Same versus separate sessions of endoscopic ultrasound-guided fine-needle biopsy and endoscopic retrograde cholangiopancreatography for distal malignant biliary obstruction: a propensity score-matched study.

BACKGROUND: Same-session endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) is an attractive policy for patients with distal malignant biliary obstruction (DMBO) requiring fine-needle biopsy (FNB) and biliary drainage. However, scanty and conflicting data exists regarding safety and efficacy when comparing these two procedures performed in same versus separate sessions. METHODS: Single-center, retrospective, propensity score-matched study including patients with DMBO who underwent EUS-FNB followed by ERCP during the same or separate sessions. The primary outcome was the safety of the procedure [number of patients experiencing adverse events (AEs), overall AEs, its severity, post-ERCP pancreatitis (PEP)]. Secondary outcomes were successful ERCP, use of advanced cannulation techniques, EUS-FNB adequacy, length of hospital stay, overall procedure time, and time to recurrent biliary obstruction. RESULTS: After propensity matching, 87 patients were allocated to each group. AEs developed in 23 (26.4%) vs. 17 (19.5%) patients in the same and separate sessions group, respectively (p = 0.280). The overall number, the severity of AEs, and the rate of PEP were similar in the two groups. Secondary outcome parameters were also comparable in the 2 groups. CONCLUSIONS: Same-session EUS-FNB followed by ERCP with biliary drainage is safe and does not impair technical outcomes of tissue adequacy and biliary cannulation.

Digital ischemia: a rare immune-related adverse event of immune checkpoint inhibitors-case report and review of the literature.

Immune checkpoint inhibitors (ICIs) play a crucial role in treating various cancers. While ICIs are invaluable in the fight against different cancers, they also pose the risk of immune-related adverse events (irAEs), which can range widely in symptoms and severity. Rheumatologic complications, including digital ischemia, are among the irAEs. While rare, they require early detection for effective management. The aim of the study is to present a case report on digital ischemia related to immunotherapy and to conduct a literature review on relevant cases. We present a case involving a patient from our oncology department who developed, pericarditis, digital ischemia and anti-centromere antibodies during immunotherapy with pembrolizumab for non-small cell lung cancer (NSCLC). We collaborated with our rheumatology department to initiate treatment, including corticosteroids, iloprost, and mycophenolate mofetil. Through the follow-up, the patient showed clinical improvement. A literature review identified only 10 relevant articles, highlighting the rarity of digital ischemia as an irAE. Corticosteroids and vasodilators were commonly used treatments, with amputation unavoidable in 40% of cases. IrAEs are becoming more common due to the widespread use of ICIs. For this reason, it is crucial to diagnose and treat rare IrAEs, such as digital ischemia, as early as possible to improve outcomes.

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients.

OBJECTIVE: Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). METHODS: A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). RESULTS: Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs). CONCLUSION: ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Establishing the Vaccine Safety Health Link: A large, linked data resource for the investigation of vaccine safety concerns.

OBJECTIVE: Post-licensure vaccine safety surveillance of adverse events following immunisation is critical to ensure public safety and confidence in vaccines. This paper aims to describe the governance structure and data linkage methodology behind the establishment of the largest linked vaccine safety surveillance data resource in Australia - The Vaccine Safety Health Link (VSHL). METHODS: The Vaccine Safety Health Link contains linked records from the Australian Immunisation Register with records from hospital, perinatal, mortality, and notifiable disease datasets in near real-time. Linkage is done by the Centre for Victorian Data Linkage who receive the datasets in an identifiable format which then undergo standardisation, enrichment, linkage, quality assurance and de-identification, prior to being supplied for analysis. RESULTS: The VSHL data resource allows sensitive and rapid analysis of a broad spectrum of suspected adverse events to ensure the safety of all vaccines administered. It is also used to refute spurious concerns where no associations are found, upholding trust, and maintaining vaccine confidence. CONCLUSIONS: The Vaccine Safety Health Link's surveillance design complements existing vaccine safety surveillance methods. Challenges encountered and lessons learnt using Vaccine Safety Health Link would benefit linkage projects globally. IMPLICATIONS FOR PUBLIC HEALTH: In its first two years, The Vaccine Safety Health Link has been used for 14 vaccine safety investigations. Studies into these conditions would not have otherwise been possible. The Vaccine Safety Health Link also partners with the Global Vaccine Data Network™ for approved collaborative studies with a combined population of over 300 million people.

A Case of Patient with Atezolizumab-induced Encephalitis in Hepatocellular Carcinoma.

A 65-year-old man treated with atezolizumab plus bevacizumab for hepatocellular carcinoma was admitted to our hospital with a fever, difficulty in moving, and aphasia. The patient became comatose immediately after admission. Imaging and cerebral fluid tests revealed no evidence of malignancy or infection. A diagnosis of atezolizumab-induced encephalitis was made, and steroid pulse therapy was initiated on admission, immediately after which the patient regained consciousness and was able to talk and walk. He was discharged with slight paralysis of his legs and was able to resume chemotherapy. An early diagnosis and treatment are required to improve the prognosis of encephalitis.

Immune-related osteoblastic bone alterations mimicking bone metastasis in a small-cell lung cancer patient treated with durvalumab: a case report.

Background: Chemotherapy combined with immunotherapy is currently the standard first-line treatment for advanced small-cell lung cancer (SCLC). Immunotherapy can induce specific adverse events, called immune-related adverse events (irAEs). IrAEs of bones have rarely been reported. However, identifying bone irAEs could be important in avoiding misdiagnosis and ensuring appropriate patient management. This is the first report describing the diagnosis of irAEs of osteoblastic bone changes mimicking bone metastasis in a SCLC patient treated with durvalumab. Case Description: In this report, we describe a unique and challenging case in which a 54-year-old female patient with SCLC treated with durvalumab, an immunotherapy drug, exhibited osteoblastic bone changes that appeared similar to bone metastasis on imaging but were actually a side effect of immunotherapy. Before treatment, imaging revealed no bone metastasis. In the third month after treatment with durvalumab, computed tomography (CT) revealed multiple bone alterations, predominantly osteoblastic lesions with minor osteolytic changes. Various imaging tests suggested bone metastasis, but she had no symptoms related to bone disease. Notably, the lesions in the chest had achieved a partial response. Based on a comprehensive analysis of the CT-guided pathological biopsy results, the patient's symptoms, and the biological characteristics of SCLC, we determined that these bone changes were irAEs occurring in the skeletal system. The patient was followed up for 10 months, during which time the bone lesions remained stable. Conclusions: IrAEs of bones are rare, and their manifestations vary. Sometimes, the imaging manifestations of bone irAEs are difficult to distinguish from bone metastasis. If patients show variable treatment responses between different lesions, careful evaluation (including a pathological biopsy) is necessary.

A real-world pharmacovigilance study of KRAS G12C mutation inhibitors based on the food and drug administration adverse event reporting system.

Introduction: Sotorasib and adagrasib have been widely used for the non-small cell lung cancer (NSCLC) patients harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation. It's necessary to assess their safety profiles in the real-world population. Methods: A retrospective pharmacovigilance was conducted to examine adverse events (AEs) associated with sotorasib and adagrasib therapies using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was performed employing Venn analysis and four data-mining algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS). Results: The most commonly reported system organ classes (SOCs) for both adagrasib and sororasib were general, gastrointestinal, and investigations disorders. Notably, sotorasib exhibited significant signals for neoplasms and hepatobiliary disorders in four algorithms. Specifically, AEs related to neoplasms were predominantly associated with lung malignancies, all of which were consistent with the therapeutic indications of KRAS G12C mutation inhibitor. A total of 19 common AEs were identified in sotorasib and adagrasib, spanning gastrointestinal, general, hepatobiliary, investigations, metabolism, musculoskeletal, neoplasms, and respiratory disorders. 4 severe AEs (SAEs) were identified in sotorasib, with 3 SAEs displaying significant signals in four algorithms, including drug-induced liver injury, pancreatitis, and hepatic failure. In adagrasib, only 2 SAEs were detected, with renal failure showing significant signals in four algorithms. Conclusion: This study offers a comprehensive evaluation of the major safety signals associated with sotorasib and adagrasib, providing valuable information for clinicians regarding drug selection and safety considerations, thereby facilitating the design of future prospective safety studies.

RESTORE: Once-nightly oxybate dosing preference and nocturnal experience with twice-nightly oxybates.

