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Cardiac arrest (CA) due to cardiovascular disease is the leading cause of death in developed countries. It is estimated that over 350,000 people in Europe suffer from out-of-hospital cardiac arrest. According to the literature, the longer the episode of cardiac arrest, the greater the risk of cognitive impairment, especially short-term memory, as well as immediate and delayed recall. Other common dysfunctions include attention deficits and executive function disorders. The aim of this systematic review was to summarize current research on cognitive impairment in patients after sudden cardiac arrest. The electronic databases PubMed/MEDLINE, OVID, Web of Science, and EBSCO were searched using the following key words: ‘sudden cardiac arrest’, ‘out-of-hospital cardiac arrest’, ‘cognitive function’, ‘cognitive impairment’, ‘functional outcome’, ‘cardiopulmonary resuscitation’. The most recent studies from the last 7 years (2011–2018) were included. Cognitive disorders occurred in a broad range of cases: from 13% to even 100%. In one study, cognitive deficits did not occur at all. Amongst the reviewed articles only two studies were carried out on a large group of patients. The remaining studies were conducted on a small group of respondents; therefore there was no possibility to generalize the results to the entire population. The areas in which the most cognitive impairment occurred were memory, executive functions and visual–motor skills. One of the conclusions derived from the reviewed literature is the importance of continuous training of cognitive functions, especially for people with cardiovascular risk.

Background AMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2–3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak. Methods All records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word “AMB-FUBINACA” was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2. Findings Sixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from 1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications. Interpretation This study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ. Funding All work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.

Ovarian cancer is the major cause of death out of all the gynecologic cancers. The prognosis of this cancer is quite poor since patients only seek treatment when it is at an advanced stage. Any early biomarkers for this cancer are still unknown. Dysregulation of mitochondrial dynamics with associated resistance to apoptosis plays a crucial role in several types of human carcinogenesis, including ovarian cancers. Previous studies showed that increased mitochondrial fission occurred in ovarian cancer cells. However, several pharmacological interventions and therapeutic strategies, which modify the mitochondrial dynamics through the promotion of mitochondrial fission and apoptosis of cancer cells, have been shown to potentially provide beneficial effects in ovarian cancer treatment. Therefore the aim of the present review is to summarize and discuss the current findings from in vitro, in vivo and clinical studies associated with the alteration of mitochondrial dynamics and ovarian cancers with and without interventions., Highlights • Dysregulation of mitochondrial dynamics occurred in ovarian cancer. • Increased mitochondrial dysregulation may correlate with the increasing degree of chemoresistance in ovarian cancers. • Drugs-induced mitochondrial fission and apoptosis will be beneficial effect in ovarian cancer therapy.

Pneumonia is a significant cause of death for children, particularly those in developing countries. The records of children who were hospitalized because of pneumonia between January 2003 and December 2015 were retrospectively reviewed, and patients who met the recurrent pneumonia criteria were included in this study. During this 13-year period, 1395 patients were hospitalized with pneumonia; of these, 129 (9.2%) met the criteria for recurrent pneumonia. Underlying diseases were detected in 95 (73.6%) patients, with aspiration syndrome (21.7%) being the most common. Rhinovirus (30.5%), adenovirus (17.2%) and respiratory syncytial virus (13.9%) were the most frequent infectious agents. These results demonstrate that underlying diseases can cause recurrent pneumonia in children. Viruses are also commonly seen in recurrent pneumonia. Appropriate treatments should be chosen based on an analysis of the underlying disease, the patient’s clinical condition and the laboratory and radiological data.

Background Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics. Methods We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded “validation” cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry. Results We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease. Conclusion Urinary levels of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB. Funding This study was funded by Weill Cornell Medicine, the National Institute of Allergy and Infectious Diseases, the Clinical and Translational Science Center at Weill Cornell, the NIH Fogarty International Center grants, and the NIH Tuberculosis Research Unit (Tri-I TBRU)., Highlights • Urinary levels of small metabolites appear capable of distinguishing cases of active pulmonary tuberculosis from sick and healthy controls. • Levels of these biomarkers decrease after 60 days of treatment in a longitudinal cohort of 20 participants. • - Many of the identified biomarkers are known inflammatory intermediates that may reflect a specific immune response to tuberculosis. Urine tests are commonly used to enable non-invasive, rapid and point-of-care diagnosis of various infectious diseases. We identified diacetylspermine, neopterin, sialic acid and N-acetylhexosamine as potential urine-based biomarkers for tuberculosis from two independent patient cohorts. These metabolites are known inflammatory intermediates and appear to decrease with anti-tuberculosis therapy in a subset of participants followed over 2 months. If validated, these metabolites have potential to both improve our understanding of the immune reaction to active tuberculosis and facilitate the development of a much-needed clinical biomarker for tuberculosis.

Background death certification data are routinely collected in most developed countries. Coded causes of death are a readily accessible source and have the potential advantage of providing complete follow-up, but with limitations. Objective to investigate the reliability of using death certificates for surveillance of dementia, the time trend of recording dementia on death certificates and predictive factors of recording of dementia. Subjects individuals aged 65 and over in six areas across England and Wales were randomly selected for the Medical Research Council Cognitive Function and Ageing Study (CFAS) and CFAS II with mortality follow-up. Methods prevalence of dementia recorded on death certificates were calculated by year. Reporting of dementia on death certificates compared with the study diagnosis of dementia, with sensitivity, specificity and Cohen’s κ were estimated. Multivariable logistic regression models explored the impact of potential factors on the reporting of dementia on the death certificate. Results the overall unadjusted prevalence of dementia on death certificates rose from 5.3% to 25.9% over the last 26 years. Dementia reported on death certificates was poor with sensitivity 21.0% in earlier cohort CFAS, but it had increased to 45.2% in CFAS II. Dementia was more likely to be recorded on death certificates in individuals with severe dementia, or those living in an institution, yet less likely reported if individuals died in hospital. Conclusion recording dementia on death certificate has improved significantly in the England and Wales. However, such information is still an underestimate and should be used alongside epidemiological estimations.

Reynolds Risk Score (RRS) is regarded as a good screening tool for cardiovascular disease (CVD) risk. Since CVD is the leading cause of death in Montenegro, we aimed to assess the risk of CVD as assessed by RRS and to examine its association with cardiometabolic parameters in apparently healthy middle-aged population. In addition, we aimed to test whether obesity had an independent influence on RRS. A total of 132 participants (mean age 56.2±6.73 years, 69% females) were included. Body mass index (BMI), waist circumference (WC), blood pressure (BP) and biochemical parameters (fasting glucose, insulin, lipid parameters, creatinine and high sensitivity C-reactive protein) were determined. Insulin resistance (HOMA-IR) and glomerular filtration rate (eGFR) were calculated. Compared with females, a significantly higher number of males were in the high RRS subgroup (χ2=45.9, p, Reynoldsov zbir rizika (Reynolds Risk Score, RRS) se smatra dobrim algoritmom probira za procjenu rizika od kardiovaskularnih bolesti (KVB). Kako su KVB vodeći uzrok smrtnosti u Crnoj Gori, cilj studije je bio procijeniti KV rizik primjenom algoritma RRS i ispitati njegovu povezanost s kardiometaboličkim čimbenicima rizika u populaciji odraslih zdravih ispitanika. Cilj je također bio ispitati nezavisan utjecaj pretilosti na RRS. U studiju su bile uključene 132 osobe srednje dobi od 56,2±6,73 godine; 69% su bile žene. Mjereni su sljedeći parametri: indeks tjelesne mase, obim struka, krvni tlak te biokemijski parametri (glikemija natašte, inzulin, lipidni parametri i visoko osjetljiv C-reaktivni protein). Izračunata je inzulinska rezistencija (HOMA-IR) i procijenjena razina glomerularne filtracije (eGFR). U usporedbi sa ženama, značajno veći broj muškaraca bio je u skupini s većim KV rizikom (χ2=45,9; p

Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.

