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Background and Purpose: We assessed risk and determinants of new-onset depression in acute ischemic stroke (AIS) patients of all ages and no known history of depression. Additionally, we assessed patterns of post-stroke depression (PSD) treatment with pharmacotherapy. Methods: Retrospective cohort study of de-identified Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Datasets for adults age ≥18 years admitted with AIS from July 1, 2016-July 1, 2017. We created Kaplan-Meier curves of cumulative risk of PSD up to 1.5 years following index AIS admission. We performed Cox regression to report hazard ratios for determinants of PSD up to 1.5 years following AIS. We summarized proportions treated with pharmacotherapy and identified the most commonly prescribed medications. Results: Of 8089 AIS patients, 1059 were diagnosed with PSD. At 1 year, cumulative risk of PSD was 13.4% (standard error .4) and 15.3% (standard error .5) at 1.5 years. History of anxiety was most strongly associated with PSD and discharge home least. Among those with PSD, 68.8% were prescribed an antidepressant and 8.4% an antipsychotic. The most commonly prescribed antidepressant was sertraline (28.5%). Conclusions: Among AIS patients of all ages, there is a persistently elevated cumulative risk of new diagnosis of PSD in the 1.5 years following AIS. Of the >2/3 treated with an antidepressant, sertraline was most commonly prescribed. Screening and treatment strategies for PSD require further study.

ImportanceAutism spectrum disorder (ASD) affects 1 in 44 children. The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured observation developed for use in research but is considered a component of gold standard clinical diagnosis. The ADOS adds time and cost to diagnostic assessments.ObjectiveTo evaluate consistency between clinical diagnosis (index ASD diagnosis) and diagnosis incorporating the ADOS (reference standard ASD diagnosis) and to examine clinician and child factors that predict consistency between index diagnoses and reference standard diagnoses.Design, Setting, and ParticipantsThis prospective diagnostic study was conducted between May 2019 and February 2020. Developmental-behavioral pediatricians (DBPs) made a diagnosis based on clinical assessment (index ASD diagnosis). The ADOS was then administered, after which the DBP made a second diagnosis (reference standard ASD diagnosis). DBPs self-reported diagnostic certainty at the time of the index diagnoses and reference standard diagnoses. The study took place at 8 sites (7 US and 1 European) that provided subspecialty assessments for children with concerns for ASD. Participants included children aged 18 months to 5 years, 11 months, without a prior ASD diagnosis, consecutively referred for possible ASD. Among 648 eligible children, 23 refused, 376 enrolled, and 349 completed the study. All 40 eligible DBPs participated.ExposuresADOS administered to all child participants.Main Outcomes and MeasuresIndex diagnoses and reference standard diagnoses of ASD (yes/no).ResultsAmong the 349 children (279 [79.7%] male; mean [SD] age, 39.9 [13.4] months), index diagnoses and reference standard diagnoses were consistent for 314 (90%) (ASD = 250; not ASD = 64) and changed for 35. Clinician diagnostic certainty was the most sensitive and specific predictor of diagnostic consistency (area under curve = 0.860; P Conclusions and RelevanceIn this prospective diagnostic study, clinical diagnoses of ASD by DBPs with vs without the ADOS were consistent in 90.0% of cases. Clinician diagnostic certainty predicted consistency of index diagnoses and reference standard diagnoses. This study suggests that the ADOS is generally not required for diagnosis of ASD in young children by DBPs and that DBPs can identify children for whom the ADOS may be needed.

Previous studies have suggested an association between bone mineral density (BMD) and heart failure (HF) risk that may be race-dependent.We evaluated the relationship between BMD and incident HF in a cohort of older adults, the Health, Aging, and Body Composition (Health ABC) study (n = 2835), and next performed a pooled analysis involving a second older cohort, the Cardiovascular Health Study (n = 1268). Hip BMD was measured by dual-energy X-ray absorptiometry in both cohorts and spine BMD by computed tomography in a subset from Health ABC.In Health ABC, lower BMD at the total hip was associated with higher incident HF in Black women after multivariable adjustment. Similar associations were found for BMD at the femoral neck and spine. In both cohorts, pooled analysis again revealed an association between lower total hip BMD and increased risk of HF in Black women (HR = 1.41 per 0.1-g/cmLower BMD was associated with higher risk of HF and especially HFpEF in older Black women and White men, highlighting the need for additional investigation into underlying mechanisms.

