Sin3a associated protein 130 kDa, sap130, plays an evolutionary conserved role in zebrafish heart development.

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease where the left ventricle is reduced in size. A forward genetic screen in mice identified SIN3A associated protein 130 kDa (Sap130), part of the chromatin modifying SIN3A/HDAC complex, as a gene contributing to the etiology of HLHS. Here, we report the role of zebrafish sap130 genes in heart development. Loss of sap130a, one of two Sap130 orthologs, resulted in smaller ventricle size, a phenotype reminiscent to the hypoplastic left ventricle in mice. While cardiac progenitors were normal during somitogenesis, diminution of the ventricle size suggest the Second Heart Field (SHF) was the source of the defect. To explore the role of sap130a in gene regulation, transcriptome profiling was performed after the heart tube formation to identify candidate pathways and genes responsible for the small ventricle phenotype. Genes involved in cardiac differentiation and cardiac function were dysregulated in sap130a, but not in sap130b mutants. Confocal light sheet analysis measured deficits in cardiac output in MZsap130a supporting the notion that cardiomyocyte maturation was disrupted. Lineage tracing experiments revealed a significant reduction of SHF cells in the ventricle that resulted in increased outflow tract size. These data suggest that sap130a is involved in cardiogenesis via regulating the accretion of SHF cells to the growing ventricle and in their subsequent maturation for cardiac function. Further, genetic studies revealed an interaction between hdac1 and sap130a, in the incidence of small ventricles. These studies highlight the conserved role of Sap130a and Hdac1 in zebrafish cardiogenesis.

Sin3a Associated Protein 130kDa, sap130, plays an evolutionary conserved role in zebrafish heart development.

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease where the left ventricle is reduced in size. A forward genetic screen in mice identified SIN3A associated protein 130kDa ( Sap130 ), a protein in the chromatin modifying SIN3A/HDAC1 complex, as a gene contributing to the digenic etiology of HLHS. Here, we report the role of zebrafish sap130 genes in heart development. Loss of sap130a, one of two Sap130 orthologs, resulted in smaller ventricle size, a phenotype reminiscent to the hypoplastic left ventricle in mice. While cardiac progenitors were normal during somitogenesis, diminution of the ventricle size suggest the Second Heart Field (SHF) was the source of the defect. To explore the role of sap130a in gene regulation, transcriptome profiling was performed after the heart tube formation to identify candidate pathways and genes responsible for the small ventricle phenotype. Genes involved in cardiac differentiation and cell communication were dysregulated in sap130a , but not in sap130b mutants. Confocal light sheet analysis measured deficits in cardiac output in MZsap130a supporting the notion that cardiomyocyte maturation was disrupted. Lineage tracing experiments revealed a significant reduction of SHF cells in the ventricle that resulted in increased outflow tract size. These data suggest that sap130a is involved in cardiogenesis via regulating the accretion of SHF cells to the growing ventricle and in their subsequent maturation for cardiac function. Further, genetic studies revealed an interaction between hdac1 and sap130a , in the incidence of small ventricles. These studies highlight the conserved role of Sap130a and Hdac1 in zebrafish cardiogenesis.

Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.

Gene mutations causing loss of dystrophin result in the severe muscle disease known as Duchenne muscular dystrophy (DMD). Despite efforts at genetic repair, DMD therapy remains largely palliative. Loss of dystrophin destabilizes the sarcolemmal membrane, inducing mechanosensitive cation channels to increase calcium entry and promote cell damage and, eventually, muscle dysfunction. One putative channel is transient receptor potential canonical 6 (TRPC6); we have shown that TRPC6 contributed to abnormal force and calcium stress-responses in cardiomyocytes from mice lacking dystrophin that were haplodeficient for utrophin (mdx/utrn+/- [HET] mice). Here, we show in both the HET mouse and the far more severe homozygous mdx/utrn-/- mouse that TRPC6 gene deletion or its selective pharmacologic inhibition (by BI 749327) prolonged survival 2- to 3-fold, improving skeletal and cardiac muscle and bone defects. Gene pathways reduced by BI 749327 treatment most prominently regulated fat metabolism and TGF-ß1 signaling. These results support the testing of TRPC6 inhibitors in human trials for other diseases as a novel DMD therapy.

Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain.

Trigeminal neuralgia, historically dubbed the "suicide disease," is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)-approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.

Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots.

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results - using MRI-derived, BMI-independent measures of local adiposity - confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

Radial versus femoral secondary access for transcatheter aortic valve replacement: A systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the risk of procedural complications after TAVR using secondary radial access (RA) versus femoral access (FA) through a systematic review and meta-analysis of the published literature. BACKGROUND: Transcatheter aortic valve replacement (TAVR) entails both large-bore arterial access for device delivery and secondary arterial access for hemodynamic and imaging assessments. It is unknown whether RA versus FA for this secondary access reduces the risk of procedural complications. METHODS: We searched PubMed, Embase, the Cochrane Library, and Web of Science for observational studies comparing TAVR procedural complications in RA versus FA. Event rates were compared via weighted summary odds ratios using the Mantel-Haenszel method. RESULTS: Six manuscripts encompassing 6132 patients were included. Meta-analysis showed that RA reduced the risk of major vascular complications (OR 0.58, 95% CI 0.43-0.77, p < 0.001, I2 0%) and major/life-threatening bleeding (OR 0.46, 95% CI 0.36-0.59, p < 0.001, I2 0%) as compared to FA for secondary TAVR access. We also observed a reduction 30-day mortality (OR 0.55, 95% CI 0.38-0.79, p = 0.001, I2 0%), acute kidney injury (OR 0.45, 95% CI 0.34-0.60, p < 0.001, I2 0%), and stroke and transient ischemic attack (OR 0.43, 95% CI 0.27-0.67, p < 0.001, I2 0%). CONCLUSIONS: RA reduced the risk of major vascular and bleeding complications when compared to FA for secondary access in TAVR. RA is associated with reduced risk of other adverse outcomes including mortality, but these associations may be related to selection bias and confounding given the observational study designs.

Evolving Needs of Critical Care Trainees during the COVID-19 Pandemic: A Qualitative Study.

Background: Critical care trainees were integral in the coronavirus disease (COVID-19) pandemic response. Several perspective pieces have provided insight into the pandemic's impact on critical care training. Surveys of program directors and critical care trainees have focused on curricular impact. There is a lack of data from the trainee perspective on curricular enhancements, career development, and emotional and well-being needs to succeed in a critical care career in the ongoing COVID-19 pandemic. Objective: Our objective was to elicit perspectives from critical care trainees on their personal and professional needs as they continue to serve in the COVID-19 pandemic. Methods: This was a hypothesis-generating qualitative study. Individuals in a U.S. critical care training program during the COVID-19 pandemic participated in either focus groups or semistructured interviews. Interviews were conducted between July 2020 and March 2021 until data saturation was achieved. Audio recordings were professionally transcribed and analyzed using qualitative content analysis. A codebook was generated by two independent coders, with a third investigator reconciling codes when there were discrepancies. Themes and subthemes were identified from these codes. Results: Thirteen participants were interviewed. The major themes identified were as follows: 1) Curricular adaptation is necessary to address evolving changes in trainee needs; 2) COVID-19 impacted career development and highlighted that trainees need individualized help to meet their goals; 3) receiving social support at work from peers and leaders is vital for the sustained well-being of trainees; 4) fostering and maintaining a sense of meaning and humanity in one's work is important; and 5) trainees desire assistance and support to process their emotions and experiences. Conclusion: The needs expressed by critical care trainees are only partially captured in conceptual models of physician well-being. The need for multilevel workplace social networks and identifying meaning in one's work have been magnified in this pandemic. The themes discussing curricular gaps, career development needs, and skills to process work-related trauma are less well captured in preexisting conceptual models and point to areas where further research and intervention development are needed.

Medical and mental health implications of gestational surrogacy.

Gestational surrogacy in the United States has quadrupled since 1999, but to date, only a few states explicitly permit compensated gestational surrogacy. Current legal prohibitions are often influenced by outdated and stereotyped understandings of surrogacy. It is increasingly important to understand the current literature about the medical and mental health impacts of surrogacy and how state legislatures have addressed compensated gestational surrogacy in recent years. Based on this review, we found no evidence of substantial adverse medical or psychological outcomes among women who are gestational carriers or among the children they give birth to. The literature suggests that gestational surrogacy is a safe and increasingly popular option for families as long as rigorous screening and medical, psychological, and social supports are equitably provided. As states move to responsibly legalize and regulate gestational surrogacy, there is a continued need for further longitudinal studies on the health and psychological outcomes of gestational surrogacy.

The Effects of Cannabis: Implications for the Surgical Patient.

