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Abstract Objective We examined the long-term effects of premenopausal bilateral oophorectomy (PBO) with or without concurrent or preceding hysterectomy on physical and cognitive function and on odds of chronic conditions. Methods We enrolled 274 women with PBO with or without concurrent or preceding hysterectomy and 240 referents aged 55 years and older who were residents of Olmsted County, MN as of the PBO or index date. Chronic conditions were assessed via medical record abstraction. Cognitive diagnoses were based on neurocognitive testing. A physical function assessment included measures of strength and mobility. Multivariable regression models compared characteristics for women with PBO <46 years, PBO 46–49 years, and referent women with adjustments for age and other confounders. Results The clinical visits (median age, 67 years) were a median of 22 years after the PBO or index date. Of 274 women with PBO, 161 (59%) were <46 years at PBO and 113 (41%) were 46–49 years. Compared with referents, women with a history of PBO <46 years had increased odds of arthritis (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.06–2.55), asthma (OR, 1.74; 95% CI, 1.03–2.93), obstructive sleep apnea (OR, 2.00; 95% CI, 1.23–3.26), and bone fractures (OR, 2.86; 95% CI, 1.17–6.98), and walked a shorter mean distance on a 6-minute walk test ( b = −18.43; P = 0.034). Compared with referents, women with a history of PBO at age 46–49 years had increased odds of arthritis (OR, 1.92; 95% CI, 1.16–3.18) and obstructive sleep apnea (OR, 2.21; 95% CI, 1.33–3.66). There were no significant differences in cognitive status in women with PBO compared with referents. Conclusions Women with a history of PBO with or without concurrent or preceding hysterectomy, especially at age <46 years, have more chronic conditions in late mid-life compared with referents.

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P-value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score (P<0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score (P<0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.

Abstract Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is the main cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Ann Arbor (AA) scores derived from serum biomarkers at onset of GVHD quantify GI crypt damage; AA2/3 scores correlate with resistance to treatment and higher NRM. We conducted a multicenter, phase 2 study using natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids as primary treatment for patients with new onset AA2/3 GVHD. Seventy-five patients who were evaluable were enrolled and treated; 81% received natalizumab within 2 days of starting corticosteroids. Therapy was well tolerated with no treatment emergent adverse events in &gt;10% of patients. Outcomes for patients treated with natalizumab plus corticosteroids were compared with 150 well-matched controls from the MAGIC database whose primary treatment was corticosteroids alone. There were no significant differences in overall or complete response between patients treated with natalizumab plus corticosteroids and those treated with corticosteroids alone (60% vs 58%; P = .67% and 48% vs 48%; P = 1.0, respectively) including relevant subgroups. There were also no significant differences in NRM or overall survival at 12 months in patients treated with natalizumab plus corticosteroids compared with controls treated with corticosteroids alone (38% vs 39%; P = .80% and 46% vs 54%; P = .48, respectively). In this multicenter biomarker–based phase 2 study, natalizumab combined with corticosteroids failed to improve outcome of patients with newly diagnosed high-risk GVHD. This trial was registered at www.clinicaltrials.gov as # NCT02133924.

This cross-sectional study evaluates the consistency of US medical license renewal applications with the Federation of State Medical Boards recommendations for questions regarding physician mental health.

