Citations

AimTreatment of hepatitis C genotype 4 (HCV‐G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta‐analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR).MethodsWe searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta‐analysis was used to pool the risk ratio (RR) of achieving SVR across trials.ResultsFive RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08–2.10). SVR was significantly higher in PEG IFN‐α‐2a compared to the ‐α‐2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity.ConclusionIn treatment‐naive patients with HCV‐G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.

ObjectivesTo evaluate risk factors associated with iatrogenic splenectomy during nephrectomy and to assess outcomes among patients undergoing nephrectomy for renal tumors.MethodsOf 4323 patients who underwent nephrectomy at Mayo Clinic between 1992 and 2008, 33 (0.8%) had an iatrogenic/unplanned splenectomy. In a case–control study design, controls without splenectomy were matched 1:3 based on age, sex, surgical date, side of the renal tumor, surgical approach and surgeon. Perioperative features and survival were evaluated using conditional logistic and Cox regression.ResultsAmong the 33 iatrogenic splenectomy patients, the majority (94%) underwent radical, open and left‐sided nephrectomy. Primary tumor classification ≥T3 was the only clinicopathological risk factor significantly associated with splenectomy (odds ratio 3.4; P = 0.02). Compared with controls, patients with an iatrogenic splenectomy were more likely to have longer operative time (205 vs 171 min; P = 0.02), higher estimated blood loss (1.3 vs 0.3 L; P = 0.001), longer length of stay (median 7 vs 5 days; P = 0.03) and a higher likelihood for postoperative complications (odds ratio 5.3; P = 0.002). With a median of 9.8 years of follow up, splenectomy patients tended to have greater all‐cause mortality (hazard ratio 1.6; P = 0.07), although this difference approached statistical significance.ConclusionsIatrogenic splenectomy is a rare complication during nephrectomy and is associated with locally advanced tumors (≥pT3). It also carries prognostic significance for adverse perioperative outcomes and possibly diminished survival, although this warrants further study.

Deposition of amyloid-β (Aβ) in cerebral arteries, known as cerebral amyloid angiopathy (CAA), occurs both in the setting of Alzheimer’s disease and independent of it, and can cause cerebrovascular insufficiency and cognitive deficits. The mechanisms leading to CAA have not been established, and no therapeutic targets have been identified. We investigated the role of CD36, an innate immunity receptor involved in Aβ trafficking, in the neurovascular dysfunction, cognitive deficits, and amyloid accumulation that occurs in mice expressing the Swedish mutation of the amyloid precursor protein (Tg2576). We found that Tg2576 mice lacking CD36 have a selective reduction in Aβ1-40 and CAA. This reduced vascular amyloid deposition was associated with preservation of the Aβ vascular clearance receptor LRP-1, and protection from the deleterious effects of Aβ on cerebral arterioles. These beneficial vascular effects were reflected by marked improvements in neurovascular regulation and cognitive performance. Our data suggest that CD36 promotes vascular amyloid deposition and the resulting cerebrovascular damage, leading to neurovascular dysfunction and cognitive deficits. These findings identify a previously unrecognized role of CD36 in the mechanisms of vascular amyloid deposition, and suggest that this scavenger receptor is a putative therapeutic target for CAA and related conditions.

Objectives/HypothesisTo evaluate the results of patients treated by transoral laser microsurgery and margin mapping with attention to deep margin dimensions in the lateral pharyngeal wall.Study DesignA microscopic margin analysis of multiblock surgical specimens applied to a prospectively accrued case series of squamous cell carcinoma of the palatine tonsils.MethodsThere were 128 tonsil cancers analyzed that were removed transorally, using microscopic margin mapping by surgeon and pathologist. The closest deep and peripheral margins were assessed. The results were then related to a study of the normal dimensions of the lateral pharyngeal wall in 20 healthy patients using magnetic resonance imaging. Outcome measures included number of positive margins, narrowest margin, local control, and disease‐free and overall survival.ResultsThe average closest margin was 1.98 mm (range, 0.30–6.50 mm) deep and 2.82 mm (range, 1.00–5.00 mm) peripheral. There was one positive margin encountered in the previously untreated group (1%), and one local recurrence ultimately developed. Radiographic measures revealed a mean minimal thickness of the lateral pharyngeal wall musculature of 2.4 mm. With mean follow‐up of 4.3 years (range, 2–14 years), the 5‐year estimate for local control is 99%, disease‐free survival is 94.5%, and overall survival is 76%.ConclusionsMargin mapping achieves a low rate of positive margins and is associated with good local control. Based on lateral pharyngeal wall anatomy, wide margins are often unobtainable and may be unnecessary so long as the final inked margin is clear.Level of Evidence4.

