Life-threatening Events Research Articles

Unexplained cardiac arrest (idiopathic ventricular fibrillation): clinical and genetic characteristics

AIM: The study was to evaluate the clinical and genetic characteristics of inherited arrhythmias in patients who survived unexplained cardiac arrest. MATERIALS AND METHODS: 20 patients (10 male and 10 female) aged 15 to 55 years (median age 36 [28; 44] years) with documented VT/VF on ECG were observed for 3 years. The clinical and instrumental study included registration of 12-lead ECG, 24-hour Holter ECG, genealogical history collection and family history of sudden cardiac death with ECG assessment of all family members, transthoracic echocardiography, 2D Speckle Tracking echocardiography and cardiac magnetic resonance imaging to exclude structural myocardial changes. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders. RESULTS: In 4 (20 %) of the 20 probands included in the study, likely pathogenic variants were identified (pathogenicity class IV), and in 7 (35 %) patients, variants with unknown clinical significance (pathogenicity class III) in 10 genes associated with channelopathies (KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, SCN10А, RYR2) and cardiomyopathies (MYH7, JPH2, RBM20). Several genetic variants were found in 3 cases. No significant genetic changes were detected in 9 (45 %) probands. The clinical diagnosis was established during the follow-up period and was verified due to the genetic testing in 5 (25 %) patients. From their ECGs, a prolonged QTc 460 ms was found in 1 patient, Brugada pattern in 2 individuals, and a shortening of QTc up to 323 ms in 1 proband. Subclinical structural changes associated with cardiomyopathies were revealed in 2 patients. In 15 (75 %) patients, it was unfeasible to establish a distinct clinical phenotype. In 6 (30 %) probands, the diagnosis was clarified due to detected genetic variants. CONCLUSION: Clinical manifestations and diverse genetic variants have been studied in patients who have survived unexplained cardiac arrest. In the course of genotyping patients who suffered unexplained cardiac arrest, genetic changes associated with LQTS were detected in 30 % of cases, while the QTc in most cases did not exceed 440 ms, which makes it difficult to establish a diagnosis at an early stage before the development of life-threatening arrhythmic events. The data from our study confirm the idea that in patients with idiopathic ventricular fibrillation, who have suffered unexplained cardiac arrest, cardiac channelopathy or subclinical manifestations of cardiomyopathy are commonly the cause. This phenomenon imposes a need for genetic testing in this category of patients.

Acute Ischemic Stroke and STEMI in A 78-Year-Old Female: A Case Report of Dual Life-Threatening Events and Complicated Recovery

Ischemic stroke and ST-elevation myocardial infarction (STEMI) occurring at the same time, are very rare conditions that cause major difficulties in management and present high mortality rates. This manuscript brings into focus a 78-year-old woman who had known diabetes mellitus (DM), hypertension (HTN), dyslipidemia, and ischemic strokes in the past, who presented with focal neurological deficits in the form of sudden onset slurring of speech and facial asymmetry which on investigation revealed a large left middle cerebral artery (MCA) infarction. Few hours later she developed STEMI with ECG changes and raised troponin levels. The patient experienced respiratory difficulty for which the patient was intubated. A percutaneous intervention (PCI) was attempted with moderate results. Complications included heart failure, atrial fibrillation (AF), and septic shock due to a urinary tract infection (UTI) that delayed her discharge from the hospital. Nevertheless, the effective treatment and cooperation between cardiologists and neurologists, stabilized her condition. This case shows the challenges of managing dual pathology (stroke and STEMI simultaneously); therefore, early diagnosis and multidisciplinary management offer the best prognosis to realize optimal outcomes.

Targeted NGS Revealed Pathogenic Mutation in a 13-Year-Old Patient with Homozygous Familial Hypercholesterolemia: A Case Report

Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder.

Optimizing Pediatric Sedation: Evaluating Remimazolam and Dexmedetomidine for Safety and Efficacy in Clinical Practice.

