[Posted 31/May/2023]

AUDIENCE: Hematology, Infectious Disease

DETAILS: The U.S. Food and Drug Administration finalized recommendations for assessing blood donor eligibility using a set of individual risk-based questions to reduce the risk of transfusion-transmitted HIV. These questions will be the same for every donor, regardless of sexual orientation, sex or gender. Blood establishments may now implement these recommendations by revising their donor history questionnaires and procedures.

This updated policy is based on the best available scientific evidence and is in line with policies in place in countries like the United Kingdom and Canada. It will potentially expand the number of people eligible to donate blood, while also maintaining the appropriate safeguards to protect the safety of the blood supply.

These final recommendations are consistent with the policy initially proposed in January. The FDA worked diligently to review and consider all comments submitted to the agency to finalize these recommendations as quickly as possible. "The FDA has worked diligently to evaluate our policies and ensure we had the scientific evidence to support individual risk assessment for donor eligibility while maintaining appropriate safeguards to protect recipients of blood products. The implementation of these recommendations will represent a significant milestone for the agency and the LGBTQI+ community," said Peter Marks, M.D., PhD., director of the FDA’s Center for Biologics Evaluation and Research. "The FDA is committed to working closely with the blood collection industry to help ensure timely implementation of the new recommendations and we will continue to monitor the safety of the blood supply once this individual risk-based approach is in place."

This policy eliminates time-based deferrals and screening questions specific to men who have sex with men (MSM) and women who have sex with MSM. Under the final guidance issued today, all prospective blood donors will answer a series of individual, risk-based questions to determine eligibility. All prospective donors who report having a new sexual partner, or more than one sexual partner in the past three months, and anal sex in the past three months, would be deferred to reduce the likelihood of donations by individuals with new or recent HIV infection who may be in the window period for detection of HIV by nucleic acid testing.

Additionally, under these final recommendations, those taking medications to treat or prevent HIV infection (e.g., antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP)), will also be deferred. Though these antiretroviral drugs are safe, effective, and an important public health tool, the available data demonstrate that their use may delay detection of HIV by currently licensed screening tests for blood donations, which may potentially give false negative results. Although HIV is not transmitted sexually by individuals with undetectable viral levels, this does not apply to transfusion transmission of HIV because a blood transfusion is administered intravenously, and a transfusion involves a large volume of blood compared to exposure with sexual contact. As stated in the guidance, individuals should not stop taking their prescribed medications, including PrEP, or PEP, in order to donate blood. The FDA remains committed to evaluating additional data and new technological developments as they become available to inform our donor eligibility recommendations.

The FDA has been evaluating alternatives to time-based deferrals for MSM and helping to facilitate the generation of scientific evidence that would support an individual risk based- assessment blood donor questionnaire. This scientific information has given the agency a solid foundation to support this new policy. The FDA strongly believes the implementation of an individual risk-based approach will not adversely affect the safety or availability of the U.S. blood supply.

The FDA carefully reviewed numerous data sources, including data from countries with similar HIV epidemiology that have implemented an individual risk-based approach for assessing donor eligibility, surveillance information obtained from the Transfusion Transmissible Infections Monitoring System, performance characteristics of nucleic acid testing for HIV and the FDA-funded Assessing Donor Variability And New Concepts in Eligibility study. The ADVANCE study examined the rates of HIV risk factors, such as anal sex and rates of HIV infection, as well as the usage of medications to treat or prevent HIV infection, among MSM study participants.

Copyright © FDA. All rights reserved.

Source: FDA Finalizes Move to Recommend Individual Risk Assessment to Determine Eligibility for Blood Donations. FDA. Published: May 11, 2023.

[Posted 11/Dec/2025]

AUDIENCE: Hematology

KEY FINDINGS: Together with other published data, these findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron-mediated hepcidin regulation in the absence of BMP2 and BMP6.

BACKGROUND: The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. Authors have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo.

DETAILS: Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis. Although both HJV and HFE regulate hepcidin, at least partly, by functionally interacting with the BMP–SMAD pathway, the mechanisms are incompletely understood. Notably, both HJV and HFE can regulate hepcidin in a BMP6-independent manner. To understand whether HJV and HFE influence hepcidin regulation by BMP2 and/or BMP5, authors investigated the iron phenotype of mice with combined mutations in endothelial Bmp2/Hjv and Bmp5/Hfe. Authors found that endothelial Bmp2/Hjv double knockout (KO) mice exhibit more severe hepcidin deficiency and iron overload than single endothelial Bmp2 or Hjv KO mice, similar to previous findings in mice with double endothelial Bmp2/Hfe KO and Bmp6/Hjv KO, or a functional loss of both Bmp6 and Hfe. Moreover, authors found that iron completely fails to induce hepcidin in both endothelial Bmp2/Hjv and Bmp2/Hfe double KO mice. In contrast, a functional loss of BMP5 does not worsen hemochromatosis in Hfe KO mice.

Copyright © Wiley Periodicals LLC. All rights reserved.

Source: Xiao, X., Moschetta, G. A., Chowdhury, S. B., et al. Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis. American Journal of Hematology. 2025; 100(12): 2175-2184. Published: December, 2025. DOI: 10.1002/ajh.70055.

[Posted 4/Nov/2025]

AUDIENCE: Oncology, Gastroenterology

KEY FINDINGS: In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP. The second-line setting appears inadequate to offer precision choices, given the short survival observed.

BACKGROUND: Goal of this study is to assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX [mFFX]) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.

