MHV68 Latency Modulates the Host Immune Response to Influenza A Virus

Murine gammaherpesvirus 68 (MHV68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. Like other herpesviruses, MHV68 causes acute infection and establishes life-long latency in the host. Recently, it has been shown that mice latently infected with MHV68 have resistance to unrelated pathogens in secondary infection models. We therefore hypothesized that latent MHV68 infection could modulate the host response to influenza A virus. To test this hypothesis, mice were infected intranasally with influenza virus following the establishment of MHV68 latency. Mice latently infected with MHV68 showed significantly higher survival to influenza A virus infection than did PBS mock-infected mice. Latent MHV68 infection led to lower influenza viral loads and decreased inflammatory pathology in the lungs. Alveolar macrophages of mice latently infected with MHV68 showed activated status, and adoptive transfer of those activated macrophages into mice followed the infection with influenza A virus had significantly greater survival rates than control mice, suggesting that activated alveolar macrophages are a key mechanistic component in protection from secondary infections.     

Comparing downstream consequences of normal exercise stress echocardiograms and cardiac computed tomography angiography scans in patients suspected of having of obstructive coronary artery disease: a retrospective cohort study of Tricare beneficiaries

The International Journal of Cardiovascular Imaging - To compare overall number of downstream tests and total costs between negative exercise stress echocardiograms (ESE) or cardiac computed...     

Anatomic correlates of reduced hip extension during walking in individuals with mild‐moderate radiographic hip osteoarthritis

To identify radiographic and MR features of hip osteoarthritis (OA) related to reduced hip extension during walking. Sixty six subjects, were stratified into those with (n = 36, KL = 2, 3) and without (n = 30, KL = 0, 1) radiographic hip OA. Cartilage and labrum lesions were graded semi‐quantitatively on hip MRI. Alpha angle and lateral center edge (LCE) angle were measured. Sagittal kinematics and kinetics were calculated during walking at speed of 1.35 m/s using 3‐D motion capture. All subjects completed Hip disability and Osteoarthritis Outcome Score (HOOS), timed up and go, and 6 min walk tests. Variables were compared between the two groups using one‐way ANOVA (adjusting for age). Correlations of radiographic and MR parameters with peak hip extension were calculated. The OA group was older, had greater pain, and limitation of function. They also had lower peak hip extension and higher peak hip flexion; and worse acetabular and femoral cartilage lesions. Peak hip extension and flexion correlated with KL grade, cartilage lesions in the inferior and posterior femur. Reduced hip extension and greater hip flexion during walking are present in high functioning (HOOS > 85%) individuals with mild‐moderate hip OA, and are associated with cartilage lesions. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:527–534, 2015.     

Neoadjuvant radiation therapy and its impact on complications after pancreaticoduodenectomy for pancreatic cancer: analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)

Objectives

This study investigated the impact of neoadjuvant radiation therapy (XRT) on postoperative outcomes following pancreaticoduodenectomy for pancreatic cancer.

Methods

The American College of Surgeons National Quality Improvement Program database was queried for the period 2005–2010 to assess complication rates following pancreaticoduodenectomy for pancreatic cancer. Two groups of patients were identified, comprising those who received neoadjuvant XRT and those who did not (control group).

Results

A total of 4416 patients were identified, including 200 in the XRT group and 4216 in the control group. There were differences in patient characteristics between the groups, including in age, hypertension and bilirubin level. Despite the fact that weight loss was more common, median operative time was longer (423 min versus 368 min; P < 0.001), and vascular reconstruction was more commonly required (20.5% versus 8.4%; P < 0.001) in the XRT group. In addition, the XRT group had a shorter median hospital stay than the control group (9 days versus 10 days; P = 0.005). Mortality (3.0% versus 2.7%; P = 0.818) and morbidity (40.5% versus 37.6%; P = 0.404) rates were not influenced by neoadjuvant XRT. Blood transfusion rates were increased in the XRT group (13.0% versus 7.4%; P = 0.003). Severe complications were influenced by age >70 years, American Society of Anesthesiologists (ASA) class >2, preoperative sepsis, dyspnoea, weight loss, impaired functional status, peripheral vascular disease and operative time of >8 h.

Conclusions

Neoadjuvant XRT is not associated with an increase in complications after pancreaticoduodenectomy.     

Acute pulmonary vein reconnection is a predictor of atrial fibrillation recurrence following pulmonary vein isolation

Purpose

Arrhythmia recurrence following pulmonary vein isolation (PVI) occurs predominantly due to the reconnection of previously isolated pulmonary veins (PVs). The prognostic implications of detection and treatment of acute PV reconnection are not well understood. We aim to examine the prognostic significance of acute PV reconnection on arrhythmia recurrence at 1 year following PVI.

Methods

This prospective study included 44 patients (22 men, 60?±?7 years) who underwent index PVI procedure for treatment of atrial fibrillation (AF). Acute PV reconnection and/or dormant PV conduction were assessed sequentially in response to a 30-min waiting period, intravenous isoproterenol infusion and/or adenosine. All cases of acute PV reconnection and/or dormant conduction were successfully targeted with additional ablation.

Results

Freedom from AF at 1 year was 75 % (83.3 % in paroxysmal and 65 % in persistent AF, p?=?ns). Acute PV reconnection and/or dormant conduction were evident in 16 of 44 patients (36.3 %). AF recurrence was documented in eight of 16 patients with, but only in three of 28 patients without acute reconnection (p?=?0.009). Three patients underwent a redo procedure, all from the group of patients with acute PV reconnection. In a multivariate model, acute PV reconnection was a strong independent predictor of arrhythmia recurrence (hazards ratio [HR], 6.36; 95 % confidence interval [CI], 1.12–31.6).

Conclusion

Identification of acute PV reconnection, even when successfully targeted, is a strong predictor of arrhythmia recurrence following PVI.     

Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in post-liver transplant patients with previous direct-acting antiviral failure: Six case reports

BACKGROUNDDirect-acting antiviral (DAA) therapy regimens are highly effective at eliminating hepatitis C virus (HCV) infection but rates of sustained virologic response (SVR) are lower in patients with decompensated cirrhosis or hepatocellular carcinoma. Since many of these patients will be referred for liver transplant, they will require retreatment after transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data.CASE SUMMARYWe present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant.CONCLUSIONThis case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients achieving SVR, it was well tolerated, and there were minimal drug-drug interactions with their immunosuppressants.