Main Cause Of Early Death Research Articles

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.

All-Trans-Retinoic Acid Induction Overcomes Immune Evasion through Downregulating Immune Checkpoint Molecules and Inducing a Cytokine Storm Triggered By Overexpression of S100A8/A9 Signaling

Background: More than 95% of acute promyelocytic leukemia (APL) patients can achieve complete remission by dual induction of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). However, early death is a treatment obstacle of APL. The main causes of early death in APL include hemorrhage, differentiation syndrome (DS) related to induction therapy, and infection. Currently, the mechanism of DS in APL largely remains unclear. This study aims to investigate the pathogenetic mechanism and treatment pattern for APL DS and find a suitable biomarker for DS using multiomics approaches. Methods: Eighty newly diagnosed APL patients were recruited through Jan 2019 to Jan 2021 from a clinical trial (NCT04446806). Matched RNA and plasma samples of APL at presentation and DS were studied by RNA-seq and Human Cytokine Array. Two matched peripheral blood samples at presentation and DS from 2 severe DS patients were selected for 10×scRNA-seq analysis, compared with 3 peripheral blood and 2 bone marrow controls. Results: The incidence of DS was 35.3% (29/80), including 21.3% (17/80) moderate DS and 15% (12/80) severe DS. Bulk RNA-seq suggested immune response and cytokines interaction might play important roles in the development of DS ( Figure 1A and B). Significant downregulation of immune checkpoint molecules was shown in the DS period, such as GAL-9, which plays a crucial role in regulating the immune response ( Figure 1C). The activated CD4 +T and CD8 +T cells were amplification at diagnosis period compared with the corresponding CR/CRi period, then declined dramatically at DS period ( Figure 1 D). 10×scRNA-seq analysis revealed the activation of neutrophils and monocytes through innate immune response and inflammatory response ( Figure 1 E). Consistent with bulk RNA-seq results, apparent elevated expression of multiple inflammatory storm-related cytokines/receptors are shown in the DS period in monocytes and neutrophils, which indicates they contribute to the inflammatory cytokine storm ( Figure 1 F). These results indicated that ATRA induction overcomes immune evasion and induces highly activated immune response through downregulating immune checkpoint molecules. Based on 10×scRNA-seq data, differentiated promyelocytic leukemic cell, neutrophils and monocytes are major cell populations and expressed significantly higher cytokine and chemokine in DS stage, indicating that these cells might be major sources of the cytokine storm ( data not shown). We found S100A8 and S100A9, which function as danger-associated molecular pattern (DAMP) molecules and activate innate immune responses via binding to PRRs, significantly upregulated among all known alarmins ( Figure 1G). S100A8/A9 can be induced by ATRA induction, and also activate ERK, JAK-STAT and NF-κB signaling pathways ( Figure 1H). S100A8/A9 expression can be repressed by ERK inhibitor ( Figure 1I). Knockdown of S100A9 induced lower phosphorylation level of STAT1 and P65 ( Figure 1J). These results indicated S100A8/A9 were regulated by the ERK signaling and controlled the JAK-STAT and NF-κB signaling pathway. As a result, JAK-STAT related cytokines could be regulated by S100A8/A9 signaling. Importantly, ROC analysis showed that S100A8/A9 displayed both high sensitivity and specificity as a biomarker for predicting APL DS ( Figure 1K). According to clinical and cytokine storm characteristics of APL DS patients, Dexamethasone (DEX) and Ruxolitinib (RUX) were applied in the treatment of APL DS patients. The percentage of severe DS reduced remarkably after DEX prevention ( Figure 1L, P&amp;lt;0.05). The early death rate of APL declined under the DEX prevention and RUX treatment, and no patient died due to DS ( Figure 1M). The expression of a series of inflammatory cytokines dramatically decreased, indicating that the cytokine storm was effectively suppressed by the treatment of DEX and/or RUX ( Figure 1N). Conclusion s : Our data indicate that ATRA induction could overcome immune evasion through downregulating immune checkpoint molecules. ATRA-induced upregulation of S100A8/A9 may contribute to the cytokine storm observed in the DS stage of APL patients by activating the JAK-STAT and NF-κB signaling pathway. S100A8/A9 is recommended as a biomarker for predicting APL DS. Dexamethasone and Ruxolitinib are appropriate prevention and treatment pattern for APL DS patients.

