Laparoscopic Reversal of Roux-en-Y Gastric Bypass with Hand-Sewn Gastro-Gastrostomy and Resection of the Alimentary Limb.

Introduction: Roux-en-Y gastric bypass (RYGB) reversal might be necessary to alleviate refractory surgical or nutritional complications, such as postprandial hypoglycemia, malnutrition, marginal ulceration, malabsorption, chronic diarrhea, nausea and vomiting, gastro-esophageal reflux disease, chronic pain, or excessive weight loss. The surgical technique of RYGB reversal is not standardized; potential strategies include the following: (1) gastro-gastrostomy: hand-sewn technique, linear stapler, circular stapler; (2) handling of the Roux limb: reconnection or resection (if remaining intestinal length ≥ 4 m).

Case Presentation: We demonstrate the surgical technique of a laparoscopic reversal of RYGB with hand-sewn gastro-gastrostomy and resection of the alimentary limb with the aim of improving the patient's quality of life.

Chemical perturbations impacting histone acetylation govern colorectal cancer differentiation.

Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype.

Relationship between medication regimen complexity and pharmacist engagement in fluid stewardship.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Update and narrative review of avian influenza (H5N1) infection in adult patients.

The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s.

Plasma Ceramide C24:0/C16:0 Ratio is Associated with Improved Survival in Patients with Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high fatality rate, with surgery as the only curative treatment. Identification of new biomarkers related to survival may help guide discovery of new pathophysiologic pathways and potential therapeutic targets. As long-chain ceramides have been linked to tumor proliferation, we sought to determine if ceramide levels were prognostic in PDAC.

Modulation of blood-tumor barrier transcriptional programs improves intra-tumoral drug delivery and potentiates chemotherapy in GBM.

Glioblastoma (GBM) is the most common malignant primary brain tumor. GBM has an extremely poor prognosis and new treatments are badly needed. Efficient drug delivery to GBM is a major obstacle as the blood-brain barrier (BBB) prevents passage of the majority of cancer drugs into the brain.

An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.

Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene regulation. More recently, IDRs have been shown to promote multivalent protein-protein interactions between coregulators and TFs to drive their association into condensates. By contrast, here we demonstrate how the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements.

Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated.

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer.

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition.

Intratumoral T-cell receptor repertoire composition predicts overall survival in patients with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is refractory to immune checkpoint inhibitor therapy. However, intratumoral T-cell infiltration correlates with improved overall survival (OS). Herein, we characterized the diversity and antigen specificity of the PDAC T-cell receptor (TCR) repertoire to identify novel immune-relevant biomarkers.

The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.

Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh.

sc2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data.

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications.

Neoadjuvant Chemotherapy is Associated with Increased Risk of Postoperative DVT After Distal Pancreatectomy for Pancreatic Adenocarcinoma: a NSQIP Analysis.

Background: Venous thromboembolism (VTE) remains a persistent source of postoperative morbidity despite prevention and mitigation efforts. Cancer, surgery, and chemotherapy are known risk factors for VTE. Existing literature suggests that neoadjuvant therapy (NAT) may contribute to increased VTE risk in the postoperative period, but few authors specifically examine this relationship in distal pancreatic adenocarcinoma (PDAC).

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

Rationale And Objectives: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).

Materials And Methods: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually.

The Intrinsically Disordered N Terminus in Atg12 from Yeast Is Necessary for the Functional Structure of the Protein.

The Atg12 protein in yeast is an indispensable polypeptide in the highly conserved ubiquitin-like conjugation system operating in the macroautophagy/autophagy pathway. Atg12 is covalently conjugated to Atg5 through the action of Atg7 and Atg10; the Atg12-Atg5 conjugate binds Atg16 to form an E3 ligase that functions in a separate conjugation pathway involving Atg8. Atg12 is comprised of a ubiquitin-like (UBL) domain preceded at the N terminus by an intrinsically disordered protein region (IDPR), a domain that comprises a major portion of the protein but remains elusive in its conformation and function.

Translating Clinical Decision-Making Skills From a Critical Care Pharmacy Elective to the Required Curriculum.

Objective: To examine the impact of a critical care pharmacy elective (CCPE) on student performance in other courses in the Doctor of Pharmacy curriculum that emphasize clinical reasoning and decision making.

Methods: This is a retrospective, cohort study including all students from the 2019-2021 graduating classes enrolled in required courses, Pharmacotherapy and Integrated Patient Cases (IPCs). Students were divided for comparison based on completion of the CCPE.

Area deprivation and rurality impact overall survival and adjuvant therapy administration in patients with pancreatic ductal adenocarcinoma (PDAC).

Background: The impact of neighborhood deprivation on outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) is not well-described and represents an area to improve disparities.

Methods: We retrospectively queried our prospectively maintained database of patients with PDAC (2014-2022). Patients were grouped by Area Deprivation Index (ADI) and rural-urban commuting area (RUCA) codes.

Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease.