Occurrence Of Death Research Articles

The Prognostic Value of Right Ventricle Strain In Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)

Background: RV dysfunction has been recognized as a powerful independent predictor of poor prognosis. Therefore, accurate evaluation of RV function is helpful for risk stratification in patients with HF, so as to guide clinicians to choose the best treatment and improve the prognosis of patients. Therefore, assessment of RV function is clinically important in almost all patients with heart disease. Objective: The main purpose of this study was to evaluate the prognostic value of right ventricular free wall longitudinal strain in patients with heart failure with reduced ejection fraction (HFrEF). Methods: We evaluated a prospective cohort of 126 patients with known or suspected HFrEF referred for echocardiographic evaluation. All underwent measurement of RV free-wall longitudinal strain (RVFWLS) by 2D transthoracic echocardiography. The primary study endpoint was the occurrence of death for any cause or hospitalization for heart failure. Results: From 126 eligible patients with chronic heart failure, 10 (8%) with RVFWLS not suitable for strain analysis were excluded, leaving a final study population of 116 patients. During the follow-up period of 24 months, 44 patients (38%) reached the composite end point: 18 patients died (15%), and 26 patients (22%) were hospitalized for worsening HF. Compared with patients without events, patients who reached the composite end point were older and prevalently men (P <0.05). Patients with events also showed higher LV volumes, lower LVEF%, increased left atrial volume index (LAVI), increased pulmonary artery systolic pressure, and higher prevalence of severe MR and TR than event-free patients. Diastolic RV diameter was also significantly greater in this group. In this study, we found that a RVFWLS less negative of -19.3% was associated to outcomes with 75% sensitivity and 67% specificity P < 0.001. A value of RVFWLS less than -19.3% was strongly associated to outcome with HR 1.9, 95% CI 1.487–2.7; P < 0.001. Conclusion: RV free wall longitudinal strain seems to be more sensitive and accurate for the diagnosis of RV systolic dysfunction in patients with HFrEF, therefore assessment of RV function should be implemented by analysis of RVFWLS in patients with HFrEF, to improve identification of patients who are at high risk for adverse events.

Meta-analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin.

To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double-blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta-analysis was the hazard ratio (HR) for the time to first occurrence of non-fatal stroke, non-fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non-inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non-fatal stroke, non-fatal MI or CV death (MACE), tested for non-inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non-inferiority objective with a P value of less than 0.0001. Non-inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.

Sex-disparities in chest pain workup: a retrospective cohort review of a university based clinical decision pathway

BackgroundFemales have historically lower rates of cardiovascular testing when compared to males. Clinical decision pathways (CDP) that utilize standardized risk-stratification methods may balance this disparity. We sought to determine whether clinical decision pathways could minimize sex-based differences in the non-invasive workup of chest pain in the emergency department (ED). Moreover, we evaluated whether the HEART score would minimize sex-based differences in risk-stratification.MethodsWe conducted a retrospective cohort review of adult ED encounters for chest pain where CDP was employed. Primary outcome was any occurrence of non-invasive imaging (coronary CTA, stress imaging), invasive testing, intervention (PCI or CABG), or death. Secondary outcomes were 30-day major adverse cardiac events (MACE). We stratified HEART scores and primary/secondary outcomes by sex.ResultsA total of 1078 charts met criteria for review. Mean age at presentation was 59 years. Females represented 47% of the population. Low, intermediate, and high-risk patients as determined by the HEART score were 17%, 65%, and 18% of the population, respectively, without any significant differences between males and females. Non-invasive testing was similar between males and females when stratified by risk. Males categorized as high risk underwent more coronary angiogram (33% vs. 16%, p = 0.01) and PCI (18% vs. 8%, p = 0.04) than high risk females, but this was not seen in patients categorized as low or intermediate risk. Males experienced more MACE than females (8% vs. 3%, p = 0.001).ConclusionsWe identified no sex-based differences in risk-stratification or non-invasive testing when the CDP was used. High risk males, however, underwent more coronary angiogram and PCI than high risk females, and consequently males experienced more overall MACE than females. This disparity may be explained by sex-based differences in the pathophysiology driving each patient’s presentation.