Estimation of prevalence of risk factor of hypertension among population of Wardha district between age group of 35-60 years: a study protocol.

A serious medical condition known as hypertension or elevated blood pressure significantly rises the risk of brain, heart, kidney, and other medical conditions. It is the most common cardiovascular disease globally and is now recognized as a major health issue that needs to be addressed. It serves as a warning sign for serious illnesses including myocardial infarction, stroke and renal failure. An estimated 46% of the population with hypertension are not aware of the condition they have. Only 42% of those diagnosed with hypertension receive a diagnosis and treatment. 21% (1/5) of the population who have hypertension have it under control. Around the world, high blood pressure (HBP) is a main cause of early death. Knowledge on the prevalence of risk factors for hypertension is needed because there are relatively few community-based research projects on the condition. The objective of this study is to assess the prevalence of hypertension risk factor in the Wardha district in the state of Maharashtra in western India. A cross-sectional study will be performed. The study’s strength lies in the use of a standardized risk factor check list, which will ensure consistency in data collection and minimize bias. The use of a large sample size (165 patients) will also improve the precision of study and increase the generalization of the result.

Estimation of prevalence of risk factor of hypertension among population of Wardha district between age group of 35-60 years: a study protocol.

A serious medical condition known as hypertension or elevated blood pressure significantly rises the risk of brain, heart, kidney, and other medical conditions. It is the most common cardiovascular disease globally and is now recognized as a major health issue that needs to be addressed. It serves as a warning sign for serious illnesses including myocardial infarction, stroke and renal failure. An estimated 46% of the population with hypertension are not aware of the condition they have. Only 42% of those diagnosed with hypertension receive a diagnosis and treatment. 21% (1/5) of the population who have hypertension have it under control. Around the world, high blood pressure (HBP) is a main cause of early death. Knowledge on the prevalence of risk factors for hypertension is needed because there are relatively few community-based research projects on the condition. The objective of this study is to assess the prevalence of hypertension risk factor in the Wardha district in the state of Maharashtra in western India. A cross-sectional study will be performed. The study’s strength lies in the use of a standardized risk factor check list, which will ensure consistency in data collection and minimize bias. The use of a large sample size (165 patients) will also improve the precision of study and increase the generalization of the result.

Perinatal Anoxia: Clinical Aspects and Prognosis at the Commune II Reference Health Centre in Bamako, Mali

Reducing neonatal morbidity and mortality linked to anoxia is a real problem for neonatology units in Mali's health districts. Perinatal anoxia is the main cause of early death in Commune II. The aim of our study was to describe the clinical characteristics and immediate outcome of perinatal anoxia and the factors associated with neonatal mortality in this condition. Materials and methods: We conducted a retrospective cross-sectional study from 1 May 2022 to 30 April 2023 in the paediatric department of the Bamako commune II referral health centre. It concerned all births with anoxia in the commune. Results: Out of 2224 newborns seen for consultation, 83 were hospitalised for anoxia, a frequency of 3.73%. These were newborns delivered vaginally (77.1%), from our centre's maternity unit (80.7%), whose mothers were primiparous (41%), between 18 and 25 years of age (43.4%). The main pathology associated with anoxia was neonatal infection (80.7%). According to the Sarnat classification, the severity of brain damage was stage II in 20.5% of cases and stage III in 68.7%. The case fatality rate was 16.8%. Conclusion: Perinatal anoxia is a real health problem because of its frequency and prognosis.

Influence of cytokines on early death and coagulopathy in newly diagnosed patients with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a better prognosis. But early death (ED) rate remains high. APL patients are simultaneously accompanied by coagulopathy and hyperinflammation at the onset. It is not known what effects cytokines have on ED and coagulopathy in these patients. Therefore, the purposes of this study are to explore the clinical differences between APL and other types of AML, the link between cytokines and coagulopathy in newly diagnosed APL, and their roles in the ED for APL. This study retrospectively collected the information of 496 adult patients with AML (age ≥14 years at admission) newly diagnosed in the First People's Hospital of Yunnan Province between January 2017 to February 2022, including 115 APL patients. The difference of clinical manifestations between two groups [APL and AML (non-APL)] was statistically analyzed. Then, the factors affecting ED in APL patients were screened, and the possible pathways of their influence on ED were further analyzed. The results indicate APL at the onset have a younger age and higher incidence of ED and DIC than other types of AML. Intracranial hemorrhage (ICH), age, and PLT count are found to be independent factors for ED in newly APL, among which ICH is the main cause of ED, accounting for 61.54% (8/13). The levels of cytokines in newly APL are generally higher than that in AML (non-APL), and those in the group of ED for APL were widelymore than the control group. IL-17A and TNF-β are directly related to the ED in newly APL, especially IL-17A, which also affects ICH in these patients. Moreover, the increase of IL-17A and TNF-β cause the prolongation of PT in APL patients, which reflected the exogenous coagulation pathway. However, they have no effect on APTT prolongation and FIB reduction. Thus, it is speculated that IL-17A leads to early cerebral hemorrhage death in newly APL by inducing tissue factor (TF) overexpression to initiate exogenous coagulation and further leading to excessive depletion of clotting factors and prolongation of PT. In conclusion, compared with other types of AML, APL patients have a younger age of onset and high inflammatory state, and are more likely to develop into DIC and die early. Age, and PLT count at diagnosis are independent factors for ED of APL, especially ICH. IL-17A is confirmed to be an independent risk factor for ED and ICH of newly APL. Hence, IL-17A may serve as a predictor of ED in newly diagnosed APL patients, and controlling its expression probably reduce ED in these patients.

High Concentration Hydrogen Mitigates Sepsis-Induced Acute Lung Injury in Mice by Alleviating Mitochondrial Fission and Dysfunction.

Background: Multiple organ failure (MOF) is the main cause of early death in septic shock. Lungs are among the organs that are affected in MOF, resulting in acute lung injury. A large number of inflammatory factors and stress injury in sepsis can lead to alterations in mitochondrial dynamics. Numerous studies have confirmed that hydrogen can alleviate sepsis in the animal model. The purpose of this experiment was to explore the therapeutic effect of high concentration (67%) hydrogen on acute lung injury in septic mice and its mechanism. Methods: The moderate and severe septic models were prepared by cecal ligation and puncture. Hydrogen with different concentrations was inhaled for one hour at 1 h and 6 h after the corresponding surgery. The arterial blood gas of mice during hydrogen inhalation was monitored in real time, and the 7-day survival rate of mice with sepsis was recorded. The pathological changes of lung tissues and functions of livers and kidneys were measured. The changes of oxidation products, antioxidant enzymes and pro-inflammatory cytokines in lungs and serums were detected. Mitochondrial function was measured. Results: The inhalation of 2% or 67% hydrogen improves the 7-day survival rate and reduces acute lung injury as well as liver and kidney injury in sepsis. The therapeutic effect of 67% hydrogen inhalation on sepsis was related to increasing antioxidant enzyme activity, reducing oxidation products and pro-inflammatory cytokines in lungs and serums. Compared with the Sham group, mitochondrial dysfunction was alleviated in hydrogen groups. Conclusions: Hydrogen inhalation by high or low concentration can both significantly improve sepsis; however, a high concentration demonstrates a better protective effect. High concentration hydrogen inhalation can significantly improve the mitochondrial dynamic balance and reduce the lung injury in septic mice.

An Antenatal Diagnostic of Meckel Gruber Syndrome (Mks): Case Report

MKS, Meckel Gruber syndrome is a rare, lethal, genetic multiple congenital anomaly characterized by the following triad: cerebral malformation (primarily occipital encephalocele), polycystic kidneys, and polydactyly, as well as associated abnormalities that may include cleft lip/palate, cardiac and genital abnormalities, central nervous system (CNS) malformations, hepatic fibrosis, and bone dysplasia. The mode of transmission of MKS is autosomal recessive. Genetic counseling should be offered to couples at risk. MKS is lethal in utero or in the very early neonatal period, with pulmonary hypoplasia and renal failure being the main causes of early death. Our case illustrates the importance of prenatal diagnosis, essentially by ultrasound, in order to ensure adequate management.

Clinical characteristics and prediction model of early death in severe/very severe aplastic anemia with immunosuppressive therapy

Objective: Early death (ED) characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia (SAA/VSAA) treated with intensive immunosuppression therapy and establish an ED prediction model. Methods: The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin (ATG) at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected. The characteristics and causes of ED within 90 days were analyzed retrospectively. Cox proportional hazards model was used to screen the ED risk factors and build a prediction model. Results: Only 19 patients (8.2% ) developed ED with a median time of 24 (3-85) days among the 232 patients with SAA/VSAA who received ATG treatment. The main cause of ED was infection (84.2% ) , followed by cerebral hemorrhage (10.5% ) . Multivariate analysis showed that VSAA (HR=15.359, 95% CI 1.935-121.899, P=0.010) , fungal infection prevention by posaconazole (HR=0.147, 95% CI 0.019-1.133, P=0.066) , lymphocyte count (LYM) ≤ 0.5×10(9)/L (HR=3.386, 95% CI 1.123-10.206, P=0.030) , and PLT ≤ 5×10(9)/L (HR=8.939, 95% CI 1.948-41.019, P=0.005) were ED's independent influencing factors. To build a clinical prediction model, VSAA, fungal infection prevention by posaconazole, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L were scored with 3, -2, 1, and 2, respectively. The integral model AUC=89.324 (95% CI 80.859-97.789) . The ED risk in patients with a score ≥ 3 was 23.1 (95% CI 5.3-100.2) times that in patients with a score<3. Conclusion: ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG. VSAA, LYM ≤ 0.5×10(9)/L, and PLT ≤ 5×10(9)/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

Outgrowth Endothelial Cell Conditioned Medium Negates TNF-α-Evoked Cerebral Barrier Damage: A Reverse Translational Research to Explore Mechanisms

Improved understanding of the key mechanisms underlying cerebral ischemic injury is essential for the discovery of efficacious novel therapeutics for stroke. Through detailed analysis of plasma samples obtained from a large number of healthy volunteers (n = 90) and ischemic stroke patients (n = 81), the current study found significant elevations in the levels of TNF-α at baseline (within the first 48 h of stroke) and on days 7, 30, 90 after ischaemic stroke. It then assessed the impact of this inflammatory cytokine on an invitro model of human blood–brain barrier (BBB) and revealed dramatic impairments in both barrier integrity and function, the main cause of early death after an ischemic stroke. Co-treatment of BBB models in similar experiments with outgrowth endothelial cell-derived conditioned media (OEC-CM) negated the deleterious effects of TNF-α on BBB. Effective suppression of anti-angiogenic factor endostatin, stress fiber formation, oxidative stress, and apoptosis along with concomitant improvements in extracellular matrix adhesive and tubulogenic properties of brain microvascular endothelial cells and OECs played an important role in OEC-CM-mediated benefits. Significant increases in pro-angiogenic endothelin-1 and monocyte chemoattractant protein-1 in OEC-CM compared to the secretomes of OEC and HBMEC, detected by proteome profiling assay, accentuate the beneficial effects of OEC-CM. In conclusion, this reverse translational study identifies TNF-α as an important mediator of post-ischemic cerebral barrier damage and proposes OEC-CM as a potential vasculoprotective therapeutic strategy by demonstrating its ability to regulate a wide range of mechanisms associated with BBB function. Clinical trial registration NCT02980354.Graphical

Assessment of colonization and infection epidemiology in patients undergoing autologous hematopoietic stem cell transplantation: a single-center study

Introduction: Infections are one of the main causes of early death after autologous hematopoietic stem cell transplantation (auto-HSCT). Material and methods: We present a single-center retrospective analysis of colonization and infection epidemiology in 115 patients with median age 63 years (range 21–72), who underwent auto-HSCT in 2017 or 2018 in the course of multiple myeloma [79.1% (n = 91)], Hodgkin lymphoma [18.3% (n = 21)] and non-Hodgkin lymphoma [2.6% (n = 3)]. Results: Colonization was observed in 40.9% of patients before auto-HSCT, the most common location being the urinary tract — 54.3%. Multi-drug resistant bacteria (MDR) accounted for 20.9% of positive colonization cultures before auto-HSCT. In the post-transplantation period, infections occurred in 77.4% of patients after auto-HSCT. Bacteremia was observed in 43.5% of patients and it was mostly caused by methicillin-resistant coagulase-negative Staphylococcus epidermidis (MRCNSE) — 27.6%. Infection of the skin near the central vascular catheter was found in 18.3% of patients, urinary tract infections in 11.3%, and gastrointestinal infections in 20.9%. MDR pathogens accounted for 65.2%. The most common of these was methicillin-resistant coagulase-negative Staphylococcus (MRCNS) — 73.9%. Fungal and viral infections were reported in 21.7% and 7%, respectively. The median duration of empirical and targeted antibiotic therapy was 5 (range 1–20) and 7 (range 4–31) days, respectively. Death due to septic shock occurred in 2/115 (1.7%) patients during the neutropenia period. Conclusions: Evaluation of the epidemiology of colonization and infection in patients undergoing auto-HSCT can be an effective tool in providing control and therapy for infections in HSCT recipients. Such knowledge is also essential in monitoring potential pathogen transmission and helping to improve local infection management standards.

Machine Preservation and Ex Situ Assessment of the Donor Heart: A New Paradigm in Heart Transplantation

Heart transplantation is the gold standard treatment for advanced heart failure in selected patients. Organ shortage is however a major concern, leading transplant teams to expand the criteria for donor selection. Organ retrieval is routinely performed nowadays in donors older than 55 years, with impaired left ventricular function and/or hypertrophy, or after prolonged cardiac arrest such as after circulatory-determined death. All these conditions are associated with an increased high of primary graft failure, the main cause of early death after heart transplantation. Machine preservation technology has been recently applied to allow for extended preservation of the donor heart. Compared to conventional static cold storage, this approach can also provide viability assessment of the donor heart before transplant, especially in case of ex situ normothermic blood perfusion. After a brief review of currently available preservation machines, we sought to describe different approaches for assessment of the donor heart using ex situ organ perfusion, from metabolic monitoring to cardiac imaging and hemodynamic investigations.

Machine preservation and ex situ assessment of the donor heart: a new paradigm in heart transplantation

Heart transplantation is the gold standard treatment for advanced heart failure in selected patients. Organ shortage is however a major concern, leading transplant teams to expand the criteria for donor selection. Organ retrieval is routinely performed nowadays in donors older than 55 years, with impaired left ventricular function and/or hypertrophy, or after prolonged cardiac arrest such as after circulatory-determined death. All these conditions are associated with an increased high of primary graft failure, the main cause of early death after heart transplantation. Machine preservation technology has been recently applied to allow for extended preservation of the donor heart. Compared to conventional static cold storage, this approach can also provide viability assessment of the donor heart before transplant, especially in case of ex situ normothermic blood perfusion. After a brief review of currently available preservation machines, we sought to describe different approaches for assessment of the donor heart using ex situ organ perfusion, from metabolic monitoring to cardiac imaging and hemodynamic investigations.

Hydrogen alleviates cell damage and acute lung injury in sepsis via PINK1/Parkin-mediated mitophagy

Multiple organ failure (MOF) is the main cause of early death in septic shock. Lungs are among the organs that are affected in MOF, resulting in acute lung injury. Inflammation is an important factor that causes immune cell dysfunction in the pathogenesis of sepsis. Autophagy is involved in the process of inflammation and also occurs in response to cell and tissue injury in several diseases. We previously demonstrated that hydrogen alleviated the inflammation-induced cell injury and organ damage in septic mice. The focus of the present study was to elucidate whether mitophagy mediates the inflammatory response or oxidative injury in sepsis in vitro and in vivo. Furthermore, we evaluated the role of mitophagy in the protective effects of hydrogen against cell injury or organ dysfunction in sepsis. RAW 264.7 macrophages induced by lipopolysaccharide (LPS) were used as an in vitro model for inflammation, and cecal ligation and puncture (CLP)-induced acute lung injury mice were used as an in vivo model for sepsis. The key protein associated with mitophagy, PTEN-induced putative kinase 1 (PINK1), was knocked down by PINK1 shRNA transfection in RAW 264.7 macrophages or mice. Hydrogen ameliorated cell injury and enhanced mitophagy in macrophages stimulated by LPS. PINK1 was required for the mitigation of the cell impairment in LPS-stimulated macrophages by hydrogen treatment. PINK1 knockdown abrogated the beneficial effects of hydrogen on mitophagy in LPS-stimulated macrophages. Hydrogen inhibited acute lung injury in CLP mice via activation of PINK1-mediated mitophagy. These results suggest that PINK1-mediated mitophagy plays a key role in the protective effects of hydrogen against cell injury in LPS-induced inflammation and CLP-induced acute lung injury.

Comprehensive Mechanism, Novel Markers and Multidisciplinary Treatment of Severe Acute Pancreatitis-Associated Cardiac Injury - A Narrative Review.

Acute pancreatitis (AP) is one of the common acute abdominal inflammatory diseases in clinic with acute onset and rapid progress. About 20% of the patients will eventually develop into severe acute pancreatitis (SAP) characterized by a large number of inflammatory cells infiltration, gland flocculus flaky necrosis and hemorrhage, finally inducing systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Pancreatic enzyme activation, intestinal endotoxemia (IETM), cytokine activation, microcirculation disturbance, autonomic nerve dysfunction and autophagy dysregulation all play an essential role in the occurrence and progression of SAP. Organ dysfunction is the main cause of early death in SAP. Acute kidney injury (AKI) and acute lung injury (ALI) are common, while cardiac injury (CI) is not, but the case fatality risk is high. Many basic studies have observed obvious ultrastructure change of heart in SAP, including myocardial edema, cardiac hypertrophy, myocardial interstitial collagen deposition. Moreover, in clinical practice, patients with SAP often presented various abnormal electrocardiogram (ECG) and cardiac function. Cases complicated with acute myocardial infarction and pericardial tamponade have also been reported and even result in stress cardiomyopathy. Due to the molecular mechanisms underlying SAP-associated cardiac injury (SACI) remain poorly understood, and there is no complete, unified treatment and sovereign remedy at present, this article reviews reports referring to the pathogenesis, potential markers and treatment methods of SACI in recent years, in order to improve the understanding of cardiac injury in severe pancreatitis.

Management of Hyperleukocytosis in Childhood Acute Leukemia Without Leukapheresis and Rasburicase Prophylaxis.

Indications of leukapheresis (LPh) and the prophylactic use of rasburicase in tumor lysis syndrome (TLS) of patients with acute leukemia with hyperleukocytosis are not clear. In this retrospective single-center pediatric study, the outcomes of patients with hyperleukocytosis were reviewed. There were 48 patients with acute lymphoblastic leukemia (ALL) and 13 patients with acute myeloblastic leukemia (AML). The treatment strategies included hyperhydration, allopurinol administration, strict monitoring, and early initiation of induction chemotherapy (CT). No patient underwent LPh because it was not available. Rasburicase was used only in 3 ALL patients with hyperuricemia when the drug was available. Laboratory and clinical TLS developed in 54.16% and 14.58% of patients with ALL, respectively. Laboratory and clinical TLS developed in 76.92% and 15.38% of patients with AML, respectively. No patient developed grade III to V TLS requiring dialysis. Thirteen patients (21.3%) had pulmonary leukostasis on admission, but recovered with CT and nasal oxygen. During the first 14 days of presentation, cerebral leukostasis/coagulopathy-related early death (ED) was 4.2% and 7.7% in patients with ALL and AML, respectively, and all of these patients had a white blood cell count ≥400,000/µL. There was also 1 infection-related death. Patients with hyperleukocytosis can be treated without LPh and liberal use of rasburicase. Renal failure is no longer a cause of ED. Intracranial hemorrhage is the main cause of ED, especially in patients already presenting with this complication. LPh may be performed in patients with leukostasis, if it is not possible to start induction CT early. When resources are limited, rasburicase should be administered in patients presenting with or developing hyperuricemia and/or renal dysfunction.

