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Introduction Increased fiber intake has been associated with decreased breast cancer risk, while increased animal protein intake with increased risk. The objective of this study is to examine the relationship of dietary fiber and protein intake to estrogen and sex hormone–binding globulin (SHBG) concentrations at puberty onset. Methods These analyses were conducted using the Cincinnati puberty cohort of the Breast Cancer and the Environment Research Program, with girls followed every 6 months from ages 6 and 7. The analyses included serum measurements at 6-month intervals for estrogen and SHBG concentrations, from 18 months prior to breast stage 2 (onset of puberty). Dietary intake was documented via 24-hour dietary recalls every 3 months. Dietary factors of interest included total energy intake; total and animal protein; total, soluble, and insoluble fiber; and lignan and flavanol intake. Results This study included 260 participants who generated 871 serum specimens and 3,000 days of diet intake. In longitudinal models, estradiol was associated inversely with insoluble fiber intake; estrone positively with animal protein intake; SHBG with greater insoluble fiber and lower total protein intake; and ratio of estrone to SHBG, a measure of bioavailable estrogen, positively with animal protein. Conclusions Greater protein intake, especially animal protein, led to greater estrogen concentrations and lower SHBG; greater animal protein and greater caloric intake led to increased bioavailable estrogen. This relationship may have served an evolutionary advantage in the past for greater fertility with adequate high-quality protein; in contemporary women, a modest decrease in animal protein may be beneficial in reducing breast cancer risk.

Context Psychological distress is highly prevalent among patients with chronic obstructive pulmonary disease (COPD), the top palliative care priority identified by such patients, and associated with poor outcomes. However, patients with COPD rarely receive care for psychological distress. Objectives To identify the barriers and opportunities to reducing psychological distress among patients with COPD in the specialty pulmonary setting. Methods We conducted semi-structured interviews based on Consolidated Framework for Implementation Research constructs with key stakeholders at two pulmonary clinics, including clinicians, staff, patients, and caregivers. We focused on the relevance, identification, and management of psychological distress in COPD care. We identified emergent patterns and concepts, developed and applied codes to the text, and examined the content in each code to identify key themes. Results Thirty-one stakeholders participated in interviews (RR=64.6%). Nearly all pulmonary clinicians felt that psychological well-being was a critical, unmet patient need. Yet, most pulmonary clinicians reported that they lacked sufficient training and available resources to support patients, prioritized physical symptoms and medication management over emotional concerns, and perceived limited cultural support for such efforts in the pulmonary clinic setting. Patient and caregiver participants desired integration and prioritization of care addressing psychological distress into routine pulmonary care. Conclusion Mitigating psychological distress is a palliative care priority in COPD. Integrating efficient, effective resources, such as tools or programs that address psychological distress, into pulmonary clinic settings serving a high volume of patients with COPD may improve the provision of supportive care to patients typically underserved by specialty palliative care.

OBJECTIVE Microsurgical resection of arteriovenous malformations (AVMs) can be aided by staged treatment consisting of stereotactic radiosurgery followed by resection in a delayed fashion. This approach is particularly useful for high Spetzler-Martin (SM) grade lesions because radiosurgery can reduce flow through the AVM, downgrade the SM rating, and induce histopathological changes that additively render the AVM more manageable for resection. The authors present their 28-year experience in managing AVMs with adjunctive radiosurgery followed by resection. METHODS The authors retrospectively reviewed records of patients treated for cerebral AVMs at their institution between January 1990 and August 2019. All patients who underwent stereotactic radiosurgery (with or without embolization), followed by resection, were included in the study. Of 1245 patients, 95 met the eligibility criteria. Univariate and multivariate regression analyses were performed to assess relationships between key variables and clinical outcomes. RESULTS The majority of lesions treated (53.9%) were high grade (SM grade IV–V), 31.5% were intermediate (SM grade III), and 16.6% were low grade (SM grade I–II). Hemorrhage was the initial presenting sign in half of all patients (49.5%). Complete resection was achieved among 84% of patients, whereas 16% had partial resection, the majority of whom received additional radiosurgery. Modified Rankin Scale (mRS) scores of 0–2 were achieved in 79.8% of patients, and 20.2% had poor (mRS scores 3–6) outcomes. Improved (44.8%) or stable (19%) mRS scores were observed among 63.8% of patients, whereas 36.2% had a decline in mRS scores. This includes 22 patients (23.4%) with AVM hemorrhage and 6 deaths (6.7%) outside the perioperative period but prior to AVM obliteration. CONCLUSIONS Stereotactic radiosurgery is a useful adjunct in the presurgical management of cerebral AVMs. Multimodal therapy allowed for high rates of AVM obliteration and acceptable morbidity rates, despite the predominance of high-grade lesions in this series of patients.

Background Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. Methods We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Results Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p=0.01) and with mechanical ventilator (r =0.45, p=0.002), ICU (r=0.44, p=0.002), and hospital days (r = 0.37, p=0.001) in influenza infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p=0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. Conclusions SP-D has potential as an early circulating biomarker reflecting degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance. This article is protected by copyright. All rights reserved.

Uterine transplant (UTx) is performed to address absolute uterine infertility in the presence of uterine agenesis, a non-functional uterus, or following a prior hysterectomy. Following the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an "experimental procedure" to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.

Diminished bone perfusion develops in response to disuse and has been proposed as a mechanism underlying bone loss. Bone blood flow (BF) has not been investigated within the unique context of severe contusion spinal cord injury (SCI), a condition that produces neurogenic bone loss that is precipitated by disuse and other physiological consequences of central nervous system injury. Herein, 4-mo-old male Sprague–Dawley rats received T(9) laminectomy (SHAM) or laminectomy with severe contusion SCI (n = 20/group). Time course assessments of hindlimb bone microstructure and bone perfusion were performed in vivo at 1- and 2-wk postsurgery via microcomputed tomography (microCT) and intracardiac microsphere infusion, respectively, and bone turnover indices were determined via histomorphometry. Both groups exhibited cancellous bone loss beginning in the initial postsurgical week, with cancellous and cortical bone deficits progressing only in SCI thereafter. Trabecular bone deterioration coincided with uncoupled bone turnover after SCI, as indicated by signs of ongoing osteoclast-mediated bone resorption and a near-complete absence of osteoblasts and cancellous bone formation. Bone BF was not different between groups at 1 wk, when both groups displayed bone loss. In comparison, femur and tibia perfusion was 30%–40% lower in SCI versus SHAM at 2 wk, with the most pronounced regional BF deficits occurring at the distal femur. Significant associations existed between distal femur BF and cancellous and cortical bone loss indices. Our data provide the first direct evidence indicating that bone BF deficits develop in response to SCI and temporally coincide with suppressed bone formation and with cancellous and cortical bone deterioration. NEW & NOTEWORTHY We provide the first direct evidence indicating femur and tibia blood flow (BF) deficits exist in conscious (awake) rats after severe contusion spinal cord injury (SCI), with the distal femur displaying the largest BF deficits. Reduced bone perfusion temporally coincided with unopposed bone resorption, as indicated by ongoing osteoclast-mediated bone resorption and a near absence of surface-level bone formation indices, which resulted in severe cancellous and cortical microstructural deterioration after SCI.

OBJECTIVEReports on basal ganglia cavernous malformations (BGCMs) are rare. Here, the authors report on their experience in resecting these malformations to offer insight into this infrequent disease subtype.METHODSThe authors retrospectively reviewed a prospectively managed departmental database of all deep-seated cerebral cavernous malformations (CCMs) treated at Stanford between 1987 and 2019 and included for further analysis those with a radiographic diagnosis of BGCM. Moreover, a systematic literature review was undertaken using the PubMed and Web of Science databases.RESULTSThe departmental database search yielded 331 patients with deep-seated CCMs, 44 of whom had a BGCM (13.3%). Headache was the most common presenting sign (53.5%), followed by seizure (32.6%) and hemiparesis (27.9%). Lesion location involved the caudate nucleus in 21.4% of cases compared to 78.6% of cases within the lentiform nucleus. Caudate BGCMs were larger on presentation and were more likely to present to the ependymal surface (p < 0.001) with intraventricular hemorrhage and hydrocephalus (p = 0.005 and 0.007, respectively). Dizziness and diplopia were also more common with lesions involving the caudate. Because of their anatomical location, caudate BGCMs were preferentially treated via an interhemispheric approach and were less likely to be associated with worsening perioperative deficits than lentiform BGCMs (p = 0.006 and 0.045, respectively). Ten patients (25.6%) were clinically worse in the immediate postoperative period, 4 (10.2%) of whom continued to suffer permanent morbidity at the last follow-up. A long-term good outcome (modified Rankin Scale [mRS] score 0–1) was attained in 74.4% of cases compared to the 69.2% of patients who had presented with an mRS score 0–1. Relative to their presenting mRS score, 89.8% of patients had an improved or unchanged status at the last follow-up. The median postoperative follow-up was 11 months (range 1–252 months). Patient outcomes after resection did not differ among surgical approaches; however, patients presenting with hemiparesis and lesions involving the globus pallidus or posterior limb of the internal capsule were more likely to suffer neurological deficits during the immediate perioperative period. Patients who had undergone awake surgeries were more likely to suffer neurological decline at the early as well as the late follow-up. When adjusting for awake craniotomy as a potential confounder of lesion location, a BGCM involving the posterior limb was predictive of developing early postoperative deficits, but this finding did not persist at the long-term follow-up.CONCLUSIONSSurgery is a safe and effective treatment modality for managing BGCMs, with an estimated long-term permanent morbidity rate of around 10%.

The opioid crisis is a national health emergency with immense morbidity, mortality, and socioeconomic cost. Emergency department (ED) pain management is tightly linked to the issue of opioid use disorder (OUD), because opioid exposure is necessary for development of OUD. Emergency nurses are on the frontlines of this complex problem, yet little, if any, attention has been paid to the role they play in the prevention and management of either pain or OUD in this unique and important setting. A framework that conceptualizes and optimizes emergency nurses as change agents in the opioid epidemic is urgently needed. While ED pain management and OUD prevention is dependent on the entire care team, this innovative study qualitatively characterizes emergency nurse perceptions of pain management, OUD prevention, and their potential role in each. Content analysis produced 14 categories that were clustered into two themes, “nurses influence ED pain management” and “adjustments in ED pain management”, and an overarching message that “pain management depends on the care team.” By generating a more comprehensive and nuanced understanding of the role played by emergency nurses, our findings provide essential insights into potential interventions and frameworks.

Summary Background & aims Weight loss in older adults enhances physical function, but may lead to sarcopenia and osteoporosis. Whey protein is a low cost rich source of essential amino acids, may improve physical function. We evaluated the feasibility and acceptability of consuming whey protein in the context of a weight-loss intervention in older adults with obesity. Methods A 12-week pilot feasibility, non-randomized weight loss study of 28 older adults was conducted, consisting of individualized, weekly dietitian visits with twice weekly physical therapist-led group strengthening classes. Half consumed whey protein, three times weekly, following exercise. Preliminary efficacy measures of body composition, sit-to-stand, 6-min walk and grip strength and subjective measures of self-reported health and function were also evaluated. Results Of the 37 enrolled, 28 completed the study (50 % in the protein group). Attendance rates for protein vs. non-protein groups were 89.9 ± 11.1 % vs. 95.6 ± 3.4 % (p = 0.08). Protein consumption was high in those attending classes (90.3 %) as was compliance at home (82.6 %). Whey was pleasant (67.3 ± 22.1, range 30–100, above average), had little aftertaste, and was neither salty or sticky. All were compliant (0.64 ± 0.84, range 0–5, low = higher compliance). Both groups lost significant weight (protein vs. no protein, −3.45 ± 2.86 vs. −5.79 ± 3.08, p = 0.47); Sit-to-stand, 6-min walk, and gait speed were no different, grip strength was improved in the protein compared to the non-protein group (−2.63 kg vs. 4.29 kg; p Conclusions Our results suggest that whey protein is a low-cost and readily available nutritional supplement that can be integrated into a weight loss intervention.

A mortality event among recently captured feral donkeys ( Equus asinus) occurred in south-central Utah in 2016. The deaths were sporadic, and clinical signs were indicative of respiratory disease, likely associated with an infectious etiology. Ten of 13 donkeys autopsied had moderate-to-severe interstitial fibrosing pneumonia, and one had pyogranulomatous pneumonia. Consensus PCRs directed toward the DNA polymerase and DNA packaging terminase subunit 1 for herpesviruses were performed followed by sequencing of the PCR amplicons and phylogenetic analysis. Asinine herpesvirus 4 (AsHV4) and 5 (AsHV5) were consistently identified in lung tissues of affected donkeys. No other herpesviruses were identified, and herpesviral DNA was not detected in lung tissues of 2 donkeys without evidence of respiratory disease. The detection of asinine gammaherpesviruses may have been associated with the lesions described. AsHV4 and AsHV5 have been reported in previous studies as novel gammaherpesviruses based on sequences obtained from donkeys with interstitial pneumonia and marked syncytial cell formation. Our findings suggest that the association of asinine gammaherpesviruses with respiratory conditions in equids deserves further attention.

BACKGROUND CONTEXT Despite increased awareness of the ongoing opioid epidemic, opioid and benzodiazepine use remain high after spine surgery. In particular, long-term co-prescription of opioids and benzodiazepines have been linked to high risk of overdose-associated death. Tumor patients represent a unique subset of spine surgery patients and few studies have attempted to develop predictive models to anticipate long-term opioid and benzodiazepine use after spinal tumor resection. METHODS The IBM Watson Health MarketScan Database and Medicare Supplement were assessed to identify admissions for intradural tumor resection between 2007 and 2015. Adult patients were required to have at least 6 months of continuous preadmission baseline data and 12 months of continuous postdischarge follow-up. Primary outcomes were long-term opioid and benzodiazepine use, defined as at least 6 prescriptions within 12 months. Secondary outcomes were durations of opioid and benzodiazepine prescribing. Logistic regression models, with and without regularization, were trained on an 80% training sample and validated on the withheld 20%. RESULTS A total of 1,942 patients were identified. The majority of tumors were extramedullary (74.8%) and benign (62.5%). A minority of patients received arthrodesis (9.2%) and most patients were discharged to home (79.1%). Factors associated with postdischarge opioid use duration include tumor malignancy (vs benign, B=19.8 prescribed-days/year, 95% confidence interval [CI] 1.1–38.5) and intramedullary compartment (vs extramedullary, B=18.1 prescribed-days/year, 95% CI 3.3–32.9). Pre- and perioperative use of prescribed nonsteroidal anti-inflammatory drugs and gabapentin/pregabalin were associated with shorter and longer duration opioid use, respectively. History of opioid and history of benzodiazepine use were both associated with increased postdischarge opioid and benzodiazepine use. Intramedullary location was associated with longer duration postdischarge benzodiazepine use (B=10.3 prescribed-days/year, 95% CI 1.5–19.1). Among assessed models, elastic net regularization demonstrated best predictive performance in the withheld validation cohort when assessing both long-term opioid use (area under curve [AUC]=0.748) and long-term benzodiazepine use (AUC=0.704). Applying our model to the validation set, patients scored as low-risk demonstrated a 4.8% and 2.4% risk of long-term opioid and benzodiazepine use, respectively, compared to 35.2% and 11.1% of high-risk patients. CONCLUSIONS We developed and validated a parsimonious, predictive model to anticipate long-term opioid and benzodiazepine use early after intradural tumor resection, providing physicians opportunities to consider alternative pain management strategies.