DETAILS: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2. The primary end point was progression-free survival (PFS) between arms with 0.3 significance. The per-protocol (PP) population included patients who received one dose of chemotherapy. Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical). Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months. The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio [HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat. Median overall survival (OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017). Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%. The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months (P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months (P = .36). The median OS in basal-like was 7.5 (mFFX) and 8.9 (GnP) months (P = .75) versus in classical OS was 9.7 (mFFX) and 13.9 (GnP) months (P = .047). Overall, 75 (54%) of patients received second-line treatment, 33/75 (44%) correlate-guided. The median time on second-line treatment was only 2.1 months with a median OS of 5.4 months for a correlate-guided choice versus 4.4 months on a standard chemotherapy approach (P = .45).

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Knox, J. J., O'Kane, G., King, D., et al. PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer. Journal of Clinical Oncology. 2025; 43(31):3325. Published: November, 2025. DOI: 10.1200/JCO-25-004.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.

[Posted 18/Oct/2025]

AUDIENCE: Ob/Gyn, Family Medicine

KEY FINDINGS: This qualitative study describes Black cisgender women’s perspectives on biopsy as a first-line approach in evaluating abnormal bleeding to rule out endometrial cancer in this population. Authors find that a patient-centered communication approach that incorporates trust-building, shared decision-making, and education may be most successful when recommending biopsy. These findings can inform culturally competent clinical guideline development and public health education to improve timely diagnosis—and ultimately survival—of endometrial cancer among Black women.

BACKGROUND: Black people in the United States with endometrial cancer have a 5-year mortality rate that is more than twice that of White patients. This disparity is driven, in part, by Black individuals’ higher likelihood of advanced-stage diagnosis. Transvaginal ultrasound—as a triage tool for referral to tissue sampling—underperforms among Black women. In this context, tissue sampling as an early step for symptomatic Black patients may improve timely diagnosis of endometrial cancer. Patient acceptability of biopsy as a priority test is necessary to ensure success of this clinical approach. Yet, little is known about the perspective of Black women on biopsy in the diagnostic workup for endometrial cancer.

DETAILS: The goal of this qualitative study was to identify facilitators and barriers to acceptability of a biopsy-first approach to rule out endometrial cancer among cisgender Black women. In this community-engaged qualitative study, 3 focus groups were conducted among cisgender Black women at risk for endometrial cancer. Convenience sampling was carried out using social media and newsletter networks. A focus group guide was developed based on the theory of planned behavior and contained questions about past experiences, initial impressions of a biopsy-first approach, an educational presentation, and final thoughts about a biopsy-first approach. Transcripts of focus group recordings were coded using a combined inductive and deductive approach and analyzed using directed and thematic content analysis. Twenty-five women participated in focus groups, with 6 to 10 participants per group. Participants initially expressed understandable apprehension and rejection of a biopsy-first approach in the context of symptom presentation, informed by concerning past experiences and awareness of medical racism. Yet, by the end of the focus groups, there was overall acceptability of biopsy as a priority test to rule out endometrial cancer. Barriers of biopsy acceptability include negative past experiences, including mismatch of pain expectations with actual experiences, and known incidents of medical racism. Facilitators of biopsy acceptability included fostering patient–provider trust through explicit acknowledgment of medical racism, sharing information, personalized recommendations, and racial concordance in care; and health education about racial disparities in endometrial cancer, the biopsy procedure, physical risks of forgoing biopsy, emotional benefits of biopsy, and the range of possible pain experiences.

Copyright © The Authors. Published by Elsevier Inc. All rights reserved.

Source: Alson, J. G., Orellana, M., Robinson, W. R., et al. Facilitators and Barriers to Acceptability of a Biopsy-First Approach in the Diagnostic Evaluation for Endometrial Cancer Among Black Women. American Journal of Obstetrics & Gynecology,. 2025; 233(4): 294.e1-294.e11. Published: October, 2025. DOI: 10.1016/j.ajog.2025.03.012.

A Systematic Review and Meta-analysis.

[Posted 17/Oct/2025]

AUDIENCE: Gastroenterology, Internal Medicine, Oncology

KEY FINDINGS: ESD is a safe and effective option for managing RNDLs with a low recurrence rate. Adverse events such as postprocedural perianal pain, postprocedural bleeding, and anal stenosis seem to be more common compared with colorectal ESD done for more proximal lesions. However, these can typically be managed conservatively or with minimally invasive endoscopic techniques.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a superior, minimally invasive technique compared with other snare-based endoscopic resection techniques for rectal neoplasms extending to the dentate line (RNDLs). However, performing a successful ESD in the anal canal can be challenging due to vascularity and limited scope stability. In this meta-analysis, we aim to evaluate the safety and efficacy of ESD for RNDLs.

DETAILS: Authors performed a comprehensive electronic database search from January 2005 through January 2024 for studies evaluating outcomes of ESD performed for managing RNDLs. Pooled proportions were calculated using random-effect models. Heterogeneity was evaluated using I2 and Q statistics. Data were extracted from 11 studies comprising 496 patients. The pooled en bloc resection rates were 93.60% (95% CI = 90.70-95.70). The pooled R0 resection rate was 80.60% (95% CI = 70.50-87.80). The pooled recurrence rate was 4.00% (95% CI = 2.40-6.50). There was no evidence of significant heterogeneity calculated using the Q test and I2 statistic. The main adverse events were anal pain, postprocedural bleeding, and anal stricture with pooled rates of 20.20% (95% CI = 14.80-26.90), 8.20% (95% CI = 4.70-14.0), and 3.50% (95% CI = 2.10-5.70), respectively.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Gopakumar, H., Dahiya, D., Draganov, P. V., et al. Safety and Efficacy of Endoscopic Submucosal Dissection for Rectal Neoplasms Extending to the Dentate Line: A Systematic Review and Meta-analysis. Journal of Clinical Gastroenterology. 2025; 59(10): 954-963. Published: November/December, 2025. DOI: 10.1097/MCG.0000000000002090.