Early mortality in STXBP1-related disorders.

INTRODUCTION: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. METHODS: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. RESULTS: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). CONCLUSION: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

The short-term outcomes and risk factors of post-myocardial infarction ventricular septal rupture: a multi-center retrospective Study.

OBJECTIVES: Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. METHODS: A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. RESULTS: Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172-2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689-0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). CONCLUSION: The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.

Development and validation of a new tool to estimate early mortality in patients with advanced cancer treated with immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced solid cancers. Resistance to ICIs, both primary and secondary, poses challenges, with early mortality (EM) within 30-90 days indicating a lack of benefit. Prognostic factors for EM, including the lung immune prognostic index (LIPI), remain underexplored. METHODS: We performed a retrospective, observational study including patients affected by advanced solid tumors, treated with ICI as single agent or combined with other agents. Logistic regression models identified factors associated with EM and 90-day progression risks. A nomogram for predicting 90-day mortality was built and validated within an external cohort. RESULTS: In total, 637 patients received ICIs (single agent or in combination with other drugs) for advanced solid tumors. Most patients were male (61.9%), with NSCLC as the prevalent tumor (61.8%). Within the cohort, 21.3% died within 90 days, 8.4% died within 30 days, and 34.5% experienced early progression. Factors independently associated with 90-day mortality included ECOG PS 2 and a high/intermediate LIPI score. For 30-day mortality, lung metastasis and a high/intermediate LIPI score were independent risk factors. Regarding early progression, high/intermediate LIPI score was independently associated. A predictive nomogram for 90-day mortality combining LIPI and ECOG PS achieved an AUC of 0.76 (95% CI 0.71-0.81). The discrimination ability of the nomogram was confirmed in the external validation cohort (n = 255) (AUC 0.72, 95% CI 0.64-0.80). CONCLUSION: LIPI and ECOG PS independently were able to estimate 90-day mortality, with LIPI also demonstrating prognostic validity for 30-day mortality and early progression.

PirA- or PirB-binding nanobodies can protect whiteleg shrimp from the acute hepatopancreatic necrosis disease toxin.

Acute hepatopancreatic necrosis disease (AHPND) is a devastating shrimp disease caused by a binary toxin, PirAB, produced by Vibrio parahaemolyticus and other closely related bacteria. To address AHPND, over 300 unique single-domain antibodies (also known as nanobodies) derived from the VHH domains of Lama glama heavy-chain-only antibodies were raised against either PirA or PirB and characterized. Nanobodies were shortlisted based on their affinities for either PirA or PirB, their relative stability in intestinal fluids, and their ability to reduce PirAB-induced death in brine shrimp Artemia salina. From these data, a subset of nanobodies was tested for their ability to reduce AHPND in whiteleg shrimp Penaeus vannamei, and nanobodies targeting either PirA or PirB provided significant disease protection to whiteleg shrimp. These results show that nanobodies can be a new option for shrimp farmers to reduce or eliminate the impact of AHPND on their operations.

Determinants of Early Mortality Among Deaths at Adult Emergency Departments in Southern Ethiopia.

BACKGROUND: In Ethiopia, the first 3 days (72 h) after admission to the emergency department (ED) account for more than half (59.8%) of all deaths. However, little is known about the prevalence of early mortality and its associated factors in southern Ethiopia. OBJECTIVE: The main objective of this study is to assess the prevalence and associated factors of early mortality among deaths in adult EDs at selected public hospitals in Hawassa, southern Ethiopia. METHODS: An institutional-based retrospective cross-sectional study design was applied. A systematic random sampling technique was used to select 369 charts of patients who died in the adult EDs of selected public hospitals in the past 2 years. The data were collected using a standardized and pretested data abstraction tool using the Kobo Toolbox data collection tool. Logistic regression analyses were carried out to assess the strength of the association. Statistical significance was declared at p-value < 0.05, and an adjusted odds ratio (AOR) with a 95% confidence interval was used to report the strength of the association. RESULT: According to the results of the current study, 288 patients, or 78% of the total, passed away within 72 h of admission to the ED. The following variables were significantly associated with early mortality: delayed initial intervention (AOR 2.338), red triage categories (AOR 3.9), lack of investigation (AOR 3.4), comorbid illness (AOR 3.2), absence of prehospital treatment (AOR 4.2), and road traffic accidents (AOR 4.1). CONCLUSION: There was an increased early mortality rate seen in this investigation. The following factors were significantly associated with an early death in the ED: comorbidity, delayed intervention, red warning score, road traffic accidents, absence of prehospital treatment, and lack of diagnostic testing. By addressing the variables that are strongly linked to an early mortality, every intervention should be undertaken to reduce the risk of an early death.

