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Because of the limited published information on complications that obstructive sleep apnea (OSA) patients experience during and after cardiac surgery, we investigated OSA as a risk factor for postoperative outcomes.This project used the Northern New England Cardiovascular Disease Study Group's data collected between 2011 and 2017 based on The Society of Thoracic Surgeons Adult Cardiac Surgery Database Data Collections form. A retrospective analysis of 1555 patients with OSA and 10,450 patients without OSA across 5 medical centers undergoing isolated coronary artery bypass grafting, isolated valve surgery, and combined coronary artery bypass grafting valve surgery was conducted. We used 1:1 nearest-neighbor propensity score matching with no replacement to balance characteristics among patients with and without OSA.There was a statistically significant increased risk of postoperative pneumonia, increased length of total and postoperative stay, and time to initial extubation. Two outcomes trended toward significance: intra- and postoperative intraaortic balloon pump use. Outcomes that failed to show statistical significance were surgical site infection, atrial fibrillation, cerebrovascular accident, permanent pacemaker placement, and blood products given. A chart review conducted on a subset of the study cohort revealed that more than 40% of OSA patients did not receive continuous positive airway pressure or bilevel positive airway pressure therapy postoperatively during their hospitalization.Our study aligns with the literature in concluding that OSA has deleterious effects on postoperative outcomes of cardiac surgery patients. Further research to better stratify OSA patients by severity are still needed. Additionally heightened awareness of the need to screen, diagnose, and properly treat patients for OSA is needed.

RASopathies are multisystemic disorders caused by germline mutations in genes linked to the RAS/mitogen-activated protein kinase pathway. Diagnosis of RASopathy can be triggered by clinical clues ("red flags") which may direct the clinician toward a specific gene test. Compared with sarcomeric hypertrophic cardiomyopathy, hypertrophic cardiomyopathy in RASopathies (R-HCM) is associated with higher prevalence of congestive heart failure and shows increased prevalence and severity of left ventricular outflow tract obstruction. Biventricular involvement and the association with congenital heart disease, mainly pulmonary stenosis, have been commonly described in R-HCM. The aim of this review is to assess the prevalence and unique features of R-HCM and to define the available therapeutic options.

OBJECTIVE Minimally invasive surgery (MIS) techniques can effectively stabilize and decompress many thoracolumbar injuries with decreased morbidity and tissue destruction compared with open approaches. Nonetheless, there is limited direction regarding the breadth and limitations of MIS techniques for thoracolumbar injuries. Consequently, the objectives of this study were to 1) identify the range of current practice patterns for thoracolumbar trauma and 2) integrate expert opinion and literature review to develop an updated treatment algorithm. METHODS A survey describing 10 clinical cases with a range of thoracolumbar injuries was sent to 12 surgeons with expertise in spine trauma. The survey results were summarized using descriptive statistics, along with the Fleiss kappa statistic of interrater agreement. To develop an updated treatment algorithm, the authors used a modified Delphi technique that incorporated a literature review, the survey results, and iterative feedback from a group of 14 spine trauma experts. The final algorithm represented the consensus opinion of that expert group. RESULTS Eleven of 12 surgeons contacted completed the case survey, including 8 (73%) neurosurgeons and 3 (27%) orthopedic surgeons. For the 4 cases involving patients with neurological deficits, nearly all respondents recommended decompression and fusion, and the proportion recommending open surgery ranged from 55% to 100% by case. Recommendations for the remaining cases were heterogeneous. Among the neurologically intact patients, MIS techniques were typically recommended more often than open techniques. The overall interrater agreement in recommendations was 0.23, indicating fair agreement. Considering both literature review and expert opinion, the updated algorithm indicated that MIS techniques could be used to treat most thoracolumbar injuries. Among neurologically intact patients, percutaneous instrumentation without arthrodesis was recommended for those with AO Spine Thoracolumbar Classification System subtype A3/A4 (Thoracolumbar Injury Classification and Severity Score [TLICS] 4) injuries, but MIS posterior arthrodesis was recommended for most patients with AO Spine subtype B2/B3 (TLICS > 4) injuries. Depending on vertebral body integrity, anterolateral corpectomy or mini-open decompression could be used for patients with neurological deficits. CONCLUSIONS Spine trauma experts endorsed a range of strategies for treating thoracolumbar injuries but felt that MIS techniques were an option for most patients. The updated treatment algorithm may provide a foundation for surgeons interested in safe approaches for using MIS techniques to treat thoracolumbar trauma.

Objective To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD). Methods KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD. Results Infants identified by newborn screening with possible KD should enter one of three clinical follow-up pathways (Early infantile KD, at-risk for LOKD, or unaffected), based on galactocerebrosidase (GALC) activity, psychosine concentration, and GALC genotype. Patients considered at-risk for LOKD based on low GALC activity and an intermediate psychosine concentration are further split into a high-risk or low-risk follow-up pathway based on genotype. Review of the historical New York State cohort found that the updated follow-up recommendations would reduce follow up testing by 88%. Conclusion The KD NBS Council has presented updated consensus recommendations for efficient and effective classification and follow-up of NBS positive patients with a focus on long-term follow-up of those at-risk for LOKD.

The Earth's mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists' education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.