Cutaneous gamma‐delta T‐cell lymphoma (γδTCL) is a rare malignancy that typically displays an aggressive clinical course. We present an unusual case of a 57‐year‐old woman with a 3‐year history of lower extremity nodules. Histopathologic, immunophenotypic and molecular genetic studies revealed a clonal, predominantly pannicular gamma‐delta T‐cell infiltrate, leading to a diagnosis of cutaneous γδTCL. The clinical course was characterized by rapid improvement within months of starting systemic corticosteroids, with relapse in ulcerations but no new lesions more than 3 years after onset of disease. Our case and seven previously reported patients with indolent and relatively localized cutaneous γδTCL provide evidence that not all cases of this entity carry a poor prognosis. This indolent subset adds complexity to treatment of cutaneous γδTCL.

Precise measurement of low enrichment of stable isotope labeled amino‐acid tracers in tissue samples is a prerequisite in measuring tissue protein synthesis rates. The challenge of this analysis is augmented when small sample size is a critical factor. Muscle samples from human participants following an 8 h intravenous infusion of L‐[ring‐13C6]phenylalanine and a bolus dose of L‐[ring‐13C6]phenylalanine in a mouse were utilized. Liquid chromatography tandem mass spectrometry (LC/MS/MS), gas chromatography (GC) MS/MS and GC/MS were compared to the GC‐combustion‐isotope ratio MS (GC/C/IRMS), to measure mixed muscle protein enrichment of [ring‐13C6]phenylalanine enrichment. The sample isotope enrichment ranged from 0.0091 to 0.1312 molar percent excess. As compared with GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS showed coefficients of determination of R2 = 0.9962 and R2 = 0.9942, and 0.9217 respectively. However, the precision of measurements (coefficients of variation) for intra‐assay are 13.0%, 1.7%, 6.3% and 13.5% and for inter‐assay are 9.2%, 3.2%, 10.2% and 25% for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. The muscle sample sizes required to obtain these results were 8 µg, 0.8 µg, 3 µg and 3 µg for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. We conclude that LC/MS/MS is optimally suited for precise measurements of L‐[ring‐13C6]phenylalanine tracer enrichment in low abundance and in small quantity samples. Copyright © 2013 John Wiley & Sons, Ltd.

Analgetika sind die am häufigsten verschriebenen Medikamente. Neben ihrer analgetischen Wirksamkeit sind diese Arzneimittel mit einem erhöhten kardiovaskulären Risiko assoziiert, das nicht zuletzt auch auf eine durch die Wirksubstanzen selbst bedingte Erhöhung des Blutdrucks zurückzuführen ist. Epidemiologische und klinische Studien zeigten bereits, dass viele nicht-selektive nicht-steroidale-Antirheumatika und selektive Cyclooxygenase-2-Hemmer mit einer Erhöhung des Blutdrucks und einem erhöhten kardiovaskulären Ereignis einhergehen. Leider fehlten bislang Ergebnisse von prospektiven, randomisierten klinischen Studien mit klinisch relevanten Endpunkten, insbesondere bezüglich des möglichen Zusammenhangs zwischen kardiovaskulären Ereignissen und Analgetika zu eruieren. Dieses Review soll einen kurzen Überblick über klinische Daten bezüglich der Wirkung des Analgetikums Paracetamol auf den Blutdruck und die klinische Bedeutung verschaffen.

BackgroundAlcohol withdrawal accounts for a significant amount of hospital admissions and can quickly progress to the development of delirium tremens (DTs), seizures, and death. Rapid identification and management of alcohol withdrawal syndrome (AWS) is vital and can be managed with a number of different treatment strategies. Diazepam loading is a treatment strategy that utilizes the pharmacokinetics of this agent to achieve a rapid reduction in symptoms followed by sustained benefit over a period of days.ObjectiveThe purpose of this review is to evaluate the role of diazepam loading for AWS.MethodsA literature search of four databases—Pubmed, PsychInfo, Biosis, and Embase—was conducted to identify publications between 1960 and August 2011 that described the use of diazepam loading for the treatment of AWS. Eight trials, both open‐label and controlled trials were identified. Only four randomized controlled‐trials (RCTs) have been published and they are reviewed in this paper.ResultsIncluded trials of hospitalized inpatients found that diazepam loading provided rapid symptom relief as well as reduced the incidence of seizures and duration of DTs. In patients diagnosed with severe DTs, rapidly administered doses of diazepam produced a quick calming effect. While no adverse events resulting from diazepam loading were noted, no formal assessment tool was used to evaluate its safety. Larger randomized controlled‐trials are needed to better evaluate safety outcomes.ConclusionsDiazepam loading is an effective treatment option for hospitalized patients experiencing AWS. Diazepam loading uses the concept of symptom‐triggered therapy, a mainstay of current AWS treatment, while exploiting its prolonged elimination half‐life and eliminating the need for additional pharmacologic therapy. Studies reviewed found diazepam loading significantly improved a number of important outcomes in AWS, including time in DTs, compared to traditional treatment strategies. (Am J Addict 2013;22:113‐118)