Transjugular Portosystemic Shunt Reductions: A Retrospective Single-Center Experience.

PURPOSE: To report the results of transjugular intrahepatic portosystemic shunt (TIPS) reductions for hepatic encephalopathy (HE), acute liver failure (ALF), and pulmonary hypertension (PH). MATERIALS AND METHODS: A single-institution retrospective review analysis was performed between 2007 and 2017 on patients undergoing TIPS reduction at single tertiary liver transplant center. A total of 27 patients (14 males and 13 females) underwent TIPS reduction for refractory HE (n = 18), ALF (n = 7), and PH (n = 2). The average age at time of reduction was 59 years (range, 23-73; standard deviation [SD], 8). Mean prereduction Model of End-State Liver Disease-Na and portosystemic pressure gradient were 19 (range, 11-29; SD, 6) and 9.4 mm Hg (range, -2 to 19; SD, 4.8), respectively. Comparison between responders and nonresponders was performed for multiple variables using a 2-tailed t test. Methods of reduction were compared in cases of HE. RESULTS: Technical success, defined as a decrease of at least 50% of the caliber of the shunt, was 100%. Clinical success rates in improving HE, ALF, and PH were calculated at 89%, 71%, and 100%, respectively. Eight patients had major and 10 had minor complications after the reductions. There were 3 shunt thrombosis. Pre- and postreduction Model of End-State Liver Disease-Na, portosystemic pressure gradient change, duration of indwelling TIPS, and reduction method were not significantly different between responders and nonresponders. Six-month survival rates were 80%, 20%, and 100% for HE, ALF, and PH, respectively. CONCLUSIONS: TIPS reduction is effective in reversing refractory HE, ALF, and PH after TIPS creation. TIPS reduction is associated with a high rate of complications and should be reserved for severe refractory overshunting complications.

Immortalization eliminates a roadblock during cellular reprogramming into iPS cells.

The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells. The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19(Arf) (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf-Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular subpopulations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis.

Management of Patients With Tricuspid Valve Endocarditis and Ongoing Intravenous Drug Abuse: Less Is More.

Right-sided infective endocarditis in patients with intravenous drug abuse portends a worse prognosis. Data on optimal management strategy in this situation are scarce. We describe outcomes of 2 different treatment strategies, including a patient treated conservatively with favorable intermediate-term results and another who was treated surgically and developed recurrent endocarditis. (Level of Difficulty: Intermediate.).

Genetic characterization of gliomas arising in patients with multiple sclerosis.

The co-occurrence of gliomas and multiple sclerosis (MS) in the same patient is uncommon, but a well-reported phenomenon. Most have been high grade astrocytic tumors that developed after the diagnosis of MS, leading authors to postulate that chronic gliosis in demyelinative plaques might be the underlying substrate for secondary induction of a glial neoplasm. Until recently, however, genetic tools have not been available to test the hypothesis that high grade gliomas might arise from longstanding chronic gliosis, with transformation to low grade glioma, and eventually GBM, i.e., be secondary GBMs. We searched our surgical neuropathology and MS Brain Bank databases over the past 25 years (1987-2011) and identified eight cases of co-occurring MS and glioma. After careful review to guarantee both diagnoses, cases were studied by fluorescence in situ hybridization for genetic markers appropriate to diagnosis, as well as by direct sequencing for IDH1/2 and P53. No unusual genetic features were detected in our cohort; further, the 4 GBMs we did identify did not have clinical features of secondary glioblastomas nor did any of the four manifest IDH-1 immunohistochemical expression or IDH1/2 mutations, as might be expected in secondary GBMs. Conversely, PTEN loss and EGFR expression, features often found in primary GBMs, but seldom identified in secondary GBMs, were found in 3 of 4 GBMs. We conclude that gliomas in MS patients have genetic features paralleling counterparts in non-MS patients. There is no strong genetic evidence for GBMs to be secondary GBMs.