BACKGROUND Perioperative stroke is associated with high rates of morbidity and mortality, yet there is no validated screening tool. The modified National Institutes of Health Stroke Scale (mNIHSS) is validated for use in nonsurgical strokes but is not well-studied in surgical patients. We evaluated perioperative changes in the mNIHSS score in noncardiac, non-neurological surgery patients, feasibility in the perioperative setting, and the relationship between baseline cognitive screening and change in mNIHSS score. METHODS Patients aged 65 years and above presenting for noncardiac, non-neurological surgery were prospectively recruited. Those with significant preoperative cognitive impairment (Montreal Cognitive Assessment score [MoCA] ≤17) were excluded. mNIHSS was assessed preoperatively, on postoperative day (POD) 0, POD 1, and POD 2, demographic data collected, and feedback solicited from participants. Changes in mNIHSS from baseline, time to completion, and relationship between baseline MoCA score and change in mNIHSS score were analyzed. RESULTS Twenty-five patients were enrolled into the study; no overt strokes occurred. Median mNIHSS score increased between baseline (0 interquartile range [IQR 0 to 1]) and POD 0 (2 [IQR 0 to 3.5]; P

LEARNING OBJECTIVES After studying this article, the participant should be able to: 1. Appreciate the evolution and increasing complexity of transplanted facial allografts over the past two decades. 2. Discuss indications and contraindications for facial transplantation, and donor and recipient selection criteria and considerations. 3. Discuss logistical, immunologic, and cost considerations in facial transplantation, in addition to emerging technologies used. 4. Understand surgical approaches and anatomical and technical nuances of the procedure. 5. Describe aesthetic, functional, and psychosocial outcomes of facial transplantation reported to date. SUMMARY This CME article highlights principles and evolving concepts in facial transplantation. The field has witnessed significant advances over the past two decades, with more than 40 face transplants reported to date. The procedure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous reconstructive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date.

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.

KCNJ16 encodes Kir5.1 and acts in combination with Kir4.1, encoded by KCNJ10, to form an inwardly rectifying K+ channel expressed at the basolateral membrane of epithelial cells in the distal nephron. This Kir4.1/Kir5.1 channel is critical for controlling basolateral membrane potential and K+ recycling, the latter coupled to Na-K-ATPase activity, which determines renal Na+ handling. Previous work has shown that Kcnj16−/− mice and SSKcnj16−/− rats demonstrate hypokalemic, hyperchloremic metabolic acidosis. Here, we present the first report of a patient identified to have biallelic loss-of-function variants in KCNJ16 by whole exome sequencing who presented with chronic metabolic acidosis with exacerbations triggered by minor infections.

Purpose Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns. Methods To minimize the false-positive rate, a two-tier screening algorithm was designed. The primary test was to quantify C16:0-sulfatide in DBS by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The screening cutoff was established based on the results from 15 MLD newborns to achieve 100% sensitivity. The secondary test was to measure the ARSA activity in DBS from newborns with abnormal C16:0-sulfatide levels. Only newborns that displayed both abnormal C16:0-sulfatide abundance and ARSA activity were considered screen positives. Results A total of 27,335 newborns were screened using this two-tier algorithm, and 2 high-risk cases were identified. ARSA gene sequencing identified these two high-risk subjects to be a MLD-affected patient and a heterozygote. Conclusion Our study demonstrates that newborn screening for MLD is highly feasible in a real-world scenario with near 100% assay specificity.

Authors have speculated that vascularized composite allotransplantation (VCA) recipients may require greater maintenance immunosuppression than solid organ transplant (SOT) recipients due to the higher antigenicity of skin. However, detailed comparisons of VCA and SOT immunosuppression regimens have been limited.Hand and face VCA recipient immunosuppression data were collected through a systematic literature review. Kidney recipient data were obtained through a retrospective chart review of the authors' institution. Prednisone and mycophenolate mofetil (MMF) doses were compared between VCA and kidney recipients at predefined follow-up intervals (1, 1-5, and5 y). Tacrolimus target trough levels (TTTL) were compared at follow-up intervals of 1-5 and5 y, and stratified into our institution's kidney transplant risk-based target ranges (4-6 ng/mL, 6-8 ng/mL) or higher (8 ng/mL).Immunosuppression data were available for 57 VCA and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. VCA recipient mean MMF dose was significantly greater at1-y (1.71 ± 0.58 versus 1.16 ± 0.55 gm/d; P = 0.01). For VCA recipients, there was a significant difference (P = 0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/mL, 6-8 ng/mL, and8 ng/mL) between 1 and 5 y (24.0%, 20.0%, 56.0%, respectively) and5 y (28.6%, 42.9%, 28.6%).At longer follow-up, VCA and kidney recipients receive comparable MMF/prednisone doses, and most VCA recipients are treated with TTTL similar to kidney recipients. Further research may improve our understanding of VCA's complex risk/benefit ratio, and enhance informed consent.

PURPOSE The purpose of this study is to use a genotype-first approach to explore highly penetrant, autosomal dominant cardiovascular diseases with external features, the RASopathies and Marfan syndrome (MFS), using biobank data. METHODS This study uses exome sequencing and corresponding phenotypic data from Mount Sinai's BioMe (n = 32,344) and the United Kingdom Biobank (UKBB; n = 49,960). Variant curation identified pathogenic/likely pathogenic (P/LP) variants in RASopathy genes and FBN1. RESULTS Twenty-one subjects harbored P/LP RASopathy variants; three (14%) were diagnosed, and another 46% had ≥1 classic Noonan syndrome (NS) feature. Major NS features (short stature [9.5% p = 7e-5] and heart anomalies [19%, p

