Budd-Chiari Syndrome as an Initial Presentation of Non-Promyelocytic Acute Myelogenous Leukemia.

Budd-Chiari syndrome (BCS) is a rare disease characterized by hepatic venous outflow tract obstruction, frequently due to an underlying thrombophilic disorder. Acute myeloid leukemia rarely presents as acute BCS due to hyperfibrinolysis, hyperleukocytosis, nonspecific proteolytic activity, and disseminated intravascular coagulation causing acute hepatic vein thrombosis. In patients presenting with acute BCS with acute liver failure (ALF), a high index of suspicion and exclusion of underlying malignancy is a must, as it is a contraindication for liver transplantation. We report a case of a 19-year-old Caucasian male who presented with acute BCS causing ALF as an initial presentation of acute myelogenous leukemia.

Peritransplant Renal Dysfunction in Liver Transplant Candidates.

Renal function is intricately tied to Model for End-Stage Liver Disease score and overall prognosis among patients with cirrhosis. The estimation of glomerular filtration rate (GFR) and etiology of renal impairment are even more magnified among cirrhotic patients in the period surrounding liver transplantation. Novel biomarkers including cystatin C and urinary neutrophil gelatinase-associated lipocalin have been demonstrated to more accurately assess renal dysfunction and aid in the diagnosis of competing etiologies. Accurately identifying the severity and chronicity of renal dysfunction among transplant candidates is an imperative component with respect to stratifying patients toward simultaneous liver-kidney transplantation versus liver transplantation alone.

Shifts in the Proportion of Distant Stage Early-Onset Colorectal Adenocarcinoma in the United States.

BACKGROUND: Carcinoids, frequently classified as "colorectal cancer" contribute to rising early-onset colorectal cancer (EOCRC) incidence rates (IR) and have distinct staging distributions compared to often advanced stage adenocarcinomas (screening target). Thus, assessing temporal shifts in early-onset distant stage adenocarcinoma can impact public health. METHODS: 2000-2016 Surveillance Epidemiology and End Results (SEER) 18 yearly adenocarcinoma IRs were stratified by stage (in situ, localized, regional, distant), age (20-29, 30-39, 40-49, 50-54-year-olds), subsite (colorectal, rectal-only, colon-only), and race [non-Hispanic whites, non-Hispanic Blacks (NHB), Hispanics] in 103,975 patients. Three-year average annual IR changes (pooled 2000-2002 IRs compared with 2014-2016) and cancer stage proportions (percent contribution of each cancer stage) were calculated. RESULTS: Comparing 2000-2002 with 2014-2016, the steepest percent increases are in distant stage cancers. Colon-only, distant adenocarcinoma increased most in 30-39-year-olds (49%, 0.75/100,000→1.12/100,00, P < 0.05). Rectal-only, distant stage increases were steepest in 20-29-year-olds (133%, 0.06/100,000→0.14/100,000, P < 0.05), followed by 30-39-year-olds (97%, 0.39/100,000→0.77/100,000, P < 0.05) and 40-49-year-olds (48%, 1.38/100,000→2.04/100,000, P < 0.05). Distant stage proportions (2000-2002 to 2014-2016) increased for colon-only and rectal-only subsites in young patients with the largest increases for rectal-only in 20-29-year-olds (18%→31%) and 30-39-year-olds (20%→29%). By race, distant stage proportion increases were largest for rectal-only in 20-29-year-old NHBs (0%→46%) and Hispanics (28%→41%). Distant colon proportion increased most in 20-29-year-old NHBs (20%→34%). CONCLUSIONS: Youngest patients show greatest burdens of distant colorectal adenocarcinoma. Although affecting all races, burdens are higher in NHB and Hispanic subgroups, although case counts remain relatively low. IMPACT: Optimizing earlier screening initiatives and risk-stratifying younger patients by symptoms and family history are critical to counteract rising distant stage disease.

African Americans have a distinct clinical and histologic profile with lower prevalence of NASH and advanced fibrosis relative to Caucasians.

BACKGROUND AND AIMS: Racial/ethnic disparities have been reported in the prevalence of nonalcoholic fatty liver disease (NAFLD). Thus, we aimed to understand the inter-ethnic clinical, biochemical, and histological differences in a large cohort of Caucasians and African-Americans (AA). METHODS: Laboratory and liver biopsy data of 942 NAFLD patients were retrospectively analyzed. Nine hundred seven patients were included in the analysis: 677 (74.6%) Caucasians and 230 (25.3%) AA. RESULTS: AA had higher mean BMI compared to Caucasians (42.6 ± 9.5 vs. 39 ± 8.6 kg/m2). The prevalence of nonalcoholic steatohepatitis (NASH), defined by NAFLD activity score (NAS . 5), was higher in the Caucasians (n = 67) compared to AA (n = 7) (9.8% vs. 3%, P = 0.0007). One hundred fifteen patients (12.8%) had advanced fibrosis: 109 (16.2%) Caucasians and six (2.6%) AA. No AA patients had stage 4 fibrosis or cirrhosis. Multivariate logistic regression analysis revealed advanced fibrosis was significantly associated with age at liver biopsy (OR 1.03, 95% CI 1.0.1.1, P = 0.017, lower platelet count (OR 0.99, 95% CI 0.98.0.99, P = <0.0001), AST/ALT ratio (OR 5.19, 95% CI 2.9.9.2, P <0.0001) and Caucasian race (OR 7.49, 95% CI 2.53.22.2, P = 0.0003). Advanced fibrosis in AA was predicted by lower platelet count and AST/ALT ratio. Whereas Advanced fibrosis in Caucasians was predicted by age at biopsy, lower platelet count and AST/ALT ratio. CONCLUSION: The AA have a distinct clinical and histologic phenotype. Caucasians have a significantly greater proportion of NASH and are eight times more likely to develop advanced fibrosis than AA.

Characterization of Gut Microbiome in Liver Transplant Recipients With Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are a growing problem globally and recur even after liver transplant (LT). We aim to characterize the gut dysbiosis in patients who developed recurrent NAFLD compared with patients without recurrence following LT. METHODS: Twenty-one patients who received LT for NASH and had a protocol liver biopsy performed beyond 1-y post-LT were included prospectively (January 2018-December 2018). Genomic DNA extraction, next-generation sequencing, and quantitative PCR analysis were performed on stool samples collected within 1.1 ± 1.6 y from time of liver biopsy. RESULTS: Recurrent NAFLD was noted in 15 of the 21 included patients. Stool microbiome analysis at the genus level showed significant loss of Akkermansia and increasing Fusobacterium associated with NAFLD recurrence. Quantitative PCR analysis revealed significantly decreased relative abundance of Firmicutes in patients with NAFLD activity scores (NASs) ≥5 as compared with patients with lower NAS scores, whereas Bacteroidetes were significantly increased with higher NAS (P < 0.05). Firmicutes (P = 0.007) and Bifidobacterium group (P = 0.037) were inversely correlated, whereas Bacteroidetes (P = 0.001) showed a positive correlation with higher hepatic steatosis content. The Firmicutes/Bacteroidetes ratios were higher in patients without NAFLD or NASH as compared with patients diagnosed with NAFLD or NASH at the time of sample collection. CONCLUSIONS: Akkermansia, Firmicutes, and Bifidobacterium may play protective roles in the development of recurrent NAFLD in LT recipients, whereas Fusobacteria and Bacteroidetes may play pathogenic roles. These findings highlight the potential role of the "gut-liver" axis in the pathogenesis of NAFLD recurrence after LT.

Similarities and Differences Between Nonalcoholic Steatohepatitis and Other Causes of Cirrhosis.

Nonalcoholic fatty liver disease includes a spectrum of liver disorders that range from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Risk factors such as obesity, hypertension, hyperlipidemia, chronic kidney disease, and smoking status increase risk of progression to cirrhosis among patients with NASH. Cirrhosis derived from non-NASH causes may share similar features with patients with NASH but embody distinct pathogenetic mechanisms, genetic associations, prognosis, and outcomes. This article discusses in detail the comparison of clinical, genetic, and outcome characteristics between patients with NASH cirrhosis as opposed to alternative causes of chronic liver disease.

Enterococcus casseliflavus, Streptococcus equinus and Klebsiella oxytoca septicaemia associated with perinephric haematoma in a post-liver transplant patient with allograft cirrhosis.

Liver transplant recipients are immunocompromised by the virtue of being on immunosuppressive agents which put them at risk of having infections from unusual and even multiple concomitant pathogens. We present a case of a 39-year-old man who developed septicaemia with Enterococcus casseliflavus, Streptococcus equinus and Klebsiella oxytoca in the setting of perinephric haematoma which resulted following a kidney biopsy performed to evaluate his nephrotic range proteinuria. E. casseliflavus has been known to cause infections in patients with liver disease/cirrhosis; however, simultaneous infection with S. equinus and K. oxytoca along with E. casseliflavus has never been reported earlier in post-transplant state.

Late toxicity and outcomes following radiation therapy for chest wall sarcomas in pediatric patients.

PURPOSE: To investigate the contribution of radiation therapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis and pneumonitis. METHODS AND MATERIALS: The data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, nonrhabdomyosarcoma-soft tissue sarcomas) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan. RESULTS: The range of scoliosis identified on follow-up imaging ranged from -47.6 to 64° (median, 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24 Gy; however, 1 of 3 surviving patients who received whole pleural surface radiation therapy developed significant restrictive lung disease. CONCLUSIONS: Acute and late radiation therapy-associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiation therapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiation therapy.

Effects of Reusing Gel Electrophoresis and Electrotransfer Buffers on Western Blotting.

SDS-PAGE and Western blotting are 2 of the most commonly used biochemical methods for protein analysis. Proteins are electrophoretically separated based on their MWs by SDS-PAGE and then electrotransferred to a solid membrane surface for subsequent protein-specific analysis by immunoblotting, a procedure commonly known as Western blotting. Both of these procedures use a salt-based buffer, with the latter procedure consisting of methanol as an additive known for its toxicity. Previous reports present a contradictory view in favor or against reusing electrotransfer buffer, also known as Towbin's transfer buffer (TTB), with an aim to reduce the toxic waste. In this report, we present a detailed analysis of not only reusing TTB but also gel electrophoresis buffer (EB) on proteins of low to high MW range. Our results suggest that EB can be reused for at least 5 times without compromising the electrophoretic separation of mixture of proteins in an MW standard, BSA, and crude cell lysates. Additionally, reuse of EB did not affect the quality of subsequent Western blots. Successive reuse of TTB, on the other hand, diminished the signal of proteins of different MWs in a protein standard and a high MW membrane protein cystic fibrosis transmembrane-conductance regulator (CFTR) in Western blotting.