Cannabis use is increasingly prevalent. Cannabinoid receptors regulate pro-inflammatory cytokines, and compounds in marijuana exert diverse physiologic effects. As more patients use cannabis, clinicians should recognize implications of perioperative cannabis use. Although the role of cannabis use in perioperative pain control has been explored, little is known about its effect on perioperative wound healing or on hematologic, pulmonary, and cardiovascular physiology. METHODS: We searched PubMed for English-language articles related to cannabis (ie, marijuana, cannabidiol oil, and tetrahydrocannabinol) and wound healing, cardiovascular, pulmonary, or hematologic outcomes, and surgery. Titles and abstracts were reviewed, and relevant articles were analyzed. Human, animal, and pathology studies were included. Editorials, case reports, and review articles were excluded. RESULTS: In total, 2549 wound healing articles were identified; 5 human studies and 8 animal/pathology studies were included. Results were conflicting. An estimated 2900 articles related to cardiovascular effects were identified, of which 2 human studies were included, which showed tetrahydrocannabinol and marijuana caused tachycardia. A total of 142 studies regarding pulmonary effects were identified. Three human studies were included, which found no difference in respiratory complications. In total, 114 studies regarding hematologic effects were identified. The 3 included human studies found conflicting venous thromboembolism risks. The overall study quality was poor. Information about dose/duration, administration route, and follow-up was reported with variable completeness. CONCLUSIONS: Surgeons should consider effects of cannabis in the perioperative setting. Little is known about its perioperative effects on wound healing, or on cardiovascular, pulmonary, and hematologic physiology. Further research should elucidate the effects of administration route, dose, and timing of cannabis use among surgical patients.

Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients.

OBJECTIVE: This open-label 12-week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment-refractory active dermatomyositis (DM). METHODS: Tofacitinib in extended-release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid-sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety. RESULTS: At 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin. CONCLUSION: This is the first prospective, open-label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan-JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.

A coding tool and abuse data for female asylum seekers.

With 1 in 3 women affected, accounting for one billion women worldwide, Violence Against Women (VAW) constitutes one of the widest reaching human rights violations globally. Although the forms they take may vary, these abuses are not confined to a single social class, geographic region, or culture. Existing studies have yet to describe the full burden of abuse that asylum-seeking women endure throughout their lifetimes. We describe a novel coding tool that classifies types of abuse, identifies abuse perpetrators, and estimates how long and how often each abuse was experienced. The authors used this tool to describe and categorize the abuses endured by 85 cisgender, adult women seeking asylum in the United States who presented to the Weill Cornell Center for Human Rights for forensic medical evaluations from 2013 to 2017. We reviewed a total of 180 legal and forensic medical affidavits that were written in support of the applicants' asylum claims. Using the coding tool, we identified each abuse, classified every perpetrator, and, whenever possible, estimated how long and how frequently each abuse was endured. Interpretations of the raw data contained in this article and a discussion of their significance can be found in our associated publication: "Gender-Based Violence experienced by Women Seeking Asylum in the United State: A Lifetime of Multiple Traumas Inflicted by Multiple Perpetrators" [1]. The coding instrument described herein characterizes VAW by classifying the narrative data that are included in interviews, focus groups, medical records, and the like. Our coding instrument is the first of its kind to describe all types and severities of violence endured by women, classify the perpetrators of that violence, and delineate the timeline of violence over each individual's life. We hope that this holistic approach to classifying and describing VAW will enable other research groups to examine untested or unrealized associations between victims, perpetrators, and abuses. Ultimately, obtaining more complete data will empower us to advocate more effectively and to design more comprehensive care for victims of VAW.

Gender-based violence experienced by women seeking asylum in the United State: A lifetime of multiple traumas inflicted by multiple perpetrators.

Estimates by the World Health Organization indicate that 1 in 3 women-more than one billion people worldwide-have experienced some form of Gender-Based Violence (GBV). Violence Against Women (VAW) is a prominent subset of GBV, defined by the United Nations as any act "that results in, or is likely to result in, physical, sexual, or mental harm or suffering to women, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life." VAW can include verbal harassment, physical abuse, sexual abuse, honor killing, and femicide and can occur at the hands of individuals, institutions, or states. Whereas numerous studies have documented the multiple forms of physical, sexual, and psychological violence experienced by women, a thorough characterization of the abuses experienced by asylum-seeking women in the United States has not yet been undertaken. Our analysis of the affidavits for 85 cisgender, female asylum seekers who applied for forensic medical evaluations through a student-run asylum clinic, reveals a life-long pattern of multiple types of VAW inflicted by multiple perpetrators. These findings have implications for the focus of the medico-legal documentation submitted in support of female asylum seekers as well as for the design of comprehensive healthcare services for women and girls who are granted relief.

