Life-threatening Adverse Events Research Articles

Splenic injury associated with colonoscopy in hospitalized patients: Incidence, risk factors, management, and outcome.

Background and study aims The frequency of splenic injuries due to coloscopy is largely unknown. Therefore, the aim of this study was to give estimate the risk for hospitalized patients. Patients and methods Using the administrative database from a health insurance company with more than 10 million insured subjects, patients undergoing inpatient colonoscopy associated with a splenic injury within 2 weeks were retrieved from the administrative records based upon OPS (comparable to International Classification of Procedures in Medicine) and ICD-10 codes. In each case identified (n = 141), the individual course of the hospital stay was reconstructed and analyzed by two experienced physicians. Patients with overt other causes of splenic injuries (e. g. abominal surgery, trauma etc.) were not further evaluated. Results Among 190,927 total colonoscopies over a 5-year period, 27 splenic lesions were most likely solely due to colonoscopy. This accounts for 14.1 splenic injuries per 100,000 colonoscopies or one lesion in 7,071 patients. Afflicted patients were older and more likely to be female than male (risk in females: 1 in 5,324 colonoscopies). Surgical interventions were carried out in 17 cases, predominantly splenectomy (n = 15) whereas 10 events were managed conservatively. Transfusions and requirement for intensive care unit treatment were strong predictors of need for surgery. Most lesions (74%) were diagnosed within 48 hours after colonoscopy. Death occurred in two patients, but less likely directly due to the splenic injury. Conclusions Administrative data analysis suggests that splenic injuries due to colonoscopy are more frequent than previously estimated. Endoscopists should be aware of this rare life-threatening adverse event.

Life-threatening complications in ophthalmic surgery: a systematic review.

Ophthalmic surgical procedures are widely acknowledged for their safety and efficacy. Undoubtedly, advances in ophthalmic surgery, along with the improvement of anaesthetic techniques, have contributed to the reduction in the occurrence of these events. However, although uncommon, systemic severe and life-threatening adverse events can still occur and it is imperative for an ophthalmologic surgeon to have a comprehensive understanding of them to act in terms of proactive prevention, prompt recognition, and optimal treatment, thus maximizing patients' outcomes. Among life-threatening complication following ophthalmic surgery, cardiovascular events represent the most common ones, including a range of different clinical entities: the oculocardiac reflex, potentially leading to haemodynamic instability and asystole; iatrogenic vascular air embolism, in form of venous air embolism or "pefluorocarbon syndrome", which can lead to obstruction of the pulmonary circulation, respiratory distress and cardiovascular collapse; postoperative venous thromboembolism, in the context of which the management of perioperative antiplatelet and anticoagulant therapy has a crucial role. Furthermore, among infectious complications, that are more commonly limited to the ocular tissues, necrotizing fasciitis represents a potentially lethal infection. This review aims to provide an up-to-date, evidence-based overview of potential life-threatening complications associated with ophthalmic surgery, exploring pathogenesis, risk factors, signs, symptoms, and, briefly, management strategies.

Association between different GLP-1 receptor agonists and acute pancreatitis: case series and real-world pharmacovigilance analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown notable advancements in managing blood sugar control. Nevertheless, there remains a gap in real-world data regarding the variation in acute pancreatitis (AP) risk among different GLP-1 RAs. Our study aimed to characterize and evaluate AP associated with different GLP-1 RAs (exenatide, lixisenatide, liraglutide, albiglutide, semaglutide, dulaglutide and tirzepatide) in a public adverse events database and to review the relevant case reports. We described a case series of patients experiencing AP while on GLP-1 RAs. Additionally, we utilized various algorithms including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) to analyze data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) regarding suspected adverse events of AP linked to GLP-1 RAs from January 2005 to September 2023. Our case series comprised thirty-nine patients who experienced AP events while on GLP-1 RAs. Within the FAERS database, we retrieved a total of 6,751 individual case safety reports (ICSRs) involving various GLP-1 RAs. The median age of the patients included in our study was 57 years (range: 14-99), with 98.3% of cases classified as serious. Signals indicating AP were observed across all GLP-1 RAs, with particular emphasis on exenatide and liraglutide. There is a notable reporting signal of AP associated with all GLP-1 RAs. Healthcare providers must remain vigilant and closely monitor this potentially life-threatening adverse event.