What Factors Influence In-Hospital Mortality Following Aseptic Revision Total Hip Arthroplasty? A Single-Center Analysis of 13,203 Patients.

BACKGROUND: Revision total hip arthroplasty (rTHA) is associated with an extended surgical period, an increased hospitalization period, expanded blood loss, and high mortality rates. The purpose of the present study was to assess the risk factors that contribute to in-hospital mortality following aseptic rTHA. METHODS: We performed a retrospective examination of the medical records of all patients who underwent elective rTHA surgery at our tertiary referral arthroplasty center between March 1996 and March 2019. The study involved a group of 13,203 patients, including 70 who expired during hospitalization and 13,133 in the control group. Baseline characteristics, medical history, comorbidities, and surgery-related parameters of the patients were recorded. Logistic regression analyses were performed to examine the association between independent variables and in-hospital mortalities, which were presented as odds ratios (ORs) and confidence intervals (CIs). RESULTS: Patient factors associated with in-hospital mortality included hepatitis C (OR 75.5, 95% CI 3.5 to 1,625.2), chronic obstructive pulmonary disease (OR 30.7, 95% CI 6.5 to 145.7), rheumatoid arthritis (OR 28.9, 95% CI 3.8 to 218.5), history of myocardial infarction (OR 24.9, 95% CI 4.4 to 140.8), history of cerebrovascular disease (OR 23.1, 95% CI 3.8 to 142), congestive heart failure (OR 18.9, 95% CI 3.8 to 94.2), and diabetes mellitus (OR 10.2, 95% CI 2.4 to 42.6). Surgical factors included the history of multiple prior revisions (OR 1.75, 95% CI 1.1 to 2.7), postoperative blood transfusion (OR 2.8, 95% CI 1.1 to 7.3), and decreased preoperative hemoglobin (OR 2.3, 95% CI 1.7 to 3.1). CONCLUSIONS: Several patient-related and intraoperative factors significantly increased the risk of in-hospital mortality following aseptic rTHA. Vigilance and close perioperative monitoring are essential for patients undergoing this complex surgery. LEVEL OF EVIDENCE: III.

Early Mortality After Curative-intent Radiotherapy in Patients With Locally Advanced Non-small Cell Lung Cancer-A Population-based Cohort Study.

AIMS: In patients with locally advanced non-small cell lung cancer (LA-NSCLC), curative-intent radiotherapy (RT) or chemoradiotherapy (CRT) is associated with considerable toxicity, and approximately half of the patients die within two years. A better understanding of early mortality is needed to improve patient selection and guide supportive interventions. In this population-based, nationwide cohort study, we investigated the incidence, temporal distribution, and risk factors of early mortality. MATERIALS AND METHODS: Patients with stage II-III NSCLC treated with curative-intent RT/CRT in Denmark from 2010-2017 were included. Patients treated with preoperative or postoperative RT/CRT or stereotactic body radiation therapy were excluded. Early mortality was defined as all-cause death within 180 days from RT/CRT initiation. Multiple logistic regression was used to assess the impact of clinical and demographic variables. RESULTS: We included 1742 patients. The early mortality rate was 10%. The temporal distribution of deaths was uniform across the first year following RT/CRT, indicating the absence of a high-risk period. In multivariable analysis, increasing age and performance status, male sex, and unspecified histology (NSCLC not otherwise specified) were associated with an increased risk. By contrast, the Charlson Comorbidity Index (CCI), TNM stage, and treatment period did not significantly alter the risk of early mortality. Overall survival rates improved throughout the inclusion period but early mortality rates did not. CONCLUSION: No high-risk period for early mortality could be identified. Early mortality was not associated with CCI and other tools should be explored to quantify comorbidity for risk stratification in this setting.

Association between longest-held occupation and mortality risk.