Objective Expert consensus increasingly recognizes intensive multidisciplinary intervention (IMI) as the standard of care to address chronic and severe feeding problems in pediatric populations. In this study, we examined the clinical presentation, intervention characteristics, and treatment outcomes for young children receiving IMI for avoidant restrictive rood intake disorder (ARFID) involving nutritional insufficiencies associated with severe food selectivity. Method We followed the Strengthening the Reporting of Observational Studies in Epidemiology statement to conduct this retrospective chart review. The review focused on consecutive patients (birth to age 21 years) admitted to the IMI program over a 5-year period (June 2014 to June 2019). Inclusion criteria required micronutrient insufficiencies (vitamins A, B12, C, D, E; folic acid; calcium; iron; and zinc) and chronic mealtime refusal behavior (e.g., turning head away from food/spoon, pushing or throwing spoon, crying, screaming, and leaving the table) associated with severe food selectivity. Results Over the 5-year period, 63 of the patients met study entry requirements. Of these, 60 patients (50 boys and 10 girls; mean age = 72 ± 39 months; range = 23-181) completed intervention (95% treatment completion rate). At discharge, dietary diversity improved by 16 new therapeutic foods (range: 8-22), rapid acceptance and swallowing of new foods exceeded clinical benchmarks (80% or > bites), and risk for nutritional inadequacies declined for this patient cohort. Discussion Results of the current study support the benefits of IMI to increase dietary variety, improve mealtime behaviors, and enhance nutritional intake for children with ARFID presenting with severe food selectivity.

Introduction Brain metastasis (BM) is one of the most common metastases from primary lung cancer (PLC). Recently, the National Lung Screening Trial revealed the efficacy of low-dose computed tomography (LDCT) screening on LC mortality reduction. Nevertheless, it remains unknown if early detection of PLC through LDCT may be potentially beneficial in reducing the risk of subsequent metastases. Our study aimed to investigate the impact of LDCT screening for PLC on the risk of developing BM after PLC diagnosis. Methods We used the National Lung Screening Trial data to identify 1502 participants who were diagnosed with PLC in 2002 to 2009 and have follow-up data for BM. Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection—that is, LDCT screen-detected versus non-LDCT screen-detected. Subgroup analyses were conducted in patients with early stage PLC and those who underwent surgery for PLC. Results Of 1502 participants, 41.4% had PLC detected through LDCT screening versus 58.6% detected through other methods, for example, chest radiograph or incidental detection. Patients whose PLC was detected with LDCT screening had a significantly lower 3-year incidence of BM (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p = 0.001), adjusting for age at PLC diagnosis, PLC stage, PLC histology, and smoking status. This significant reduction in BM risk among PLCs detected through LDCT screening persisted in subgroups of participants with early stage PLC (HR = 0.47, p = 0.002) and those who underwent surgery (HR = 0.37, p = 0.001). Conclusions Early detection of PLC using LDCT screening is associated with lower risk of BM after PLC diagnosis on the basis of a large population-based study.

ZusammenfassungDiese Arbeit gibt anhand von Fallbeispielen eine Übersicht über Indikationen und Techniken von Versteifungsoperationen bei Fingergelenksarthrosen.

Introduction Venous thromboembolism (VTE) management increasingly involves anticoagulation with direct oral anticoagulants (DOACs). Few studies have used competing-risks analyses to ascertain the mortality-adjusted hemorrhage and recurrent VTE (rVTE) risk of individual DOACs. Furthermore, hemorrhage risk factors in patients treated with apixaban remain underexplored. Materials and methods Patients diagnosed with VTE receiving anticoagulation were identified from the Optum Clinformatics Data Mart (2003–2019). Study endpoints included readmissions for intracranial hemorrhage (ICH), non-intracranial hemorrhage (non-ICH hemorrhage), and rVTE. Coarsened exact matching was used to balance baseline clinical characteristics. Complication incidence was evaluated using a competing-risks framework. We additionally modeled hemorrhage risk in apixaban-treated patients. Results Overall, 225,559 patients were included, of whom 34,201 received apixaban and 46,007 received rivaroxaban. Compared to rivaroxaban, apixaban was associated with decreased non-ICH hemorrhage (sHR = 0.560, 95%CI = 0.423–0.741), but not ICH, and rVTE (sHR = 0.802, 95%CI = 0.651–0.988) risk. This was primarily in emergent readmissions (sHR[emergent hemorrhage] = 0.515, 95%CI = 0.372–0.711; sHR[emergent rVTE] = 0.636, 95%CI = 0.488–0.830). Contributors to emergent hemorrhage in apixaban-treated patients include older age (sHR = 1.025, 95%CI = 1.011–1.039), female sex (sHR = 1.662, 95%CI = 1.252–2.207), prior prescription antiplatelet therapy (sHR = 1.591, 95%CI = 1.130–2.241), and complicated hypertension (sHR = 1.936, 95%CI = 1.134–3.307). Patients anticipated to be “high-risk” experienced elevated ICH (sHR = 3.396, 95%CI = 1.375–8.388) and non-ICH hemorrhage (sHR = 3.683, 95%CI = 2.957–4.588) incidence. Conclusions In patients with VTE receiving anticoagulation, apixaban was associated with reduced non-ICH hemorrhage and rVTE risk, compared to rivaroxaban. Risk reduction was restricted to emergent readmissions. We present a risk-stratification approach to predict hemorrhage in patients receiving apixaban, potentially guiding future clinical decision-making.

Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly in vitro models that can recapitulate the full complement of molecular attributes in the human condition. In this study, we aimed to develop a model that more closely resembles the aberrant IPF lung epithelium. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, we uncovered changes strikingly similar to those in the IPF lung epithelium. This included the acquisition of multiple phenotypic and functional characteristics of senescent cells and the adoption of previously described changes in mitochondrial homeostasis, including alterations in redox balance, energy production and activity of the mitochondrial unfolded protein response. We also uncovered dramatic changes in cellular metabolism and detected a profound loss of proteostasis, as characterized by the accumulation of cytoplasmic protein aggregates, dysregulated expression of chaperone proteins and decreased activity of the ubiquitin proteasome system. In summary, we describe an in vitro model that closely resembles the aberrant lung epithelium in IPF. We propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease.

We report 4 cases of post myocardial infarction complications due to the delay in presentation during COVID-19 era. We highlighted the need for auscultating the chest for early diagnosis. Through this case series, we urge to raise awareness among cardiac patients to access healthcare despite the fear of COVID-19., Highlights • To recognize the rise in post myocardial infarction complications in the setting of delayed presentation after acute coronary syndrome during COVID-19 pandemic era • To highlight the importance of physical examination for early diagnosis of post myocardial infarction complications • To demonstrate percutaneous options available for repairing ventricular septal rupture

It is generally assumed that left ventricular (LV) hypertrophy in aortic stenosis (AS) is a compensatory adaptation to chronic outflow obstruction. The advent of transcutaneous aortic valve replacement has stimulated more focus on AS in older patients, most of whom have antecedent hypertension. Accordingly, our aim was to investigate the interaction between hypertension and AS on LV remodeling in contemporary practice. We studied consecutive patients referred for echocardiograms with initial aortic valve (AV) peak velocity 3.5 m/s on a subsequent study performed at least 5 years later. LV size and geometry were measured echocardiographically. Midwall fractional shortening (FSmw) and peak systolic stress were calculated from 2-dimensional echocardiographic and Doppler data. Of 80 patients with progressive AS, 59% were women with mean age 82 ± 9 years. The average interval between the 2 echocardiograms was 5.9 ± 1.8 years. During the study period, peak velocity increased from 2.5 ± 0.4 to 4.2 ± 0.6 m/s (p < 0.01) and LV mass indexed to body surface area increased from 80 ± 28 to 122 ± 51 g/m2 (p < 0.01) with a corresponding shift from normal or concentric LV remodeling geometry to concentric hypertrophy. There was no correlation between change in LV mass index and AV mean gradient or valvulo-arterial impedance. However, change in LV mass index did correlate positively with initial peak velocity and inversely with initial LV mass. Plots of FSmw against circumferential stress at baseline and follow-up suggest that systolic function more than compensates for increasing load in many patients. In conclusion, most patients seen in our practice with severe AS have antecedent hypertension and LV remodeling at a time when outflow obstruction is mild. LV remodeling worsens in parallel with worsening severity of AS. Remodeling in these patients features increasing concentric remodeling of the LV, rather than LV dilation. Systolic function, as assessed by FSmw, remains compensated, or even improves relative to afterload, during progression of AS. Given these findings, we speculate that regression of LV hypertrophy to normal will not be affected by transcutaneous aortic valve replacement because LV hypertrophy preceded hemodynamically severe AS.