Background International standards for safe anesthetic care have been developed by the World Federation of Societies of Anaesthesiologists (WFSA) and the World Health Organization (WHO). Whether these standards are met is unknown in many nations, including Guatemala, a country with universal health coverage. We aimed to establish an overview of anesthesia care capacity in public surgical hospitals in Guatemala to help guide public sector health care development. Methods In partnership with the Guatemalan Ministry of Public Health and Social Assistance (MSPAS), a national survey of all public hospitals providing surgical care was conducted using the WFSA anesthesia facility assessment tool (AFAT) in 2018. Each facility was assessed for infrastructure, service delivery, workforce, medications, equipment, and monitoring practices. Descriptive statistics were calculated and presented. Results Of the 46 public hospitals in Guatemala in 2018, 36 (78%) were found to provide surgical care, including 20 district, 14 regional, and 2 national referral hospitals. We identified 573 full-time physician surgeons, anesthesiologists, and obstetricians (SAO) in the public sector, with an estimated SAO density of 3.3/100,000 population. There were 300 full-time anesthesia providers working at public hospitals. Physician anesthesiologists made up 47% of these providers, with an estimated physician anesthesiologist density of 0.8/100,000 population. Only 10% of district hospitals reported having an anesthesia provider continuously present intraoperatively during general or neuraxial anesthesia cases. No hospitals reported assessing pain in the immediate postoperative period. While the availability of some medications such as benzodiazepines and local anesthetics was robust (100% availability across all hospitals), not all hospitals had essential medications such as ketamine, epinephrine, or atropine. There were deficiencies in the availability of essential equipment and basic intraoperative monitors, such as end-tidal carbon dioxide detectors (17% availability across all hospitals). Postoperative care and access to resuscitative equipment, such as defibrillators, were also lacking. Conclusions This first countrywide, MSPAS-led assessment of anesthesia capacity at public facilities in Guatemala revealed a lack of essential materials and personnel to provide safe anesthesia and surgery. Hospitals surveyed often did not have resources regardless of hospital size or level, which may suggest multiple factors preventing availability and use. Local and national policy initiatives are needed to address these deficiencies.

A rare autosomal dominant syndrome with craniofacial dysmorphisms, skeletal abnormalities, short stature, and congenital heart defects has recently been described, associated with monoallelic truncating and frameshift bone morphogenetic protein 2 (BMP2) variants and deletions. We describe a patient harboring a novel de novo BMP2 nonsense variant, who exhibited craniofacial and skeletal features previously described for this trait and the novel findings of bicuspid aortic valve (BAV) and aortic root and ascending aortic aneurysm. This first instance of aortic valve involvement provides another potential cause of BAV and confirms the role of BMP2 in left ventricular outflow development.

Introduction The objective of this study was to evaluate real-world effectiveness of latanoprostene bunod (LBN) ophthalmic solution 0.024% in treatment-naïve patients newly diagnosed with open-angle glaucoma (OAG) or ocular hypertension. Methods This multicenter retrospective chart review included patients aged ≥ 18 years, with no history of medical, laser, or surgical intraocular pressure (IOP)-lowering intervention and at least two follow-up visits (spanning ≥ 2 months) following initiation of LBN treatment. Extracted data included age, sex, race, cup-to-disk ratio, central corneal thickness, IOP, visual acuity (VA), concomitant medications, and adverse events. In patients treated bilaterally, the eye with the higher baseline IOP was the study eye. Results Medical charts for 65 patients (mean [SD] age, 59 [14] years; 53.8% female) encompassing 125 eyes treated with LBN were reviewed across nine clinical sites. Mean (SD) IOP at baseline was 21.7 (5.9) mmHg. Mean days to first and second follow-up visit were 43 and 141, respectively. LBN use resulted in a mean (SD) reduction from baseline of 7.1 (4.7) and 7.3 (5.1) mmHg at the first and second follow-up visits, respectively (P 21 mmHg (n = 30) at baseline were 10.0 (4.5) and 11.1 (4.6) mmHg at the first and second follow-up visits (P

Headache and neck pain (cervicalgia) are frequently reported among patients with joint hypermobility but the prevalence and scope of these symptoms has not been studied in the era of contemporary Ehlers-Danlos and hypermobility disorder nosology. We performed a single-center retrospective study on the incidence of head and neck symptoms in 140 patients with hypermobility disorders over a 2-year period. Overall, 93 patients (66%) reported either headache or neck pain with 49 of those (53%) reporting both. Migraine (83%) was the most common headache type among those with headache disorders and cervical spondylosis (61%) the most common pathology among those with neck symptoms. Fifty-nine percent of spondylosis patients who underwent cervical facet procedures reported significant improvement in neck and head symptoms. Of patients with both head and neck complaints, 82% had both migraine and spondylosis, which, when combined with the high response rate to injections raises the possibility of cervicogenic headache. In this large multidisciplinary retrospective study of patients with hypermobility disorders, head and neck symptoms were highly prevalent, with migraine and cervical spondylosis common, often coexisting, and frequently responsive to targeted therapy for the cervical spine suggesting that degenerative spinal pathology may cause or contribute to headache symptoms in some patients with hypermobility disorders.

Lysosomal acid lipase (LAL) deficiency, or cholesterol ester storage disease, is a disorder affecting the breakdown of cholesterol esters and triglycerides within lysosomes. Clinical findings include hepatomegaly, hepatic dysfunction, and dyslipidemia, with a wide range of phenotypic variability and age of onset (1-3). The available clinical and molecular information of the patient presented herein was consistent with a diagnosis of LAL deficiency, but her LAL activity assay repeatedly showed normal or borderline low results. Her response to enzyme replacement therapy (4,5) and demonstrable deficiency on a newer specific enzymatic assay (6) ultimately confirmed her diagnosis of LAL deficiency.

Background Capnography is universally accepted as an essential patient safety monitor in high-income countries (HICs) yet is often unavailable in low and middle-income countries (LMICs). Increasing capnography availability has been proposed as one of many potential approaches to improving perioperative outcomes in LMICs. This scoping review summarises the existing literature on the effect of capnography on patient outcomes to help prioritise interventions and guide expansion of capnography in LMICs. Methods We searched MEDLINE and EMBASE databases for articles published between 1980 and March 2019. Studies that assessed the impact of capnography on morbidity, mortality, or the use of airway interventions both inside and outside the operating room were included. Results The search resulted in 7445 unique papers, and 31 were included for analysis. Retrospective and non-randomised data suggest capnography use may improve outcomes in the operating room, ICU, and emergency department, and during resuscitation. Prospective data on capnography use for procedural sedation suggest earlier detection of hypoventilation and a reduction in haemoglobin desaturation events. No randomised studies exist that assess the impact of capnography on patient outcomes. Conclusion Despite widespread endorsement of capnography as a mandatory perioperative monitor, rigorous data demonstrating its impact on patient outcomes are limited, especially in LMICs. The association between capnography use and a reduction in serious airway complications suggests that closing the capnography gap in LMICs may represent a significant opportunity to improve patient safety. Additional data are needed to quantify the global capnography gap and better understand the barriers to capnography scale-up in LMICs.

