Death In Patients Research Articles

Alloimmunization in myelodysplastic syndrome is associated with higher healthcare costs, longer hospitalizations, and increased mortality.

Transfusion of red blood cells (RBC) is an important component of treatment for myelodysplastic syndromes (MDS). Patients receiving frequent transfusions are more likely to develop alloimmunization, an immune reaction to minor RBC antigens that increases the risk of complications including delayed hemolysis. Phenotypic matching is believed to reduce alloimmunization although rigorous evidence is lacking. This study examines the association of alloimmunization with clinical and economic outcomes and may give insight into the potential benefit of phenotypic matching in MDS. This study used data from 1054 hospitals included in the Premier hospital chargemaster dataset. Alloimmunized MDS patients (January 2015 to June 2019) were indirectly identified by ICD-10 codes (antiglobulin crossmatch and RBC antibody identification). The primary objective was assessment of the association between incremental cost per patient encounter and alloimmunization in MDS patients. Secondary objectives were assessment of the association of length of stay, intensive care unit (ICU) admission, and inpatient mortality for alloimmunized versus non-alloimmunized MDS patients. Worse clinical and economic outcomes were observed for the alloimmunized group. Higher costs (14%), more ICU admissions (38%), longer hospital (21%) and ICU stays (55%), and greater mortality (30%) were observed among alloimmunized MDS patients compared to non-alloimmunized (p < .0001 for all comparisons). Alloimmunization may be associated with higher costs and greater risk of ICU admission and death in patients with MDS. While further mechanistic research is needed, it seems that MDS patients may benefit substantially from practices that limit risk of alloimmunization, including providing prophylactic antigen matching.

Pulmonary hypertension-related deaths in patients with acute pulmonary embolism in the United States, 2003 to 2020.

Data regarding the mortality trends in pulmonary embolism (PE)-related mortality in patients with concomitant pulmonary hypertension (PH) are lacking. We assessed the trends in PE-related mortality in patients with concomitant PH in the United States (US) over the past 2 decades and during the first year of the COVID-19 pandemic using data from the Centers for Disease Control and Prevention's (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) dataset. Mortality data were retrieved from the publicly available CDC WONDER mortality dataset from 2003 to 2020. Age-adjusted mortality rates (AAMRs), per 100,000 population, were assessed using Joinpoint regression modelling and expressed as estimated average annual percentage change (AAPC) with relative 95% CIs and stratified by urbanicity, sex, age, and race/ethnicity. Over the study period, the AAMR for PE/PH-related mortality linearly increased (AAPC: +4.3% [95% CI: 3.7 to 4.9], p < 0.001) without sex differences. The AAMR increase was more pronounced in White individuals (AAPC: +4.8% [95% CI: 4.1 to 5.5], p < 0.001) and in subjects living in rural areas (AAPC: +5.1% [95% CI: 3.8 to 6.4], p < 0.001) compared to those living in urban areas. During the first year of the COVID-19 pandemic there was a significant excess in PE/PH-related mortality among women, older than 65 years and living in rural areas. The rate of PE/PH-related mortality in the US is increasing. Although the early diagnosis of PH in patients with acute PE has become easier with improved diagnostic modalities, the mortality rate of these patients remains high.

LGI1 encephalitis: potentially complement-activating anti-LGI1-IgG subclasses 1/2/3 are associated with the development of hippocampal sclerosis.

Two-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a "benign", non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments.

Acid sphingomyelinase deficiency in France: a retrospective survival study

BackgroundAcid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.MethodsThis observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan–Meier survival analyses; standardised mortality ratio (SMR) was also explored.ResultsA total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0–18.0] months (type A), 1.0 [0–3] year (type A/B), and 5.5 [0–73] years (type B). Overall, 30 patients were deceased at the study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0–3.6] year, type A/B (n = 6) was 8.5 [3.0–30.9] years, and type B (n = 10) was 57.6 [3.4–74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8–2.7] years and 11.4 [5.5–18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6–5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).ConclusionsThis study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Years of potential life lost due to hepatitis B with or without Delta agent in the Kyrgyz Republic

Recent studies indicate that a marked percentage of chronic viral hepatitis B patients is coinfected with hepatitis D virus known to accelerate the progression of liver disease and contribute to unfavourable disease outcome. Data on premature mortality assessed by the Lost Years of Potential Life (LYPL) indicator, provide the most accurate social burden estimate for such coinfection able to contribute to strengthening viral hepatitis control measures. The aim of the study was to conducting comparative LYPL analyses due to acute and chronic hepatitis B infection without and with delta agent in the Kyrgyz Republic in the years 2014–2018. Materials and methods. LYPL magnitude was calculated using the number of recorded deaths in the reporting form of the 2014–2018 National Statistics Committee «C51-Distribution of deaths by sex, age groups and causes of death». Results. In 2014–2018, 145 cases of death of patients with viral hepatitis B without (HB) and with a delta agent (D) were registered in the Kyrgyz Republic. Of these, 66% (96/145) of patients died from hepatitis B, of which a third (32/96) had an acute disease course. And among those who died from hepatitis D (19/49), acute course was registered in 39%. LYPL for the 145 deceased patients totaled 3766 years, of which 63% (2365 years) were due to HB. Despite that only 35% of patients (51/145) died from acute forms of such hepatitides, their LYPL accounted for 52% (1968) of total years lost that decreased by 4.5-fold for 2014–2018 due to AHB (6.3‰ and 1.41‰, 2014 and 2018, respectively) but increased by 1.1-fold due to AHD (2.7‰ and 3.1‰, 2014 and 2018, respectively). Chronic hepatitis B vs CHD resulted in 1.6 times higher LYPL magnitude (1108 and 691, respectively). At the same time, LYPL due to CHB dynamically increased by 2.6 times, whereas due to CHD — by 6.3 times. Сonclusion. The high LYPL level due to hepatitis B and D infection related to pediatric cases evidence about a heavy burden of such diseases in the Kyrgyz Republic. The data obtained prove that it is necessary to increase adherence of adult population to hepatitis B vaccination and examine children at the site of infection, regardless of vaccination history. Abruptly increased LYPL due to chronic hepatitis cases requires strengthening secondary prevention measures and ensuring timely access to specialized care at infection sites. It is also necessary to evaluate epidemiological surveillance after fatal viral hepatitis.

Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury

Sepsis-associated acute kidney injury (SA-AKI) increases the risk of death in patients with sepsis, and its major pathological change is the death of renal tubular cells. However, the mechanism of its occurrence remains unclear. Sepsis can lead to circadian dysregulation, and the rhythm gene NFIL3 has been reported to regulate lipid metabolism. There is compelling evidence that has demonstrated that lipid peroxidation can cause cellular ferroptosis. In this study, we established the in vitro and in vivo models of SA-AKI and confirmed the presence of ferroptosis of the renal tubular epithelial cells in SA-AKI. In addition, analysis of the GEO database showed that NFIL3 was highly expressed in sepsis patients and was highly correlated with the key molecule of ferroptosis, ACSL4. The in vitro and in vivo data suggested that NFIL3 was involved in ferroptosis and inflammation in SA-AKI. Subsequently, loss-of-function experiments revealed that NFIL3 knockdown attenuated ferroptosis and inflammation in renal tubular epithelial cells by downregulating ACSL4 expression, thus protecting SA-AKI. In conclusion, this study is the first to illustrate the involvement of the rhythm gene NFIL3 in SA-AKI, providing new insights and potential therapeutic targets for SA-AKI.

Connected to the cloud at time of death: a case report

BackgroundOur case report provides the first clinical evaluation of autopsy practices for a patient death that occurs on the cloud. We question how autopsy practices may require adaptation for a death that presents via the ‘Internet of Things’, examining how existing guidelines capture data related to death which is no longer confined to the patient's body.Case presentationThe patient was a British man in his 50s, who came to the attention of the medical team via an alert on the cloud-based platform that monitored his implanted cardioverter defibrillator (ICD). The patient had a background of congenital heart disease, with previous ventricular fibrillation cardiac arrest, for which the ICD had been implanted two years earlier. Retrospective analysis of the cloud data demonstrated a gradually decreasing nocturnal heart rate over the previous three months, falling to a final transmission of 24 beats per minute (bpm). In the patient post-mortem the ICD was treated as medical waste, structural tissue changes precluded the effective evaluation of device hardware, potential issues related to device software were not investigated and the cause of death was assigned to underlying heart failure. The documentation from the attending law enforcement officials did not consider possible digital causes of harm and relevant technology was not collected from the scene of death.ConclusionThrough this patient case we explore novel challenges associated with digital deaths including; (1) device hardware issues (difficult extraction processes, impact of pathological tissue changes), (2) software and data limitations (impact of negative body temperatures and mortuary radio-imaging on devices, lack of retrospective cloud data analysis), (3) guideline limitations (missing digital components in autopsy instruction and death certification), and (4) changes to clinical management (emotional impact of communicating deaths occurring over the internet to members of family). We consider the implications of our findings for public health services, the security and intelligence community, and patients and their families. In sharing this report we seek to raise awareness of digital medical cases, to draw attention to how the nature of dying is changing through technology, and to motivate the development of digitally appropriate clinical practice.

Influencing and prognostic factors of end-stage hypertrophic cardiomyopathy.

End-stage hypertrophic cardiomyopathy (ES-HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES-HCM. A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF)<50% were defined as having ES-HCM, and a control group (LVEF≥50%) was generated from the collected medical records of HCM. The patients were matched in a ratio of 4:1 based on age and sex. Logistic regression analysis was used to determine the influencing factors of ES-HCM. Kaplan-Meier survival analysis was performed to analyse the clinical outcomes of ES-HCM patients. A total of 250 inpatients with HCM were enrolled in the study; 50 patients had ES-HCM, and 200 had HCM with LVEF≥50%. The mean age of the patients at enrolment was 62.5±10.3years, and 215 patients (215/250, 86.0%) were male. The median follow-up time of the patients was 2.8 (1.4-5.4) years. The incidence of all-cause death and cardiovascular death in patients with ES-HCM was higher than those in patients with HCM and LVEF≥50% (22/50 [44.0%] vs. 13/200 [6.5%]; 12/50 [24.0%] vs. 4/200 [2.0%], all P<0.001). Multivariate logistic regression analysis showed that the influencing factors associated with ES-HCM included age at first symptom onset (odds ratio [OR]=0.95, 95% CI [0.90, 1.00], P=0.042), New York Heart Association (NYHA) class (OR=7.73, 95% CI [2.93, 20.41], P<0.001), heart rate (OR=1.07, 95% CI [1.02, 1.12], P=0.003), QRS duration (OR=1.03, 95% CI [1.00, 1.05], P=0.020), left ventricular end-diastolic diameter (LVEDD) (OR=1.15, 95% CI [1.04, 1.28], P=0.006), left atrial anteroposterior diameter (LAD) (OR=1.13, 95% CI [1.03, 1.24], P=0.012), and maximum left ventricular wall thickness (MLVWT) (OR=0.80, 95% CI [0.68, 0.93], P=0.005). Among the 50 patients with ES-HCM, NYHA class (P<0.001) and heart rate (P=0.017) were each associated with a higher likelihood and earlier occurrence of heart transplantation or all-cause mortality in univariate analyses. The influencing factors for ES-HCM included the age at first symptom onset, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT. Both NYHA class and heart rate were related to the prognosis of ES-HCM.

Investigation of the relationship between COVID-19 and pancreatic cancer using bioinformatics and systems biology approaches.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, poses a huge threat to human health. Pancreatic cancer (PC) is a malignant tumor with high mortality. Research suggests that infection with SARS-CoV-2 may increase disease severity and risk of death in patients with pancreatic cancer, while pancreatic cancer may also increase the likelihood of contracting SARS-CoV-2, but the link is unclear. This study investigated the transcriptional profiles of COVID-19 and PC patients, along with their respective healthy controls, using bioinformatics and systems biology approaches to uncover the molecular mechanisms linking the 2 diseases. Specifically, gene expression data for COVID-19 and PC patients were obtained from the Gene Expression Omnibus datasets, and common differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analyses were performed on the common DEGs to elucidate the regulatory relationships between the diseases. Additionally, hub genes were identified by constructing a protein-protein interaction network from the shared DEGs. Using these hub genes, we conducted regulatory network analyses of microRNA/transcription factors-genes relationships, and predicted potential drugs for treating COVID-19 and PC. A total of 1722 and 2979 DEGs were identified from the transcriptome data of PC (GSE119794) and COVID-19 (GSE196822), respectively. Among these, 236 common DEGs were found between COVID-19 and PC based on protein-protein interaction analysis. Functional enrichment analysis indicated that these shared DEGs were involved in pathways related to viral genome replication and tumorigenesis. Additionally, 10 hub genes, including extra spindle pole bodies like 1, holliday junction recognition protein, marker of proliferation Ki-67, kinesin family member 4A, cyclin-dependent kinase 1, topoisomerase II alpha, cyclin B2, ubiquitin-conjugating enzyme E2 C, aurora kinase B, and targeting protein for Xklp2, were identified. Regulatory network analysis revealed 42 transcription factors and 23 microRNAs as transcriptional regulatory signals. Importantly, lucanthone, etoposide, troglitazone, resveratrol, calcitriol, ciclopirox, dasatinib, enterolactone, methotrexate, and irinotecan emerged as potential therapeutic agents against both COVID-19 and PC. This study unveils potential shared pathogenic mechanisms between PC and COVID-19, offering novel insights for future research and therapeutic strategies for the treatment of PC and SARS-CoV-2 infection.

Inhibitory effects of resveratrol on platelet activation and thrombosis in colon cancer through regulation of the MAPK and cGMP/VASP pathways

Thrombosis is the primary cause of death in patients with cancer. Resveratrol inhibits platelet activation, a crucial pathophysiological basis of thrombosis, in healthy individuals. However, its effects and mechanisms of action in patients with colon cancer remain unknown. Here, we investigated the effect of resveratrol on platelet adhesion and aggregation in patients with colon cancer. Through numerous in vitro and in vivo analyses, including flow cytometry, western blotting, ELISA, and immunofluorescence and colon cancer rat models, we demonstrated that resveratrol reduced thrombosis in patients with colon cancer by inhibiting the phosphorylation of the MAPK and activating the cyclic-GMP/vasodilator-stimulated phosphoprotein pathway. These findings demonstrate the potential of resveratrol in reducing thrombosis in patients with colon cancer and could be used to develop novel therapeutic strategies for this condition.

Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.

Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9h) and at 24 and 72h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.

Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy.

Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37-21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large-scale studies are needed to identify the effect of CPA in patients with LC.

Digoxin is still useful, but is still causing toxicity.

Digoxin, the oldest known cardiovascular drug, is still used today to treat heart failure and atrial fibrillation. Because it has a narrow therapeutic index and multiple interactions, it frequently causes toxicity with a wide range of symptoms and cardiac arrhythmias. More importantly, elevated serum digoxin levels have been linked to a higher risk of death in patients with heart failure or atrial fibrillation, even without signs or symptoms of toxicity. This article reviews the current state of digoxin use, its pharmacologic principles, and the mechanisms, clinical presentation, and management of toxicity.

Angiotensin receptor blockers versus angiotensin converting enzyme inhibitors in acute myocardial infarction without heart failure

BackgroundWhether angiotensin II receptor blocker (ARB) can be an alternative to angiotensin-converting enzyme inhibitor (ACEI) in patients without heart failure (HF) after acute myocardial infarction (MI) remains controversial. The aim of this study was to compare clinical outcomes between initial ARB and ACEI therapy in patients with MI without HF. MethodsBetween 2010 and 2016, a total of 31,013 patients who underwent coronary revascularization for MI with prescription of ARB or ACEI at hospital discharge were enrolled from the Korean nationwide medical insurance data. Patients who had HF at index MI were excluded. The primary outcome was all-cause death. The secondary outcomes included recurrent MI, hospitalization for new heart HF, stoke, and a composite of each outcome. ResultsOf 31,013 patients, ARBs were prescribed in 12,685 (40.9%) and ACEIs in 18,328 (59.1%). Patients receiving ARB had a lower discontinuation rate compared with those receiving ACEI (28.2% versus 43.5%, adjusted hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.31–0.37, p<0.01). During a median follow-up of 2.2 years, 2,480 patients died. The incidence rate of all-cause death in patients receiving ARB and those receiving ACEI was 27.7 and 22.9 per 1,000 person-years, respectively (adjusted HR 1.04; 95% CI, 0.95–1.13; p=0.40). There were no significant differences in the secondary outcomes between patients receiving ARB and those receiving ACEI, except stroke (19.2 vs. 13.6 per 1,000 person-years; adjusted HR 1.17; 95% CI 1.04–1.32; p=0.01). In a subgroup analysis, a higher mortality was observed with ARBs compared to ACEIs in patients with diabetes. ConclusionsIn this nationwide cohort, there was no significant difference in the incidence of all-cause death between ARB and ACEI as discharge medications in patients with MI without HF. ARBs would be an alternative to ACEIs for those intolerant to ACEI therapy.

Suicide in individuals with eating disorders who had sought mental health treatment in England: a national retrospective cohort study

Although studies have suggested a high risk of suicide in people with eating disorders, most studies have focused on suicidal ideation and attempts. There is little research on the characteristics of people with eating disorders who died by suicide, nor investigation of trends over time. We aimed to compare the characteristics of patients with eating disorders who died by suicide versus patients with other mental health diagnoses who died by suicide in England and to examine the trends in rates. In this national retrospective cohort study, data on all people (aged ≥10 years) who died by suicide in England, UK, between Jan 1, 1997, and Dec 31, 2021, while under the care (within the previous 12 months) of mental health services were obtained from the National Confidential Inquiry into Suicide and Safety in Mental Health (NCISH), in which clinical information is collected via a questionnaire completed by the mental health professional responsible for the patient's care. Incidence of suicide in, and demographic, clinical, and treatment characteristics of, patients with a diagnosis of eating disorder (as recorded by the treating clinician) who died by suicide were compared with patients with other mental health diagnoses who died by suicide within the same timeframe using univariable logistic regression analysis. People with related lived experience were involved in the study design, implementation, interpretation, and writing of the manuscript. Of 119 446 people for whom NCISH were notified of dying by suicide in England, 30 795 were under the recent care of mental health services, of whom 30 246 had known diagnoses and were included in analyses. Of these individuals, 10 373 (34%) were female and 19 873 (66%) were male; 2236 (8%) were of minority ethnicity; 382 (1%) had a diagnosis of eating disorder and 29 864 (99%) had another mental health diagnosis. Compared with patients with other mental health diagnoses who died by suicide, patients with eating disorders were younger (median age 33 years [range 15-90] vs 45 years [10-100]), more often female (343 [90%] female and 39 [10%] male in the eating disorders group; 10 030 [34%] female and 19 834 [66%] male in the other diagnoses group), and less likely to have evidence of conventional risk factors for suicide such as living alone (odds ratio [OR] 0·68, 95% CI 0·55-0·84). 22 (6%) of 382 were from a minority ethnic group. Patients with an eating disorder were characterised by a greater clinical complexity (eg, self-harm [OR 2·31, 95% CI 1·78-3·00], comorbidity [9·79, 6·81-14·1], and longer duration of illness [1·95, 1·56-2·43]), and were more likely to have died following overdoses (2·00, 1·62-2·45) than patients with other diagnoses. Childhood abuse (52 [37%] of 140) and domestic violence (18 [20%] of 91) were common in patients with eating disorders. Similar to patients with other diagnoses, most (244 [75%] of 326) of those with eating disorders who died by suicide were rated as low risk by clinicians at last contact. The number of suicide deaths in patients with eating disorders rose between 1997 and 2021 (incidence rate ratio [IRR] 1·03, 95% CI 1·02-1·05; p<0·0001), but rates fell when accounting for the greater number of patients entering mental health services (IRR 0·97, 0·95-1·00; p=0·033). This study was focused on people who sought help from mental health services. It did not consider subtypes of eating disorders or include a control group, but it does highlight possible areas for intervention. The comprehensive provision of evidence-based treatment for eating disorders and underlying conditions to address the clinical complexity in these patients might help to reduce suicide. Recognising limitations in clinical risk assessment, addressing early life experiences and current adversities, and appropriate prescribing might also be of benefit. Suicide prevention must remain a priority for eating disorder services and mental health care more widely. The Healthcare Quality Improvement Partnership.

