamines and their metabolites? a large Chinese cohort study.

Inconsistent elevation of catecholamines (CAs) and metanephrines (MNs) was observed in pheochromocytomas/paragangliomas (PPGLs). This study aimed to explore its potential causes and report the diagnostic efficacy of MNs and CAs in a large Chinese PPGL cohort. Clinical data and results of hormone tests were retrospectively collected. The sensitivity of plasma MNs and 24h-urinary CAs was analyzed. Clinical characteristics were compared between patients with positive and negative biochemical results, and among those with inconsistent elevation of MNs and CAs. Seven hundred and three patients were included, with a median onset age of 41.0 years. Plasma MNs (93% ~ 99%) showed prior diagnostic sensitivity to 24h-urinary CAs (74% ~ 89%). Patients with negative biochemical results presented as a smaller tumor (1.7 cm vs. 4.3 cm, P = 0.001), a higher proportion of normal blood pressure (60.0% vs. 20.5%, P = 0.002) and negative 131I-meta-iodobenzylguanidine (131I-MIBG) imaging (55.6% vs. 17.3%, P = 0.012). An earlier age of onset (40.0 vs. 41.0 vs. 44.5 years, P = 0.025), a higher proportion of paroxysmal hypertension (36.5% vs. 29.2% vs. 32.2%, P = 0.005) and the Epinephrine secretion type (79.3% vs. 37.7% vs. 48.0%, P < 0.001) were found in patients with the ratio of MNs/CAs elevation multiples <0.5 than those with the ratio between 0.5 and 2 or >2. Plasma MNs exhibited a superior sensitivity than 24-h-urinary CAs in the Chinese PPGL diagnosis. Patients with a small tumor, normal blood pressure and negative 131I-MIBG imaging were prone to express negative biochemical levels. Additionally, an obvious elevation of 24-h-urinary CAs than plasma MNs was correlated to paroxysmal hypertension and the Epinephrine type.

Sexual outcomes following the surgical treatment of traumatic rupture of the corpora cavernosa.

Penile fracture is a post-traumatic condition affecting the tunica albuginea of the corpora cavernosa when erect. Clinical diagnosis and urgent surgical intervention are crucial to avoid severe functional complications, particularly erectile dysfunction. We aimed to evaluate male sexual function after surgical treatment in patients with penile fracture and to identify predictive factors of postoperative erectile dysfunction. We underwent a hospital-based retrospective study on patients who underwent surgical repair for fractures of the corpora cavernosa between 2012 and 2023. Included in this study were all patients who have a postoperative follow-up of at least 12 months. Patients were clinically evaluated for the presence of erectile dysfunction and the presence of postoperative penile curvature. The patients were asked to answer the structured questionnaire of the International Index of Erectile Function (IIEF-15). We included 87 patients. The mean age was 38 ± 12years. Fourteen patients (16%) developed a fibrous plaque, with a median onset time of 30days postoperatively. Erectile dysfunction was noted in forty-four patients (51%). Active smoking (p < 0.002), the surgical approach (p = 0.02), a consultation time > 7.5h (p = 0.01), a length of the discontinuity of the corpora cavernosa > 2.5cm (p = 0.01) and the use of an erection inhibitor postoperatively (p = 0.021) were independent predictive factors of erectile dysfunction at 1 year postoperatively. Considering the results of our study, we propose rapid and urgent surgical management for penile fractures, and an elective surgical approach may be considered. We emphasize the fundamental role of sexual education, especially for young people, in preventing this sexual accident that could negatively impact their sexual life.

Clinical and genetic characteristics of hypoparathyroidism in children: a multicenter experience in China.

This study was aimed to analyze the clinical and genetic characteristics of hypoparathyroidism in children. We performed a retrospective analysis of 74 patients diagnosed with pediatric hypoparathyroidism from 2014 to 2023, recruited in five medical centers across China. Data of basic information and clinical tests were extracted from patients' records. Whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis (CMA) were utilized to identify the genetic causes. The results indicated a median onset age of 6.07 ± 4.82 years and a median diagnosis age of 6.91 ± 4.88 years. Of the 46 patients who underwent genetic tests, 35 were found to carry pathogenic variants related to hypoparathyroidism. Specifically, 19 cases (19/46, 41.30%) had 22q11.2 microdeletion, while other variations included AIRE (8/46, 17.39%), GATA3 (3/46, 6.52%), CaSR (2/46, 4.34%), and the rest 3 patients with mutations of TBCE, PTH and mitochondrial gene deletion respectively. Convulsions were the most common initial presentation, observed in 43 cases. The non-DGS group exhibited the lowest serum PTH levels compared to DiGeorge syndrome and gene-negative group. Among the 66 patients who underwent cranial CT or MR, 26 (26/66, 39.99%) presented with intracranial calcification. We reported the largest cohort of childhood hypoparathyroidism with genetic diagnoses, reinforcing the view that genetic disorders account for the majority of pediatric hypoparathyroidism, with the 22q11.2 microdeletion being the most prevalent. Identifying the genetic causes of hypoparathyroidism is crucial for predicting patient outcomes, managing comorbidities, and, importantly, informing decisions regarding the potential use of emerging recombinant human PTH therapy.