Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

Assessment of fluid and nutritional status using bioelectrical impedance methods in acute kidney injury patients requiring continuous renal replacement therapy

Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7±15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2%. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95%CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95%CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95%CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95%CI 1.72-26.82, P=0.006) between pre-CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95%CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95%CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95%CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95%CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95%CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95%CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality.     

A small molecule LS-1-2F promotes the endocytosis of macromolecules into tumor cells

In the previous research, we found that anticancer agent LS-1-2F could cause the vacuolation of tumor cells. Herein we investigated the effect of compound LS-1-2F on the endocytosis of macromolecules, including fluorescence quantum dots, human serum albumin, single-stranded RNA, and monoclonal antibody, into tumor cells. We found that LS-1-2F could accelerate the endocytosis of these large molecules by laser confocal microscope and flow cytometry. The effect of LS-1-2F on the improvement of the internalization efficiency of Herceptin biosimilar was particularly significant. Promoting endocytosis will help increase the efficiency of liquid-phase drug uptake in drug-resistant cancer cells and could potentially facilitate the use of drugs in nanoparticle delivery vehicles.     

Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy

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Adoption of the 275-patient buprenorphine treatment waiver for treating opioid use disorder: A state-level longitudinal analysis

Abstract

Background: Increasing access to buprenorphine treatment is a critical tool for addressing the opioid epidemic in the United States. In 2016, a federal policy change allowed physicians who meet specific requirements to treat up to 275 concurrent buprenorphine patients. This study examines state-level measures of buprenorphine treatment supply over 21?months since this policy change and estimates associations between the supply of 275-patient waivers and state characteristics. Methods: Monthly state-level measures of the number of physicians holding the 275-patient waiver per 100,000 residents were constructed from September 2016 to May 2018 using the Drug Enforcement Agency’s Controlled Substance Act database. State characteristics were obtained from publicly available sources. Mixed-effects regression models were estimated to examine change over time. Results: During the 21-month period, the number of physicians waivered to treat 275 patients increased from 153 to 4009 physicians. The mean supply of 275-patient physicians per 100,000 state residents significantly increased from 0.07 (SD?=?0.21) in September 2016 to 1.43 (SD?=?1.08) in May 2018 (t?=??9.84, df?=?50, P?<?.001). The final mixed-effects regression model indicated that Census division and the preexisting supply of 100-patient waivered physicians were correlated with the rate of growth in 275-patient waivers over the study period. Conclusions: Although uptake of the 275-patient waiver has exceeded initial projections, growth is uneven across the United States. Unequal patterns of growth pose a challenge to efforts to increase treatment availability as a means of addressing the opioid epidemic.     

康复运动操联合牵引在老年腰椎间盘突出症患者中的应用效果研究

目的探讨康复运动操联合牵引在老年腰椎间盘突出症患者中的应用效果及对腰椎活动度的影响。 方法选择2018年10月至2019年9月老年腰椎间盘突出症患者86例作为对象，随机分为对照组（n=43例）和观察组（n=43例）。对照组采用常规牵引治疗，观察组在对照组基础上联合康复运动操治疗，4周治疗后对患者效果进行评估，比较两组视觉模拟疼痛（VAS）评分、炎症因子水平、腰椎活动度及满意度。 结果观察组治疗后1、2、3、4周VAS评分低于对照组（P<0.05）；观察组治疗后4周IL-1β、TNF-α及TXB2水平均低于对照组（P<0.05）；观察组治疗后4周前屈、后伸、侧屈均高于对照组（P<0.05）；观察组治疗后4周遵医治疗、康复运动、定期复查、治疗效果及治疗形式满意度均高于对照组（P<0.05）。 结论康复运动操联合牵引能减轻老年腰椎间盘突出症患者疼痛，提高患者腰椎活动度，且两种方法干预能降低机体炎症瀑布联级反应，提高患者治疗满意度，值得推广应用。