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Background Human immunodeficiency virus (HIV)-associated lipodystrophy is a known consequence of long-term highly active antiretroviral therapy (HAART). However, a significant number of patients on HAART therapy were left with the stigmata of complications, including fat redistribution. Few studies have described the successful removal of focal areas of lipohypertrophy with successful outcomes. This manuscript reviews the outcomes of excisional lipectomy versus liposuction for HIV-associated cervicodorsal lipodystrophy. Methods We performed a 15-year retrospective review of HIV-positive patients with lipodystrophy. Patients were identified by query of secure operative logs. Data collected included demographics, medications, comorbidities, duration of HIV, surgical intervention type, pertinent laboratory values, and the amount of tissue removed. Results Nine male patients with HIV-associated lipodystrophy underwent a total of 17 procedures. Of the patients who underwent liposuction initially (n=5), 60% (n=3) experienced a recurrence. There were a total of three cases of primary liposuction followed by excisional lipectomy. One hundred percent of these cases were noted to have a recurrence postoperatively, and there was one case of seroma formation. Of the subjects who underwent excisional lipectomy (n=4), there were no documented recurrences; however, one patient’s postoperative course was complicated by seroma formation. Conclusions HIV-associated lipodystrophy is a disfiguring complication of HAART therapy with significant morbidity. Given the limitations of liposuction alone as the primary intervention, excisional lipectomy is recommended as the primary treatment. Liposuction may be used for better contouring and for subsequent procedures. While there is a slightly higher risk for complications, adjunctive techniques such as quilting sutures and placement of drains may be used in conjunction with excisional lipectomy.

Constraining patterns of growth using directly observable and quantifiable characteristics can reveal a wealth of information regarding the biology of the Ediacara biota—the oldest macroscopic, complex community-forming organisms in the fossil record. However, these rely on individuals captured at an instant in time at various growth stages, and so different interpretations can be derived from the same material. Here we leverage newly discovered and well-preserved Dickinsonia costata Sprigg, 1947 from South Australia, combined with hundreds of previously described specimens, to test competing hypotheses for the location of module addition. We find considerable variation in the relationship between the total number of modules and body size that cannot be explained solely by expansion and contraction of individuals. Patterns derived assuming new modules differentiated at the anterior result in numerous examples in which the oldest module(s) must decrease in size with overall growth, potentially falsifying this hypothesis. Observed polarity as well as the consistent posterior location of defects and indentations support module formation at this end in D. costata. Regardless, changes in repeated units with growth share similarities with those regulated by morphogen gradients in metazoans today, suggesting that these genetic pathways were operating in Ediacaran animals.

Introduction: SHORT syndrome is a rare autosomal dominant condition described by its acronym of short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger abnormality, and teething delay. Individuals have a distinct progeroid craniofacial appearance with a triangular face, frontal bossing, hypoplastic or thin alae nasi, large low-set ears, and mandibular retrognathia. Objectives: To systematically appraise the literature and update the clinical phenotype with emphasis on the dental condition. Design: A systematic literature search was carried out to update the clinical phenotype, identifying reports of individuals with SHORT syndrome published after August 2015. The same search strategy but not limited to publication date was carried out to identify reports of the dental phenotype. Two independent reviewers screened 1937 articles with 55 articles identified for full-text review. Results: Nineteen individuals from 11 families were identified. Facial dysmorphism including ocular depression, triangular shaped face, frontal bossing, large low-set ears, and micrognathia were the most consistent features followed by lipodystrophy, insulin resistance, and intrauterine growth restriction. Teething delay, microdontia, hypodontia, and enamel hypoplasia have all been reported. Conclusion: Features that comprise the SHORT acronym do not accurately or completely describe the clinical phenotype. The craniofacial appearance is one of the most consistent features. Lipodystrophy and insulin resistance may also be considered cardinal features. After teething delay, enamel hypoplasia and microdontia are the most common dental manifestations. We present recommendations for the dental and orthodontic/orthognathic management of individuals with SHORT syndrome.

Objectives This article is one of a series on acute, severe diseases of humans caused by emerging viruses for which there are no or limited licensed medical countermeasures. We approached this summary on South American Hemorrhagic Fevers from a clinical perspective, focusing on pathogenesis, clinical features, and diagnostics, with an emphasis on therapies and vaccines that have demonstrated potential for use in an emergency situation through their evaluation in nonhuman primates (NHPs) and/or in humans. Methods A standardized literature review was conducted on the clinical, pathological, vaccine, and treatment factors for South American Hemorrhagic Fevers as a group and for each individual virus/disease. Results We identified two treatments and one vaccine platform that have demonstrated potential benefit for treating or preventing infection in humans and four other potential treatments currently under investigation. Conclusion We provide succinct summaries of these countermeasures to give the busy clinician a head start in reviewing the literature if faced with a patient with a South American Hemorrhagic Fever. We also provide links to other authoritative sources of information.

