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Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH suspected secondary to a disseminated mucinous ovarian adenocarcinoma. A 45-year-old female presented with severe hypercalcemia and significant elevations in both PTH and PTHrP two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with numerous metastases. Ectopic PTH secretion was highly suspected after a negative parathyroid ultrasound. Pamidronate, calcitonin, and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab, etelcalcetide, and cinacalcet was attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. While patients with localized PTH-secreting tumors carry a good prognosis, disseminated malignancies can result in significant morbidity and mortality due to severe treatment-resistant hypercalcemia.

Objective The aim of this study was to examine the relationship between changes in liver fat and changes in insulin sensitivity and β-cell function 2 years after gastric banding surgery. Methods Data included 23 adults with the surgery who had prediabetes or type 2 diabetes for less than 1 year and BMI 30 to 40 kg/m2 at baseline. Body adiposity measures including liver fat content (LFC), insulin sensitivity (M/I), and β-cell responses (acute, steady-state, and arginine-stimulated maximum C-peptide) were assessed at baseline and 2 years after surgery. Regression models were used to assess associations adjusted for age and sex. Results Two years after surgery, all measures of body adiposity, LFC, fasting and 2-hour glucose, and hemoglobin A1c significantly decreased; M/I significantly increased; and β-cell responses adjusted for M/I did not change significantly. Among adiposity measures, reduction in LFC had the strongest association with M/I increase (r = -0.61, P = 0.003). Among β-cell measures, change in LFC was associated with change in acute C-peptide response to arginine at maximal glycemic potentiation adjusted for M/I (r = 0.66, P = 0.007). Significant reductions in glycemic measures and increase in M/I were observed in individuals with LFC loss >2.5%. Conclusions Reduction in LFC after gastric banding surgery appears to be an important factor associated with long-term improvements in insulin sensitivity and glycemic profiles in adults with obesity and prediabetes or early type 2 diabetes.

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.

Background: Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. Methods: This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19–associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. Results: Multivariable analysis identified cancer as an independent predictor of COVID-19–associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19–associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53–2.68; PP=.02) or CVD (HR, 1.79; 95% CI, 1.21–2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. Conclusions: Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19–associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.

Introduction: Psoriasis is a chronic disorder with certain systemic compounds. It has been associated with increase in morbidity and mortality from cardiovascular events especially in chronic cases. Aims and Objectives: To compare the levels of CRP, S.ADA and S. Lipid profile among psoriatic patients and controls. Materials and Methods: This is a cross sectional case control study conducted in department of dermatology for a period of 6 months in a teaching institute of Gujarat. Cases included patients of psoriasis attending skin OPD. Controls were taken from health check-up scheme of our hospital with minimal confounding factor. CRP, S.ADA and S. Lipid profile were assessed in both groups. Statistical Analysis: We applied Unpaired T- test for statistical analysis and p value Results: Patient and control group consisted of 25 subjects each. Serum CRP, serum cholesterol and serum TG levels were found to be more significantly elevated in cases when compared to controls with p-value (by unpaired t test) of 0.001, 0.026 and 0.044 respectively. Serum ADA, LDL, VLDL was high among cases when compared to controls but were not statistically significant. (p>0.05). Conclusion: patients of psoriasis have to be evaluated for risk factors of atherosclerosis like Serum lipid profile, CRP. Keywords: Psoriasis, CRP, ADA, Lipid profile.

Introduction: Obstructive sleep apnea syndrome (OSAS), a common but under-recognized sleep-related breathing disorder (SRBD) which is associated with significant morbidity and increased mortality. The aim of this study done in South Kerala was to assess the clinical profile and comorbidities of patients with moderate to severe form of OSAS. Materials and Methods: Patients included in the study were from a speciality sleep clinic and had symptoms of OSAS or risk factors for significant sleep apnea. They underwent a supervised polysomnography (PSG) with a portable equipment at home after history taking, relevant clinical evaluation, and pre-requisite workup. Results: One hundred and forty patients were included in the study and 87.9% (123) of the patients were detected to have moderate or severe OSAS (Apnea Hypopnea Index AHI>15 episodes/hour), 81 % (100) of these patients with significant ( moderate or severe) sleep apnea were males having a mean age of 47.9 years, mean body mass index of 33.6 kg/m2and an average neck circumference of 41.2 cm. 80% of patients with moderate to severe OSAS were between the ages of 31-60 years.61.7% and 41% of patients with significant OSAS had hypertension and diabetes respectively. Body mass index and neck circumference had a direct correlation with the severity of OSAS. Statistical analysis: The data was analysed using SPSS 20.0. The factors and co-morbidities associated with OSAS were analysed using Chi-square tests and Independent Sample t-tests. Pearson’s correlation coefficient and a linear regression model was made to find out the possible predictors for AHI Scores and a p value of less than 0.05 was taken as significant. Conclusion: Our study on the clinical profile of patients with obstructive sleep apnea syndrome from a centre in South Kerala shows male predilection, frequent association with obesity and cardiovascular comorbidities such as hypertension and diabetes. Keywords: Obstructive sleep apnea syndr

The coronavirus disease 2019 (COVID-19) pandemic currently gripping the globe is impacting the entire health care system with rapidly escalating morbidities and mortality. Although the infectious risk to the pediatric population appears low, the effects on children with congenital heart disease (CHD) remain poorly understood. The closure of congenital heart surgery programs worldwide to address the growing number of infected individuals could have an unintended impact on future health for COVID-19-negative patients with CHD. Pediatric and congenital heart surgeons, given their small numbers and close relationships, are uniquely positioned to collectively assess the impact of the pandemic on surgical practice and care of children with CHD. We present the results of an international survey sent to pediatric and congenital heart surgeons characterizing the early impact of COVID-19 on the care of patients with CHD.

Tumor lysis syndrome (TLS) is an oncological emergency characterized by a classic tetrad of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Risk assessment and prophylactic therapy is critical in preventing this oncological emergency. Treatment of established TLS involves aggressive hydration, electrolyte management, and the use of hypouricemic agents.

