Obstructive Sleep Apnea, Obesity Hypoventilation Syndrome, and Pulmonary Hypertension: A State-of-the-Art Review.

The pathophysiological interplay between sleep-disordered breathing (SDB) and pulmonary hypertension (PH) is complex and can involve a variety of mechanisms by which SDB can worsen PH. These mechanistic pathways include wide swings in intrathoracic pressure while breathing against an occluded upper airway, intermittent and/or sustained hypoxemia, acute and/or chronic hypercapnia, and obesity. In this review, we discuss how the downstream consequences of SDB can adversely impact PH, the challenges in accurately diagnosing and classifying PH in the severely obese, and review the limited literature assessing the effect of treating obesity, obstructive sleep apnea, and obesity hypoventilation syndrome on PH.

Dysregulation of the Long Noncoding RNA X-Inactive-Specific Transcript Expression in Male Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female gender as a significant risk factor. Recently, we reported that increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EHITSN), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Increased Xist expression was also detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (ECPAH) was studied in several lines of male ECPAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male ECPAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/Tsix locus. Interestingly, Xist up-regulation in male ECPAH decreases the expression of Klf2, via EHITSN interaction with EZH2, the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EHITSN-triggered p38/Elk1/c-Fos signaling is a pathologic mechanism central to ECPAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male ECPAH.

Thrombocytopenia a predictor of malaria: how far?

Malaria is an acute febrile illness. It is a dangerous disease that contributes to millions of hospital visits and hundreds of thousands of deaths, especially in children residing in sub-Saharan Africa. In a non-immune individual, symptoms usually appear 10-15 days after the infective mosquito bite. The first symptoms-fever, headache, and chills-may be mild and difficult to recognize as malaria. If not treated within 24 h, P. falciparum malaria can progress to severe illness, often leading to death. Children with severe malaria frequently develop one or more of the following symptoms: severe anaemia, respiratory distress in relation to metabolic acidosis, or cerebral malaria. In adults, multi-organ involvement is also frequent. In malaria endemic areas, people may develop partial immunity, allowing asymptomatic infections to occur. Haematological changes are well-recognised with malarial infection however background haemoglobinopathy, nutritional status, demographic factors and malaria immunity play a major role in specific changes in that geographical region. Artemisinin derivatives are new generation antimalarial drugs they are used in the treatment of acute attacks of severe malaria including cerebral malaria. Information on the safety of these new antimalarial drugs on body function is still scanty. Haematological parameters are well studied in P. falciparum infection, but now recent studies have indicated that these changes do occur in P. vivax infection also. Hematological profile together with microscopy will enable rapid diagnosis, prompt treatment and further complications can be avoided. This current review is aimed at providing an up-to-date information on the role of malaria and anti-malarial drugs on haematological parameters especially thrombocytopenia.

The Impact of a Narcotic-Sparing Enhanced Recovery Protocol on Postoperative Narcotic Use Following Colectomy.

