Magnesium-Rich Diet Score is Inversely Associated with Incident Cardiovascular Disease: The Atherosclerosis in Communities (ARIC) Study.

BACKGROUND: Numerous studies have shown inverse associations between serum magnesium (Mg) and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. AIM: To examine the association of a Mg-rich diet score with risks of CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: There were 15,022 Black and White adults without prevalent CVD at baseline (1987-89) included in this analysis. Diet was assessed at two visits 6 years apart using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created that included servings of whole grain products, nuts, vegetables, fruit, legumes, coffee, and tea. Cox proportional hazard regression evaluated associations of incident CVD, CHD and stroke across quintiles of Mg-rich diet score, adjusting for demographics, lifestyle factors, and clinical characteristics. RESULTS: Over >30 years of follow-up, there were 3,531 incident CVD events (2,562 CHD, 1,332 ischemic stroke). Participants who consumed more Mg-rich foods were older, female, White, had lower blood pressure, fewer were not current smokers, and more reported being physically active. A Mg-rich diet was inversely associated with incident CVD (HRQ5 vs Q1=0.87, 95%CI: 0.77-0.98, ptrend=0.02) CHD (HRQ5 vs Q1=0.82, 95%CI: 0.71-0.95, ptrend=0.01); however, the diet-stroke association was null (HRQ5 vs Q1=1.00, 95%CI: 0.82-1.22, ptrend=0.97). CONCLUSIONS: Consuming a diet including Mg-rich foods, such as whole grains, nuts, vegetables, fruits, legumes, coffee and tea, is associated with lower risk of CVD and CHD, but not ischemic stroke.

This study showed an inversely association between a magnesium-rich (mg-rich) diet score and risk of cardiovascular disease (CVD) in adults aged 45-64 at baseline (1987-89) and followed for over 30 years. The mg-rich diet score was created by summing the reported number of daily servings consumed from whole grain products, fruit, vegetables, legumes, nuts, coffee and tea.A mg-rich diet score may be associated with lower risk of developing CVD and coronary heart disease, but not ischemic stroke.

Automated Synthesis of DNA Nanostructures.

DNA nanotechnology has revolutionized the ability to position matter at the nanoscale, but the preparation of DNA-based architectures remains laborious. To facilitate the formation of custom structures, a fully automated method is reported to produce sequence- and size-defined DNA nanotubes. By programming the sequential addition of desired building blocks, rigid DX-tile-based DNA nanotubes and flexible wireframe DNA structures are attained, where the total number of possible constructs increases as a power function of the number of different units available. Using single-molecule fluorescence imaging, the kinetics and yield of each synthetic step can be quantitatively determined, revealing differences in self-assembly dynamics as the nanotube is built up from the solid support and providing new insights into DNA self-assembly. The exploitation of automation for both assembly and analysis (through an ad-hoc developed K-means clustering algorithm) facilitates a workflow wherein the synthesis parameters may be iteratively improved upon, demonstrating how a single-molecule "assembly-analysis-optimization" sequence can be used to generate complex, noncovalent materials in good yield. The presented synthetic strategy is generalizable, making use of equipment already available in most standard laboratories and represents the first fully automated supramolecular assembly on a solid support.

Impact of Workplace Violence against Emergency Medical Services (EMS).

OBJECTIVES: The objectives of this study were to: (1) understand the personal impact of workplace violence (WPV) on staff within a large multistate emergency medical services (EMS) agency, (2) describe the impact of WPV on subsequent patient interactions, examining how experiences of violence affect the quality of care provided by EMS clinicians, (3) examine the influence of WPV on perceived workplace safety among prehospital personnel and its correlation with retention in the EMS field, and (4) solicit recommendations from staff for the prevention and mitigation of WPV in the future.METHODS: We conducted virtual focus groups and individual interviews with 22 prehospital personnel using a descriptive qualitative design within a large multistate Midwest EMS agency between 4/5/2023-6/20/2023. Data were analyzed using Thematic Analysis to identify common perceptions among and across participants.RESULTS: Major themes of personal impact; impact on patient interactions; influence of WPV on career longevity/sustainability; and relationship between EMS culture and WPV were identified. Overall, participants shared the perception that WPV is "part of the job", and that verbal abuse was so common that they hadn't previously considered it as violence. Participants provided several examples of WPV and described how these experiences impacted them personally (e.g. hypervigilance) and impacted their subsequent interaction with patients (e.g. quicker to use restraints, loss of empathy). Participants shared the perception that EMS is no longer valued or respected by patients or communities. Several voiced concerns for the next generation of colleagues and nearly all participants reported the need for education and training in situational awareness, de-escalation, and self-defense tactics. Participants referenced desire for more coordination and communication with law enforcement, change in culture of abuse from patients without repercussions, and improved agency mental health support and peer support/mentoring following a violent event. Despite experiences with WPV, the majority reported plans to remain in EMS.CONCLUSIONS: Emergency Medical Services personnel are commonly traumatized by violence in their work and non-physical violence is underappreciated. Despite its impact on staff and subsequent patient interactions, most participants reported plans to remain within EMS. Multi-faceted system-focused efforts are needed to shift toward and support a zero-tolerance culture for WPV.