Introduction Percutaneous minimally invasive spine surgery (MISS) is a treatment option for thoracolumbar fractures and we aim to evaluate its outcomes. Methods A retrospective matched cohort study of all patients with thoracolumbar fractures treated with MISS or open posterior approach. Results We included 100 MISS and 155 open patients. After controlling for patient characteristics, our results statistically favor MISS in mean operative time, mean intraoperative blood loss, and number of patients requiring postoperative blood transfusions within 48 h. Conclusions Advantages of using MISS for treatment of thoracolumbar fractures are decreased operative time, decreased blood loss, and fewer patients requiring transfusions.

Study Design: Retrospective case series. Objectives: Postoperative urinary retention (POUR) represents a common postoperative complication of all elective surgeries. The aim of this study was to identify demographic, comorbid, and surgical factors risk factors for POUR in patients who underwent elective thoracolumbar spine fusion. Methods: Following institutional review board approval, patients who underwent elective primary or revision thoracic and lumbar instrumented spinal fusion in a 2-year period in tertiary and academic institution were reviewed. Sex, age, BMI, preoperative diagnosis, comorbid conditions, benign prostatic hyperplasia, diabetes, primary or revision surgery status, narcotic use, and operative factors were collected and analyzed between patients with and without POUR. Results: Of the 217 patients reviewed, 54 (24.9%) developed POUR. The average age for a patient with POUR was 67 ± 9, as opposed to 59 ± 10 for those without ( P < .0001). Single-level fusions were associated with a 0% incidence of POUR, compared with 54.5% in 6 or more levels. The average hospital stay was increased by 1 day for those who had POUR (5.8 ± 3.3 vs 4.9 ± 3.9 days). There was no significant association with other demographic variables, comorbid conditions, or surgical factors. Conclusions: POUR was a common complication in our patient cohort, with an incidence of 24.9%. Our findings demonstrate that patients who developed POUR are significantly older and have larger constructs. Patients who developed POUR also had longer in-hospital stays. Although our study supports other findings in the spine literature, more prospective data is needed to define diagnostic criteria of POUR as well as its management.

All physicians, regardless of their medical specialty or the setting in which they treat patients, must be able to perform a neurologic examination. In the outpatient office, up to 9 to 10% of all symptoms suggest the possibility of neurologic disease and up to 5% of emergency department visits are due to primary neurologic disease. The neurologic examination is critical in triaging these patients, selecting diagnostic tests, and indicating management. This review covers how to think about the neurologic examination, the screening examination, and diagnosis-focused neurologic examinations with an emphasis on stroke, epilepsy, encephalopathy and coma, neurodegenerative diseases, neuromuscular disease, and functional disorders. The figure shows a conceptual approach to the neurologic examination. The tables list components of the screening neurologic examination, neurologic examination focus points for suspected stroke and suspected epilepsy, lateralization and localization of common seizure semiologies, and neurologic examination focus points for encephalopathy/coma, suspected neurodegenerative disease, suspected neuromuscular disease, and suspected functional neurologic disorders. This review contains 1 figure, 13 tables, and 14 references Keywords: Neurologic examination, neurodegenerative disease, neuromuscular disease, neurologic screening

Supplemental Digital Content is available in the text., Background: Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role. Methods: To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed whole-exome sequencing of 87 HLHS parent–offspring trios, nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, single cell RNA sequencing, and 3D modeling in induced pluripotent stem cells from 3 patients with HLHS and 3 controls. Results: Gene set enrichment and protein network analyses of damaging de novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell cycle and cardiomyocyte maturation. Single-cell and 3D modeling with induced pluripotent stem cells demonstrated intrinsic defects in the cell cycle/unfolded protein response/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte subtype differentiation/maturation in HLHS. Premature cell cycle exit of ventricular cardiomyocytes from patients with HLHS prevented normal tissue responses to developmental signals for growth, leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues. Conclusions: Our results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.

Background Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signaling, providing the rationale for a combination trial with immune checkpoint inhibition. Methods An open-label, multi-institutional, dose-escalation phase I trial in rGBM subjects (NCT03636477) accrued 21 subjects in 3 dose-escalating cohorts: (1) neoadjuvant then ongoing nivolumab (1mg/kg) and VDX (10 mg) (n = 3); (2) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (10 mg) (n = 3); and (3) neoadjuvant then ongoing nivolumab (3 mg/kg) and VDX (20 mg) (n = 15). Nivolumab was administered 7 (±3) days before resection of the rGBM followed by peritumoral injection of IL-12 gene therapy. VDX was administered 3 hours before and then for 14 days after surgery. Nivolumab was administered every two weeks after surgery. Results Toxicities of the combination were comparable to IL-12 gene monotherapy and were predictable, dose-related, and reversible upon withholding doses of VDX and/or nivolumab. VDX plasma pharmacokinetics demonstrate a dose-response relationship with effective brain tumor tissue VDX penetration and production of IL-12. IL-12 levels in serum peaked in all subjects at about Day 3 after surgery. Tumor IFNγ increased in post-treatment biopsies. Median overall survival (mOS) for VDX 10 mg with nivolumab was 16.9 months and for all subjects was 9.8 months. Conclusion The safety of this combination immunotherapy was established and has led to an ongoing phase II clinical trial of immune checkpoint blockade with controlled IL-12 gene therapy (NCT04006119).

In this Viewpoint we provide a brief description of two efforts to develop drugs to treat diseases caused by tropical parasites (Malaria, human African trypanosomiasis, and Chagas disease). These efforts are largely based in a University setting but draw heavily on Pharma for a complete progression from drug hit discovery to advancement toward clinical trials. The first case is the development of protein farnesyltransferase inhibitors, and the second case is a series of benzthiazoles, the target of which is being investigated.

