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Dupilumab was approved for the treatment of several dermatologic immune-mediated inflammatory diseases, such as atopic dermatitis and bullous pemphigoid; whereas omalizumab is the first biological agent which was approved to treat chronic spontaneous urticaria. None of the published meta-analyses has provided the sufficient data regarding the safety of these two biologics, especially regarding their potential serious adverse events (SAEs). The aim of this study was, to comprehensively evaluate the safety of the two biologics dupilumab and omalizumab. In this study, we included 32 randomized trials, and performed meta-analyses on 113 types of SAEs regarding dupilumab and 61 types of SAEs regarding omalizumab. We identified that: (1) use of dupilumab was significantly associated with the lower incidence of atopic dermatitis, while use of omalizumab was significantly associated with the lower incidence of asthma; and (2) use of dupilumab was not significantly associated with the incidences of 112 other kinds of SAEs including various infectious diseases, while use of omalizumab was not significantly associated with the incidences of 60 other kinds of SAEs including various infectious diseases. This meta-analysis for the first time assessed the association between use of dupilumab or omalizumab and incidences of various SAEs, and identified that neither dupilumab use nor omalizumab use was associated with the increased risks of any SAEs including various infectious diseases. These findings further confirm the general safety of the two biologics dupilumab and omalizumab. This informs clinicians that there is no need to worry too much about the safety issues of these two biologics.

Technological advances allow continuous vital sign monitoring at the general ward, but traditional vital signs alone may not predict serious adverse events (SAE). This study investigated continuous heart rate variability (HRV) monitoring\'s predictive value for SAEs in acute medical and major surgical patients. Data was collected from four prospective observational studies and two randomized controlled trials using a single-lead ECG. The primary outcome was any SAE, secondary outcomes included all-cause mortality and specific non-fatal SAE groups, all within 30 days. Subgroup analyses of medical and surgical patients were performed. The primary analysis compared the last 24 h preceding an SAE with the last 24 h of measurements in patients without an SAE. The area under a receiver operating characteristics curve (AUROC) quantified predictive performance, interpretated as low prognostic ability (0.5-0.7), moderate prognostic ability (0.7-0.9), or high prognostic ability (> 0.9). Of 1402 assessed patients, 923 were analysed, with 297 (32%) experiencing at least one SAE. The best performing threshold had an AUROC of 0.67 (95% confidence interval (CI) 0.63-0.71) for predicting cardiovascular SAEs. In the surgical subgroup, the best performing threshold had an AUROC of 0.70 (95% CI 0.60-0.81) for neurologic SAE prediction. In the medical subgroup, thresholds for all-cause mortality, cardiovascular, infectious, and neurologic SAEs had moderate prognostic ability, and the best performing threshold had an AUROC of 0.85 (95% CI 0.76-0.95) for predicting neurologic SAEs. Predicting SAEs based on the accumulated time below thresholds for individual continuously measured HRV parameters demonstrated overall low prognostic ability in high-risk hospitalized patients. Certain HRV thresholds had moderate prognostic ability for prediction of specific SAEs in the medical subgroup.

OBJECTIVE: Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT.
METHODS: A post hoc analysis was performed using pooled databases of the \"DEVT\" and \"RESCUE BT\" trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes.
RESULTS: Of 1,182 enrolled patients, 402 (34%) had a procedural complication and 745 (63%) had 1,404 SAE occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%), and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding, or deep venous thrombosis was less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. internal carotid artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]), and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]).
CONCLUSIONS: Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time, and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patients with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

