IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma.

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs.

Development of New CD38 Targeted Peptides for Cancer Imaging.

Purpose: Multiple myeloma (MM) affects over 35,000 patients each year in the US. There remains a need for versatile Positron Emission Tomography (PET) tracers for the detection, accurate staging, and monitoring of treatment response of MM that have optimal specificity and translational attributes. CD38 is uniformly overexpressed in MM and thus represents an ideal target to develop CD38-targeted small molecule PET radiopharmaceuticals to address these challenges.

Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)-NF-кB axis.

Spasmolytic polypeptide-expressing metaplasia (SPEM), as a pre-neoplastic precursor of intestinal metaplasia (IM), plays critical roles in the development of chronic atrophic gastritis (CAG) and gastric cancer (GC). However, the pathogenetic targets responsible for the SPEM pathogenesis remain poorly understood. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), an essential subunit of the mitochondrial respiratory chain complex I, was progressively lost along with malignant transformation of human CAG, little is known about the potential link between GRIM-19 loss and CAG pathogenesis.

Epidemiology and Risk Factors for Breast Cancer: 21st Century Advances, Gaps to Address through Interdisciplinary Science.

Research methods to study risk factors and prevention of breast cancer have evolved rapidly. We focus on advances from epidemiologic studies reported over the past two decades addressing scientific discoveries, as well as their clinical and public health translation for breast cancer risk reduction. In addition to reviewing methodology advances such as widespread assessment of mammographic density and Mendelian randomization, we summarize the recent evidence with a focus on the timing of exposure and windows of susceptibility.

Combination TIGIT/PD-1 blockade enhances the efficacy of neoantigen vaccines in a model of pancreatic cancer.

Background: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

Evaluating Diversity and Inclusion Content on Graduate Medical Education Websites.

Unlabelled: Websites are important tools for programs to provide future residency applicants with freely accessible information regarding their program, including diversity, equity, and inclusion (DEI) initiatives.

Objective: To describe the variability of DEI content in residency programs and compare DEI website content by specialty.

Methods: Using the 2021 Accreditation Council for Graduate Medical Education (ACGME) list of residency programs, residency training websites were identified and evaluated.

Manipulation Under Anesthesia is Safe After Cementless Total Knee Arthroplasty: A Multicenter Study.

Background: Cementless total knee arthroplasty (TKA) is thought to facilitate durable, biological fixation between the bone and implant. However, the 4-12 weeks required for osseointegration coincides with the optimal timeframe to perform a manipulation under anesthesia (MUA) if a patient develops postoperative stiffness. This study aims to determine the impact of early MUA on cementless fixation by comparing functional outcomes and survivorship of cementless and cemented TKAs.

Medications for Opioid Use Disorder Do Help Patients.

Much of the focus on the current opioid crisis remains on how we arrived here and who is to blame. Despite having effective treatments for the management of patients with opioid use disorder (OUD), rates of overdose deaths continue to increase. As such, the focus needs to shift to increasing access to medications for OUD and better incorporation of harm reduction strategies to decrease not just the mortality but also the morbidity associated with OUD and other substance use disorders.

Cause and outcome of aborting a difficult laparoscopic cholecystectomy due to severe inflammation: a study of operative notes.

Background: Upon encountering a difficult cholecystectomy in which, after a reasonable trial of dissection, anatomical identification has not been attained due to severe inflammation, and the risk of additional dissection is deemed to be hazardous, "bail-out" strategies are encouraged safety valves. One strategy is to abort the cholecystectomy and refer the patient to a HPB center for further management.

Methods: A retrospective review was conducted of cholecystectomies performed by HPB surgeons at our center between 2005 and 2019.

Utilization of Instagram by Psychiatry Residency Programs in a Virtual Recruitment World.

Objective: Many psychiatry residency programs use Instagram to provide information about their program. This study assesses the content and engagement on psychiatry residency program Instagram accounts.

Methods: A full list of psychiatry programs was gathered from the American Medical Association Fellowship and Residency Electronic Interactive Database (FREIDA).

Antidiabetic DPP-4 Inhibitors Reprogram Tumor Microenvironment That Facilitates Murine Breast Cancer Metastasis Through Interaction With Cancer Cells a ROS-NF-кB-NLRP3 Axis.

Improvement of understanding of the safety profile and biological significance of antidiabetic agents in breast cancer (BC) progression may shed new light on minimizing the unexpected side effect of antidiabetic reagents in diabetic patients with BC. Our recent finding showed that Saxagliptin (Sax) and Sitagliptin (Sit), two common antidiabetic dipeptidyl peptidase-4 inhibitors (DPP-4i) compounds, promoted murine BC 4T1 metastasis a ROS-NRF2-HO-1 axis in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. However, the potential role of DPP-4i in BC progression under immune-competent status remains largely unknown.

Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma.

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug.

Utility of Social Media for Recruitment by Orthopaedic Surgery Residency Programs.

Background: As the use of social media continues to rise, the presence of social media accounts among orthopaedic surgery residency programs can foster connections with other specialties, highlight departmental achievements, and be a resource for applicants to learn more about the program. This study evaluated the current utility and landscape of social media, with an emphasis on the use of Instagram, in orthopaedic surgery residency programs in the United States.

Methods: A cross-sectional study of orthopaedic surgery residency Instagram accounts was performed.

Safety and Effectiveness of the SVELTE Fixed-Wire and Rapid Exchange Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Systems for the Treatment of Atherosclerotic Lesions: Results of the OPTIMIZE Randomized Study.

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MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Comparison of Revision Risk Based on Timing of Knee Arthroscopy Prior to Total Knee Arthroplasty.

Background: Knee arthroscopy may be performed prior to total knee arthroplasty (TKA) in patients with symptomatic degenerative knee changes that do not yet warrant TKA. The purpose of this study was to determine whether the time interval between knee arthroscopy and subsequent primary TKA is associated with increased rates of revision and certain complications following TKA.

Methods: Data from 2006 to 2017 were collected from a national insurance database.

Child and Adolescent Psychiatry Fellowship Program Website Content and Accessibility.

Objective: When child and adolescent psychiatry fellowship applicants are applying to programs, many will use fellowship websites to gather information. This study assesses the accessibility and content available on child and adolescent fellowship websites.

Methods: Using the Electronic Residency Application Service (ERAS) list of child and adolescent fellowship programs for 2020, 139 child and adolescent fellowship training websites were compiled.