A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on 10th and 11th of August 2018 at the All India Institute of Medical Sciences, New Delhi. The meeting was supported by Children’s HeartLink, a non-governmental organization based in Minnesota, USA. To frame evidence based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases; (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. Evidence based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus and others), obstructive lesions (pulmonary stenosis, aortic stenosis and coarctation of aorta) and cyanotic congenital heart diseases (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein anomaly and others). In addition, protocols for follow-up of post surgical patients are also described, disease wise.

We conducted a randomized phase III trial to evaluate whether adjuvant pembrolizumab for one year (647 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison with high-dose IFNα-2b for one year or ipilimumab for up to three years (654 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies [HR, 0.77; 99.62% confidence interval (CI), 0.59–0.99; P = 0.002]. There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI, 0.61–1.09; P = 0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with IFNα-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared with the prior standard-of-care immunotherapies for patients with high-risk resected melanoma. Significance: Adjuvant PD-1 blockade therapy decreases the rates of recurrence, but not survival, in patients with surgically resectable melanoma, substituting the prior standard-of-care immunotherapies for this cancer. See related commentary by Smithy and Shoushtari, p. 599. This article is highlighted in the In This Issue feature, p. 587

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant β-values >7). Myocardial oxygen consumption had almost no effect on T2 (β-values

Decades ago, Chikungunya and Dengue viruses were lesser known terms, with just some sporadic cases in the Asian and African continents, but with mutations in the virus and the vectors as well, these viruses have spread to the population of the whole globe, causing various outbreaks at various time periods, leaving researchers dumbfound. Infectious diseases are on a rampant rise, and the modern world has found just the perfect defense against them—Vaccines. The genome of structural polyprotein of Chikungunya virus and whole genome of Dengue Virus Serotype 3 were used for this study. These sequences were utilized for predicting suitable B-cell and T-cell epitopes, which can be considered as candidates for a future peptide vaccine. From this study, we were able to find that YSQAPSGFKYWL and RTLTPQPMELKY were the best possible candidates for Chikungunya and Dengue virus, respectively.

Abdominal wall reconstruction is indicated when 1 or more of the abdominal wall components (skin, fascia, or muscle) are either injured or absent. When faced with defects requiring flap reconstruction, the decision regarding flap choice should take into consideration the volume of soft tissue required, the extent of the defect, donor site morbidity, and prior surgical scars that affect flap vascularity. We present a case of an abdominal wall defect with limited reconstructive options in which a spare ileal bowel segment was filleted to create a seromuscular flap for improving the abdominal wall blood supply. The postoperative course was complicated by abdominal fluid collection, which resolved following an ultrasound-guided drain. The patient had normal wound healing and recovery without further postoperative complications at the 7-month follow-up. Seromuscular flaps are a practical option in the armamentarium of plastic surgeons performing abdominal wall reconstruction, especially when other alternatives are limited.

Background: Abfraction is a loss of tooth structure along the gingival margin and manifests with different clinical appearances. It has multifactorial etiology and may occur due to normal and abnormal tooth function and may also be accompanied by pathological wear, such as abrasion and erosion. The theory behind the abfraction is that the tooth flexure in the cervical area is caused due to occlusal compressive forces and tensile stresses. This results in the fractures in the hydroxyapatite (HA) crystals. It is also caused by the low packing density of the Hunter–Schreger band (HSB) at the cervical area. Unfortunately, there is a lack of evidence regarding the outcome of abfraction with or without intervention. The aim of this review is to collect clinical information from the literature and discuss the etiology, pathogenesis, clinical representation, and management. Also, search databases for clinical studies that describe the role of sclerotic dentine in non-carious cervical lesions (NCCLs) are becoming a clinical challenge. Methods: The literature was searched that described the etiology, pathogenesis, clinical representation, and management of the abfraction lesions. Also, a specific question regarding the formation of sclerotic dentin in the NCCL lesion was described and searched for evidence that challenges etching, bonding, and successfully restoring NCCLs. The databases PUBMED, SCOPUS, MEDLINE, WEB of SCIENCE, and EMBASE were searched using the key terms. The inclusion criteria were the randomized controlled clinical trial, cohort studies, and cross-sectional studies that aimed at determining the role of sclerotic dentine in NCCLs and its effect on etching, bonding. Results: One clinical study was retrieved according to the PRISMA flowchart and PICO format. The longer etching time, total-etch adhesive system, and EDTA pre-treatment of the sclerotic dentin of cervical wedge-shaped defects could improve the bonding strength in lesions like NCCL's. Conclusion: In conclusion, clinical challenges that occur due to NCCLs are better managed by a proper understanding of factors like etiopathogenesis, ultra-structure of enamel, and dentine and their effect on the bonding of restorations of the tooth.

Introduction Although an infrequent cause of small penile size in adult men, acquired penile shortening represents a particular reconstructive challenge due to preexisting penile anatomic deformities. Aim With numerous techniques being performed, the purpose of our study is to assess available literature on length enhancement procedures used for acquired penile shortening deformities. Methods A systematic review was performed using the guidelines outlined in the Preferred Reporting Items for Systematic reviews and Meta-analyses. Medline/PubMed, Scopus, and Cochrane Databases were used to identify papers on augmentation Phalloplasty in non-transgender males with acquired penile shortening from 1990 to 2018. Main Outcome Measure Outcomes, complications, and patient-reported satisfaction were analyzed. Results 12 articles, involving 931 patients and 8 primary procedures, met our inclusion criteria. The majority of articles had level of evidence of 4 (83%) and Newcastle Ottawa Scale score of 6 (92%, moderate risk of bias). All studies reported mean penile length gain; however, inconsistent methodology was used when measuring penile dimensions. Mean length gain ranged from 0.6 to 6.4 cm. Overall, the mean complication rate for all techniques ranged from 0% to 50%. Post-operative satisfaction was reported in 10 (83%) studies, 7 of which used a validated scale. Patients were generally satisfied, with reported satisfaction rates ranging from 77% to 100%. Clinical Implications While numerous procedures have been described, the significant limitations in the available data preclude identifying a single superior procedure. Strengths & Limitations The significant heterogeneity in the reported literature is a limitation of this study and highlights the need for standardized reporting. However, this study is the first to analyze augmentation phalloplasty literature in the setting of acquired penile shortening. Conclusion Augmentation phalloplasty techniques for acquired penile shortening are evolving and are continuously being modified; best-practice guidelines are crucial to achieve safe and satisfactory outcomes in this population.