Cardiovascular diseases, including coronary artery disease (CAD), are the leading cause of death among women and men. Mortality among women is higher than in men. Women more often report atypical anginal symptoms. Non-invasive diagnostic testing of CAD is less sensitive and characteristic in women than in men. Coronary angiography and rewascularization of coronary arteries is less common in women. However, women, who undergo angiography have lower rates of obstructive CAD. The worse prognosis of CAD in women is associated with the fact that the onset of obstructive coronary artery disease in women occurs 7-10 years later than in men. Older women are also more often burdened with comorbidities. The aim of this study was to compare the clinical characteristics, diagnostics, and treatment of CAD in women and men.Choroby sercowo-naczyniowe, w tym choroba wieńcowa (CAD), są główną przyczyną zgonów u kobiet i mężczyzn. Liczba zgonów z powodu CAD jest wyższa u kobiet niż u mężczyzn. Kobiety częściej zgłaszają nietypowe dolegliwości bólowe w klatce piersiowej. Diagnostyka nieinwazyjna CAD jest mniej czuła i swoista u kobiet niż u mężczyzn. Koronarografię i rewaskularyzację tętnic wieńcowych wykonuje się rzadziej u kobiet, natomiast w trakcie koronarografii u kobiet częściej stwierdza się nieistotne zmiany w naczyniach wieńcowych bądź „czyste naczynia wieńcowe”. Wielu autorów badań klinicznych podkreśla, że gorsze rokowanie u kobiet z CAD wiąże się z faktem, iż kobiety zapadają na chorobę wieńcową 7–10 lat później niż mężczyźni. Ponadto kobiety w starszym wieku są bardziej obciążone chorobami współistniejącymi. Celem niniejszej pracy jest porównanie charakterystyki klinicznej, diagnostyki i leczenia CAD u kobiet i mężczyzn.

Background: There are limited data regarding the incidence and long-term impact of acute kidney injury (AKI) according to the KDIGO guidelines on the outcome in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). The aim of the study was to evaluate the prevalence of AKI, as classified by the KDIGO criteria, and its association with long-term mortality. Methods: Data from 5,859 MI patients undergoing PCI at our institution were analyzed. We compared the group without and with AKI according to the KDIGO criteria in relation to long-term mortality. Results: AKI was documented in 499 (8.5%) patients. AKI stage 1 occurred in 6.2% of patients, AKI stage 2 in 0.9% of patients, and AKI stage 3 in 1.5% of patients. Patients with AKI had a higher long-term mortality (57.3 vs. 20.6%; p < 0.0001). The mortality was 50.3% in AKI stage 1, 56.9% in AKI stage 2, and 87.2% in AKI stage 3. The hazard ratios for all-cause mortality for AKI stages 1–3 were 1.77, 1.85, and 6.30 compared to patients with no AKI. Cardiogenic shock, bleeding, heart failure, age, renal dysfunction, diabetes, hyperlipidemia, ST-elevation MI, contrast volume/glomerular filtration ratio, P2Y12 receptor antagonists, and radial access were associated with the development of AKI. Conclusion: A slight increase in serum creatinine was associated with a progressive increase in long-term mortality in patients with AKI according to the KDIGO definition.

Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid). Hazard ratio (HR) and 95% confidence interval (CI) were calculated for each independent prognosticator. After univariate and multivariate survival analysis, low apoAI level (< 1.125 mmol/L) appeared to predict poor 5-year overall survival (OS), disease-free survival (DFS) and distant-metastasis-free survival (DMFS).The HRs were 1.549 (95% CI, 1.137-2.109), 1.293 (95% CI, 1.047-1.597) and 1.288 (95% CI, 1.022-1.623), respectively. Subgroup survival analysis showed that the apoAI maintained predicting independence for OS, DFS and DMFS in patients with locally advanced NPC, even in those treated with concurrent chemoradiotherapy. Conclusions / Significance: NPC patient with low serum level of pretreatment apoAI might be at risk of distant metastasis. Treatment aiming to eradicate distant metastasis might improve survival of these patients.

Cardiovascular diseases are the world’s leading cause of death. Human physiologic activities and state during illness are under the control of circadian rhythm. The aim of the study was to determine the potential association of chronotype and daytime sleepiness with susceptibility to myocardial infarction. We conducted a case-control study on 200 patients hospitalized due to myocardial infarction and 200 healthy controls. Systematic information on the past and present medical history was obtained from all participants. Chronotype was assessed using the Morningness-Eveningness Questionnaire (MEQ), and daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). The mean age of the study population was 64±13 years, and 54.5% were male. There was no significant difference in MEQ (58.88±6.52 vs. 58.46±7.78, p=0.601) or ESS (5 (interquartile range, IQR 4-7.5) vs. 6 (IQR 3-8), p=0.912) score between patients and controls. Nevertheless, we found statistically significant differences related to risk factors for cardiovascular diseases, such as hypertension, dyslipidemia, and diabetes mellitus. However, there was no association of MEQ and ESS score with myocardial infarction in the study population., Kardiovaskularne bolesti su vodeći uzrok smrtnosti u svijetu. Pod kontrolom cirkadijalnog sata su humana fiziologija i fiziološka stanja tijekom bolesti. Cilj ovoga istraživanja bio je utvrditi potencijalnu povezanost kronotipa i dnevne pospanosti s infarktom miokarda. Provedeno je istraživanje slučajeva i kontrola na 200 bolesnika s infarktom miokarda te 200 zdravih kontrolnih ispitanika. Od svih ispitanika prikupljeni su podaci o prošloj i trenutnoj medicinskoj anamnezi. Kronotip je procijenjen pomoću upitnika MEQ (Morningness-Eveningness Questionnaire), a dnevna pospanost pomoću Epworthove ljestvice pospanosti (ESS, Epworth Sleepiness Scale). Prosječna životna dob ispitivane populacije bila je 64±13 godina, a 54,5% ispitanika činili su muškarci. Statistički značajna razlika nije pronađena između bolesnika i kontrola u kronotipu (58,88±6,52 nasuprot 58,46±7,78; p=0,601) i dnevnoj pospanosti (5 (IQR 4-7,5) nasuprot 6 (IQR 3-8); p=0,912). Unatoč tome, pronađena je statistički značajna razlika povezana sa čimbenicima rizika za kardiovaskularne bolesti kao što su hipertenzija, dislipidemija i dijabetes. Međutim, u ovom istraživanju nije utvrđena povezanost kronotipa i dnevne pospanosti s infarktom miokarda.