Background Thromboembolism is a recognized component of severe coronavirus disease 2019 (COVID-19) disease. However, research into racial disparities in COVID-19-related pulmonary embolism is limited. Materials and methods In this retrospective cohort study, we examined adults diagnosed with COVID-19 between January 20 and September 30, 2020, using a multicenter electronic health record dataset of over 73 million patients (TriNetX), mostly in the USA. The main study outcomes were development of pulmonary embolism or mortality within 30 days of COVID-19 diagnosis. Secondary outcome analysis included hospitalization, mechanical ventilation, and ICU admission within 30 days of diagnosis, as well as lab values within 0–1 days of diagnosis. Sociodemographic and clinical variables were used to create balanced cohorts via propensity matching. Results 346,953 patients were identified, with 56.0% non-Hispanic white and 14.7% non-Hispanic black; the mean age was 47.6 years. 3879 patients developed PE, with 2036 (1.30% of 157,049) white and 1088 (2.16% of 50,376) black patients. After propensity matching, black race was associated with higher mortality (risk ratio 1.890 [95% CI 1.727–2.067]) and PE (RR 1.537 [1.380–1.711]; p

ObjectiveAvoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather than duodenal biopsies. This study aimed to check the accuracy of a cut-off value of ≥10 upper limit of normal of anti-tissue transglutaminase antibody (anti-TTG IgA) titres for CD diagnosis in adult patients.MethodWe retrospectively analysed adult patients (≥16 years) who underwent gastroscopy from 2013 to 2018 for positive coeliac serology. The relationship between titres and disease was determined by using linear models, whereas sensitivity and specificity were assessed by receiver operator curve.ResultsWe analysed 144 newly anti-TTG antibody-positive adult patients with a median age of 48.5 years (IQR 32–62); among them, 86 (60%) patients had CD (Marsh III: n=68 and Marsh II and I: n=18) with a higher prevalence in females (n=59 (69%)) and Europeans (n=60 (70%)). Fifty (58%) patients with CD had colonoscopy and five (6%) had imaging; only six patients were diagnosed with additional conditions. An anti-TTG IgA titre cut-off value of 150 U/L was 100% specific for CD in our dataset, with 70% (95% CI: 60% to 88%) sensitivity for this patient group.ConclusionCoeliac serology using anti-TTG IgA with titres ≥10× normal value is an excellent predictor of CD, irrespective of age, gender and ethnicity. Duodenal biopsy may not be necessary in selected adult patients with CD, especially younger than 50 years of age without additional gastrointestinal red-flag signs and symptoms.

ObjectiveTo identify novel disease associated loci for amyotrophic lateral sclerosis (ALS), we used sequencing data and performed in vitro and in vivo experiments to demonstrate pathogenicity of mutations identified inTP73.MethodsWe analyzed exome sequences of 87 patients with sporadic ALS and 324 controls, with confirmatory sequencing in independent ALS cohorts of >2,800 patients. For the top hit,TP73, a regulator of apoptosis and differentiation and a binding partner and homolog of the tumor suppressor geneTP53, we assayed mutation effects using in vitro and in vivo experiments. C2C12 myoblast differentiation assays, characterization of myotube appearance, and immunoprecipitation of p53-p73 complexes were performed in vitro. In vivo, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 targeting of zebrafishtp73to assay motor neuron number and axon morphology.ResultsFour heterozygous rare, nonsynonymous mutations inTP73were identified in our sporadic ALS cohort. In independent ALS cohorts, we identified an additional 19 rare, deleterious variants inTP73. PatientTP73mutations caused abnormal differentiation and increased apoptosis in the myoblast differentiation assay, with abnormal myotube appearance. Immunoprecipitation of mutant ΔN-p73 demonstrated that patient mutations hinder the ability of ΔN-p73 to bind p53. CRISPR/Cas9 knockout oftp73in zebrafish led to impaired motor neuron development and abnormal axonal morphology, concordant with ALS pathology.ConclusionTogether, these results strongly suggest that variants inTP73correlate with risk for ALS and indicate a role for apoptosis in ALS disease pathology.

Background Development of clinical risk factors linked to metabolic syndrome (MetS) in adolescence is associated with higher incidence of atherosclerotic cardiovascular events in adulthood. Given the increasing burden of obesity and MetS in African-American (AA) youth, there is a need to establish the relation of MetS with modifiable risk factors such as diet quality, because these data may enhance preventative and treatment approaches. Objectives The purpose of this study was to assess diet quality, measured by the Alternative Healthy Eating Index 2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) pattern score, in AA adolescents and youth (aged 12-21 y) from the NHANES, and to investigate the association of diet quality with MetS and its components. Methods This study is a cross-sectional analysis of NHANES data from the 2005-2016 cycles (n = 2459). Survey-weighted logistic regression models were used to assess the association of diet quality with the prevalence of MetS and individual cardiometabolic components [overweight/obesity, hypertensive blood pressure (BP), impaired fasting glucose, low HDL cholesterol, hypertriglyceridemia]. Results The mean ± SD AHEI-2010 score was 38.9 ± 9.7 and DASH pattern score was 21.8 ± 4.4, which is equivalent to 35% adherence to recommendations to achieve an optimal diet quality and 45% adherence to the DASH-style dietary pattern, respectively. Compared with those within the lowest quartile of DASH pattern score, individuals in the fourth quartile group had 0.63 (95% CI: 0.41, 0.97) times the odds of having hypertensive BP. Among individuals with complete clinical measures (n = 1007), individuals within the highest-quartile AHEI-2010 group had 0.25 (95% CI: 0.06, 0.99) times the odds of having MetS compared with those within the lowest quartile. Conclusions Diet quality in US AA youth is low. Higher DASH pattern scores were associated with lower odds of hypertensive BP and higher AHEI-2010 scores were associated with lower odds of MetS.

