Case Report Pulmonary Tumor Thrombotic Microangiopathy from Metastatic Prostate Carcinoma

Pulmonary tumor thrombotic microangiopathy is a rare but serious malignancy-related respiratory complication. The most common causative neoplasm is gastric adenocarcinoma. We report a case caused by metastatic prostate adenocarcinoma, diagnosed postmortem in a 58-year-old male. To our knowledge, this is the second reported case from metastatic prostate adenocarcinoma

General Public’s knowledge, awareness, and perception of Cardiometabolic diseases: data from a Singapore study population

BackgroundHealth literacy and illness perception play crucial roles in tackling the cardiometabolic disease epidemic. We aim to compare the attitudes, knowledge, self-perceived risks and actions taken, between individuals with and without metabolic risk factors (MFs).MethodsFrom 5 June to 5 October 2022, participants of the general public were invited to complete a self-administered questionnaire. MF status was defined as the presence of hypertension, hyperlipidemia, diabetes mellitus and/or current/previous smoking. Participants were assessed based on four categories (knowledge-based, attitude-based, perceived risk, and action-based) of questions pertaining to four cardiometabolic diseases – diabetes mellitus, hypertension, hyperlipidemia, and non-alcoholic fatty liver disease.ResultsA total of 345 participants were enrolled, of whom 34.5% had at least one MF. Compared to those without MFs, participants with MFs had lower knowledge scores, but higher perceived risk scores across all cardiometabolic diseases. The largest knowledge gap pertained to hypertension-related questions. After adjustment, linear regression demonstrated that the presence of MFs (β:2.752, 95%CI: 0.772–4.733, p = 0.007) and higher knowledge scores (β:0.418, 95%CI: 0.236–0.600, p < 0.001) were associated with higher perceived risk. Despite increased perceived risk in those with MFs, this translated to only few increased self-reported preventive actions, when compared to those without MFs, namely the reduction in red meat/processed food consumption (p = 0.045) and increase in fruits/vegetables consumption (p = 0.009).ConclusionThis study identified a vulnerable subpopulation living with MFs, with high perceived risks, and discordant levels of knowledge and preventive actions taken. Nationwide efforts should be channeled into addressing the knowledge-to-action gap

Cardiovascular Outcomes in Acute Coronary Syndrome and Malnutrition: A Meta-Analysis of Nutritional Assessment Tools

Background: There is emerging evidence that malnutrition is associated with poor prognosis among patients with acute coronary syndrome (ACS). // Objectives: This study seeks to elucidate the prognostic impact of malnutrition in patients with ACS and provide a quantitative review of most commonly used nutritional assessment tools. // Methods: Medline and Embase were searched for studies reporting outcomes in patients with malnutrition and ACS. Nutritional screening tools of interest included the Prognostic Nutrition Index, Geriatric Nutritional Risk Index, and Controlling Nutritional Status. A comparative meta-analysis was used to estimate the risk of all-cause mortality and cardiovascular events based on the presence of malnutrition and stratified according to ACS type, ACS intervention, ethnicity, and income. // Results: Thirty studies comprising 37,303 patients with ACS were included, of whom 33.5% had malnutrition. In the population with malnutrition, the pooled mortality rate was 20.59% (95% CI: 14.95%-27.67%). Malnutrition was significantly associated with all-cause mortality risk after adjusting for confounders including age and left ventricular ejection fraction (adjusted HR: 2.66, 95% CI: 1.78-3.96, P = 0.004). There was excess mortality in the group with malnutrition regardless of ACS type (P = 0.132), ethnicity (P = 0.245), and income status (P = 0.058). Subgroup analysis demonstrated no statistically significant difference in mortality risk between individuals with and without malnutrition (P = 0.499) when using Controlling Nutritional Status (OR: 7.80, 95% CI: 2.17-28.07, P = 0.011), Geriatric Nutritional Risk Index (OR: 4.30, 95% CI: 2.78-6.66, P < 0.001), and Prognostic Nutrition Index (OR: 4.67, 95% CI: 2.38-9.17, P = 0.023). // Conclusions: Malnutrition was significantly associated with all-cause mortality risk following ACS, regardless of ACS type, ethnicity, and income status, underscoring the importance of screening and interventional strategies for patients with malnutrition

Effects of Renin-Angiotensin system blockers on outcomes from COVID-19: a systematic review and meta-analysis of randomised controlled trials

Background and aims: Randomized controlled trials (RCTs) have assessed the effects of renin–angiotensin system (RAS) blockers in adults with coronavirus disease 2019 (COVID-19). This meta-analysis provides estimates of the safety and efficacy of treatment with (vs. without) RAS blockers from these trials. Methods: PubMed, Web of Science, and ClinicalTrials.gov were searched (1 March–12 April 2023). Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment with no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled. Results: Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU [risk ratio (RR) 0.96, 0.66–1.41], ventilation (RR 0.77, 0.55–1.09), vasopressors (RR 0.92, 0.58–1.44), AKI (RR 1.01, 0.40–2.56), RRT (RR 1.01, 0.46–2.21), or thromboembolic events (RR 1.07, 0.36–3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47–1.08), ventilation (RR 1.12, 0.91–1.38), AKI (RR 1.28, 0.89–1.86), RRT (RR 1.66, 0.89–3.12), or thromboembolic events (RR 1.20, 0.06–23.70), although vasopressor use increased (RR 1.27, 1.02–1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80–1.92), and 1.22 (0.96–1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01–1.72). Conclusion: ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients. PROSPERO registration number: CRD42023408926

PTPN11 mosaicism causes a spectrum of pigmentary and vascular neurocutaneous disorders and predisposes to melanoma

Phakomatosis pigmentovascularis (PPV) is a diagnosis which denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement including central nervous system disease, asymmetrical growth and a predisposition to malignancy. Using a tightly phenotyped group and high depth next generation sequencing of affected tissues we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of PPV type III or spilorosea. Within an individual the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to demonstrate that the same variants can cause either the specific pigmentary or vascular phenotypes alone, as well as driving melanoma development within the pigmentary lesion. Protein conformational modelling highlights that while variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modelling of the missense variants confirms downstream MAPK pathway overactivation, and widespread disruption of human endothelial cell angiogenesis. Importantly, PTPN11-mosaic patients theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of naevus spilus and capillary malformation syndromes, paving the way for better clinical management

Impact of COVID-19 on liver transplantation in Hong Kong and Singapore: A modelling study

Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries. The impact of various policies restricting LT on outcomes of potential LT candidates is unclear. We studied all patients on the nationwide LT waitlists in Hong Kong and Singapore between January 2016 and May 2020. We used continuous time Markov chains to model the effects of different scenarios and varying durations of disruption on LT candidates

Heart failure with preserved ejection fraction, red cell distribution width, and sacubitril/valsartan

Aims: Red cell distribution width (RDW) is a strong prognostic marker in patients with heart failure (HF) and reduced ejection fraction and other conditions. However, very little is known about its prognostic significance in HF with preserved ejection fraction. We examined the relationship between RDW and outcomes and the effect of sacubitril/valsartan, compared with valsartan, on RDW and clinical outcomes in PARAGON-HF. Methods and results: PARAGON-HF enrolled patients with a left ventricular ejection fraction of ≥45%, structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary endpoint was a composite of total HF hospitalizations and cardiovascular deaths. Median RDW at randomization was 14.1% (interquartile range 13.5–15.0%). Patients with higher RDW levels were more often men and had more comorbidity, a higher heart rate and NT-proBNP concentration, more advanced New York Heart Association class, and worse Kansas City Cardiomyopathy Questionnaire scores. There was a graded relationship between quartiles of RDW at randomization and the primary endpoint, with a significantly higher risk associated with increasing RDW, even after adjustment for NT-proBNP and other prognostic variables {Quartile 1, reference; Quartile 2, rate ratio 1.03 [95% confidence interval (CI) 0.83 to 1.28]; Quartile 3, 1.25 [1.01 to 1.54]; Quartile 4, 1.70 [1.39 to 2.08]}. This association was seen for each of the secondary outcomes, including cardiovascular and all-cause death. Compared with valsartan, sacubitril/valsartan reduced RDW at 48 weeks [mean change −0.09 (95% CI −0.15 to −0.02)]. The effect of sacubitril/valsartan vs. valsartan was not significantly modified by RDW levels at randomization. Conclusions: RDW, a routinely available and inexpensive biomarker, provides incremental prognostic information when added to established predictors. Compared with valsartan, sacubitril/valsartan led to a small reduction in RDW

Effect of dapagliflozin on cause-specific mortality in patients with heart failure across the spectrum of ejection fraction

Importance: In 2 trials enrolling patients with heart failure (HF) across the spectrum of ejection fraction (EF), dapagliflozin has been shown to reduce the rate of the composite of worsening HF events or death from cardiovascular (CV) causes. Objective: To examine the effects of dapagliflozin on cause-specific CV and non-CV mortality across the spectrum of EF. Design, Setting, and Participants: This was a participant-level, pooled, prespecified secondary analysis of data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, or DAPA-HF trial (participant left ventricular EF [LVEF] ≤40%), and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure, or DELIVER trial (participant LVEF &gt;40%), to assess the effects of randomized treatment on cause-specific mortality. The trials assigned adjacent populations of patients with chronic HF, New York Heart Association class II-IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The primary outcome for each study was a composite of worsening HF events (hospitalization or urgent heart failure visits) or CV death. Clinical outcomes, including all deaths, were adjudicated as to cause by clinical end points committees blinded to treatment assignment. Intervention: Dapagliflozin vs placebo. Main Outcomes and Measures: The mode of death in relation to baseline EF was examined, as well as the effect of randomized treatment on cause-specific death in Cox regression models. Relationships with continuous EF were modeled using Poisson regression. Results: Of 11 007 patients in the pooled data set, there were 1628 deaths during follow-up (mean [SD] age, 71.7 [10.3] years; 1139 male [70.0%]). Of those who died, 872 (53.5%) were ascribed to CV deaths, 487 (29.9%) to non-CV deaths, and 269 (16.5%) to undetermined causes. Of CV deaths, 289 (33.1%; this represented 17.8% of total deaths) were due to HF, 441 (50.6%; 27.1% of total deaths) were sudden, 69 (7.9%; 4.2% of total deaths) were due to stroke, 47 (5.4%; 2.9% of total deaths) to myocardial infarction, and 26 (3.0%; 1.6% of total deaths) were due to other CV causes. The proportion of non-CV deaths was higher in those with higher EF. In the pooled population, across the spectrum of EF, treatment with dapagliflozin was associated with lower rates of CV death (hazard ratio [HR], 0.86; 95% CI, 0.75-0.98; P = .02), principally due to lower rates of sudden death (HR, 0.84; 95% CI, 0.70-1.01; P = .07) and HF death (HR, 0.88; 95% CI, 0.70-1.11; P = .30), with little difference in rates of death from stroke or MI. Conclusions and Relevance: In a pooled analysis of patients with HF in the DAPA-HF and DELIVER randomized clinical trials, across the full spectrum of LVEF, dapagliflozin significantly reduced risks of CV death with contributions from lower rates of sudden death and death from progressive HF. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124, NCT0361921

Trends and predictions of malnutrition and obesity in 204 countries and territories: an analysis of the Global Burden of Disease Study 2019.

BackgroundMalnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030.MethodsUsing data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed.FindingsIn 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries.InterpretationThe ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further.FundingNone