BACKGROUND: In the United States, 37% of all opioids are prescribed in the surgical setting, many of which report initial exposure in the postoperative period. OBJECTIVE: This study aimed to assess the impact of a narcotic-sparing enhanced recovery after surgery protocol on postoperative narcotic use by patients and to assess its impact on the narcotic-prescribing practices of physicians. DESIGN: Data regarding consecutive narcotic-naïve patients who underwent a surgical procedure from January 2013 to August 2017 were retrospectively reviewed. SETTINGS: Patients were divided into 2 cohorts: preimplementation (2013-2015) and postimplementation (2015-2017) of the enhanced recovery after surgery protocol. PATIENTS: This study included patients who underwent elective inpatient abdominal colorectal surgery at the University of Florida Health. MAIN OUTCOME MEASURES: The primary outcome measure was 30-day postoperative narcotic use (inpatient and outpatient). Other outcomes measured included pain scores, time to diet institution, length of hospital stay, cost of hospitalization, and postoperative complications. RESULTS: Baseline characteristics were similar between the preprotocol group (n = 537) and postprotocol group (n = 790). Protocol implementation was associated with a decrease in the total 30-day postoperative narcotic amount used by patients (2481 vs 31 morphine milligram equivalents; p = 0.05), inpatient patient-controlled analgesia use (63% vs 0.5%; p < 0.00001; dosage 1254 vs 5 morphine milligram equivalents), inpatient on-demand oral narcotic use (90% vs 32%; p = 0.001; dosage 47 vs 5 morphine milligram equivalents), and outpatient narcotic amount used (46 vs 6 morphine milligram equivalents; p = 0.001). Average pain scores were similar. LIMITATIONS: Retrospective nature of the study and possible underestimation of pre- and postoperative narcotic use. CONCLUSIONS: Implementation of a narcotic-sparing enhanced recovery after surgery protocol was associated with a decrease in both inpatient and 30-day outpatient postoperative narcotic use. Variation in resident physician prescribing practices suggests the need for ongoing education to accompany these protocols. See Video Abstract at http://links.lww.com/DCR/B936 . EL IMPACTO DE UN PROTOCOLO DE RECUPERACIN MEJORADO CON AHORRO DE NARCTICOS EN EL USO POSTOPERATORIO DE NARCTICOS DESPUS DE UNA COLECTOMA: ANTECEDENTES:En los Estados Unidos, el 37 % de todos los opioides se prescriben en el entorno quirúrgico. Entre los adictos a los narcóticos, muchos reportan una exposición inicial en el período posoperatorio.OBJETIVO:Nuestro objetivo fue evaluar el impacto de un protocolo de recuperación mejorada después de la cirugía que ahorra narcóticos en el uso de narcóticos postoperatorios por parte de los pacientes y evaluar su impacto en las prácticas de prescripción de narcóticos de los médicos.DISEÑO:Se revisaron retrospectivamente los datos de pacientes consecutivos sin tratamiento previo con narcóticos que se sometieron a un procedimiento quirúrgico colorrectal abdominal electivo para pacientes hospitalizados desde enero de 2013 hasta agosto de 2017.AJUSTE:Los pacientes se dividieron en 2 cohortes: antes de la implementación (2013-2015) y después de la implementación (2015-2017) del protocolo de recuperación mejorada después de la cirugía.PACIENTES:Pacientes de cirugía colorrectal abdominal electiva para pacientes internados en University of Florida Health.MEDIDAS DE RESULTADO PRINCIPALES:La medida de resultado primaria fue el uso de narcóticos postoperatorios de 30 días (pacientes hospitalizados y ambulatorios). Otros resultados medidos incluyeron puntuaciones de dolor, tiempo hasta la institución de la dieta, duración de la estancia hospitalaria, costo de la hospitalización y complicaciones postoperatorias.RESULTADOS:Las características iniciales fueron similares entre los grupos antes (n = 537) y después del protocolo (n = 790). La implementación del protocolo se asoció con una disminución en la cantidad total de narcóticos postoperatorios de 30 días utilizada por los pacientes (2481 mg frente a 31 mg de equivalentes de morfina, p = 0,05), uso de analgesia controlada por pacientes hospitalizados (63 % frente a 0,5 %, p < 0,00001; dosis 1254 mg frente a 5 mg), uso de narcóticos orales a demanda en pacientes hospitalizados (90 % frente a 32 %, p = 0,001; dosis de 47 mg frente a 5 mg) y cantidad de narcóticos utilizados en pacientes ambulatorios (46 mg frente a 6 mg, p = 0,001). Las puntuaciones medias de dolor fueron similares.LIMITACIONES:La naturaleza retrospectiva del estudio y la posible sub estimación del uso de narcóticos antes y después de la operación fueron limitaciones de los hallazgos del estudio.CONCLUSIÓN:La implementación de un protocolo de recuperación mejorada después de la cirugía que ahorra narcóticos se asoció con una disminución en el uso de narcóticos en el postoperatorio de pacientes hospitalizados y ambulatorios de 30 días. La variación en las prácticas de prescripción de los médicos residentes sugiere la necesidad de una educación continua que acompañe a estos protocolos. Consulte Video Resumen en http://links.lww.com/DCR/B936 . (Traducción-Dr. Mauricio Santamaria ).