Positively charged oligo(poly(ethylene glycol) fumarate) (OPF+) hydrogel scaffolds, implanted into a complete transection spinal cord injury (SCI), facilitate a permissive regenerative environment and provide a platform for controlled observation of repair mechanisms. Axonal regeneration after SCI is critically dependent upon nutrients and oxygen from a newly formed blood supply. Our objective was to investigate fundamental characteristics of revascularization in association with the ingrowth of axons into hydrogel scaffolds, thereby defining spatial relationships between axons and the neovasculature. A novel combination of stereologic estimates and precision image analysis techniques quantitate neurovascular regeneration in rats. Multichannel hydrogel scaffolds containing Matrigel-only (MG), Schwann cells (SCs), or SCs with rapamycin-eluting poly(lactic co-glycolic acid) microspheres (RAPA) were implanted for 6 weeks following complete spinal cord transection. Image analysis of 72 scaffold channels identified a total of 2494 myelinated and 4173 unmyelinated axons at 10 μm circumferential intervals centered around 708 individual blood vessel profiles. Blood vessel number, density, volume, diameter, intervessel distances, total vessel surface and cross-sectional areas, and radial diffusion distances were compared. Axon number and density, blood vessel surface area, and vessel cross-sectional areas in the SC group exceeded that in the MG and RAPA groups. Individual axons were concentrated within a concentric radius of 200–250 μm from blood vessel walls, in Gaussian distributions, which identified a peak axonal number (Mean Peak Amplitude) corresponding to defined distances (Mean Peak Distance) from each vessel, the highest concentrations of axons were relatively excluded from a 25–30 μm zone immediately adjacent to the vessel, and from vessel distances >150 μm. Higher axonal densities correlated with smaller vessel cross-sectional areas. A statistical spatial algorithm was used to generate cumulative distribution F- and G-functions of axonal distribution in the reference channel space. Axons located around blood vessels were definitively organized as clusters and were not randomly distributed. A scoring system stratifies 5 direct measurements and 12 derivative parameters influencing regeneration outcomes. By providing methods to quantify the axonal-vessel relationships, these results may refine spinal cord tissue engineering strategies to optimize the regeneration of complete neurovascular bundles in their relevant spatial relationships after SCI. IMPACT STATEMENT: Vascular disruption and impaired neovascularization contribute critically to the poor regenerative capacity of the spinal cord after injury. In this study, hydrogel scaffolds provide a detailed model system to investigate the regeneration of spinal cord axons as they directly associate with individual blood vessels, using novel methods to define their spatial relationships and the physiologic implications of that organization. These results refine future tissue engineering strategies for spinal cord repair to optimize the re-development of complete neurovascular bundles in their relevant spatial architectures.

To examine breastfeeding, individual and household risk factors for malnutrition (i.e., overweight and stunting) among Mexican-origin children aged 6 to 35 months living in Mexico and the US. We ran logistic regression models using subsamples of the 2012 Mexican National Health and Nutrition Survey, and four waves (2007-2014) of the US National Health and Nutrition Examination Survey. We found evidence for a protective effect of any breastfeeding on stunting in Mexico. Risk factors for overweight and stunting across countries were high- and low-birthweight, correspondingly. An additional risk factor for overweight was introducing complementary foods before 6 months; while being male, living in Mexico and moderate-severe household food insecurity were additional risk factors for stunting. To prevent malnutrition among Mexican-origin children, pre- and post-natal culturally-sensitive policies and interventions in both countries should be aimed toward preventing high- and low-birthweight, and promoting positive maternal health behaviors such as appropriate child feeding practices.

Introduction Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. Objective This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. Discussion Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. Conclusion This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.

In the third and final article in this series, patient and provider dynamics are explored, built from real-life telehealth experiences. The Four Habits Model is utilized to examine the virtual visit.

Autologous fat grafting (AFG) serves as an effective method to address volume defects, contour irregularities, and asymmetry in both aesthetic and reconstructive procedures. In recent years, there has been growing concern about the potential of cancer recurrence and interference with cancer surveillance in oncologic patients receiving AFG. The adipose tissue contains adipose-derived stem cells (ASCs), a specific type of mesenchymal stem cells, that facilitate secretion of numerous growth factors which in turn stimulate tissue regeneration and angiogenesis. As such, it has been theorized that ASCs may also have the potential to stimulate cancer cell proliferation and growth when used in oncologic patients. Multiple research studies have demonstrated the ability of ACSs to facilitate tumor proliferation in animal models. However, clinical research in oncologic patients has yielded contradictory findings. Although the literature pertaining to oncologic safety in head and neck, as well as sarcoma, cancer patients remains limited, studies demonstrate no increased risk of tumor recurrence in these patient populations receiving AFG. Similarly, both the efficacy and safety of AFG have been well established in breast cancer patients through numerous clinical studies. More recently, preclinical research in animal models has shown that AFG has the potential to facilitate tissue regeneration and improve joint contracture following irradiation. Ultimately, further research is needed to elucidate the safety of AFG in a variety of oncologic patients, as well as explore its use in tissue regeneration, particularly in the setting of radiotherapy. Level of Evidence: 4

This article presents a comprehensive review of the use of quantitative measurements based on breast images to assess fat retention, breast aesthetics, and fat necrosis after autologous fat grafting. Breast volume measured from MRI and 3-dimensional surface images is widely used as a measure of fat retention. Breast aesthetics are assessed from a combination of anthropometric (distance and contour) measurements on breast surface images. Examination of radiologic images (ultrasonography, mammography, and MRI) is utilized to assess fat necrosis. The article discusses implementation guidelines for objective outcome assessment to support robust quantification and enable investigations of fat grafting efficacy. Level of Evidence: 4

One of the earliest reported cases of autologous fat grafting (AFG) was by Neuber in 1893 and consisted of the transfer of small lobules of fat from the upper arm for cicatrical depression of the face. He advocated the use of smaller grafts, noting that pieces larger than the size of a bean would form cysts. In 1895, Czerny excised a lumbar lipoma and transplanted it to the chest for breast reconstruction. Since these early reports, the knowledge base around AFG has expanded exponentially, as illustrated by the other papers within this special topic. As we embark on the next phase of AFG in the clinical setting, there are several directions which are near-clinical translation. This paper discusses future directions in fat grafting that build on optimization of our current techniques as clinical indications expand, such as supplementing purified lipoaspirate and the associated regulatory burden, or deconstructing adipose tissue to selectively use adipose graft components for a variety of regenerative indications.

OBJECTIVES: Lung cancer survivors have a high risk of developing a second primary lung cancer (SPLC). While national screening guidelines have been established for initial primary lung cancer (IPLC), no consensus guidelines exist for SPLC. Furthermore, the factors that contribute to SPLC risk have not been established. This study examines the potential for using serum metabolomics to identify metabolite biomarkers that differ between SPLC cases and IPLC controls. MATERIAL AND METHODS: In this pilot case-control study, we applied an untargeted metabolomics approach based on ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) to serum samples of 82 SPLC cases and 82 frequency matched IPLC controls enrolled in the Boston Lung Cancer Study. Random forest and unconditional logistic regression models identified metabolites associated with SPLC. Candidate metabolites were integrated into a SPLC risk prediction model and the model performance was evaluated through a risk stratification approach. RESULTS: The untargeted analysis detected 1,008 named and 316 unnamed metabolites among all study participants. Metabolites that were significantly associated with SPLC (False Discovery Rate q-value < 0.2) included 5-methylthioadenosine (odds ratio [OR]=2.04, 95% confidence interval [CI] 1.39–3.01; P=2.8×10(−4)) and phenylacetylglutamine (OR=2.65, 95% CI 1.56–4.51; P=3.2×10(−4)), each exhibiting approximately 1.5-fold increased levels among SPLC cases versus IPLC controls. In stratifying the study participants across quartiles of estimated SPLC risk, the risk prediction model identified a significantly higher proportion of SPLC cases in the fourth compared to the first quartile (68.3% versus 39.0%; P=0.044). CONCLUSION: SPLC cases may have distinct metabolomic profiles compared to those in IPLC patients without SPLC. A risk stratification approach integrating metabolomics may be useful for distinguishing patients based on SPLC risk. Prospective validation studies are needed to further evaluate the potential for leveraging metabolomics in SPLC surveillance and screening.

In this second article of a three-part series, we explore how stakeholders can be educated on the use of telehealth technology and telemedicine. We address the need for staff and patient support for the transition to telehealth and offer suggestions to NPs for appropriate presentation and interaction with interdisciplinary teams and patients regarding telehealth.

OBJECTIVE The only effective treatment for ischemic moyamoya disease (iMMD) is cerebral revascularization by an extracranial to intracranial bypass. The preferred revascularization method remains controversial: direct versus indirect bypass. The purpose of this study was to test the hypothesis that method choice should be personalized based on angiographic, hemodynamic, and clinical characteristics to balance the risk of perioperative major stroke against treatment efficacy. METHODS Patients with iMMD were identified retrospectively from a prospectively maintained database. Those with mild to moderate internal carotid artery or M1 segment stenosis, preserved cerebrovascular reserve, intraoperative M4 segment anterograde flow ≥ 8 ml/min, or the absence of frequent and severe transient ischemic attacks (TIAs) or stroke had been assigned to indirect bypass. The criteria for direct bypass were severe ICA or M1 segment stenosis or occlusion, impaired cerebrovascular reserve or steal phenomenon, intraoperative M4 segment retrograde flow or anterograde flow < 8 ml/min, and the presence of frequent and severe TIAs or clinical strokes. The primary study endpoint was MRI-confirmed symptomatic stroke ≤ 7 days postoperatively resulting in a decline in the modified Rankin Scale (mRS) score from preoperatively to 6 months postoperatively. As a secondary endpoint, the authors assessed 6-month postoperative DSA-demonstrated revascularization, which was classified as < 1/3, 1/3–2/3, or > 2/3 of the middle cerebral artery territory. RESULTS One hundred thirty-eight patients with iMMD affecting 195 hemispheres revascularized in the period from March 2016 to June 2018 were included in this analysis. One hundred thirty-three hemispheres were revascularized with direct bypass and 62 with indirect bypass. The perioperative stroke rate was 4.7% and 6.8% in the direct and indirect groups, respectively (p = 0.36). Degree of revascularization was higher in the direct bypass group (p = 0.03). The proportion of patients improving to an mRS score 0–1 (from preoperatively to 6 months postoperatively) tended to be higher in the direct bypass group, although the difference between the two bypass groups was not statistically significant (p = 0.27). CONCLUSIONS The selective use of an indirect bypass procedure for iMMD did not decrease the perioperative stroke rate. Direct bypass provided a significantly higher degree of revascularization. The authors conclude that direct bypass is the treatment of choice for iMMD.

Background: Radium-223 dichloride ([223Ra]RaCl2) is the first approved alpha particle-emitting therapy and is indicated for treatment of bone metastatic castrate resistant prostate cancer. Approximately half of the dose is absorbed into the gastrointestinal (GI) tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here, we investigate the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects. Methods: Utilizing primary human duodenal organoids (enteroids) as in vitro models of the functional GI epithelium, we found that Amiloride (ENaC blocker) and NS-1619 (K+ channel activator) presented significant effects in 223Ra membranal transport. The radioactive drug distribution was evaluated for lead combinations in vivo, and in osteosarcoma and prostate cancer models. Results: Amiloride shifted 223Ra uptake in vivo from the gut, to nearly double the uptake at sites of bone remodeling. Bone tumor growth inhibition with the combination as measured by bioluminescent and X-ray imaging was significantly greater than single agents alone, and the combination resulted in no weight loss. Conclusion: This combination of approved agents may be readily implemented as a clinical approach to improve outcomes of bone metastatic cancer patients with the benefit of ameliorated tolerability.

Background Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow. Methods In previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to Results We evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation. Conclusions Successful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.

Background Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. Methods TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. Results Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. Conclusions This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov : NCT00977574 .

Background Iron deficiency anemia [IDA] has emerged as public health concern with poor bioavailability, reliance on dietary cereals and presence of anti-nutritional factors further exacerbating the issue. Strategies like dietary diversification, supplementation, food fortification and bio-fortification have been suggested yet the problem keep on staggering large populations globally. Scope & approach Recent evidence has shown that prebiotics reasoned to fermentation by gut microbiota may lower the pH of the luminal content, boost reduction of Fe (III) to Fe (II), and stimulate expression of mineral-transport proteins in epithelial cells that may enhance the absorption of iron among anemic subjects. However, a detailed study and research needs to be executed to establish this connection. Key findings & conclusions The present review is an attempt to relate the cumulative effect of prebiotics on bioavailability of iron fortificants to effectively address the problem of iron deficiency anemia.

Background The demographics, weight statuses, and dietary patterns of people with autism or the broad autism phenotype who experience a severe nutrient deficiency disease due to symptoms of avoidant/restrictive food intake disorder have not been well established. Objective The primary objective of this review was to examine the relationship between the demographics, weight statuses, dietary patterns, and nutrient deficiency diseases that characterize the most severe manifestations of avoidant/restrictive food intake disorder symptomology associated with autism or the broad autism phenotype. Methods A systematic review of English and non-English articles published up to August 29, 2019, on the Scopus, PubMed, and Cumulative Index to Nursing and Allied Health Literature Plus electronic databases was conducted. Additional cases were identified through the reference list of all included articles. The search terms used were “autis∗ AND (deficiency OR scurvy)”. Only case reports or case series in which a person of any age who had been identified as having a formal diagnosis of autism or autism symptoms and a disease of nutritional deficiency due to self-imposed dietary restrictions were included. Data were independently extracted by 8 authors using predefined data fields. Results A total of 76 cases (patients were aged 2.5 to 17 years) from 63 articles that were published from 1993 through 2019 were found. More than 85% cases (65 of 76 patients) were from articles published in the past 10 years. The largest percentage of published cases (69.7% [53 of 76]) involved scurvy, a vitamin C deficiency. The second-largest percentage of published cases (17.1% [13 of 76]) involved eye disorders secondary to vitamin A deficiency. Other primary nutrient deficiencies reported were thiamin, vitamin B-12, and vitamin D. In 62.9% (22 of 35) of the patients for which a body mass index or a weight percentile for age was provided, the patient was within normal weight parameters, per Centers for Disease Control weight status categories. Conclusions Based on the 63 articles extracted for this systematic review, nutritional deficiency diseases related to inadequate intakes of vitamin A, thiamin, vitamin B-12, vitamin C, and vitamin D were found in individuals with autism and the broad autism phenotype who had severe self-imposed dietary restrictions. When weight information was provided, most of the youth in these cases were not reported to be underweight. Individuals of any weight who present with symptoms of avoidant/restrictive food intake disorder can benefit from early and frequent screening for adequacy of micronutrient intake, regardless of whether they have a clinical diagnosis of autism.

Providing safe nonemergent care during the coronavirus disease 2019 (COVID-19) pandemic has been challenging for NPs. This article, the first of a three-part series, will overview telehealth and telemedicine and provide a brief history of the two. The benefits, challenges, and temporary changes due to COVID-19 will also be addressed.

Spontaneous left ventricular pseudoaneurysms are very rare and can have catastrophic consequences if unrecognized. A case of combined spontaneous left ventricular aneurysm and pseudoaneurysm in Behcet's disease (BD) has been reported. The case emphasizes advanced techniques for percutaneous closure of the defects with the use of an ex-vivo three-dimensional cardiac printed model as a tool to facilitate the procedure.

INTRODUCTION Breast reconstruction surgery is an integral part of breast cancer treatment that aims to restore breast appearance after mastectomy. We assessed breast symmetry following breast reconstruction using measures of distance and volume. MATERIAL AND METHODS Patients undergoing breast reconstruction surgery were enrolled in an IRB approved study from 2011 to 2014 at The University of Texas MD Anderson Cancer Center. We utilized pre- and post-operative 3D surface images (3dMDtorso, 3dMD LLC, Atlanta, GA) from 53 women who had completed the breast reconstruction process (83% at 18 months (M), 9.4% at 12M and 7.6% at 9M). Patients provided approved consent. Thirty-six women had bilateral and 17 had unilateral surgery. Eleven patients in the unilateral group had symmetry surgery on the contralateral breast (5 had mastopexy, 4 had reduction, 1 had augmentation, and 1 had augmentation and mastopexy). Within the bilateral group, 9 patients underwent autologous reconstruction, 21 received implants, and 6 had mixed (autologous and implant) procedures. Within the unilateral group, there were 10 implant and 7 autologous reconstructions. We measured the sternal notch (SN) to lowest visible point (LVP) distance and volume for each breast. Breast symmetry was assessed using 1) Difference between the left and right breasts for the SN-LVP distance and volume measures, 2) SN-LVP distance ratio and volume ratio computed using values for the left and right breast. The smaller value was divided by the larger, so that a ratio of 1.0 indicated perfect symmetry [1]. Differences < 5 mm for SN-LVP distance and < 50 cc for breast volume were used as indicators of symmetry [1]. RESULTS Overall, pre-operatively 50.9% patients showed a SN-LVP difference < 5 mm compared to 35.9% post-operatively, whereas 43.4% showed a breast volume difference < 50 cc pre-operatively compared to 62.3% post-operatively. Mean pre- and post-operative SN-LVP distance ratios were found to be 0.97 ± 0.03 and 0.96 ± 0.03, respectively, whereas the breast volume ratios were 0.91 ± 0.06 and 0.92 ± 0.08, respectively. Shapiro-Wilk tests showed non-normal distribution for both ratios; thus, non-parametric analysis was performed using Mann-Whitney U-test and, for matched pairs, the Wilcoxon Matched Pairs Sign-Ranked test. For both distance and volume ratios, we failed to reject the null hypothesis that the median of the paired differences between the pre- and post-operative values was zero. Also, no significant differences were found for both ratios when comparing autologous and implant-based surgeries. Bilateral reconstructions were compared to unilateral procedures that included a contralateral symmetry procedure. Significantly higher distance ratios (0.97 ± 0.03, median of 0.98, p = 0.005) were found for bilateral reconstructions compared to unilateral (0.94 ± 0.04, median of 0.94), but no differences in volume ratios were noted. Significant differences were noted for both distance (p = 0.033) and volume (p = 0.009) ratios when comparing bilateral (distance: 0.96 ± 0.02, median of 0.97 and volume: 0.96 ± 0.03, median of 0.97) to unilateral implant-based reconstructions (distance: 0.93 ± 0.04, median of 0.94 and volume: 0.91 ± 0.05, median of 0.90), but no difference in symmetry was found between unilateral and bilateral autologous reconstructions. CONCLUSION Distance symmetry was noted in a higher percentage of the pre-operative population compared to post-operative, whereas a larger proportion of the post-operative patients showed volume symmetry compared to the pre-operative group. Implant-based bilateral procedures showed improved symmetry compared to the unilateral procedures. REFERENCES 1.Cheong AL, Liu J, Reece GP, Nicklaus KM, Bordes MC, Hanson SE, Markey MK, Merchant, FA “Natural Breast Symmetry in Preoperative Breast Cancer Patients”, Plastic and Reconstructive Surgery - Global Open: 2019;7(7):e2297. Citation Format: Thao Bui, Urmila Sampathkumar, Zhale Nowroozilarki, Jun Liu, Mary Catherine Borders, Summer E Hanson, Gregory P Reece, Mia K Markey, Fatima A Merchant. Symmetry of breasts following reconstructive surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-24.

Background: The prognosis of early-stage, hormone receptor-positive breast cancer is excellent with 5-year overall survival rates greater than 90%. In the context of excellent survival, it is important to quantify the long-term comorbidities associated with endocrine therapy. Methods: Eligible patients were women diagnosed with stages 1-3, hormone receptor-positive and Her2-negative breast cancer from January 1999 to December 2016 and treated at one or more of two healthcare systems in the San Francisco Bay Area (Stanford University or the community-based Palo Alto Medical Foundation, N=3,044). Duration of therapy with aromatase inhibitors and/or tamoxifen was ascertained. Long-term comorbidities analyzed were congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cerebrovascular accidents (CVA), dementia, depression/anxiety, diabetes mellitus (DM), peptic ulcer disease (PUD), hyperlipidemia (HLD), myocardial infarction (MI), non-alcoholic steatohepatitis (NASH), osteonecrosis of the jaw, osteoporosis, peripheral vascular disease (PVD), and venous thrombotic events (VTE). Pre-existing comorbidities were defined as those diagnosed any time up to 1 year after breast cancer diagnosis. Incident comorbidities that developed on or after endocrine therapy were defined as those diagnosed any time after 1 year following breast cancer diagnosis. Results: The median patient age was 58.1 years. Patients were 67.8% non-Hispanic white, 22.1% Asian, 7.6% Hispanic, 1.7% non-Hispanic Black, and 0.8% other. Most (69.6%) had private insurance. For endocrine therapy, almost half (48.3%) used aromatase inhibitors only (median duration 35.1 months), 20.6% used tamoxifen only (median duration 29.4 months), and the remainder used both aromatase inhibitors (AI) and tamoxifen (median duration of any endocrine therapy: 47.8 months). Comorbidity results are in the Table. Notable unadjusted hazard ratios for the association of incident comorbidities with tamoxifen (versus AI) use include: HLD 0.45 [95% confidence interval, CI 0.25-0.8]; MI 0.66 [CI 0.04-9.88]; CHF 1.23 [CI 0.29-5.1]; CVA 0.46 [CI 0.14-1.54]; depression/anxiety 0.89 [CI 0.45-1.76]; osteoporosis 0.37 [CI 0.23-0.59]; and DM 1.34 [CI 0.44-4.07]. Results of multivariable analysis will be presented, adjusting for comorbidities present before cancer diagnosis, age, race and insurance status. Conclusions: In a diverse, real-world cohort of breast cancer patients treated in two healthcare systems, incident HLD and osteoporosis were significantly less common with tamoxifen versus AI use, while other comorbidities did not vary with type of endocrine therapy. These results may inform clinical decision-making about endocrine therapy for early-stage, hormone receptor-positive breast cancer. Table. Comorbidities relative to timing of breast cancer diagnosisComorbidityPrevalence before cancer diagnosisIncidence after cancer diagnosisCongestive heart failure65 (2.1)70 (2.3)Chronic obstructive pulmonary disease348 (11.4)127 (4.2)Cerebrovascular accident83 (2.7)77 (2.5)Dementia15 (0.5)25 (0.8)Depression/Anxiety599 (19.7)245 (8)Diabetes239 (7.9)101 (3.3)Peptic ulcer disease36 (1.2)19 (0.6)Hyperlipidemia870 (28.6)363 (11.9)Myocardial infarction12 (0.4)18 (0.6)Non-alcoholic steatohepatitis40 (1.3)62 (2)Osteonecrosis of jawNA (NA)2 (0.1)Osteoporosis/Fracture791 (26)608 (20)Peripheral vascular disease22 (0.7)31 (1)Venous thrombotic event65 (2.1)74 (2.4) Citation Format: Tanya Gupta, Natasha Purington, Mina Liu, Summer Han, George Sledge, Lidia Schapira, Allison Kurian. Incident comorbidities in a diverse cohort of women treated for early-stage, hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-24.

Graphical abstract, Highlights • Cardiac interdependence in conjoined twins is a rare phenomenon. • Presence of congenital heart disease may be an important prognostic factor. • There is high risk of high-output heart failure and pulmonary hypertension in the donor twin. • If reconstruction is feasible, early separation may improve the chance of survival.

BackgroundMitochondrial dysfunction has emerged as an important player in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a common cause of idiopathic interstitial lung disease in adults. Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that causes a similar type of pulmonary fibrosis in younger adults, although the role of mitochondrial dysfunction in this condition is not understood.MethodsWe performed a detailed characterization of mitochondrial structure and function in lung tissues and alveolar epithelial cells deficient in the adaptor protein complex 3 beta 1 (Ap3b1) subunit, the gene responsible for causing subtype 2 of HPS (HPS-2).ResultsWe observed widespread changes in mitochondrial homeostasis in HPS-2 cells, including the acquisition of abnormally shaped mitochondria, with reduced number of cristae, and markedly reduced activity of the electron transport chain and the tricarboxylic acid cycle. We also found that mitochondrial redox imbalance and activity of the mitochondrial unfolded protein response were dysregulated in HPS-2 cells and this associated with various other changes that appeared to be compensatory to mitochondrial dysfunction. This included an increase in glycolytic activity, an upregulation in the expression of mitochondrial biogenesis factors and enhanced activation of the energy-conserving enzyme AMP-activated protein kinase.ConclusionIn summary, our findings indicate that mitochondrial function is dramatically altered in HPS-2 lung tissues, suggesting dysfunction of this organelle might be a driver of HPS lung disease.

Objective: Prior research suggests maximal physical exertion (MPE) may negatively affect the reliability and validity of computerized neurocognitive testing (CNT); the purpose of this study was to ...

The purpose of this study was to systematically investigate the performance of different radiographic views in the identification of scaphoid fractures in children. This case-control study compared 4-view radiographic examinations of the wrist between children with scaphoid fracture and age- and sex-matched children without fractures performed between January 2008 and July 2019. After randomization, each examination was reviewed 3 times, at least 1 week apart, first using each view separately and later using multiple views without (3-view) and with the posteroanterior (PA) scaphoid view (4-view), to determine the presence or absence of a scaphoid fracture. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with inter-rater agreement. The study group of 58 children (48 boys and 10 girls; mean age 13.1 ± 2.1 years) included 29 with scaphoid fractures (8 corner, 9 distal pole, 10 waist, and 2 proximal pole) and 29 without fractures. Multiple views had higher sensitivity (3-view, 93.0%; 4-view, 96.5%) for fracture identification when compared to individual views (41.0–89.6%). The oblique view was 100% specific for the identification of a scaphoid fracture, but it lacked sensitivity. The PA scaphoid view had the highest sensitivity (89.6%) and NPV (90%) when compared to other individual views and its inclusion in the 4-view examinations produced the highest inter-rater agreement (93%, κ = 0.86). Multiple radiographic views of the wrist with the inclusion of a PA scaphoid view (4-view) produced the highest sensitivity, NPV, and inter-rater agreement for the identification of a scaphoid fracture in children.

Background The perioperative management of patients taking a direct oral anticoagulant (DOAC) who require a high‐bleed‐risk surgery and/or neuraxial anesthesia is uncertain. We surveyed clinician practices relating to DOAC interruption and related perioperative management in patients having high‐bleed‐risk surgery with neuraxial anesthesia, and assess the suitability of a randomized trial of different perioperative DOAC management strategies. Methods We surveyed members of the American Society of Regional Anesthesia and Pain Medicine, the Canadian Anesthesia Society and Thrombosis Canada. We developed four clinical scenarios involving DOAC‐treated patients who required anticoagulant interruption for elective high‐bleed‐risk surgery. In three scenarios, patients were to receive neuraxial anesthesia, and in one scenario they were to receive general anesthesia. We also asked about the merit of a randomized trial to compare a 2‐day versus longer (3‐ to 5‐day) duration of DOAC interruption. Results There were 399 survey respondents of whom 356 (89%) were anesthetists and 43 (11%) were medical specialists. The responses indicate uncertainty about the DOAC interruption interval for high‐bleed‐risk surgery and/or neuraxial anesthesia; anesthetists favor 3‐ to 5‐day interruption whereas medical specialists favor 2‐day interruption. Anesthetists were unwilling to proceed with neuraxial anesthesia in patients with a 2‐day DOAC interruption interval, preferring to cancel the surgery or switch to general anesthesia. There is general agreement on the need for a randomized trial in this field to compare a 2‐day and a 3‐ to 5‐day DOAC interruption management strategy. Conclusions There is variability in practices relating to the perioperative management of DOAC‐treated patients who require a high‐bleed‐risk surgery with neuraxial anesthesia; this variability relates to the duration of DOAC interruption in such patients.

The United States Food and Drug Administration (FDA) recently recognized the necessity for improved patient education and public awareness of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). BIA-ALCL is an uncommon T-cell lymphoma that can arise years after placement of a textured breast implant or tissue expander. Patients and providers would greatly benefit from a broader awareness of BIA-ALCL and how it presents with both common and rare symptoms. Disease awareness can be improved with specific steps moving forward. This includes improved counseling about annual recommendations from the FDA, standard of care guidelines, current estimates of disease prevalence, and manufacturer-specific risk for developing the malignancy. Informed consent for implant-based breast surgery should include a discussion of BIA-ALCL, symptoms, inherent risks and alternatives. Consideration should be given for reasonable efforts to retroactively contact patients with textured implants to inform them of recent regulatory actions as well as the risk of developing the disease and the signs and symptoms to watch for. Where risk can be reduced, all steps should be taken to ensure patient safety. In keeping with our commitment to patient safety, the strategies moving forward for implant-based breast surgery should be marked by patient awareness, physician vigilance, and defined by evidence-based diagnosis and treatment.

BACKGROUND Posterior segment eye diseases, such as glaucoma and retinal diseases (such as diabetic retinopathy, age-related macular degeneration, and retinal detachment), are chronic diseases that are among the major causes of visual impairment. OBJECTIVE We investigated the prevalence of anxiety disorders, depressive disorders, and common mental disorders in these patients and also the incidence of depression. METHODS We examined baseline (2008-2010) and follow-up (2012-2014) data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We used the Clinical Interview Schedule-Revised (CIS-R) to perform International Classification of Diseases-10-based diagnoses of anxiety and depressive disorders. Common mental disorder was defined as a Clinical Interview Schedule-Revised >11. We used multinomial logistic regression models to investigate associations between eye diseases and mental disorders, adjusted by age, gender, educational level, self-reported ethnicity, cardiovascular conditions, and self-reported quality of vision. RESULTS Out of 10,775 subjects, 249 (2.3%), 303 (2.8%), and 30 (0.3%) reported having retinal diseases, glaucoma, or both, respectively. Patients with retinal diseases and those with glaucoma and retinal diseases presented a higher prevalence of common mental disorders (relative-risk ratios of 1.7 and 3.7, respectively, P

Introduction This study quantifies the differences in infant outcomes by mother's self-identified race among Arab Americans and by self-identified race and ethnicity for Arabs and non-Arabs. Methods This study used data from the Standard Certificate of Live Birth on 8,204 infants born to Arab and 325,354 infants born to non-Arab mothers between 2012 and 2016 in Massachusetts; data were analyzed between 2019 and 2020. Mothers’ race was categorized as White, Black, or Other. Mothers’ ethnicity was categorized as Arab or non-Arab. Outcomes included birth weight, preterm birth, low-birth weight, small for gestational age, and large for gestational age. Linear and logistic regression models assessed the association between race and infant health outcomes. Results Black Arab mothers had higher odds of preterm birth (AOR=1.37, 95% CI=1.07, 1.76) and low-birth weight (AOR=1.35, 95% CI=0.99, 1.84) than White Arab mothers. Arab mothers who self-identified as Other had babies that were 51.4 grams lighter than babies born to White Arab mothers. White Arab mothers had higher odds of low birth weight (AOR=1.19, 95% CI=1.06, 1.34) and small-for-gestational-age babies (AOR=1.22, 95% CI=1.11, 1.36) but lower odds of large-for-gestational-age babies (AOR=0.77, 95% CI=0.70, 0.86) than White non-Arab mothers. Conclusions Both ethnicity and race are important determinants of the health of Arab American infants. Arab ethnicity may play a negative role in the infant health of Arab Americans who identify as White. A better understanding of the lived experiences of Arab American mothers, with regard to their racial and ethnic identity, may help better inform clinical practice.

Autistic people, by definition, differ in social behavior from non-autistic individuals. One characteristic common to many autistic people is a special interest in a particular topic—something spoken about with such frequency and intensity that it may be stigmatized by non-autistic peers. We investigated college students’ interest in interacting with peers described as behaving in ways characteristic of autism (or not), and additionally described as having a special interest (or not). As expected, autistic characters were more stigmatized, but autistic characters with a special interest were not more stigmatized than those without. Only among non-autistic characters was having a special interest associated with greater stigmatization. Findings give further insight into factors influencing the stigmatization of autistic college students.