BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Human metapneumovirus (hMPV) is a paramyxovirus that causes acute respiratory-tract infections in humans. The histopathological and immunological responses to hMPV infection in BALB/c mice immunized with inactivated hMPV were characterized. Animals were immunized intraperitoneally with PBS, supernatant from non-infected LLC-MK2 cells and from heatinactivated influenza A-or hMPV-infected cells, all in incomplete Freund's adjuvant, or with heat-inactivated hMPV without adjuvant, and then infected intranasally with 10 8 TCID 50 virus. Following infection, lung samples and bronchoalveolar lavages were collected for determination of viral titre and cytokine levels and for histopathological studies. On day 1, 26 % of mice immunized with inactivated hMPV and adjuvant died, compared with none in the other groups. There was more significant lung inflammation associated with eosinophilic infiltration, as well as increased levels of interleukin-4 (IL-4) and IL-5, in the bronchoalveolar lavages of mice immunized with hMPV alone or with the adjuvant. Mice from the last two groups had a 4-5 log 10 decrease in their pulmonary viral titres compared with controls. Our data demonstrate the risks associated with immunization using inactivated hMPV in this animal model and that this aberrant response should be considered in the development of hMPV vaccines. INTRODUCTIONHuman metapneumovirus (hMPV) is a newly described member of the family Paramyxoviridae assigned to the genus Metapneumovirus in the subfamily Pneumovirinae (van den Hoogen et al., 2001). Since its discovery in 2001, hMPV has been identified in many countries from all continents, indicating its worldwide distribution (reviewed by Hamelin et al., 2004). hMPV is associated with acute respiratory-tract infections (ARTI) in all age groups, with more severe diseases such as bronchiolitis/bronchitis and pneumonia occurring in young children, elderly individuals and immunocompromised hosts (Boivin et al., 2003;Falsey et al., 2003; Larcher et al., 2005). Using RT-PCR methods, hMPV has been found in approximately 5 % of children with upper respiratory-tract infections (URTI) (Williams et al., 2006), in 5-12 % of those hospitalized for ARTI (Boivin et al., 2003;Williams et al., 2004) and also in persons with acute wheezing and asthma exacerbations (Jartti et al., 2002;Schildgen et al., 2006;Williams et al., 2005).The hMPV genome consists of a single negative strand of RNA of approximately 13 kb, containing eight genes that are presumed to encode nine different proteins (Biacchesi et al., 2003;. hMPV isolates can be separated into two major groups (A and B) and at least four subgroups Peret et al., 2002). Nucleotide and amino acid sequence identities between representative members of the two hMPV groups are 80 and 90 %, respectively (Biacchesi et al., 2003). Of the three hMPV surface glycoproteins [fusion (F), attachment (G) and small hydrophobic (SH) proteins], the F protein is probably the major antigen that induces a protective immune response in hamsters and African green m...

Purpose: Cyclooxygenase-2 (COX-2) overexpression has been associated with a poor prognosis in many cancers. However, the role of COX-2 overexpression in head and neck cancers remains undetermined.The objective of this study was to evaluate whether COX-2 is a prognostic factor in glottic cancer. Experimental Design: This study was part of a phase III placebo-controlled randomized trial evaluating the efficacy of a-tocopherol in reducing second primary cancers (SPC) in head and neck cancer patients. Immunohistochemical analyses were conducted on pretreatment biopsies of 301patients with early-stage glottic cancer treated by radiotherapy. The median value of 50% of positive tumor cells was the cutoff point used to define COX-2 overexpression. Outcomes considered in the statistical analysis were recurrence, SPC, and death. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and their 95% confidence intervals (95% CI). Results: The HR associated with COX-2 overexpression was 0.94 (95% CI, 0.55-1.62) for recurrence. The HR associated with SPC was 2.63 (95% CI, 1.32-5.23) for the first 3.5 years of follow-up and 0.55 (95% CI, 0.22-1.32) for the following 3.5 years. The HR associated with COX-2 overexpression was 1.57 (95% CI, 1.01-2.45) for overall mortality. Conclusions: COX-2 overexpression in glottic cancer was associated with increased overall mortality and an increased risk of SPC during the early follow-up period. Future studies are needed to explain observed effects on SPC. COX-2 expression may prove helpful in defining an individual patient's prognosis.Glottic cancer is the most common early-stage head and neck cancer. The 5-year overall survival rate is between 72% and 85% for stage I cancer and from 59% to 77% for stage II cancer (1 -3). Local recurrence occurs in about 6% to 28% of patients within 5 years (1). Another important outcome for patients with early-stage glottic cancer is the occurrence of a second primary cancer (SPC), which is discovered in 15% to 18% of the patients within 5 years and is associated with poor survival (2, 4, 5). The most common site of SPC is the upper aerodigestive tract (2, 5). SPCs are attributed to a ''field cancerization'' effect induced by carcinogens such as tobacco, which can alter the respiratory, oral, and esophageal mucosa (6, 7). Although the early stage of glottic cancer is relatively well controlled by therapy, prognosis of these patients is often compromised by the occurrence of SPC.Cyclooxygenase (COX) is the rate-limiting enzyme in the conversion of arachidonic acid into prostaglandins. It exists in two isoforms, COX-1, which is constitutional, and COX-2, which can be induced by stimuli such as smoking and radiotherapy (8-10). COX-2 overexpression increases prostaglandins, which are known to promote tumor development, invasion, and metastasis by many mechanisms, most importantly by stimulating angiogenesis through the action of vascular endothelial growth (11)(12)(13). Prostaglandins also induce cell proliferation, reduce apop...

We are reporting a case of arterial hypertension in a young woman who had an atrophic kidney with a cortical groove and histological features of the AskUpmark kidney. Her hypertension was renin dependent and the patient was cured following nephrectomy. Case ReportThis report is one of the series 'Hypertension Illustrated' and presents a case of arterial hypertension in an 18-year-old woman who had an atrophic kidney with a cortical grove and histological features of Ask-Upmark kidney as originally described. 1 The physical examination was unremarkable except for high blood pressure (BP) (160/ 100 mmHg). Serum potassium (3.6 mmol/l) and serum creatinine (81 mmol/l) were normal. There was no proteinuria, bacteriuria or haematuria. Serum calcium, plasma control and TSH were normal as were urinary catecholamines. Renal ultrasound showed a small left (6.5 cm) kidney with normal contralateral kidney (10 cm). The renal 99 Tc-Mag 3 scan revealed decreased uptake which was more obvious in the lower pole of the atrophic kidney, which contributed for 10% of the total function. Renal arteriography showed a normal but small (from the origin of the aorta) left renal artery irrigating an atrophic kidney. The right artery and kidney was normal. Active renin concentrations (mass assay immunometric method) under captopril stimulation were 154 ng/l in the left renal vein, 63 ng/l in the right vein (ratio 2.4) and 58 ng/l in the inferior vena cava. The patient underwent a leftlaparoscopic nephrectomy. BP normalized 130-135/ 80 mmHg without antihypertensive medication.The macroscopic examination revealed a 40 g (7 Â 4.5 Â 2.2 cm) kidney with a cortical groove in the mediolateral area (Figure 1). Histology of the groove area showed no glomerulus and microcystic tubules filled with colloid casts. The arcuate and interlobular arteries were prominent with myointimal hypertrophy (Figure 2). This atrophic area was sharply demarcated from the rest of the renal parenchyma, which was normal.The pathogenesis of the Ask-Upmark kidney is controversial. Some authors put forward the hypothesis that this entity originates from a congenital defect in the development of the renal vasculature. This phenomenon could account for the segmental hypoplasia, the absence of glomeruli and the thickening of arterial wall. 2,3 On the other hand, cases have also been associated with vesicoureteral reflux. 4,5 It has been argued that the absence of reflux at the time of diagnosis does not rule it out as the initial cause of the atrophic kidney.

Background Spinal disease (spd) in multiple myeloma (mm) can be a major source of morbidity in newly diagnosed patients and long-term survivors. We retrospectively assessed the incidence of spinal disease in patients newly diagnosed with myeloma, its effect on survival, and the possible effect of spinal radiation therapy (rt).Methods Patients diagnosed with mm between 2010 and 2014 were identified through the provincial cancer registry. Plain radiography, computed tomography, and magnetic resonance imaging were reviewed to detect and document the type of spd. Data related to rt and systemic therapy were collected. Kaplan–Meier and time-varying Cox regression models were used to describe overall survival.Results Of 306 identified patients with newly diagnosed mm, 51% had spd, including 17% with lytic disease, 68% with compression fractures, and 15% with spinal cord compression. Of the patients with spd, 61% received spinal rt. Of those patients, 84% received spinal rt within 3 months after their diagnosis. Median dose was 20 Gy. Most patients (89.2%) received chemotherapy, and 22.5% underwent autologous stem-cell transplantation. Only 6 of the patients treated with spinal rt received re-irradiation to the same site. Overall survival was similar for patients with and without spd. On multivariate analysis, spinal rt had no effect on survival.Conclusions In patients newly diagnosed with mm, spd is a common presentation. With current systemic therapy, the presence of spd had no adverse effect on overall survival. The effect of spinal rt on overall survival was nonsignificant.