Introduction According to statistics, gastric cancer remains one of the most common causes of death due to neoplastic disease in the world's population. It is a common conception that this type of cancer mostly affects people in their fifth or sixth decade of life. So, when it comes to young people, for example in their twenties or early thirties, who present to a doctor with symptoms suggesting a cancer of the gastrointestinal tract, these are quite often ignored because of their young age. Aim In this study we at The Second Department of General and Gastroenterological Surgery of the Medical University of Bialystok, Poland decided to enlighten the problem of stomach cancer in people under 40 years old as a cause of death and complications most likely because of an incorrect diagnosis at the beginning of therapy. Material and methods Major analysis involved 350 cases of gastrointestinal tumours treated surgically, of which 14 cases (7 men and 7 women) were patients aged 18-39 years diagnosed with different stages of gastric cancer. Results Statistical analysis has shown that gastric cancer in women occurred much earlier than in men, and the average survival time was 16 months after the surgery. Conclusions Because of the false suggestion that gastric cancer affects mostly older people, there is a risk of ignoring the symptoms in young people and finding advanced neoplastic lesions at the time of diagnosis, which has a negative effect on long-term treatment results.

Introduction This study aimed to assess the case completeness of out-of-hospital cardiac arrests (OHCA) in the Norwegian Cardiac Arrest Registry (NorCAR) and describe the differences between the registered and missing patients identified from the case-control assessment. Methods We identified the relevant patients in the Norwegian Patient Registry and the Norwegian Cause of Death Registry and compared them with the patients in NorCAR. Data processors used patient records to confirm if the potential cardiac arrest cases met the inclusion criteria in NorCAR. Results Between 2015 and 2017, 8612 OHCA patients were registered in NorCAR. Through the Patient Registry and the Cause of Death Registry we identified 11,114 potential OHCA patients, 3469 of these were already registered in NorCAR. After evaluating the patient records for the remaining 7645 patients, we found 344 patients (4%), were eligible for inclusion in NorCAR, giving a case completeness of 96%. The registered and missing patients were similar in age and gender distribution. Initial shockable rhythm and presumed cause were also comparable. However, the missing patients more frequently achieved return of spontaneous circulation, were more often transported to hospital, and had higher survival rates. The already registered patients had more key variables registered than the missing patients. Conclusion Our results indicate high case completeness in NorCAR. The missing patients were too few to introduce significant changes in the distribution of patient characteristics, indicating that NorCAR is representative of the Norwegian OHCA population.

Background Actual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported. Objective This study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC. Methods We performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses. Results We included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P Conclusions Ovarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.

Birth defects are the leading cause of infant death in the United States and a major cause of death and hospitalization among children of all ages. Despite the devastating impact of birth defects, we understand little of their etiology impeding progress towards treatment and prevention. Our inability to accurately predict, diagnose and treat the common sequelae of birth defects leaves the economic, social and public health burden of birth defects unacceptably high. Emerging genomic sequencing technologies provide an unprecedented opportunity to identify genetic variants, including those that cause birth defects. It is essential that we leverage these advances to enhance our understanding of birth defects. Such an effort will lead to new avenues for treatment and provide benefits to families, including improved understanding of the cause of a child’s condition and the risks to any future children. However, understanding the genetics of human birth defects presents many challenges. This White Paper outlines the need for a birth defect genomics initiative, the challenges to overcome, and suggested solutions. Ultimately, we conclude that understanding birth defects must be a trans-NIH effort and involve the development of a new type of interdisciplinary team working together in all aspects of the enterprise.

Triggering factors of Acute Chest Syndrome (ACS) is a leading cause of death in patients with Sickle Cell Disease (SCD) and targeted therapies are limited. Chlorine (Cl2) inhalation happens frequently, but its role as a potential trigger of ACS has not been determined. In this study, we hypothesized that Cl2 exposure resembling that in the vicinity of industrial accidents induces acute hemolysis with acute lung injury, reminiscent of ACS in humanized SCD mice. When exposed to Cl2 (500 ppm for 30 min), 64% of SCD mice succumbed within 6 h while none of the control mice expressing normal human hemoglobin died (p, Graphical abstract Image 1, Highlights • Chlorine inhalation induces exaggerated hemolysis in sickle mice. • Free heme results in fatal acute chest syndrome in sickle versus control mice. • Chlorinated lipids mediate the effects of chlorine on the red blood cells. • Hemopexin alleviates chlorine induced hypoxia, and acute lung injury. • Therefore, postexposure hemopexin injection improves the survival of sickle mice.

Background Tuberculosis (TB) is a pandemic, being one of the top 10 causes of death and the main cause of death from a single source of infection. Drug-induced liver injury (DILI) is the most common and serious side effect during the treatment of TB. Objective We aim to predict the status of liver injury in patients with TB at the clinical treatment stage. Methods We designed an interpretable prediction model based on the XGBoost algorithm and identified the most robust and meaningful predictors of the risk of TB-DILI on the basis of clinical data extracted from the Hospital Information System of Shenzhen Nanshan Center for Chronic Disease Control from 2014 to 2019. Results In total, 757 patients were included, and 287 (38%) had developed TB-DILI. Based on values of relative importance and area under the receiver operating characteristic curve, machine learning tools selected patients’ most recent alanine transaminase levels, average rate of change of patients’ last 2 measures of alanine transaminase levels, cumulative dose of pyrazinamide, and cumulative dose of ethambutol as the best predictors for assessing the risk of TB-DILI. In the validation data set, the model had a precision of 90%, recall of 74%, classification accuracy of 76%, and balanced error rate of 77% in predicting cases of TB-DILI. The area under the receiver operating characteristic curve score upon 10-fold cross-validation was 0.912 (95% CI 0.890-0.935). In addition, the model provided warnings of high risk for patients in advance of DILI onset for a median of 15 (IQR 7.3-27.5) days. Conclusions Our model shows high accuracy and interpretability in predicting cases of TB-DILI, which can provide useful information to clinicians to adjust the medication regimen and avoid more serious liver injury in patients.

Background: Cancer survivors are at greater risk for cardiovascular disease (CVD) than second malignancy, resulting in a decreased quality of life and increased cost of care. Additional knowledge of CVD prevention by identifying possible risk factors has clinical relevance. Our main objective was to determine the relevance of a clinical index of arterial stiffness, pulse pressure, in predicting CVD mortality in cancer patients, with a second objective to examine its relationship with cancer mortality. Methods: We retrospectively analyzed 781 cancer patients from Third National Health and Nutrition Examination Survey and Linked Mortality File, including demographic, anthropometric, blood pressure, and cause of death. Kaplan-Meier survival curve and Cox hazard regression analyses were performed to assess the relationship between pulse pressure and cardiovascular, cancer, and all-cause mortality. Results: During a mean follow-up time of 8.1 years, 603 deaths, 257 cancer and 151 CVD, occurred. In unadjusted models, the risk of CVD, cancer, and all-cause mortality were 3.8-fold, 5.3-fold, and 1.6-fold higher, respectively, for pulse pressure ≥70 ​mmHg compared to