Introduction Children with Apert syndrome have hypertelorism and midfacial hypoplasia, which can be treated with facial bipartition (FB), often aided by rigid external distraction. The technique involves a midline osteotomy that lateralizes the maxillary segments, resulting in posterior cross-bites and midline diastema. Varying degrees of spontaneous realignment of the dental arches occurs postoperatively. This study aims to quantify these movements and assess whether they occur as part of a wider skeletal relapse or as dental compensation. Methods Patients who underwent FB and had high quality computed tomography scans at the preoperative stage, immediately postsurgery, and later postoperatively were reviewed. DICOM files were converted to three-dimensional bone meshes and anatomical point-to-point displacements were quantified using nonrigid iterative closest point registration. Displacements were visualized using arrow maps, thereby providing an overview of the movements of the facial skeleton and dentition. Results Five patients with Apert syndrome were included. In all cases, the arrow maps demonstrated initial significant anterior movement of the frontofacial segment coupled with medial rotation of the orbits and transverse divergence of the maxillary arches. The bony position following initial surgery was shown to be largely stable, with primary dentoalveolar relapse correcting the dental alignment. Conclusions This study showed that spontaneous dental compensation occurs following FB without compromising the surgical result. It may be appropriate to delay active orthodontic for 6-months postoperatively until completion of this early compensatory phase.

Background Symptom intensity during a common cold is highly variable, particularly after the illness peaks, contributing to delay in recovery. Rhinoviruses frequently cause colds and, during acute infections, generate leukotriene B4 and prostaglandin E2 (PGE2). PGE2 is known to initiate oxylipin class switching and resolution of acute inflammation. Thus, we hypothesized that during acute rhinovirus colds, oxylipins with pro-resolving capabilities reduce symptom severity and speed recovery. Methods Four groups of healthy volunteers were inoculated with placebo or 3 different doses of rhinovirus A16. Participants kept daily records of symptoms and contributed serial nasal lavage fluid samples. We collected semi-quantitative mass spectrometry data for 71 oxylipins in these acute samples from all participants. An ensemble analysis approach was used to further reduce this dataset. Results Levels of 15-keto-PGE2 at day 3 of the cold were consistently among the top candidates in these models of recovery symptoms. 15-keto-PGE2 was the only oxylipin with an interaction between inoculum dose and time. Acute 15-keto-PGE2 levels were inversely associated with symptoms during cold recovery in a multivariable analysis (P = .0043). Conclusions These findings show that high 15-keto-PGE2 levels during the acute cold are associated with fewer symptoms during recovery.

Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking.We used Scientific Registry of Transplant Recipients to identify 285 pediatric (18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival.DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03).Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.

Wiedemann‐Steiner syndrome (WDSTS) is an exceptionally rare autosomal dominant syndrome with considerable phenotypical variation. Clinical features include dysmorphic facial and skeletal features, growth deficiency, developmental delay, hypertrichosis cubiti and various dental features. We present a 7‐year‐old female with premature exfoliation of primary teeth and premature eruption of permanent teeth., Premature exfoliation of primary teeth is a significant diagnosis that necessities further investigation. Differential diagnoses are vast, comprising of multisystemic disorders, and life‐threatening illnesses, such as hematological malignancies.

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients ( 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.

Objective: Atherosclerosis is a chronic inflammatory disease that can be undetected in middle-aged patients. Abdominal aortic calcifications (AACs) are one form of cardiovascular disease (CVD), and these can go undetected during a routine physician visit. Sonography has the potential to assess CVD progression, quantify plaque in the aorta, and help to quantify risk in asymptomatic patients. Methodology: This pilot study modified a current AAC grading system to create a scoring method for sonographic images among a small cohort of asymptomatic participants. A traditional portable ultrasound unit was used to image participants, and a subset underwent the same imaging with a handheld transducer and tablet. Results: In this cohort, six males and five females, it was possible to adequately visualize and assess plaque, utilizing both types of ultrasound equipment. The abdominal aorta was divided into segments on the sonogram for quality of grading. Ten participants were categorized with a grade II and one participant was given a grade IIIA. Conclusion: Replication of this modified grading system is needed to better understand the clinical utilization of sonography as a risk assessment tool. The risk assessment scoring was not dependent on the type of device used.

BACKGROUND Preoperative thrombocytopenia is associated with inferior outcomes in surgical patients, though concurrent anemia may obfuscate these relationships. This investigation assesses the prevalence and clinical significance of preoperative thrombocytopenia with thorough consideration of preoperative anemia status. METHODS This is an observational cohort study of adults undergoing elective surgery with planned postoperative hospitalization from January 1, 2009 to May 3, 2018. Patients were designated into 4 groups: normal platelet and hemoglobin concentrations, isolated thrombocytopenia (ie, platelet count

Summary Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. Methods We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. Findings We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0–75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8–90·9), for 3 years was 97·3% (95·2–98·6), and for 5 years was 98·6% (97·6–100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3–95·9), for 3 years was 97·8% (96·6–99·3), and for 5 years was 96·6% (94·0–98·9). Interpretation These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. Funding European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d’HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.

Rectal cancer patients frequently receive pre-operative radiotherapy (RT), prior to surgical resection. However, colorectal cancer is heterogeneous and the degree of tumour response to pre-operative RT is highly variable. There are currently no clinically approved methods of predicting response to RT, and a significant proportion of patients will show no clinical benefit, despite enduring the side-effects. We evaluated the use of Raman spectroscopy (RS), a non-destructive technique able to provide the unique chemical fingerprint of tissues, as a potential tool to stratify patient response to pre-operative RT. Raman measurements were obtained from the formalin-fixed, paraffin-embedded (FFPE) pre-treatment biopsy specimens of 20 rectal cancer patients who received pre-operative RT. A principal component analysis and linear discriminant analysis algorithm was able to classify patient response to pre-operative RT as good or poor, with an accuracy of 86.04 ± 0.14% (standard error). Patients with a good response to RT showed greater contributions from protein-associated peaks, whereas patients who responded poorly showed greater lipid contributions. These results demonstrate that RS is able to reliably classify tumour response to pre-operative RT from FFPE biopsies and highlights its potential to guide personalised cancer patient treatment.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