Study Design Retrospective cohort study. Objectives This study aims to analyze outcomes and complications of patients with thoracic and lumbar fractures in the setting of ankylosing spinal disorders (ASD) treated with minimally invasive surgery (MIS). Methods The operative logs from 2012 to 2019 from one academic, Level I trauma center were reviewed for cases of thoracic and lumbar spinal fractures in patients with ASD treated with a MIS approach. Variables were compared between patients with ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and advanced spondylosis. Results A total of 48 patients with ASD and concomitant thoracic or lumbar spinal fracture managed with an MIS approach were identified. A total of 11 patients were identified with AS, 21 with DISH, and 16 with advanced spondylosis. A total of 27 (56.3%) patients experienced complications. Complications differed between groups; DISH patients experienced a greater number of post-operative complications compared to AS and advanced spondylosis patients ( P = .009). There was no significant difference in length of surgery, estimated blood loss, length of stay, readmission, and reoperation rates between AS and DISH patients. There were 3 mortalities unrelated to the surgery. Conclusion Percutaneous stabilization of patients with ankylosing spinal disorder fractures remains a viable management method. Operative characteristics were similar between AS, DISH, and advanced spondylosis patients; however, DISH patients experienced a greater number of post-operative complications.

Genetic diseases that affect the cardiovascular system are relatively common and include cardiac channelopathies, cardiomyopathies, aortopathies, hypercholesterolemias, and structural diseases of the heart and great vessels. The rapidly expanding availability of clinical genetic testing leverages decades of research into the genetic origins of these diseases, helping inform diagnosis, clinical management, and prognosis. Although a number of guidelines and statements detail best practices for cardiovascular genetic testing, there is a paucity of pediatric-focused statements addressing the unique challenges in testing in this vulnerable population. In this scientific statement, we seek to coalesce the existing literature around the use of genetic testing for cardiovascular disease in infants, children, and adolescents.

Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define—for the first time—the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries—who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators—at the basic level—should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies., Justine Davies and colleagues discuss the development of updated indicators to support global achievement of access to safe surgical, anaesthetic, and obstetric care.

BACKGROUND: Hospitals seek to reduce costs and improve patient outcomes by decreasing length of stay (LOS), 30-day all-cause readmissions, and preventable complications. We evaluated hospital-reported outcome measures for elective single-level anterior cervical discectomy and fusions (ACDFs) between tertiary (TH) and community hospitals (CH) to determine location-based differences in complications, LOS, and overall costs. METHODS: Patients undergoing elective single-level ACDF in a 1-year period were retrospectively reviewed from a physician-driven database from a single medical system consisting of 1 TH and 4 CHs. Adult patients who underwent elective single-level ACDF were included. Patients with trauma, tumor, prior cervical surgery, and infection were excluded. Outcomes measures included all-cause 30-day readmissions, preventable complications, LOS, and hospital costs. RESULTS: A total of 301 patients (60 TH, 241 CH) were included. CHs had longer LOS (1.25 ± 0.50 versus 1.08 ± 0.28 days, P = .01). There were no differences in complication and readmission rates between hospital settings. CH, orthopaedic subspecialty, female sex, and myelopathy were predictors for longer LOS. Overall, costs at the TH were significantly higher than at CHs ($17 171 versus $11 737; Δ$ = 5434 ± 3996; P < .0001). For CHs, the total costs of drugs, rooms, supplies, and therapy were significantly higher than at the TH. TH status, orthopaedic subspecialty, and myelopathy were associated with higher costs. CONCLUSION: Patients undergoing single-level ACDFs at CHs had longer LOS, but similar complications and readmission rates as those at the TH. However, cost of ACDF was 1.5 times greater in the TH. To improve patient outcomes, optimize value, and reduce hospital costs, modifiable factors for elective ACDFs should be evaluated. LEVEL OF EVIDENCE: 3.

RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non-NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates.

Study Design:Broad narrative review.Objective:To review and summarize the current literature on guidelines, outcomes, techniques and indications surrounding multiple modalities of minimizing blood loss in spine surgery.Methods:A thorough review of peer-reviewed literature was performed on the guidelines, outcomes, techniques, and indications for multiple modalities of minimizing blood loss in spine surgery.Results:There is a large body of literature that provides a consensus on guidelines regarding the appropriate timing of discontinuation of anticoagulation, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and herbal supplements prior to surgery. Additionally, there is a more heterogenous discussion the utility of preoperative autologous blood donation facilitated by erythropoietin and iron supplementation for healthy patients slated for procedures with high anticipated blood loss and for whom allogeneic transfusion is likely. Intraoperative maneuvers available to minimize blood loss include positioning and maintaining normothermia. Tranexamic acid (TXA), bipolar sealer electrocautery, and topical hemostatic agents, and hypotensive anesthesia (mean arterial pressure (MAP) Conclusion:As the volume and complexity of spinal procedures rise, intraoperative blood loss management has become a pivotal topic of research within the field. There are many tools for minimizing blood loss in patients undergoing spine surgery. The current literature supports combining techniques to use a cost- effective multimodal approach to minimize blood loss in the perioperative period.

Study Design: Prospective cohort study. Objectives: To determine the prevalence of bacterial infection, with the use of a contaminant control, in patients undergoing anterior cervical discectomy and fusion (ACDF). Methods: After institutional review board approval, patients undergoing elective ACDF were prospectively enrolled. Samples of the longus colli muscle and disc tissue were obtained. The tissue was then homogenized, gram stained, and cultured in both aerobic and anaerobic medium. Patients were classified into 4 groups depending on culture results. Demographic, preoperative, and postoperative factors were evaluated. Results: Ninety-six patients were enrolled, 41.7% were males with an average age of 54 ± 11 years and a body mass index of 29.7 ± 5.9 kg/m2. Seventeen patients (17.7%) were considered true positives, having a negative control and positive disc culture. Otherwise, no significant differences in culture positivity was found between groups of patients. However, our results show that patients were more likely to have both control and disc negative than being a true positive (odds ratio = 6.2, 95% confidence interval = 2.5-14.6). Propionibacterium acnes was the most commonly identified bacteria. Two patients with disc positive cultures returned to the operating room secondary to pseudarthrosis; however, age, body mass index, prior spine surgery or injection, postoperative infection, and reoperations were not associated with culture results. Conclusion: In our cohort, the prevalence of subclinical bacterial infection in patients undergoing ACDF was 17.7%. While our rates exclude patients with positive contaminant control, the possibility of contamination of disc cultures could not be entirely rejected. Overall, culture results did not have any influence on postoperative outcomes.

Introduction Online resources have become a major source of medical information for the general public. To date, there has not been an assessment of patient-oriented online resources for face and upper extremity transplantation candidates and patients. The goal of this study is to perform a comprehensive assessment of these resources. Methods Our analysis relied on 2 dimensions: comprehensiveness and readability. Comprehensiveness was evaluated using 14 predetermined variables. Readability was evaluated using 8 different readability scales through the Readability Studio Professional Edition Software (Oleander Software, Ltd, Vandalia, Ohio). Data were also collected from solid organ transplantation (SOT), specifically kidney and liver, programs for comparison. Results Face and upper extremity transplantation programs were significantly more likely to list exclusion criteria (73.9% vs 41.2%; P = 0.02), the need for life-long immunosuppression (87.0% vs 58.8%; P = 0.02), and benefits of transplantation (91.3% vs 61.8%; P = 0.01) compared with SOT programs. The average readability level of online resources by all face and upper extremity transplantation programs exceeded the sixth grade reading level recommended by the National Institutes of Health and the American Medical Association. The average reading grade level of online resources by these programs was also significantly higher than those of SOT with both exceeding the recommended reading level (13.95 ± 1.55 vs 12.60 ± 1.65; P = 0.003). Conclusions Future efforts in face and upper extremity transplantation should be directed toward developing standardized, comprehensive, and intelligible resources with high-quality content and simple language.

Background:Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade.Methods:The authors’ team has successfully treated patients with extensiv

Background: Tandem spinal stenosis (TSS) is defined as simultaneous spinal stenosis in the cervical, thoracic, and/or lumbar regions and may present with both upper and lower motor neuron symptoms, neurogenic claudication, and gait disturbance. Current literature has focused mainly on the prevalence of TSS and treatment methods, while the incidence of delayed TSS diagnosis is not well defined. The purpose of this study was to determine the incidence of delayed TSS diagnosis at our institution and describe the clinical characteristics commonly observed in their particular presentation. Methods: Following institutional review board approval, an institutional billing database review was performed for patients who underwent a spinal decompression procedure between 2006 and 2016. Thirty-three patients who underwent decompression on 2 separate spinal regions within 1 year were included for review. Patients with delayed diagnosis of TSS following the first surgery were differentiated from those with preoperative diagnosis of TSS. Results: TSS requiring surgical decompression occurred in 33 patients, with the incidence being 2.06% in this cohort. Fifteen patients received a delayed diagnosis after the first surgical decompression (45%) and were found to have a longer interval between decompressions (7.6 ± 2.1 months versus 4.01 ± 3 months, P = .0004). Patients undergoing lumbar decompression as the initial procedure were more likely to have a delayed diagnosis of TSS (8 versus 2 patients, P = .0200). The most common presentation of delayed TSS was pain and myelopathic symptoms that persisted after decompressive surgery. Conclusion: TSS should remain within the differential diagnosis for patients at initial presentation of spinal stenosis. In addition, suspicion of TSS should be heightened if preoperative symptoms fail to expectedly improve following decompression even if overt myelopathic signs are not present. Level of Evidence: 4

Study Design: Retrospective cohort study. Objective: As hospital compensation becomes increasingly dependent on pay-for-performance and bundled payment compensation models, hospitals seek to reduce costs and increase quality. To our knowledge, no reported data compare these measures between hospital settings for elective lumbar procedures. The study compares hospital-reported outcomes and costs for elective lumbar procedures performed at a tertiary hospital (TH) versus community hospitals (CH) within a single health care system. Methods: Retrospective review of a physician-maintained, prospectively collected database consisting of 1 TH and 4 CH for 3 common lumbar surgeries from 2015 to 2016. Patients undergoing primary elective microdiscectomy for disc herniation, laminectomy for spinal stenosis, and laminectomy with fusion for degenerative spondylolisthesis were included. Patients were excluded for traumatic, infectious, or malignant pathology. Comparing hospital settings, outcomes included length of stay (LOS), rates of 30-day readmissions, potentially preventable complications (PPC), and discharge to rehabilitation facility, and hospital costs. Results: A total of 892 patients (n = 217 microdiscectomies, n = 302 laminectomies, and n = 373 laminectomy fusions) were included. The TH served a younger patient population with fewer comorbid conditions and a higher proportion of African Americans. The TH performed more decompressions ( P < .001) per level fused; the CH performed more interbody fusions ( P = .007). Cost of performing microdiscectomy ( P < .001) and laminectomy ( P = .014) was significantly higher at the TH, but there was no significant difference for laminectomy with fusion. In a multivariable stepwise linear regression analysis, the TH was significantly more expensive for single-level microdiscectomy ( P < .001) and laminectomy with single-level fusion ( P < .001), but trended toward significance for laminectomy without fusion ( P = .052). No difference existed for PPC or readmissions rate. Patients undergoing laminectomy without fusion were discharged to a facility more often at the TH ( P = .019). Conclusions: We provide hospital-reported outcomes between a TH and CH. Significant differences in patient characteristics and surgical practices exist between surgical settings. Despite minimal differences in hospital-reported outcomes, the TH was significantly more expensive.

Diabetes mellitus (DM) significantly increases susceptibility to central nervous system (CNS) pathologies, including stroke, vascular dementia, cognitive deficits and Alzheimer’s disease. Previous studies (mostly using the streptozotocin model) suggested that blood-brain barrier (BBB) disruption is involved in these conditions. Here, we examined the integrity of brain capillaries and BBB permeability in Leprdb/db obesity-related diabetic mice. Surprisingly, significant BBB leakage was observed only in young mice at the pre-hyperglycemic stage. Thorough examination of barrier permeability at later diabetic stages showed no evidence for significant BBB leakage during the hyperglycemic state. Electron microscopy imaging of mice with short-term hyperglycaemia supported normal BBB permeability but indicated other stress-related changes in capillary ultrastructure, such as mitochondrial degeneration. Based on our study with this mouse genetic model of obesity-related DM, we suggest that previously reported hyperglycaemia-induced BBB leakage is most likely not the underlying mechanism of DM-related CNS pathologies. Finally we propose that BBB hyper-permeability might be an early and transient phenomenon while stress-related endothelial pathologies do correlate with a short-term diabetic state.

BACKGROUND CONTEXT The incidence of pyogenic vertebral osteomyelitis (PVO) continues to increase in the United States, highlighting the need to recognize unique challenges presented by these cases and develop effective methods of surgical management. To date, no prior research has focused on the outcomes of PVO requiring two or more contiguous corpectomies. PURPOSE To describe our experience in the operative management of PVO in 56 consecutive patients who underwent multilevel corpectomies (≥2 vertebral bodies) via a combined approach. STUDY DESIGN/SETTING Single institution retrospective cohort review between January 2002 and December 2015. All patients had been treated at an academic tertiary referral center by one of two fellowship-trained orthopedic spine surgeons. PATIENT SAMPLE Patient records were cross-referenced with International Classification of Diseases osteomyelitis codes and paravertebral abscess code. Inclusion criteria for the study were patients within the cohort who had adequate medical records for review, a minimum patient age of 18 years, active vertebral osteomyelitis as an indication for surgical intervention, a minimum of 1-year radiographic follow-up, and surgical intervention that included at least two complete vertebral corpectomies. Subsequently, 56 patients met the inclusion criteria and were reviewed for this retrospective analysis. OUTCOME MEASURES Outcomes of interest were readmission and reoperation rates related to treatment of PVO, 30-day and 1-year mortality rates, radiographic outcomes, perioperative complications, infection control, and length of stay. METHODS After obtaining approval from the Institutional Review Board, retrospective review was performed on records of all adults with PVO refractory to standard nonoperative treatment who underwent complete corpectomy of two or more contiguous vertebrae at a single institution between January 2002 and December 2015. This study was not funded, and no potential conflict of interest-associated biases were present. RESULTS Fifty-six patients were identified (63% men; mean age 56.8 years; mean radiographic follow-up 2.8 years). Median length of stay was 13 days with nearly half readmitted (47%) after a median of 222.5 days after surgery. Twelve (22%) posterior revisions were required after a median 54 days for infection, painful or failed hardware, proximal junction kyphosis, adjacent level disease, or extension of the fusion. Thirty-day and 1-year mortality rates were 7.14% and 19.6%, respectively, with an infectious etiology as the most common cause of death. CONCLUSIONS Multilevel vertebral corpectomy for treatment of refractory vertebral osteomyelitis is associated with relatively high rates of complications and mortality compared with historical controls for 1 or 2 level procedures. We found clinical resolution and absence of complications requiring return to the operating room in 75% of patients when complete extirpation of the involved vertebrae is achieved. Our findings suggest multilevel anterior corpectomies with posterior stabilization may be a reasonable surgical option when approaching patients with complicated spondylodiscitis.

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of LV size and function were compared between patients with and without dysautonomia, as well as to reported values from healthy controls. Dysautonomia was identified in 71% of female and 56% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 39% to >80%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is highly prevalent in patients with hEDS/HSD, exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning.

Background: Acute myocarditis (AM) is a well-known cause of sudden death and heart failure, often caused by prevalent viruses. We previously showed that some pediatric AM correlates with putatively damaging variants in genes related to cardiomyocyte structure and function. We sought to evaluate whether deleterious cardiomyopathic variants were enriched among fatal pediatric AM cases in New York City compared with ancestry-matched controls. Methods: Twenty-four children (aged 3 weeks to 20 years) with death due to AM were identified through autopsy records; histologies were reviewed to confirm that all cases met Dallas criteria for AM and targeted panel sequencing of 57 cardiomyopathic genes was performed. Controls without cardiovascular disease were identified from a pediatric database and matched by genetic ancestry to cases using principal components from exome sequencing. Rates of putative deleterious variations (DV) were compared between cases and controls. Where available, AM tissues underwent viral analysis by polymerase chain reaction. Results: DV were identified in 4 of 24 AM cases (16.7%), compared with 2 of 96 age and ancestry-matched controls (2.1%, P =0.014). Viral causes were proven for 6 of 8 AM cases (75%), including the one DV+ case where tissue was available for testing. DV+ cases were more likely to be female, have no evidence of chronic inflammation, and associate with sudden cardiac death than DV− cases. Conclusions: Deleterious variants in genes related to cardiomyocyte integrity are more common in children with fatal AM than controls, likely conferring susceptibility. Additionally, genetically mediated AM may progress more rapidly and be more severe.