Abstract Under the influence of standard developmental physiology on the Earth’s surface (1 gravity equivalent known as “1G”), 70% of body fluids reside below the level of the heart.Fluid shifts towards the cephalic region during microgravity have also been speculated to contribute towards spaceflight associated neuro-ocular syndrome (SANS).Although a significant barrier to spaceflight, the underlying mechanism of SANS is not well understood, partially due to the spaceflight environment and limited medical capabilities including invasive diagnostic testing. Thus, non-invasive approaches to studying real-time fluid shifts in weightlessness could serve as critical areas of research to further SANS study and effective countermeasure protocol development. For continuous fluid shift monitoring and management, the goal is to establish baseline assessments utilizing real time point of care noninvasive imaging devices (NIID). NIID will first need to be quantified and validated through ground-based analogues, with subsequent acquisition of near continuous imaging from arrival in the weightlessness of LEO and during the time of adaptation, which may be variable among crew members. The purpose of this study was to examine temperature differential alterations, superficial venous flow patterns (head, neck, upper torso), and venous flow patterns along the lymphatic ventromedial bundles of the medial calves and thighs. Imaging was obtained in three different positions using three standards of care medical NIIDs: SnapShotTM by Kent Imaging, Scout by WoundVisionTM and LymphScannerTM by Delfin. 30 volunteers were assessed for temperature and lymphatic/venous flow using three different non-invasive devices that can measure temperature, perfusion, and image the lymphatic and venous structures. The volunteers were assessed in the sitting, supine, and 6-degree head down tilt (HDT) positions, with pre/post assessments for the HDT position. Venous and lymphatic flow patterns may vary upon position changes (sitting vs. supine vs. 6-degree head down tilt), and in response to MLD performance in the treatment group. Fifteen subjects per group (N = 30) completed all visits and were used in the full analysis. The sitting and supine position data did not show statistical significance at any of the time points and with the devices used. The HDT data from SnapShot (looking at perfusion, deoxy and oxyhemoglobin) and Wound Vision Scout (thermal imaging) did not show statistical significance between the control and treatment groups at any time points. No significant difference for any of the within-group comparisons were found with the Lymphscanner. A significant reduction in left temple TDC for the treatment group was found at post-30-minutes (5.77, 95% CI: 1.24, 10.30) and post-180-minutes. A significant reduction in right subclavicular TDC for the treatment group was found at post-180-Minutes (5.09, 95% CI: 0.16, 10.03). A significant increase in the left ventromedial bundle for the treatment group was found at post-90-Minutes (5.72, 95% CI: 0.34, 11.10) and post-120-Minutes (5.85, 95% CI: 0.47, 11.23). A significant increase in the right ventromedial bundle for the treatment group was found at post-90 minutes (5.53, 95% CI: 0.21, 10.84). This is the first HDT spaceflight analogue study, to our knowledge, in which dermal fluid shifts were evaluated using point-of-care noninvasive imaging modalities including Near Infrared Spectroscopy (NIRS), thermography and a subcutaneous edema monitor, with subsequent application of manual lymphatic drainage (MLD) techniques to stimulate dermal lymphatic function as a countermeasure and mitigation therapeutic for intervention in cephalad fluid shifts. Further validating studies are indicated for NIIDs to further quantify fluid shifts in both analogues and weightlessness.

Depression, suicidal ideation, burnout, and moral injury are on the rise among physicians. Depression and suicidal ideation are mental health disorders that result from multiple interacting factors including biological vulnerabilities and acute stressors. Medical treatment for depression and suicidal ideation is critical to interrupt the potentially deadly progression to suicide that occurs when one’s ability to find hope and other solutions is clouded by despair. Yet, stigma and perceived stigma of seeking treatment for mental health disorders still plagues medical providers. Transitions during medical training and practice can be particularly vulnerable time periods, though newer evidence suggests that overall, physicians are not at an increased risk of suicide compared to the general population. While burnout and moral injury are common among rehabilitation physicians, unlike depression, they are not directly associated with suicidal ideation. Opportunities for continued improvement in mental health resources and institutional support exist across the spectrum from medical student to staff physician. With wellness now increasingly supported and promoted by various medical organizations and recognition of the importance of access to effective mental health treatment, regaining hope and positivity while restoring resiliency in physicians, trainees, and medical students is possible.

Abstract Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged &lt;55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.

Amid the pandemic, people express the cause and consequences of their mental disturbance on social media platforms with ease. The causal analysis through cause detection, cause inference, and cause classification, and identifying consequences such as loneliness and low self-esteem expedite the interpersonal risk factors. The interpersonal risk factors of thwarted belongingness and perceived burdensomeness trigger clinical depression, which if left untreated advances to suicidal ideation and self-harm. The mental health practitioners are reliable on mental health triaging and motivational interviewing. To this end, this chapter models the evolution of mental disturbance through self-reported texts generated by users suffering with mental disturbance. The clinical psychology theories on interpersonal needs questionnaire (INQ) supporting a theory on thwarted belongingness and perceived burdensomeness is followed by extracting causes and consequences in a given text.

AbstractThe Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co‐pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI‐4 aims to address by enrolling a diverse cohort.