Citations

Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65–89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC −0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM. METHODS: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction. RESULTS: The genome-wide association study identified a highly suggestive locus that mapped to the 5′-flanking region of the CDCP1 (CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435; P =7.12×10 −7 ). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis. CONCLUSIONS: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

Abstract Prior to the 1970s, blending food and liquids and putting them through an enteral access device (EAD) was the most common form of enteral nutrition (EN). However, in the 1970s, blenderized tube feedings (BTFs) became less popular due to the emergence of modern commercial enteral formulas (CEFs). Recently, a cultural shift toward consuming a natural diet, consisting of whole foods, has led to a resurgence in the use of BTF. The increasing use of BTF in a variety of patient care settings identifies a need for practice recommendations that provide guidance for nutrition professionals and patients. Members of the American Society for Parental and Enteral Nutrition (ASPEN) Enteral Nutrition Committee identified salient clinical questions concerning BTF, conducted a comprehensive literature search, and subsequently developed practice recommendations pertaining to the use of BTF. This paper was approved by the ASPEN 2022–2023 Board of Directors.

Background: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. Design: A prospective, observational cohort study. Methods: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. Results: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml (P = 0.003) and -55.6 ng/ml (P = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 (r = 0.64, P = 0.002; r = 0.58, P = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks. Conclusion: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.

PURPOSE To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)–positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

AbstractThough survival outcomes among adolescents and young adults (AYAs) with lymphoma have improved over the last three decades, socially vulnerable populations including non‐White, low‐income, and publicly insured groups continue to trail behind on survival curves. These disparities, while likely the result of both biological and non‐biological factors, can be largely attributed to inequities in care over the full cancer continuum. Nationally representative studies have demonstrated that from diagnosis through therapy and into long‐term survivorship, socially vulnerable AYAs with lymphoma face barriers to care that impact their short and long‐term survival. Thus, improving outcomes for all AYAs with lymphoma requires dedicated study to understand, and then address the unique challenges faced by non‐White and low‐income lymphoma populations within this age group.

Hyponatraemia on hospital admission is associated with increased length of stay, healthcare expenditures and mortality. Urine studies collected before fluid or diuretic administration are essential to diagnose the underlying cause of hyponatraemia, thereby empowering admitting teams to employ the appropriate treatment. A multidisciplinary quality improvement (QI) team led by internal medicine residents performed a QI project from July 2020 through June 2021 to increase the rate of urine studies collected before fluid or diuretic administration in the emergency department (ED) in patients admitted with moderate to severe hyponatraemia. We implemented two plan-do-study-act (PDSA) cycles to address this goal. In PDSA Cycle #1, we displayed an educational poster in employee areas of the ED and met with nursing staff at their monthly meetings to communicate the project and answer questions. We also obtained agreement from ED attending physicians and nursing leaders to support the project. In PDSA Cycle #2, we implemented a structural change in the nursing triage process to issue every patient who qualified for bloodwork with a urine specimen container labelled with a medical record number on registration so that the patient could provide a sample at any point, including while in the waiting area. After PDSA Cycle #1, urine specimen collection increased from 34.5% to 57.5%. After PDSA Cycle #2, this increased further to 59%. We conclude that a combination of educational and structural changes led to a significant increase in urine specimen collection before fluid or diuretic administration among patients presenting with moderate-to-severe hyponatraemia in the ED.

Background: Graft-versus-host disease (GVHD) is a common complication of hematopoietic cell transplantation, and its incidence is low in liver transplantation (LT). Estimating the incidence of GVHD after LT is challenging due to the paucity of available data from the United Network for Organ Sharing. This is the first national analysis of the incidence and risk factors of GVHD after LT. Methods: This retrospective cohort study used the National Readmission Database to calculate the incidence rate of GVHD within 1 year of LT using survival analysis. The predictors of GVHD were identified using univariate and multivariate Cox regression analyses. Results: From 2010 to 2020, of 88,433 LTs, 383 cases of GVHD occurred within 1 year after LT, resulting in an incidence rate of 1.0% (95% CI: 0.8%–1.3%). We observed no statistically significant change in the incidence of GVHD after LT from 2010 to 2020 (beta-coefficient, −0.07%; 95% CI: −0.17% to 0.04%, p = 0.188). Interestingly, alcohol-associated liver disease was associated with a lower risk of GVHD (adjusted HR, 0.57; 95% CI: 0.36–0.91, p = 0.018), whereas a higher risk was found to be related to a secondary diagnosis of COVID-19 on index admission. Conclusion: Our study found that the incidence rate of GVHD within 1 year of LT in the United States was 1.0% and remained stable from 2010 to 2020. The predictors associated with GVHD include alcohol-associated liver disease and COVID-19. Our study provides valuable insights into the incidence, risk factors, and outcomes of GVHD after LT.