BACKGROUND: To minimize ventilator-induced lung injury, the primary clinical focus is currently expanding from measuring static indices of the individual tidal cycle (eg, plateau pressure and tidal volume) to more inclusive indicators of energy load, such as total power and its elastic components. Morbid obesity may influence these components. We characterized the relative values of elastic subcomponents of total power (ie, driving power and dynamic power) in subjects with severe hypoxemia, morbid obesity, or their combination. METHODS: We analyzed data from subjects receiving mechanical ventilation divided into 4 groups. [Formula: see text] / [Formula: see text] < 150 mm Hg (severe hypoxemia) indicated probable reduction of lung compliance while body mass index > 40 kg/m(2) (morbid obesity) suggested a possible contribution to reduced respiratory system compliance from the chest wall. Group 1 included subjects with no expected abnormality of lung compliance or chest wall compliance; Group 2 included subjects with expected reduction of lung compliance on the basis of severe hypoxemia but with no morbid obesity; Group 3 included subjects with morbid obesity without severe hypoxemia; and Group 4 included subjects with morbid obesity and severe hypoxemia. All ventilator-induced lung injury predictors were compared among groups using mixed-effects linear models. RESULTS: Groups 1–4 included 61, 52, 49, and 51 subjects, respectively. Mean body mass index averaged 28.7 kg/m(2) for nonobese subjects and 52.1 kg/m(2) for morbidly obese subjects. Mean driving pressure, dynamic power, and driving power of Groups 2 and 3 exceeded the corresponding values of Group 1 but fell into similar ranges when compared with each other. These values were highest in Group 4 subjects. In Group 2, mean dynamic power and driving power values were comparable to those in Group 3. CONCLUSIONS: In mechanically ventilated subjects, stress and energy-based ventilator-induced lung injury indicators are influenced by the relative contributions of chest wall and lung to overall respiratory mechanics. Numerical guidelines for ventilator-induced lung injury risk must strongly consider adjustment for these elastic characteristics in morbid obesity.

Background Microtia is an inherited condition that results in varying degrees of external ear deformities; the most extreme form is anotia. Effective surgical reconstruction techniques have been developed. However, these usually require multistage procedures and have other inherent disadvantages. Tissue engineering technologies offer new approaches in the field of external ear reconstruction. In this setting, chondrocytes are cultured in the laboratory with the aim of creating bioengineered cartilage matrices. However, cartilage engineering has many challenges, including difficulty in culturing sufficient chondrocytes. To overcome these hurdles, the authors propose a novel model of cartilage engineering that involves co-culturing chondrocytes and adipose-derived stem cells on an allograft adipose-derived extracellular matrix scaffold. Methods Auricular chondrocytes from porcine ear were characterized. Adipose-derived stem cells were isolated and expanded from human lipoaspirate. Then, the auricular chondrocytes were cultured on the allograft adipose matrix either alone or with the adipose-derived stem cells at different ratios and examined histologically. Results Cartilage induction was most prominent when the cells were co-cultured on the allograft adipose matrix at a ratio of 1:9 (auricular chondrocyte-to-adipose-derived stem cell ratio). Furthermore, because of the xenogeneic nature of the experiment, the authors were able to determine that the adipose-derived stem cells contributed to chondrogenesis by means of a paracrine stimulation of the chondrocytes. Conclusions In this situation, adipose-derived stem cells provide sufficient support to induce the formation of cartilage when the number of auricular chondrocytes available is limited. This novel model of cartilage engineering provides a setting for using the patient's own chondrocytes and adipose tissue to create a customized ear framework that could be further used for surgical reconstruction.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6 + epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

Lymph node (LN)–positive cervical cancer is associated with a poor prognosis. We report outcomes for women with LN-positive cervical cancer treated with intensity-modulated radiation therapy (IMRT) with dose-escalated simultaneous integrated boost (SIB) to involved LNs. Between 2005 and 2017, 59 women with LN-positive, non-metastatic, cervical cancer underwent definitive chemoradiotherapy (CRT) with an image-guided LN boost to a median dose of 56.25 Gy in 25 fractions. Acute and late adverse events (AEs) were recorded per common terminology criteria for adverse events. The Kaplan-Meier method was used to estimate the overall survival (OS), progression-free survival (PFS), and locoregional control (LRC). Median age was 49 years (IQR 37–56). Women had involved LNs in the pelvis (56%) or pelvis and para-aortic (PA) LNs (44%), with a median of 3 (IQR 2–6) grossly involved LNs per patient. Median follow-up was 30 months (IQR 11–45). Estimated 3-year OS, PFS, and LRC were 67% (95% CI, 51%–84%), 60% (95% CI, 45%–76%), and 89% (95% CI, 76%–99%), respectively. PA LN involvement (HR 2.51; 95% CI, 1.05–5.99; p = 0.04) and the presence of ≥ 4 grossly involved LNs (HR 2.79; 95% CI, 1.16–6.71; p = 0.02) were associated with a higher risk of disease progression on univariate analysis. The incidence of treatment-related acute grade 3+ acute GI or GU AEs was 3%, while late GI or GU treatment-related AEs occurred in 12%. Chemoradiation with a LN-directed SIB for women with LN-positive cervical cancer is well tolerated and is associated with excellent oncologic outcomes. In this report, we evaluated the oncologic efficacy and adverse events associated with definitive chemoradiotherapy with a simultaneous integrated boost to grossly involved lymph nodes for women with lymph node–positive cervical cancer. We have identified acceptable rates of adverse events and excellent oncologic outcomes, even in a very high risk cohort of women with cervical cancer.

Purpose To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice. Patients and Methods We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs). P Results Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82, P = .04; MVA: HR, 3.64, P = .03), advanced stage disease (UVA: HR, 4.68, P 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99, P Conclusions Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.

The COVID-19 pandemic has created profound challenges for health care systems worldwide. The exponential spread of COVID-19 has forced mental health providers to find new ways of providing mental health services that maintain physical distance and keeps providers and patients at home limiting possible exposure to the deadly virus. The pandemic has thus sparked a sudden interest in providing mental health services via telepsychotherapy (otherwise known as telehealth or telemedicine). Telepsychotherapy care has some inherent challenges that must always be mastered by providers to render effective care. Previous research and professional guidelines understandably note possible concerns about providing telepsychotherapy care to high-risk suicidal patients in a remote location. The coronavirus pandemic now poses all new ethical concerns about the routine practice of having an acutely suicidal patient go to an emergency department and/or admitting such patients to an inpatient psychiatric unit (if the public health goal is to limit the spread of this deadly virus). To this end, this article describes a pandemic-driven effort to rapidly provide support, guidance, and resources to providers around the world to use a suicide-focused and evidence-based intervention called the Collaborative Assessment and Management of Suicidality (CAMS) within a telepsychotherapy modality. Additional suicide-relevant resources are being made available to provide further guidance and support to mental health professionals worldwide. In the midst of a global pandemic, there are emerging ways to help reduce further loss of life to suicide through the medium of telepsychotherapy to provide effective clinical care that is suicide-focused and evidence-based.

Context and Objectives The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). Design & Participants 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. Results Offspring’s measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. Conclusions Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

Objectives There are limited case series reporting the impact on women affected by coronavirus during pregnancy. In women affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the case fatality rate appears higher in those affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the Royal College of Obstetricians and Gynaecologists' (RCOG) guidelines on COVID-19 infection in pregnancy. Methods Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomized controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the Royal College of Paediatrics and Child Health (RCPCH) and RCOG who provided expert consensus on areas in which data were lacking. Results From 9965 search results in PubMed and 600 in MedRxiv, 21 relevant studies, all of which were case reports or case series, were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU), one of whom remained on extracorporeal membrane oxygenation. No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with reverse transcription polymerase chain reaction after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester. Conclusions Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and that one woman remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK's reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, RCOG, in consultation with RCPCH, developed guidance for delivery and neonatal care in pregnancies affected by COVID-19, which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of affected mothers and their babies. We hope that this review will be helpful for maternity and neonatal services planning their response to COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The outbreak of a novel coronavirus (COVID-19) with symptoms that mimic bronchitis and other chest infections has created a need for quick diagnosis to prevent disease spread. Traditionally, computed tomography (CT) has been used as the primary method to identify infection and staging of the virus. While effective, repeated use of ionizing radiation, particularly in susceptible patient populations, can add risk as the disease is monitored through full recovery. Sonography of the chest may be a viable alternative for diagnosis and monitoring of COVID-19. In addition, new technology such as the remote robotic ultrasound equipment being used at Zhejiang Provincial People’s Hospital in Hangzhou, China, has the potential to facilitate sonographic evaluation with minimal disease exposure to the sonologist and to other patients by eliminating the need for patient transport to imaging facilities. Additional studies will need to be conducted to evaluate the effectiveness of sonography versus other imaging modalities in the diagnosis and treatment of COVID-19 and other novel diseases.

BACKGROUND: Hyperpolarized helium 3 magnetic resonance imaging ((3)He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children. OBJECTIVE: To evaluate the safety of (3)He MRI in children and adolescents with asthma. MATERIALS AND METHODS: This was a retrospective observational study. (3)He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 (3)He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO(2)) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models. RESULTS: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO(2) after (3)He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after (3)H inhalation, and an increased SpO(2) post MRI. CONCLUSION: The use of (3)He MRI is safe in children and adolescents with asthma.

Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown.We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models.The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race.We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.

Background Interventions that induce ketosis simultaneously lower blood glucose and the explanation for this phenomenon is unknown. Additionally, the glucose‐lowering effect of acute ketosis is greater in people with type 2 diabetes (T2D). On the contrary, L‐alanine is a gluconeogenic substrate secreted by skeletal muscle at higher levels in people with T2D and infusing of ketones lower circulating L‐alanine blood levels. In this study, we sought to determine whether supplementation with L‐alanine would attenuate the glucose‐lowering effect of exogenous ketosis using a ketone ester (KE). Methods This crossover study involved 10 healthy human volunteers who fasted for 24 h prior to the ingestion of 25 g of d‐β‐hydroxybutyrate (βHB) in the form of a KE drink (ΔG®) on two separate visits. During one of the visits, participants additionally ingested 2 g of L‐alanine to see whether L‐alanine supplementation would attenuate the glucose‐lowering effect of the KE drink. Blood L‐alanine, L‐glutamine, glucose, βHB, free fatty acids (FFA), lactate and C‐peptide were measured for 120 min after ingestion of the KE, with or without L‐alanine. Findings The KE drinks elevated blood βHB concentrations from negligible levels to 4.52 ± 1.23 mmol/L, lowered glucose from 4.97 ± SD 0.39 to 3.77 ± SD 0.40 mmol/L, and lowered and L‐alanine from 0.56 ± SD 0.88 to 0.41 ± SD 0.91 mmol/L. L‐alanine in the KE drink elevated blood L‐Alanine by 0.68 ± SD 0.15 mmol/L, but had no significant effect on blood βHB, L‐glutamine, FFA, lactate, nor C‐peptide concentrations. By contrast, L‐alanine supplementation significantly attenuated the ketosis‐induced drop in glucose from 28% ± SD 8% to 16% ± SD 7% (p, This was crossover study involved two separate visits for 10 healthy human volunteers who fasted for 24 h prior to the ingestion of 25 g of d‐β‐hydroxybutyrate (βHB) monoester (ΔG®). During one of the visits, participants ingested 2 g of L‐alanine. Blood L‐alanine, L‐glutamine, glucose, βHB, free fatty acids (FFA), lactate and C‐peptide were measured. Demonstrating that ketosis induces hypoglycemia, in part, by limiting L‐alanine availability for gluconeogenesis.

