Experience with direct acting anti-viral agents for treating hepatitis C virus infection in renal transplant recipients

In recent past, direct-acting anti-viral drugs (DAAs) have become the standard of care for the treatment of hepatitis C virus (HCV) infection. However, the experience with the use of these drugs in Indian renal transplant recipients is limited. We retrospectively reviewed our experience with DAA-based treatment for HCV infection in such patients. Between April 2015 and December 2016, six adults (median age 41 [range 34–52] years, male 5; GT1 2, GT3 3, and GT4 1; including three with prior failed interferon-based treatment) had received genotype-guided, DAA-based anti-HCV treatment 1 to 158 (median 15) months after renal transplantation. Of them, four completed the planned 24-week treatment without any significant adverse event. One of them had increase in serum creatinine after 16 weeks of treatment with sofosbuvir and daclatasvir, with acute interstitial nephritis on kidney biopsy; his renal function improved on stopping the drugs. The other patient had preexisting mild renal dysfunction, which worsened after 8 weeks of sofosbuvir-ledipasvir treatment; this did not reverse on stopping treatment. All the six patients achieved undetectable HCV RNA after 4 weeks of treatment and also achieved sustained virologic response, i.e. lack of detectable HCV RNA in serum 12 weeks after stopping treatment. Overall, DAA-based treatment was effective in treating HCV infection in our renal transplant recipients; however, caution and monitoring of renal function during such treatment is advisable in patients who have additional factors that predispose to renal injury.     

Open-source,vendor-independent,automated multi-beat tissue Doppler echocardiography analysis

Current guidelines for measuring cardiac function by tissue Doppler recommend using multiple beats, but this has a time cost for human operators. We present an open-source, vendor-independent, drag-and-drop software capable of automating the measurement process. A database of ~8000 tissue Doppler beats (48 patients) from the septal and lateral annuli were analyzed by three expert echocardiographers. We developed an intensity- and gradient-based automated algorithm to measure tissue Doppler velocities. We tested its performance against manual measurements from the expert human operators. Our algorithm showed strong agreement with expert human operators. Performance was indistinguishable from a human operator: for algorithm, mean difference and SDD from the mean of human operators’ estimates 0.48?±?1.12 cm/s (R²?=?0.82); for the humans individually this was 0.43?±?1.11 cm/s (R²?=?0.84), ?0.88?±?1.12 cm/s (R²?=?0.84) and 0.41?±?1.30 cm/s (R²?=?0.78). Agreement between operators and the automated algorithm was preserved when measuring at either the edge or middle of the trace. The algorithm was 10-fold quicker than manual measurements (p?<?0.001). This open-source, vendor-independent, drag-and-drop software can make peak velocity measurements from pulsed wave tissue Doppler traces as accurately as human experts. This automation permits rapid, bias-resistant multi-beat analysis from spectral tissue Doppler images.     

Radiotherapy for craniopharyngioma

Radiotherapy remains the mainstay of multidisciplinary management of patients with incompletely resected and recurrent craniopharyngioma. Advances in imaging and radiotherapy technology offer new alternatives with the principal aim of improving the accuracy of treatment and reducing the volume of normal brain receiving significant radiation doses. We review the available technologies, their technical advantages and disadvantages and the published clinical results. Fractionated high precision conformal radiotherapy with image guidance remains the gold standard; the results of single fraction treatment are disappointing and hypofractionation should be used with caution as long term results are not available. There is insufficient data on the use of protons to assess the comparative efficacy and toxicity. The precision of treatment delivery needs to be coupled with experienced infrastructure and more intensive quality assurance to ensure best treatment outcome and this should be carried out within multidisciplinary teams experienced in the management of craniopharyngioma. The advantages of the combined skills and expertise of the team members may outweigh the largely undefined clinical gain from novel radiotherapy technologies.     

Interactions between leptin and the human sympathetic nervous system

Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1+/-1.2 vs 12.8+/-3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7+/-1.1 ng/mL vs 4.0+/-0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0+/-30.5 mL/min, compared with 56.9+/-18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.