Effect of acute histologic chorioamnionitis on bronchopulmonary dysplasia and mortality rate among extremely low gestational age neonates: A retrospective case-control study.

To evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN). This Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage ≥2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants). Among 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71). This is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.

Life expectancy of patients with diabetic foot sepsis post-lower extremity amputation at a regional hospital in a South African setting. A retrospective cohort study

BackgroundDiabetes foot sepsis (DFS) is the leading cause of amputation of lower extremities. Over 50 % of patients who have had major lower extremity amputation due to DFS are dead within 4 years following the procedure. AimTo determine the life expectancy of patients following amputation for DFS at a regional hospital in South Africa. MethodsWe conducted an audit of patients who had DFS and were admitted over a 5-year period. The duration from admission to time of death was recorded in days. Occurrence of death was confirmed from family members of the deceased using structured telephonic interview questionnaires. Categorical findings were summarized using actual counts and percentages and compared using either the Chi-square or Fisher's exact test. We used the mean with standard deviation or median and range to compare parametric and non-parametric continuous data, respectively. The Shapiro-Wilk test was used to test normality of data. Multivariate logistic regression was done to establish factors that were strongly associated with the mortalities. Adjusted survival curves were added to compare the rate of occurrence of mortality between males and females with age as a confounder. Statistical significance was set at a p-value below 0.05. Results197 were found of which 100 % of participants had Type 2 diabetes mellitus and 63.5 % were males. Associated comorbidities included hypertension in 73.6 %, obesity in 66 %, alcohol use in 64.5 % and smoking in 58.4 %. 190 participants had an amputation and 19.3 % died. ConclusionDFS was more common in males and 96 % of the patients had an amputation. Mortality rate within 4 years following amputation was 19.3 % and was higher in females and individuals with multiple comorbidities.

Cases, deaths and lethality due to COVID-19: analysis of social and assistance data from the Brazilian Northeast

Objective: To analyze the impact of the coverage of Primary Health Care, Human Development Index and Bolsa Família on the occurrence of cases, deaths and lethality due to COVID-19 in the Brazilian Northeast. Method: Descriptive, cross-sectional study, with data extracted from the state platforms for COVID-19, the Health Information System for Primary Care and the Institute for Applied Economic Research. Spearman and Kruskal-Wallis correlation tests were used. Results: It was found that 483,793 confirmed cases of COVID-19 and 19,307 deaths from this condition were reported in the Brazilian Northeast. Regarding the occurrence of COVID-19, the State of Ceará had the highest rate of cases (1200.83/100,000 inhabitants). It was observed that the greater the coverage of FHS, the greater the number of confirmed cases (r=0.855 and p-value=0.002) and deaths (r=0.818 and p-value=0.004) due to COVID-19. Conclusion: The Family Health Strategy is an organizational model of Primary Health Care powerful to cope with the pandemic, based on prevention, tracking among the most vulnerable groups, identification and notification of cases and deaths due to COVID-19.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry

Background and aimsSeveral studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. MethodsPatients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. ResultsStudy population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin.Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803).At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74–1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04–1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20–2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83–3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68–3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62–3.10, p < 0.001) were associated with increased mortality. ConclusionsStatin therapy after a TTS event was not associated with better prognosis at follow-up.

Morphological and genetic aspects of Marfan Syndrome as demonstrated by a case of death during pregnancy with the discovery of two de novo missense mutations in the FBN1 gene

Marfan Syndrome (MFS) is an autosomal dominant disease caused in most cases by mutations in the FNB1 gene, which encodes for fibrillin 1. MFS does not alway shows typical phenotypic signs. Indeed, the occurrence of sudden death of unknown cause is increasingly seen in young adults without ante mortem preexisting pathology to explain the event. In many cases the diagnosis of Marfan Syndrome (MFS) is carried out post mortem, especially in cases where the disease’s external phenotype is absent. Here is reported a case of a young woman who died during a twin pregnancy investigated with medico-legal and forensic anthropological procedures. The autopsy showed the absence of a typical marfanoid habitus and the presence of a dissecting aneurysm of the aorta with histopathological degeneration of the aortic elastic fibers. The genetic investigation revealed two previously undetected de novo mutations of the FBN1 gene: c.T6181C: p.C2061R and c.G1415A: p.C472Y. This new mutations, together with a comprehensive analysis, demonstrates the existence of a causal relationship between these mutations and the dissecting aneurysm of the aorta. This also stresses the importance of a combined multidisciplinary approach to this condition which includes morphological and genetic studies.

Predictive Model of All-Cause Death in Patients with Heart Failure using Heart Rate Variability.

Central Illustration : Predictive Model of All-Cause Death in Patients with Heart Failure using Heart Rate Variability. Short and long-duration heart rate variability (HRV) data from Holter monitoring could identify predictors of all-cause death in heart failure (HF) patients. To build a predictive model of all-cause death in patients with HF using HRV. Retrospective study including patients with suspected or confirmed HF who were admitted for decompensated HF or syncope that underwent Holter monitoring. In analysis of augmented sympathetic tonus, we evaluated the lowest HRV in nonoverlapping 10-minutes periods throughout 24h continuous electrocardiographic signal recording (short HRV variables). Variables with p<0.01 were included in a multivariate Cox regression model to determine the occurrence of the all-cause death. Variables with statistical significance in Cox regression were chosen to build the predictive model. P<0.05 was considered significant. A total of 116 patients were included, mean age of 71.9±16.3 years, 45.7% men, mean follow-up of 2.83±1.27 years. Thirty-nine deaths occurred (33.6%). By comparing survivors vs. non-survivors, the variables that showed statistical significance were lowest SDNN, lowest rMSSD, age and left ventricular ejection fraction (LVEF). In Cox regression, independent predictors of all-cause death were: age>69 years (HR 3.95, 95%CI 1.64-9.52); LVEF≤57% (HR 4.70, 95%CI 2.38-9.28) and lowest rMSSD≤12ms (HR 5.54, 95%CI 2.04-15.08). An integer value was assigned to each variable. Score<3 showed AUC=0.802 (95%CI 0.72-0.87). In HF patients hospitalized for decompensated HF or syncope, independent long-term predictors of all-cause death were age, LVEF, and 10-minutes rMSSD. These findings indicate that even brief moments of high sympathetic tone can impact survival, specifically in the elderly and patients with HF with reduced ejection fraction.

Psychological Experiences of Midwives Regarding Maternal Deaths at Two Selected Public Hospitals in Lesotho

Maternal deaths are a pervasive problem that frequently occurs in developing countries, driven by socio-economic issues, healthcare service-related issues, pre-existing health conditions, health professional-related issues, and socio-cultural issues. This paper describes the psychological experiences of midwives regarding maternal deaths at two selected public hospitals in Lesotho. A qualitative, phenomenological inquiry was employed to collect data from a purposively selected sample of 10 midwives through face-to-face interviews. Audiotapes were used to record the interviews, and the data were transcribed verbatim. The qualitative content analysis method was used to analyse the data. Permission to conduct the study was sought and granted by the Ministry of Health Lesotho (ID58-2022). Participants’ identities were confidential, and they were allowed to withdraw from the study without any prejudice. Psychological experiences such as trauma, shock, fear, stress, depression, loss of trust, helplessness, bad dreams, and insomnia were reported by the midwives after the occurrence of maternal deaths. They resorted to individual coping strategies such as crying, alcohol and other substance-related use, and recreational activities. Unfortunately, these strategies were not guided, hence the need for trained healthcare professionals who will take care of midwives’ psychological and emotional problems emanating from maternal deaths.

Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Diagnosis of Malignant Pulmonary Nodules Using a Combination of Tumor-associated Autoantibodies and Computed Tomography.

