Early Death Research Articles

Risk factors and nomograms for diagnosis and early death in patients with combined small cell lung cancer with distant metastasis: a population-based study.

Combined small cell lung cancer (CSCLC) with distant metastasis (DM) is an aggressive disease with a poor prognosis. Effective nomograms are needed to predict DM and early death in patients with CSCLC and DM. This retrospective study included patients with CSCLC from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Risk factors for DM and early death were analyzed by univariate and multivariate logistic regression. Nomograms were constructed based on the results in a training cohort and confirmed in a validation cohort, and their performances were assessed by concordance index (C-index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). A total of 788 patients with CSCLC were selected, including 364 patients with metastatic CSCLC. Sex, tumor site, T stage, and N stage were independent risk factors for DM, while age, surgery, chemotherapy, and liver metastasis were independent risk factors for early death. C-index, ROC, calibration, and DCA curve analyses all showed good predictive performances for both nomograms. These nomograms could reliably predict DM risk in CSCLC patients and early death in CSCLC patients with DM, and may thus help clinicians to assess these risks and implement individualized therapies.

A novel homozygous mutation in the DNAAF3 gene leads to severe asthenozoospermia and teratospermia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder characterized by ultrastructural defects in the cilia or flagella of cells, causing respiratory abnormalities, sinusitis, visceral transposition, and male infertility. DNAAF3 plays an important role in the assembly and transportation of axonemal dynein complexes in cilia or flagella and has been shown to be associated with PCD. To date, only two cases of PCD with infertility associated with DNAAF3 mutations have been reported, and no mouse models for this gene have been successfully constructed. This study was conducted on an infertile Chinese male patient with a history of bronchitis. Examination of the patient's semen revealed severe asthenozoospermia and teratospermia. Whole exome sequencing revealed a new homozygous loss-of-function DNAAF3 mutation. CRISPR-Cas9 gene-editing technology was used to construct the same mutation in C57/B6 mice, revealing that homozygous C57/B6 mice were characterized by severe hydrocephalus and early death. The results of this study expand the mutation spectrum of DNAAF3 and confirm its correlation with PCD pathogenesis. This study provides new insights on the mechanisms underlying male infertility related to DNAAF3 mutation and PCD.

Inflammatory Markers Influencing Mortality Rates in Diabetic Foot Ulcer – A Prospective Study

This study aimed to explore the relationship between inflammatory markers, apolipoprotein E (ApoE) levels, renal function, and mortality in patients with diabetic foot ulcers (DFUs). Conducted as a single-center prospective study at the Clinical County Emergency Hospital of Arad, Romania, the study included 90 patients diagnosed with infected DFUs. The main objective was to determine the risk factors for mortality over a three-year follow-up period, focusing on early versus late deaths. The results indicated a significant correlation between elevated levels of ApoE, pentraxin 3 (PTX3), procalcitonin (PCT), and impaired renal function with increased mortality. Patients with higher levels of these biomarkers, particularly those with impaired renal function, were more likely to experience early death, especially within the first 90 days after surgery. The findings underscore the critical role of these factors in predicting mortality and highlight the need for early intervention and aggressive management of these risk factors to improve outcomes in this vulnerable population. Despite advancements in medical and surgical care, the prognosis for patients with DFUs remains poor, particularly due to the recurrent nature of the ulcers and the presence of comorbidities like chronic kidney disease.

Low smoking exposure and development and prognosis of COPD over four decades: a population-based cohort study.

A diagnosis of COPD is mainly considered in individuals with >10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis. We followed non-obstructed adult smokers from the Copenhagen City Heart Study for COPD, defined as a forced expiratory volume in 1 s (FEV1)/forced vital capacity <0.70 and FEV1 <80% predicted, and for related clinical outcomes. First, we followed individuals for 5 years according to baseline smoking for risk of developing COPD, and thereafter for up to four decades for severe exacerbations and death. In 6098 non-obstructed smokers, 1781 (29%) developed COPD after 5 years of follow-up: 23% of individuals with <10 pack-years of smoking at baseline, 26% of those with 10-19.9 pack-years, 30% of those with 20-39.9 pack-years and 39% of those with ≥40 pack-years. During four decades of follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10 pack‑years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94 (95% CI 1.36-2.76) in those without COPD and ≥10 pack-years, 2.83 (95% CI 1.72-4.66) in those with COPD and <10 pack-years, 4.34 (95% CI 2.93-6.43) in those with COPD and 10-19.9 pack-years, 4.39 (95% CI 2.98-6.46) in those with COPD and 20-39.9 pack-years and 4.98 (95% CI 3.11-7.97) in those with COPD and ≥40 pack-years. Corresponding HRs for all-cause mortality were 1.20 (95% CI 1.10-1.32), 1.31 (95% CI 1.13-1.53), 1.59 (95% CI 1.40-1.79), 1.81 (95% CI 1.62-2.03) and 1.81 (95% CI 1.55-2.10). Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.

Foreseeably Early Deaths in Patients With Psychiatric Disorders: Challenges in Caring for Patients Manifesting Likely Fatal Trajectories.

Patients with psychiatric disorders often have foreshortened lives, attributed both to "natural" medical and "unnatural" external causes of death such as suicide, homicide, and accident. Many deaths are foreseeable due to circumstances linked to patients' psychiatric disorders. These can include illness-associated disparities, adverse treatment effects, lack of self-care, and behaviors stemming directly from psychopathological processes. Whereas some of these processes contribute indirectly to patients' causes of death, others are more directly consequential, causing patients to "die from" their psychiatric disorders. Some patients manifest likely fatal trajectories that may lead to "end-stage" psychiatric disorders. Palliative approaches may optimize their quality of life and potentially alter these trajectories, but patients with psychiatric disorders are less likely to receive optimal end-of-life care. Although assuring a "good death" can be challenging, systematic efforts can assist in providing patients with psychiatric disorders deaths with dignity rather than indignity.

Оптимізація стратифікації ризику несприятливого найближчого прогнозу у хворих із високим ризиком тромбоемболії легеневої артерії

The aim – to develop and validate a scale for the additional risk of early death in patients with high-risk pulmonary embolism.Materials and methods. At the 1st stage of the study, a formula for additional stratification of the risk of early death of high-risk PE patients was developed. With the help of ROC analysis, it was established that the sensitivity of the received prognostic formula is 64.0 %; specificity 92.1 %. Based on the formula, we proposed the SBAFS scale (S – saturation, B – bifurcation, A – arterial hypotension, F – ejection fraction, S – female gender). To further verify the proposed scale and formula, the II stage of the study was conducted on a multicenter cohort (8 centers in Ukraine that provided information on high-risk PE patients who were hospitalized for the period from 01.01.2023 to 12.2023). At this stage, 75 high-risk PE patients were included, the average age was (60.60±13.40) years, among them there were 38 (50.7 %) men, 37 (49.3 %) women. The first group consisted of 65 (80 %) patients who were discharged from the hospital with improvement, and the second group – 15 (20 %) patients died during hospitalization due to an acute episode of PE. Clinical and anamnestic, laboratory and instrumental indicators were analyzed, statistical analysis was performed data.Results and discussion. It was established that in the II subgroup of patients with high-risk PE, not only the average value of the Y indicator was significantly higher than in the I subgroup: (0.785±0.250) and (0.306±0.330), p=0.00002, but also the proportion of patients with indicator Y&gt;0.5: 13 (86.7 %) and 16 (26.7 %), respectively, p=0.00001. In order to check the sensitivity and specificity of the formula, we performed a ROC analysis for the II stage of our research: the sensitivity of the prognostic formula we obtained is 93.3 %; specificity of 74.6 %, which confirms the result of the 1st stage. When checking the SBAFS scale recommended by us, it was also established that the average score on the scale was (2.53±0.83) in patients of the II group and was higher than in the I group: (1.57±0.96), p=0,0006.Conclusions. The main factors associated with the risk of in-hospital death in high-risk PE patients are a decrease in oxygen saturation, thrombus localization in the LA bifurcation according to MSCT-angiography, arterial hypotension, female sex, and a decrease in the left gastric ejection fraction according to Echo-CG. The previously proposed SBAFS risk scale confirmed its value when tested with the participation of cardiologists from 8 regions of Ukraine – sensitivity 93 %, specificity – 75 %. The possibility of using a simplified assessment of the risk of early death in patients with PE with a high total score was confirmed, as this indicator was significantly higher in the deceased – 2.5 against 1.6 (р=0.0006).

Early neonatal mortality and determinants in Ethiopia: multilevel analysis of Ethiopian demographic and health survey, 2019

IntroductionDespite remarkable achievements in improving maternal and child health, early neonatal deaths still persist, with a sluggish decline in Ethiopia. As a pressing public health issue, it requires frequent and current studies to make appropriate interventions. Therefore, by using the most recent Ethiopian Mini Demographic Health Survey Data of 2019, we aimed to assess the magnitude and factors associated with early neonatal mortality in Ethiopia.MethodsSecondary data analysis was conducted based on the demographic and health survey data conducted in Ethiopia in 2019. A total weighted sample of 5,753 live births was included for this study. A multilevel logistic regression model was used to identify the determinants of early neonatal mortality. The adjusted odds ratio at 95% Cl was computed to assess the strength and significance of the association between explanatory and outcome variables. Factors with a p-value of < 0.05 are declared statistically significant.ResultsThe prevalence of early neonatal mortality in Ethiopia was 26.5 (95% Cl; 22.5–31.08) per 1000 live births. Maternal age 20–35 (AOR, 0.38; 95% Cl, 0.38–0.69), richer wealth index (AOR, 0.47; 95% Cl, 0.23–0.96), having no antenatal care visit (AOR, 1.86; 95% Cl, 1.05–3.30), first birth order (AOR, 3.41; 95% Cl, 1.54–7.56), multiple pregnancy (AOR, 18.5; 95% Cl 8.8–38.9), presence of less than two number of under-five children (AOR, 5.83; 95% Cl, 1.71–19.79) and Somali region (AOR, 3.49; 95% Cl, 1.70-12.52) were significantly associated with early neonatal mortality.ConclusionThis study showed that, in comparison to other developing nations, the nation had a higher rate of early newborn mortality. Thus, programmers and policymakers should adjust their designs and policies in accordance with the needs of newborns and children’s health. The Somali region, extreme maternal age, and ANC utilization among expectant moms should all be given special consideration.

Early neonatal mortality in Ethiopia from 2000 to 2019: an analysis of trends and a multivariate decomposition analysis of Ethiopian demographic and health survey

BackgroundEarly neonatal deaths, occurring within the first six days of life, remain a critical public health challenge. Understanding the trends and factors associated with this issue is crucial for designing effective interventions and achieving global health goals. This study aims to examine the trends in early neonatal mortality in Ethiopia and identify the key factors associated with changes in early neonatal mortality over time.MethodsThis study utilized five consecutive Ethiopian Demographic and Health Survey datasets from 2000 to 2019. To investigate the trends and identify factors influencing changes in early neonatal mortality over time, conducted a trend analysis and a logit-based multivariate decomposition analysis. Data management and analyses were performed using STATA version 17/MP software. All analyses were weighted to account for sampling probabilities and non-response. Statistical significance was determined at a two-sided p-value threshold of less than 0.05.ResultThe analysis included a total of 12,260 weighted women from the 2000 survey and 5,527 weighted women from the 2019 survey. Over the study period, there was an overall downward trend in early neonatal mortality, decreasing from 34 deaths per 1000 live births in 2000 to 27 deaths per 1000 live births in 2019. The annual rate of reduction was estimated to be 1.03%. Approximately 45% of the observed decline in early neonatal mortality rate can be attributed to changes in population characteristics or endowments (E) during the study period. Factors such as the mother’s age, maternal education, marital status, preceding birth interval, types of pregnancy, and the sex of the child significantly contributed to the compositional change in the early neonatal mortality rate.ConclusionOver the past two decades, Ethiopia has seen a modest decline in early neonatal mortality, but this progress falls short of the Sustainable Development Goal (SDGs) targets. To achieve the SDGs, the Ministry of Health and its partners should intensify efforts to reduce early neonatal mortality. Strategies like preventing early/late pregnancies, promoting appropriate marriage timing, and prioritizing education could help further reduce early neonatal deaths. Further research is also needed to explore the factors driving this issue.

Development of New Diffuse Large B Cell Lymphoma Mouse Models.

Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, with ~40% of patients experiencing refractory or relapsed disease. Given the low response rates to current therapy, alternative treatment strategies are necessary to improve patient outcomes. Here, we sought to develop an easily accessible new xenograft mouse model that better recapitulates the human disease for preclinical studies. We generated two Luciferase (Luc)-EGFP-expressing human DLBCL cell lines representing the different DLBCL cell-of-origin subtypes. After intravenous injection of these cells into humanized NSG mice, we monitored the tumor growth and evaluated the organ-specific engraftment/progression period. Our results showed that human IL6-expressing NSG (NSG-IL6) mice were highly permissive for DLBCL cell growth. In NSG-IL6 mice, systemic engraftments of both U2932 activated B cell-like- and VAL germinal B cell-like-DLBCL (engraftment rate; 75% and 82%, respectively) were detected within 2nd-week post-injection. In the organ-specific ex vivo evaluation, both U2932-Luc and VAL-Luc cells were initially engrafted and expanded in the spleen, liver, and lung and subsequently in the skeleton, ovary, and brain. Consistent with the dual BCL2/MYC translocation association with poor patient outcomes, VAL cells showed heightened proliferation in human IL6-conditioned media and caused rapid tumor expansion and early death in the engrafted mice. We concluded that the U2932 and VAL cell-derived human IL6-expressing mouse models reproduced the clinical features of an aggressive DLBCL with a highly consistent pattern of tumor development. Based on these findings, NSG mice expressing human IL6 have the potential to serve as a new tool to develop DLBCL xenograft models to overcome the limitations of standard subcutaneous DLBCL xenografts.

Analysis of serious trauma injury patterns in Navarre (Spain) (2010-2019)

The aim of this study is to describe major trauma cases in Navarre and analyze differences based on mortality groups, sex, and mode of injury. Cross-sectional study of major traumas (severity =3) registered in Navarre between 2010 and 2019. We analyzed the type of trauma, intentionality, the mode of injury, and the affected anatomical area. The odds ratio for major trauma associated with different variables was calculated. The study included 2,609 patients; mean age was 54.7 years (0-101) and 70.9% were male. A predominance of accidental (84%) / blunt (94.7%) major traumas was recorded, primarily resulting from falls (46.5%) and car accidents (18.4%). Women experienced more falls and pedestrian accidents, while men had more motorcycle, bicycle, knife/firearm accidents, and contusions. Most major traumas affected the head and thorax. Head trauma was significantly more common in deceased individuals and women, while thoracic trauma was more frequent in patients who died on-site and in men. Head injuries were caused by falls from low heights and firearms, whereas thoracic injuries resulted from car accidents and falls from height. The risk of major trauma decreased with age; deceased patients were between two and three times more likely to present lesions in all anatomical areas. Gender differences are observed in intentionality, type, and mode of injury. Head and thoracic injuries are potentially life-threatening and abdominal and extremity/pelvic ring injuries are associated with early deaths. This suggests that the extent and severity of these injuries complicate treatment and management.

Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.

Therapeutics that rescue folding, trafficking, and function of disease-causing missense mutants are sought for a host of human diseases, but efforts to leverage model systems to test emerging strategies have met with limited success. Such is the case for Niemann-Pick type C1 disease, a lysosomal disorder characterized by impaired intracellular cholesterol trafficking, progressive neurodegeneration, and early death. NPC1, a multipass transmembrane glycoprotein, is synthesized in the endoplasmic reticulum and traffics to late endosomes/lysosomes, but this process is often disrupted in disease. We sought to identify small molecules that promote folding and enable lysosomal localization and functional recovery of mutant NPC1. We leveraged a panel of isogenic human induced neurons expressing distinct NPC1 missense mutations. We used this panel to rescreen compounds that were reported previously to correct NPC1 folding and trafficking. We established mo56-hydroxycholesterol (mo56Hc) as a potent pharmacological chaperone for several NPC1 mutants. Furthermore, we generated mice expressing human I1061T NPC1, a common mutation in patients. We demonstrated that this model exhibited disease phenotypes and recapitulated the protein trafficking defects, lipid storage, and response to mo56Hc exhibited by human cells expressing I1061T NPC1. These tools established a paradigm for testing and validation of proteostatic therapeutics as an important step toward the development of disease-modifying therapies.

Synthesis, crystal structure, Hirshfeld surface, computational and biological studies of spiro-oxindole derivatives as MDM2-p53 inhibitors.

The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, 1H, 13C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC50 value of 8.13 ± 0.66µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.

Pediatric Sickle Cell Disease Patients' Hematological Changes during Vaso-Occlusive Crises (VOCS) Versus Steady State

Background: The primary acute outcome of sickle cell disease (SCD) is a vaso-occlusive crisis (VOC) with extreme pain. More than three vaso-occlusive crisis (VOC) hospitalizations in a year increase the risk of early death. The objective of the study was to evaluate the hematological alterations in complete blood count (hemoglobin, red blood cell indices, white blood cell count, and platelets) and C-reactive protein levels during vaso-occlusive crises in patients with sickle cell anemia (HbSS) compared to a stable symptomatic state. Methodology: This study is a prospective descriptive study conducted in a hospital setting. During the period from February to June 2015, a Sudan Sickle Cell Anemia Center (SSCAC) in North Kordofan State, Sudan, treated a total of 100 patients with sickle cell anemia. Out of these patients, 74 had a vaso-occlusive crisis and 26 had a steady-state condition. All patients had measurements of their complete blood count (CBC) and C-reactive protein (CRP) levels. We calculated the average values of CBC and CRP level counts during vaso-occlusive crises and compared them to the values during steady state using independent t-tests. We analyzed the collected data using the Statistical Tool for Social Sciences (SPSS) software tool, specifically version 13. Results: The statistical analysis of the patient sample during vaso-occlusive crisis and steady state revealed that the concentration of hemoglobin (Hb) was 6.55 g/dl ± 1.3 and 9.8 g/dl ± 2.4, respectively, with a p-value of 0.000. The packed cell volume (PCV) was 20.4% ± 3.9 and 30.7% ± 7.1, respectively, with a p-value of 0.000. The red blood cell (RBC) count was 2.5×106/µl ± 0.57 and 3.9×106/µl ± 1.1, respectively, with a p-value of 0.000. A lot more white blood cells (WBC) were present in vasoocclusive than in steady state, with numbers 19.36 x 109/l ± 10.645 and 76.76 x 109/l ± 20.19, respectively, and a P-value of ≤0.000. There was a notable statistical disparity in the platelet count, with values of (357.108109/l ± 162.838) and (290.4610×9/l ± 124.40), with a P value of 0.05. In vaso-occlusive crises, the amounts of hemoglobin, packed cell volume (PCV), and red blood cells (RBCs) are lower than they are in the steady-state phase. Conversely, white blood cell (WBC) and platelet levels are much greater in patients experiencing vaso-occlusive crises compared to those in a steady state. The levels of C-reactive protein (CRP) were significantly different between patients experiencing vaso-occlusive crises and those in a stable condition.

Histone deacetylase inhibitor, Trichostatin A mitigates ionizing radiation induced redox imbalance by regulating NRF2/GPX4/PINK1/PARKIN signaling in mice intestine.

Gastrointestinal-acute radiation syndrome (GI-ARS) caused by moderate to high doses of ionizing radiation exposurecontribute to early death in humans. GI injury is also a common adverse effect seen in cancer patients undergoing abdominal/pelvic radiotherapy. Currently, no countermeasure agents have been approved for medical management of GI-ARS. The present study aims to evaluate the mechanism of action of Trichostatin A(TSA), a pan histone deacetylaseinhibitor, against radiation-induced GI injury. TSA (150ng/kg bw) was administered to mice 1h and 24h after 15Gy abdominal irradiation. Expression of various markers of oxidative stress, mitochondrial dysfunction, and apoptosis were checked in the jejunum, and their possible regulation throughthe Nrf2 signaling pathway was evaluated. TSA administered post-irradiation (15Gy + TSA) elevated intestinal total antioxidant and glutathione levels by regulating the expression of Slc7A11 and antioxidant proteins, GCLC, GPX4, and TXNRD1. Improved mitochondrial membrane potential, ATP levels, downregulation of mitochondrial quality control proteins, (PINK1 and PARKIN), and differential regulation of the apoptotic proteins, (BAX, PUMA and BCL2) with reduced intestinal epithelial cell apoptosis in the TSA-adminstered groupwere observed. TSA also upregulated Nrf2 in the presence of its specific inhibitor, ML385, suggesting its involvement in regulating Nrf2 signaling during oxidative stress induced by radiation in intestine. H & E stained jejunumcross-sections revealed that TSA mitigated radiation-mediated intestinalinjury in mice. Present findingsindicate that TSA is beneficial in mitigating the damaging effects of ionizing radiation in the intestine.

Analysis of early death in critically ill patients with acute promyelocytic leukaemia in the HICU

This study was conducted to identify the characteristics and risk factors for early death in critically ill acute promyelocytic leukaemia (APL) patients in the Hemato-oncology ICU (HICU). A total of 44 APL patients from 2017 to 2023 were included. The mortality among APL patients in the HICU was high (27/44, 61.36%). Compared with patients who survived, nonsurvivors had a longer prothrombin time (P = 0.002), lower fibrinogen (P = 0.022), higher white blood cell count (P = 0.004) and higher creatinine (P = 0.037) on hosipital admission. Severe bleeding was the most frequent complication (34 cases, 77.27%), which occurred either preinduction or on Day 5 (IQR 3–7.5 days) of induction. Cerebral bleeding associated with consciousness disturbance was the main reason for HICU admission (18 cases, 40.9%). The leading cause of death was fatal haemorrhage (18/34, 52.94%), which occurred either preinduction or on Day 4 (IQR 3–7 days) of induction. Another common cause of death was sepsis (8/18, 44.44%), which occurred on Day 12 (IQR 9.5–24.75 days) during induction. In conclusion, the main cause of death in APL patients treated in the HICU was primary being attributed to fatal bleeding, followed by sepsis.

A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS.

Clinical characteristics and analysis of related factors associated with early death in newly diagnosed patients with acute promyelocytic leukemia

ObjectiveThe objective of this study was to investigate the clinical characteristics and analysis of related factors associated with early death in newly diagnosed patients with acute promyelocytic leukemia (APL).MethodsThis retrospective study included patients who visited our hospital between January 2010 and August 2022 and were diagnosed with APL for the first time. We analyzed their clinical and laboratory characteristics and analysis of related factors associated with early death.ResultsA total of 269 patients with a primary diagnosis of APL were collected. The male to female ratio was 6:5, and the median age was 42 years (range 7–80). Among patients with initial APL diagnosis, there were 34 early deaths, resulting in an early mortality rate of 13%. The median time from diagnosis to death was 8.5 days (range 3–24). Comparative analysis of the clinical characteristics between patients who died early and those who did not, using a logistic regression model, revealed that age, white blood cell count (WBC) at initial diagnosis, and prolongation time of prothrombin time (PT) were independent risk factors for early death in patients with primary APL (P < 0.05). Comparing the clinical characteristics during hospitalization between the early death group and the non-early death group, it was observed that the daily mean of WBC during hospitalization was significantly higher in patients who died early than in those who did not (P < 0.001). Conversely, the daily mean of platelet count (PLT) was significantly lower in patients who died early compared to those who did not (P < 0.001). Furthermore, statistically significant differences were found in the mean daily infusion of PLT (P < 0.05), fibrinogen (Fib) (P < 0.05), and fresh frozen plasma (FFP) (P < 0.05) during hospitalization between patients who died early and those who did not. Specifically, the mean daily infusion of PLT and FFP was significantly higher in the early-death group than in the non-early-death group. Cerebral hemorrhage was identified as the immediate cause of death in 25 out of the 34 early-death patients (74%). The remaining causes of death included infection in 5 cases (15%), all of which were severe pulmonary infections, including 2 cases of combined differentiation syndrome, and abandonment of treatment in 4 patients (11%) at initial diagnosis.ConclusionIn patients with primary APL, age, WBC at initial diagnosis, and PT prolongation time were identified as independent risk factors for early death (P < 0.05). Laboratory findings regarding WBC and PLT during hospitalization, as well as the infusion of PLT, Fib, and FFP during hospitalization, were also statistically significant. Cerebral hemorrhage was found to be the main cause of early death in patients with primary APL.

Medical history and lifestyle factors have limited impact on time‐to‐first‐treatment in patients with chronic lymphocytic leukemia

AbstractBackgroundChronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non‐modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease.MethodIn 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non‐modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time‐to‐first‐treatment (TTFT) and adjusted all results for the CLL‐International Prognostic Index (CLL‐IPI).ResultsTTFT was shorter for patients with high/very high‐risk CLL‐IPI than those with low/intermediate risk CLL‐IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL‐IPI from any environmental characteristics assessed.ConclusionsWe found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis.

Interrogating the Influence of &amp;lt;i&amp;gt;Babaláwo-Ifá&amp;lt;/i&amp;gt; Priest’s Lifestyle on &amp;lt;i&amp;gt;Ọmọ Awo&amp;lt;/i&amp;gt;-Neophytes as Found in &amp;lt;i&amp;gt;Ìrẹ́tẹ̀-Ọ̀kànràn&amp;lt;/i&amp;gt; in &amp;lt;i&amp;gt;Ifá&amp;lt;/i&amp;gt; Divination and the Lessons for the Contemporary Society

Leadership, the ability to lead by good example, is universal and it cuts across every aspect of human life, be it political, social, economic and religious. Leadership quality must be displayed by the people at the top so that their followers/disciples will not be led astray. However, not all leaders are leading by good examples, the effects of which are felt by the led at the receiving end and the society at large because the disciples or the followers tend to emulate some of the characters of their leaders. Therefore, it is imperative for a leader to demonstrate quality examples for the followers to imitate as demonstrated by Ọ̀rúnmìlà in Ìrẹ́tẹ̀-Ọ̀kànràn and other similar tenets of Ifá divination system. This is found in the lifestyle of the Babaláwo-Ifá priests that followed the teachings/lifestyle of Ọ̀rúnmìlà, the custodian of Ifá and by extension their neophytes, particularly, in the aspect of greed. Greed is evidently displayed in leadership especially in contemporary third world nations. Conversely, how has the lifestyle of Babaláwo been able to curtail this among their followers and of what benefits to the contemporary generation? The study proffered answers to the questions from the data generated from fifteen Babaláwo-Ifá priests and twenty Ọmọ Awo-trainees/ neophytes and their views content analysed. The study was able to discover that Ifá priesthood is a service to humanity (not a money-making venture) and discipline against greed is their watchword for them to achieve this. If the contemporary generation could imbibe this culture, it is going to be the best antidote against many social vices particularly the get-rich quick syndrome that is rampant among the youths nowadays that is responsible for their early death.

Impact of postpartum maternal fever or hypothermia on newborn and early infant illness and death in Southwestern Uganda

BackgroundDeaths occurring during the neonatal period contribute close to half of under-five mortality rate (U5MR); over 80% of these deaths occur in low- and middle-income countries (LMICs). Poor maternal antepartum and perinatal health predisposes newborns to low birth weight (LBW), birth asphyxia, and infections which increase the newborn’s risk of death.MethodsThe objective of the study was to assess the association between abnormal postpartum maternal temperature and early infant outcomes, specifically illness requiring hospitalisation or leading to death between birth and six weeks’ age. We prospectively studied a cohort of neonates born at Mbarara Regional Referral Hospital in Uganda to mothers with abnormal postpartum temperature and followed them longitudinally through early infancy. We performed a logistic regression of the relationship between maternal abnormal temperature and six-week infant hospitalization, adjusting for gestational age and 10-minute APGAR score at birth.ResultsOf the 648 postpartum participants from the parent study who agreed to enrol their neonates in the sub-study, 100 (15%) mothers had abnormal temperature. The mean maternal age was 24.6 (SD 5.3) years, and the mean parity was 2.3 (SD 1.5). There were more preterm babies born to mothers with abnormal maternal temperature (10%) compared to 1.1% to mothers with normal temperature (p=˂0.001). While the majority of newborns (92%) had a 10-minute APGAR score > 7, 14% of newborns whose mothers had abnormal temperatures had APGAR score ˂7 compared to 7% of those born to mothers with normal postpartum temperatures (P = 0.02). Six-week outcome data was available for 545 women and their infants. In the logistic regression model adjusted for gestational age at birth and 10-minute APGAR score, maternal abnormal temperature was not significantly associated with the composite adverse infant health outcome (being unwell or dead) between birth and six weeks’ age (aOR = 0.35, 95% CI 0.07–1.79, P = 0.21). The 10-minute APGAR score was significantly associated with adverse six-week outcome (P < 0.01).ConclusionsWhile our results do not demonstrate an association between abnormal maternal temperature and newborn and early infant outcomes, good routine neonate care should be emphasized, and the infants should be observed for any abnormal findings that may warrant further assessment.Target journalBMC Pregnancy and Childbirth (https://bmcpregnancychildbirth.biomedcentral.com/).