An emergent approach to bacterial infection is the use of host rather than bacterial-directed strategies. This approach has the potential to improve efficacy in especially challenging infection settings, including chronic, recurrent infection due to intracellular pathogens. For nearly two decades, the pleiotropic effects of statin drugs have been examined for therapeutic usefulness beyond the treatment of hypercholesterolemia. Interest originated after retrospective studies reported decreases in the risk of death due to bacteremia or sepsis for those on a statin regimen. Although subsequent clinical trials have yielded mixed results and earlier findings have been questioned for biased study design, in vitro and in vivo studies have provided clear evidence of protective mechanisms that include immunomodulatory effects and the inhibition of host cell invasion. Ultimately, the benefits of statins in an infection setting appear to require attention to the underlying host response and to the timing of the dosage. From this examination of statin efficacy, additional novel host-directed strategies may produce adjunctive therapeutic approaches for the treatment of infection where traditional antimicrobial therapy continues to yield poor outcomes. This review focuses on the opportunistic pathogen, Staphylococcus aureus, as a proof of principle in examining the promise and limitations of statins in recalcitrant infection.

Introduction Ketogenic diets have shown to improve glycaemic control in patients with type 2 diabetes. This study investigated the safety, tolerability, and effects on glycaemic control in patients with type 2 diabetes of an exogenous ketone monoester (KE) capable of inducing fasting‐like elevations in serum β‐hydroxybutyrate (βHB) without the need for caloric or carbohydrate restriction. Methods Twenty one participants (14 men and 7 women, aged 45 ± 11 years) with insulin‐independent type 2 diabetes, and unchanged hypoglycaemic medication for the previous 6 months, were recruited for this non‐randomised interventional study. Participants wore intermittent scanning glucose monitors (IS‐GM) for a total of 6 weeks and were given 25 ml of KE 3 times daily for 4 weeks. Serum electrolytes, acid‐base status, and βHB concentrations were measured weekly and cardiovascular risk markers were measured before and after the intervention. The primary endpoints were safety and tolerability, with the secondary endpoint being glycaemic control. Results The 21 participants consumed a total of 1,588 drinks (39.7 litres) of KE over the course of the intervention. Adverse reactions were mild and infrequent, including mild nausea, headache, and gastric discomfort following fewer than 0.5% of the drinks. Serum electrolyte concentrations, acid‐base status, and renal function remained normal throughout the study. Compared to baseline, exogenous ketosis induced a significant decrease in all glycaemic control markers, including fructosamine (335 ± 60 μmol/L to 290 ± 49 μmol/L, p, This study involved a month of closely supervised exogenous ketosis using a ketone monoester. Additionally, it involved six weeks of continuous glucose monitorization to compare glucose control before, during and after exogenous ketosis. Exogenous ketosis was safe, well‐tolerated and improved glucose control.

Objective: LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia and severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in LIPA which unexpectedly associate with increased mRNA expression. However, an exonic variant (rs1051338 resulting in T16P) in linkage with intronic variants lies in the signal peptide region and putatively disrupts trafficking. We sought to functionally investigate the net impact of this locus on LIPA and whether rs1051338 could disrupt LIPA processing and function to explain coronary artery disease risk. Approach and Results: In monocytes isolated from a large cohort of healthy individuals, we demonstrate both exonic and intronic risk variants are associated with increased LIPA enzyme activity coincident with the increased transcript levels. To functionally isolate the impact of rs1051338, we studied several in vitro overexpression systems and consistently observed no differences in LIPA expression, processing, activity, or secretion. Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk. Conclusions: Our findings show that common LIPA exonic variants in the signal peptide are of minimal functional significance and suggest coronary artery disease risk is instead associated with increased LIPA function linked to intronic variants. Understanding the mechanisms and cell-specific contexts of LIPA function in the plaque is necessary to understand its association with cardiovascular risk.

End-stage renal disease (ESRD) is a prevalent disease that results from kidney failure in the last stage of chronic kidney disease. This disease has many chronic and debilitating symptoms, including muscle wasting. Unfortunately, current methods to diagnose muscle wasting, in this patient population, are rather imprecise and/or expensive. To develop a better method, this study examined the use of sonography across four separate patients with ESRD in a typical clinical setting. Multiple muscle measurements were taken in the patients’ upper arm via sonography, which were compared to laboratory test results and skinfold measurements. This multiple case comparison demonstrates the feasibility of using sonography to measure subcutaneous tissue and muscle mass in this patient population. It also has the potential to correlate with or support other clinical measures of disease severity. Further study is recommended to examine these correlations and to identify clinical implications for sonographic measurement of overall muscle wasting.