Diagnosis of malignant pulmonary nodules can greatly reduce the occurrence of lung cancer death, and computed tomography (CT) is commonly used in diagnosis. In addition, tumor-associated autoantibodies (TAAbs) show high specificity and stability. We aim to establish a computable risk model of pulmonary nodules by combining CT with TAAb detection. The concentrations of 7 TAAbs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, MAGEA1, and CAGE) were assayed using the enzyme-linked immunosorbent assay in 136 patients with pulmonary nodules (84 with newly diagnosed lung adenocarcinoma, 21 with squamous cell carcinoma, and 31 with benign nodules) and 42 control subjects without pulmonary nodules. We then drew receiver operating characteristic curves and conducted logistic regression to analyze the diagnostic efficiency of our method in the detection of lung cancer. The positivity rate of the 7 TAAbs was 49.5%, and the specificity was 83.6%. Our regression results indicated 65% overall accuracy, 44.76% sensitivity, and 76.71% specificity. Notably, when combined with CT imaging and the demographic characteristics, diagnostic accuracy increased to 73.4%, sensitivity to 61.5%, and specificity to 87.1%. The positive predictive value and negative predictive value were 93% and 41%, respectively. Our study provides a method that combines 7 serum TAAbs with imaging and demographic characteristics to diagnose malignant pulmonary nodules more accurately than existing methods.

PP124 Patisiran For Patients With Hereditary Transthyretin Amyloidosis (hATTR) With Stage 2 Polyneuropathy Or Who Have An Inadequate Response To Tafamidis

IntroductionHereditary Transthyretin amyloidosis (hATTR) is a rare autosomal dominant, multisystemic, progressive, and potentially fatal genetic disease. Currently, the only drug made available in the Brazilian National Health System to treat hATTR is tafamidis meglumine, indicated for symptomatic adult patients in early stage (stage 1) and not undergoing liver transplantation for amyloidosis associated with hATTR.MethodsA systematic review was conducted in the databases MEDLINE via Pubmed, Embase, The Cochrane Library, and LILACS addressing the question “Is patisiran treatment effective and safe for patients diagnosed with ATTRh amyloidosis with stage 2 polyneuropathy or who have an inadequate response to tafamidis?”ResultsThe 13 studies included in the review demonstrate the efficacy of patisiran in reducing the neuropathic progression of the disease, as evidenced by decreased mNIS+7 scale scores following 18-month use of the drug. Improvements in the quality of life of patients taking patisiran have been reported, as measured by reduced scores on the Norfolk-QoL-DN scale. Patisiran has also been shown to be effective in reducing NT-proBNP, a marker related to cardiac stress. Improvements in the nutritional status of patients taking patisiran were demonstrated by increasing modified body mass index (BMI). Good tolerability of patisiran was observed by patients using it. Most adverse events were classified as mild or moderate. The studies indicated that the occurrence of deaths is similar between the patisiran and placebo groups. Most deaths were related to cardiac events and were not associated with the use of patisiran.ConclusionsThe use of patisiran in patients with hATTR demonstrated efficacy in reducing the neuropathic progression of the disease, evidenced by decreased mNIS+7 scale scores, improvements in quality of life as measured by reduced Norfolk-QoL-D scale scores, and reduced NT-proBNP. The drug patisiran was well tolerated, with most adverse events rated as mild and moderate.

Pathogenic Profile Characteristics and Clinical Risk Factor Analysis of Patients Who Died from Sepsis Combined with Pulmonary Infection by Metagenomic Next-Generation Sequencing.