Does the timing of postoperative showering impact infection rates? A systematic review and meta-analysis.

INTRODUCTION: Optimum timing of postoperative showering varies. Earlier showering improves patient satisfaction, but the impact of the timing of showering on postoperative infection is unclear. We conducted a systematic literature review and meta-analysis to investigate the outcomes of various postoperative showering practices. METHODS: We searched PubMed to identify relevant human clinical studies in English, and searched these for additional references. Articles were reviewed for patient demographics, surgical specialty and procedure, wound closure method, placement of drains, showering protocol, and rates of infection and complications. Only randomized controlled trials were analyzed. A random-effects meta-analysis model was used to determine overall infection and complication rates between patients allowed to shower within the first 48 h postoperatively or later. RESULTS: Out of 357 studies, seven and five were included in the infection and complications rate meta-analyses, respectively. A total of 1,881 and 958 patients were included in each analysis; 605 and 477 patients in each analysis were allowed to shower on or before postoperative day 2 ("early"), while the remainder were prohibited from showering until postoperative day 3 to beyond one week ("delayed") postoperatively. There was no difference in infection (p = 0.45, [-0.0052, 2 × 0.007 95% CI]) or complication rate (p = 0.36, [-0.0046, 2 × 0.005 95% CI]) with earlier vs. delayed showering protocols. CONCLUSION: Published literature demonstrates no increase in the overall rate of wound infections or complications when patients showered earlier in the postoperative period. Additional randomized studies are needed to determine the ideal time for postoperative showering. These data should be considered by surgeons while determining when to permit patients to shower after surgery.

Epigenetic activation and memory at a TGFB2 enhancer in systemic sclerosis.

In systemic sclerosis (SSc), previously healthy adults develop an inflammatory prodrome with subsequent progressive fibrosis of the skin and viscera. SSc has a weak signature for genetic contribution, and there are few pathogenic insights or targeted treatments for this condition. Here, chromatin accessibility and transcriptome profiling coupled with targeted epigenetic editing revealed constitutive activation of a previously unannotated transforming growth factor-ß2 (TGFB2) enhancer maintained through epigenetic memory in SSc. The resulting autocrine TGFß2 signaling enforced a profibrotic synthetic state in ex vivo fibroblasts from patients with SSc. Inhibition of NF-κB or BRD4 achieved sustained inhibition of TGFB2 enhancer activity, mitigated profibrotic gene expression, and reversed dermal fibrosis in patient skin explants. These findings suggest a potential epigenetic mechanism of fibrosis in SSc and inform a regulatory mechanism of TGFB2, a major profibrotic cytokine.

Targeting of dermal myofibroblasts through death receptor 5 arrests fibrosis in mouse models of scleroderma.

Scleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA+ MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA+ MFBs is a viable therapy for fibrosis in scleroderma.

Lineage-specific events underlie aortic root aneurysm pathogenesis in Loeys-Dietz syndrome.

The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors of the transforming growth factor-ß (TGF-ß) pathway. Using a mouse model of Loeys-Dietz syndrome (LDS) that carries a heterozygous kinase-inactivating mutation in TGF-ß receptor I, we found that the effects of this mutation depend on the lineage of origin of vascular smooth muscle cells (VSMCs). Secondary heart field-derived (SHF-derived), but not neighboring cardiac neural crest-derived (CNC-derived), VSMCs showed impaired Smad2/3 activation in response to TGF-ß, increased expression of angiotensin II (AngII) type 1 receptor (Agtr1a), enhanced responsiveness to AngII, and higher expression of TGF-ß ligands. The preserved TGF-ß signaling potential in CNC-derived VSMCs associated, in vivo, with increased Smad2/3 phosphorylation. CNC-, but not SHF-specific, deletion of Smad2 preserved aortic wall architecture and reduced aortic dilation in this mouse model of LDS. Taken together, these data suggest that aortic root aneurysm predisposition in this LDS mouse model depends both on defective Smad signaling in SHF-derived VSMCs and excessive Smad signaling in CNC-derived VSMCs. This work highlights the importance of considering the regional microenvironment and specifically lineage-dependent variation in the vulnerability to mutations in the development and testing of pathogenic models for aortic aneurysm.

Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty.

