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BSLD-10 Characterization of Cerebrospinal Fluid to Better Anticipate Systemic Progression of Cancers in Patients With Leptomeningeal Carcinomatosis (Lmc): Dual Institutional Analysis
No full textPURPOSE:
Leptomeningeal carcinomatosis (LMC) is a rapidly fatal metastasis of systemic cancer to the leptomeninges commonly treated with intrathecal (IT) chemotherapy. Earlier identification of progression or treatment effects could earlier inform failing response to systemic therapy and extend patient quality survival.
QUESTION:
Are there measurable changes in cerebrospinal fluid (CSF) associated with systemic cancer progression in LMC patients treated with IT chemotherapy?
METHODS:
We retrospectively analyzed CSF and imaging data for LMC patients treated with IT chemotherapy between 2017–2025 as part of established Ommaya Clinics. We identified dates of systemic progression as determined by body CT/PET scans over the patient’s treatment course. We then evaluated CSF changes in protein, glucose, and white blood cells (WBCs) 6–8 weeks prior to noted systemic progression.
RESULTS:
Of 123 patients evaluated, 51% (n=63) developed 1st or 2nd radiographically assessed systemic disease progressions while being treated with IT chemotherapy. Of these progressed cases, 70% (n=44) were preceded within 6 weeks by an average protein elevation of 32 mg/dL, 79% (n=50) showed an average WBC elevation of 2 cells/mm3, and 35% (n=22) had an average glucose reduction of 14 mg/dL as compared to serum glucose. Seventy-two percent of patients did not have clear worsening neurologic deficits obvious clinical decline prior to radiographic progression.
CONCLUSIONS:
There are measurable changes in CSF markers that precede systemic and CNS events in cancer patients undergoing IT therapy. Accurate assessment of these markers has potential implications for predicting systemic progression and offers a window of opportunity for earlier therapeutic intervention, limiting clinical decline, and informing treatment response
Integrating Mental Health into Diabetes Care: Closing the Treatment Gap for Better Outcomes—A Systematic Review
No full textBackground: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20-30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services into diabetes management is recommended by international organizations to improve patient outcomes. Objectives: To systematically review the evidence on integrated mental health interventions in diabetes care, compared to usual diabetes care, in improving patient outcomes (glycemic control, mental health, adherence, quality of life). Methods: We searched PubMed/MEDLINE, Embase, PsycINFO, and Scopus (2000 through July 2024) for studies of diabetes care integrating mental health support (e.g., collaborative care, co-location, stepped care, or digital interventions). Inclusion criteria were controlled trials or cohort studies involving individuals with type 1 or type 2 diabetes receiving an integrated mental health intervention, with outcomes on glycemic control and/or mental health. Two reviewers independently screened titles/abstracts and full texts, with disagreements resolved by consensus. Data on study design, population, intervention components, and outcomes were extracted. Risk of bias was assessed using Cochrane or appropriate tools. Results: Out of records identified, 64 studies met inclusion criteria (primarily randomized controlled trials). Integrated care models consistently improved depression and anxiety outcomes and diabetes-specific distress, and yielded modest but significant reductions in glycated hemoglobin (HbA1c) compared to usual care. Many interventions also enhanced treatment adherence and self-management behaviors. For example, collaborative care trials showed greater depression remission rates and small HbA1c improvements (~0.3-0.5% absolute reduction) relative to standard care. Co-located care in diabetes clinics was associated with reduced diabetes distress, depression scores, and HbA1c over 12 months. Digital health integrations (telepsychiatry, online cognitive-behavioral therapy) improved psychological outcomes and adherence, with some reporting slight improvements in glycemic control. Integrated approaches often increased uptake of mental health services (e.g., higher referral completion rates) and showed high patient satisfaction. A subset of studies reported fewer emergency visits and hospitalizations with integrated care, and one economic analysis found collaborative care cost-effective in primary care settings. Conclusions: Integrating mental health into diabetes care leads to better mental health outcomes and modest improvements in glycemic control, without adverse effects. Heterogeneity across studies is noted, but the overall evidence supports multidisciplinary, patient-centered care models to address the psychosocial needs of people with diabetes. Healthcare systems should prioritize implementing and scaling integrated care, accompanied by provider training and policy support, to improve outcomes and bridge the persistent treatment gap. Future research should focus on long-term effectiveness, cost-effectiveness, and strategies to reach diverse populations
Looking back at the TEDDY study: lessons and future directions
No full textThe goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1-3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2-4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM
Impact of Dynamic Operations Complexity on Performance: The Role of National Culture
No full textWe build on the national culture, complex adaptive systems, and operations complexity literature to develop hypotheses about the moderating role of national culture on the negative relationship between dynamic operations culture and operational complexity. Monthly performance data were collected from 179 plants in a multinational corporation's global plant network that spans all national culture clusters. We use random effects time series modeling to incorporate the transitory nature of this relationship and control unobserved heterogeneity over time. The results indicate that the relationship between dynamic operations complexity and operational performance is moderated by every dimension of national culture except gender egalitarianism and institutional collectivism. We contribute to the literature on complexity by introducing the dynamic operations complexity construct and showing the moderating effect of national culture. We contribute to the national culture literature by comprehensively examining the role of national culture supporting the national culture divergence thesis. Managerial implications relate to locating new plants in regions whose national culture is supportive of key goals and allocating tasks and products accordingly
Relationship between gastroesophageal reflux and chronic kidney disease: A meta-analysis of 4 million patients
No full textBackground: Chronic kidney disease (CKD) has been associated with higher risk of gastrointestinal disorders, particularly Gastroesophageal reflux disease (GERD). However, the magnitude of this association and the underlying mechanisms remains unclear.