Self-Expanding Metal Stents in the Acute Management of Oesophageal Variceal Bleeding: A Systematic Review.

Acute variceal bleeding (AVB) continues to challenge physicians and healthcare systems. Despite significant advances in our multimodal approach to managing this problem, namely medical, endoscopic, and radiological techniques, the mortality rates for this patient cohort remain as high as 20% on the index admission. This mortality rate has remained unchanged over the past 25 years. A crucial tool in the management of AVB is the balloon tamponade technique. However, this is associated with numerous severe and potentially life-threatening adverse events. Due to the limitations of oesophageal balloon tamponade devices, there has been an increased interest in using self-expanding metal stents (SEMS) to manage refractory variceal bleeding. There is a base of experience in using SEMS derived from their use in managing malignant obstructions. This study aimed to synthesise all available evidence, for the first time, on using SEMS to manage refractory oesophageal AVB. This study was a systematic review of published papers, which is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We identified 16 suitable studies for review. These comprised one randomised controlled trial comparing SEMS to balloon tamponade, one prospective cohort study, nine retrospective cohort studies, four case reports, and one case series. In total, 246 patients were included. An average survival rate of 49% was seen among the 11 studies that reported a six-week survival rate; this included a cohort of 225 patients. The SEMS were left in situ for an average of 7.5 days, with a maximum average of 18 days in one study. The average rate for controlling the acute bleeding episode in patients receiving a SEMS was 96%. The re-bleeding rate on the removal of SEMS was 5%, far superior to the widely reported 50% re-bleeding rate for the balloon tamponade technique. The adverse event profile for the SEMS appears superior to the balloon tamponade technique overall. The rate of stent-related adverse events in patients receiving a SEMS was 25%. The most common adverse events were technical issues related to stent functioning, namely stent migration. The most severe stent-related adverse event was compression of the left main bronchus in two cases, which required the removal of the stent. Our study has several limitations, which we have alluded to throughout the paper. The studies on this issue are of poor quality, with only one randomised controlled trial performed. As a result, we must interpret the results of our research with caution. Our study supports the use of SEMS in managing AVB as a promising area of research. We have highlighted that further well-designed randomised controlled trials are needed to assess the efficacy of this technique, ideally compared directly to the balloon tamponade technique. However, based on this systematic review, the current body of evidence would suggest that the SEMS is superior to the balloon tamponade technique in terms of adverse event profile, re-bleeding rate, and length of time the device can safely be left in situ. Current evidence suggests that SEMS are as effective at controlling acute bleeding episodes as the balloon tamponade technique.

German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran.

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 'Sporadic Attacks, 5 'Symptomatic High Excretors', 5 'Prophylactic Heme', and 5 "Recurrent Attacks'. The mean time from diagnosis to treatment was 9.2 years (range in months 1-324), and the mean duration of treatment was 30 months (range 3-68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients' ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients' chronic and acute porphyria symptoms improved. The total patient populations' annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0-12.0) vs. Givo AAR: 0.45 (0-3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = -0.522, p = 0.0061). All patients' indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good-very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health.

Evaluating the safety of procedural sedation in emergency department settings among the pediatric population: a systematic review and meta-analysis of randomized controlled trials.

Our meta-analysis aimed to evaluate the safety of procedural sedation and analgesia in pediatric emergency department (ED) settings by investigating the incidence of cardiac, respiratory, gastrointestinal, and neurological adverse events associated with different sedation medications. In accordance with PRISMA guidelines, a comprehensive database search for randomized controlled trials was performed across ten databases from January 2005 to June 2024. Our inclusion criteria included randomized controlled trials involving children under 18years old undergoing pediatric sedation and analgesia in the ED. Data on medication types, dosages, administration routes, and adverse events were extracted and analyzed. Primary endpoints included cardiac, respiratory, gastrointestinal, and neurological adverse events. Seventeen studies met the inclusion criteria, a total of 2,302 procedural sedations. The most common adverse events were vomiting, agitation, and hypoxia, which occurred in 104.9 [95% CI = 76.9-132.9], 37.5 [95% CI = 20.6-54.4], 38.3 [95% CI = 23.9-52.6] of each 1000 sedations, respectively. Other adverse events included apnea, hypotension, and the need for bag-valve mask ventilation, which occurred in 8.6 [95% CI: 3.5-13.6], 9.3 [95% CI: -1.4 to 20.1], and 13.5 [95% CI: 3.2-23.8] of each 1,000 sedations, respectively. Severe adverse events were rare, with no reported instances of intubation and only one case of laryngospasm. Subgroup analyses revealed varying incidence rates of adverse events across different sedation protocols, with ketamine and its combinations showing higher rates of specific respiratory complications. Procedural sedation in pediatric EDs is generally safe, with a low incidence of adverse events, such as vomiting, agitation, and hypoxia. Life-threatening respiratory adverse events are extremely rare. Our findings thus support the careful selection and monitoring of sedation protocols to minimize risks.