Purpose: Although medical care for transgender and gender nonbinary (TGNB) individuals is rapidly expanding, numerous gaps in the organization of quality care for TGNB individuals remain. In 2018, ...

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell-lymphoma patient cohort from five centers in Germany and the United States (Germany, N=66; US, N=106, Total, N=172), we demonstrate that wide-spectrum antibiotics treatment (‘high-risk antibiotics’) prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely confounded by an increased pre-treatment tumor burden and systemic inflammation in high-risk antibiotics-pre-treated patients. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were uncovered between pre-CAR-T-infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-months survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine-learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also associating with pre-infusion peripheral T cell levels in these patients. Collectively, we uncover conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.

The intestinal microbiota is essential for the fermentation of dietary fiber into short-chain fatty acids (SCFA) such as butyrate, acetate, and propionate. SCFAs can bind to the G-protein-coupled receptors GPR43 and GPR109A (HCAR2), with varying affinities to promote cellular effects in metabolism or changes in immune function. We explored the role of GPR109A as the main receptor for butyrate in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Deletion of GPR109A in allo-HCT recipients did not affect GVHD, but transplantation of T cells from GPR109A knockout (KO) (Gpr109a−/−) mice into allo-HCT recipient mice significantly reduced GVHD morbidity and mortality compared with recipients of wild-type (WT) T cells. Recipients of Gpr109a−/− T cells exhibited less GVHD-associated target organ pathology and decreased proliferation and homing of alloreactive T cells to target tissues. Although Gpr109a−/− T cells did not exhibit immune deficits at a steady state, following allo-activation, Gpr109a−/− T cells underwent increased apoptosis and were impaired mitochondrial oxidative phosphorylation, which was reversible through antioxidant treatment with N-acetylcysteine (NAC). In conclusion, we found that GPR109A expression by allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary features to induce GVHD after allo-HCT.

OBJECTIVES To compare risk of reoperation for femoral neck fracture patients undergoing fixation with cancellous screws (CS) or sliding hip screws (SHS) based on surgeon fellowship (trauma-fellowship-trained versus non-trauma-fellowship-trained). DESIGN Retrospective review of FAITH data. SETTING Eighty-one centers across eight countries. PATIENTS/PARTICIPANTS 819 patients ≥ 50 years-old with low energy hip fractures requiring surgical fixation. INTERVENTION Patients were randomized to CS or SHS in the initial dataset. MAIN OUTCOME MEASUREMENTS The primary outcome was risk of reoperation. Secondary outcomes included death, serious adverse events, radiographic healing, discharge disposition, and use of ambulatory devices postoperatively. RESULTS There was no difference in risk of reoperation between the two surgeon groups (p > 0.05). Patients treated by orthopaedic trauma surgeons were more likely to be overweight/obese and have major medical comorbidities (p < 0.05). There was a higher risk of serious adverse events, higher likelihood of radiographic healing, and higher odds of discharge to a facility for patients treated by trauma-fellowship-trained surgeons (p < 0.05). CONCLUSIONS Based on this data, risk of reoperation for low energy femoral neck fracture fixation is equivalent regardless of fellowship training. The higher likelihood of radiographic healing noted in the trauma-trained group does not appear to have a major clinical implication as it did not affect risk of reoperation between the two groups. Patient-specific factors present pre-injury, such as body habitus and medical comorbidities, may account for the lower odds of discharge to home and higher risk of postoperative medical complications for patients treated by orthopaedic trauma surgeons. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Historically, the traditional pathways into plastic surgery required board eligibility in a surgical specialty such as general surgery, orthopedics, urology, neurosurgery, otolaryngology, or ophthalmology. This requirement resulted in plastic surgery residents who had served as chief residents before plastic surgery training. Their maturity emotionally and surgically allowed them to immediately concentrate on the new language and principles of plastic surgery. They had led others and were capable of leading themselves in a new surgical discipline. Today, medical students typically match into surgical specialties directly out of medical school and need to spend their time learning basic surgical skills and patient care because of the contracted time afforded to them. Formal leadership training has historically been limited in surgical training. The authors set out to delineate the creation, implementation, and perceptions of a leadership program within a surgical residency and provide guideposts for the development of engaged, conscious, and dedicated leaders within the residencies they lead.

Background: Artificial intelligence (AI) software is increasingly applied in stroke diagnostics. Viz LVO (large vessel occlusion) is an AI-based software that is FDA-approved for LVO detection in CT Angiography (CTA) scans. We sought to investigate differences in transfer times [from peripheral (spoke) to central (hub) hospitals] for LVO patients between spoke hospitals that utilize Viz LVO and those that do not. Methods: In this retrospective cohort study, we used our institutional database to identify all suspected/confirmed LVO transferred patients from spokes (peripheral hospitals) within and outside of our healthcare system, from January 2020 to December 2021. The “Viz transfers” group includes all LVO transfers from spokes within our system where Viz LVO is readily available, while the “Non-Viz transfers” group (control group) is comprised of all LVO transfers from spokes outside our system, without Viz LVO. Primary outcome included all available time metrics from peripheral CTA commencement. Results: In total, 78 patients required a transfer. Despite comparable peripheral hospital door to peripheral hospital CTA times [20.5 (24.3) vs. 32 (45) min, p=0.28] and transfer (spoke to hub) time [23 (18) vs. 26 (13.5), p=0.763], all workflow metrics were statistically significantly shorter in the Viz-transfers group. Peripheral CTA to interventional neuroradiology team notification was 12 (16.8) vs. 58 (59.5), p

Introduction: There has been a shift in prehospital systems of care to prioritize transporting acute ischemic stroke (AIS) patients with suspected emergent large vessel occlusion (ELVO) stroke to thrombectomy capable stroke centers (TSCs), as opposed to primary stroke centers (PSCs) which may be closer and offer intravenous thrombolysis faster. Large scale data on clinical outcomes in direct triage are lacking. Methods: We conducted a systematic review and meta-analysis using PRISMA guidelines with the Nested Knowledge AutoLit platform to search PubMed for relevant terms from 01/2015 to 05/2022. Our primary endpoint was proportion of patients with a good clinical outcome [modified Rankin Score (mRS) 0-2] at 90 days. Results: We identified 390 studies, 16 of which compared direct triage to various models and were included. Amongst these, Mobile Stroke Unit (MSU; n=1), Mothership only (n=1), Drip-and-Ship only (n=3), and Mothership + Drip-and-Ship (n=11) were compared to Direct Triage. Among the eleven that reported 90-day functional status outcomes, there were no discernible trends. Four studies that compared 90-day functional outcomes amongst patients who received EVT and compared Direct Triage to Drip-and-Ship + Mothership models were analyzed. Baseline age, sex, and presenting NIHSS were similar. Patients who underwent Direct Triage were more likely to have a good outcome (mRS 0-2) at 90-days (OR 1.35, 95% CI 1.03-1.76). Conclusions: Amongst patients who received EVT, patients who underwent Direct Triage were more likely to have better functional outcomes at 90 days. Direct Triage of AIS patients is a promising strategy to improve clinical outcomes in patients who undergo EVT. More research is needed in patients who do not receive EVT.

Objective: The aim of the study was to model the effect of prehospital triage of emergent large vessel occlusion (ELVO) to endovascular capable center (ECC) on the timing of thrombectomy and intravenous (IV) thrombolysis using real-world data from a multihospital system. Methods: We selected a cohort of 77 consecutive stroke patients who were brought by emergency medical services (EMS) to a nonendovascular capable center and then transferred to an ECC for mechanical thrombectomy (MT) (“actual” drip and ship [DS] cohort). We created a hypothetical scenario (bypass model [BM]), modeling transfer of the patients directly to an ECC, based on patients’ initial EMS pickup address and closest ECC. Using another cohort of 73 consecutive patients, who were brought directly to an ECC by EMS and underwent endovascular intervention, we calculated mean door-to-needle and door-to-arterial puncture (AP) times (“actual” mothership [MS] cohort). Timings in the actual MS cohort and the actual DS cohort were compared to timings from the BM cohort. Results: Median first medical contact (FMC) to IV thrombolysis time was 87.5 min (interquartile range [IQR] = 38) for the DS versus 78.5 min (IQR = 8.96) for the BM cohort, with p = 0.1672. Median FMC to AP was 244 min (IQR = 97) versus 147 min (IQR = 8.96) (p < 0.001), and median FMC to TICI 2B+ time was 299 min (IQR = 108.5) versus 197 min (IQR = 8.96) (p < 0.001) for the DS versus BM cohort, respectively. Conclusions: Modeled EMS prehospital triage of ELVO patients’ results in shorter MT times without a change in thrombolysis times. As triage tools increase in sensitivity and specificity, EMS triage protocols stand to improve patient outcomes.