Antimicrobial Resistance Patterns of Fecal Escherichia coli in Wildlife, Urban Wildlife, and Livestock in the Eastern Region of Sri Lanka, and Differences between Carnivores, Omnivores, and Herbivores.

Antimicrobial resistance (AMR) is a major public health concern. We identified AMR in fecal Escherichia coli of wildlife (WL), urban wildlife (UWL), and livestock in the eastern region in Sri Lanka and compared the prevalence of AMR bacteria from carnivores, omnivores, and herbivores. Fecal samples were collected from 165 animals: WL (n=47), UWL (n=54), and livestock (n=64). Esherichia coli was cultured from 129 samples, with isolation rates of 76% from WL (36/47), 70% from UWL (45/54), and 75% from livestock (48/64). Testing E. coli isolates against 12 antimicrobials using the disk diffusion method revealed that the proportions of E. coli isolates resistant to at least one antimicrobial were WL 52.7%, UWL 20%, and livestock 52%. Multidrug-resistant E. coli isolates were detected in WL, UWL, and livestock. Overall, the prevalence of E. coli isolates with AMR was significantly lower in UWL compared with WL and livestock. The number of isolates showed AMR was significantly higher in E. coli from carnivores than in isolates from omnivores and in herbivores. We conclude that AMR E. coli in Sri Lanka is widespread in WL, UWL, and livestock. The higher incidence of AMR bacteria in carnivores compared with herbivores and omnivores suggest that the mechanisms of spread of AMR may vary among wild animals, which requires further investigation.

The Impact of Sex Chromosomes in the Sexual Dimorphism of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease with a poorly understood female prevalence. Emerging research suggests that nonhormonal factors, such as the XX or XY sex chromosome complement and sex bias in gene expression, may also lead to sex-based differences in PAH incidence, penetrance, and progression. Typically, one of females' two X chromosomes is epigenetically silenced to offer a gender-balanced gene expression. Recent data demonstrate that the long noncoding RNA X-inactive specific transcript, essential for X chromosome inactivation and dosage compensation of X-linked gene expression, shows elevated levels in female PAH lung specimens compared with controls. This molecular event leads to incomplete inactivation of the females' second X chromosome, abnormal expression of X-linked gene(s) involved in PAH pathophysiology, and a pulmonary artery endothelial cell (PAEC) proliferative phenotype. Moreover, the pathogenic proliferative p38 mitogen-activated protein kinase/ETS transcription factor ELK1 (Elk1)/cFos signaling is mechanistically linked to the sexually dimorphic proliferative response of PAECs in PAH. Apprehending the complicated relationship between long noncoding RNA X-inactive specific transcript and X-linked genes and how this relationship integrates into a sexually dimorphic proliferation of PAECs and PAH sex paradox remain challenging. We highlight herein new findings related to how the sex chromosome complement and sex-differentiated epigenetic mechanisms to control gene expression are decisive players in the sexual dimorphism of PAH. Pharmacologic interventions in the light of the newly elucidated mechanisms are discussed.

Characterization and Antimicrobial Resistance of Environmental and Clinical Aeromonas Species Isolated from Fresh Water Ornamental Fish and Associated Farming Environment in Sri Lanka.

The aims of this study were to characterize and investigate antimicrobial susceptibility and presence of integrons in 161 Aeromonas spp. isolated from ornamental freshwater fish farming environment, apparently healthy and diseased fish. Phylogenetic analyses of the gyrB gene sequences identified Aeromonas veronii as the most abundant species (75.8%) followed by Aeromonashydrophila (9.3%), Aeromonas caviae (5%), Aeromonas jandaei (4.3%), Aeromonas dhakensis (3.7%), Aeromonas sobria (0.6%), Aeromonas media (0.6%), and Aeromonas popoffii (0.6%). Susceptibility to thirteen antimicrobials was determined and antimicrobial resistance frequencies were: amoxicillin (92.5%), enrofloxacin (67.1%), nalidixic acid (63.4%), erythromycin (26.1%), tetracycline (23.6%), imipenem (18%), trimethoprim-sulfamethoxazole (16.8%), and gentamicin (16.8%). Multi-drug resistance (MDR) was widespread among the isolates (51.6%, 83/161) with 51.6% (63/122) A. veronii isolates being MDR. In addition, 68.3% of isolates had multiple antibiotic resistance (MAR) indexes higher than 0.2, suggesting that they originated from a high-risk source of contamination where antimicrobials are often used. In all, 21.7% isolates carried class 1 integrons, with 97.1% having gene cassettes, while there were 12 isolates carrying class 2 integron gene cassettes. Our findings highlight that the aquatic environment and ornamental fish act as reservoirs of multidrug resistant Aeromonas spp. and underline the need for a judicious use of antimicrobials and timely surveillance of antimicrobial resistance (AMR) in aquaculture.

Up-Regulation of the Long Noncoding RNA X-Inactive-Specific Transcript and the Sex Bias in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease. Increased expression and activity of the long-noncoding RNA X-inactive-specific transcript (Xist), essential for X-chromosome inactivation and dosage compensation of X-linked genes, may explain the sex bias of PAH. The present studies used a murine model of plexiform PAH, the intersectin-1s (ITSN) heterozygous knockout (KOITSN+/-) mouse transduced with an ITSN fragment (EHITSN) possessing endothelial cell proliferative activity, in conjunction with molecular, cell biology, biochemical, morphologic, and functional approaches. The data demonstrate significant sex-centered differences with regard to EHITSN-induced alterations in pulmonary artery remodeling, lung hemodynamics, and p38/ETS domain containing protein/c-Fos signaling, altogether leading to a more severe female lung PAH phenotype. Moreover, the long-noncoding RNA-Xist is up-regulated in the lungs of female EHITSN-KOITSN+/- mice compared with that in female wild-type mice, leading to sex-specific modulation of the X-linked gene ETS domain containing protein and its target, two molecular events also characteristic to female human PAH lung. More importantly, cyclin A1 expression in the S and G2/M phases of the cell cycle of synchronized pulmonary artery endothelial cells of female PAH patients is greater versus controls, suggesting functional hyperproliferation. Thus, Xist up-regulation leading to female pulmonary artery endothelial cell sexual dimorphic behavior may provide a better understanding of the origin of sex bias in PAH. Notably, the EHITSN-KOITSN+/- mouse is a unique experimental animal model of PAH that recapitulates most of the sexually dimorphic characteristics of human disease.

Objective predictors of intern performance.

