Intra-abdominal clear-cell sarcoma: a report of 3 cases, including 1 case with unusual morphological features, and review of the literature

Clear-cell sarcoma (CCS) is a soft-tissue neoplasm that morphologically resembles cutaneous malignant melanoma but has a distinct molecular profile. Gastrointestinal and intra-abdominal CCSs are very rare. Here, the authors present 3 cases of intra-abdominal CCS and review the literature. Of these cases, 2 involved the small bowel, and 1 involved the peritoneum. Cases 1 and 3 had the characteristic CCS morphology, but case 2 was morphologically unusual and therefore difficult to diagnose. It had relatively small cells with less prominence of clear cells; many pseudoglandular structures were also present. It also showed aberrant expression of epithelial membrane antigen (EMA). The other 2 cases also involved some diagnostic uncertainty and were therefore referred to specialized centers. The authors wish to emphasize the importance of molecular studies in making a conclusive diagnosis of intra-abdominal CCS.     

Evaluation of the measles,mumps and rubella vaccination catch-up campaign in England in 2013

In January–March 2013 in England, confirmed measles cases increased in children aged 10–16 years. In April–September 2013, the National Health System and Public Health England launched a national measles-mumps-rubella (MMR) campaign based on data from Child Health Information Systems (CHIS) estimating that approximately 8% in this age group were unvaccinated. We estimated coverage at baseline, and, of those unvaccinated (target), the proportion vaccinated up to 20/08/2013 (mid-point) to inform further public health action.     

Efficacy,safety and patient‐reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor‐experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study)

Objectives

Studies evaluating the efficacy and safety of the fixed‐dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV‐1 and hepatitis C virus (HCV) have mainly included treatment‐naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment‐experienced patients with and without cirrhosis.

Methods

We conducted a multicentre, open‐label, double‐arm, nonrandomized study in patients coinfected with HIV‐1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first‐generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed‐dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient‐reported outcomes.

Results

Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty‐five patients [95.6%; 95% confidence interval (CI): 87.6–99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient‐reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14–0.96; P = 0.04]. Mean tenofovir area under the plasma concentration–time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified.

Conclusions

LDV/SOF provided a high SVR rate in PI‐experienced subjects coinfected with HCV genotype 1 and HIV‐1, including patients with cirrhosis.     

Influence of extracellular and intracellular pH on GABA-gated chloride conductance in crayfish muscle fibres.

The effect of intracellular and extracellular pH on GABA-gated Cl- conductance was studied using H(+)-selective microelectrodes and a three-microelectrode voltage clamp in crayfish leg opener muscle fibres in bicarbonate-free solutions. Experimental variation of intracellular pH in the range 6.4-8.0 did not affect the GABA-gated conductance. In contrast to this, the GABA-gated conductance was sensitive to changes in external pH. Raising the external pH from 7.4 to 8.4 decreased the GABA-gated peak conductance observed immediately following application of GABA by 30%, and a change from 7.4 to 6.4 produced an increase of 26%. The effect of extracellular pH on the GABA-gated peak conductance was approximately linear in the pH range 6.4-8.9. A slight decrease in the slope of the pH-conductance relationship was evident in the pH range 5.4-6.4. The desensitization of the GABA-gated conductance was also affected by external pH. At pH 6.9 the conductance produced by 1 mM GABA showed a desensitization of about 15%, and at pH 8.9 this value was 34%. Raising the external pH in the presence of GABA decreased the GABA-gated peak conductance and increased the fractional desensitization, while lowering the external pH produced opposite effects, and was capable of repriming the conductance from a desensitized state to the non-desensitized state. The above results show that the GABA-gated conductance is sensitive to changes in external pH in the physiological range, and suggest that pH-dependent changes in the postsynaptic efficacy of GABA-mediated inhibition may contribute to H+ modulation of neuronal excitability.