BACKGROUND: Occupation is associated with a large part of daily activities, affecting lifestyle and social status. However, limited research exists on the association between longest-held occupation (LHO) and early mortality. We examine if LHO is associated with mortality risk among US adults 51 years of age and older. METHODS: Using Health and Retirement Study data from 1992 to 2020, we followed 26,758 respondents 51 years of age and older for up to 29 years. We used competing-risks analysis methodology to estimate the risk of mortality. RESULTS: Across the average 20.5 follow-up years, women with LHO in the categories of machine operators (subhazard ratio [SHR]: 1.42), food preparation (SHR: 1.39), handlers and helpers (SHR: 1.35), and sales (SHR: 1.15), were more likely to die earlier than women with the LHO in the professional and technical support occupation, the reference occupation. Men with LHO in the categories of food preparation (SHR: 1.43), machine operators (SHR: 1.36), personal services (SHR: 1.34), handlers and helpers (SHR: 1.32), protective services (SHR: 1.31), clerical (SHR: 1.27), farming and fishing (SHR: 1.26), sales (SHR: 1.23), and precision production (SHR: 1.20) had elevated risks of mortality compared to men whose LHO was in the referent professional and technical support occupation. CONCLUSIONS: Findings from this study provide comprehensive and current evidence that occupation can be one of the risk factors for adverse health outcomes and ultimately for early mortality.

Risk factors for early mortality following transcatheter edge-to-edge repair of mitral regurgitation.

BACKGROUND: While transcatheter edge-to-edge repair (TEER) with MitraClip is increasingly used, data on the risk stratification for assessing early mortality after this procedure are scarce. OBJECTIVE: This study aimed to assess early mortality and analyze the risk factors of early mortality among patients who underwent TEER. METHODS: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who had TEER between January 2017 and November 2020. We categorized the cohort into two groups depending on the occurrence of early mortality (death within 30 days after the procedure). Based on the ICD-10, we identified the trend of early mortality after TEER and further analyzed the risk factors associated with early mortality. RESULTS: A total of 15,931 patients who had TEER were included; 292 (1.8 %) with early mortality and 15,639 (98.2 %) without. There was a decreasing trend in early mortality from 2.8 % in the first quarter of 2017 to 1.2 % in the fourth quarter of 2020, but it was not statistically significant (p = 0.18). In multivariable analysis, the independent risk factors for early mortality were chronic kidney disease not requiring dialysis (adjusted odds ratio [aOR]: 1.57; 95 % confidence interval [CI]: 1.11-2.22, p = 0.01), end-stage renal disease (aOR: 2.34; CI: 1.44-3.79, p < 0.01), chronic liver disease (aOR: 4.90; CI: 3.29-7.29, p < 0.01), coagulation disorder (aOR: 3.42; CI: 2.35-5.03, p < 0.01), systolic heart failure (aOR: 2.81; CI: 1.34-5.90, p < 0.01), diastolic heart failure (aOR: 2.69; CI: 1.24-5.84, p = 0.01) and unspecified heart failure (aOR: 3.23; CI: 1.49-7.01, p < 0.01). Among those who died during 30-day readmission following TEER, the most common cardiac cause and non-cardiac-cause of readmission were heart failure (18.2 %) and infection (26.6 %), respectively. CONCLUSION: The early mortality following TEER was low at 1.8 %. The independent risk factors associated with early mortality were chronic kidney disease (including end-stage renal disease), chronic liver disease, coagulation disorder, and heart failure (both systolic and diastolic).

Bloodstream infection: Derivation and validation of a reliable and multidimensional prognostic score based on a machine learning model (BLISCO).

BACKGROUND: A bloodstream infection (BSI) prognostic score applicable at the time of blood culture collection is missing. METHODS: In total, 4,327 patients with BSIs were included, divided into a derivation (80%) and a validation dataset (20%). Forty-two variables among host-related, demographic, epidemiological, clinical, and laboratory extracted from the electronic health records were analyzed. Logistic regression was chosen for predictive scoring. RESULTS: The 14-day mortality model included age, body temperature, blood urea nitrogen, respiratory insufficiency, platelet count, high-sensitive C-reactive protein, and consciousness status: a score of ≥ 6 was correlated to a 14-day mortality rate of 15% with a sensitivity of 0.742, a specificity of 0.727, and an area under the curve of 0.783. The 30-day mortality model further included cardiovascular diseases: a score of ≥ 6 predicting 30-day mortality rate of 15% with a sensitivity of 0.691, a specificity of 0.699, and an area under the curve of 0.697. CONCLUSIONS: A quick mortality score could represent a valid support for prognosis assessment and resources prioritizing for patients with BSIs not admitted in the intensive care unit.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Hippocampal infarction and generalized seizures predict early mortality after endovascular middle cerebral artery occlusion in mice.