BACKGROUND: Residency programs select medical students for interviews and employment using metrics such as the United States Medical Licensing Examination (USMLE) scores, grade-point average (GPA), and class rank/quartile. It is unclear whether these metrics predict performance as an intern. This study tested the hypothesis that performance on these metrics would predict intern performance. METHODS: This single institution, retrospective cohort analysis included 244 graduates from four classes (2015-2018) who completed an Accreditation Council for Graduate Medical Education (ACGME) certified internship and were evaluated by program directors (PDs) at the end of the year. PDs provided a global assessment rating and ratings addressing ACGME competencies (response rate = 47%) with five response options: excellent = 5, very good = 4, acceptable = 3, marginal = 2, unacceptable = 1. PDs also classified interns as outstanding = 4, above average = 3, average = 2, and below average = 1 relative to other interns from the same residency program. Mean USMLE scores (Step 1 and Step 2CK), third-year GPA, class rank, and core competency ratings were compared using Welch's ANOVA and follow-up pairwise t-tests. RESULTS: Better performance on PD evaluations at the end of intern year was associated with higher USMLE Step 1 (p = 0.006), Step 2CK (p = 0.030), medical school GPA (p = 0.020) and class rank (p = 0.016). Interns rated as average had lower USMLE scores, GPA, and class rank than those rated as above average or outstanding; there were no significant differences between above average and outstanding interns. Higher rating in each of the ACGME core competencies was associated with better intern performance (p < 0.01). CONCLUSIONS: Better performance as an intern was associated with higher USMLE scores, medical school GPA and class rank. When USMLE Step 1 reporting changes from numeric scores to pass/fail, residency programs can use other metrics to select medical students for interviews and employment.

Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer.

LESSONS LEARNED: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC. BACKGROUND: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer. METHODS: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m2 p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls. RESULTS: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment. CONCLUSION: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.

Performance Improvement With Implementation of a Surgical Skills Curriculum.

OBJECTIVE: To assess the efficacy of an intern surgical skills curriculum involving a boot camp for core open and laparoscopic skills, self-guided practice with positive and negative incentives, and semiannual performance evaluations. DESIGN: Longitudinal cohort study. SETTING: Academic tertiary care center. PARTICIPANTS: Intervention group (n = 15): residents who completed the intern surgical skills curriculum and had performance evaluations in fall of intern year, spring of intern year, and fall of second year. Control group (n = 8): second-year residents who were 1 year ahead of the intervention group in the same residency program, did not participate in the curriculum, and had performance evaluations in fall of second year. RESULTS: In fall of second year of residency, the intervention group had better performance (presented as median values with interquartile ranges) than the control group on one-hand ties (left hand: 9.1 [6.3-10.1] vs 14.6 [13.5-15.4] seconds, p = 0.007; right hand: 8.7 [8.5-9.6] vs 11.5 [9.9-16.8] seconds, p = 0.039). The intervention group also had better performance on all open suturing skills, including mattress suturing (vertical: 33.4 [30.0-40.0] vs 55.8 [50.0-67.6] seconds, p = 0.001; horizontal: 28.7 [27.3-39.9] vs 52.7 [40.7-57.8] seconds, p = 0.003), and a water-filled glove clamp, divide, and ligate task (28.0 [25.0-31.0] vs 59.1 [53.0-93.0] seconds, p < 0.001). Finally, the intervention group had better performance on all laparoscopic skills, including peg transfer (66.0 [59.0-82.0] vs 95.2 [87.5-101.5] seconds, p = 0.018), circle cut (82.0 [69.0-124.0] seconds vs 191.8 [155.5-231.5] seconds, p = 0.002), and intracorporeal suturing (195.0 [117.0-200.0] seconds vs 359.5 [269.0-450.0] seconds, p = 0.002). CONCLUSIONS: Implementation of a comprehensive surgical skills curriculum was associated with improved performance on core open and laparoscopic skills. Further research is needed to understand and optimize motivational factors for deliberate practice and surgical skill acquisition.

Prevalence and extent of industry support for program directors of surgical fellowships in the United States.