Objective/Background: Preference for extended-release, once-nightly sodium oxybate (ON-SXB, FT218) vs twice-nightly immediate-release (IR) oxybate was assessed in participants switching from IR oxybate to ON-SXB in an open-label/switch study, RESTORE (NCT04451668). Patients/Methods: Participants aged ≥16 years with narcolepsy who completed the phase 3 REST-ON trial, were oxybate-naive, or were on a stable IR oxybate dose (≥1 month) were eligible for RESTORE. For participants who switched from twice-nightly dosing to ON-SXB, initial doses were closest or equivalent to their previous nightly IR oxybate dose. These participants completed a questionnaire at baseline about nocturnal adverse events associated with the middle-of-the-night IR oxybate dose in the preceding 3 months, a preference questionnaire after 3 months of stable-dose ON-SXB, and an end-of-study (EOS) questionnaire. Results: There were 130 switch participants; 92/98 (93.9 %) who completed the preference questionnaire preferred ON-SXB. At baseline, 69.2 % reported missing their second IR oxybate dose at least once; in these cases, 80 % felt worse the next day. Approximately 39 % reported taking a second nightly IR oxybate dose >4 h after the first dose, 51 % of whom felt somewhat to extremely groggy/unsteady the next morning; 120 participants (92 %) reported getting out of bed after their second oxybate dose. Of those, 9 (8 %) reported falls and 5 (4 %) reported injuries. Of the switch participants who completed the EOS questionnaire, 91.2 % felt better able to follow the recommended ON-SXB dosing schedule. Conclusions: The second nightly IR oxybate dose presents significant treatment burdens and adherence concerns. Participants overwhelmingly preferred the once-nightly dosing regimen of ON-SXB.

Case reports of immune-related cystitis and the antibody combination hypothesis.

Immune-related cystitis is a rare condition, and its diagnostic criteria and pathogenesis are not yet fully understood. Here, we report two cases of immune-related cystitis. Both patients were previously diagnosed with lung squamous cell carcinoma and received combined treatment with immune checkpoint inhibitors and chemotherapy, leading to hemorrhagic cystitis. We reviewed the cystoscopic images and pathological features of previous cases and found that autoantibodies against hemidesmosomes may be the cause of immune-related cystitis, proposing the "antibody combination" hypothesis to explain the tissue specificity of the condition.

Lung squamous cell carcinoma can produce certain proteins called autoantigens. Some patients treated with immune checkpoint inhibitors might develop antibodies against these autoantigens. A specific combination of these antibodies may cause the bladder lining to slough, leading to immune-related cystitis. Symptoms of this condition include frequent urination, urgent need to urinate, painful urination and blood in the urine. These patients typically require treatment with steroids.

Toxicity profiles of immune checkpoint inhibitors in nervous system cancer: a comprehensive disproportionality analysis using FDA adverse event reporting system.

BACKGROUND: Immune-related adverse events (irAEs) always occur during treatment with immune checkpoint inhibitors (ICIs). Patients with nervous system cancer (NSC) may gain clinical benefit from ICIs, but irAEs in NSC patients are rarely examined. Therefore, our study systematically summarized reports of irAEs in NSC. METHODS: We obtained information from the FDA adverse event reporting system from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2022. We examined use of a combination of ICIs and chemotherapy (ICI_Chemo) or chemotherapy only (ICI_Chemo) for patients with NSC. Multiple disproportionality analyses were applied to assess irAEs. Multiomics data from the gene expression omnibus (GEO) database were analyzed to explore potential molecular mechanisms associated with irAEs in NSC patients. RESULTS: Fourteen irAEs were identified in 8,357 NSC patients after removing duplicates; the top five events were seizure, confused state, encephalopathy, muscular weakness and gait disturbance. Older patients were more likely to develop irAEs than were younger patients. From the start of ICIs_Chemo to irAE occurrence, there was a significant difference in the time to onset of irAEs between age groups. irAEs may occur via mechanisms involving the inflammatory response, secretion of inflammatory mediators, and aberrant activation of pathologic pathways. CONCLUSIONS: This study helps to characterize irAEs in NSC patients treated with ICIs. We combined GEO database analysis to explore the potential molecular mechanisms of irAEs. The results of this study provide a basis for improving the toxic effects of ICIs in NSC patients.

Developing a process for assessing the safety of a digital mental health intervention and gaining regulatory approval: a case study and academic's guide.

BACKGROUND: The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. METHODS: The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study's development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. RESULTS: We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist-which assesses 15 different categories of adverse events-that was constructed from this and used in the STOP trial. CONCLUSIONS: The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products.

Systemic toxicity of CAR-T therapy and potential monitoring indicators for toxicity prevention.

Malignant tumors of the hematologic system have a high degree of malignancy and high mortality rates. Chimeric antigen receptor T cell (CAR-T) therapy has become an important option for patients with relapsed/refractory tumors, showing astonishing therapeutic effects and thus, it has brought new hope to the treatment of malignant tumors of the hematologic system. Despite the significant therapeutic effects of CAR-T, its toxic reactions, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cannot be ignored since they can cause damage to multiple systems, including the cardiovascular system. We summarize biomarkers related to prediction, diagnosis, therapeutic efficacy, and prognosis, further exploring potential monitoring indicators for toxicity prevention. This review aims to summarize the effects of CAR-T therapy on the cardiovascular, hematologic, and nervous systems, as well as potential biomarkers, and to explore potential monitoring indicators for preventing toxicity, thereby providing references for clinical regulation and assessment of therapeutic effects.

Intervention time and adverse events in a canadian epilepsy monitoring unit: An updated audit.

Background: Optimizing patient safety in the epilepsy monitoring unit (EMU) has become a topic of increasing interest. We performed an audit of our center's new single-floor EMU, assessing intervention rate (IR), intervention time (IT), and adverse events (AEs). Methods: A prospective study was conducted on all clinical seizures of patients admitted over a one-year period at our Canadian academic tertiary care center's new single-floor EMU. This single-floor EMU was supervised by EEG technologists during daytime (similar to the old set-up) and beneficiary attendants during nighttime/weekends (versus live video feed to the central nursing station on the neurology ward previously). Among 153 admissions, 79 were analyzed, and a total of 537 seizures were reviewed to assess IR, IT, and AEs. Univariate comparisons were performed with our double-floor EMU, which we reported in a previous publication. Results: In our new single-floor EMU, the IR was 61.1 % and overall median IT was 29.0s (19.0s-45.9s). The AE rate was 4.8 %. Compared to previously reported numbers for our old double-floor EMU (IR = 27.8 %; IT = 21.0s; AE = 1.2 %), the IR was significantly higher ((p < 0.001) but unexpectedly, the median IT was higher (p < 0.001) as well as the AE rate (p < 0.001). Conclusion: This prospective evaluation revealed a small but non-negligible rate of complications in our EMU, higher than our prior retrospective audit. Heightened levels of supervision in our new single-floor EMU led to higher IR. This may have led to artificially longer ITs.

The impact of serum albumin levels on postoperative complications in lumbar and cervical spine surgery: an analysis of the Michigan Spine Surgery Improvement Collaborative registry.

OBJECTIVE: Patients with serum albumin levels < 3.5 g/dL are considered malnourished, but there is a paucity of data regarding the outcomes of patients with albumin levels > 3.5 g/dL. The objective of this study was to evaluate the effect of albumin on postoperative outcome in patients undergoing elective cervical and lumbar spine procedures. METHODS: The Michigan Spine Surgery Improvement Collaborative database was queried for lumbar and cervical fusion surgeries between January 2020 and December 2022. Patients were grouped by preoperative serum albumin levels: < 3.5 g/dL, 3.5-3.7 g/dL, 3.8-4.0 g/dL, and > 4.0 g/dL. Primary outcomes included urinary retention, ileus, dysphagia, surgical site infection (SSI), readmission within 30 and 90 days, return to the operating room, and length of stay (LOS) ≥ 4 days. Multivariate analysis was conducted to adjust for potential confounders. RESULTS: This study included 15,629 lumbar cases and 6889 cervical cases. Within the lumbar cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of readmission at 30 days (p = 0.048) and 90 days (p = 0.005) and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of an LOS ≥ 4 days (p < 0.001). Within the cervical cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of SSI (p = 0.023), readmission at 30 days (p < 0.002) and 90 days (p < 0.001), return to the operating room (p = 0.002), and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of readmission at 30 days (p = 0.012) and 90 days (p = 0.001) and an LOS ≥ 4 days (p < 0.001). CONCLUSIONS: This study maintains that patients with hypoalbunemia undergoing spine surgery are at risk for postoperative adverse events. However, there also exist significant associations between borderline serum albumin levels of 3.5-4.0 g/dL and increased risk of postoperative adverse events.

The value of cesarean scar diverticulum in diagnosis of adverse events during dilatation and curettage in patient with cesarean scar pregnancy.

OBJECTIVE: The aim of the present study was to explore the relationship between the size of cesarean scar diverticulum (CSD) measured on preoperative magnetic resonance imaging (MRI) and adverse events during dilatation and curettage (D&C) procedure in patients with cesarean scar pregnancy (CSP). METHODS: The MRI of 197 CSP patients from October 2019 to August 2023 were retrospectively reviewed. The volume, area, and depth of CSD, residual myometrium thickness (RMT), and gestational sac diameter were recorded and tested for correlation with intraoperative estimated blood loss (EBL), and operation time and for any association with the intraoperative adverse events (intraoperative massive hemorrhage [39 cases] and D&C procedure failure [15 cases]). The Spearman test was used to characterize the correlation between the five MRI variables and both the EBL and operation time. The correlation between the five MRI variables and intraoperative adverse events was evaluated with student's t test and Mann-Whitney U test. Diagnostic power of the MRI variables was evaluated by the area under receiver operating characteristic curve (AUC). RESULTS: The volume, area, and depth of CSD and gestational sac diameter were positively correlated with both EBL and operation time, with the CSD volume having the highest correlation with them (r = 0.543 and 0.461, respectively). Conversely, the RMT displayed a negative correlation with the EBL and operation time. All five MRI variables were significantly associated with both intraoperative massive hemorrhage and D&C failure (all P < 0.001). The CSD volume demonstrated the highest AUC for diagnosing intraoperative massive hemorrhage and D&C failure at 0.893 (95% CI: 0.82-0.92) and 0.901 (95% CI: 0.85-0.94), respectively. The optimal cutoff values for CSD volume in predicting massive hemorrhage and D&C failure were determined to be 5.41 and 8.92 cm3, respectively, with corresponding sensitivities/specificities of 92.31/74.68 and 93.33/82.42, respectively. CONCLUSION: Quantifying the size of CSD based on preoperative MRI could aid in evaluating risk during D&C in CSP patients, with CSD volume possessing higher diagnostic efficacy than the other four MRI indicators.

Assessment of Cardiovascular Events Caused by New-Generation Androgen Receptor Pathway Inhibitors Used for Prostate Cancer: A Real-World Study in Japan.

INTRODUCTION: Androgen receptor pathway inhibitors (ARPIs) that significantly improve the prognosis of patients with prostate cancer include abiraterone acetate (androgen synthesis inhibitor) and enzalutamide (androgen receptor inhibitor). A recent analysis of ARPI and cardiovascular events using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) has been reported; however, the evidence on cardiovascular events for abiraterone acetate and enzalutamide in real-world clinical practice is insufficient. Using a large Japanese database of medical institutions, the Japanese Medical Data Center (JMDC) medical institution database (JMDC Inc., Tokyo, Japan), this study tested the hypothesis that the risk of cardiovascular events with enzalutamide is lower than that with abiraterone acetate. METHOD: Using the JMDC medical institution database, patients with new use of abiraterone acetate or enzalutamide who had not experienced a major cardiovascular event between October 2014 and February 2022 were included. After adjusting for age, comorbidities, and concomitant medications using propensity score matching, cumulative incidence rates were compared for cardiovascular death and all cardiovascular events as the primary endpoints, and major cardiovascular events, myocardial infarction, heart failure, and stroke as secondary endpoints. RESULT: A total of 3,033 patients in the enzalutamide group and 2,021 in the abiraterone group met the eligibility criteria. After propensity score matching, the cohort included 1,940 patients in the enzalutamide group and 1,940 patients in the abiraterone group. Enzalutamide was associated with significantly lower cumulative rates of cardiovascular death (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.93), all cardiovascular events (HR: 0.79, 95% CI: 0.64-0.98), major cardiovascular events (HR: 0.79, 95% CI: 0.64-0.97), and myocardial infarction (HR: 0.62, 95% CI: 0.46-0.84) compared to abiraterone. CONCLUSION: In a national sample of males with prostate cancer, those newly treated with enzalutamide had a lower risk of adverse cardiovascular events than those treated with abiraterone acetate.

Clinical features, treatment, and outcome of nivolumab induced cholangitis.

Background Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging and treatment of nivolumab induced cholangitis.Methods Case reports, case series and clinical studies of nivolumab induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023.Results Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was 7 cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and 7 patients (18.4%) did not improve.Conclusions Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.

Quality and safety in prehospital airway management - retrospective analysis of 18,000 cases from an air rescue database in Germany.

BACKGROUND: Prehospital airway management remains crucial with regard to the quality and safety of emergency medical service (EMS) systems worldwide. In 2007, the benchmark study by Timmermann et al. hit the German EMS community hard by revealing a significant rate of undetected oesophageal intubations leading to an often-fatal outcome. Since then, much attention has been given to guideline development and training. This study evaluated the incidence and special circumstances of tube misplacement as an adverse peri-intubation event from a Helicopter Emergency Medical Services perspective. METHODS: This was a retrospective analysis of a German helicopter-based EMS database from January 1, 2012, to December 31, 2020. All registered patients were included in the primary analysis. The results were analysed using SPSS 27.0.1.0. RESULTS: Out of 227,459 emergency medical responses overall, a total of 18,087 (8.0%) involved invasive airway management. In 8141 (45.0%) of these patients, airway management devices were used by ground-based EMS staff, with an intubation rate of 96.6% (n = 7861), and alternative airways were used in 3.2% (n = 285). Overall, the rate of endotracheal intubation success was 94.7%, while adverse events in the form of tube misplacement were present in 5.3%, with a 1.2% rate of undetected oesophageal intubation. Overall tube misplacement and undetected oesophageal intubation occurred more often after intubation was carried out by paramedics (10.4% and 3.6%, respectively). In view of special circumstances, those errors occurred more often in the presence of trauma or cardiopulmonary resuscitation, with rates of 5.6% and 6.4%, respectively. Difficult airways with a Cormack 4 status were present in 2.1% (n = 213) of HEMS patients, accompanied by three or more intubation attempts in 5.2% (n = 11). CONCLUSIONS: Prehospital airway management success has improved significantly in recent years. However, adverse peri-intubation events such as undetected oesophageal intubation remain a persistent threat to patient safety. TRIAL REGISTRATION: The study was registered in the German Register for Clinical Studies (number DRKS00028068).

The descriptive epidemiology of adverse events following two doses of mRNA COVID-19 vaccination in Curaçao, the Caribbean.

BACKGROUND: BNT162b2 and mRNA-1273 COVID-19 vaccines have been used for mass vaccinations in Curaçao, the Caribbean but information on adverse events (AEs)in this population is unavailable. This study describes the characteristics of vaccinees that incurred AEs, explores the associations between AEs by vaccine and doses, and estimates the rate of AEs. METHODS: Vaccination and AEs data for all persons of age 5 years (range 5-105 years) and older who received two doses of COVID-19 vaccine at 71 centres in Curaçao between February 24, 2021, and April 5, 2023, were included in this retrospective observational study. RESULTS: The vaccines differed significantly in the frequency distribution of vaccinees by age, age groups, sex, AEs, and prior COVID-19 infection. Occurrence of AEs was strongly associated with mRNA vaccine brand, sex, number of doses, but not with age, age group, and prior COVID-19 infection. Of 209,720 doses, 84 persons (0.04%) incurred AEs following two doses of mRNA vaccines (overall rate of 40.1 per 100,000 persons (95% CI 32.4-49.6). AEs were also significantly higher in females compared to males.AE rates associated with BNT162b2, and mRNA-1273 vaccines were low, but BNT162b2 vaccinees incurred substantially significantly higher AE rates (58.3 per 100,000 persons, 95% CI 45.4-74.9) than mRNA-1273 vaccinees (21.9 per 100,000 persons, 95% CI 14.6-32.8). mRNA-1273 vaccine was associated with a significantly lower risk of AEs. CONCLUSIONS: AE reporting varied by age, sex, and vaccine used as well as the number of doses. Future studies with follow-up and longer-term reporting of AEs should be conducted.