Citations

Summary Background Emerging data suggest that oral antibiotics may have therapeutic effects in primary sclerosing cholangitis ( PSC ), but published studies are limited. Aims To investigate the safety and efficacy of oral vancomycin and metronidazole in patients with PSC . Methods Thirty‐five patients with PSC were randomised in a double‐blind manner into four groups: vancomycin 125 mg or 250 mg four times/day, or metronidazole 250 mg or 500 mg three times/day for 12 weeks. The primary endpoint was decrease in alkaline phosphatase ( ALK ) at 12 weeks. Secondary end points included serum bilirubin and Mayo PSC risk score; pruritus; and adverse effects ( AE s). Nonparametric tests were used for analysis. Results The primary endpoint was reached in the low‐dose (−43% change in ALK , P = 0.03) and high‐dose (−40%, P = 0.02) vancomycin groups, with two patients in the former experiencing ALK normalisation. Bilirubin decreased significantly in the low‐dose metronidazole group (−20%, P = 0.03) and trended towards significance in the low‐dose vancomycin group (−33%, P = 0.06). Mayo PSC risk score decreased significantly in the low‐dose vancomycin (−0.55, P = 0.02) and low‐dose metronidazole group (−0.16, P = 0.03). Pruritus decreased significantly in the high‐dose metronidazole group (−3.4, P = 0.03). AE s led to medication discontinuation in six patients, four of whom were receiving metronidazole. Conclusions Both vancomycin and metronidazole demonstrated efficacy; however, only patients in the vancomycin groups reached the primary endpoint, and with less adverse effects. Larger, longer‐term studies are needed to further examine the safety and efficacy of antibiotics as a potential treatment for patients with primary sclerosing cholangitis ( clinicaltrials.gov NCT01085760 ).

Background/Aim: Despite existing diagnostic criteria for Charles Bonnet syndrome (CBS), clinical manifestations vary greatly. We examined the clinical course and mortality of patients diagnosed with CBS. Methods: We conducted a retrospective chart review of patients with CBS. We collected demographic and clinical information and medical burden scores. Kaplan-Meier mortality curves were compared using log-rank test. Cox proportional hazard model was used for multivariate analysis and hazard ratio (HR). Mortality was compared to expected mortality from Minnesota population. Results: Seventy-seven patients with CBS had a mean age of 79.5 (standard deviation ± 13.0) and were predominantly Caucasian (97%) and female (73%). In all, 20 (26%) subsequently developed a dementia syndrome, most often Lewy body. A total of 46 (60%) deaths occurred with an average follow-up time of 33.0 months. Characteristics associated with mortality included older age (75-84 [HR 3.34, P = .029], >85 [HR 4.58, P = .007]) and renal disease (HR 3.39 with 95% confidence interval 1.31-8.80, P = .012). Medical burden scores were not associated with overall mortality. Mortality was high compared to Minnesota population ( P < .0001). Conclusions: A large proportion of patients with CBS developed dementia, and there was a high mortality rate associated with older age and renal disease. Medical burden was not associated with mortality.

Guillain-Barré syndrome is an immune-mediated polyneuropathy that frequently presents with progressive muscle weakness. Hyponatremia has recently been described as a feature of this condition, generally appearing over the course of the illness and following the diagnosis of this demyelinating process. We report a case of Guillain-Barré syndrome presenting with severe hyponatremia that is further exacerbated by intravenous immune globulin therapy. Awareness should be raised for consideration of both Guillain-Barré syndrome and its treatment with intravenous immune globulin therapy as the cause of hyponatremia.

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.