Background At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient’s microbiome through multiple confounders. Methods To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). Results In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. Conclusions In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

The human microbiome constitutes a complex multikingdom community that symbiotically interacts with the host across multiple body sites. Host-microbiome interactions impact multiple physiological processes and a variety of multifactorial disease conditions. In the past decade, microbiome communities have been suggested to influence the development, progression, metastasis formation, and treatment response of multiple cancer types. While causal evidence of microbial impacts on cancer biology is only beginning to be unraveled, enhanced molecular understanding of such cancer-modulating interactions and impacts on cancer treatment are considered of major scientific importance and clinical relevance. In this review, we describe the molecular pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer. We highlight advances, limitations, challenges, and prospects in understanding how the microbiome may causally impact cancer and its treatment responsiveness, and how microorganisms or their secreted bioactive metabolites may be potentially harnessed and targeted as precision cancer therapeutics.

Background and Purpose: Despite the Joint Commission’s certification requirement of ≥15 stroke thrombectomy (ST) cases per center and proceduralist annually, the relationship between ST case volumes and outcomes is uncertain. We sought to determine whether a proceduralist or hospital volume threshold exists that is associated with better outcomes among Medicare beneficiaries. Methods: Retrospective cohort study using validated International Classification of Diseases, Tenth Revision , Clinical Modification codes to identify admissions with acute ischemic stroke and treatment with ST. We used de-identified, national 100% inpatient Medicare data sets from January 1, 2016, to December 31, 2017 for US individuals aged ≥65 years. We calculated total procedures by proceduralist and hospital. We performed adjusted logistic regression of total cases as a predictor of inpatient mortality, good outcome (defined by dichotomized discharge disposition of inpatient rehabilitation or better), and 30-day readmission. We adjusted for sex, age, Charlson Comorbidity Index, availability of neurocritical care, teaching hospital status, socioeconomic status, 2-year stroke volume, and urban versus rural hospital location. We dichotomized case numbers incrementally to determine a volume threshold for better outcomes. Results: Thirteen thousand three hundred thirty-five patients were treated with ST by 2754 proceduralists at 641 hospitals. For every 10 more proceduralist cases, patients had 4% lower adjusted odds of inpatient mortality (adjusted odds ratio, 0.96 [95% CI, 0.95–0.98], P P P =0.0003) and 2% greater odds of good outcome (adjusted odds ratio, 1.02 [95% CI, 1.01–1.02], P Conclusions: Nationally, higher proceduralist and hospital ST case volumes were associated with reduced inpatient mortality and better outcome. These data support volume requirements in guidelines for ST training and certification.

Background and Purpose: Risk of 30-day stroke readmission has been attributed to medical comorbidities, stroke severity, and hospitalization metrics. The leading etiologies appear to vary across institutions and remain a moving target. We hypothesized that patients with increased medical complexity have higher odds of 30-day readmission and the immediate time after discharge may be most vulnerable. We aimed to characterize patients with 30-day readmission after acute ischemic stroke (IS) and identify predictors of post-IS readmission. Methods: We performed a retrospective case-control study analyzing post-IS 30-day readmission between January 2016-December 2019 using data from Mount Sinai Hospital’s Get With The Guidelines database. We performed chi square analyses and multivariate adjusted logistic regression model including age, sex, coronary artery disease (CAD), renal insufficiency (RI), history of prior stroke or TIA, length of stay (LOS) > 7, and NIHSS ≥ 5. Results: 6.7% (n = 115) of 1,706 IS encounters had 30-day readmission. The 115 cases were compared to 1,591 controls without 30-day readmission. In our adjusted model, CAD (OR = 1.7, p = 0.01), history of prior stroke or TIA (OR = 1.6, p = 0.01), LOS >7 (OR = 1.7, p = 0.02), and NIHSS ≥ 5 (OR = 4.5, p < 0.001) predicted 30-day readmission. 65% (n = 75) of readmitted patients had readmission within 14 days post-discharge. Conclusions: Patients with post-IS 30-day readmission were more likely to have complex medical comorbidities and history of stroke or TIA compared to controls. Patients with more severe stroke and longer LOS may benefit from individualized transition of care plans and closer follow up during the vulnerable 30-day post-stroke period.

Cardiac autonomic dysfunction in idiopathic Parkinson’s disease (PD) manifests as reduced heart rate variability (HRV). In the present study, we explored the deceleration capacity of heart rate (DC) in patients with idiopathic PD, an advanced HRV marker that has proven clinical utility. Standard and advanced HRV measures derived from 7-min electrocardiograms in 20 idiopathic PD patients and 27 healthy controls were analyzed. HRV measures were compared using regression analysis, controlling for age, sex, and mean heart rate. Significantly reduced HRV was found only in the subcohort of PD patients older than 60 years. Low- frequency power and global HRV measures were lower in patients than in controls, but standard beat-to-beat HRV markers (i.e., rMSSD and high-frequency power) were not significantly different between groups. DC was significantly reduced in the subcohort of PD patients older than 60 years compared to controls. Deceleration-related oscillations of HRV were significantly reduced in the older PD patients compared to healthy controls, suggesting that short-term DC may be a sensitive marker of cardiac autonomic dysfunction in PD. DC may be complementary to traditional markers of short-term HRV for the evaluation of autonomic modulation in PD. Further study to examine the association between DC and cardiac adverse events in PD is needed to clarify the clinical relevance of DC in this population.

RATIONALE Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD. OBJECTIVES We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing. RESULTS Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P

BACKGROUND Belantamab mafodotin (belamaf) has demonstrated clinically meaningful antimyeloma activity in patients with heavily pretreated multiple myeloma. However, the drug is highly active against dividing cells, which contributes to off-target adverse events, particularly ocular toxicity. Investigators or providers routinely use changes in best corrected visual acuity (BCVA) and corneal examination findings to determine Keratopathy Visual Acuity (KVA) grade to inform belamaf dose modification. We sought to model and translate the complexity of the ophthalmologic examination using the KVA scale into a mobile application that is easily applicable to patients presenting with ocular toxicities. OBJECTIVE We aimed to develop a semiautomated mobile app to facilitate the grading of ocular events in clinical trials involving belamaf. METHODS The paper process was semiautomated by creating a library of finite-state automaton (FSA) models to represent all permutations of KVA grade changes between baseline and current BCVA readings. The transition states in the FSA models operated independently of eye measurement units (eg, Snellen, logMAR, decimal) and provided a uniform approach to determining KVA grade changes. Together with the FSA, the complex decision tree for determining the grade change based on corneal examination findings was converted into logical statements that provide accurate and efficient computation of the overall KVA grade. First, a web-based user interface, conforming to clinical practice settings, was developed to simplify the input of key criteria for overall KVA grading. Subsequently, a mobile app was developed that included additional guided steps to assist in clinical decision-making. RESULTS The app underwent a robust Good Clinical Practice validation process in alignment with GSK standard operating procedures, and the outcomes were reviewed by key stakeholders, our medical lead for belamaf, and the systems integration team. The time to compute a patient’s overall KVA grade using the Belamaf Eye Exam (BEE) app was reduced from a 20- to 30-minute process to less than 1 to 2 minutes using our semiautomated KVA computational framework. The BEE app was well received, with most investigators surveyed selecting “satisfied” or “highly satisfied” for its accuracy and time efficiency. Based on current US Food and Drug Administration and EU standards, the BEE app is considered a nondevice clinical decision support software. CONCLUSIONS We conclude that our semiautomated approach provides for an accurate, simplified method of assessment of patients’ corneal status that reduces the number of potential errors and more quickly delivers information critical for potential belamaf dose modifications related to ocular changes. The app is currently available on the Apple iOS and Android platforms for use by investigators of the DREAMM clinical trials. Moreover, this mobile app could extend to the clinic as a tool to support healthcare providers in making informed belamaf treatment decisions for their patients.

ObjectiveWe sought to comprehensively evaluate predictors of poststroke depression (PSD) in the United States and to compare PSD to post–myocardial infarction (MI) depression to determine whether ischemic stroke uniquely elevates risk of depression.MethodsThis is a retrospective cohort study of 100% deidentified inpatient, outpatient, and subacute nursing Medicare data from 2016 to 2017 for US patients ≥65 years of age from July 1, 2016, to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression up to 1.5 years after the index admission. We performed Cox regression to report the hazard ratio for diagnosis of depression up to 1.5 years after stroke vs MI and independent predictors of PSD, and we controlled for patient demographics, comorbid conditions, length of stay, and acute stroke interventions.ResultsIn fully adjusted models, patients with stroke (n = 174,901) were ≈50% more likely than patients with MI (n = 193,418) to develop depression during the 1.5-year follow-up period (Kaplan-Meier cumulative risk 0.1596 ± 0.001 in patients with stroke vs 0.0973 ± 0.000778 in patients with MI, log-rank p < 0.0001). History of anxiety was the strongest predictor of PSD, while discharge home was most protective. Female patients, White patients, and patients ConclusionsDespite the similarities between MI and stroke, patients with stroke were significantly more likely to develop depression. There were several predictors of PSD, most significantly history of anxiety. Our findings lend credibility to a stroke-specific process causing depression and highlight the need for consistent depression screening in all patients with stroke.

BackgroundAlthough national organizations recognize the importance of regionalized acute ischemic stroke (AIS) care, data informing expansion are sparse. We assessed real-world regional variation in emergent AIS treatment, including growth in revascularization therapies and stroke center certification. We hypothesized that we would observe overall growth in revascularization therapy utilization, but observed differences would vary greatly regionally.MethodsA retrospective cross-sectional analysis was carried out of de-identified national inpatient Medicare Fee-for-Service datasets from 2016 to 2019. We identified AIS admissions and treatment with thrombolysis and endovascular thrombectomy (ET) with International Classification of Diseases, 10th Revision, Clinical Modification codes. We grouped hospitals in Dartmouth Atlas of Healthcare Hospital Referral Regions (HRR) and calculated hospital, demographic, and acute stroke treatment characteristics for each HRR. We calculated the percent of hospitals with stroke certification and AIS cases treated with thrombolysis or ET per HRR.ResultsThere were 957 958 AIS admissions. Relative mean (SD) growth in percent of AIS admissions receiving revascularization therapy per HRR from 2016 to 2019 was 13.4 (31.7)% (IQR −6.1–31.7%) for thrombolysis and 28.0 (72.0)% (IQR 0–56.0%) for ET. The proportion of HRRs with decreased or no difference in ET utilization was 38.9% and the proportion of HRRs with decreased or no difference in thrombolysis utilization was 32.7%. Mean (SD) stroke center certification proportion across HRRs was 45.3 (31.5)% and this varied widely (IQR 18.3–73.4%).ConclusionsOverall growth in AIS treatment has been modest and, within HRRs, growth in AIS treatment and the proportion of centers with stroke certification varies dramatically.

Few studies have examined associations of public library use and shared book reading to kindergarten children’s academic skills.The study sample consisted of 13,385 kindergarten students enrolled i...

Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its associations with symptom burden, nutrition, chemotherapy pharmacokinetics (PK), and the oral microbiome.We conducted a single-center, prospective feasibility study (NCT03276481) of patients with multiple myeloma undergoing auto-HCT. CG was performed longitudinally testing five flavors (sweet, sour, salty, bitter, umami) to calculate a total taste score (maximum score, 30). We measured caloric intake and patient-reported symptoms, assessing their correlation with oral microbiota composition and salivary and blood melphalan PK exposure.Among all 45 patients, 39 (87%) completed at least four (60%) and 22 (49%) completed all six CG assessments. Median total CG scores remained stable over time but were lowest at day +7 (27, range 24-30) with recovery by day +100. Symptom burden was highest by day +10 (area under the curve, 2.9; range, 1.0-4.6) corresponding with the lowest median overall caloric intake (1624 kcal; range, 1345-2267). Higher serum/salivary melphalan levels correlated with higher patient-reported dysgeusia and lower caloric intake. Oral microbiota α-diversity was stable early and increased slightly by day +100.Assessment of dysgeusia by CG is feasible after auto-HCT. Most dysgeusia, symptom burden, and lowest caloric intake occurred during the blood count nadir. Higher melphalan concentrations correlated with more dysgeusia and poorer caloric intake. Future studies will aim to modulate melphalan exposure by PK-targeted dosing and characterize patient taste preferences to personalize diets for improved nutritional intake.Taste changes after cancer treatments are very common. We used chemical gustometry (taste testing) to study taste changes and to better understand why patients with multiple myeloma experience this symptom after autologous hematopoietic cell transplantation. We found that taste testing was feasible, taste changes peaked when blood counts were lowest, and most patients recovered their taste by 100 days after transplantation. Taste changes correlated with lower food intake and with higher levels of chemotherapy in the body. Future work will focus on using personalized chemotherapy doses to reduce taste changes and to match patients' individual taste preferences with their diets.

Suicide and depression among orthopaedic surgeons have recently emerged as rising concerns. Prior research has suggested that orthopaedic surgeons have the highest prevalence of suicide among surgical specialties. We sought to determine the factors associated with depression and suicidal ideation (SI) in orthopaedics, including subspecialty.A survey including demographic questions, the Beck Depression Inventory, and the Columbia-Suicide Severity Rating Scale was administered electronically via a listserv to the orthopaedic subspecialties of trauma, adult reconstruction, hand and upper extremity, shoulder and elbow, foot and ankle, spine, pediatrics, sports medicine, and oncology. The responses were quantified according to previously published criteria. The associations of demographic factors, training, and current practice environment with depression and suicidality were assessed using Fisher exact tests. Reverse stepwise multivariable logistic regression models were developed to identify factors associated with depression and SI.The responses were obtained from 661 board-certified, practicing orthopaedic surgeons. In this study, 156 surgeons (23.6%) endorsed some level of active SI in their lifetime, 200 surgeons (30.3%) reported either active or passive SI in their lifetime, and 33 surgeons (5%) reported that, on at least 1 occasion in their lifetime, they had experienced active SI with a specific plan and intention to harm themselves. Gender, relationship status, having children, and residency and/or current practice region were significantly associated with depression and/or SI. Younger age, divorce, adult reconstruction and foot and ankle subspecialties, and attending residency in the Western U.S. were found on multivariable testing to be associated with symptoms of depression and SI (odds ratios, 1.03 [per 1-year decrease in age] to 8.28).Symptoms of depression and suicidality are not uncommon among orthopaedic surgeons, and variation by gender, relationship status, and geographic location are supported by prior research. Based on our results, depression and/or SI likely affect someone close to you or someone with whom you work. The normalization of discussions surrounding emotional well-being, depression, and SI is imperative.

OBJECTIVE The autonomic nervous system (ANS) innervates pancreatic endocrine cells, muscle, and liver, all of which participate in glucose metabolism. We tested whether measures of cardiovascular ANS function are independently associated with incident diabetes and annual change in fasting glucose (FG) levels as well as with insulin secretion and insulin sensitivity in older adults without diabetes. RESEARCH DESIGN AND METHODS Heart rate (HR) and measures of HR variability (HRV) were derived from 24-h electrocardiographic monitoring. Blood pressure, seated and standing, was measured. Cox proportional hazards models and linear mixed models were used to analyze the associations between HRV, HR, and orthostatic hypotension (SBP >20 mmHg decline) and incident diabetes or longitudinal FG change. RESULTS The mean annual unadjusted FG change was 1 mg/dL. Higher detrended fluctuation analyses (DFA) values, averaged over 4–11 (DFA1) or 12–20 beats (DFA2)—reflecting greater versus less organization of beat-to-beat intervals—were associated with less FG increase over time (per 1-SD increment: DFA1: −0.49 mg/dL/year [−0.96, −0.03]; DFA2: −0.55 mg/dL/year [−1.02, −0.09]). In mutually adjusted analyses, higher SD of the N-N interval (SDNN) was associated with less FG increase over time (per 1-SD increment: SDNN: −0.62 mg/dL/year [−1.22, −0.03]). Higher values of DFA1, DFA2, and SDNN were not significantly associated with insulin secretion, insulin sensitivity, or incident diabetes. We observed no association of HR or orthostatic hypotension with diabetes or FG change. CONCLUSIONS Specific measures of cardiac autonomic function are prospectively related to FG level changes.

Objectives This study compares outcomes for patients with displaced femoral neck fractures undergoing hemiarthroplasty (HA) or total hip arthroplasty (THA) by surgeons of different fellowship training. Design Retrospective review of HEALTH trial data. Setting Eighty clinical sites across 10 countries. Patients/participants One thousand four hundred forty-one patients ≥50 years with low-energy hip fractures requiring surgical intervention. Intervention Patients were randomized to either HA or THA groups in the initial data set. Surgeons' fellowship training was ascertained retrospectively, and outcomes were compared. Main outcome measurements The main outcome was an unplanned secondary procedure at 24 months. Secondary outcomes included death, serious adverse events, prosthetic joint infection (PJI), dislocation, discharge disposition, and use of ambulatory devices postoperatively. Results There was a significantly higher risk of PJI in patients treated by surgeons without fellowship training in arthroplasty (P = 0.01), surgeons with unknown fellowship training (P = 0.03), and surgeons with no fellowship training (P = 0.02) than those treated by an arthroplasty-trained surgeon. There were significantly higher odds of being discharged to a facility rather than home in patients who underwent surgery by a surgeon with no fellowship training compared with arthroplasty-fellowship-trained surgeons (P = 0.03). Conclusions Arthroplasty for hip fracture can be performed by all orthopaedic surgeons with equivalent reoperation rates. Infection prevention strategies and use of "care pathways" by arthroplasty-fellowship-trained surgeons may account for the lower risk of PJI and higher rate of discharge to home. The authors advocate for the use of evidence-based infection prevention initiatives and standardized care pathways in this patient population. Level of evidence Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