Sepsis is one of the major diseases that seriously threatens human health, and its incidence and in-hospital morbidity and mortality rates remain high. Applying metagenomic next-generation sequencing (mNGS) technology to analyze the differences in pathogenic profiles and clinical factors in patients surviving and dying from sepsis combined with pulmonary infections provides diagnostic value and application for clinical purposes. Sixty-three BALF samples from patients with sepsis combined with pulmonary infection from Fuqing Hospital Affiliated to Fujian Medical University were collected, and all of them were tested by simultaneous mNGS and conventional microbial combined test (CMT) to compare the pathogenic profiles and clinical indices of patients who survived and died of sepsis combined with pulmonary infection and to further compare the diagnostic differences between mNGS and CMT in patients who survived and died of sepsis combined with pulmonary infection. We analyzed the diagnostic value of mNGS for sepsis combined with pulmonary infection. A total of 141 strains of pathogens were isolated from 63 samples of patients with sepsis combined with pneumonia at suspected infection sites, Klebsiella pneumoniae, Acinetobacter baumannii, and Stenotrophomonas maltophilia are predominant, and higher ApacheII, LAC, P and PT are all risk factors affecting the death of septic patients. Applying the mNGS method to patients with sepsis combined with pneumonia can improve the positive detection rate of pathogenic microorganisms and focus on death-related risk factors such as pathogenic bacteria species as well as clinical laboratory indices, which can guide clinicians to take appropriate measures to treat patients with sepsis and reduce the occurrence of death.

Behavior of Pregnant Women In Pregnancy Examinations In Manisa Village, Baranti District

The occurrence of maternal deaths is related to direct causal factors and indirect causes. The direct causes of maternal death in Indonesia are still dominated by factors. by bleeding, eclampsia, and infection, while the indirect factors causing maternal death are because there are still many cases, 3 too late and 4 too late, which are related to access, socio-cultural, educational and economic factors. This research uses a combination method with a sequential explanatory design. The first uses quantitative methods, and the second uses qualitative methods. A quantitative approach is used to identify and explain variables that influence behavior such as knowledge, attitudes, facilities and encouragement of officers. A qualitative approach is used to support and complement quantitative research results. The chi-square test shows that there is a significant relationship between knowledge, facilities and encouragement of health workers on the behavior of pregnant women in pregnancy checks. P value = 0.001. If the significance value is &lt;0.05, it is recognized that there is a statistically significant correlation. Meanwhile, attitudes show no statistical correlation. The logistic regression test shows that there is an influence between knowledge and facilities on the behavior of pregnant women. There are two substantial findings, namely regarding knowledge about antenatal care and the availability of facilities which influence the behavior of pregnant women in antenatal care.

Free Thyroxine (fT4) as a Potential Biomarker of Neurological and Functional Outcome in Acquired Brain Injury: A Prospective Multicenter Cohort Study

The potential involvement of thyroid hormones (THs) in the neurological and functional recovery of patients with brain damage has been hypothesized. We aimed at investigating the role of THs and their variations during the rehabilitation process as predictive biomarkers of neurological and functional outcome in patients with acquired brain injury (ABI). This prospective, multicenter cohort study included 220 patients with ABI consecutively admitted for a 6-month neurorehabilitation program. Data on the etiology of the brain injury, occurrence of seizures, neurosurgical procedures, and death during hospitalization were collected. Both at the baseline (T0) and at the end of the rehabilitation process (T1), the following variables were evaluated: thyroid function (TSH, fT4, and fT3) and outcome measure including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale-Extended (GOS-E), and Functional Independence Measure (FIM) scale. During neurorehabilitation, a significant decrease in fT4 levels was documented in the population as a whole and in patients with severe ABI (p &lt; 0.0001), whereas no significant variations were found in TSH and fT3 levels. No significant associations were found between THs and seizure occurrence, while the neurological and functional outcomes were associated with the variation in fT4 levels during rehabilitation. In particular, a higher magnitude of decrease in fT4 levels emerged as an independent predictor of more severe neurological damage (OR = 3.48, CI 95% 1.04–11.69, p = 0.04) and a lower functional recovery (β = −0.22, p = 0.01). In conclusion, serum fT4 variation during neurorehabilitation could represent a potential biomarker of neurological and functional outcome in patients with ABI. Further studies are needed to investigate the mechanisms underlying this association.

