Citations

Abstract Objective: We examined post-traumatic reactions and quality of life in women with recurrent gynecologic cancer who underwent a pelvic exenteration (PE), a rare, potentially life-saving radical surgery associated with life-altering sequalae. Methods: Twenty-one women who had completed PE at least 6 months prior completed measures of post-traumatic stress, post-traumatic growth, depression, and quality of life. Quality of life scores were compared to normative values for the general and gynecologic cancer populations. Results: Thirty percent of women reported clinically significant post-traumatic stress symptoms and 71% endorsed clinically significant depressive symptoms. More post-traumatic stress was associated with less post-traumatic growth, more depressive symptoms, and worse quality of life. In general, women’s quality of life was worse than the general population but comparable to women with stage III-IV ovarian cancer and women with cervical cancer. Social functioning was markedly lower in our sample and women reported more pain, diarrhea, and financial difficulties post-PE compared to published norms. There were no differences in quality of life based on age, type of PE, or cancer type. Conclusions: Findings support long-term continued symptom management and the ongoing rehabilitation of patients to optimize physical, psychological, and social well-being in PE survivorship.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.

AbstractCore‐binding factor acute myeloid leukemia (CBF‐AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33‐targeting antibody‐drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF‐AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF‐AML. We included 200 patients with CBF‐AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow‐up for the whole cohort was 2.5 years. Three‐year overall survival (OS) was 70% and 3‐year event‐free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3‐year EFS of 50% compared to those treated with IC alone who experienced a 3‐year EFS of 47%, with no statistically significant difference (p = 0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (p = 0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3‐year EFS of 85% compared to those with IC with or without GO (p = 0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF‐AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

Oral health is an essential component of overall health for all individuals. The oral health of children and youth with developmental disabilities (CYDD) involves unique characteristics and needs of which pediatricians and pediatric clinicians can be aware. Risk for oral disease in CYDD is multifactorial and includes underlying medical conditions, medications, and ability to participate in preventive oral health care and treatment, and lack of access to providers is common for this population despite being eligible for Medicaid. Pediatric clinicians are uniquely positioned to support the oral health needs of CYDD and their families through the medical home. This clinical report aims to inform pediatric clinicians about the unique oral health needs of CYDD. It provides guidance on assessing caries risk and periodontal status using structured screening instruments; understanding dental trauma, the role of diet and caries risk, trauma prevention, and malocclusion; and providing anticipatory guidance on oral hygiene that includes tooth brushing, use of fluoridated toothpaste, assessing community water fluoridation, advocating for a dental home by 1 year of age, and transition to adult dental care as part of adolescent health care. It also highlights special considerations for dental treatment rendered under sedation or general anesthesia that CYDD may need. Pediatric clinicians can help reduce risk of CYDD developing dental disease by understanding the unique needs of their patients and their barriers to accessing oral health care in their community, communicating with the child’s dental home, and advocating for safe and accessible dental procedures.

AbstractINTRODUCTIONThe apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid‐beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex‐dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.METHODSIn 2023, the Alzheimer's Association convened multidisciplinary researchers at the “AAIC Advancements: APOE” conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE‐targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function.RESULTSThis manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field.DISCUSSIONUnderstanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine.Highlights APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid‐beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

AbstractBackgroundDisorders of gut–brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world.MethodsWe performed an ecological study utilizing peer‐reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI).Key ResultsThe regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = −0.57, 95% CI: −0.92, −0.22, p = 0.002) and happiness scores (β = −0.433 95% CI: 0.821, −0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = −0.50, 95% CI: −0.86, −0.13, p = 0.01) and happiness scores (β = −0.497, 95% CI: −0.863, −0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = −0.43, 95% CI: −0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = −0.40, 95% CI: −0.79, −0.014, p = 0.043) and happiness scores (β = −0.390, 95% CI: −0.778, −0.003, p = 0.049).Conclusions & InferencesUtilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio‐cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world.

Abstract Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 patients with CCUS investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count of <100 × 109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the clonal cytopenia risk score (CCRS), which stratified patients into low- (score of <2.5 points), intermediate- (score of 2.5 to <5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray test (P < .0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P = .005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.

OBJECTIVES: To evaluate tranexamic acid (TXA) when administered immediately on hospital presentation in patients with extracapsular peritrochanteric hip fractures to determine its effect on (1) transfusion rates, (2) estimated blood loss, and (3) complications. METHODS: Design: Prospective, double-blinded, randomized clinical trial. Setting: Single-center, Level 1 trauma center. Patient Selection Criteria: All patients with isolated OTA/AO 31-A fracture patterns from 2018 to 2022 were eligible for inclusion. Study drug was administered in the emergency department at the time of presentation—1-g bolus over 10 minutes followed by a 1-g infusion over 8 hours. Outcome Measures and Comparisons: The primary outcome was the rate of red blood cell transfusion hospital days 1–4. Secondary outcomes included estimated blood loss and complications including venous thromboembolic events, stroke, myocardial infarction, all-cause 90-day readmissions, and all-cause mortality. RESULTS: One hundred twenty-eight patients were included—64 patients were randomized to intravenous TXA and 64 patients to intravenous normal saline (ie, placebo). There was no difference in the rate of red blood cell transfusion between treatment arms between hospital days 1–4 (27% in the TXA arm vs. 31% in the placebo arm, P = 0.65). Patients randomized to placebo who required transfusion received a mean of 2.30 units compared with 1.94 units in the TXA cohort (P = 0.55). There was no difference in the estimated blood loss between hospital days 1–4. There was no difference in the incidence of postoperative complications including venous thromboembolic events, stroke, myocardial infarction, 90-day readmission, or death. CONCLUSIONS: The results of this study do not support the use of preoperative TXA for reducing blood loss for geriatric patients with extracapsular hip fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Abstract Background Provider burnout due to workload is a significant concern in primary care settings. Workload for primary care providers encompasses both scheduled visit care and non–visit care interactions. These interactions are highly influenced by patients' health conditions or acuity, which can be measured by the Adjusted Clinical Group (ACG) score. However, new patients typically have minimal health information beyond social determinants of health (SDOH) to determine ACG score. Objectives This study aims to assess new patient workload by first predicting the ACG score using SDOH, age, and gender and then using this information to estimate the number of appointments (scheduled visit care) and non–visit care interactions. Methods Two years of appointment data were collected for patients who had initial appointment requests in the first year and had the ACG score, appointment, and non–visit care counts in the subsequent year. State-of-art machine learning algorithms were employed to predict ACG scores and compared with current baseline estimation. Linear regression models were then used to predict appointments and non–visit care interactions, integrating demographic data, SDOH, and predicted ACG scores. Results The machine learning methods showed promising results in predicting ACG scores. Besides the decision tree, all other methods performed at least 9% better in accuracy than the baseline approach which had an accuracy of 78%. Incorporating SDOH and predicted ACG scores also significantly improved the prediction for both appointments and non–visit care interactions. The R 2 values increased by 95.2 and 93.8%, respectively. Furthermore, age, smoking tobacco, family history, gender, usage of injection birth control, and ACG were significant factors for determining appointments. SDOH factors such as tobacco usage, physical exercise, education level, and group activities were strongly correlated with non–visit care interactions. Conclusion The study highlights the importance of SDOH and predicted ACG scores in predicting provider workload in primary care settings.