BRAF mutations are relatively common in many cancers, particularly melanoma, colorectal cancer, and thyroid cancer and to a lesser extent in lung cancer. These mutations can be targeted by BRAF and MEK inhibitors, which exhibit good clinical activity. There are conflicting reports of the various relative rates of BRAF Class I mutations (V600 locus), defined as those that exhibit extremely strong kinase activity by stimulating monomeric activation of BRAF, Class II, define as non-V600 mutations that activate BRAF to signal as a RAS-independent dimer, and Class III mutations, defined as “kinase-dead” with low kinase activity as compared to wild type BRAF. Prospective studies have largely focused on patients with tumors harboring Class I BRAF mutations (limited to the V600 locus) where response rates up to 70% with BRAF plus MEK inhibition have been demonstrated. We report on the relative prevalence of various types of BRAF mutations across human cancers in a cohort of 114,662 patients that received comprehensive genomic profiling using next-generation sequencing. Of these patients, 4517 (3.9%) a pathogenic or presumed pathogenic BRAF mutation (3.9%). Of these, 1271 were seen in melanoma, representing 39.7% of all melanomas sequenced, representing the highest rate in all tumors. Class I (V600) mutations were seen overall in 2841 patients (62.1% of BRAF mutations, 2.4% of total cancers). Class II mutations were seen in 746 tumors (16.5% of BRAF mutant, 0.7% of total), and Class III mutations were seen in 801 tumors (17.7% of BRAF, 0.7% of total). Knowledge of the relative prevalence of these types of mutations can aid in the development of agents that might better address non-V600 mutations in cancer. Impact statement These data represent the largest aggregation of BRAF mutations within a single clinical database to our knowledge. The relative proportions of both BRAF V600 mutations and non-V600 mutations are informative in all cancers and by malignancy, and can serve as a definitive gold-standard for BRAF mutation cancer incidence by malignancy. The rate of BRAF mutation in human cancer in a real-world large database is lower than previously reported likely representing testing more broadly across tumor types. The relative percentages of Class II and Class III BRAF mutations are higher than previously reported, representing almost 35% of BRAF mutations in cancer. These findings provide support for the development of effective treatments for non-V600 BRAF mutations in cancer.

Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR)30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population.The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679).A total of 93 patients with GFR30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%).Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir.In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.

Objectives: With expanding coverage of gender-affirming care in the United States, many insurers default to the World Professional Association for Transgender Health (WPATH) Standards of Care 7 (SOC 7) to establish eligibility requirements for surgery coverage. Informed by bariatric and transplant surgery evaluation models, the Mount Sinai Center for Transgender Medicine and Surgery (CTMS) developed patient-centered criteria to assess readiness for surgery, focusing on concerns that could impair recovery. To make recommendations for the next version of the WPATH SOC, SOC 8, we compared Mount Sinai patient-centered surgical readiness criteria with the WPATH SOC 7 criteria. Methods: Data were extracted from a deidentified data set developed as part the quality dashboard for CTMS. The data set included all patients seeking vaginoplasty who were evaluated by a single mental health provider, from July 2016 through August 2018, and who completed the full CTMS assessment. The number of patients eligible for surgery based on the Mount Sinai CTMS criteria was compared with the number of patients eligible for surgery according to WPATH SOC 7 criteria. Results: Of 139 patients identified, 63 (45%) were ready for surgery immediately based on the Mount Sinai patient-centered model. By contrast, only 21 (15%) out of the 139 met criteria for surgery based on WPATH SOC 7. Fifty patients (40%) were ready for surgery as per Mount Sinai patient-centered readiness review but not WPATH criteria. Conclusion: An assessment designed to better prepare patients for surgery may also result in fewer barriers to care than existing criteria used by insurance companies in the United States.