SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
AbstractIndividuals diagnosed with metastatic triple-negative breast cancer (mTNBC) suffer worse survival rates than their metastatic non-TNBC counterparts. There is little information on survival, treatment patterns, and medical costs of mTNBC patients in Asia. Therefore, this study aimed to examine 5-year survival, regimens of first-line systemic therapy, and healthcare costs of mTNBC patients in Taiwan. Adult females newly diagnosed with TNBC and non-TNBC as well as their survival data, treatment regimens and costs of health services were identified and retrieved from the Cancer Registry database, Death Registry database, and National Health Insurance (NHI) claims database. A total of 9691 (19.27%) women were identified as TNBC among overall BC. The 5-year overall survival rate of TNBC and non-TNBC was 81.28% and 86.50%, respectively, and that of mTNBC and metastatic non-TNBC was 10.81% and 33.46%, respectively. The majority of mTNBC patients received combination therapy as their first-line treatment (78.14%). The 5-year total cost in patients with metastatic non-TNBC and with mTNBC was NTD1,808,693 and NTD803,445, respectively. Higher CCI scores were associated with an increased risk of death and lower probability of receiving combination chemotherapy. Older age was associated with lower 5-year medical costs. In sum, mTNBC patients suffered from poorer survival and incurred lower medical costs than their metastatic non-TNBC counterparts. Future research will be needed when there are more treatment options available for mTNBC patients.
Determining the prognosis of poisoning by plants containing pyrrolizidine alkaloids is usually challenging. This study aimed to identify important prognostic parameters that can determine the severity of spontaneous poisoning by Crotalaria spectabilis in horses. Blood samples from 42 horses spontaneously poisoned by oats contaminated with C. spectabilis seeds were evaluated. Complete blood counts (CBC) and serum biochemical tests [urea, creatinine, total protein, albumin, total and direct bilirubin concentrations, aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and creatine kinase (CK) activities] were performed. Horses were followed up for 12 months to determine the long-term survival rate; after 12 months, they were divided into two groups: survivors (n = 30) and non-survivors (n = 12). Horses spontaneously poisoned with C. spectabilis had higher levels of urea, globulin, bilirubin (total, direct, and indirect), AST, GGT, and CK than the reference values. Non-survivor horses showed significantly higher (p < 0.05) values of hemoglobin, GGT, and direct bilirubin than the survivor horses. Horses with serum GGT activity higher than 95 U/l had 14.0 times the risk of death compared to animals showing activities equal to or lower than this value, whereas horses with serum direct bilirubin concentration higher than 0.6 mg/dl (10.26 μmol/L) had 5.78 times the risk of death compared to the others. In summary, serum GGT activity and direct bilirubin concentration may be useful prognostic indicators for assessing the severity of C. spectabilis-poisoned horses.
AbstractThe novel coronavirus disease (COVID-19) is currently a big concern around the world. Recent reports show that the disease severity and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. In addition, some steroid structures have been reported to affect coronavirus, SARS-CoV-2, function and activity. The entry of SARS-CoV-2 into host cells depends on the binding of coronavirus spike protein to angiotensin converting enzyme-2 (ACE2). Viral main protease is essential for the replication of SARS-CoV-2. It was hypothesized that steroid molecules (e.g., estradiol, progesterone, testosterone, dexamethasone, hydrocortisone, prednisone and calcitriol) could occupy the active site of the protease and could alter the interaction of spike protein with ACE2. Computational data showed that estradiol interacted more strongly with the main protease active site. In the presence of calcitriol, the binding energy of the spike protein to ACE2 was increased, and transferring Apo to Locked S conformer of spike trimer was facilitated. Together, the interaction between spike protein and ACE2 can be disrupted by calcitriol. Potential use of estradiol and calcitriol to reduce virus invasion and replication needs clinical investigation.
AbstractTo optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I2 = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.
The past decade has seen tremendous growth in patients with ambulatory ventricular assist devices. We sought to identify patients that present to the emergency department (ED) at the highest risk of death.
Methods and Results
This retrospective analysis of ED encounters from the Nationwide Emergency Department Sample includes 2010 to 2017. Using a random sampling of patient encounters, 80% were assigned to development and 20% to validation cohorts. A risk model was derived from independent predictors of mortality. Each patient encounter was assigned to 1 of 3 groups based on risk score.
A total of 44 042 ED ventricular assist device patient encounters were included. The majority of patients were male (73.6%), <65 years old (60.1%), and 29% presented with bleeding, stroke, or device complication. Independent predictors of mortality during the ED visit or subsequent admission included age ≥65 years (odds ratio [OR], 1.8; 95% CI, 1.3–4.6), primary diagnoses (stroke [OR, 19.4; 95% CI, 13.1–28.8], device complication [OR, 10.1; 95% CI, 6.5–16.7], cardiac [OR, 4.0; 95% CI, 2.7–6.1], infection [OR, 5.8; 95% CI, 3.5–8.9]), and blood transfusion (OR, 2.6; 95% CI, 1.8–4.0), whereas history of hypertension was protective (OR, 0.69; 95% CI, 0.5–0.9). The risk score predicted mortality areas under the curve of 0.78 and 0.71 for development and validation. Encounters in the highest risk score strata had a 16‐fold higher mortality compared with the lowest risk group (15.8% versus 1.0%).
We present a novel risk score and its validation for predicting mortality of patients with ED ventricular assist devices, a high‐risk, and growing, population.
Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Herein we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to the blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes upregulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes upregulated in mouse cells stimulated with LPS are enriched in genes upregulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.
Background: It's critical to identify COVID-19 patients with a higher death risk at early stage to give them better hospitalization or intensive care. However, thus far, none of the machine learning models has been shown to be successful in an independent cohort. We aim to develop a machine learning model which could accurately predict death risk of COVID-19 patients at an early stage in other independent cohorts.
Methods: We used a cohort containing 4711 patients whose clinical features associated with patient physiological conditions or lab test data associated with inflammation, hepatorenal function, cardiovascular function and so on to identify key features. To do so, we first developed a novel data preprocessing approach to clean up clinical features and then developed an ensemble machine learning method to identify key features.
Results: Finally, we identified 14 key clinical features whose combination reached a good predictive performance of AUC 0.907. Most importantly, we successfully validated these key features in a large independent cohort containing 15,790 patients.
Conclusions: Our study shows that 14 key features are robust and useful in predicting the risk of death in patients confirmed SARS-CoV-2 infection at an early stage, and potentially useful in clinical settings to help in making clinical decisions.
ObjectiveTo identify clinical and biochemical characteristics associated with 7- & 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19.Research Design and MethodsWe conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome.ResultsWe analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p < 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (<70 years) had a greater risk of death [OR 2.74 (1.31-5.76)]. BMI, microvascular and macrovascular complications, HbA1c, and random non-fasting blood glucose on admission were not associated with mortality. On multivariate analysis, CRP and age remained associated with the primary outcome [OR 3.44 (2.17, 5.44)] allowing for a validated predictive model for death by day 7.ConclusionsHigher CRP and advanced age were associated with and predictive of death by day 7. However, BMI, presence of diabetes complications, and glycaemic control were not. A high proportion of these patients required insulin infusion warranting increased input from the inpatient diabetes teams.
Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings.Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics.Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.