BACKGROUND: It has been proposed that negative pressure wound therapy (NPWT) applied prophylactically to a closed incision may decrease the incidence of wound complications. Patients undergoing reduction mammaplasty are at risk of wound complications such as delayed healing, infection, and dehiscence, and the bilateral nature of the surgery allows for a within-patient randomized study to evaluate incisional NPWT's effect in reducing healing complications. METHODS: In this multicenter trial, 200 patients undergoing bilateral reduction mammaplasty were treated with PICO Single-Use NPWT System or standard wound-care dressings randomized to right or left breast for up to 14 days to enable within-patient comparison. Follow-up assessments were conducted to evaluate the difference in incision healing complications up to 21 days postsurgery. Healing complications (for the primary endpoint) were defined as delayed healing (incision not 100% closed by 7 days) and occurrence of dehiscence or infection within 21 days. Individual healing complications were assessed separately as secondary endpoints. RESULTS: Significantly fewer healing complications (primary endpoint) were noted in NPWT-treated breasts [113 (56.8%)] versus standard care [123 (61.8%)]. The difference of 10 (5.0%) patients with fewer healing complications using NPWT was statistically significant (P = 0.004). NPWT also resulted in a significantly lower incidence of dehiscence (secondary endpoint) compared with standard care [32 patients (16.2%) versus 52 patients (26.4%)] by day 21, a relative reduction of 38% (P < 0.001). CONCLUSIONS: This is the first major prospective, within-patient, randomized, controlled, multicenter study to provide evidence for an incisional NPWT strategy to reduce healing complications.

Medical Students' Attitudes toward Torture, Revisited.

This paper reports the findings of a survey of medical students' attitudes toward torture and discusses variables that may correlate with those attitudes. In late 2016, 483 enrolled medical and MD-PhD students at the Weill Cornell Medical College received an anonymous, institutional review board-approved survey that included questions about torture and its effectiveness, demographic questions, inquiries about personal experiences of harassment or discrimination, and questions regarding engagement in human rights activities. Some questions were drawn from a 2008 University of Illinois survey of medical students' attitudes toward torture, the only prior such survey at a US medical university. Of the 483 students who were contacted, 121 (25%) returned completed questionnaires, with responses indicating strong opposition to torture and skepticism about its usefulness. Respondents expressed greater opposition to torture in this survey than those who participated in the 2008 survey. Respondents' involvement in Weill Cornell's human rights program was associated with significantly stronger opposition to torture, while personal experiences of harassment were associated with a trend toward weaker opposition to torture. Respondents' answers closely approximate the clearly stated ethics of the profession, suggesting that human rights education during medical school may contribute to the development of proper values in young physicians even before they proceed into practice.

Abdominal Contouring: Can the American Society of Anesthesiologists Classification System Help Determine When to Say No?

BACKGROUND: The purpose of this study was to determine whether the American Society of Anesthesiologists classification system could be used preoperatively to identify patients at high risk for complications after abdominal contouring. METHODS: Using the National Surgical Quality Improvement Program database from 2007 to 2012, patients undergoing abdominal contouring procedures were identified and stratified by American Society of Anesthesiologists class. The primary outcome was any complication within 30 days. Secondary outcomes included minor wound, major surgical, and medical complication. Adjusted odds ratios were calculated using logistic regression. RESULTS: A total of 3637 patients were analyzed; 14.6 percent of patients were class I, 59.1 percent were class II, 23.4 percent were class III, and 2.9 percent were class IV. Overall complication and mortality rates were 12 percent and 0.2 percent, respectively. There was a significant trend of increasing odds of any complication with increasing class (class I, OR, 1.0; class II, OR, 1.5; class III, OR, 2.5; class IV, OR, 5.6; p-trend < 0.001). This trend was seen consistently for minor wound complications, medical complications, and major surgical complications (p = 0.007, p = 0.005, and p = 0.001, respectively). CONCLUSIONS: The American Society of Anesthesiologists classification system, which is simple and universally applicable, appears to predict significant complications and can be used to rapidly screen patients before abdominal contouring. Furthermore, the authors' results can be used to inform patient-physician discussion about the risks incurred when undergoing these procedures based on their individual class. Together with optimization of high-risk patients, patient selection using American Society of Anesthesiologists classification may prevent complications and improve outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Bullous Kaposiform Hemangioendothelioma Masquerading as Aplasia Cutis Congenita.

We present the case of a male infant with violaceous bullae on the scalp that were initially thought to be bullous aplasia cutis but at 3 months of age were diagnosed as a kaposiform hemangioendothelioma. This diagnosis should be considered when evaluating newborns with bullous plaques on the scalp that do not heal in the first 2-3 weeks of life. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that typically presents as a violaceous to purpuric plaque at birth or early infancy. It may be associated with Kasabach-Merritt phenomenon (KMP), a potentially life-threatening consumptive coagulopathy.