Efficacy and safety of adrenomedullin for acute ischemic stroke (AMFIS): a phase 2, randomized, double-blinded, placebo-controlled, clinical trial

Adrenomedullin has angiogenic and vasoprotective effects in acute ischemic stroke (AIS). This investigator-initiated trial aimed to evaluate the safety, efficacy, and optimal administration of adrenomedullin in treating AIS. In this single-center, multi-cohort, double-blinded, randomized, placebo-controlled, Phase II trial, patients with AIS received pulsed adrenomedullin (9ng/kg/min for 8h daily over 7 days) or placebo in the first-half cohort, and continuous-pulsed adrenomedullin (9ng/kg/min for 72h during the first 3 days and 8h daily between Day 4-7) or placebo in the second-half cohort. We included male and female patients aged 20-90 years with newly confirmed ischemic lesions on diffusion-weighted magnetic resonance imaging, and for whom protocol treatment could be initiated within 24h of symptom onset. The primary safety endpoint was the occurrence of intervention-related severe adverse events. For the primary efficacy endpoint, the least square means and 95% confidence intervals of National Institutes of Health Stroke Scale (NIHSS) scores up to 7 days post-intervention initiation were calculated using generalized estimating equation models. This trial was registered at Japan Registry of Clinical Trials, jRCT2051190092. Between January 16, 2020, and November 14, 2021, 60 patients were enrolled (median [interquartile range] age, 75 [66-81] years; NIHSS score, 3 [2-4]; 21 [35.0%] females). Neither intervention-related serious adverse events nor severe adverse events were observed in patients receiving adrenomedullin. No life-threatening adverse events or deaths were reported. The least square means (95% confidence intervals) of the changes in NIHSS scores from pre-treatment to Day 7 were-0.76 (-1.43 to-0.09) in the adrenomedullin group (-1.08 [-2.17 to 0.00] in the pulsed adrenomedullin group and-0.42 [-1.12 to 0.29] in the continuous-pulsed adrenomedullin group) and-1.08 (-2.11 to-0.05) in the placebo group. Adrenomedullin was well tolerated in patients with non-severe, non-embolic AIS, although its beneficial effects were not demonstrated. It is necessary to show the efficacy of adrenomedullin in further clinical trials. Japan Agency for Medical Research and Development.

Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial

Abstract Background Myositis is an infrequent (&amp;lt;1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance. Methods The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Findings From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela. Interpretation Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.

Diaphragmatic Palsy Due to a Paraneoplastic Autoimmune Syndrome Revealed by Checkpoint Inhibitors

Background and Clinical Significance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but may underlie diverse and potentially life-threatening immune-related adverse events (irAEs). They may cause various conditions leading to respiratory failure, including myasthenic syndromes and myositis. However, diaphragmatic paralysis (DP) has rarely been reported. To describe patients with diaphragmatic paralysis in a pharmacovigilance registry, we searched the prospective REISAMIC registry at the Gustave Roussy Cancer Center (Villejuif, France) for cases of diaphragmatic palsy (DP) occurring from September 2014 to December 2021. Case Presentation: We identified three patients, in whom DP was confirmed by diaphragmatic ultrasonography, pulmonary function tests, and/or diaphragmatic electroneuromyogram. Diaphragmatic palsy was life-threatening in all patients, as it caused respiratory failure requiring mechanical ventilation. In all cases, a pre-existing subclinical paraneoplastic syndrome was detected. Onconeural antibodies (anti-titin and anti-VGCC) were detected in these patients before and after the initiation of ICI therapy, suggesting a mixed paraneoplastic syndrome with features overlapping those of myasthenic syndrome (myasthenia gravis in one patient and Lambert–Eaton syndrome in another) and myositis. Conclusions: Diaphragmatic palsy is a severe irAE potentially resulting from different mechanisms, including myositis and neuromuscular junction involvement (myasthenia gravis, Lambert–Eaton). Antineuronal antibodies associated with such conditions were already present in our patients prior to immunotherapy initiation, suggesting ICIs could trigger flare-ups of pre-existing silent paraneoplastic autoimmune conditions.

COVID-19 mRNA booster vaccination induces robust antibody responses but few adverse events among SARS-CoV-2 naïve nursing home residents

Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with ‘any AE’ and ‘no AE’ among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities.

7967 Ruxolitinib Prevents Immune-Checkpoint Inhibitor-Related Diabetes Mellitus Via Inhibition Of Pathogenic IL-21 And IFNγ-Producing CD4+ T Cells

Abstract Disclosure: N.L. Huang: None. J. Ortega: None. S.J. Wang: None. L.N. Scott: None. K. Kimbrell: None. E. McCarthy: None. J. Olay: None. J.N. Nguyen: None. K. Kim: None. J. Lee: None. M.G. Lechner: None. The use of immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment landscape for many advanced cancers by leveraging immune activation through the blockade of checkpoint proteins, including programmed death protein-1 (PD-1). Unfortunately, autoimmune attack of healthy tissue can occur in up to 60% of patients. ICI-induced Type 1 diabetes mellitus (ICI-T1DM) is a rare but life-threatening adverse event during ICI therapy that leads to rapid destruction of pancreatic islets, hyperglycemia, and lifetime dependence on insulin. While cytotoxic CD8+ T cells are recognized as important players in ICI-T1DM, the role for CD4+ helper T cells in disease pathogenesis is less well understood. Using a mouse model of ICI-autoimmunity, in which male and female NOD mice treated with anti-PD-1 (10mg/kg/day, i.p., twice weekly) develop multi-organ autoimmune infiltrates including insulitis and DM, we identified interleukin-21 (IL-21) and interferon gamma (IFNγ) CD4+ T cells as key contributors to ICI-T1DM. Antibody depletion of CD4+ T cells in NOD mice significantly delayed the onset of ICI-T1DM. Immunophenotyping of pancreatic islet infiltrates in ICI-treated mice revealed increased IL-21+ IFNγ+ CD4+ T follicular helper (Tfh; ICOS+ PD1+ CXCR5+) and T peripheral helper (Tph; ICOS+PD1+ CXCR5- CXCR6+) cells. In vitro, IL-21 increased effector CD8+ T cell function and IFNγ promoted production of T cell-attracting chemokines CXCL9, CXCL10, and CXCL16 by macrophages. Given the potential role for IL-21 and IFNγ to amplify ICI-DM progression, we sought to target these signaling pathways as potential interventions. Genetic inhibition of IL-21 or IFNγ signaling in NOD mice reduced insulitis and DM in anti-PD-1 treated mice. Considering that IL-21 and IFNγ act through JAK/STAT signaling in immune cells, we proposed to block this pathway to prevent ICI-DM using ruxolitinib, a clinically available JAK1/2 inhibitor. Indeed, ruxolitinib blocked STAT3 and STAT1 phosphorylation in mouse splenocytes in response to IL-21 or IFNγ, respectively, and completely protected ICI-treated NOD mice from DM. Finally, in a syngeneic tumor model, use of ruxolitinib after initiation of anti-PD-1 therapy did not abrogate ICI anti-tumor effects. Taken together, these data suggest that IL-21 and IFNγ producing CD4+ T cells are important drivers of ICI-T1DM, and that the use of JAK inhibitors may be a promising clinical intervention to reduce ICI-T1DM toxicities in patients. Presentation: 6/2/2024

A GWAS of ACE Inhibitor-Induced Angioedema in a South African Population.

Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is a life-threatening adverse event and, globally, the commonest cause of emergency presentations with angioedema. Several large genome-wide association studies (GWAS) have found genomic associations with AE-ACEI. However, despite African Americans having a 5-fold increased risk of AE-ACEI, there are no published GWAS from Africa. The aim of this study was to conduct a case-control GWAS of AE-ACEI in a South African population and perform a meta-analysis with an African American and European American population. The GWAS included 202 South African adults with a history of AE-ACEI and 513 controls without angioedema following angiotensin-converting enzyme inhibitor (ACEI) treatment for at least 2 years. A meta-analysis was conducted with GWAS summary statistics from an African American and European American cohort (from Vanderbilt/Marshfield with 174 cases and 489 controls). No SNPs attained genome-wide significance. However, 26 SNPs in the post-imputation standard GWAS of the South African cohort and 37 SNPs in the meta-analysis were associated to AE-ACEI with suggestive threshold(p-value<5.0×10-06). Some of these SNPs were found to be located close to the genes PRKCQ and RIMS1, previously linked with drug-induced angioedema, and also close to the CSMD1 gene linked to ACEI cough, providing replication at the gene level, but with novel lead SNPs. Our results highlight the importance of African populations to detect novel variants in replication studies. Further increased sampling across the continent and matched functional work are needed to confirm the importance of genetic variation in understanding the biology of AE-ACEI.

Cerebral Embolic Protection Devices: Are There Any Indications in Transcatheter Aortic Valve Replacement?

Stroke following transcatheter aortic valve replacement (TAVR) is a significant and life-threatening adverse event. The vast majority of these incidents occur during the TAVR procedure or within the first 24 h following TAVR, with a notable prevalence of cerebral embolic events. In response to this concern, cerebral embolic protection devices (CEPDs) have been designed to mitigate the risk of peri-procedural ischemic stroke during TAVR. The primary objective of CEPDs is to diminish the intraprocedural burden associated with new silent ischemic brain injuries. Despite the development of several CEPDs, their clinical efficacy remains uncertain. In this review, we delve into a comprehensive analysis of the utilization of CEPDs in patients undergoing TAVR, exploring insights from the existing literature. Additionally, we aim to present future perspectives and discuss the clinical implications associated with the incorporation of CEPDs in TAVR procedures.

Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis

BackgroundCheckpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies.MethodsWe retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed.ResultsThe BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31–78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs.ConclusionsThe CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

Occurrence of adverse events following vaccination in patients with allergies: a prospective study.

Allergic patients may be concerned about more frequent and/or more severe adverse events following vaccination, which may lead to the refusal of vaccines among these patients. The aim of this study is to assess whether allergic patients have more frequent adverse events (AEs) after vaccination than healthy individuals. Study participants (N = 591) underwent vaccination of their choice at a selected Vaccination and Travel Medicine Centre. At a 10 to 14-day interval, they were contacted for a telephone questionnaire survey on the occurrence of AEs after vaccination. A group of allergic patients (n = 188) and healthy controls (n = 403) were followed in the study. No significant difference was found in the occurrence of AEs between study and control group. Only in redness and swelling, which was more common in allergic patients, but only in a few individuals. All side effects were minor, such as pain at the injection site or fatigue. No participant experienced a serious or life-threatening adverse event. In the studied group, no statistically significant differences were found even in the occurrence of AEs after singular vs. simultaneous administration of vaccines (p = 0.094), nor after vaccination with inactivated vs. attenuated vaccines (p = 0.655), or after vaccination against bacterial vs. viral infections (p = 0.140). Vaccination of allergic patients did not cause more frequent and/or more serious adverse events in our study compared to healthy people. If general contraindications are observed, then vaccination of allergic patients is considered safe.

Clinical impact of sex differences and procedural setting in transcatheter aortic valve implantation

BackgroundTranscatheter aortic valve implantation (TAVI) is a well-established treatment for symptomatic patients with aortic stenosis. Yet, the impact of sex differences and public vs. private procedural setting on TAVI outcomes remain uncertain. MethodsThe RIBAC-NT (Brazilian Registry for Evaluation of Transcatheter Aortic Valve Replacement Outcomes) dataset included 3194 TAVI patients from 2009 to 2021. This retrospective analysis explored disparities in baseline characteristics, procedural and in-hospital outcomes stratifying patients by sex and procedural setting. Temporal trends were also investigated. ResultsWe included 1551 (49 %) female and 1643 (51 %) male patients. Women were older (83 [78–87] vs. 81 [75–85] years; p < 0.01) but had a lower prevalence of diabetes mellitus (30.2 % vs. 36.3 %, p < 0.01) and coronary artery disease (39.0 % vs. 52.2 %, p < 0.01). However, women had a 3-fold higher higher risk of life-threatening bleeding (6.1 % vs. 2.4 %, p < 0.01). Women presented higher procedural and in-hospital mortality rates (4.4 % vs. 2.5 % and 7.7 % vs. 4.5 %, all p < 0.01, respectively). Although public hospitals presented ~2-fold higher procedural mortality rate compared with private settings (5.0 % vs. 2.7 %, p < 0.01), after multivariable analysis procedural setting was not independently associated with in-hospital mortality. ConclusionsWomen had higher procedural and in-hospital mortality rates after TAVI as compared with men, while facing higher life-threatening bleeding and adverse events rates. Although public hospitals exhibited higher mortality rates than private centers, procedural setting was not independently associated with in-hospital mortality.