Clofarabine and High-Dose Melphalan Reduced Intensity Conditioning Regimen with Methotrexate-Based GvHD Prophylaxis

Introduction: Reduced-intensity conditioning (RIC) allogeneic stem cell transplant (allo-SCT) remains a curative option for elderly and/or unfit patients with hematologic malignancies. Fludarabine-containing regimens make up the cornerstone of RIC regimens, however, during the nation-wide fludarabine shortage in 2022, many institutions used fludarabine-free RIC regimens out of necessity though data was extremely limited. Clofarabine is a second-generation purine analog with more potent anti-leukemic activity and a different adverse effect profile compared to fludarabine. We report our experience with clofarabine-based RIC conditioning for adult patients with non-Hodgkin's lymphoma (NHL) and myeloid malignancies. Methods: In this retrospective single-center matched cohort study at Stanford Health Care, we compared adult RIC allo-SCT patients receiving clofarabine and melphalan (CloMel) with a matched cohort receiving fludarabine and melphalan (FluMel) from January 1, 2022 to December 31, 2022. CloMel consisted of clofarabine 30 mg/m 2 on days -6 to -2 followed by melphalan 140 mg/m 2 on day -1, while FluMel consisted of fludarabine 30 mg/m 2 on days -5 to -2 followed by melphalan 140 mg/m 2 on day -1. Clofarabine dose adjustments were made in patients with renal dysfunction according to the following institutional guidelines based on creatinine clearance (CrCl): 22.5 mg/m 2 for CrCl 60 to 79 mL/min, 15 mg/m 2 for CrCl 30 to 59, and avoiding clofarabine for CrCl less than 30 mL/min. Dose modifications for fludarabine and melphalan due to renal dysfunction were at the discretion of the care team. Patients received graft versus host disease (GvHD) prophylaxis with tacrolimus and methotrexate. Efficacy and safety outcomes were assessed. Data were analyzed using Mann-Whitney U and chi-square tests. Results: We identified 9 matched pairs for a total of 18 patients. Most patients received an allo-SCT for a myeloid malignancy (8 patients with AML, 8 patients with MDS, and 2 patients with NHL). All patients received a peripheral blood stem cell transplant, with 89% receiving a matched unrelated donor and 11% receiving a matched related donor transplant. Baseline characteristics were balanced between groups. There was no difference in time to neutrophil engraftment (mean 14 vs 14 days; p=0.42), time to platelet engraftment (mean 16 vs 24 days; p=0.33), or 100% donor whole blood chimerism (71% vs 78%; p=0.32) at 6 months in the CloMel and FluMel groups, respectively. No statistically significant difference was observed for the number of patients who experienced acute (2 vs 0; p=0.13) and chronic GvHD (0 vs 4, p=0.09) at 6 months between groups. At 6 months, 2 patients in the CloMel group and no patients in the FluMel group experienced early non-relapse mortality (p=0.13). Both patients who died experienced acute renal failure secondary to conditioning chemotherapy with a median onset of renal dysfunction 6 days after initiation of clofarabine, followed by sepsis and multi-organ failure. Both patients required initiation of external renal replacement therapy and ultimately passed 12 days and 29 days post-transplant, prior to engraftment. Notably, both patients had a history of kidney dysfunction prior to transplant, one patient with chronic kidney disease (CKD) stage 3 and the other patient with lymphomatous involvement of the kidneys, and received appropriate clofarabine renal dose adjustments per institutional standards. Conclusion: CloMel demonstrated similar efficacy outcomes at 6 months and represents a feasible alternative to FluMel as a RIC regimen. However, given the notable occurrence of renal failure and early death in the CloMel arm, careful consideration and particular caution in administering to patients with a prior history of renal disease is recommended.