Purpose: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of 11C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy. Methods and Materials: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.25 Gy), all in 25 fractions. RT-naïve patients had the prostatic fossa included in the initial treatment volumes followed by a sequential boost (median dose, 68 Gy). GI and GU AEs were reported per Common Terminology Criteria for Adverse Events (version 4.0) with data gathered retrospectively. Differences in maximum GI and GU AEs at baseline, immediately post-RT, and at early (median, 4 months) and late (median, 14 months) follow-up were assessed. Results: Median follow-up was 16 months (interquartile range [IQR], 11-25). Median prostate-specific antigen at time of positive CholPET was 2.3 ng/mL (IQR, 1.3-4.8), with a median of 2 (IQR, 1-4) choline-avid LNs per patient. Most recurrences were within the pelvis (53%) or pelvis + paraortic (40%). Baseline rates of grade 1 to 2 GI AEs were 8.4% compared with 51.9% (4.7% grade 2) of patients post-RT (P

Obesity has been linked to several chronic health conditions, including increased risk for cardiovascular disease, type 2 diabetes, some cancers, and metabolic syndrome. Understanding the trends in metabolic syndrome and examining those who are at an increased risk for metabolic conditions is paramount. Currently body mass index (BMI), waist circumference (WC), and dual-energy X-ray absorptiometry (DXA) are believed to be appropriate screening measures for assessing body composition and metabolic syndrome risk. This approach uses diagnostic medical sonography (DMS) as a tool for assessing abdominal adiposity in hopes of this methodology being adopted to help determine an individual’s risk for metabolic conditions. A convenience sample of overweight and obese cancer survivors provided several anthropometric measures as well as imaging data to determine if sonographic measures of abdominal fat could be assessed longitudinally. These measures were then compared to corresponding measures of BMI, WC, and DXA (android percent body fat, subscores). These measures demonstrated moderately positive association and were statistically significant. DMS is an indirect imaging tool that could be used in correlation with other measures to help determine an individual’s risk for metabolic syndrome.

Background: Much of the research exploring psychological distress with meningioma stem from studies including several brain tumour types (including malignant tumours) meaning that focus on meningio...

Ocular injury and vision loss are rare complications of surgery. Spine surgery has been identified as particularly high risk for postoperative vision loss; nevertheless, ocular injuries have not been comprehensively assessed in this patient population. This historical cohort study assessed incidence, cause, and risk factors of perioperative ocular injury after spine surgery at a tertiary care medical centre from January 1, 2006 through January 31, 2018. Patients were included who had ocular injury identified during an ophthalmology consultation in the first seven postoperative days. Differences in demographic, laboratory, intraoperative, and postoperative characteristics between those experiencing or not experiencing ocular injury were assessed with Fisher exact and Wilcoxon signed-rank tests for categorical and continuous variables, respectively. Of 20,128 qualifying spine surgeries, 39 cases of perioperative ocular injuries were identified (39/20,128; 0.19% [95% confidence interval (CI), 0.14 to 0.26]). The most common ocular injury was blurry vision of unknown cause (13/39; 33%; 95% CI, 18.6 to 46.4), followed by ischemic optic neuropathy (9/39; 23%; 95% CI, 12.6 to 38.3) and corneal abrasion (7/39; 18%; 95% CI, 9.0 to 32.7). All cases of blurry vision of unknown cause were diagnosed via ophthalmology consultation and resolved within several days. Patients with perioperative ocular injury were more likely to have baseline anemia, have undergone fusion and instrumentation procedures, and had longer operative times with greater crystalloid, colloid, and transfusion requirements and more blood loss. Although not representing a causal relationship, these data suggest that surgical factors may have a greater role than demographic characteristics or other clinical factors in the development of perioperative ocular injury. Surgeons, anesthesiologists, and patients should be aware of the increased risk of ocular injury that accompanies longer, more extensive spine operations.

Purpose This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). Methods and Materials Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naive T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. Results Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032). Conclusions An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

In FGFR2 craniosynostosis, midfacial hypoplasia features oculo-orbital disproportion and symptomatic exorbitism. Clinical consequences may mandate surgery at a young age to prevent globe subluxation, corneal ulceration, and potential loss of vision. Monobloc osteotomy and distraction osteogenesis (monobloc distraction) seek to correct exorbitism. A report of the age-related impact of monobloc osteotomy and distraction osteogenesis on orbital volume, globe volume, and globe protrusion is presented.Computed tomographic scan data from 28 Crouzon-Pfeiffer patients were assessed at preoperative, early postoperative, and 1-year follow-up time points. Orbital volumes, globe volumes, and globe protrusions were measured by manual and semiautomatic segmentation techniques, and these were compared to 40 age-matched controls.Crouzon-Pfeiffer syndrome orbital volumes are significantly small, and are significantly overexpanded by distraction to endpoints correcting symptomatic exorbitism. Globe volumes are significantly larger than controls under 5 years, do not independently correlate with globe protrusion, and are unaffected by surgery. Correlation between orbital volume expansion and reduction of globe protrusion is not significant. Age-related variations of postoperative growth potential occur to 1 year postoperatively. The Crouzon-Pfeiffer syndrome FGFR2 orbit exhibits early growth acceleration followed by premature growth arrest at 10 to 14 years.Orbital volume expansion by monobloc osteotomy and distraction osteogenesis is not the sole determinant of reduced globe protrusion. Mean volume relapse of the orbit at 1 year is insignificant across the series. Derived Crouzon-Pfeiffer growth curves suggest that "early functional monobloc" in infants occurs on a background of dynamic orbital growth, which remains programmed to a Crouzon-Pfeiffer FGFR2 phenotype and aligns with the incidence of delayed clinical regression and later secondary surgery.Therapeutic, IV.