Improving physical health in people with severe mental illness

People with severe mental illness have a higher mortality than the general population. Sheila Hardy explains how nurses can address the health disparities that people with severe mental illness facePeople with severe mental illness have a higher mortality than the general population, with the main cause of early death being from a physical condition. Practice nurses are well placed to address the health disparities that people with severe mental illness face. This article describes the reasonable adjustments that can be made to increase engagement with patients.

GSTM1-null allele predicts rapid disease progression in nondialysis patients and mortality among South Indian ESRD patients.

Chronic kidney disease (CKD) is one of the main causes of early death in humans worldwide. Glutathione S-Transferases (GSTs) are involved in a series of xenobiotics metabolism and free radical scavenging. The previous studies elucidated the interlink between GST variants and to the development of various diseases. The present case-control study performed to ascertain whether GST polymorphisms are associated with the incidence and advancement of CKD. From the Southern part of India, a total of 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. Patients were followed-up for 70months. Serum biochemical parameters were recorded, and the extraction of DNA was done from the patient's blood samples. To genotype study participants, multiplex PCR for GSTM1/T1 was performed. Statistical analysis was carried out to analyze the relationship between gene frequency and sonographic grading, as well as biochemical parameters for disease development. The GSTM1-null genotype showed threefold increased risk (OR = 2.9304; 95% CI 1.8959 to 4.5296; P < 0.0001) to CKD development and twofold increased risk (OR = 1.8379; 95% CI 1.1937 to 2.8299; P = 0.0057) to ESRD progression. During the mean follow-up of 41months study, multivariate Cox regression analysis revealed that GSTM1-null genotype has 4 times increased the risk for all-cause rapid disease progression to ESRD among ND patients and 3.85-fold increased risk for death among ESRD patients. Survival analysis revealed that patients with GSTM1-present allele showed a significantly diminished risk of mortality compared to patients bearing the GSTM1-null allele among ESRD patients with a hazard ratio of 4.6242 (P < 0.0001). Thus, present data confirm that GSTM1-null genotype increased the risk for all-cause rapid disease progression to ESRD among ND patients. Based on our results, GSTM1-null genotype could be considered as a significant predictor for causing mortality among CKD patients when compared to all other variables.

Causes and predictors of early mortality in patients treated with left ventricular assist device implantation in the European Registry of Mechanical Circulatory Support (EUROMACS)

PurposeThe aim of the study was to analyze early mortality after continuous-flow left ventricular assist device (LVAD) implantation which remains high.MethodsWe analyzed consecutive (n = 2689) patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) undergoing continuous-flow LVAD implantation. The primary outcome was early (< 90 days) mortality. Secondary outcomes were differential causes of early post-operative death following LVAD implantation.ResultsUnivariable and multivariable analysis as well as regression analysis were used to examine determinants and differential causes of early (< 90 days) mortality after LVAD implantation. During the first 90 days, 2160 (80%) patients were alive with ongoing LVAD support, 40(2%) patients underwent heart transplantation, and 487(18%) deceased. The main causes of early death were MOF (36%), sepsis (28%), cardiopulmonary failure (CPF; 10%), CVA (9%), and right-sided heart failure (RHF, 8%). Furthermore, MOF and sepsis are 70% of causes of death in the first week. Independent clinical predictors of early death were age, female sex, INTERMACS profile 1 to 3, and ECMO. Laboratory predictors included elevated serum creatinine, total bilirubin, lactate, and low hemoglobin. Furthermore, hemodynamic predictors included elevated RA-to-PCWP ratio, pulmonary vascular resistance, and low systemic vascular resistance. Longer total implantation time was also independent predictor of early mortality. A simple model of 12 variables predicts early mortality following LVAD implantation with a good discriminative power with area under the curve of 0.75.ConclusionsIn the EUROMACS registry, approximately one out of five patients die within 90 days after LVAD implantation. Early mortality is primarily dominated by multiorgan failure followed by sepsis. A simple model identifies important parameters which are associated with early mortality following LVAD implantation.

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience

BackgroundAcute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population. Patients and MethodsWe analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy. ResultsThe probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 109/L). ConclusionED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.