UNASSIGNED: There are almost 2 million adult patients with congenital heart disease in China, and the number of moderate and severe patients is increasing. However, few studies have investigated the risk of serious adverse events (SAE) after catheterization among them. The aim of this study was to identify risk factors for SAE related to cardiac catheterization and to provide the risk scoring model for predicting SAE.
UNASSIGNED: A total of 690 patients with moderate and severe adult patients with congenital heart disease (ACHD) who underwent cardiac catheterization in Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to January 2022 were retrospectively collected and subsequently divided into a modeling group and a verification group. A univariate analysis was performed on the identified SAE risk factors, and then significant factors were included in the multivariate logistic regression model to screen for independent predictors of SAE. The receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model, respectively.
UNASSIGNED: A SAE occurred in 69 (10.0%) of the 690 catheterization procedures meeting inclusion criteria. The established SAE risk calculation formula was logit(p) = -6.134 + 0.992 × pulmonary artery hypertension (yes) + 1.459 × disease severity (severe) + 2.324 × procedure type (diagnostic and interventional) + 1.436 × cTnI ( ≥ 0.028 μ g/L) + 1.537 × NT-proBNP ( ≥ 126.65 pg/mL). The total score of the final risk score model based on the effect size of each predictor was 0 to 7, involving pulmonary artery hypertension (1 point), disease severity (1 point), procedure type (2 points), cTnI (1 point) and NT-proBNP (2 points), and the score greater than 3 means high risk. The C-statistic of the area under the ROC curve was 0.840 and 0.911 for the derivation and validation cohorts, respectively. According to the Hosmer-Lemeshow test, the p values in the modeling group and the verification group were 0.064 and 0.868, respectively.
UNASSIGNED: The risk prediction model developed in this study has high discrimination and calibration, which can provide reference for clinical prediction and evaluation of SAE risk after cardiac catheterization in patients with moderate and severe ACHD.

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

UNASSIGNED: Biovigilance (BV) systems aim to improve the quality and safety of tissues and organs for transplantation. This study describes the Catalan BV system and analyzes its utility.
UNASSIGNED: It is a retrospective analysis of notifications on serious adverse events (SAEs) and reactions (SARs) since the implementation of the BV system (2008 for tissues and 2016 for organs) until 2020. Variables are presented to describe the most common critical steps of the pathway and complications associated with the quality and safety of tissues and organs.
UNASSIGNED: A total of 154 and 125 notifications were reported to the Tissue and the Organ BV systems, respectively. Most SAEs were related to unexpected donor diseases and implemented actions were assured on those deemed preventable. Regarding SARs, donor-transmitted infections and malignancies (only organs) were the most common, followed by graft failure (tissues) and process-related (organs). The incidence of SAEs and SARs related to tissue was 3.44‰ and 0.22‰, respectively. The corresponding figures for organs were 31.48‰ and 8.8‰, respectively.
UNASSIGNED: The analysis of the notifications to the Catalan BV systems has provided useful information about existing risks associated with the quality and safety of tissues and organs, and enabled the implementation of actions targeted to diminish risks and mitigate damage.

We present the case of a 51-year-old male with known congestive heart failure and acute myocarditis who presented to the emergency department (ED) with swollen testicles and urinary symptoms two weeks after the initiation of sodium glucose cotransporter 2 (SGLT2) inhibitor treatment. Abdominal and pelvic computed tomography (CT) scan was consistent with the diagnosis of Fournier\'s gangrene (FG). Intravenous antibiotics were administered and surgical exploratory intervention and excision of necrotic tissue were performed, stopping the evolution of necrotizing fasciitis. FG, a reported adverse event, may rarely occur when SGLT2 inhibitors are administered in patients with diabetes. To our knowledge, there have been no reported cases of FG in Romania since SLGT2 inhibitors were approved. The distinguishing feature of this case is that the patient was not diabetic, which emphasizes that patients without diabetes who are treated for heart failure with SGLT2 inhibitors may also be at risk of developing genitourinary infections. The association of predisposing factors may have contributed to the development of FG in this case and even though the benefits of SGLT2 inhibitors outweigh the risks, serious adverse events need to be voluntarily reported in order to intervene promptly, verify the relationship, and minimize the risk of bias.

UNASSIGNED: Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization.
UNASSIGNED: This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes.
UNASSIGNED: The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities (P < .001), lower surgical rates (P = .002), and delayed surgical times (P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications.
UNASSIGNED: Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.

Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs).
to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD.
In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded.
From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up.
The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.