Prediction of Time to Hemodynamic Stabilization of Unstable Injured Patient Encounters Using Electronic Medical Record Data.

BACKGROUND: This study sought to predict time to patient hemodynamic stabilization during trauma resuscitations of hypotensive patient encounters using electronic medical records (EMR) data. METHODS: This observational cohort study leveraged EMR data from a nine-hospital academic system composed of Level I, Level II and non-trauma centers. Injured, hemodynamically unstable (initial systolic blood pressure < 90 mmHg) emergency encounters from 2015-2020 were identified. Stabilization was defined as documented subsequent systolic blood pressure > 90 mmHg. We predicted time to stabilization testing random forests, gradient boosting and ensembles using patient, injury, treatment, EPIC Trauma Narrator and hospital features from the first four hours of care. RESULTS: Of 177,127 encounters, 1347 (0.8%) arrived hemodynamically unstable; 168 (12.5%) presented to Level I trauma centers, 853 (63.3%) to Level II, and 326 (24.2%) to non-trauma centers. Of those, 747 (55.5%) were stabilized with a median of 50 minutes (IQR 21-101 min). Stabilization was documented in 94.6% of unstable patient encounters at Level I, 57.6% at Level II and 29.8% at non-trauma centers (p < 0.001). Time to stabilization was predicted with a C-index of 0.80. The most predictive features were EPIC Trauma Narrator measures; documented patient arrival, provider exam, and disposition decision. In-hospital mortality was highest at Level I, 3.0% vs. 1.2% at Level II, and 0.3% at non-trauma centers (p < 0.001). Importantly, non-trauma centers had the highest re-triage rate to another acute care hospital (12.0%) compared to Level II centers (4.0%, p < 0.001). CONCLUSION: Time to stabilization of unstable injured patients can be predicted with EMR data.

Evaluation of the Therapeutic Potential of Sulfonyl Urea Derivatives as Soluble Epoxide Hydrolase (sEH) Inhibitors.

The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising anti-inflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template.

Changes in risk behaviour following a network peer education intervention for HIV prevention among male Tajik migrants who inject drugs in Moscow: a cluster-randomized controlled trial.

INTRODUCTION: The "Migrants' Approached Self-Learning Intervention in HIV/AIDS for Tajiks" (MASLIHAT) recruits and trains Tajik labour migrants who inject drugs as peer educators (PEs) in delivering HIV prevention information and encouragement to adopt risk-reduction norms and practices within their diaspora social networks while reducing their own HIV risk. METHODS: The MASLIHAT intervention was tested in Moscow in a cluster-randomized controlled trial with 12 recruitment sites assigned to either the MASLIHAT intervention or an equal-time peer-educator training focused on other health conditions (TANSIHAT). From October 2021 to April 2022, 140 male Tajik migrants who inject drugs were recruited as PEs to attend the 5-session MASLIHAT training or the TANSIHAT non-HIV comparison condition. Each participant in both groups recruited two network members (NMs) who inject drugs with the intent to share with them the information and positive strategies for change they had learned (n = 280). All PEs and NMs (n = 420) participated in baseline and follow-up interviews at 3-month intervals for 1 year. All received HIV counselling and testing. Modified mixed effects Poisson regressions tested for group differences in injection practices, sexual risk behaviours and heavy alcohol use over time. RESULTS: At baseline, across both groups, 75% of participants reported receptive syringe sharing (RSS), 42% reported condomless sex and 20% reported binge drinking at least once a month. In contrast to TANSIHAT where HIV risk behaviours remained the same, significant intervention effects that were sustained over the 12 months were observed for receptive syringe and ancillary equipment sharing among both MASLIHAT PEs and NMs (p < 0.0001). Significant declines in the prevalence of sexual risk behaviours were also associated with the MASLIHAT intervention (p < 0.01), but not the comparison condition. Binge alcohol use was not affected in either condition; the MASLIHAT intervention had a transitory effect on drinking frequency that dissipated after 9 months. CONCLUSIONS: The MASLIHAT peer-education intervention proved highly effective in reducing HIV-related injection risk behaviour, and moderately effective in reducing sexual risk behaviour among both PEs and NMs. Network-based peer education is an important tool for HIV prevention among people who inject drugs, especially in environments that are not amenable to community-based harm reduction.