Systemic Chemotherapy with or without Hepatic Arterial Infusion Chemotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Oligometastasis: A Propensity Score–Matched Analysis

PurposeTo compare the effectiveness of hepatic arterial infusion chemotherapy (HAIC) plus systemic chemotherapy (SYS) with that of SYS alone in patients with intrahepatic cholangiocarcinoma (ICC) with extrahepatic oligometastasis in terms of overall survival (OS) and mortality related to liver failure. Materials and MethodsConsecutive patients diagnosed with ICC with extrahepatic oligometastasis who received either HAIC plus SYS or SYS alone between January 2019 and January 2021 were included in this retrospective cohort study. Propensity score matching (PSM) analysis was performed to address potential confounding factors. OS, progression-free survival (PFS), and intrahepatic progression–free survival (IPFS) were analyzed. The occurrence of death due to liver failure was also assessed. ResultsThe study included a total of 179 patients, with 96 receiving SYS alone and 83 receiving HAIC plus SYS. After PSM, 83 pairs were included for further analysis. The median OS and IPFS were significantly longer in the HAIC plus SYS group compared to the SYS alone group (OS: 15.8 months vs 12.7 months; P = .023; IPFS: 9.7 vs 6.1 months; P < .001). No difference was found in PFS between the 2 groups. The HAIC plus SYS group had a significantly lower rate of mortality due to liver failure compared to the SYS alone group (42% vs 72%; P = .002). ConclusionsHAIC plus SYS is a promising treatment approach for patients with ICC and extrahepatic oligometastasis with improved OS, IPFS, and freedom from liver failure mortality compared with SYS alone.

Minor head injury in anticoagulated patients: Outcomes and analysis of clinical predictors. A prospective study

BackgroundThe optimal management of patients taking oral anticoagulants who experience minor head injury (MHI) is unclear. The availability of validated protocols and reliable predictors of prognosis would be of great benefit. We investigated clinical factors as predictors of clinical outcomes and intracranial injury (ICI). MethodsWe conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The primary outcome was the occurrence of MHI-related death or re-admission to ED at day +30. The secondary outcome was the rate of delayed ICI (dICI), defined as second positive CT scan after a first negative CT scan. We assessed some clinical predictors derived from guidelines and clinical prediction rules as potential risk factors for the outcomes. Results450 patients with a negative first CT scan who underwent a second CT scan composed our ‘study population’. The rate of the primary outcome was 4%. The rate of the secondary outcome was 4.7%. Upon univariate and multivariate analysis no statistically significant predictors for the outcomes were found. ConclusionsPrevious retrospective studies showed a lot of negative predictive factors for anticoagulated patients suffering a minor head injury. In our prospective study no clinical factors emerged as predictors of poor clinical outcomes and dICI. So, even if we confirmed a low rate of adverse outcomes, the best management of these patients in ED remains not so clear and future trials are needed.

Deep learning framework for epidemiological forecasting: A study on COVID-19 cases and deaths in the Amazon state of Pará, Brazil.

Modeling time series has been a particularly challenging aspect due to the need for constant adjustments in a rapidly changing environment, data uncertainty, dependencies between variables, volatile fluctuations, and the need to identify ideal hyperparameters. The present study presents a Framework capable of making projections from time series related to cases and deaths by COVID-19 in the Amazonian state of Pará, in Brazil. For the first time, deep learning models such as TCN, TRANSFORMER, TFT, N-BEATS, and N-HiTS were assessed for this purpose. The ARIMA statistical model was also used in post-processing for residual adjustment and short-term smoothing of the generated forecasts. The Framework generates probabilistic forecasts, with multivariate support, considering the following variables: daily cases per day of the first symptom, cases published daily, the occurrence of deaths, deaths published daily, and percentage of daily vaccination. The generated predictions are statistically evaluated by determining the best model for 7-day moving average projections using evaluating metrics such as MSE, RMSE, MAPE, sMAPE, r2, Coefficient of Variation, and residual analysis. As a result, the generated projections showed an average error of 5.4% for Cases Publication, 8.0% for Cases Symptoms, 11.12% for Deaths Publication, and 4.6% for Deaths Occurrence, with the N-HiTS and N-BEATS models obtaining better results. In general terms, the use of deep learning models to predict cases and deaths from COVID-19 has proven to be a valuable practice for analyzing the spread of the virus, which allows health managers to better understand and respond to this kind of pandemic outbreak.