Daily, children undergo countless investigations and interventions, which require sedation and immobilization to ensure safety and accuracy. This remains associated with a persistent risk of sedation-induced life-threatening events as children are particularly vulnerable to adverse medical events and complications. Consequently, there is an urgent need to increase the safety of pediatric sedation and anesthesia. An ideal approach involves the use of drugs with fewer intrinsic side effects. In this context, on the basis of their pharmacokinetic properties, remimazolam (RMZ) and dexmedetomidine (DEX) were evaluated for their suitability as ideal sedatives. RMZ and DEX, both of which are currently available in pediatric medicine, have shown great promise in initial publications. To date, only very limited data concerning RMZ in small children are available. RMZ is a novel, ultrashort-acting benzodiazepine that is metabolized by tissue esterase, largely independent of organ function. It has a context-sensitive half-life of approximately 10 min, with minimal accumulation even with prolonged use. Its effects can be completely reversed with flumazenil. DEX, an isomer of medetomidine, is a potent α2-receptor-agonist with multiple indications in anesthesia and intensive care medicine. It has coanalgesic potential, allows for 'arousal sedations' and has a low profile for cardiorespiratory side effects. DEX is metabolized in the liver and is predominantly excreted renally. Both drugs show potential in the prevention and treatment of delirium, with DEX having additional neuroprotective effects. DEX and RMZ possess several properties of an optimal sedative, including clinically insignificant main metabolites and a broad dosage range, indicating their potential to reduce the incidence of sedation-related life-threatening events in children. However, further clinical research is necessary to better evaluate their potential risks.

Brainstem Anesthesia and Cardiac Arrest Following Peribulbar Block: A Case Report and Systematic Review of the Literature

Background: We report a case of brainstem anesthesia (BSA) and subsequent cardiac arrest following a routinary peribulbar block (PB) in a patient scheduled for cataract extraction and intraocular lens (IOL) implantation, thus providing a reference for further analysis of this potentially catastrophic life-threatening complication and to evaluate the current knowledge in terms of incidence, physiopathology management, and treatment of the BSA following PB. Methods: Three databases (PubMed, Embase, and Scopus) were checked to perform a systematic review of all available studies in the English Language following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate relevant studies that clearly described BSA following BSA. Results: Our literature search identified 15 cases. All the patients experienced BSA-related symptoms, including respiratory arrest, seizure, heart rate, and blood pressure abnormalities. All the patients with respiratory arrest required assisted ventilation with intubation, whereas patients with seizures were administered intravenous midazolam. Only one patient experienced cardiac arrest and underwent cardiac resuscitation. Surgery was aborted and deferred in 5 out of 15 patients, whereas 4 out of 15 underwent surgery after extubation. Conclusions: Despite the BSA incidence after the PB being very low, this possible life-threatening rare event should be considered in patients losing their consciousness and becoming apneic after the block. Therefore, prompt recognition and immediate treatment are paramount to cope with this potentially catastrophic scenario and save the patient’s life.

Tumor Lysis Syndrome Following PSMA Radioligand Therapy.

Tumor lysis syndrome (TLS) is a rare complication following treatment in prostate cancer patients. We present a 65-year-old man with history of castration-resistant prostate cancer who developed TLS following 2 sessions of 177Lu-PSMA therapy. The patient presented with bulky axillary and mediastinal lymphadenopathies, an unusual site for prostate cancer metastasis. Although his PSA levels declined following treatment, he reported excessive weakness leading to immobility. Laboratory correlation showed markedly increased lactate dehydrogenase, from 413 to 543,000 U/L, suggesting the occurrence of TLS. Although being considered a relatively safe treatment, 177Lu-PSMA can sometime lead to life-threatening events, which is reviewed here.