First do no harm: Predicting futility of intervention in geriatric emergency general surgery.

BACKGROUND: Emergent surgical conditions are common in geriatric patients, often necessitating major operative procedures on frail patients. Understanding risk profiles is crucial for decision-making and establishing goals of care. METHODS: We queried NSQIP 2015-2019 for patients ≥65 years undergoing open abdominal surgery for emergency general surgery conditions. Logistic regression was used to identify 30-day mortality predictors. RESULTS: Of 41,029 patients, 5589 (13.6 â€‹%) died within 30 days of admission. The highest predictors of mortality were ASA status 5 (aOR 9.7, 95 â€‹% CI,3.5-26.8, p â€‹< â€‹0.001), septic shock (aOR 4.9, 95 â€‹% CI,4.5-5.4, p â€‹< â€‹0.001), and dialysis (aOR 2.1, 95 â€‹% CI,1.8-2.4, p â€‹< â€‹0.001). Without risk factors, mortality rates were 11.9 â€‹% after colectomy and 10.2 â€‹% after small bowel resection. Patients with all three risk factors had a mortality rate of 79.4 â€‹% and 100 â€‹% following colectomy and small bowel resection, respectively. CONCLUSIONS: In older adults undergoing emergent open abdominal surgery, septic shock, ASA status, and dialysis were strongly associated with futility of surgical intervention. These findings can inform goals of care and informed decision-making.

Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota.

Protein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify the proteins that make up different dietary protein sources before and after digestion in germ-free and conventionally raised mice. Contrary to expectation, we detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with a high digestive efficiency make it in part to the colon where they can serve as a substrate for the microbiota. Additionally, we found clear patterns where specific component proteins of the dietary protein sources were used as a preferred substrate by the microbiota or were not as accessible to the microbiota. We found that specific proteins with functions that could impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut that could explain some of their differential health impacts.

Ultra-processed food consumption and risk of diabetes: results from a population-based prospective cohort.

AIMS/HYPOTHESIS: Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesised that a higher intake of ultra-processed foods is associated with a higher risk of incident diabetes. METHODS: The study included 13,172 participants without diabetes at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed with a 66-item semiquantitative food frequency questionnaire, and foods were categorised by processing level using the Nova classification system. Ultra-processed food was analysed categorically (quartiles of energy-adjusted intake) and continuously (per one additional serving/day). We used Cox regression to evaluate the association of ultra-processed food intake with risk of diabetes with adjustment for sociodemographic characteristics, total energy intake, health behaviours and clinical factors. RESULTS: Over a median follow-up of 21 years, there were 4539 cases of incident diabetes. Participants in the highest quartile of ultra-processed food intake (8.4 servings/day on average) had a significantly higher risk of diabetes (HR 1.13; 95% CI 1.03, 1.23) compared with participants in the lowest quartile of intake after adjustment for sociodemographic, lifestyle and clinical factors. Each additional serving of ultra-processed food consumed daily was associated with a 2% higher risk of diabetes (HR 1.02; 95% CI 1.00, 1.04). Highest quartile consumption of certain ultra-processed food groups, including sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks, was associated with a 29%, 21% and 16% higher risk of diabetes, respectively, compared with the lowest quartile. CONCLUSIONS/INTERPRETATION: We found that a higher intake of ultra-processed food was associated with higher risk of incident diabetes, particularly sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks. Our findings suggest interventions reducing ultra-processed food consumption and specific food groups may be an effective strategy for diabetes prevention.