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.

Introduction: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. Process: Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on the 10th and 11th of August, 2018 at the All India Institute of Medical Sciences. Objectives: The aim of the study was to frame evidence-based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases and (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. Recommendations: Evidence-based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts, obstructive lesions, and cyanotic congenital heart diseases. In addition, protocols for follow-up of postsurgical patients are also described. Keywords: Congenital heart disease, Intervention, Surgery

The RASopathies are a class of developmental disorders caused by a genetic mutation in the Ras signaling pathway and asso ciated mitogen-activated protein kinases that control the cell cycle, differentiation and senescence. These diseases encompass a diverse set of clinical syndromes including neurofibromatosis type 1 and Noonan syndrome. Although the pathophysi ological manifestations of these conditions are diverse, they share some common phenotypic features. The prevalence of pul monary hypertension in the RASopathies is not well established as compared to cardiac and neurocognitive impairments. This paper reviews the cases of pulmonary hypertension in these member syndromes. Due to the aggressive and often fatal nature of pulmonary hypertension, a diagnosis of a RASopathy should also include screening for pulmonary hypertension.

The liver is the most common site of metastatic disease1. Although this metastatic tropism may reflect the mechanical trapping of circulating tumour cells, liver metastasis is also dependent, at least in part, on the formation of a 'pro-metastatic' niche that supports the spread of tumour cells to the liver2,3. The mechanisms that direct the formation of this niche are poorly understood. Here we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. During early pancreatic tumorigenesis in mice, hepatocytes show activation of signal transducer and activator of transcription 3 (STAT3) signalling and increased production of serum amyloid A1 and A2 (referred to collectively as SAA). Overexpression of SAA by hepatocytes also occurs in patients with pancreatic and colorectal cancers that have metastasized to the liver, and many patients with locally advanced and metastatic disease show increases in circulating SAA. Activation of STAT3 in hepatocytes and the subsequent production of SAA depend on the release of interleukin 6 (IL-6) into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6-STAT3-SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis. Our data identify an intercellular network underpinned by hepatocytes that forms the basis of a pro-metastatic niche in the liver, and identify new therapeutic targets.

OBJECTIVES: Pediatric Non-Alcoholic Fatty Liver Disease is prevalent among Hispanics, which may partially result from a higher frequency of the C > G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Our prior work showed an interaction between the GG genotype and high dietary sugar, resulting in higher liver fat. Additionally, studies show that extreme sugar depletion improves liver fat in children with obesity. This trial aimed to test whether a clinical intervention for sugar reduction versus standard diet advice in Hispanic youth differentially impacts liver fat, liver fibrosis, body weight and composition, and whether effects differed by PNPLA3 genotype. METHODS: Hispanic youth with obesity (n = 105; 72% GG) were randomized to a healthy eating control group or a sugar reduction group (goal, 0.05). No treatment by PNPLA3 genotype interaction was observed for any endpoint (P > 0.05). While there was no significant change in fat mass in either study arm, secondary analyses revealed that participants who reduced fat mass, significantly reduced liver fat compared to those without fat mass reduction [−1.8% (−6.2, −3.4) vs. 0.3% (−1.0, 1.1), P

Purpose of Review Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher. Recent Findings Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes. Summary Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.

Background: Soluble CD163 (sCD163) is a scavenger receptor that is shed during inflammation and monocyte/macrophage activation and appears to be useful in resolution of the inflammation. This marker has been associated with increased mortality and morbidity in several inflammatory conditions. Hypothesis: sCD163 levels are related to myocardial fibrosis (MF) in people living with HIV infection (PLWH) and controls. Methods: sCD163 levels were measured in serum samples of 92 participants (54 PLWH and 38 HIV- controls, mean age 47±14 years, 28% female).. Myocardial structure and function were assessed using CMR (GE 3.0T; acquisition: RT-Hawk, Heart Vista Inc; analysis: cvi42, Circle Inc, v5.10). Our protocol included cine, pre-contrast, 12-minute post contrast T1 mapping and LGE after infusion of 0.1mmol/kg of gadolinium (Multihance). 12-minute ECV (extra cellular volume) maps were generated from T1 maps. Results: We studied 40 PLWH and 28 HIV- controls (mean age 45±14 years, 46% men). HIV-positive individuals had significantly higher levels of sCD163, compared to controls ( mean±SD: 78±6 versus 54±5 ng/dL, p-value Conclusions: Soluble CD163, as a marker of monocyte/macrophage activation, is associated with increased diffuse subclinical MF, estimated by postcontrast ECV, in virologically-suppressed PLWH. Importantly, this association is independent of demographic factors, LV function, and ART medication use. These findings highlight the importance of chronic sustained inflammation in development of MF in PLWH.

Introduction: Recent studies have suggested that increased risk of cardiovascular disease (CVD) in people living with HIV (PLWH) extends beyond coronary artery disease to involve myocardial fibrosis. Cardiac MRI can accurately detect overt scar and diffuse fibrosis in this population. Hypothesis: Compared to controls, virologically-suppressed PLWH without known clinical CVD have increased risk of myocardial fibrosis and scar, as demonstrated by T1/ECV (extracellular volume) mapping and late gadolinium enhancement (LGE) respectively. Methods: Myocardial structure and function were assessed using CMR (GE 3.0T; acquisition: RT-Hawk, Heart Vista Inc; analysis: cvi42, Circle Inc, v5.10). Our protocol included cine, pre-contrast images, LGE and post contrast T1 mapping 12 minutes after infusion of 0.1mmol/kg of gadolinium (Multihance). 12-minute ECV maps were generated and ECV>32% was considered increased extracellular volume indicating diffuse fibrosis. Results: We studied 92 participants (54 PLWH and 38 HIV- controls, mean age 47±14 years, 28% female). There was no difference in LV systolic function and mass between groups. Clinically detectable LGE was observed in 5 PLWH (10%) and no controls (p :0.04). While there was no significant difference in pre-contrast T1 values in cases vs controls (1044±14 vs 1023±15 ms, p: 0.30), PLWH were more likely to have 12mECV values above the median of 25.5% (57% vs 41%, p: 0.23). In regression models, PLWH had higher ECV values (coefficient: 3.4%, p:0.04) and higher odds of increased ECV (OR: 3.9, 95%CI: 1.0-15.6, p:0.05) adjusted for age, gender, and ethnicity. In multivariable models, women had significantly lower ECV values (p: 0.04). African Americans (AAs) had significantly higher chance of having LGE (OR:12.6, p: 0.03). However, while non-black PLWH had a significantly higher odds of increased ECV (adjusted OR:6.0, p: 0.03), this association was not significant in AAs (p:0.9). Conclusion: Virologically suppressed PLWH are at higher risk of clinically detectable LGE in myocardium and diffuse myocardial fibrosis, independent of their demographics and cardiac function. HIV infection is associated with higher risk of LGE in AAs, while subclinical increased ECV is the more common finding in other ethnicities.

