Retreatment of patients with chronic hepatitis C,subtype 1b and cirrhosis,who failed previous direct‐acting antiviral therapy including first‐ and second‐generation NS5A inhibitors with ombitasvir/paritaprevir/ritonavir,dasabuvir + sofosbuvir + ribavirin

The use of direct‐acting antiviral agents (DAAs) in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95%‐97%, but 3%‐5% of patients experience virologic failure. We observed 17 patients infected with HCV subtype 1b who failed previous treatment with DAA, including 13 subjects (76.5%) with liver cirrhosis. Twelve subjects (70.6%) previously received NS5A inhibitors of the first generation (ledipasvir or daclatasvir) and five subjects (29.4%) – the second generation (velpatasvir). All patients were retreated with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR₁₂ rates depending on fibrosis stage, presence of just single or double NS5A mutations (L31M/V/I and/or Y93H), and on the generation of previously used NS5A inhibitor. Observed SVR₁₂ rates were as follows: 94.1% (16/17 patients) overall; 100% in patients without cirrhosis (n = 4) vs 92.3% in those with cirrhosis (n = 13); 100% with single L31M/V/I or Y93H mutation (n = 7) vs 88.9% with double mutations (n = 9); 100% in patients who previously failed first generation (n = 12) vs 80.0% in those failed second‐generation NS5A inhibitors (n = 5). Retreatment with 3D + 0SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection who failed previous use of NS5A inhibitors. Fibrosis stage, baseline presence of NS5A RAS mutations and the generation of previously used NS5A inhibitors may impact the probability of achieving SVR₁₂, but statistical significance was not demonstrated in our small retrospective cohort. Further studies in a larger population are needed to confirm or not the predictive value of these baseline factors.     

Rapid spread of influenza A(H1N1)pdm09 viruses with a new set of specific mutations in the internal genes in the beginning of 2015/2016 epidemic season in Moscow and Saint Petersburg (Russian Federation)

A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole‐genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole‐genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA‐X) that probably emerged before the beginning of 2015/2016 epidemic season.     

Prospective evaluation of vascular complications after liver transplantation: comparison of conventional and microbubble contrast-enhanced US

PURPOSE: To prospectively compare diagnostic performance of conventional Doppler ultrasonography (US) and microbubble contrast material-enhanced US for assessment of vascular complications after liver transplantation, with clinical follow-up or angiography as reference standard. MATERIALS AND METHODS: This study was approved by institutional review board and was HIPAA compliant. Written informed consent was obtained. Seventy-two patients (49 men, 23 women; average age, 52.3 years) were included in this study. Patients who had undergone liver transplantation underwent conventional color Doppler and contrast-enhanced US of the liver. Quality of hepatic artery (HA) and portal vein (PV) visualization, contrast material arrival time, and time for complete evaluation of vasculature were compared for both techniques. McNemar test was used to compare vascular flow visualization scores; Student t test was used to compare mean study times with both techniques. Patients without HA flow at Doppler US underwent angiography; those with flow were followed up clinically. McNemar test was used to compare sensitivity of both techniques. RESULTS: Contrast-enhanced US helped significantly improve flow visualization in hepatic vessels (P < .001). Mean contrast material arrival time was 13.7 seconds +/- 3.8 (standard deviation) in proper HA and 20.7 seconds +/- 6.3 in PV. Mean study time decreased from 27.4 minutes +/- 13.9 to 9.3 minutes +/- 4.5 (P < .01). Doppler US failed to depict HA flow in eight patients; contrast-enhanced US showed flow in six and no flow in two of these patients. Follow-up results confirmed contrast-enhanced US findings. Sensitivity, specificity, and accuracy for Doppler US were 91.3%, 100%, and 91.5%, respectively. Sensitivity, specificity, and accuracy of contrast-enhanced US were all 100%. Sensitivity and accuracy values of the two techniques were significantly different (P < .014); there was no significant difference in specificity (P > .99) CONCLUSION: Contrast-enhanced US helped improve flow visualization in the HA and PV, decrease scanning time, and correctly differentiate between thrombosis and a patent artery in patients without HA flow at conventional Doppler US.     

Mesenteric ischemia and protein S deficiency: a rare case report

We present an unusual case of a 31-year-old nulliparous woman who was in her normal state of health until 3 weeks before her Emergency Department visit, when she began to have generalized abdominal pain that got acutely worse over a few days. She had a soft abdomen, but complained of excruciating pain. Her computed tomography (CT) scan revealed thrombosis in the superior mesenteric, splenic, and portal veins. Her hematological work-up detected a protein S deficiency, which is associated with recurrent venous thrombosis. The finding of mesenteric venous thrombosis associated with protein S deficiency is rare. The most important factor in survival is early diagnosis and prompt treatment with anticoagulants. Properly treated, patients with mesenteric venous thrombosis should have a good long-term prognosis. Past medical or family history of thrombosis in combination with abdominal symptoms should increase the suspicion for the disease.     

Multicentric reticulohistiocytosis with positive anticyclic citrullinated antibodies

This is a case report of a woman with multicentric reticulohistiocytosis with positive anticyclic citrullinated antibodies. This patient had been misdiagnosed with rheumatoid arthritis for many years. Recently, she presented with symmetric distal interphalangeal joint destruction and papules along her nail beds. Her clinical presentation, laboratory data, radiographic and histologic findings were all consistent with multicentric reticulohistiocytosis, not rheumatoid arthritis. This is the first case report of a patient with multicentric reticulohistiocytosis that tested positive for anticyclic citrullinated antibodies.     

Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D₃, 25(OH)D₂, 1,25(OH)₂D₃, 3-epi-25(OH)D₃ and 24,25(OH)₂D₃), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D₃ levels (p > 0.05) and higher 25(OH)D₃/24,25(OH)₂D₃ ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D₃/24,25(OH)₂D₃ ratio (r = 0.36, p < 0.05). The increase in 25(OH)D₃ after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D₃/24,25(OH)₂D₃ ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.     

Causative role for defective expression of mitochondria‐eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors

Oncocytic cell tumor of the thyroid is composed of large polygonal cells with eosinophilic cytoplasm that is rich in mitochondria. These tumors frequently have the mutations in mitochondrial DNA encoding the mitochondrial electron transport system complex I. However, the mechanism for accumulation of abnormal mitochondria is unknown. A noncanonical mitophagy system has recently been identified, and mitochondria‐eating protein (MIEAP) plays a key role in this system. We therefore hypothesized that accumulation of abnormal mitochondria could be attributed to defective MIEAP expression in these tumors. We first show that MIEAP was expressed in all the conventional thyroid follicular adenomas (FAs)/adenomatous goiters (AGs) but not in oncocytic FAs/AGs; its expression was defective not only in oncocytic thyroid cancers but also in the majority of conventional thyroid cancers. Expression of MIEAP was not correlated with methylation status of the 5′‐UTR of the gene. Our functional analysis showed that exogenously induced MIEAP, but not PARK2, reduced the amounts of abnormal mitochondria, as indicated by decreased reactive oxygen species levels, mitochondrial DNA / nuclear DNA ratios, and cytoplasmic acidification. Therefore, together with previous studies showing that impaired mitochondrial function triggers compensatory mitochondrial biogenesis that causes an increase in the amounts of mitochondria, we conclude that, in oncocytic cell tumors of the thyroid, increased abnormal mitochondria cannot be efficiently eliminated because of a loss of MIEAP expression, ie impaired MIEAP‐mediated noncanonical mitophagy.