An Early Gestation Plasma Inflammasome in Rural Bangladeshi Women.

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research.

Mechanochemical Synthesis of a Sodium Anion Complex [Na+(2,2,2-cryptand)Na-] and Studies of Its Reactivity: Two-Electron and One-Electron Reductions.

Group 1 metal molecular chemistry is dominated by a +1 oxidation state, while a 0 oxidation state is widespread in the metals. A more exotic, yet still available, oxidation state of group 1 metal is -1, i.e., alkalide. Reported as early as the 1970s, the alkalides appear in every modern inorganic chemistry textbook as an iconic chemical curiosity, yet their reactivity remains unexplored. This is due to their synthetic hurdles. In this work, we report the first facile synthesis of the archetypical alkalide complex, [Na+(2,2,2-cryptand)Na-], which allows us to unveil a versatile reactivity profile of this once exotic species.

Case report: Characterization of the immunologic and molecular landscape in a unique presentation of invasive lobular carcinoma with concurrent uterine carcinosarcoma treated with immunotherapy.

Invasive lobular breast cancer (ILC) is characterized by a relatively high risk for late recurrence and a unique metastatic pattern with an increased risk for metastasis to gynecologic organs and peritoneum. We present a unique case of recurrent ILC with metastasis to the abdominal peritoneum as well as the uterine myometrium and cervix. Treatment was complicated by the discovery of concomitant uterine carcinosarcoma. This patient was effectively treated with a combination of hormonal therapy for her metastatic ILC and a combination of chemotherapy and immunotherapy for uterine carcinosarcoma. Molecular evaluation revealed a characteristic CDH1 mutation within the ILC and a PI3KCA mutation within the uterine carcinosarcoma, both of which have been linked to epithelial-to-mesenchymal transitions. Examination of the tumor immune microenvironment revealed proportionally more cytotoxic NK cells. This robust immune infiltration may be an indicator of the response to immunotherapy observed in this tumor or a result of the metastatic breast cancer within the uterus. This report provides a characterization of the molecular and immunologic landscape in this case with metastatic ILC and uterine carcinosarcoma.

Plasma proteins associated with plant-based diets: Results from the Atherosclerosis Risk in Communities (ARIC) study and Framingham Heart Study (FHS).

BACKGROUND & AIMS: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort. METHODS: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics. RESULTS: In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests). CONCLUSIONS: Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.

Association of Homelessness with Before Medically Advised Discharge After Surgery.

BACKGROUND: Before medically advised (BMA) discharge, which refers to patients leaving the hospital at their own discretion, is associated with higher rates of readmission and death in other settings. It is not known if housing status is associated with this phenomenon after surgery. METHODS: We identified all admitted adults who underwent an operation by one of 11 different surgical services at a single tertiary care hospital between January 2013 and June 2022. Chi-square tests and t-tests were used to compare demographic and clinical features between BMA discharges and standard discharges. Multivariable logistic regression was used to evaluate the association between housing status and BMA discharge, adjusting for demographic and admission characteristics. Documented reasons for BMA discharge were also abstracted from the medical record. RESULTS: Of 111,036 patient admissions, 242 resulted in BMA discharge (0.2%). After adjusting for observable confounders, patients experiencing homelessness had substantially higher odds of BMA discharge after surgery (adjusted odds ratio 4.4, 95% confidence interval 3.0-6.4; p < 0.001) when compared to housed. Patients who underwent emergency surgery, patients with a documented substance use disorder, and those insured by Medicaid also had significantly higher odds of BMA discharge. System- or provider-related reasons (including patient frustration with the hospital environment, challenges in managing substance dependence, and perceived inadequacy of paint control) were documented in 96% of BMA discharges for patients experiencing homelessness (vs. 66% in housed patients). CONCLUSION: BMA discharge is more common in patients experiencing homelessness after surgery even after adjusting for observable confounding characteristics. Deeper understanding of the drivers of BMA discharge in patients experiencing homelessness through qualitative methods are critical to promote more equitable and effective care.

Lack of effects of online HD-tDCS over the left or right DLPFC in an associative memory and metamemory monitoring task.

