Citations

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.

Abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Abstract Rationale Constantly exposed to the external environment and mutagens such as tobacco smoke, human lungs have one of the highest somatic mutation rates among all human organs. However, the relationship of these mutations to lung disease and function is not known. Objectives To identify the prevalence and significance of clonal somatic mutations in chronic lung diseases. Methods We analyzed the clonal somatic mutations from 1,251 samples of normal and diseased noncancerous lung tissue RNA sequencing with paired whole-genome sequencing from the Lung Tissue Research Consortium. We examined the associations of somatic mutations with lung function, disease status, and computationally deconvoluted cell types in two of the most common diseases represented in our dataset, chronic obstructive pulmonary disease (COPD; 29%) and idiopathic pulmonary fibrosis (IPF; 13%). Measurements and Main Results Clonal somatic mutational burden was associated with reduced lung function in both COPD and IPF. We identified an increased prevalence of clonal somatic mutations in individuals with IPF compared with normal control subjects and individuals with COPD independent of age and smoking status. IPF clonal somatic mutations were enriched in disease-related and airway epithelial–expressed genes such as MUC5B in IPF. Patients who were MUC5B risk variant carriers had increased odds of developing somatic mutations of MUC5B that were explained by increased expression of MUC5B. Conclusions Our identification of an increased prevalence of clonal somatic mutation in diseased lung that correlates with airway epithelial gene expression and disease severity highlights for the first time the role of somatic mutational processes in lung disease genetics.

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.

Perioperative cardiac arrest (POCA) is a catastrophic complication that requires immediate recognition and correction of the underlying cause to improve patient outcomes. While the hypoxia, hypovolemia, hydrogen ions (acidosis), hypo-/hyperkalemia, and hypothermia (Hs) and toxins, tamponade (cardiac), tension pneumothorax, thrombosis (pulmonary), and thrombosis (coronary) (Ts) mnemonic is a valuable tool for rapid differential diagnosis, it does not cover all possible causes leading to POCA. To address this limitation, we propose using the preload-contractility-afterload-rate and rhythm (PCARR) construct to categorize POCA, which is comprehensive, systemic, and physiologically logical. We provide evidence for each component in the PCARR construct and emphasize that it complements the Hs and Ts mnemonic rather than replacing it. Furthermore, we discuss the significance of utilizing monitored variables such as electrocardiography, pulse oxygen saturation, end-tidal carbon dioxide, and blood pressure to identify clues to the underlying cause of POCA. To aid in investigating POCA causes, we suggest the Anesthetic care, Surgery, Echocardiography, Relevant Check and History (A-SERCH) list of actions. We recommend combining the Hs and Ts mnemonic, the PCARR construct, monitoring, and the A-SERCH list of actions in a rational manner to investigate POCA causes. These proposals require real-world testing to assess their feasibility.

Background: Traditionally, the reconstruction of severe distal humeral bone loss at the time of revision total elbow arthroplasty (TEA) has used allograft-prosthetic composites (APCs) stabilized with cerclage wires or cables. We have migrated to plate fixation when revision TEA using a humeral APC is performed. This study shows the outcomes of patients treated with a humeral APC with plate fixation during revision TEA. Methods: Between 2009 and 2019, 41 humeral APCs with plate fixation of distal humeral allograft to the native humerus were performed in the setting of revision TEA. There were 12 male patients (29%) and 29 female patients (71%), with a mean age of 63 years (range, 41 to 87 years). The mean allograft length was 12 cm. All elbows had a minimum follow-up of 2 years (mean follow-up, 3.3 years). Patients were evaluated for visual analog scale pain scores, range of motion, the ability to perform select activities of daily living, and the Mayo Elbow Performance Score (MEPS). Outcomes including reoperations, complications, and revisions were noted. The most recent radiographs were evaluated for union at the allograft-host interface, failure of the plate-and-screw construct, or component loosening. Results: The mean postoperative flexion was 124° (range, 60° to 150°) and the mean postoperative extension was 26° (range, 0° to 90°); the mean arc of motion was 99° (range, 30° to 150°). The mean MEPS was 58 points (range, 10 to 100 points). Two surgical procedures were complicated by neurologic deficits. The overall reoperation rate was 14 (34%) of 41. Of the 33 patients with complete radiographic follow-up, 12 (36%) had evidence of nonunion at the allograft-host interface with humeral component loosening, 1 (3%) had evidence of partial union, and 1 (3%) had ulnar stem loosening. Conclusions: Revision TEA with a humeral APC using compression plating was successful in approximately two-thirds of the elbows. Further refinement of surgical techniques is needed to improve union rates in these complex cases. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.