BACKGROUND: Fellowship program directors have a considerable influence on the future practice patterns of their trainees. Multiple studies have demonstrated that industry can also exert substantial influence on the practice patterns of physicians as a whole. The purpose of this study is to quantify industry support of fellowship program directors across surgical subspecialties and to assess the prevalence of this support within specific subspecialties. METHODS: Fellowship program directors for acute care, breast, burn, cardio-thoracic, critical care, colon and rectal, endocrine, hepato-pancreato-biliary, minimally invasive, plastic, oncologic, pediatric, and vascular surgery for 2017 were identified using a previously described database. The Open Payments Database for 2017 was queried and data regarding general payments, research, associated research payments, and ownership were obtained. The national mean and median payouts to nonfellowship program director surgeons were used to determine subspecialties with substantial industry support. RESULTS: Five hundred and seventy-six fellowship program directors were identified. Of these, 77% of the fellowship program directors had a presence on the Open Payments Database. The subspecialties with the most fellowship program directors receiving any industry payment, regardless of amount, included vascular (93.5%), cardio-thoracic (92.8%), minimally invasive surgery (90.5%), plastics (85.3%), and colon and rectal (81.0%). The subspecialty with the greatest mean payment was minimally invasive surgery (21,175 US dollars); the greatest median payment was vascular (1,871 US dollars). The 3 most common types of payments were for general compensation (31.4%), consulting fees (28.7%), and travel and lodging (14.7%). Vascular surgery had the greatest percentage of fellowship program directors receiving research payments (48%). The greatest amount paid to any individual fellowship program director was 382,368 US dollars. Excluding outliers, fellowship program directors received substantially more payments than those received on average by general surgeons. CONCLUSION: The majority of fellowship program directors receive some industry support. Most payments are for compensation for noncontinuing medical education related services and consulting fees. Certain specialties were more likely to have industry payments than others. Overall, only a minority of fellowship program directors received research support from industry. We advocate for transparent discussions between fellowship program directors and their trainees to help foster healthy academic-industry collaborations.

Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy.

The sex-biased disease pulmonary arterial hypertension (PAH) is characterized by the proliferation and overgrowth of dysfunctional pulmonary artery endothelial cells (PAECs). During inflammation associated with PAH, granzyme B cleaves intersectin-1 to produce N-terminal (EHITSN) and C-terminal (SH3A-EITSN) protein fragments. In a murine model of PAH, EHITSN triggers plexiform arteriopathy via p38-ELK1-c-Fos signaling. The SH3A-EITSN fragment also influences signaling, having dominant-negative effects on ERK1 and ERK2 (also known as MAPK3 and MAPK1, respectively). Using PAECs engineered to express tagged versions of EHITSN and SH3A-EITSN, we demonstrate that the two ITSN fragments increase both p38-ELK1 activation and the ratio of p38 to ERK1 and ERK2 activity, leading to PAEC proliferation, with female cells being more responsive than male cells. Furthermore, expression of EHITSN substantially upregulates the expression and activity of the long non-coding RNA Xist in female PAECs, which in turn upregulates the X-linked gene ELK1 and represses expression of krüppel-like factor 2 (KLF2). These events are recapitulated by the PAECs of female idiopathic PAH patients, and may account for their proliferative phenotype. Thus, upregulation of Xist could be an important factor in explaining sexual dimorphism in the proliferative response of PAECs and the imbalanced sex ratio of PAH.

Associations Between National Board Exam Performance and Residency Program Emphasis on Patient Safety and Interprofessional Teamwork.

OBJECTIVE: Several aspects of medical training may contribute to the ultimate goal of producing excellent physicians whose patients will have the best possible outcomes. However, the relative importance of education, evaluation and feedback, duty hours, practice structure, and program culture in achieving this goal is unclear. This study assessed associations among in-training exam performance, Accreditation Council for Graduate Medical Education (ACGME) Resident Survey responses, and American Board of Medical Specialties (ABMS) national board exam performance. METHODS: Residency training programs at a university teaching hospital were classified as having 5-year first-time ABMS pass rates above (n=12) or below (n=3) the national average for their specialty. These groups were compared by ACGME Resident Survey data and in-training exam performance. RESULTS: Surveys were collected from 484/543 eligible residents (89%), including 177 surveys from programs with below-average board pass rates and 307 surveys from programs with aboveaverage board pass rates. In-training exam performance was similar between groups. Aboveaverage programs had stronger agreement with statements that their culture reinforced patient safety (4.72 vs. 4.30, p=0.006) and that information was not lost during transitions of care (4.14 vs. 3.63, p=0.001). Although the occurrence of interprofessional teamwork was similar between groups, above-average programs had stronger agreement with the statement that interprofessional teamwork was effective (4.60 vs. 4.17, p=0.003). CONCLUSION: Residency programs emphasizing patient safety and effective interprofessional teamwork had above-average first-time national board pass rates.

STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn's Disease.

Crohn's disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele "A" with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 "A" risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

Gender differences among surgical fellowship program directors.

BACKGROUND: Although women are increasingly represented in American surgery, data regarding sex and academic rank of the leadership of fellowship programs are lacking. METHODS: Demographics and academic ranks for fellowship program directors were analyzed for 811 surgery fellowship programs across 14 specialties. Associations between academic rank and sex were assessed using a χ2 independence test. Correlation between subspecialty compensation and percentage of female fellowship program directors was assessed using Pearson r. RESULTS: Women represented 18% of all fellowship program directors. Eighteen percent of fellowship program directors were assistant professors (25% women vs 17% men, P = .049), 36% were associate professors (39% women vs 35% men, P = .379), and 46% were full professors (36% women vs 48% men, P = .018). The percentage of women program directors was greatest in breast surgery (65%) and least in minimally invasive surgery (6%). There was a negative correlation between subspecialty compensation and percentage of female fellowship program directors (r = -0.62, P = .04). CONCLUSION: Women are underrepresented among surgery fellowship program directors. Female fellowship program directors had lesser academic ranks compared with males. It remains unclear whether women surgeons achieve program director appointments at lesser academic ranks or if promotion among fellowship program directors is influenced by sex.

Sigmoido-rectal intussusception.

Rectal prolapse is usually of benign etiology. Rarely, sigmoido-rectal intussusception results from a malignant lead-point. We report the case of a patient with a partially obstructing sigmoid cancer causing a full thickness rectal prolapse requiring surgical intervention. An 82-year-old woman presented with 1 week of rectal bleeding, fecal incontinence, and weight loss. Computed tomography identified sigmoido-rectal intussusception. Colonoscopic biopsy revealed high-grade dysplasia. Magnetic resonance imaging demonstrated a 6-cm mass forming the lead point of the intussusceptum with epiploic appendages seen within the rectal lumen. She underwent laparoscopic low anterior resection with final pathology consistent with T2N0 adenocarcinoma, and recovered well. Among adult patients with rectal prolapse, suspicion for underlying malignancy should prompt a thorough investigation to inform the decision for resection, which may be safely performed by minimally invasive techniques.

Plexiform Arteriopathy in Rodent Models of Pulmonary Arterial Hypertension.

As time progresses, our understanding of disease pathology is propelled forward by technological advancements. Much of the advancements that aid in understanding disease mechanics are based on animal studies. Unfortunately, animal models often fail to recapitulate the entirety of the human disease. This is especially true with animal models used to study pulmonary arterial hypertension (PAH), a disease with two distinct phases. The first phase is defined by nonspecific medial and adventitial thickening of the pulmonary artery and is commonly reproduced in animal models, including the classic models (ie, hypoxia-induced pulmonary hypertension and monocrotaline lung injury model). However, many animal models, including the classic models, fail to capture the progressive, or second, phase of PAH. This is a stage defined by plexogenic arteriopathy, resulting in obliteration and occlusion of the small- to mid-sized pulmonary vessels. Each of these two phases results in severe pulmonary hypertension that directly leads to right ventricular hypertrophy, decompensated right-sided heart failure, and death. Fortunately, newly developed animal models have begun to address the second, more severe, side of PAH and aid in our ability to develop new therapeutics. Moreover, p38 mitogen-activated protein kinase activation emerges as a central molecular mediator of plexiform lesions in both experimental models and human disease. Therefore, this review will focus on plexiform arteriopathy in experimental animal models of PAH.