Background ICI revolutionized modern Oncology landscape and being utilized in metastatic to adjuvant and neo-adjuvant settings. As Oncologists, we are treating cancer patients with ICI every day, yet there is still a lot that is unknown about these drugs. We don’t have clear understanding of the efficacy and toxicity when sequencing one ICI for another. We conducted a retrospective review of real world data at Lahey Hospital and Medical Center to understand further and to pave path for prospective studies to understand this issue further to improve patient care. Methods We retrospectively reviewed Oncology patient charts who received ICI between January1, 2014 to December 18, 2018. Total 483 patients received ICI during this time frame and 22 of these patients received a second ICI either as monotherapy or in combination with other ICI or chemotherapy. Results A total of 22 patients received subsequent ICI after the initial ICI as showed in table 1. 15 of the 22 (68%) patients were transitioned from one ICI to another monotherapy. 11 of these patients were transitioned secondary to disease progression (73%), three had immune related adverse events and one was switched per standard of care. One patient had ICI re-challenge. Three patients had a transition from ICI monotherapy to combination ICI therapy. One patient went onto chemo-immunotherapy and 2 patients transitioned from combination ICI to chemo-immunotherapy. Conclusions ICI therapy is evolving and patients are being treated with multiple lines of ICI. In current practices, ICI is frequently being transitioned from cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) classes or combined with chemotherapy or targeted therapy. It would be prudent to explore the effects of sequencing these medications either as a monotherapy or in combination with other therapies to better serve our patients and to prevent financial toxicity.

Background: Papillary muscle rupture in the perinatal period is a rare event that leads to severe mitral or tricuspid insufficiency due to a flail leaflet. Neonatal tricuspid chordal reconstruction for this condition is rarely reported. Early recognition and treatment have the potential to be lifesaving. We present our surgical experience with five such patients, along with their midterm follow-up. Methods: Between August 2010 and November 2012, five neonates (aged 1-30 days) underwent surgery for severe atrioventricular valve regurgitation. All neonates had severe tricuspid regurgitation due to ruptured chordae. In addition, two had moderate mitral regurgitation; one due to ruptured chordae of the posterior mitral leaflet and the other due to prolapse of the anterior mitral leaflet. All underwent emergent surgery where the ruptured chordae to the anterior tricuspid leaflet were replaced with neochordae made with expanded polytetrafluoroethylene (ePTFE) suture. The mitral valve was repaired in two patients. Results: All patients survived surgery without the need for postoperative mechanical circulatory assist. Predischarge echocardiograms showed good coaptation of tricuspid and mitral leaflets with minimal regurgitation in all. At follow-up between 75 months to 102 months, four patients had excellent outcomes with less than mild tricuspid regurgitation. One child with flail tricuspid and mitral leaflets developed progressive tricuspid and mitral regurgitation requiring surgical re-repair at 20 months following the initial surgery. Conclusion: Repair of chordal rupture of the tricuspid valve in neonates using e PTFE neo-chordae can provide acute salvage and gratifying midterm results in the management of this potentially fatal condition.

Patients undergoing cardiovascular and thoracic procedures are at an accentuated risk of higher morbidity and mortality, which are a consequence of the proliferative nature of the severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) on the lung vasculature, which in turn reflects as a cascading effect on the interdependent physiology of the cardiovascular and pulmonary organ systems. These are secondary to systemic inflammatory response syndrome and immunosuppressive responses to surgery and mechanical ventilation. Thus, the need to establish guidelines for the practice of cardiothoracic surgery which is safe for both the patient and the healthcare team presents as a priority, which is the mainstay of this article.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Uncovering mechanisms responsible for the heterogeneous clinical features of this disease is an essential step toward developing improved and more specific therapeutic approaches. Here, we sought to identify transcriptional regulators of aggressive PDAC growth through in vivo CRISPR screening of epigenetic and transcription factors in an orthotopic model. We identified the ISL LIM homeobox 2 (ISL2) gene as a tumor suppressor whose depletion enhances the proliferation of human PDAC cells in vitro and in vivo and cooperates with activated KRAS to initiate PDAC in a murine model. Conversely, the upregulation of ISL2 expression through CRISPR-mediated locus-specific epigenetic editing results in reduced cell proliferation. Importantly, ISL2 is epigenetically silenced through DNA methylation in ~60% of PDAC tumors, which correlates with poor patient outcome. Functional studies showed that ISL2 loss rewires metabolic gene expression, and consequently potentiates oxidative phosphorylation while reducing glycolysis. This metabolic shift creates selective vulnerability to small molecule inhibitors of mitochondrial respiration and fatty acid oxidation. Collectively, these findings reveal ISL2 as a novel tumor suppressor whose inactivation drives metabolic reprogramming in an aggressive PDAC subset and point to potential therapeutic vulnerabilities in these tumors.

Intraoperative echocardiography is an integral component of the peri-operative management of pediatric heart disease. It confirms the adequacy of surgery, identifies residual lesions, and can provide useful hemodynamic data. It, therefore, helps to decide on the need for revision of repair and guides the postoperative management strategy. Intraoperative echocardiography is done with the use of either an epicardial probe or a transesophageal probe. Epicardial echocardiography is a simple, useful modality and has the ability to perform imaging in cases where transesophageal echocardiography cannot be easily performed, for example, in low birth weight babies. We attempt to describe in detail the technique of epicardial echocardiography and the various views that we have found useful for a complete postsurgical evaluation. The limitations of the technique are also discussed in detail.