Background Cause of death data are essential for rational health planning yet are not routinely available in Papua New Guinea (PNG) and Solomon Islands. Indirect estimation of cause of death patterns suggests these populations are epidemiologically similar, but such assessments are not based on direct evidence. Methods Verbal autopsy (VA) interviews were conducted at three sites in PNG and nationwide in Solomon Islands. Training courses were also facilitated to improve data from medical certificates of cause of death (MCCODs) in both countries. Data were categorised into broad groups of endemic and emerging conditions to aid assessment of the epidemiological transition. Findings Between 2017 and 2020, VAs were collected for 1,814 adult deaths in PNG and 819 adult deaths in Solomon Islands. MCCODs were analysed for 662 deaths in PNG and 1,408 deaths in Solomon Islands. The VA data suggest lower NCD mortality (48.8% versus 70.3%); higher infectious mortality (27.0% versus 18.3%) and higher injury mortality (24.5% versus 11.4%) in PNG compared to Solomon Islands. Higher infectious mortality in PNG was evident for both endemic and emerging infections. Higher NCD mortality in Solomon Islands reflected much higher emerging NCDs (43.6% vs 21.4% in PNG). A similar pattern was evident from the MCCOD data. Interpretation The cause of death patterns suggested by VA and MCCOD indicate that PNG is earlier in its epidemiological transition than Solomon Islands, with relatively higher infectious mortality and lower NCD mortality. Injury mortality was also particularly high in PNG. This study was funded by Bloomberg Philanthropies.

BACKGROUND The aim of this study was to find the main risk factors for development of cardiac allograft vasculopathy (CAV), especially factors identified before the surgical procedure and factors related to the recipient profile and the medical history of the donor. MATERIAL AND METHODS There were 147 patients who had heart transplantation (HT) included in this study: mean age was 45.8±15.3 years. All study patients had coronary angiography after HT. Analyzed risk factors were: non-immunologic recipient risk factors (age of transplantation, smoking, hypertension, lipids, diabetes, obesity and weight gain after HT), immunologic recipient risk factors (acute cellular rejection (ACR), acute humoral rejection (AMR), cytomegalovirus (CMV) episodes), and donor-related risk factors (age, sex, catecholamine usage, ischemic time, compatibility of sex and blood groups, cause of death, cardiac arrest). RESULTS CAV was recognized in 48 patients (CAV group); mean age 53.6±13.6 years. There were 99 patients without CAV (nonCAV group); mean age 48.3±15.5 years. A univariate Cox analysis of the development of coronary disease showed statistical significance (p

Background/Aim: Cardiovascular disease is the most serious cause of death in patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca) levels have been associated with poor outcome and cardiovascular mortality in patients on maintenance and initiation dialysis. As a more accurate marker is warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause and cardiovascular mortality that indicates vessel calcification. Methods: We recruited 378 consecutive patients with end-stage renal disease who started dialysis between January 2009 and December 2015 at the Japanese Red Cross Ishinomaki Hospital. We collected data of patients' demographic characteristics and comorbidities from their electronic medical records. We retrospectively examined the association of the serum Ca-Mg ratio with all-cause and cardiovascular mortality using the Cox proportional hazard model, and determined the value that predicted cardiovascular death using the receiver operating characteristic (ROC) curve. Results: Overall, 253 patients with serum Mg and Ca data were analyzed. The 3-year survival rate of this group was 0.70 (95% confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12 (95% CI 0.05-0.23), which was significantly higher than that of the other groups. The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037). Conclusion: A high Ca-Mg ratio was significantly associated with all-cause and cardiovascular mortality, and it was more accurate than serum Mg.

Introduction: Male breast cancer accounts for less than 1% of breast cancers with published overall and disease free survival being lower than in females. Aims: To determine treatment and long term outcomes for male breast cancer patients in our unit. Methods: A database has been maintained for all breast cancer patients diagnosed in our unit since 1993. Patients were identified using the database and information was collated on patient demographics, tumour pathology, treatment and outcomes using the database and retrospective chart review. Patients were followed to cause of death. Results: From 1994-2009 twenty-four cancers were diagnosed in twenty-two patients. Mean age at diagnosis was 69. Male breast cancer patients were treated using similar principles to female breast cancer. Twenty patients underwent mastectomy, two patients underwent wide local excision. No patients developed local recurrence. One patient died from their breast cancer with systemic metastases. 10-year overall survival was 22%, 10 year disease-specific survival was 80%. Other causes of death included medical co-morbidity and secondary cancers. Discussion: Disease free survival in our unit is comparable to other published studies. High age at diagnosis and co-morbidity are the most important factors in determining overall outcome. Treatment pathways for male breast cancer should follow guidelines for female disease in order to optimise outcomes. Future research at national or international level is necessary to ensure the most effective treatments are implemented for male breast cancer patients.

A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. 6745 patients (mean age 64.9 ± 12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1 ± 1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p

Background: Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease with an elevated risk of developing lymphoproliferative malignancies (LM). Whether pSS is a risk factor or not for non-lymphoma malignancies (NLM) has been scarcely evaluated in the literature. Age is per se a risk factor for malignancies: patients over 70 years old have 4 times higher risk for cancers than adults. Even if the mean age of pSS onset usually is in the 4th and 5th decade, its onset in patients aged over 65 years (Elderly Onset pSS – EOpSS) is not uncommon. Material and methods: To evaluate pSS as a risk factor for NLM we performed a systematic electronic search on PubMed in the period 2006–2016 to identify all the publications on this topic. The studies were eligible for inclusion if they reported specific Standardized Incidence Ratio (SIR) with 95% CI. Studies that did not report sufficient published and/or original data were excluded. Results: Only 7 articles of 494 that we found in PubMed fulfilled the inclusion criterion. In the vast majority of these, SIR values were not statistically significant for NLM. The occurrence of NLM after LM was statistically significant in some studies and a NLM represented the most frequent cause of death. The possibility that NLM may represent a paraneoplastic syndrome seems much more frequent than LM, the risk of which increases with time after the diagnosis. Data regarding the neoplastic weight of EOpSS are mainly pointed out by case reports. Conclusions: Primary Sjögren’s syndrome is not associated with an increased risk for NLM. However the possibility that NLM may appear after recovery from lymphoma should be carefully considered because it could be cause of the patient’s death. Similarly the possibility that NLM may represent a paraneoplastic syndrome must be highlighted. The relationship between EOpSS and SIRs for NLM should be deepened with studies on ad hoc cohorts.

Objectives In many African countries, child mortality is higher in the rainy season than in the dry season. We investigated the effect of season on child mortality by time periods, sex, and age in rural Guinea-Bissau. Methods Bandim health project follows children under-five in a health and demographic surveillance system in rural Guinea-Bissau. We compared the mortality in the rainy season (June to November) between 1990 and 2013 with the mortality in the dry season (December to May) in Cox proportional hazards models providing rainy versus dry season mortality rate ratios (r/d-mrr). Seasonal effects were estimated in strata defined by time periods with different frequency of vaccination campaigns, sex and age (

Pancreatic cancer occupies the fourth place as a cause of death from cancer, and the mortality rate is similar to the number of newly detected cases. Due to the late diagnosis, only 5-6% of patients with pancreatic cancer survive for five years. Given that early diagnosis is critical for improving patients’ survival rates, there is an urgent need for the discovery and validation of new biomarkers with sufficient sensitivity and specificity to help diagnose pancreatic cancer early. Detection of serum tumor markers (CA19-9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer. The combination of miR-16, miR-196a and CA19-9 plasma level was more effective, especially in early tumor screening. Furthermore, recent studies reported that mainly miR-21, miR-155 and miR-196 were dysregulated in IPMN (intraductal papillary mucinous neoplasms) and PanIN (pancreatic intraepithelial neoplasia) lesions, suggesting their usefulness as early biomarkers of these diseases. The reduced rate of apoptosis plays a crucial role in carcinogenesis, and it is one of the most important characteristics acquired by pancreatic cancer cells, which protects them from attack by the immune system and reduces the effectiveness of pharmacological treatment. This review summarizes the data concerning the clinical utility of selected biomarkers in pancreatic cancer patients. The review mainly focuses on the genetic aspects of signaling pathway disorders associated with apoptosis in the pathogenesis and diagnosis of pancreatic cancer.

Cardiovascular diseases (CVDs) represent the world's leading cause of death among women. Women with premature ovarian insufficiency (POI) may be at higher risk of cardiovascular disease, such as myocardial infarction or stroke, than women with normal menopause. The increased burden may be mediated by a worsening of cardiovascular risk factors, such as lipid profiles, with accompanying loss of ovarian function. In contrast, the increased burden may be caused by factors that precede and potentially contribute to both CVD events and ovarian decline, such as smoking. Women with X chromosome-related POI like Turner syndrome (TS) are a distinct group with unique medical needs. Regardless of the cause, women with POI may serve as an important population to target for CVD screening and prevention strategies. These strategies should include the use of CVD risk stratification tools to identify women who may benefit from lifestyle modification and pharmacological therapy to prevent CVD.

The aim of this study was to assess the agreements of both biplane and short-axis Simpson’s (SAX) methods for left atrial ejection fraction (LAEF) calculation utilising cardiovascular magnetic resonance imaging (CMR) in heart failure with preserved ejection fraction (HFpEF) and evaluate their relation to clinical outcomes. One hundred and thirty six subjects (HFpEF n = 97, controls n = 39) underwent CMR, six-minute walk tests and blood sampling in our prospective, observational, single-centre study. Overall, LAEF (%) was lower in HFpEF patients compared to controls (SAX 34 ± 13 vs 47 ± 8, biplane 34 ± 16 vs 51 ± 11; p

Background The prospective WEARIT-II-EUROPE registry aimed to assess the value of the wearable cardioverter-defibrillator (WCD) prior to potential ICD implantation in patients with heart failure and reduced ejection fraction considered at risk of sudden arrhythmic death. Methods and results 781 patients (77% men; mean age 59.3 ± 13.4 years) with heart failure and reduced left ventricular ejection fraction (LVEF) were consecutively enrolled. All patients received a WCD. Follow-up time for all patients was 12 months. Mean baseline LVEF was 26.9%. Mean WCD wearing time was 75 ± 47.7 days, mean daily WCD use 20.3 ± 4.6 h. WCD shocks terminated 13 VT/VF events in ten patients (1.3%). Two patients died during WCD prescription of non-arrhythmic cause. Mean LVEF increased from 26.9 to 36.3% at the end of WCD prescription (p Conclusions Mortality after WCD prescription was mainly driven by heart failure and non-cardiovascular death. In patients with HFrEF and a potential risk of sudden arrhythmic death, WCD protected observation of LVEF progression and appraisal of competing risks of potential non-arrhythmic death may enable improved selection for beneficial ICD implantation. Graphic abstract

Background: Variable selection is an important issue when developing prognostic models. Missing data occur frequently in clinical research. Multiple imputation is increasingly used to address the presence of missing data in clinical research. The effect of different variable selection strategies with multiply imputed data on the external performance of derived prognostic models has not been well examined. Methods and Results: We used backward variable selection with 9 different ways to handle multiply imputed data in a derivation sample to develop logistic regression models for predicting death within 1 year of hospitalization with an acute myocardial infarction. We assessed the prognostic accuracy of each derived model in a temporally distinct validation sample. The derivation and validation samples consisted of 11 524 patients hospitalized between 1999 and 2001 and 7889 patients hospitalized between 2004 and 2005, respectively. We considered 41 candidate predictor variables. Missing data occurred frequently, with only 13% of patients in the derivation sample and 31% of patients in the validation sample having complete data. Regardless of the significance level for variable selection, the prognostic model developed using only the complete cases in the derivation sample had substantially worse performance in the validation sample than did the models for which variables were selected using the multiply imputed versions of the derivation sample. The other 8 approaches to handling multiply imputed data resulted in prognostic models with performance similar to one another. Conclusions: Ignoring missing data and using only subjects with complete data can result in the derivation of prognostic models with poor performance. Multiple imputation should be used to account for missing data when developing prognostic models.

Background Chronic obstructive pulmonary disease (COPD) is the second-leading cause of death in the United Kingdom and accounts for 1.7% of bed days in acute hospitals. An estimated two-third of patients with COPD remain undiagnosed. Objective Modern Innovative Solutions in Improving Outcomes in Chronic Obstructive Pulmonary Disease (MISSION COPD) aimed to proactively identify patients from primary care who were undiagnosed or had uncontrolled COPD and to provide a comprehensive integrated multidisciplinary clinic to address the needs of this complex group for improving diagnosis, personalizing therapy, and empowering patients to self-manage their condition. Methods This clinic was led by a respiratory specialist team from Portsmouth Hospitals NHS Trust working with five primary care surgeries in Wessex. A total of 108 patients were reviewed, with 98 patients consenting to provide additional data for research. Diagnoses were changed in 14 patients, and 32 new diagnoses were made. Results Reductions were seen across all aspects of unscheduled care as compared to the prior 12 months, including in emergency general practitioner visits (3.37-0.79 visits per patient, P Conclusions This pilot demonstrates that the MISSION model may be an effective way to provide comprehensive gold-standard care that is valued by patients and to promote integration across sectors.

Background Coronary heart disease (CHD) is the leading cause of death and disability among American women. The prevalence of CHD is expected to increase by more than 40% by 2035. In 2015, the estimated cost of caring for patients with CHD was US $182 billion in the United States; hospitalizations accounted for more than half of the costs. Compared with men, women with CHD or those who have undergone coronary revascularization have up to 30% more rehospitalizations within 30 days and up to 1 year. Center-based cardiac rehabilitation is the gold standard of care after an acute coronary event, but few women attend these valuable programs. Effective home-based interventions for improving cardiovascular health among women with CHD are vital for addressing this gap in care. Objective The ubiquity of mobile phones has made mobile health (mHealth) behavioral interventions a viable option to improve healthy behaviors of both women and men with CHD. First, this study aimed to examine the usability of a prototypic mHealth intervention designed specifically for women with CHD (herein referred to as HerBeat). Second, we examined the influence of HerBeat on selected health behaviors (self-efficacy for diet, exercise, and managing chronic illness) and psychological (perceived stress and depressive symptoms) characteristics of the participants. Methods Using a single-group, pretest, posttest design, 10 women participated in the 12-week usability study. Participants were provided a smartphone and a smartwatch on which the HerBeat app was installed. Using a web portal dashboard, a health coach monitored participants’ ecological momentary assessment data, their behavioral data, and their heart rate and step count. Participants then completed a 12-week follow-up assessment. Results All 10 women (age: mean 64.4 years, SD 6.3 years) completed the study. The usability and acceptability of HerBeat were good, with a mean system usability score of 83.60 (SD 16.3). The participants demonstrated statistically significant improvements in waist circumference (P=.048), weight (P=.02), and BMI (P=.01). Furthermore, depressive symptoms, measured with the Patient Health Questionnaire-9, significantly improved from baseline (P=.04). Conclusions The mHealth prototype was feasible and usable for women with CHD. Participants provided data that were useful for further development of HerBeat. The mHealth intervention is expected to help women with CHD self-manage their health behaviors. A randomized controlled trial is needed to further verify the findings.

Introduction Tobacco use remains the most preventable cause of death and disability, with prisoners being a neglected population of tobacco users. The aim was to determine the prevalence of tobacco use and attitudes toward its prevention among adult male prisoners. Methods We conducted a descriptive cross-sectional study among 349 adult male inmates from three prisons in Khartoum State. The interview questionnaire included questions related to tobacco use status, type of tobacco used, previous attempts to quit, smoking inside a room, frequency of tobacco use before and after incarceration, and attitude toward its prevention. Chi-squared and paired t-test were used to compare between different variables, with the level of significance set at p≤0.05. Results The majority (69.1%) were in the age group 30-50 years. All of the studied prisoners were tobacco users of which: 43.8% used oral snuff (toombak); 22.1% were cigarette smokers; 30.9% used both cigarette and toombak; 0.6% used cigarette and waterpipe; and 3.2% used cigarette, toombak and waterpipe. Toombak users (alone or with other types of tobacco) were 272 (78%) with the majority (62.4%) dipping 2-5 times per day. There were 96 (57%) cigarette smokers (alone or with other types), and waterpipe users were 12 (3.8%). The majority (74.6%) of cigarette users shared their cell with other toombak users. For the majority (79.6%), the number of cigarettes and snuff dipping per day was directly proportional to the period of incarceration. Almost all (99.1%) prisoners know the harmful effects of tobacco use, and 64.5% had previously attempted to quit. Also, 98% of tobacco users reported a desire to quit and expressed willingness to participate in a tobacco-cessation program. Conclusions Different patterns and methods of tobacco use were explored, and all the studied prisoners were users. Tobacco use increased after incarceration. The willingness to participate in tobacco-cessation counselling should be met with the implementation of a planned and well-designed prevention program.

Background: Cancer is the second leading cause of death worldwide. Few studies have investigated if recurrent pregnancy loss is associated with an increased risk of cancer. We aimed to assess whether pregnancy loss is associated with later cancer development.Methods: We identified all invasive cancers after age 40, among all Danish women born between January 1957 and December 1972, ensuring a full reproductive history. Cases were matched by birth year 1:10 to cancer-free controls. Women were followed until the end of 2017. The number of pregnancy losses (miscarriages or still births) was correlated to long-term cancer risk using conditional logistic regression, providing odds ratios for specific cancers with different numbers of pregnancy losses, all adjusted for age, education, and other potential confounders.Findings: The study included 28,785 women with cancer (mean age 48.7 [SD 5.0]) and 283,294 matched controls (mean age 48.6 [SD 5.0]). We found no overall association between pregnancy loss and later development of 11 site-specific types of cancer or cancer overall. Taking the sequence of pregnancy losses into account, primary recurrent pregnancy loss (three consecutive pregnancy losses without prior live birth) was associated with later overall cancer by an odds ratio of 1.27 (1.04-1.56). Secondary recurrent pregnancy loss showed no association to cancer.Interpretation: Pregnancy loss was not associated with later cancer development. Women with primary recurrent pregnancy loss had a borderline significant association to later cancer overall, this may be a chance finding.Funding: Ole Kirk's Foundation and Copenhagen University Hospital Rigshospitalet's Research Grant.

BackgroundPatients with serious mental disorders have poorer healthcare outcomes at the end of life and are at greater risk of dying from unnatural causes.AimsTo explore place of death and demographic and clinical correlates of unnatural causes of death in patients with serious mental disorders.MethodRoutinely collected patient data were used to explore bivariate and adjusted associations between covariates and natural/unnatural cause of death.ResultsIn multivariable analysis (n = 1029), dying at home (odds ratio (OR) = 1.87, 95% CI 1.03–3.40), ‘other’ locations (OR = 16.50, 95% CI 7.57–36.00), younger age (OR = 17.26, 95% CI 8.28–36.00) and a diagnosis other than schizophrenia spectrum disorder (OR = 1.69, 95% CI 1.04–2.73) were correlates of unnatural cause of death.ConclusionsDeaths from unnatural causes were high and more likely to occur at home and non-healthcare settings. Unnatural causes of death were higher in younger patients with non-schizophrenia spectrum disorder diagnoses.Declaration of interestF.G. has received support or honoraria for CME, advisory work and lectures from Bristol-Myers Squibb, Janssen, Lundbeck, Otsuka, Roche, and Sunovion, and has a family member with professional links to Lilly and GSK, including shares.

Background The Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previous studies have investigated whether the Duke treadmill score and its individual components based on bicycle exercise testing predict cardiovascular death. Design Two populations with a standard bicycle testing were used: 3936 patients referred for exercise testing (2371 men, age 56 ± 13 years) from the Finnish Cardiovascular Study (FINCAVAS) and a population-based sample of 2683 men (age 53 ± 5.1 years) from the Kuopio Ischaemic Heart Disease study (KIHD). Methods Cox regression was applied for risk prediction with cardiovascular mortality as the primary endpoint. Results In FINCAVAS, during a median 6.3-year (interquartile range (IQR) 4.5–8.2) follow-up period, 180 patients (4.6%) experienced cardiovascular mortality. In KIHD, 562 patients (21.0%) died from cardiovascular causes during the median follow-up of 24.1 (IQR 18.0–26.2) years. The Duke treadmill score was associated with cardiovascular mortality in both populations (FINCAVAS, adjusted hazard ratio (HR) 3.15 for highest vs. lowest Duke treadmill score tertile, 95% confidence interval (CI) 1.83–5.42, P Conclusions The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor.

Viral pneumonia is an important cause of death and morbidity among infants worldwide. Transmission of non-influenza respiratory viruses in households can inform preventative interventions and has not been well-characterised in South Asia. From April 2011 to April 2012, household members of pregnant women enrolled in a randomised trial of influenza vaccine in rural Nepal were surveyed weekly for respiratory illness until 180 days after birth. Nasal swabs were tested by polymerase chain reaction for respiratory viruses in symptomatic individuals. A transmission event was defined as a secondary case of the same virus within 14 days of initial infection within a household. From 555 households, 825 initial viral illness episodes occurred, resulting in 79 transmission events. The overall incidence of transmission was 1.14 events per 100 person-weeks. Risk of transmission incidence was associated with an index case age 1–4 years (incidence rate ratio (IRR) 2.35; 95% confidence interval (CI) 1.40–3.96), coinfection as initial infection (IRR 1.94; 95% CI 1.05–3.61) and no electricity in household (IRR 2.70; 95% CI 1.41–5.00). Preventive interventions targeting preschool-age children in households in resource-limited settings may decrease the risk of transmission to vulnerable household members, such as young infants.