Craniofacial microsomia is characterized by an asymmetric hypoplasia of derivatives of the first and second pharyngeal arch, leading to a variety of phenotypic presentations. Studies on surgical correction of patients with craniofacial microsomia have small cohorts, leaving controversial opinions on the optimal treatment modality, the indication for surgery, and the optimal timing of surgery. The purpose of this study was to evaluate the types of, timing of, and total number of surgical corrections performed and the number of surgical procedures in correlation to the severity of the phenotype.A retrospective chart study was conducted including patients diagnosed with craniofacial microsomia from three large craniofacial units. Demographic, radiographic, and clinical information was obtained, including type and number of surgical procedures and age at the time of surgery.A total of 565 patients were included. In total, 443 (78.4 percent) of all patients underwent some form of surgery during their life, varying from skin tag removal to major craniofacial operations. The number of surgical interventions was higher with increasing severity of phenotype, bilateral presentation, and a younger age at the first intervention.Multiple surgical corrections are frequently seen in patients with a more severe or bilateral presentation. Furthermore, those who are treated earlier in life for correction of asymmetry of the mandible will undergo significantly more surgical procedures to correct the asymmetry later on, independent of the Pruzansky-Kaban type mandible. A prospective international multicenter study is designed with a uniform registration and outcome measurement tool to identify the optimal treatment strategy.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P

Defects involving the esophagus can pose a complex challenge to the reconstructive surgeon. Appropriate choice of recipient vessel lays the foundation for these operations. These cases often involve a “vessel-depleted” or “frozen” neck secondary to resection and treatment of malignancy, making knowledge of the various recipient vessel options vital. This chapter describes the recipient vessels available in esophagus reconstruction, and the pertinent anatomy, benefits, and downsides associated with each vessel option.

During the 2015–16 winter, the US experienced a relatively mild influenza season compared to Taiwan, which had a higher number of total and severe cases. While H1N1pdm viruses dominated global surveillance efforts that season, the global distribution of genetic variants and their contributions to disease severity have not been investigated. Samples collected from influenza A-positive patients by the Johns Hopkins Center of Excellence for Influenza Research and Surveillance active surveillance in the emergency rooms in Baltimore, Maryland, USA, and northern Taiwan between November 2015 and April 2016, were processed for influenza A virus whole-genome sequencing. In Baltimore, the majority of the viruses were the H1N1pdm clade 6B.1 and no H1N1pdm clade 6B.2 viruses were detected. In northern Taiwan, more than half of the H1N1pdm viruses were clade 6B.1 and 38% were clade 6B.2, consistent with the global observation that most 6B.2 viruses circulated in Asia and not North America. Whole virus genome sequence analysis identified two genetic subgroups present in each of the 6B.1 and 6B.2 clades and one 6B.1 interclade reassortant virus. Clinical data showed 6B.2 patients had more disease symptoms including higher crude and inverse probability weighted odds of pneumonia than 6B.1 patients, suggesting 6B.2 circulation may be one of the reasons for the severe flu season in Taiwan. Local surveillance efforts linking H1N1pdm virus sequences to patient clinical and demographic data improve our understanding of influenza circulation and disease potential.

Vascular compromise and blindness are reported but rare complications of facial soft tissue filler injections. Stroke is an even rarer complication resulting from intraarterial injection of fillers. We present a case of a patient suffering all 3 complications following hyaluronic acid filler injection: forehead skin vascular compromise, unilateral blindness, and ipsilateral subclinical strokes. Were it not for a stroke workup protocol, the incidental strokes may have otherwise gone undetected, suggesting the incidence of stroke from intraarterial injection may be higher than reported. Further, we review the literature and recommendations for prevention and management of threatened tissue ischemia and vision loss from facial filler injection. Level of Evidence: 5

Asthma with severe exacerbation is the most common cause of hospitalization among young children. We aim to increase the understanding of this clinically important disease entity through a genome-wide association study. The discovery analysis comprises 2866 children experiencing severe asthma exacerbation between ages 2 and 6 years, and 65,415 non-asthmatic controls, and we replicate findings in 918 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) birth cohorts. We identify rs281379 near FUT2/MAMSTR on chromosome 19 as a novel risk locus (OR = 1.18 (95% CI = 1.11–1.25), Pdiscovery = 2.6 × 10−9) as well as a biologically plausible interaction between functional variants in FUT2 and ABO. We further discover and replicate a potential causal mechanism behind this interaction related to S. pneumoniae respiratory illnesses. These results suggest a novel mechanism of early childhood asthma and demonstrates the importance of phenotype-specificity for discovery of asthma genes and epistasis., Genetic variants discovered through genome-wide association studies for asthma together account for a small portion of the heritability. Here, the authors identify a possible epistatic relationship between coding variants in FUT2 and ABO, especially pronounced in severe and early onset asthma.

Background Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. Objectives In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. Methods Children participating in the Childhood Origins of Asthma study (n=285) provided nasopharyngeal mucus samples in the first two years of life, during routine healthy study visits (2, 4, 6, 9, 12, 18 and 24 months of age) and episodes of respiratory illnesses, which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and correlated these with presence of asthma at 6, 8, 11, 13 and 18 years of age. Results Of the four microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. Conclusion In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma. Clinical Implication Identifying factors that promote early colonization with S. aureus may lead to future interventional studies to prevent childhood asthma., Capsule summary: In a birth cohort study, early colonization of the upper airway with Staphylococcus aureus and detection of rhinoviruses and Moraxella catarrhalis during illnesses were associated with subsequent childhood asthma.

Pulp canal calcification is 1 of the possible outcomes after certain types of dental trauma. This can make endodontic treatment more challenging should it become necessary. Because of the increased degree of difficulty, sometimes procedural incidents do occur during root canal treatment. This case report demonstrates an unusual clinical presentation of a root perforation and missed canal, which had undergone calcification as a result of trauma some years earlier. A contemporary approach to treatment involved a combination of treating the biological complication of the calcified canal combined with surgical repair of the iatrogenic complication of a perforation using modern imaging techniques and materials.

Highlight • Social disconnection – both objective social isolation as well as perceived social isolation (otherwise known as loneliness) – is a prevalent affliction among older adults, with profound effects on mental health. • Mechanistic understanding of how mental illness contributes to, is exacerbated by, or is otherwise linked to social disconnection remains elusive, and therapeutic interventions which leverage social connection to enhance compliance with or efficacy of mental health treatment, though promising, remain scarce. • The National Institute of Mental Health (NIMH) is committed to transforming the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. To translate basic knowledge into new methods for diagnosis, treatment, and prevention of mental illness demands appreciation for the broader milieu of social and environmental factors in which mental illness prevails – of which, social connection or disconnection is one.

Aortic stiffening, assessed as pulse-wave velocity (PWV), increases with age and is an important antecedent to, and independent predictor of, cardiovascular diseases (CVD) and other clinical disorders of aging. Aerobic exercise promotes lower levels of aortic stiffness in older adults, but the underlying mechanisms are incompletely understood, largely due to inherent challenges of mechanistic studies of large elastic arteries in humans. Voluntary wheel running (VWR) is distinct among experimental animal exercise paradigms in that it allows investigation of the physiologic effects of aerobic training without potential confounding influences of aversive molecular signaling related to forced exercise. In this study, we investigated whether VWR in mice may be a suitable model for mechanistic studies (i.e., “reverse translation”) of the beneficial effects of exercise on arterial stiffness in humans. We found that 10 weeks of VWR in old mice (~ 28 months) reversed age-related elevations in aortic PWV assessed in vivo (Old VWR: 369 ± 19 vs. old sedentary: 439 ± 20 cm/s, P

BackgroundTumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development.MethodsMicroarrays were used to analyze the gene expression profile of macrophages (MΦs) in the context of breast cancer and to examine the impact of TFEB overexpression. Cell culture studies were performed to define the mechanisms by which TFEB affects MΦ gene expression and function. Mouse studies were carried out to investigate the impact of MΦ TFEB deficiency or activation on breast tumor growth. Human cancer genome data were analyzed to reveal the prognostic value of TFEB and its regulated genes.ResultsTAM-mimic MΦs display a unique gene expression profile, including significant reduction in TFEB expression. TFEB overexpression favorably modulates TAM gene expression through multiple signaling pathways. Specifically, TFEB upregulates suppressor of cytokine signaling 3 (SOCS3) and peroxisome proliferator-activated receptor γ (PPARγ) expression and autophagy/lysosome activities, inhibits NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome and hypoxia-inducible factor (HIF)-1α mediated hypoxia response, and thereby suppresses an array of effector molecules in TAMs including arginase 1, interleukin (IL)-10, IL-1β, IL-6 and prostaglandin E2. MΦ-specific TFEB deficiency promotes, while activation of TFEB using the natural disaccharide trehalose halts, breast tumor development by modulating TAMs. Analysis of human patient genome database reveals that expression levels of TFEB, SOCS3 and PPARγ are positive prognostic markers, while HIF-1α is a negative prognostic marker of breast cancer.ConclusionsOur study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer by favorably modulating TAM function and the TME.

Background We aimed to evaluate the risk of major bleeding in non-surgical critically ill patients who received aspirin in conjunction with therapeutic anticoagulation (concomitant therapy) compared to those who received therapeutic anticoagulation alone. Methods This is a retrospective cohort study of critically ill patients initiated on therapeutic anticoagulation at a large academic medical center from 2007 to 2016. The exposure of interest was aspirin therapy during anticoagulation. The primary outcome was the incidence of major bleeding during hospitalization. Secondary outcomes included in-hospital mortality, hospital free days, and new myocardial infarction or stroke. Results 5507 (73.2%) patients received anticoagulation alone and 2014 (26.8%) received concomitant therapy; major bleeding occurred in 19.0% and 22.2%, respectively. There was no increased risk of major bleeding [OR 1.10 (95% CI: 0.93–1.30); p = .27] or mortality [OR 0.93 (95% CI: 0.77–1.11); p = .43] with concomitant therapy. Patients receiving concomitant therapy had fewer hospital-free days (mean decrease of 0.73 [1.36, 0.09]; p = .03) and were more likely to experience new myocardial infarction or stroke [OR 2.61 (95% CI: 1.72–3.98); p Conclusions In non-surgical critically ill patients receiving therapeutic anticoagulation, concomitant use of aspirin was not associated with an increased risk of bleeding or in-hospital mortality.