Citations

Abstract Patients with Crohn’s disease (CD) who undergo terminal ileum (TI) resection experience altered bile acid absorption, which may influence colorectal cancer (CRC) risk. We conducted a propensity-matched cohort study using TriNetX to compare CRC risk in patients with CD who underwent TI resection versus those who did not. Terminal ileum resection was associated with an increased risk of CRC (aHR = 2.58, 95% CI, 1.72–3.86). Patients with TI resection also had higher odds of colorectal polyps. These findings suggest the need for heightened CRC surveillance in patients with CD undergoing TI resection.

Key Points Circulating proteins independently associated with kidney stone diagnosis are related to kidney stone matrix. Lower circulating uromodulin and higher scavenger receptor cysteine-rich domain-containing group B protein levels were associated with higher kidney stone risk, whereas kidney stone presence elevates plasma matrix metalloproteinase 7 level. The protective effect of uromodulin against kidney stones was independent of kidney function. Background Kidney stones are increasingly recognized as a systemic disorder with a high global prevalence. However, large proteomics studies are lacking. Methods An individual-level proteomics study with rigorous adjustments was performed on 35,331 UK Biobank participants to uncover the independent associations between 2922 circulating proteins and prevalent kidney stone disease. Mendelian randomization analysis was used to assess causal relationships. Findings were validated using genomic data from the Mayo Clinic Biobank ( N =43,744), concentration-response analysis, transcriptomics analyses, and additional genome-wide association studies. Results Nine plasma proteins were independently associated with a kidney stone diagnosis, including reduced uromodulin (UMOD; β , −0.10; 95% confidence interval [CI], −0.15 to −0.05) and elevated scavenger receptor cysteine-rich domain-containing group B protein (SSC4D; β , 0.28; 95% CI, 0.17 to 0.38) and were enriched in extracellular matrix pathways. Mendelian randomization analysis revealed that the presence of kidney stone contributed to elevated levels of matrix metalloproteinase 7. Conversely, lower plasma UMOD (odds ratio [OR], 0.93; 95% CI, 0.90 to 0.97) and higher plasma SSC4D (OR, 1.10; 95% CI, 1.02 to 1.18) were associated with kidney stone risk. These associations were consistently replicated in the Mayo Clinic Biobank dataset (UMOD; OR, 0.92; 95% CI, 0.86 to 0.98; SSC4D; OR, 1.13; 95% CI, 1.01 to 1.27) and further validated by a concentration-response analysis. Single-nucleus RNA sequencing and quantitative trait loci analyses confirmed consistent associations between thick ascending limb UMOD expression and stone former status and with blood and urine UMOD concentrations. Genome-wide association study analysis, adjusted for eGFR, suggested that the protective role of UMOD against kidney stones was independent of kidney function. Conclusions This study highlights significant associations between concentrations of specific blood proteins and a history of kidney stones. Several implicated proteins are related to kidney stone matrix, with UMOD independently associated with lower risk and SSC4D with higher risk of kidney stones.

Key Points First US national study showing angiodysplasia-related gastrointestinal bleeding incidence and readmissions rises progressively with worsening CKD stage. Patients with kidney failure were less likely to receive endoscopy, which was linked to higher mortality, revealing a potential care gap. Recurrent angiodysplasia-related gastrointestinal bleeding was the leading cause of 30-day readmission; lack of endoscopy was an independent predictor of readmission. Background Angiodysplasia-related gastrointestinal bleeding (AGIB) is an increasingly recognized cause of hospitalization, particularly among patients with CKD. Although AGIB has been linked to kidney failure (KF), its burden across CKD stages remains unclear. This study aimed to evaluate AGIB incidence, outcomes, and readmissions across CKD stages using the largest inpatient and readmission databases in the United States. Methods We conducted a retrospective cohort study using the 2022 National Inpatient Sample and Nationwide Readmissions Database. Adult patients hospitalized with AGIB were identified and stratified into five groups: non-CKD, early CKD (stage 3), advanced CKD (stages 4–5 not on dialysis), KF (ESKD requiring chronic dialysis), and others. The primary outcome was AGIB hospitalization incidence. Secondary outcomes included in-hospital mortality, disease severity, treatment interventions, health care utilization, and 30-day readmission. Multivariable regression models were used to identify independent risk. Results In 2022, 46,670 adults were hospitalized with AGIB (0.17% of all admissions). CKD/KF was an independent risk factor for AGIB hospitalization, with risk increasing progressively with worsening kidney function (adjusted odds ratio [aOR]: 1.42 [1.34 to 1.50; early CKD], 1.89 [1.72 to 2.07; advanced CKD], 2.51 [2.32 to 2.72; KF]; all P < 0.001). The overall in-hospital mortality rate was 1.04%, higher among patients with CKD. KF was independently associated with higher mortality (aOR, 1.87 [1.06 to 3.27]), lower rates of endoscopic evaluation (aOR, 0.53 [0.43 to 0.65]), and longer hospital stays. Endoscopy was associated with lower mortality (aOR, 0.54 [0.32 to 0.92]). The 30-day all-cause readmission rate was 22.3%, with recurrent AGIB as the leading cause. Readmission risk increased progressively with CKD stage. Conclusions CKD progression is strongly associated with increased risk of AGIB hospitalization and readmission. KF and lack of endoscopic evaluation were independent mortality risk factors. These findings highlight the need for proactive management strategies in this high-risk population.

Abstract Pseudoarthroses (false joints) occur as a complication of fracture healing in the normotopic skeleton but have not been reported at ectopic sites. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO) and congenital skeletal abnormalities including developmental arthropathy in the normotopic skeleton. Here, we report ectopic pseudojoint formation in 6 patients with FOP, all occurring after painful flare-ups and HO in soft connective tissues of the knee, hip, and forearm. To our knowledge, FOP is the only human condition in which ectopic pseudojoint formation occurs. These findings support that dysregulated BMP pathway signaling from mutant ACVR1 mediates not only HO, but also ectopic pseudojoint formation, and that ectopic pseudojoints can arise from de novo musculoskeletal elements.

Abstract Background and Objectives Research has established that unpaid family members, friends, or others who care for persons with dementia (ie, caregivers) may encounter socioemotional and physical health concerns as a consequence of providing extensive assistance. Similarly, caregivers for people living with traumatic brain injury (TBI) often experience a range of stressors and negative mental health outcomes due to care demands. Individuals with TBI often develop Alzheimer’s disease and Alzheimer’s disease-related dementia (AD/ADRD). This history of TBI may introduce complications to AD/ADRD caregiving. A comprehensive intervention grounded in the understanding of the complex caregiving context of both diagnoses is warranted to address the unique needs and concerns of TBI-AD/ADRD caregivers. Research Design and Methods This study evaluated the feasibility of the TBI-AD/ADRD Caregiver Support Intervention (TACSI) psychoeducational program, designed to support the unique subset of caregivers facing the challenge of assisting relatives with AD/ADRD and a history of TBI. TACSI, a 6-session telehealth intervention, provides tailored psychosocial and psychoeducational coaching. In partnership with the 2 national healthcare centers, 15 caregivers enrolled in the 3-month feasibility study evaluating the design and subsequent refinement of TACSI. Mixed methods data were collected from 3-month follow-up surveys and qualitative data from postintervention interviews. Results The feasibility, utility, and acceptance of TACSI were established. Caregivers liked the telehealth delivery and the personalized nature of TACSI, yet some expressed it would have been more beneficial earlier in their caregiving journey. Discussion and Implications Caregivers valued the TACSI program. Their feedback has been applied to improve TACSI content and delivery for a larger pilot randomized controlled trial that is currently underway.

Purpose of review We present a review of the natural progression, response to hormonal therapy, and risk of malignancy associated with deep endometriosis (DE) to guide evidence-based discussion of conservative treatment. Recent findings Advanced imaging protocols have enhanced nonsurgical detection of DE, allowing noninvasive diagnosis, treatment, and surveillance. While some DE is progressive, 50% of disease appears stable over time, and progression is reduced by half with hormonal treatments (21 versus 12%). Hormonal treatment can reduce the size of DE lesions by 1 cm³, with reductions occurring after 6 months and remaining stable up to 3 years. Most hormonal therapies improve symptoms and quality of life, regardless of changes in DE size, with combined contraceptives and progestins being the most studied. DE may present a higher risk of ovarian and extraovarian cancer than previously hypothesized, though further research is needed to confirm findings. Limitations of DE research include differing imaging strategies, definitions of disease and progression, short follow-up, focus on rectosigmoid DE only, and lack of randomized trials. Summary DE is a subtype of endometriosis that is increasingly diagnosed and treated with noninvasive strategies. Hormonal treatments improve symptoms and reduce progression of DE. Further research on optimal conservative management and risk of malignancy is warranted.

Abstract Background Dasatinib is an oral inhibitor of the Src kinase family, with preclinical data indicating impact on gliomagenesis, tumor invasion, and radiosensitivity. Methods North Central Cancer Treatment Group N0877 is a phase 1 dose escalation and phase II randomized study evaluating the maximum tolerated dose (MTD), safety, and efficacy of dasatinib with radiation and temozolomide (TMZ) for glioblastoma. Following identification of the MTD, adult patients with a histologic diagnosis of glioblastoma were randomized 2:1 between dasatinib given with standard concurrent and adjuvant TMZ, versus placebo with standard concurrent and adjuvant TMZ. Radiation dose was 60 Gy in 30 fractions. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life. Results Thirteen patients were enrolled in the phase I component and established the MTD and phase II dose of 150 mg given daily. A total of 204 patients were enrolled in the phase II component. OS was not different between arms (median OS 15.6 months for dasatinib compared to 19.3 months for placebo, hazard ratio:1.21 favoring placebo, 95% CI: 0.88–1.65, log-rank P-value: .238). Similarly, PFS was not significantly different between the dasatinib and placebo arms. There was a significant increase in anemia, nausea, and creatinine elevation with dasatinib, but significantly more grade 3 lymphopenia with placebo. Conclusions The addition of dasatinib to standard chemoradiation did not improve outcomes for patients with glioblastoma. Clinical Trial Identifier NCT00869401.

Introduction Given the rising incidence and importance of treatment adherence for gestational diabetes (GDM), this study aimed to examine patient perspectives on social support's role in gestational diabetes (GDM) management during pregnancy and early postpartum. Methods This is an analysis of qualitative data collected during a feasibility randomized controlled trial of postpartum patient navigation for individuals with GDM. Participants completed semistructured interviews at 4 to 12 weeks postpartum on their experiences with GDM as well as facilitators and barriers to its management, including social support. Data were analyzed using the constant comparative method. Results Of 38 participants, 55% reported a family member or friend with a history of GDM, type 1, or type 2 diabetes mellitus. The analysis identified 4 themes: (1) communal support, (2) indirect GDM support (ie, removing logistical barriers to care), (3) direct GDM support, and (4) barriers of social support (eg, stigma), which impeded disease understanding. Participants identified communal support as a catalyst for lifestyle change and a source for advice and emotional support. Indirect support included transportation, childcare, and work accommodations. Direct support included providing healthy food, giving insulin shots, or providing accountability. Discussion Harnessing social support may be a key strategy to activate and sustain lifestyle and self‐management skills in GDM and should be considered in intervention development.

AbstractDespite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden. Numerous studies have demonstrated that negative MRD status—across diverse methodologies, assessment timepoints and thresholds, patient subgroups, and clinical settings—independently predicts improved survival. Although MRD can inform therapeutic decisions at the patient level, its formal integration as a primary surrogate end point in regulatory frameworks for clinical trials requires rigorous validation. MRD Partnership and Alliance in AML Clinical Treatment (MPAACT) is a research consortium among industry and academic leaders. MPAACT actively engages with regulatory agencies, health technology assessment bodies, technology vendors, and patient groups to establish a pathway for validating MRD as a surrogate end point in AML clinical trials. For the current article, the authors reviewed the status of MRD assessment, its use in recent clinical trials, current MRD assessment methodologies, standardization, regulatory guidance, statistical approaches, and patient access considerations necessary for MRD to become a surrogate clinical trial end point. The extensive collaboration between MPAACT, global industry, and academic partners—including data sharing and resource integration—underscores the collective commitment to advancing AML therapies. Establishing MRD as a surrogate end point could accelerate the development and approval of innovative treatments, ultimately improving patient outcomes.