BK virus kinetics and associated cystitis/urethritis symptoms after PTCy-based allogeneic hematopoietic cell transplant.

BK virus-associated cystitis/urethritis (BK-C) is a major cause of morbidity in allogeneic hematopoietic cell transplantation (HCT) recipients. We prospectively followed weekly plasma and urine BK viral loads and associated symptoms in 169 recipients of post-transplantation cyclophosphamide (PTCy)-based HCT. Patients with ≥2 positive BK specimens before day +100 were considered at-risk for developing BK-C.

A phase 2 study of sacituzumab govitecan with or without atezolizumab in rare genitourinary tumors (SMART) - design and rationale.

Sacituzumab govitecan (SG) is a TROP2-directed antibody-drug conjugate with a payload of SN-38, a topoisomerase inhibitor. SG monotherapy has demonstrated activity in multiple solid tumors, including metastatic breast and bladder cancer. Rare tumors of the genitourinary tract often exhibit aggressive clinical behavior yet lack effective treatment options.

R01 Funding for Surgeons; What Are the Key Factors for Success?

Introduction: Recent studies report a decrease in R01 grants awarded to surgeon-scientists compared to nonsurgeons. We determined the key factors associated with a successful R01 grant application for surgeon-scientists.

Methods: Surgeon-scientist principal new investigators (PIs) who applied for an R01 grant during fiscal years (FY) 2018-2023 were identified using an National Institutes of Health internal data platform.

The Road from NIH-training Grants for Surgeons: What is the Return on Investment?

Objective: This study examines the success of surgeon-scientists to non-surgeon physician-scientists in obtaining NIH funding after participation on a research training grant.

Summary Background Data: Dedicated research time during postgraduate training for physician-scientists is advantageous for obtaining future independent funding from NIH.

Methods: NIH Reporter was used to identify F32 and T32 grants awarded to internal medicine and surgery departments from 2005-2015, and an internal NIH database was used to determine funding outcomes.

Disease Control and Voice Outcomes Following Treatment With PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis.

Objective: More than 50% of adult patients with recurrent respiratory papillomatosis that receive PRGN-2012 develop a protocol-defined complete response. The relationship between papilloma disease control and change in voice handicap following PRGN-2012 treatment requires clarity as patients and providers consider treatment.

Study Design: A post hoc study of pretreatment and post treatment Derkay and Voice Handicap Index-10 (VHI-10) data collected prospectively as predetermined exploratory outcome measures on a completed single-arm, single-cohort, phase 1/2 registration clinical trial of PRGN-2012 monotherapy.

Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1 With MEK Inhibitor Selumetinib: A Nonrandomized Clinical Trial.

Importance: Cutaneous neurofibromas (cNFs) can cause itching, disfigurement, pain, and emotional difficulties in people with neurofibromatosis type 1 (NF1).

Objective: To determine the impact of the mitogen-activated protein kinase kinase inhibitor selumetinib on cNF including change in tumor volume and patient-reported outcome measures.

Design, Setting, And Participants: Adults with NF1 and 9 or more measurable cNFs were enrolled in this nonrandomized pilot trial at the National Cancer Institute and the University of Alabama at Birmingham, which spanned from August 26, 2017, to August 21, 2023.

Intermediate-dose posttransplantation cyclophosphamide for myeloablative HLA-haploidentical bone marrow transplantation.

High-dose posttransplantation cyclophosphamide (HD-PTCy), given at 50 mg/kg/day on days +3/+4, is a standard-of-care graft-versus-host disease (GVHD) prophylaxis for allogeneic hematopoietic cell transplantation (HCT). Our murine MHC-haploidentical HCT studies suggested intermediate-dose PTCy produces superior GVHD control compared with HD-PTCy and PTCy is maximally effective on day +4. We conducted a single-institutional prospective phase 1/2 trial to reduce PTCy dosing to 25 mg/kg/day on days +3/+4 or on day +4 only for myeloablative HLA-haploidentical bone marrow HCT using PTCy, sirolimus, and mycophenolate mofetil.

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response.

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIV acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17NKp44 innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.

Altruistic feeding and cell-cell signaling during bacterial differentiation actively enhance phenotypic heterogeneity.

Starvation triggers bacterial spore formation, a committed differentiation program that transforms a vegetative cell into a dormant spore. Cells in a population enter sporulation nonuniformly to secure against the possibility that favorable growth conditions, which put sporulation-committed cells at a disadvantage, may resume. This heterogeneous behavior is initiated by a passive mechanism: stochastic activation of a master transcriptional regulator.

Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study.

Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women.

Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.

Immunomodulatory imide drugs (IMiDs) play a crucial role in the treatment landscape across various stages of multiple myeloma. Despite their evident efficacy, some patients may exhibit primary resistance to IMiD therapy, and acquired resistance commonly arises over time leading to inevitable relapse. It is critical to develop novel therapeutic options to add to the treatment arsenal to overcome IMiD resistance.

Utility of Large Language Models for Health Care Professionals and Patients in Navigating Hematopoietic Stem Cell Transplantation: Comparison of the Performance of ChatGPT-3.5, ChatGPT-4, and Bard.

Background: Artificial intelligence is increasingly being applied to many workflows. Large language models (LLMs) are publicly accessible platforms trained to understand, interact with, and produce human-readable text; their ability to deliver relevant and reliable information is also of particular interest for the health care providers and the patients. Hematopoietic stem cell transplantation (HSCT) is a complex medical field requiring extensive knowledge, background, and training to practice successfully and can be challenging for the nonspecialist audience to comprehend.

Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.

Background: LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies.

Methods: A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation.

Pulmonary Metastasectomy for Adrenocortical Carcinoma-Not If, but When.

Background: Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options.

Methods: All ACC patients with initially only lung metastases (LM) from a single institution constituted this observational case series. Kaplan-Meier and Cox proportional hazard analyses evaluated the association with potential prognostic factors and outcomes.

Comparison of Large Language Models in Answering Immuno-Oncology Questions: A Cross-Sectional Study.

Background: The capability of large language models (LLMs) to understand and generate human-readable text has prompted the investigation of their potential as educational and management tools for patients with cancer and healthcare providers.

Materials And Methods: We conducted a cross-sectional study aimed at evaluating the ability of ChatGPT-4, ChatGPT-3.5, and Google Bard to answer questions related to 4 domains of immuno-oncology (Mechanisms, Indications, Toxicities, and Prognosis).

Comparison of Large Language Models in Answering Immuno-Oncology Questions: A Cross-Sectional Study.

Background: The capability of large language models (LLMs) to understand and generate human-readable text has prompted the investigation of their potential as educational and management tools for cancer patients and healthcare providers.

Materials And Methods: We conducted a cross-sectional study aimed at evaluating the ability of ChatGPT-4, ChatGPT-3.5, and Google Bard to answer questions related to four domains of immuno-oncology (Mechanisms, Indications, Toxicities, and Prognosis).

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4 T-Cells.

At the heart of the DNA/ALVAC/gp120/alum vaccine's efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIV acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4 cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination.

Efficacy and safety of PARP inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis of clinical trials.

Introduction: PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer.

Polymorphism in Men With Prostate Cancer Treated With Androgen Deprivation Therapy.

Background/aim: Gonadotropin-releasing hormone 2 (GNRH2) is a poorly-studied peptide hormone that is widely distributed in the central nervous system and expressed in peripheral tissues of mammals. The non-synonymous rs6051545 variant in GNRH2 (A16V) has been linked to higher serum testosterone concentrations. This study investigated whether the A16V variant is associated with altered androgen-deprivation therapy (ADT) progression-free survival (PFS) and overall survival (OS).

Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques.

The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV) acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIV, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected.

HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.

The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14 monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10).