Methods: A systematic search was conducted across major databases from inception to November 2024. We included cross-sectional and case-control studies evaluating the relationship between CKD and GERD. Data were extracted and analyzed using a random-effects model to calculate pooled odds ratios (ORs) and prevalence rates. Study quality was assessed using the Newcastle-Ottawa Scale, and heterogeneity was evaluated using the Cochran's Q test and I² statistic.
Results: Nine studies involving 4,650,709 participants were included. The pooled prevalence of GERD among CKD patients was 18% (95% CI: 0.10-0.26, I² =93.64%). The pooled crude OR for the association between CKD and GERD was 2.53 (95% CI: 1.30-4.92) and adjusted OR was 1.48 (95% CI: 1.05-2.08).
Conclusion: This meta-analysis reveals a marginally significant association between CKD and GERD, highlighting higher prevalence of GERD among individuals with CKD. Furthers studies are needed to elucidate the underlying pathophysiological mechanisms and potential clinical implications
Bone complications after hand and face transplantation: Mechanisms and management
No full textVascularized composite allotransplantation (VCA) has expanded the frontiers of reconstructive surgery by enabling restoration of form and function in patients with devastating facial and extremity defects. While advances in surgical techniques and immunosuppression have improved short- and mid-term outcomes, bone-related complications remain a critical yet underexplored challenge. This review provides a comprehensive overview of the mechanisms and clinical manifestations of bone problems in VCA, including delayed union, nonunion, avascular necrosis, and osteoporosis. Particular emphasis is placed on the detrimental effects of long-term immunosuppressive therapy on bone metabolism and repair. Current and emerging strategies to address these issues—such as glucocorticoid-sparing regimens, pharmacological therapies like bisphosphonates and teriparatide, and regenerative medicine approaches—are also discussed. By synthesizing clinical experience, translational studies, and experimental models, this review underscores that bone complications represent a major determinant of graft integration, functional recovery, and long-term success in VCA. Greater recognition of these challenges and development of targeted management strategies are essential to optimize outcomes for recipients of bone-containing allotransplants
A Simulative Deep Learning Model of SNP Interactions on Chromosome 19 for Predicting Alzheimer's Disease Risk and Rates of Disease Progression
No full textIUIBackground: Understanding Alzheimer’s disease (AD) genetic dynamics is key to unraveling its pathophysiology and advancing precision medicine. Current genetic studies, however, fall short in analyzing epistatic interactions between single nucleotide polymorphisms (SNPs). Here, we introduce a novel capsule network–based deep learning framework designed to model and quantify these complex SNP–SNP interactions on AD risk. Methods: In Chapter 1, we developed a novel deep learning model that can examine epistatic interactions of SNPs. Chromosome 19 genetic data from ADNI and ImaGene were used. Their epistatic impacts on AD development were quantified and the top 35 AD-risk SNPs were identified. In Chapter 2, we explored the clinical utility of the top 35 AD-risk SNPs. We performed computational gene-editing simulations, i.e., substituting each risk allele with its reference counterpart, to estimate how these edits would alter an individual’s Alzheimer’s risk. Further, we correlated each SNP’s quantified impact with the rate of cognitive declines and cerebrospinal fluid proteins changes using regression analysis. Results: The model was successfully trained and mapped genetic dynamics of AD in chromosome 19. Rs561311966 (APOC1) and rs2229918 (ERCC1) emerged as the strongest AD-risk SNPs. Computational gene-editing simulation with rs56131196 reduced the likelihood of AD by 7.9%, converting 36% of predicted AD participants to cognitive unimpaired individuals. Regression analyses using the top 35 SNPs yielded significant associations (p < 0.05) with disease progression, with the strongest correlations observed for executive function decline (adjusted r² = 0.433) and the ratio of amyloid beta over total tau change. (adjusted r² = 0.973).
Discussion: Our model provided a comprehensive view of SNP interactions on chromosome 19 underlying Alzheimer’s development in a fully hypothesis free manner. The top 35 risk variants formed clusters in six genes: APOC1, TOMM40, ZNF473, VRK3, ERCC1 and APOC2. Multiple biological and clinical studies demonstrate that variants in these genes contribute to Alzheimer’s pathology, particularly through oxidative stress related mechanisms. We quantified the individual impact of these risk variants, enabling in-silico gene editing simulations and prediction of disease progression. This work has the potential to transform preventive precision medicine
Cardiac Point of Care Ultrasound (POCUS) Used to Diagnose Infective Endocarditis Following Multiple Negative Echocardiograms
No full textInfective endocarditis (IE) is a life-threatening condition often diagnosed using the modified Duke's criteria, including bacteremia and pathognomonic echocardiographic findings. However, up to 30% of cases yield inconclusive results with transthoracic echocardiograms (TTE) or transesophageal echocardiograms (TEE). We present a case of a 68-year-old man with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and recurrent fevers, in which multiple echocardiograms failed to detect valvular vegetations. However, an advanced cardiac point of care ultrasound (POCUS) examination identified a vegetation on the aortic valve, later confirmed by TTE and TEE. Although generalization is limited due to operator expertise and patient characteristics, this case demonstrates the utility of advanced cardiac POCUS in diagnosing IE in critically ill patients with negative initial echocardiograms. Incorporating advanced cardiac POCUS into routine diagnostic workflows may improve diagnostic accuracy and patient outcomes. Increasing use of advanced cardiac POCUS also highlights the importance of expanding proficiency among intensivists