109 Endotracheal tube cuff detachment secondary to patient bite during extubation as a potential life-threatening adverse airway event complicating emergence from general anesthesia

109 Endotracheal tube cuff detachment secondary to patient bite during extubation as a potential life-threatening adverse airway event complicating emergence from general anesthesia

Remimazolam anesthesia in pediatric patients undergoing cardiac catheterization for congenital heart disease: a retrospective observational study.

Benzodiazepines are used in pediatric patients with congenital heart disease (CHD) because of their mild hemodynamic depressant effects. A novel short-acting benzodiazepine, remimazolam, is expected to be suitable for these patients. We examined the characteristics of remimazolam anesthesia in pediatric patients with CHD undergoing cardiac catheterization. This single-center retrospective study included pediatric patients undergoing cardiac catheterization for CHD. The primary outcome was the remimazolam dose for loss of consciousness. Secondary outcomes included the mean maintenance remimazolam dose, recovery time from anesthesia, predicted remimazolam concentration at emergence, decrease in blood pressure and heart rate, vasopressor administration during anesthesia, electroencephalogram index (bispectral index: BIS or patient state index: PSI), and life-threatening adverse events. Thirty-nine patients, aged 2months to 16years, were included. Thirty-three patients received a median [interquartile] midazolam dose of 0.10 [0.10-0.10] mg.kg-1 in the pre-anesthesia room. The remimazolam dose for loss of consciousness was 0.34 [0.26-0.45] mg.kg-1. The mean maintenance dose was 1.0 [0.8-1.4] mg.kg-1.h-1. The recovery time was 15 [12-17] min. The predicted remimazolam concentration at emergence was 0.4-1.2µg.ml-1 in 3-6-year-old patients. Blood pressure and heart rate decreased by 30% in 15 and 6 patients, respectively. Vasopressors were administered as a bolus in 8 patients. The BIS or PSI did not fall ≤ 60 or ≤ 50, respectively, in 51% of patients before tracheal intubation. No life-threatening adverse events were reported. Remimazolam is a good alternative anesthetic agent for pediatric patients undergoing cardiac catheterization for CHD.

Cerebral arterial air embolism after esophageal stenting for recurrence of gastroesophageal junction cancer: a case report.

Cerebral arterial air embolism (CAE) is a rare complication after esophageal stenting, but it can be life-threatening. It is especially a concern for those with a history of previous gastrointestinal cancer therapies. We report a case of CAE after esophageal stenting in a patient with recurrent gastroesophageal junction cancer and a history of multiple cancer treatments. A 71year-old man with a history of a proximal gastrectomy, resection of the lower esophagus, chemotherapy, and radiation presented to our hospital 2weeks after stenting with epigastric and back pain. Mediastinitis was suspected and conservative treatment was begun. The patient suddenly developed altered mental status, left hemiplegia, and anisocoria after drinking water. A brain computed tomography (CT) revealed right-sided predominance of multifocal CAE. Chest and abdominal CT showed a hematoma in the gastric and duodenal wall and an intraluminal hematoma from the esophagus, around the stent, to the upper ileum. CAE was thought to be due to rupture of the recurrent tumor. Unfortunately, despite intensive care, the patient died about 5h after the onset of neurological symptoms. It has been reported that prior treatments, such as chemotherapy and radiotherapy, increase the risk of life-threatening adverse events, including CAE after esophageal stenting. Clinicians should keep in mind the possibility of CAE after esophageal stenting in patients with a history of multiple cancer treatments.