Neuroimaging studies have shown that activity in the prefrontal cortex correlates with two critical aspects of normal memory functioning: retrieval of episodic memories and subjective "feelings-of-knowing" about our memory. Brain stimulation can be used to test the causal role of the prefrontal cortex in these processes, and whether the role differs for the left versus right prefrontal cortex. We compared the effects of online High-Definition transcranial Direct Current Stimulation (HD-tDCS) over the left or right dorsolateral prefrontal cortex (DLPFC) compared to sham during a proverb-name associative memory and feeling-of-knowing task. There were no significant effects of HD-tDCS on either associative recognition or feeling-of-knowing performance, with Bayesian analyses showing moderate support for the null hypotheses. Despite past work showing effects of HD-tDCS on other memory and feeling-of-knowing tasks, and neuroimaging showing effects with similar tasks, these findings add to the literature of non-significant effects with tDCS. This work highlights the need to better understand factors that determine the effectiveness of tDCS, especially if tDCS is to have a successful future as a clinical intervention.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]). Setting & Participants: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without diabetes in the ARIC, REGARDS, and MESA studies. Exposures: Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1. Outcome: Incident CKD or end-stage kidney disease. Analytical Approach: Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts. Results: 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m2. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31). Limitations: Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts. Conclusions: In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

This study analyzed 3 cohorts (ARIC, MESA, and REGARDS) of adults without diabetes or prevalent chronic kidney disease (CKD) to determine the associations of 5 urinary biomarkers of kidney tubulointerstitial health with incident CKD, independent of traditional measures of kidney health. Meta-analysis of results from all 3 cohorts suggested that higher baseline levels of urine alpha-1-microglobulin were associated with incident CKD at follow-up. Results from individual cohorts suggested that in addition to alpha-1-microglobulin, monocyte chemoattractant protein-1, kidney injury molecule-1, and epidermal growth factor may also be associated with the development of CKD. These findings underscore the importance of kidney tubule interstitial health in defining risk of CKD independent of creatinine and urine albumin.

Medial Femoral Trochlea Osteochondral Flap Reconstruction of the Previously Unsalvageable Kienbock-Associated Lunate With a Coronal Split.

PURPOSE: Patients with Kienbock disease can present with coronal fracture and collapse of the proximal lunate (Unified B2/Bain grade 1, 2B). Traditionally, this was considered unsalvageable. However, medial femoral trochlea (MFT) osteochondral reconstruction, used to recreate the proximal lunate surface, can be paired with reduction and repair of the coronal plane fracture, thus restoring midcarpal congruity. The purpose of this study was to report radiographic and clinical outcomes following lunate coronal fracture fixation at the time of MFT osteochondral reconstruction. METHODS: This was a retrospective study performed at a single institution. We identified patients with Kienbock disease who underwent MFT osteochondral reconstruction from 2014 to 2023. Patients were included if they had a coronal fracture of the lunate distal articular surface fixed at the time of surgery. Radiographic and clinical parameters were evaluated, including carpal height ratio, union rate, presence of heterotopic ossification, need for revision surgery, and patient-reported outcome measures. RESULTS: Thirty-three patients were included, with a mean age of 27.5 years (range: 15-41); 19 (58%) were women. Mean radiographic follow-up time was 5.8 months, and mean clinical follow-up time was 22.6 months. Union was achieved in 30/33 patients (91%). Carpal height ratio improved from 1.32 to 1.4. Two patients (6%) required reoperation, one for removal of heterotopic ossification and another for conversion to proximal row carpectomy. Patients demonstrated meaningful improvement in brief Michigan Hand Questionnaire and Patient-Reported Outcomes Measurement Information Upper Extremity scores. Range of motion before and after surgery was similar. CONCLUSIONS: Lunate coronal fracture fixation with MFT osteochondral reconstruction represents an additional management option in select patients with Kienbock disease. This technique restores the midcarpal joint during lunate reconstruction and may allow patients to avoid salvage procedures. Early radiographic and clinical outcomes are promising. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

OBJECTIVES: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. DISCUSSION: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Associations between race and ethnicity and treatment setting among gynecologic cancer patients.

INTRODUCTION: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients. MATERIALS & METHODS: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression. RESULTS: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival. DISCUSSION: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.