Evaluate if dural tears (DTs) are an indirect risk factor for venous thromboembolic disease through increased recumbency in patients undergoing elective lumbar decompression and instrumented fusion.This was a retrospective cohort study of consecutive patients undergoing elective lumbar decompression and instrumented fusion at a single institution between 2016 and 2019. Patients were divided into cohorts: those who sustained a dural tear and those who did not. The cohorts were compared using Student's t-test or Wilcoxon Rank Sum for continuous variables and Fisher exact or chi-squared test for nominal variables.Six-hundred and eleven patients met inclusion criteria, among which 144 patients (23.6%) sustained a DT. The DT cohort tended to be older (63.6 vs. 60.6 years, P = 0.0052) and have more comorbidities (Charlson Comorbidity Index 2.75 vs. 2.35, P = 0.0056). There was no significant difference in the rate of symptomatic deep vein thrombosis (2.1% vs. 2.6%, P = 1.0) or pulmonary embolus (1.4% vs. 1.50%, P = 1.0). Intraoperatively, DT was associated with increased blood loss (754 mL vs. 512 mL, P0.0001), operative time (224 vs. 195 minutes, P0.0001), and rate of transfusion (19.4% vs. 9.4%, P = 0.0018). Postoperatively, DT was associated with increased time to ambulation (2.6 vs. 1.4 days, P0.0001), length of stay (5.8 vs. 4.0 days, P0.0001), and rate of discharge to rehab (38.9 vs. 25.3%, P = 0.0021).While DTs during elective lumbar decompression and instrumentation led to later ambulation and longer hospital stays, the increased recumbency did not significantly increase the rate of symptomatic venous thromboembolic disease.

The goal of newborn screening is to enhance the outcome of individuals with serious, treatable disorders through early, pre-symptomatic detection. The lysosomal storage disorders (LSDs) comprise a group of more than 50 diseases with a combined frequency of approximately 1:7000. With the availability of existing and new enzyme replacement therapies, small molecule treatments and gene therapies, there is increasing interest in screening newborns for LSDs with the goal of reducing disease-related morbidity and mortality through early detection. Novel screening methods are being developed, including efforts to enhance accuracy of screening using an array of multi-tiered, genomic, statistical, and bioinformatic approaches. While NBS data for Gaucher disease, Fabry disease, Krabbe disease, MPS I, and Pompe disease has demonstrated the feasibility of widespread screening, it has also highlighted some of the complexities of screening for LSDs. These include the identification of infants with later-onset, untreatable, and uncertain phenotypes, raising interesting ethical concerns that should be addressed as part of the NBS implementation process. Taken together, these efforts will provide critical, detailed data to help guide objective, ethically sensitive decision-making about NBS for LSDs.

Increasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests and considerations of cost, interpretation, and diagnostic yield for emerging modalities like whole-genome sequencing.The NYCKidSeq project is a randomized controlled trial recruiting 1130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories: neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo, or trio whole-genome sequencing (depending on sample availability) and proband targeted gene panels. Clinical utility, cost, and diagnostic yield of both testing modalities will be assessed. This study will evaluate the use of a novel, digital platform (GUÍA) to digitize the return of genomic results experience and improve participant understanding for English- and Spanish-speaking families. Surveys will collect data at three study visits: baseline (0 months), result disclosure visit (ROR1, + 3 months), and follow-up visit (ROR2, + 9 months). Outcomes will assess parental understanding of and attitudes toward receiving genomic results for their child and behavioral, psychological, and social impact of results. We will also conduct a pilot study to assess a digital tool called GenomeDiver designed to enhance communication between clinicians and genetic testing labs. We will evaluate GenomeDiver's ability to increase the diagnostic yield compared to standard practices, improve clinician's ability to perform targeted reverse phenotyping, and increase the efficiency of genetic testing lab personnel.The NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound.ClinicalTrials.gov NCT03738098 . Registered on November 13, 2018 Trial Sponsor: Icahn School of Medicine at Mount Sinai Contact Name: Eimear Kenny, PhD (Principal Investigator) Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email: eimear.kenny@mssm.edu.

BACKGROUND: Recent studies have emphasized the difficulty of early detection of chronic obstructive pulmonary disease (COPD) in symptomatic smokers with normal routine spirometry. This includes post-bronchodilator normal forced expiratory volume in 1 second (FEV1)(L)≥80% predicted, forced vital capacity (FVC)(L)≥80% predicted, and FEV1/FVC ≥70% or greater than age corrected lower limit of normal (LLN). However, in COPD the pathologic site of small airway obstruction and emphysema begins in the small peripheral airways ≤2 mm id which normally contribute

Author(s): Moreno, Gerardo; Mangione, Carol M; Tseng, Chi-Hong; Weir, Melanie; Loza, Rosaneli; Desai, Lisa; Grotts, Jonathan; Gelb, Eve | Abstract: ObjectivePatients with multiple medical conditions and complex social issues are at risk for high utilization and poor outcomes. The Connecting Provider to Home program deployed teams of a social worker and a community health worker (CHW) to support patients with social issues and access to primary care. Our objectives were to examine the impact of the program on utilization and satisfaction with care among older adults with complex social and medical issues.DesignRetrospective quasi-experimental observational study with matched comparator group.SettingCommunity-based program in Southern California.ParticipantsFour hundred twenty community dwelling adults.InterventionCommunity-based healthcare program delivered by a social worker and CHW team for older adults with complex medical and social needs.MeasurementsAcute hospitalization and emergency department (ED) visits in the 12 months preceding and following enrollment in the pilot program. A "difference-in-difference" analysis using a matched comparator group was conducted. Comparator group data of patients receiving usual care were obtained. Surveys were conducted to assess patient satisfaction and experiences with the program.ResultsThe mean age of patients was 74 years, and the program demonstrated statistically significant reductions in acute hospitalizations and ED use compared with 700 comparator patients. Pre/post-acute hospitalizations and ED visits were reduced in the intervention group. The average per patient per year reduction in acute hospitalizations was -0.66, whereas the average per patient reduction in ED use was -0.57. Patients enrolled in the program reported high levels of satisfaction and rated the program favorably.ConclusionsA care model with a social worker and CHW can be linked to primary care to address patient social needs and potentially reduce utilization of healthcare services and enhance patient experiences with care.