We investigated mortality, causes, timing and risk factors for death until hospital discharge in very-low-birth-weight (VLBW) infants born in two Croatian perinatal care regions. This retrospective study included 252 live born VLBW infants. The mortality rate until hospital discharge was 30.5% (77/252). VLBW in-fants who died had by 4 weeks lower gestational age (GA) than surviving infants (median GA, 25 vs. 29 weeks), lower birth weight (BW) (mean BW, 756.4 vs. 1126.4 g), lower 5-minute Apgar score (median 5 vs. 8) and were more often resuscitated at birth (41.6 vs. 19.4%; p12 hours to necrotizing enterocolitis., Istraživali smo smrtnost, uzroke, vrijeme i rizične čimbenike za smrt do otpusta iz bolnice u novorođenčadi vrlo niske porođajne težine (VNPT) rođene u dvije hrvatske perinatalne regije. Ova retrospektivna studija je uključila 252 živo-rođena novorođenčeta VNPT. Smrtnost do otpusta iz bolnice bila je 30.5% (77/252). Novorođenčad VNPT koja su umrla bila su 4 tjedna manje gestacijske dobi od novorođenčadi koja je preživjela (medijan gestacijske dobi 25 prema 29 tjedana; p12 sati glavni uzrok smrti je nekrotizirajući enterokolitis.

Statistical models are commonly employed in the estimation of influenza-associated excess mortality that, due to various reasons, is often underestimated by laboratory-confirmed influenza deaths reported by healthcare facilities. However, methodology for timely and reliable estimation of that impact remains limited because of the delay in mortality data reporting. We explored real-time estimation of influenza-associated excess mortality by types/subtypes in each year between 2012 and 2018 in Hong Kong using linear regression models fitted to historical mortality and influenza surveillance data. We could predict that during the winter of 2017/2018, there were ~634 (95% confidence interval (CI): (190, 1033)) influenza-associated excess all-cause deaths in Hong Kong in population ⩾18 years, compared to 259 reported laboratory-confirmed deaths. We estimated that influenza was associated with substantial excess deaths in older adults, suggesting the implementation of control measures, such as administration of antivirals and vaccination, in that age group. The approach that we developed appears to provide robust real-time estimates of the impact of influenza circulation and complement surveillance data on laboratory-confirmed deaths. These results improve our understanding of the impact of influenza epidemics and provide a practical approach for a timely estimation of the mortality burden of influenza circulation during an ongoing epidemic.

Aims: Over the last four decades, in-hospital mortality from acute coronary syndromes (ACS) has declined. We characterized the patients who died in our cardiovascular intensive care unit (CICU) over a 15-year period. Based on these data, we described the changing patient population in the CICU. Methods: This retrospective study compared characteristics of patients who died in our CICU in 2005–6, 2013–4 and 2019. During these 5 years, 13,931 patients were hospitalized; 251 (1.8%) died. The mean age of the patients who died was 76 years, 144 (57%) were men. ACS was the leading cause of admission (93 patients, 37%), and 145 (58%) patients had a history of heart failure prior to hospitalization. The leading cause of death was cardiogenic shock in 104 (41%) patients, septic shock in 48 (19%) patients, and combined cardiogenic and septic shock in 31 (12%). Patients hospitalized in the later years of the study were significantly older (67.7, 69.0 and 70.5 years, 2005–6, 2013–4 and 2019, respectively, p

Background Liver transplant (LT) remains a life-saving procedure with a high mortality rate. The present study investigated the causes of death and sought to identify predictive factors of mortality during the initial LT hospitalization. Material/Methods We retrieved data on first-time adult recipients who underwent LT between November 2017 and October 2019 receiving grafts from donation after citizen’s death. The risk factors for mortality during the initial LT hospitalization were confirmed by univariate analysis. We also analyzed the causes of death. Results We enrolled 103 recipients, including 86 males and 17 females, with a mean age of 47.7 years. Thirty-eight (36.9%) recipients were labeled as non-cholestatic cirrhosis-related indications. Approximately 8% of all recipients had diabetes prior to LT. Induction therapy was used in 11 (10.7%) recipients, along with maintenance therapy. The median model for end-stage liver disease score at LT was 32.4 (21.4–38.4). The in-hospital mortality rate of LT recipients was 6.8% (7/103), and infections were responsible for most of the deaths (6/7). The 1 remaining death resulted from primary graft failure. Univariate analysis showed recipients with postoperative pneumonia (p2 mg/dL, and alanine transaminase on day 1 after LT >1800 μmol/L (all P

// Qian Chen 1, 2 , Ding Ding 1 , Yuan Zhang 3 , Yunou Yang 1 , Qing Li 1 , Xuechen Chen 1 , Gang Hu 2 , Wenhua Ling 1 1 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangdong, China 2 Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA 3 Department of Cardiology, General Hospital of Guangzhou Military Command of People’s Liberation Army, Guangdong, China Correspondence to: Wenhua Ling, email: lingwh@mail.edu.cn Gang Hu, email: gang.hu@pbrc.edu Keywords: coronary heart disease, risk score, mortality, cohort study Received: August 23, 2016 Accepted: October 17, 2016 Published: November 07, 2016 ABSTRACT Background: The aim of the study is to develop risk scores with traditional factors for all-cause and cardiovascular mortality among coronary heart disease (CHD) patients. Methods and Results: We performed a prospective cohort study of 1911 CHD patients aged 40 and older. Cox models were used to estimate the association of traditional factors [sex, age, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood pressure (BP), and cigarette use] and risk scores with all-cause and cardiovascular mortality. During a mean follow-up of 4.9 years, 232 deaths were identified, 159 of which were cardiovascular-related. Both 4-year and whole follow-up data showed age, sex, HDL-C, LDL-C, and FBG were significantly associated with the risk of mortality, while BP and smoking were not significant predictors in all models. We incorporated age, sex, FBG, HDL-C, and LDL-C to establish risk scores for all-cause and cardiovascular mortality in the 4-year and whole follow-up study. These risk scores were positively associated with the risk of death as quartiles and continuous variables. Assessed by the area under the receiver operating characteristic curves (AUROCs), these risk scores demonstrated strong discriminatory capacity, from 0.744 to 0.763; and the utility of these scores was confirmed with AUROCs from 0.736 to 0.756 (all P

Smoking is associated with the risks of mortality from breast cancer (BC) or all causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A search of PubMed and Embase was performed, and a random-effect model was used to yield summary hazard ratios (HRs). Eleven prospective cohort studies were included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase were 1.10 (95% confidence interval (CI) = 1.04-1.16), 1.09 (95% CI = 1.06-1.12), 1.10 (95% CI = 1.06-1.14) for BC specific mortality, and 1.15 (95% CI = 1.10-1.19), 1.15 (95% CI = 1.10-1.20), 1.17 (95% CI = 1.11-1.23) for all-cause mortality, respectively. The linear or non-linear associations between smoking and risks of mortality from BC or all causes were revealed. Subgroup analyses suggested a positive association between ever or former smoking and the risk of all-cause mortality in BC patients, especially in high doses consumption. In conclusion, higher smoking intensity, more cumulative amount of cigarettes consumption and longer time for smoking is associated with elevated risk of mortality from BC and all causes in BC individuals. The results regarding smoking cessation and "ever or former" smokers should be treated with caution due to limited studies.

Background we aimed to develop and validate a population-representative 10-year mortality risk index for older adults in England. Methods data were from 10,798 men and women aged 50 years and older in the population-based English Longitudinal Study of Ageing in 2002/03, randomly split into development (n = 5,377) and validation cohorts (n = 5,421). Participants were asked about their sociodemographics, health behaviours, comorbidities, and functional status in the home-based interviews. Variables that were independently associated with all-cause mortality through March 2013 in the development cohort were weighted relative to one another to develop risk point scores for the index that was calibrated in the validation cohort. Results the validated 10-year mortality risk index assigns points for: increasing age (50–59 years: 0 points; 60–64: 1 point; 65–69: 3 points; 70–74: 5 points; 75–79: 7 points; 80–84: 9 points; ≥85: 12 points), male (2 points), no vigorous physical activity (1 point), smoking (2 points), having a diagnosis of cancer (1 point), chronic lung disease (2 points) or heart failure (4 points), and having difficulty preparing a hot meal (2 points), pushing or pulling large objects (1 point) or walking 100 yards (1 point). In the full study cohort, 10-year mortality rates increased from 1.7% (11/664) in those with 0 points to 95% (189/199) among those with ≥16 points. Conclusion this highly predictive 10-item mortality risk index is valid in the English population aged 50 years and older. It uses simple information that is often available in research studies and patient reports, and does not require biomarker data to predict mortality.

// Omid Azimzadeh 1 , Tamara Azizova 2 , Juliane Merl-Pham 3 , Vikram Subramanian 1 , Mayur V. Bakshi 1 , Maria Moseeva 2 , Olga Zubkova 2 , Stefanie M. Hauck 3 , Natasa Anastasov 1 , Michael J. Atkinson 1, 4 , Soile Tapio 1 1 Helmholtz Zentrum Munchen-German Research Center for Environmental Health (GmbH), Institute of Radiation Biology, Neuherberg, Germany 2 Southern Urals Biophysics Institute, Russian Federation, Ozyorsk, Russia 3 Helmholtz Zentrum Munchen-German Research Center for Environmental Health (GmbH), Research Unit Protein Science, Munich, Germany 4 Chair of Radiation Biology, Technical University of Munich, Munich, Germany Correspondence to: Soile Tapio, email: soile.tapio@helmholtz-muenchen.de Keywords: ionising radiation, proteomics, heart disease, PPAR alpha, mitochondrial dysfunction Received: April 08, 2016 Accepted: June 17, 2016 Published: July 06, 2016 ABSTRACT Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans. The cardiac proteome response to irradiation was analysed in Mayak workers who were exposed only to external doses of gamma rays. All participants were diagnosed during their lifetime with IHD that also was the cause of death. Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, 500 mGy). The groups could be separated using principal component analysis based on all proteomics features. Proteome profiling showed a dose-dependent increase in the number of downregulated mitochondrial and structural proteins. Both proteomics and immunoblotting showed decreased expression of several oxidative stress responsive proteins in the irradiated hearts. The phosphorylation of transcription factor PPAR alpha was increased in a dose-dependent manner, which is indicative of a reduction in transcriptional activity with increased radiation dose. These data suggest that chronic external radiation enhances the risk for IHD by inhibiting PPAR alpha and altering the expression of mitochondrial, structural, and antioxidant components of the heart.

// Hui Kong 1 , Ying Wu 1 , Mengou Zhu 2 , Changwen Zhai 3 , Jing Qian 1 , Xue Gao 4 , Shuyang Wang 1 , Yingyong Hou 3 , Shaohua Lu 3, * , Hongguang Zhu 1, 4, * 1 Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China 2 Harvard College, Harvard University, Cambridge, MA, USA 3 Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China 4 Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Hongguang Zhu, email: hongguang_702@163.com Keywords: prognostic biomarker, long non-coding RNA, early stage colorectal cancer, liver metastasis, quantitative RT-PCR Received: December 06, 2015 Accepted: June 12, 2016 Published: July 06, 2016 ABSTRACT Liver metastasis is the primary cause of death for colorectal cancer (CRC) patients. To investigate the prognostic value of long non-coding RNAs (lncRNAs) on colorectal liver metastases, quantitative reverse-transcriptase PCR (quantitative RT-PCR) was performed on 15 lncRNAs in 51 stage IV CRC with liver metastases and 57 stage I/II CRC specimens. The expression levels of four lncRNAs (GAS5, H19, MEG3 and Yiya) were significantly different between liver metastases and primary tumors of stage IV CRC patients. Furthermore, the high expression levels of GAS5 and Yiya were significantly associated with future occurrence of liver metastases in early stage CRC patients. Kaplan-Meier analysis showed that the high expression levels of GAS5 or Yiya were correlated with poor prognosis of early stage CRC patients (p = 0.0206 and 0.0005 for GAS5 and Yiya, respectively). Yiya expression was proved to be an independent prognostic indicator of colorectal liver metastases in a multivariate analysis (relative risk = 10.7; p < 0.0001). Our study revealed that GAS5 and Yiya were promising prognostic biomarkers of liver metastases for early stage CRC patients.

// Hyo Song Kim 1 , Su-Jin Shin 2 , Seung-Hoon Beom 1 , Minkyu Jung 1 , Yoon Young Choi 3 , Taeil Son 3 , Hyoung-Il Kim 3 , Jae-Ho Cheong 3 , Woo Jin Hyung 3 , Sung Hoon Noh 3 , Hyunsoo Chung 4 , Jun Chul Park 4 , Sung Kwan Shin 4 , Sang Kil Lee 4 , Yong Chan Lee 4 , Woong Sub Koom 5 , Joon Seok Lim 6 , Hyun Cheol Chung 1 , Sun Young Rha 1 , Hyunki Kim 2 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Sun Young Rha, email: rha7655@yuhs.ac Keywords: gastric cancer, molecular subtypes, immunohistochemistry, in-situ hybridization Received: April 04, 2016 Accepted: May 29, 2016 Published: June 16, 2016 ABSTRACT Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials.

BACKGROUND fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations. METHODS in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy. RESULTS one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models. CONCLUSIONS our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship.

To investigate the rate and time trends of neonatal mortality from 1997 to 2014 in Shenyang, which were previously rarely reported upon by developing countries, data on 4719 neonatal deaths (0–28 days) and 970,583 live births from the Shenyang Women and Children Health Care Centre were analyzed. Neonatal mortality rates (per 1000 live births), percent change, and annual percent change (APC) were calculated. During the observation period, neonatal mortality in Shenyang significantly decreased by 7.04%, 8.33%, and 5.35% per year overall, in urban and rural areas, respectively. When grouped by category of neonatal death, the time trends of three categories showed statistically significant decreases: congenital malformations (APC = −9.97%), diseases of the perinatal period (APC = −6.04%), and diseases of the respiratory system (APC = −8.52%). Congenital malformations, diseases of the respiratory system, and diseases of the nervous system and sense organs were the three major contributors to the aforementioned decreasing trend, which accounted for 58.71% in overall areas. Among selective causes of neonatal death, the neonatal mortality rates of pneumonia, congenital heart disease, preterm birth and low birth weight, birth asphyxia, and intracranial hemorrhage of the newborn significantly decreased 7.87%, 7.32%, 2.47%, 11.04%, and 10.68% per year, respectively. In summary, neonatal mortality rates decreased in Shenyang during the 17-year study period. Future studies are warranted to further investigate the factors contributing to the neonatal mortality trends in China.