Long-term risk of hospitalization and death in patients with mechanical prosthetic heart valves.

Mechanical prosthetic heart valves (MPHV) are commonly used for valvular heart disease in patients with long life expectancy. Few longitudinal data on hospitalizations specific causes in MPHV patients are available. We investigated the risk of all-cause hospitalization and mortality in MPHV patients. We performed a prospective observational ongoing study including MPHVs consecutive patients referring to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist (VKA) management. Study endpoints were all-cause, cardiovascular hospitalization and overall mortality. We included 305 MPHV patients (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5% and mitro-aortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery and bleeding. Predictors of cardiovascular hospitalization were atrial fibrillation (Hazard ratio [HR] 1.75, 95% confidence interval [95%CI] 1.04-2.95, p= 0.035), previous stroke/transient ischemic attack (HR 2.96, 95%CI 1.59-5.48, p=0.001) and peripheral artery disease (HR 2.42, 95%CI 1.09-5.36, p=0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95%CI 1.054-1.122, p<0.001), while time in therapeutic range above the median was inversely associated (HR 0.436, 95%CI 0.242-0.786, p= 0.006).In conclusion, MPHV patients had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high, but it may be reduced by maintaining a good quality of anticoagulation.

Analysis of early warning indicators of death in patients with severe fever with thrombocytopenia syndrome

BackgroundSince its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients.MethodsThis is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed.ResultsA total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients’ death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563–0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699–0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645–0.854), p < 0.001.ConclusionPatients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician’s attention, and require early and effective interventions to avoid further disease progression.

A competing risks model to estimate the risk of graft failure and patient death after kidney transplantation using continuous donor-recipient age combinations

Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well-described in real-world transplant data.This retrospective cohort study analyzed data from the European Collaborative Transplant Study (CTS; n = 125 250) and from the American Scientific Registry of Transplant Recipients (SRTR; n = 190 258). Separate cause-specific hazard models, using donor and recipient age as continuous predictors, were developed for graft failure and recipient death.The hazard of graft failure increased quadratically with increasing donor age and decreased decaying with increasing recipient age. The hazard of recipient death increased linearly with increasing donor and recipient age. The cumulative incidence overestimation due to competing risk-censoring was largest in high-risk populations for both outcomes (old donors/recipients), sometimes amounting to 8.4 and 18.8 percentage points for graft failure and recipient death, respectively.In our illustrative model for post-transplant risk prediction, the absolute risk of graft failure and death is overestimated when censoring for the competing event, mainly in older donors and recipients. Prediction models for absolute risks should treat graft failure and death as competing events.

A NOVEL CIRC_SUPT3/MIR-185-5P/G3BP2 CERNA NETWORK REGULATES HIGH GLUCOSE-INDUCED INJURY IN MOUSE PODOCYTE MPC5 CELLS.

Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. Methods: High glucose (HG) treatment of mouse podocyte (MPC5) cells to mimic DN cell injury. Quantitative real-time polymerase chain reaction was performed to detect the expression of circ_Supt3, microRNA-185-5p (miR-185-5p), and GTPase-activating protein-binding protein 2 (G3bp2). 5-Ethynyl-2'-deoxyuridine (EdU) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assays were used to examine cell proliferation, and flow cytometry was used to detect cell apoptosis. Western blot was used to assess the levels of relative proteins. Enzyme-linked immunosorbent assay detected the inflammation cytokines. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction of miR-185-5p and circ_Supt3 or G3bp2. Results: Circ_Supt3 and G3bp2 were highly expressed and miR-185-5p expression was diminished in DN mice. HG treatment inhibited cell proliferation and accelerated cell apoptosis and inflammation response, and the knockdown of circ_Supt3 reversed these effects. Bioinformatics predicted that circ_Supt3 contained a binding site for miR-185-5p, and G3bp2 was a direct target of miR-185-5p. Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.