Endovascular middle cerebral artery occlusion (MCAO) is a widely used experimental ischemic stroke model. However, the model carries high early mortality. Our aim was to investigate the factors that influence early mortality within 48 h of reperfusion after transient MCAO. Using C57BL/6 mice, we induced 1-hour endovascular filament MCAO. To introduce heterogeneity of infarct volumes, a subset of animals had additional tandem common carotid artery occlusion (MCAO+CCAO). Continuous video monitoring was used to gain insight into the cause of death. Mortality within 48 h was 25% in the pooled cohort. All animals with early mortality suffered from infarcts in the hippocampus, sometimes accompanied by infarcts in the thalamus and midbrain, which occurred exclusively in the MCAO+CCAO group. All animals with early mortality developed convulsive seizures captured on video monitoring. None of the animals that did not develop convulsive seizures died. Among the three regions, hippocampal infarction appeared necessary for convulsive seizures and early mortality. Our data highlight seizures as the primary cause of mortality within the first 48 h after endovascular filament MCAO, linked to hippocampal infarction. Since hippocampal blood supply is mainly from the posterior cerebral artery (PCA), avoiding concurrent PCA ischemia can decrease mortality in proximal MCAO models.

Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts.

BACKGROUND: The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years. MATERIALS AND METHODS: The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. In this study, we analyzed data on patient and tumor characteristics from participants in the KBP-2020 cohort and compared the characteristics of patients who died within 3 months of diagnosis with those of all other patients within the cohort. We also carried out a comparative analysis with the KBP-2000 and KBP-2010 cohorts. RESULTS: Overall, 8999 patients from 82 centers were included in the KBP-2020 cohort. Three-month survival data were available for 8827 patients, of whom 1792 (20.3%) had died. Risk factors for early mortality were: male sex, age >70 years, symptomatic disease at diagnosis, ever smoker, weight loss >10 kg, poor Eastern Cooperative Oncology Group performance status (≥1), large-cell carcinoma or not otherwise specified, and stage ≥IIIC disease. The overall 3-month mortality rate was found to have decreased significantly over the last 20 years, from 24.7% in KBP-2000 to 23.4% in KBP-2010 and 20.3% in KBP-2020 (P < 0.0001). CONCLUSION: Early mortality among patients with lung cancer has significantly decreased over the last 20 years which may reflect recent improvements in treatments. However, early mortality remained extremely high in 2020, particularly when viewed in light of improvements in longer-term survival. Delays in lung cancer diagnosis and management could contribute to this finding.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Development and validation of an early mortality risk model for pediatric hemophagocytic lymphohistiocytosis: a comparison with HScore, PELOD-2, P-MODS, and pSOFA.

There has been no severity evaluation model for pediatric patients with hemophagocytic lymphohistiocytosis (HLH) that uses readily available parameters. This study aimed to develop a novel model for predicting the early mortality risk in pediatric patients with HLH using easily obtained parameters whatever etiologic subtype. Patients from one center were divided into training and validation sets for model derivation. The developed model was validated using an independent validation cohort from the second center. The prediction model with nomogram was developed based on logistic regression. The model performance underwent internal and external evaluation and validation using the area under the receiver operating characteristic curve (AUC), calibration curve with 1000 bootstrap resampling, and decision curve analysis (DCA). Model performance was compared with the most prevalent severity evaluation scores, including the PELOD-2, P-MODS, and pSOFA scores. The prediction model included nine variables: glutamic-pyruvic transaminase, albumin, globulin, myohemoglobin, creatine kinase, serum potassium, procalcitonin, serum ferritin, and interval between onset and diagnosis. The AUC of the model for predicting the 28-day mortality was 0.933 and 0.932 in the training and validation sets, respectively. The AUC values of the HScore, PELOD-2, P-MODS and pSOFA were 0.815, 0.745, 0.659 and 0.788, respectively. The DCA of the 28-day mortality prediction exhibited a greater net benefit than the HScore, PELOD-2, P-MODS and pSOFA. Subgroup analyses demonstrated good model performance across HLH subtypes. The novel mortality prediction model in this study can contribute to the rapid assessment of early mortality risk after diagnosis with readily available parameters.

Prognostic Value of Fibrosis 4 (FIB-4) Index in Sepsis Patients.

BACKGROUND: Sepsis remains a major health challenge worldwide, characterized by a dysregulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. METHOD: this study retrospectively analyzed 309 sepsis patients admitted to the Internal Medicine and An-aesthesia ICUs between 12 December 2021 and 15 December 2023 to investigate the relationship between FIB-4 levels, the Acute Physiology and Chronic Health Evaluation (APACHE), the Sequential Organ Failure Assessment (SOFA), and clinical outcomes. RESULTS: This study found that higher FIB-4 measurements were statistically significantly associated with increased 28-day mortality, with a cut-off value of 4.9, providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients. CONCLUSIONS: by elucidating the potential role of the FIB-4 index in sepsis prognosis, this study contributes to the ongoing efforts to improve risk stratification and enhance patient care in sepsis management.

A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis.

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.

Difference in early all-cause mortality among patients having hip arthroplasty a Swedish perioperative registry study 2013-2022.

INTRODUCTION: Hip arthroplasty is a common orthopaedic procedure worldwide. There is an ongoing debate related to the fixation and anaesthesia impact on the 30-day mortality, particularly in the aging population with higher American Society of Anaesthesiology (ASA) Physical-Status. AIM: To study the 30-day all-cause mortality in patients undergoing primary hip arthroplasty, with regards to the impact of age, ASA-class, anaesthesia techniques, indication for surgery and fixation techniques. MATERIALS AND METHODS: Perioperative data for primary hip arthroplasty procedures for osteoarthritis and hip fractures registered in the Swedish Perioperative Registry (SPOR) between 2013 and June 2022 were collected. Binary logistic regressions were performed to assess the impact of age, ASA-class, anaesthetic technique, indication for surgery and fixation on odds ratio for 30-day mortality in Sweden. RESULTS: In total, 79,114 patients, 49,565 with osteoarthritis and 29,549 with hip fractures were included in the main study cohort. Mortality was significantly higher among hip fracture patients compared with osteoarthritis, cumulative 8.2% versus 0.1% at 30-days respectively (p < 0.001). Age above 80 years (OR3.7), ASA 3-5 (OR3.3) and surgery for hip fracture (OR 21.5) were associated with significantly higher odds ratio, while hybrid fixation was associated with a significantly lower odds ratio (OR0.4) of 30-day mortality. In the same model, for the subgroups of osteoarthritis and hip fracture, only age (OR 3.7) and ASA-class (OR 3.3) had significant impact, increasing the odds ratio for 30-day mortality. Hemi arthroplasty was commonly used among the hip fracture patients 20.453 (69.2%), and associated with a significantly higher odds ratio for all-cause 30-day mortality as compared to total hip arthroplasty when adjusting for age and ASA-class and fixation 2.3 (95%CI 1.9-2.3, p < 0.001). CONCLUSIONS: All-cause 30-day mortality associated with arthroplasty differed significantly between the two cohorts, hip fracture, and osteoarthritis (8.2% and 0.1% respectively) and mortality expectedly increased with age and higher ASA-class. Anaesthetic method and cement-fixation did not impact the odds ratio for all-cause 30-day mortality after adjustment for age and ASA-class.

The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program: Metformin, Enalapril, caffeic acid phenethyl ester, green tea extract, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride.

The National Institute on Aging Interventions Testing Program (ITP) has so far identified 12 compounds that extend the lifespan of genetically heterogeneous mice using the log-rank test. However, the log-rank test is relatively insensitive to any compound that does not uniformly reduce mortality across the lifespan. This test may thus miss compounds that only reduce mortality before midlife, for example, a plausible outcome if a compound only mitigates risk factors before midlife or if its efficacy is reduced at later ages. We therefore reanalyzed all data collected by the ITP from 2004-2022 using the Gehan test, which is more sensitive to mortality differences earlier in the life course and does not assume a uniformly reduced mortality hazard across the lifespan. The Gehan test identified 5 additional compounds, metformin, enalapril, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), caffeic acid phenethyl ester (CAPE), and green tea extract (GTE), which significantly increased survival but were previously missed by the log-rank test. Three (metformin, enalapril, and 17-DMAG) were only effective in males and two (CAPE and GTE) were only effective in females. In addition, 1,3-butanediol, which by log-rank analysis increased survival in females but not males, increased survival in males by the Gehan test. These results suggest that statistical tests sensitive to non-uniformity of drug efficacy across the lifespan should be included in the standard statistical testing protocol to minimize overlooking geroprotective interventions.

Predictors of early mortality after lung transplantation for idiopathic pulmonary arterial hypertension.

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short-term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90-day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR: 3; CI: 1.4-5), pulmonary artery diastolic pressure (OR: 1.3 per 10 mmHg; CI: 1.07-1.56), forced expiratory volume in the first second percent predicted (OR: 0.8 per 10%; CI: 0.7-0.94), recipient total bilirubin >2 mg/dL (OR: 3; CI: 1.4-7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01-2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90-day mortality after lung transplant for IPAH.