D-Dimer and Risk for Thrombosis In Adults with Newly Diagnosed Acute Lymphoblastic Leukemia
D-dimer level at ALL diagnosis is associated with venous or arterial thrombosis during the first 100 days of therapy. Future studies should include D-dimer with other known risk factors to build a risk assessment model for thrombosis in newly diagnosed ALL.
KEY FINDINGS: D-dimer levels at ALL diagnosis are associated with venous or arterial thrombosis at 100 days. Future studies should include D-dimer collated with other known risk factors to build a risk assessment model for thrombosis in patients with newly diagnosed ALL.
BACKGROUND: Patients with acute lymphoblastic leukemia (ALL) are at increased risk of thrombotic and/or bleeding events during early chemotherapy, especially when receiving asparaginase.
DETAILS: D-dimer is a marker of fibrinolysis that has been associated with thrombotic risk in solid cancers and acute myeloid leukemia; however, to date, no ALL-based study has assessed D-dimer level and risk for thrombosis. Sought to examine D-dimer as a biomarker for risk of thrombosis or bleeding during ALL treatment in a retrospective cohort study at The University of Chicago. Identified 61 consecutive adult patients with ALL, gathering demographic characteristics, treatment regimens, initial biomarkers including D-dimer, and assessing occurrence of venous or arterial thrombosis and bleeding in the first 100 days after diagnosis (index). The 100-day cumulative incidence (95% confidence interval [CI]) of venous or arterial thrombosis in patients with high D-dimer (>=4 µg/mL) was 52.9% (95% CI, 26.4-73.8) compared with 13.8% (95% CI, 5.5-25.7) in patients with low to moderate D-dimer (<4 µg/mL), corresponding with a hazard ratio of 5.04 (95% CI, 1.79-14.22). When testing for potential confounders in a series of bivariate logistic regression models, the association between D-dimer and thrombosis remained after adjusting for body mass index, age, sex, asparaginase treatment, disseminated intravascular coagulation score, initial platelet level, and ALL phenotype.
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Source: Anderson, D. R., Stock, W., Karrison, T. G., et al. (2022). D-Dimer and Risk for Thrombosis In Adults with Newly Diagnosed Acute Lymphoblastic Leukemia. Blood Adv. 2022; 6(17): 5146-5151. Published: September 13, 2022. DOI: 10.1182/bloodadvances.2022007699.
Facilitators and Barriers to Acceptability of a Biopsy-First Approach in the Diagnostic Evaluation for Endometrial Cancer Among Black Women
This qualitative study describes Black cisgender womens perspectives on biopsy as a first-line approach in evaluating abnormal bleeding to rule out endometrial cancer in this population.
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.
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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.
Safety and Efficacy of Endoscopic Submucosal Dissection for Rectal Neoplasms Extending to the Dentate Line
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.
Summary
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.
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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.
Antipsychotic Prescriptions in People With Dementia in Primary Care
This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.
Summary
A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines
[Posted 14/Oct/2025]
AUDIENCE: Psychiatry, Family Medicine
KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.
BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.
DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).
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Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.
DUOX2 Activation Drives Bacterial Translocation and Subclinical Inflammation in IBD-Associated Dysbiosis
Elevated DUOX2 signalling contributes to epithelial barrier dysfunction, microbiome alterations and subclinical inflammation. Butyrate and HDAC inhibitors reversed these effects, indicating that DUOX2 may be a therapeutic target in IBD.
KEY FINDINGS: Elevated DUOX2 signalling contributes to epithelial barrier dysfunction, microbiome alterations and subclinical inflammation. Butyrate and HDAC inhibitors reversed these effects, indicating that DUOX2 may be a therapeutic target in IBD.
BACKGROUND: Inflammatory bowel diseases (IBDs) are characterised by dysbiosis and a leaky gut. The NADPH oxidase dual oxidase 2 (DUOX2) is upregulated in patients with IBD, yet its role in driving the disease remains unclear. Authors interrogated the functional consequences of epithelial DUOX2 activity for the host and microbiome.
DETAILS: DUOX2 function was studied in mice with epithelial-specific DUOX2 overactivation (vTLR4), inactivation (vTLR4 DUOXA IEC-KO) and wild-type controls. Authors assessed the effect of dysbiosis on DUOX2 signalling and intestinal permeability (FITC-dextran, serum zonulin, bacterial translocation) with germ-free (GF) mice engrafted with IBD or healthy microbiota. RNA sequencing of colonic mucosa and microbiota and faecal metabolomics were used to characterise the host-microbe interface. Mechanistic studies were conducted in mouse colonoids, IBD biopsies and patient serum samples. DUOX2 activity increased permeability and bacterial translocation and induced subclinical inflammation in vTLR4 mice. GF vTLR4 mice had increased DUOX2 activity and permeability but no subclinical inflammation. In patients with IBD, DUOX2 expression was positively associated with plasma zonulin levels and negatively associated with ZO-1 expression. Engraftment of GF mice with IBD stool increased DUOX2 activity and triggered low-grade inflammation and permeability defects in mice. DUOX2 activity functionally altered the microbiome, reduced butyrate metabolism and promoted proinflammatory and pro-oncogenic bacterial metabolites. Butyrate and histone deacetylase (HDAC) inhibitors blocked DUOX2 activation and reversed its effects.
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Source: Hazime, H., Ducasa, G. M., Santander, A. M., et al. (2025). DUOX2 Activation Drives Bacterial Translocation and Subclinical Inflammation in IBD-Associated Dysbiosis. dysbiosisGut. 2025; 74: 1589-1601. Published: October, 2025. DOI: 10.1136/gutjnl-2024-334346.
Nivolumab and Ipilimumab for Metastatic Castration-Resistant Prostate Cancer With an Immunogenic Signature
Nivolumab 1 mg/kg + ipilimumab 3 mg/kg is an active treatment in ImS+ pretreated mCRPC. Nivolumab 3 mg/kg + ipilimumab 1 mg/kg has less toxicity but may have lower efficacy. HII is a promising prospectively tested predictive biomarker in prostate cancer that could be integrated into future trials.
KEY FINDINGS: Nivolumab 1 mg/kg + ipilimumab 3 mg/kg is an active treatment in ImS+ pretreated mCRPC. Nivolumab 3 mg/kg + ipilimumab 1 mg/kg has less toxicity but may have lower efficacy. HII is a promising prospectively tested predictive biomarker in prostate cancer that could be integrated into future trials.
BACKGROUND: Efficacy of immune checkpoint inhibitors in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) is limited. The NEPTUNES study evaluated combination nivolumab and ipilimumab in patients with immunogenic signature-positive (ImS+) mCRPC.
DETAILS: This open-label, 2-cohort, phase II trial enrolled patients with ImS+ mCRPC progressing on >=1 previous line of treatment. ImS+ was defined by (1) mismatch repair deficiency (MMRD); (2) DNA damage repair gene loss; and/or (3) high inflammatory infiltrate (HII). Patients received four doses of nivolumab 1 mg/kg + ipilimumab 3 mg/kg (C1) or nivolumab 3 mg/kg + ipilimumab 1 mg/kg (C2) followed by nivolumab 480 mg once every 4 weeks up to 10 cycles. The primary end point was composite response rate (CRR) assessed radiologically, biochemically, and by reduction of circulating tumor cells. Secondary end points included toxicity, progression-free survival, overall survival, and duration of response. Between May 2018 and June 2022, 35 (C1) and 36 (C2) patients commenced treatment. The CRR in C1 was 14/35 (40%, 90% CI, 26% to 55%) and in C2 was 9/36 (25%, 90% CI, 14% to 40%). The overall CRR was 23/71 (32%, 90% CI, 23% to 43%). Response rates were higher in patients with MMRD (7/10), BRCA2 loss (4/8), and HII ± other ImS+ features (13/30). Duration of response for patients with HII without other ImS+ features, DNA repair gene loss without MMRD, and MMRD was 2.6, 17.3, and 10 months, respectively. Grade 3 to 4 treatment-related adverse events occurred in 22/35 (63%) in C1 and 12/36 (33%) patients in C2. There were no treatment-related deaths.
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Source: Leone, G., Wong, Y. N. S., Jones, R. J., et al. (2025). Nivolumab and Ipilimumab for Metastatic Castration-Resistant Prostate Cancer With an Immunogenic Signature: The Multicenter, Two-Cohort, Phase II NEPTUNES Study. Journal of Clinical Oncology. 2025; 43(28): 3070-3080. Published: October 1, 2025. DOI: 10.1200/JCO-24-02637.
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