Prepectoral implant-based reconstruction reemerged as a viable approach following recent advances in reconstructive techniques and technology. To achieve successful outcomes, careful patient selection is critical. Obesity increases the risk of complications and has been suggested as a relative contraindication for prepectoral breast reconstruction.Retrospective chart review of patients who underwent immediate two-stage implant-based reconstruction at the authors' institution was performed. Only women having a body mass index of 30 kg/m or greater were included. Patient demographics, operative details, and surgical outcomes of prepectoral and subpectoral reconstruction were compared.One hundred ten patients (189 breasts) who underwent prepectoral and 83 (147 breasts) who underwent subpectoral reconstruction were included. Complications were comparable between the two groups. Twelve devices (6.4 percent), including implants and tissue expanders, required explantation in the prepectoral group, and 12 devices (8.2 percent) required explantation in the subpectoral group (p =0.522). Final implant-based reconstruction was achieved in 180 breasts (95.2 percent) in the prepectoral group and 141 breasts (95.9 percent) in the subpectoral group. Regardless of type of reconstruction (prepectoral or subpectoral), for each point increase in body mass index, the odds of complications and device explantation increased by 3.4 percent and 8.6 percent, respectively; and the optimal cutoff to predict higher complications and explantation rates was a body mass index of 34.8 kg/m and 34.1 kg/m, respectively.Obesity increases complications and failure rates in a positive correlation; however, complications and final reconstruction rates are comparable between the prepectoral and subpectoral groups. The authors believe that obesity should not be a contraindication for prepectoral breast reconstruction but that care should be taken in patients with a body mass index above 35 kg/m.Therapeutic, III.

OBJECTIVE Type 2 diabetes (T2D) results from progressive loss of β-cell function. The BetaFat study compared gastric banding and metformin for their impact on β-cell function in adults with moderate obesity and impaired glucose tolerance (IGT) or recently diagnosed, mild T2D. RESEARCH DESIGN AND METHODS Eighty-eight people aged 21–65 years, BMI 30–40 kg/m2, with IGT or diabetes known for 25 mmol/L) were performed at baseline, 12 months, and 24 months to measure steady-state C-peptide (SSCP) and acute C-peptide response to arginine at maximum glycemic potentiation (ACPRmax) and insulin sensitivity (M/I). RESULTS At 24 months, the band group lost 10.7 kg; the metformin group lost 1.7 kg (P < 0.01). Insulin sensitivity increased 45% in the band group and 25% in the metformin group (P = 0.30 between groups). SSCP adjusted for insulin sensitivity fell slightly but not significantly in each group (P = 0.34 between groups). ACPRmax adjusted for insulin sensitivity fell significantly in the metformin group (P = 0.002) but not in the band group (P = 0.25 between groups). HbA1c fell at 12 and 24 months in the band group (P < 0.004) but only at 12 months (P < 0.01) in the metformin group (P > 0.14 between groups). Normoglycemia was present in 22% and 15% of band and metformin groups, respectively, at 24 months (P = 0.66 between groups). CONCLUSIONS Gastric banding and metformin had similar effects to preserve β-cell function and stabilize or improve glycemia over a 2-year period in moderately obese adults with IGT or recently diagnosed, mild T2D.

The main aim of this study was to evaluate the safety and efficacy of diode laser transscleral cyclophotocoagulation (TSCPC) in eyes with good visual acuity.A retrospective chart review identified patients who underwent TSCPC for uncontrolled intraocular pressure (IOP) from 2014 to 2016. Enrollment criteria included pretreatment best-corrected visual acuity (BCVA) of 20 of 40 or better, and a minimum of 6 months of postoperative follow-up.Thirty-three eyes of 33 patients(mean age, 72.1±16.0 y) were enrolled (mean follow-up 12.6±6.1 mo). The mean (SD) IOP was reduced 48.3% from 27.1 mm Hg (7.8) at baseline to 13.1 mm Hg (4.2) at last follow-up. Reduction of ≥1 glaucoma medications was achieved in 17 eyes (51.5%) at last follow-up. The cumulative probability of complete success (BCVA loss2 Snelling lines, 20% reduction IOP, no reoperation for glaucoma, no IOP5 mm Hg) was 78.8% and 50% at months 6 and 12, respectively. The cumulative probability of qualified success (BCVA≥2 lines with ≥20% reduction IOP, no reoperation for glaucoma, no IOP5 mm Hg) was 90.1% and 81.3% at month 6 and 1 year, respectively. Significant vision loss, defined as BCVA≥2 lines, occurred in 33% of patients. The most common complications were postoperative iritic (56.3%) and cystoid macular edema (12.5%).TSCPC demonstrates a strong reduction in IOP and glaucoma medication use. However, with significant vision loss in 33% of patients, future prospective studies with a comparison group receiving traditional glaucoma surgery are needed to determine comparative safety and efficacy.

Background Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression. Method A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results. Result Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy. Conclusion Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance.

This study examines the incidence of visually significant cystoid macular edema (CME) after glaucoma drainage implant (GDI) surgery and analyses risk factors associated with developing CME and prognosis with treatment.In total, 185 eyes from 185 glaucoma patients (mean age, 72.46±13.94 y) who underwent GDI surgery at a tertiary eye institute were recruited. Patients were classified based on the presence (CME) or absence (No-CME) of CME. Pre-GDI and post-GDI best-corrected visual acuity, number of intraocular pressure (IOP)-lowering medications, IOP, standard automated perimetry and post-GDI complications, were recorded and compared between the 2 groups. Optical coherence tomography (OCT) was used to quantify retinal thickness and monitor CME.In total, 41 (22.2%) eyes developed visually significant CME after GDI surgery. Patients with CME had a higher incidence of pre-GDI nonsteroidal anti-inflammatory drug (P0.01) use and higher number of prior glaucoma surgeries (P0.01). CME patients had a higher (P0.01) incidence of iritis, epiretinal membrane, and hypotony. CME eyes responded well to steroids, with resolving macular edema (458.4±151.9 vs. 322.0±92.0 µm, P0.01) and improving visual acuity (0.73±0.48 vs. 0.56±0.56 logarithm of minimum angle of resolution, P0.01). Both CME and non-CME groups had equivalent lowering of IOP and post-GDI glaucoma medications; with no significant elevation in IOP in the steroid-treated CME group.Post-GDI surgery visually significant CME rates are potentially higher in a real hospital scenario compared with controlled clinical trials. With diligent treatment, CME resolves effectively restoring visual acuity and central macular thickness.

INTRODUCTION: Appendix in a nger like projection situated just near the caecum. It is located in the right iliac fossa of the abdomen. The most common pathology which arises is appendicitis and is mostly treated surgically. Although appendix is considered to be a vestigial organ, it accounts for immune function upto some extent. OBJECTIVES: To study and analyse the various histopathological forms of appendicitis MATERIALS AND METHODOLOGY: A descriptive study was undertaken to analyse the different histopathological forms of appendicitis over a period of one year in the Department of Pathology, Government Medical College, Omandurar Government Estate. The acquired data was fed into Microsoft Excel and analysis was done. RESULT: A total of 100 specimens were analysed during the study period. Maximum number of cases (62% of cases) were reported amongst females. The most common age group which was affected was 9 years to 19 years. The most common histopathological form of appendicitis was analysed to be acute appendicitis (76% of cases) The statistical data for various histo pathological types of appendicitis are as follows Subacute appendicitis – 10 cases ; Acute appendicitis – 76 cases ; Chronic appendicitis – 13 cases ; Granulomatous appendicitis – 1 case. CONCLUSION: The incidence of appendicitis is higher in the second decade of life and is remarkably high amongst females. Among the pathological types, incidence of acute appendicitis is the highest and that is seen in the second decade of life

Background: Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH from a disseminated mucinous ovarian adenocarcinoma. Case Presentation: A 45-year-old female presented with confusion, constipation, fatigue, and abdominal pain two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with metastasis to the bladder, parametrium, vagina, right ovary, and rectosigmoid. Subsequent CT revealed numerous bilateral pulmonary nodules, hilar adenopathy, liver lesions, and abdominal adenopathy. On exam, she was tachycardic and hypertensive with diaphoresis, dry mucous membranes, respiratory distress, guarded abdominal tenderness, and altered mental status. Her labs were significant for a serum calcium of 21.7 mg/dL, creatinine of 1.93 mg/dL, ferritin of 2,379 ng/mL, leukocytosis of 21.9 bil/L, PTH of 1,061 pg/mL, and PTHrP of 29 pmol/L. Ectopic PTH secretion was highly suspected after negative parathyroid ultrasound. Pamidronate (60 mg IV), calcitonin (200 U IM), and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab (120 mg SQ), etelcalcetide (5 mg IV), and cinacalcet (60 mg PO) was also attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. Discussion: Hypercalcemia of malignancy typically arises from tumor secretion of PTHrP, cytokine release from osteolytic metastases, or tumor production of calcitriol. In cases of hypercalcemia due to excess PTH secretion, primary parathyroid etiologies are typically considered while ectopic PTH-secreting tumors are rare. PTH staining of biopsy specimens and total body sestamibi scan may prove useful in the early detection and treatment of these tumors, but HCM offers a poor prognosis with mean survival of 2 to 3 months and in-hospital mortality of 6.8%. Currently, there are only three cases in the reported literature of ectopic PTH-induced hypercalcemia related to ovarian cancer. To our knowledge, this is the fourth reported case. Conclusion: Ectopic PTH-secreting tumors carry a poor prognosis and should be considered in cancer patients presenting with PTH-associated hypercalcemia. Biopsy staining for PTH and total body sestamibi scan may assist in the early detection of these tumors, but current treatment strategies offer suboptimal outcomes.

Treatment of advanced heart failure with implantable LVADs is increasing, driven by profound unmet patient need despite potential serious complications: bleeding, infection, and thrombus. The experimental objective was to develop a sensitive imaging approach to assess early thrombus accumulation in LVADs under operational high flow and high shear rates. Methods: A monomeric bifunctional ligand with a fibrin-specific peptide, a short spacer, and 99mTc chelating amino acid sequence (F1A) was developed and compared to its tetrameric PEG analogue (F4A). Results:99mTc attenuation by LVAD titanium (1 mm) was 23%. 99mTc-F1A affinity to fibrin was Kd ~10 µM, whereas, the bound 99mTc-F4A probe was not displaced by F1A (120,000:1). Human plasma interfered with 99mTc-F1A binding to fibrin clot (p

The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) is the largest professional organization in the world dedicated to pediatric and congenital heart surgery. The purpose of this article is to document the first decade of the history of WSPCHS from its formation in 2006, to summarize the current status of WSPCHS, and to consider the future of WSPCHS. The WSPCHS was incorporated in Canada on April 7, 2011, with a head office in Montreal, Canada. The vision of the WSPCHS is that every child born anywhere in the world with a congenital heart defect should have access to appropriate medical and surgical care. The mission of the WSPCHS is to promote the highest quality comprehensive cardiac care to all patients with congenital heart disease, from the fetus to the adult, regardless of the patient’s economic means, with an emphasis on excellence in teaching, research, and community service.

PURPOSE Transit delay is a potential source of error in cardiac arterial spin-labeled (ASL) in heart failure or with collateral circulation. This study demonstrates the feasibility of using transit delay insensitive velocity selective ASL and compares its performance with flow-sensitive alternating inversion recovery (FAIR) ASL. METHODS Velocity selective labeling was achieved using an adiabatic BIR8 preparation. FAIR and velocity-selective ASL (VSASL) with various velocity cutoffs (VC = 10-40 cm/s) and labeling directions (anterior-posterior X, lateral-septal Y, and apical-basal Z) were carried out in 10 healthy volunteers (1F/9M age 23-30 y). Myocardial blood flow (MBF) and temporal signal-to-noise (TSNR) were measured. RESULTS VSASL sensitivity to perfusion decreased with increasing VC . At low VC (

Summary Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However, its origin remains a debated question. Using human data and various hepatocarcinogenesis mouse models, we show that, in early stages, transformed hepatocytes, independent of their proliferation status, activate hepatic progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes reveals that, in all models, HCC originates from hepatocytes. However, whereas in various models tumors do not emanate from HPCs, tracking of progenitors in a model mimicking human hepatocarcinogenesis indicates that HPCs can generate benign lesions (regenerative nodules and adenomas) and aggressive HCCs. Mechanistically, galectin-3 and α-ketoglutarate paracrine signals emanating from oncogene-expressing hepatocytes instruct HPCs toward HCCs. α-Ketoglutarate preserves an HPC undifferentiated state, and galectin-3 maintains HPC stemness, expansion, and aggressiveness. Pharmacological or genetic blockage of galectin-3 reduces HCC, and its expression in human HCC correlates with poor survival. Our findings may have clinical implications for liver regeneration and HCC therapy., Graphical Abstract, Highlights • HPCs expand in the early stages of hepatocarcinogenesis • HCC predominantly originates from hepatocytes • Oncogene-induced hepatocyte transformation activates HPCs via galectin-3 and αKG • Activated HPCs contribute to liver tumor heterogeneity, Tummala et al. demonstrate that hepatocytes and hepatic progenitor cells participate in liver tumor heterogeneity. Malignant hepatocytes crosstalk and activate the neighboring progenitor cells through releases of galectin-3 and α-ketoglutarate. Blocking galectin-3 reduces hepatocarcinogenesis and may have important clinical implications.

Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid artery stenosis, although the optimal surgical technique is debated. The literature suggests that patch angioplasty reduces complication risk, although primary closure shortens cross-clamp time and eliminates complications associated with grafts.The objective of this study was to assess the complication rate after CEA with primary closure.Retrospective review of 240 consecutive patients between 2002 and 2010. Of these patients, 70% returned for follow-up visits for at least 2 or more years.Primary closure was used in all patients. The average cross-clamp time was 18 minutes. Complications in the immediate postoperative period within 30 days were as follows: stroke (n = 3; 1.1%), transient ischemic attack (TIA; n = 4; 1.5%), myocardial infarction (MI; n = 3; 1.1%), and death (n = 1; 0.4%). Short-term follow-up revealed eight patients who were found to have significant restenosis (>80%) by carotid duplex imaging. Two to ten year postoperative complication rates were as follows: stroke (n = 7; 4.2%), TIA (n = 7; 4.2%), amaurosis fugax (n = 1; 0.6%), MI (n = 8; 4.8%), and death (n = 28; 17%). Mortality was due to stroke or heart attack (n = 2; 1.2%), cancer (n = 7; 4.2%), and unknown causes (n = 19; 11%).This study presents our experience with complications after primary closure after CEA. In our experience, CEA is a safe and effective surgical means of preventing stroke in the short term. Well-designed prospective studies are needed to confirm specific patient characteristics in which primary closure and patch angioplasty are indicated.

Purpose To determine if a real-time magnetic resonance imaging (RT-MRI) method during continuous positive airway pressure (CPAP) can be used to measure neuromuscular reflex and/or passive collapsibility of the upper airway in individual obstructive sleep apnea (OSA) subjects. Materials and Methods We conducted experiments on four adolescents with OSA and three healthy controls, during natural sleep and during wakefulness. Data were acquired on a clinical 3T scanner using simultaneous multislice (SMS) RT-MRI during CPAP. CPAP pressure level was alternated between therapeutic and subtherapeutic levels. Segmented airway area changes in response to rapid CPAP pressure drop and restoration were used to estimate 1) upper airway loop gain (UALG), and 2) anatomical risk factors, including fluctuation of airway area (FAA). Results FAA significantly differed between OSA patients (2–4× larger) and healthy controls (Student's t-test, P 0.7). Conclusion SMS RT-MRI during CPAP can reproducibly identify physiological traits and anatomical risk factors that are valuable in the assessment of OSA. This technique can potentially locate the most collapsible airway sites. Both UALG and FAA possess large variation among OSA patients. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1400–1408.

Cardiac myxomas are the most common primary cardiac tumors and are typically attached to the interatrial septum. Left ventricular myxomas are exceedingly rare and presentation in children is all the more uncommon. We report a case of left ventricular myxoma with very atypical cystic appearance raising an initial suspicion of a hydatid cyst. Subsequently, cardiac magnetic resonance imaging was done, which ruled out the diagnosis of hydatid cyst. Complete surgical excision was done through transaortic and transmitral route. Histopathological examination revealed it to be a cardiac myxoma with vascular proliferation, which on echocardiography had appeared as a polycystic lesion. This is a very unusual histopathological presentation of cardiac myxoma.

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.

Coronary endothelial dysfunction (CED) is an independent predictor of cardiovascular disease, but its assessment has been limited to invasive coronary angiography. Myocardial perfusion imaging using arterial spin labeled (ASL) cardiac magnetic resonance (CMR) may be an effective non-invasive alternative for detection of CED. Thirty-four patients were recruited: 10 healthy volunteers, 13 at high-risk for coronary artery disease (CAD), and 11 with established CAD. ASL-CMR was performed continuously in a single mid-short axis slice during rest, stress, and recovery. Stress was induced with sustained isometric handgrip exercise, an endothelial dependent stressor. Myocardial perfusion (MP) during rest, peak stress, and recovery were calculated and compared. After excluding subjects unable to complete the protocol or who exhibited poor data quality, 6 healthy, 10 high-risk, and 7 CAD patients were included in the analysis. Average MP (ml/g/min) was 1.31 ± 1.23, 1.61 ± 1.12, and 1.40 ± 0.97 at rest, and 1.64 ± 1.49, 2.31 ± 1.61, and 2.84 ± 1.77 during stress, for the CAD, high-risk and healthy group, respectively. The average MP response (MPstress - MPrest , ml/g/min) was 0.32 ± 1.93, 0.69 ± 1.34, and 1.44 ± 1.46 for CAD, high-risk and healthy group, respectively. MP during handgrip stress was significantly lower for both the CAD (p = 0.0005) and high-risk groups (p = 0.05) compared to the healthy volunteers. In only the healthy subjects, MP was significantly higher in stress compared to rest (p = 0.0002). Participants with CAD had significantly lower MP response compared to healthy volunteers, as detected by ASL-CMR. These findings support the feasibility of ASL-CMR for non-invasive assessment of CED.

Background In the last decade, some institutions have begun combining the CFNG and masseteric nerve to provide dual innervation to the gracilis muscle for dynamic facial reanimation in facial paralysis patients. We reviewed the various ways that these two nerves have been coapted to provide dual innervation, and summarized the functional outcome for these methods. Methods A search of the Ovid EMBASE, MEDLINE, Cochrane, and Scopus databases was performed from 1946 to May 2019 for dual innervation of gracilis muscle using CFNG plus masseteric nerve for facial reanimation. Results A total of 184 articles were identified in the initial search, of which seven met our inclusion criteria. Three additional abstracts with 43 patients were identified but the level of details was not sufficient to include the results in the analysis. A total of 57 patients were reviewed (mean age of 42.1 years (6–79 years)). The majority of dual innervation procedures were performed using the ipsilateral masseteric nerve sutured end-to-end to the obturator nerve, and an additional CFNG connected end-to-side to the obturator nerve. In the 26 patients with Terzis scores available, there were no differences between masseteric nerve coapted end-to-end and CFNG as end-to-side to the obturator, or the reverse coaptation. All but two patients achieved function of the gracilis activated by the masseteric nerve within 2–5 months. Conclusions This review shows that dual innervation of the gracilis is safe; and in some cases, does appear to provide early onset gracilis activation as well as an eventual spontaneous smile.

BACKGROUND Interest in facial masculinization surgery is expected to increase as gender-affirming surgery becomes more widely accepted and available. The purpose of this study is to summarize the current literature describing operative techniques in facial masculinization surgery and provide an algorithmic approach to treating this patient population. METHODS PubMed, EMBASE, and Medline databases were queried for literature on operative techniques and outcomes of facial masculinization surgery in transgender and cisgender patients, published through July 2018. Data on patient demographics, follow-up, operative techniques, complications, and outcomes were collected. RESULTS Fifteen of the 24 identified studies met inclusion criteria. Two studies discussed the outcomes of 7 subjects (6 trans-male and 1 cis-male) who underwent facial masculinization procedures. No objective outcomes were reported in either study; however, subjects were generally satisfied and there were no complications. The remaining studies reviewed operative techniques utilized in the cisgender population. CONCLUSION A summary of considerations for each facial anatomic subunit and respective operative techniques for facial masculinization is presented. Current facial masculinization procedures in cisgender patients may be considered in the transgender patient population with favorable outcomes. However, further research is needed on techniques and objective outcome measures of facial masculinization procedures in the transgender population.

Objectives Multiparametric renal magnetic resonance imaging (MRI), including diffusion-weighted imaging, magnetic resonance elastography, and magnetization transfer imaging (MTI), is valuable in the noninvasive assessment of renal fibrosis. However, hemodynamic changes in diseased kidneys may impede their ability to measure renal fibrosis. Because MTI assesses directly tissue content of macromolecules, we test the hypothesis that MTI would be insensitive to renal hemodynamic changes in swine kidneys with acute graded ischemia. Materials and methods Seven domestic pigs underwent placement of an inflatable silicone cuff around the right renal artery to induce graded renal ischemia. Multiparametric MRI was performed at baseline, 50%, 75%, and 100% renal artery stenosis as well as reperfusion. Measurements included regional perfusion, R2*, apparent diffusion coefficient (ADC), stiffness, and magnetization transfer ratio (MTR) using arterial spin-labeled MRI, blood oxygenation-dependent MRI, diffusion-weighted imaging, magnetic resonance elastography, and MTI, respectively. Histology was performed to rule out renal fibrosis. Results During graded ischemia, decreases in renal perfusion were accompanied with elevated R2*, decreased ADC, and stiffness, whereas no statistically significant changes were observed in the MTR. No fibrosis was detected by histology. After release of the obstruction, renal perfusion showed only partial recovery, associated with return of kidney R2*, ADC, and stiffness to baseline levels, whereas cortical MTR decreased slightly. Conclusions Renal MTI is insensitive to decreases in renal perfusion and may offer reliable assessment of renal structural changes.

Weight loss induced by gastric banding improves insulin sensitivity and reduces secretory demand on β-cells in the Restoring Insulin Secretion (RISE) Consortium BetaFat Study. Here we examined the role of liver fat in this process. Total % body fat (%BF) was measured by DXA; visceral fat volume (VFV) and hepatic fat fraction (HFF) by MRI; and insulin sensitivity (steady-state glucose infusion rate/insulin [M/I]) and β-cell function (acute, steady state [SSCP] and arginine-stimulated maximum ([ACPRmax]) C-peptide concentrations by hyperglycemic clamp. Associations were assessed using linear regression models adjusted for age and sex. Baseline included 73 adults with moderate obesity and impaired glucose tolerance or early type 2 diabetes (81% female; mean±SD age of 49±10 years., BMI 35±3 kg/m2, %BF 44±6%, VFV 3.3±1.4 L and HFF 12±8%). At baseline, BMI and HFF were significantly associated with M/I (r=-0.27 and -0.33 respectively; p≤0.02) and SSCP (r=0.26 for each; p=0.02). Adjustment for M/I eliminated the significance of the associations with SSCP (r≤0.11 for each; p>0.3). %BF and VFV were not significantly associated with M/I or β-cell measures. During follow-up, 23 subjects from the gastric banding group repeated baseline tests at 2-years after surgery. BMI, %BF, VFV and HFF decreased by 3.7±2.9 kg/m2, 3.2±3.6%, 0.6±0.7 L, and 5.0±7.2% respectively during the 2-years follow-up (all p≤0.0003). Change in BMI was significantly associated with change in M/I (r=-0.42, p=0.049) but not with changes in β-cell measures. Change in HFF was significantly associated with changes in M/I (r=-0.59, p=0.003) and ACPRmax (r=0.55, p=0.007); adjustment for change in M/I reduced the association of HFF with ACPRmax to r=0.39 (p=0.06). Changes in %BF and VFV were not significantly associated with changes in M/I or β-cell measures. Thus, changes in hepatic fat may contribute to improved insulin sensitivity and reduced secretory demand on β-cells following gastric banding. Disclosure A. Xiang: None. J. Wu: None. T. Chow: None. M.P. Martinez: None. D.H. Hwang: None. E. Trigo: None. N. Katkhouda: Consultant; Self; Bard davol, Baxter, Medtronic, Storz. E. Beale: None. K.S. Nayak: None. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. Funding National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases