Mona Ascha

Management of immunosuppressant agents following liver transplantation: Less is more

Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.

Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis.

AIM To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH). METHODS We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival. RESULTS A comparison of model for end-stage liver disease (MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD (area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54 (0.18, 0.91); P = 0.005], homocitrulline [0.66 (0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53 (0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers (carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.

A review of imaging modalities in pulmonary hypertension

Pulmonary hypertension (PH) is defined as resting mean pulmonary artery pressure ≥25 mmHg measured by right heart catheterization. PH is a progressive, life-threatening disease with a variety of etiologies. Swift and accurate diagnosis of PH and appropriate classification in etiologic group will allow for earlier treatment and improved outcomes. A number of imaging tools are utilized in the evaluation of PH, such as chest X-ray, computed tomography (CT), ventilation/perfusion (V/Q) scan, and cardiac magnetic resonance imaging. Newer imaging tools such as dual-energy CT and single-photon emission computed tomography/computed tomography V/Q scanning have also emerged; however, their place in the diagnostic evaluation of PH remains to be determined. In general, each imaging technique provides incremental information, with varying degrees of sensitivity and specificity, which helps suspect the presence and identify the etiology of PH. The present study aims to provide a comprehensive review of the utility, advantages, and shortcomings of the imaging modalities that may be used to evaluate patients with PH.

Predictors of mortality after transjugular portosystemic shunt

AIM To investigate if echocardiographic and hemodynamic determinations obtained at the time of transjugular intrahepatic portosystemic shunt (TIPS) can provide prognostic information that will enhance risk stratification of patients. METHODS We reviewed medical records of 467 patients who underwent TIPS between July 2003 and December 2011 at our institution. We recorded information regarding patient demographics, underlying liver disease, indication for TIPS, baseline laboratory values, hemodynamic determinations at the time of TIPS, and echocardiographic measurements both before and after TIPS. We recorded patient comorbidities that may affect hemodynamic and echocardiographic determinations. We also calculated Model for End-stage Liver Disease (MELD) score and Child Turcotte Pugh (CTP) class. The following pre- and post-TIPS echocardiographic determinations were recorded: Left ventricular ejection fraction, right ventricular (RV) systolic pressure, subjective RV dilation, and subjective RV function. We recorded the following hemodynamic measurements: Right atrial (RA) pressure before and after TIPS, inferior vena cava pressure before and after TIPS, free hepatic vein pressure, portal vein pressure before and after TIPS, and hepatic venous pressure gradient (HVPG). RESULTS We reviewed 418 patients with portal hypertension undergoing TIPS. RA pressure increased by a mean ± SD of 4.8 ± 3.9 mmHg (P < 0.001), HVPG decreased by 6.8 ± 3.5 mmHg (P < 0.001). In multivariate linear regression analysis, a higher MELD score, lower platelet count, splenectomy and a higher portal vein pressure were independent predictors of higher RA pressure (R = 0.55). Three variables predicted 3-mo mortality after TIPS in a multivariate analysis: Age, MELD score, and CTP grade C. Change in the RA pressure after TIPS predicted long-term mortality (per 1 mmHg change, HR = 1.03, 95%CI: 1.01-1.06, P < 0.012). CONCLUSION RA pressure increased immediately after TIPS particularly in patients with worse liver function, portal hypertension, emergent TIPS placement and history of splenectomy. The increase in RA pressure after TIPS was associated with increased mortality. Age, splenectomy, MELD score and CTP grade were independent predictors of long-term mortality after TIPS.

Abstract: Fibrin Tissue Sealant and Minor Skin Grafts in Burn Surgery

METHODS: A retrospective analysis of 107 lower extremity wounds were identified in 68 patients, who underwent treatment with a direct, low-frequency (22.4kHz), highintensity (~60 W/cm) ultrasonic device at the University of Pennsylvania between January 2010 and January 2016. Eighty-two wounds in fifty-one patients met inclusion criteria and were retrospectively reviewed. Wound healing outcomes were assessed at 180-day post-ultrasonic debridement. Descriptive statistics, cost, and univariate analysis were conducted for analysis.

Identification of Risk Factors in Lymphatic Surgeries for Melanoma: A National Surgical Quality Improvement Program Review

Introduction Sentinel lymph node biopsy (SLNB) and lymphadenectomy (LAD) are commonly performed in the staging and care of patients with malignant melanoma. These procedures are accompanied by complications that may result in hospital readmission, negatively affecting patient outcomes and potentially affecting surgical procedure reimbursement. The National Surgical Quality Improvement Program (NSQIP) database offers a large data set allowing physicians to evaluate 30-day readmission for surgical complications. We used this database to explore predictors of 30-day hospital readmission for SLNB and LAD in the axillary, cervical, and inguinal regions. Methods Data from the years 2005 to 2014 of the American College of Surgeons NSQIP database were used. Cohorts were constructed according to International Classification of Diseases, Ninth Revision, classification and current procedural terminology codes. The outcome of 30-day return to hospital was defined as patients who were readmitted to the hospital or the operating room within 30 days. Multiple logistic regression results are presented for a prespecified set of predictors and predictors that were significant on univariate logistic regression analysis. Odds ratios and confidence intervals were calculated using maximum likelihood estimates, along with Wald test P values. Results A total of 3006 patients were included. Of those, 151 (5.0%) returned to the hospital. Among 1235 LAD patients, 65 (5.3%) returned; among 1771 SLNB patients, 86 (4.9%) returned. Smoking was a predictor of hospital readmission for overall SLNB and for cervical SLNB on multivariate analysis. Age was a significant predictor for cervical and inguinal LAD. Hypertension was significant for cervical LAD. Diabetes, preoperative hematocrit, and male sex were predictors for inguinal SLNB. There were no significant predictors for axillary SLNB and axillary LAD, as well as overall LAD procedures. Conclusions This is the first and largest study using American College of Surgeons NSQIP to examine 30-day readmission after SLNB and LAD for melanoma in 3 commonly operated anatomical regions. We have found several significant risk factors associated with hospital readmission, which are now being used as a quality measure for hospital performance and reimbursement, that may help surgeons optimize patient selection for SLNB and LAD.

Pediatric disorders of pigmentation commonly seen in skin of color.

There are certain disorders of hyper- and hypopigmentation that are more common in children with skin of color. It is imperative that practitioners can swiftly and accurately diagnose these pigmentary disorders to prevent delay in treatment and enhance quality of life. Pigmentary disorders have many etiologies and may present similarly in the clinical setting; however treatment varies widely and is dependent on accurate diagnosis. Herein, we present a review of common disorders of hyperpigmentation and hypopigmentation in children with skin of color. We aim to provide physicians with information that can enhance clinical detection of common pigmentary disorders in this vulnerable population.

A 50-Year-Old Woman With Reticulate Hyperpigmentation

A 50-year-old woman presented with a 20-year history of slowly progressive red-tobrown pruritic hyperkeratotic papules and reticulated hyperpigmentation involving her face, neck, chest, back, and upper and lower extremities (Figure, A and B). She was previously diagnosed with Darier disease after biopsy revealed acantholytic dyskeratosis. She was treated with fluorouracil and tazarotene, 0.1%, cream with mild improvement, but she continued to develop new lesions. Social, family, and past medical history were noncontributory. Physical examination revealed reddish-brown hyperkeratotic papules on the neck, trunk, and extremities and diffuse brown macules, many in a reticulated pattern, on the face, neck, trunk, and extremities. There were no nail or mucosal changes. Laboratory data was noncontributory. A punch biopsy specimen was collected from both the arm and trunk and histologic examination was performed (Figure, C and D). Neck and chest A

278 Metabolomics Studies Identify Novel Prognostic Indicators in Patients With End-Stage Liver Disease

value <10-8), and between hepatic fibrosis and metabolic traits revealed a significant association between hepatic fibrosis and HbA1c (p-value <0.001). There was no significant shared gene effect between hepatic steatosis and hepatic fibrosis. Conclusions: Utilizing a wellcharacterized prospective cohort of community-dwelling twins, this study demonstrates that both hepatic steatosis and hepatic fibrosis are heritable traits. Although both are heritable, they appear to have distinct basis for their genetic susceptibility.