Sudden Cardiac Death Risk Prediction Based on Noise Interfered Single-Lead ECG Signals

Sudden cardiac death (SCD) represents a critical acute cardiovascular event characterized by rapid onset of cardiac and respiratory arrest, posing a significant threat to patients due to its high fatality rate. Monitoring indices related to SCD using wearable devices holds profound implications for preemptive measures aimed at reducing the incidence of such life-threatening events. Hence, this study proposed a predictive algorithm for SCD leveraging single-lead electrocardiogram (ECG) signals featuring low signal-to-noise ratios. Initially, simulated electrode motion artifact noise was introduced to ideal ECG signals to emulate the signal conditions with low signal-to-noise ratios encountered in everyday scenarios. To meet the criteria of simplicity and cost-effectiveness required for wearable devices, the analysis focused exclusively on single-lead signals. The proposed algorithm in this study employed a lightweight machine learning approach to extract 12-dimensional features encompassing ventricular late potentials, T-wave electrical alternation, and corrected QT intervals from the signal. The algorithm achieved an average prediction accuracy of 93.22% within 30 min prior to SCD onset, and 95.43% when utilizing a normal sinus rhythm database as a control, demonstrating robust performance. Additionally, a comprehensive Sudden Cardiac Death Index (SCDI) was devised to quantify the risk of SCD, formulated by integrating pivotal two-dimensional features contributing significantly to the algorithm. This index effectively distinguishes high-risk signals indicative of SCD from normal signals, thereby offering valuable supplementary insights in clinical settings.

Favourable lifestyle changes 1 year after acute myocardial infarction

Abstract Background Acute myocardial infarction (AMI) is a life-threatening event that should be an excellent motivator to adopt a healthy lifestyle. We aimed to evaluate the proportion of patients with AMI who reported favourable lifestyle changes 1 year after AMI. Methods Harnessing a nationwide prospective cohort of patients with AMI in Switzerland, ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients enrolled in the AMIS Plus registry between 2012 and 2022 were followed-up 1 year after the event by telephone interview. Favourable lifestyle changes, often addressed in hospitals or rehabilitation programmes were defined as smoking cessation, weight reduction (for overweight patients at index presentation), dietary changes, increased physical activity and stress reduction. Self-reported lifestyle changes were stratified according to AMI type, sex, and age. Results From 7906 AMI patients, 7234 (91.5%) with follow-up data were included. Of these, 5627 (77.8%) were male, 1607 (22.2%) female, 4664 (64.5%) had a STEMI, and 2570 (35.5%) a NSTEMI. At a median follow-up of 397 (interquartile range 371 to 465) days, 861 (50.9%) smokers at the time of the AMI had quit smoking, 1297 (35.0%) overweight patients had lost weight, 2567 (44.8%) patients had implemented nutritional changes, 2415 (41.2%) had increased their physical activity, and 1729 (30.5%) had reduced their stress levels. Patients with STEMI were more likely to stop smoking (53.0% vs. 45.1%, p=0.005), change their diet (46.4% vs. 41.6%, p<0.001), increase their physical activity (43.5% vs. 36.8%, p<0.001), or reduce stress (31.4% vs. 28.7%, p=0.04) compared to NSTEMI patients. Male sex was associated with smoking cessation [52.5% vs. 44.4%; p=0.008; age-adjusted odds ratio (OR), 0.78; 95% confidence interval (CI), 0.61-0.99; p=0.043], dietary change (47.8% vs. 33.7%; p<0.001; age-adjusted OR, 0.67; 95% CI, 0.58-0.77; p<0.001), and an increase in physical activity (43.5% vs. 32.9%; p<0.001; age-adjusted OR, 0.77; 95% CI, 0.67-0.88; p<0.001). However, after adjusting for age, stress reduction was comparable between males and females (30.9% vs. 28.9%; p<0.001; age-adjusted OR, 1.09; 95% CI, 0.94-1.26; p=0.25). Conclusions A substantial proportion of patients with AMI in Switzerland reported favourable lifestyle changes within 1 year after the index event. In general, STEMI as well as male patients were more likely to report multiple favourable lifestyle changes. Nevertheless, there is still room for improvement in terms of secondary prevention measures.

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

Objectives: The frequency of splenic injuries due to coloscopy is largely unknown. Therefore, the aim of this study was to give an estimate on the risk for hospitalized patients. Methods: Using an administrative data base of a health insurance company with more than 10 million insured subjects, patients undergoing in-patient colonoscopy associated with a splenic injury within 2 weeks were retrieved from the administrative records based upon OPS (comparable to ICPM) and ICD-10 codes. In each case identified (n=141), the individual course of the hospital stay was reconstructed and analyzed by 2 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 1 lesion in 7,071 patients. Afflicted patient 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 conservately. Transfusions and requirement of intensive care unit treatment were strong predictors for the need of surgery. Most lesions (74%) were diagnosed within 48 hours after colonoscopy. Death occurred in 2 patients, but less likely directly due to the splenic injury. Conclusion: Adminstrative 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.

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 (<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.

Exploring Immersive Multimodal Virtual Reality Training, Affective States, and Ecological Validity in Healthy Firefighters: Quasi-Experimental Study.

Firefighters face stressful life-threatening events requiring fast decision-making. To better prepare for those situations, training is paramount, but errors in real-life training can be harmful. Virtual reality (VR) simulations provide the desired realism while enabling practice in a secure and controlled environment. Firefighters' affective states are also crucial as they are a higher-risk group. To assess the impact on affective states of 2 simulated immersive experiences in a sample of healthy firefighters (before, during, and after the simulation), we pursued a multivariate approach comprising cognitive performance, situational awareness, depression, anxiety, stress, number of previous adverse events experienced, posttraumatic stress disorder (PTSD) severity, and emotions. The efficacy and ecological validity of an innovative VR haptic system were also tested, exploring its impact on performance. In collaboration with the Portuguese National Fire Service School, we exposed 22 healthy firefighters to 2 immersive scenarios using the FLAIM Trainer VR system (neutral and arousing scenarios) while recording physiological data in a quasi-experimental study. Baseline cognitive performance, depression, anxiety, stress, number of adverse events, and severity of PTSD symptoms were evaluated. Positive and negative affective states were measured before, between, and after each scenario. Situational awareness, sense of presence, ecological validity, engagement, and negative effects resulting from VR immersion were tested. Baseline positive affect score was high (mean 32.4, SD 7.2) and increased after the VR tasks (partial η2=0.52; Greenhouse-Geisser F1.82,32.78=19.73; P<.001). Contrarily, mean negative affect score remained low (range 11.0-11.9) throughout the study (partial η2=0.02; Greenhouse-Geisser F2.13,38.4=0.39; P=.69). Participants' feedback on the VR sense of presence was also positive, reporting a high sense of physical space (mean score 3.9, SD 0.8), ecological validity (mean score 3.8, SD 0.6), and engagement (mean score 3.8, SD 0.6). Engagement was related to the number of previously experienced adverse events (r=0.49; P=.02) and positive affect (after the last VR task; r=0.55; P=.02). Conversely, participants reported few negative effects (mean score 1.7, SD 0.6). The negative effects correlated positively with negative affect (after the last VR task; r=0.53; P=.03); and avoidance (r=0.73; P<.001), a PTSD symptom, controlling for relevant baseline variables. Performance related to situational awareness was positive (mean 46.4, SD 34.5), although no relation was found to metacognitively perceived situational awareness (r=-0.12; P=.59). We show that VR is an effective alternative to in-person training as it was considered ecologically valid and engaging while promoting positive emotions, with few negative repercussions. This corroborates the use of VR to test firefighters' performance and situational awareness. Further research is needed to ascertain that firefighters with PTSD symptomatology are not negatively affected by VR. This study favors the use of VR training and provides new insights on its emotional and cognitive impact on the trainee.

Coronary artery disease and the risk of life-threatening cardiac events after age 40 in long QT syndrome.

Long QT syndrome (LQTS) and coronary artery disease (CAD) are both associated with increased risk of ventricular tachyarrhythmia. However, there are limited data on the incremental risk conferred by CAD in adult patients with congenital LQTS. We aimed to investigate the risk associated with CAD and life threatening events (LTEs) in patients with LQTS after age 40 years. The risk of LTEs (comprising aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shock) from age 40 through 75 years was examined in 1,020 subjects from the Rochester LQTS registry, categorized to CAD (n = 137) or no-CAD (n = 883) subgroups. Survival analysis showed that patients with CAD had a significantly higher cumulative event rate of LTEs from 40 to 75 years (35%) compared with those without CAD (7%; p < 0.001 for the overall difference during follow-up). Consistently, multivariate analysis showed that the presence of CAD was associated with a 2.5-fold (HR = 2.47; p = 0.02) increased risk of LTEs after age 40 years. Subgroup analyses showed that CAD vs. no CAD was associated with a pronounced >4-fold (p = 0.008) increased risk of LTEs among LQTS patients with a lower-range QTc (<500 ms). The increased risk of LTEs associated with CAD was not significantly different among the 3 main LQTS genotypes. Patient treatment was suboptimal, with only 63% on β-blockers and 44% on non-selective β-blockers. Our findings suggest that CAD is associated with a higher risk of LTEs in LQTS patients, with the risk being more pronounced in those with QTc <500 ms.

Fear of death: everyday experience-based nurses ’observations in working with elderly and old patients ill with chronic cardiovascular diseases

Fear of death occurs when elderly and old patients (EOPs) are faced with life-threatening events or extreme psychological stress. For most, anticipation of death triggers negative emotions such as the fear of losing of oneself, helplessness, and a loss of control. Fear of death is one of the most prevalent psychiatric consequences of chronic health conditions. Nurses face challenges in caring for EOPs ill with chronic cardiovascular diseases (CCVDs) snd this is related to high emotional stress and fatigue associated with constant monitoring of patients and managing their anxiety and fears. Fear of death is a common concern among EOP with CCVDs. There is relatively little research that examines the relationship between EOPs ’CCVDs and experienced fear of death phenomena from the perspective of nurses. Research question, to which the answer was sought was ‘How do nurses de scribe the symptoms, signs of fear of death among EOPs ’ill with CCVDs and how they recognise the features of patients ’fear of death?’ A total of 15 nurses had participated in the study. Data were collected by using semi-structured interviews. The manifest qualitative content analysis for data anal ysis were applied. Findings revealed that the related emotional/psychological, physiological and be havioural changes were observed by nurses and the characteristics for recognising the feeling of death in patients were identified. Characteristics of EOPs ill with CCVDs and experiencing fear of death are related to changes in emotions, behaviour and physical/physiological symptoms/signs that are interrelated with their emotional state. The social, spiritual and creative needs of patients are intensi fied while they experience fear of death.

Spiritual dryness and its predictors in Iranian Muslims

Abstract Illness, disability, and life-threatening events rank among the most significant crises that give rise to spiritual challenges. These challenges can lead to a dichotomy of spiritual dryness and cohesion, a phenomenon that can manifest in any demographic group due to illness or other crises. Within the Iranian Muslim community, various groups – healthy and sick, religious and non-religious – have consistently experienced spiritual dryness. This observation aligns with findings from other studies, particularly those involving Christians. However, the factors predicting spiritual dryness in these individuals have differed from those in other populations. Given that spirituality often serves as a potent strategy for navigating life’s crises, it is crucial to provide holistic support and spiritual care to those grappling with this phenomenon. This approach can help mitigate negative outcomes and foster positive ones, such as post-traumatic growth.

Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome

The canonical G406R mutation that increases Ca2+ influx through the CACNA1C-encoded CaV1.2 Ca2+ channel underlies the multisystem disorder Timothy syndrome (TS), characterized by life-threatening arrhythmias. Severe episodic hypoglycemia is among the poorly characterized non-cardiac TS pathologies. While hypothesized from increased Ca2+ influx in pancreatic beta cells and consequent hyperinsulinism, this hypoglycemia mechanism is undemonstrated because of limited clinical data and lack of animal models. We generated a CaV1.2 G406R knockin mouse model that recapitulates key TS features, including hypoglycemia. Unexpectedly, these mice do not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. Patient data confirm the absence of hyperinsulinism. We discover multiple alternative contributors, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic control of glucose homeostasis. These data provide new insights into contributions of CaV1.2 channels and reveal integrated consequences of the mutant channels driving life-threatening events in TS.

Eighteen-year trends in the rates of intra-operative cardiac arrest and associated mortality at a public university hospital in Brazil.

Intra-operative cardiac arrest is a rare but life-threatening event. Over the past two decades, various initiatives have improved the care of patients undergoing surgery at our quaternary teaching hospital in Brazil. We aimed to evaluate the epidemiology of intra-operative cardiac arrest and associated 30-day mortality over an 18-year period. A secondary aim was to identify associated risk factors. We conducted a retrospective observational study using data collected from 1 January 2005 to 31 December 2022. Factors associated with cardiac arrest and mortality were identified using multivariable logistic regression analysis. Among the 154,178 cases, the overall rates of intra-operative cardiac arrest (n = 297) and associated 30-day mortality (n = 248) were 19.3 (95%CI (16.6-21.9)) and 16.1 (95% CI 13.9-18.3) per 10,000 anaesthetics, respectively. These decreased over time (2005-2010 vs. 2017-2022) from 26.3 (95%CI 21.0-31.6) to 15.4 (95%CI 12.0-18.7) per 10,000 anaesthetics, and from 23.4 (95%CI 18.8-28.1) to 13.7 (95%CI 10.8-16.7) per 10,000 anaesthetics, respectively. Factors associated with intra-operative cardiac arrest included children aged < 1 year (adjusted OR (95%CI) 3.51 (1.87-6.57)); ASA physical status 3-5 (adjusted OR (95%CI) 13.85 (8.86-21.65)); emergency surgery (adjusted OR (95%CI) 10.06 (7.85-12.89)); general anaesthesia (adjusted OR (95%CI) 8.79 (4.60-19.64)); surgical procedure involving multiple specialities (adjusted OR (95%CI) 9.13 (4.24-19.64)); cardiac surgery (adjusted OR (95%CI) 7.69 (5.05-11.71)); vascular surgery (adjusted OR (95%CI) 6.21 (4.05-9.51)); and gastrointestinal surgery (adjusted OR (95%CI) 2.98 (1.91-4.65)). We have shown an important reduction in intra-operative cardiac arrest and associated 30-day mortality over an 18-year period. Identification of relative risk factors associated with intra-operative cardiac arrest can be used to improve the safety and quality of patient care, especially in a resource-limited setting.

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.

Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan.

SGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan. We conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12months. After 6months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01-0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30-0.84, P = 0.009) compared to DPP4i. SGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.

Life-threatening event in laparoscopic hepatic surgery: Training curriculum on sudden hepatic artery haemorrhage

BackgroundExposure of the hepatic artery is a fundamental step in many surgeries, during which iatrogenic hepatic artery injury may occur. Although the incidence of hepatic artery haemorrhage is low, its occurrence can lead to life-threatening haemorrhage. It is difficult and dangerous to accumulate clinical experience in laparoscopic hepatic artery repair in actual patients, and simulation training models for laparoscopic hepatic artery repair are currently lacking. In this study, a 3D printed model was designed to simulate the training curriculum for sudden hepatic artery haemorrhage, but whether training with the 3D printed model could yield superior skill improvement for surgeons remained to be determined.MethodsA new 3D printed model was designed for this study. Surgeons from the General Surgery Department of Sir Run Run Shaw Hospital participated in this simulation training. The surgical performance of each model was compared, and the authenticity of the model was evaluated and mechanically tested.ResultsExperienced surgeons performed better on the 3D printed model. After repeated training, inexperienced surgeons showed significant improvement of their laparoscopic hepatic artery repair skills. The authenticity of the model was generally satisfactory, but shortcomings persisted in the mechanical testing of artery wall tearing, necessitating further improvement.ConclusionsFew studies have investigated laparoscopic simulation training for sudden hepatic artery haemorrhage. This simulation model distinguishes surgeons with different levels of experience and allows those with less experience to improve their laparoscopic hepatic artery repair skills through training on the model.

A safety comparison of heparin and argatroban anticoagulation in veno-venous extracorporeal membrane oxygenation with a focus on bleeding.

Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.