Citations

Background: Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation. However, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative mitral regurgitation with a flail leaflet. Methods: MIDA (Mitral Regurgitation International Database) is a multicenter registry enrolling patients with degenerative mitral regurgitation with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1709) and replacement (n=213) overall, by propensity score matching, and by inverse probability-of-treatment weighting. Results: At baseline, patients undergoing MV repair were younger, had more comorbidities, and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching and inverse probability-of-treatment weighting, the 2 treatments groups were balanced, and absolute standardized differences were usually <10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement in both the entire population (1.3% versus 4.7%; P <0.001) and the propensity-matched population (0.2% versus 4.4%; P <0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement in both the entire population (46% versus 23%; P <0.001) and the matched population (41% versus 24%; P <0.001). Similar superiority of MV repair was obtained in patient subsets on the basis of age, sex, or any stratification criteria (all P <0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications. Conclusions: Among patients with degenerative mitral regurgitation with a flail leaflet referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival, and fewer valve-related complications compared with MV replacement.

Context.— Transbronchial cryobiopsy has recently been proposed as an alternative to surgical biopsy in the diagnosis of diffuse lung disease. Objective.— To familiarize pathologists with transbronchial cryobiopsy, including what it is, how it is performed, how it compares to other techniques of lung biopsy in diffuse lung disease, what are the technical issues relating to it, what the complications are, how cryobiopsies should be interpreted, and the clinical usefulness of cryobiopsy. Data Sources.— All the available literature on cryobiopsy in diffuse lung disease through May 2016, primarily in the last 5 years, was reviewed, and some unpublished data known to the authors were included. Conclusions.— Cryobiopsies are considerably larger than forceps biopsies and allow pattern recognition approaching that of a surgical lung biopsy in many cases. Artifacts associated with cryobiopsy are minimal. In comparison with surgical lung biopsies, the diagnosis rate with cryobiopsies is lower, in the neighborhood of 80%, versus higher than 90% for surgical lung biopsies. Cryobiopsy is proposed as an alternative to surgical lung biopsy and a technique that may appreciably decrease the number of patients who require surgical lung biopsy for diagnosis. This is important because the mortality from cryobiopsy is very small (0.1% to date) compared with surgical lung biopsy (1.7% for elective procedures and considerably higher for nonelective procedures).

ObjectivePolyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium‐sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single‐organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis.MethodsRetrospective cohorts were assembled, consisting of patients with PAN, CA, and GI vasculitis between 1980 and 2014. The demographics, clinical characteristics, treatment, and outcomes of patients were abstracted from medical records.ResultsWe included 48 patients with PAN, 41 patients with CA, and 19 patients with GI vasculitis. The disease of 1 patient evolved from CA to systemic PAN during the disease course. At diagnosis, 94% of patients with PAN, 93% of patients with CA, and 67% of patients with GI vasculitis were treated with glucocorticoids. Additional immunosuppressive agents were used in 67% of PAN, 37% of GI vasculitis, and 32% of CA cases. The 5‐year cumulative relapse rate was 45.2% in CA, and only 9.6% in PAN during a followup of approximately 6 years. No deaths were observed in the CA group. The survival rate at 10 years was 66% in the PAN group and 61% in the GI vasculitis group.ConclusionSystemic PAN, CA, and GI vasculitis take different clinical courses and therefore may be different diseases, rather than existing on a spectrum of the same disease. Progression of CA to systemic PAN is very rare. Relapse risk is low during followup in PAN. Patients with CA have a higher relapse rate than those with systemic PAN, possibly due to less use of immunosuppressive therapy in CA.

The chronic lymphocytic leukemia International Prognostic Index (CLL‐IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2‐microglobulin) to predict survival and time‐to‐first‐treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL‐IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL‐IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL‐IPI was originally developed to predict survival, we next investigated the optimal cut‐off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n = 139), 1 (n = 90), and ≥ 2(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P < 0.0001.; C‐statistic:c = 0.72; 95% CI:0.58‐0.81). This optimized CLL‐IPI scoring for TTFT was subsequently validated in an independent cohort of Binet A patients from the Mayo Clinic (n = 525). The ability of either original or optimized CLL‐IPI to predict TTFT was equivalent to other prognostic models specifically designed for this endpoint (2011 MDACC score and O‐CLL1 score). Although originally developed to predict suvival, the CLL‐IPI is useful for predicting TTFT in early stage CLL patients. Am. J. Hematol. 91:1090–1095, 2016. © 2016 Wiley Periodicals, Inc.

Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.

AbstractThis viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra‐epidermal blistering through the “desmoglein (Dsg) compensation” hypothesis, according to which an antibody‐dependent disabling of Dsg 1‐ and/or Dsg 3‐mediated cell–cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra‐epidermal blistering through the “multiple hit” hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self‐repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non‐Dsg‐specific autoantibodies, and (iii) determine the extent of the contribution of non‐Dsg antibodies in disease pathophysiology.

ABSTRACTObjectiveTo evaluate the effect on perinatal and postnatal survival of vesicoamniotic shunt (VAS) as treatment for fetal lower urinary tract obstruction (LUTO).MethodsAn electronic search of Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus using relevant search terms was conducted from inception to June 2015 to identify studies comparing outcomes of VAS vs conservative management for treatment of LUTO. Cohort studies and clinical trials were considered eligible. Single‐arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for exclusion. Two reviewers extracted independently data in a standardized form, including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratio (OR) and 95% CI.ResultsOf the 423 abstracts retrieved, nine studies were eligible for inclusion. These studies included 112 fetuses treated with VAS and 134 that were managed conservatively. There was heterogeneity in study design. Although the data demonstrated a difference in effect estimates between the study arms in terms of perinatal survival (OR, 2.54 (95% CI, 1.14–5.67)), there was no difference in 6–12‐month survival (OR, 1.77 (95% CI, 0.25–12.71)) or 2‐year survival (OR, 1.81 (95% CI, 0.09–38.03)). In addition, there was no difference in effect on postnatal renal function between fetuses that underwent intervention and those that did not (OR, 2.09 (95% CI, 0.74–5.94)).ConclusionsAvailable data seem to support an advantage for perinatal survival in fetuses treated with VAS compared with conservative management. However, 1–2‐year survival and outcome of renal function after VAS procedure remain uncertain. Further studies are necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies according to GRADE guidelines. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Introduction: We aim to describe changes in exercise habits and barriers to physical activity over 5 years in menopausal women at low–intermediate risk for cardiovascular disease. Materials and Methods: Women in the Stress Echocardiography in Menopausal Women at Risk for Coronary Artery Disease trial were prospectively enrolled in a multisite study from 2004 to 2007. Inclusion criteria were as follows: peri- and postmenopausal women with symptoms and/or risk factors for cardiovascular disease resulting in referral for stress echocardiography. A questionnaire, which assessed details of medical history, physical activity, and body mass index (BMI), was administered at baseline and 5 years. Results: 216 menopausal women (62.5% hypertensive, 15.3% diabetic, 52.3% prior or current smokers) were studied. At baseline, age was 54.9 ± 4.8 years, BMI was 30.7 ± 6.4 kg/m 2 , and Framingham risk score was 4.05% ± 3.76%. One hundred women (46.3%) were obese, 79 (36.6%) overweight, and 37 (17.1%) had a normal BMI. Women changed their self-reported aerobic exercise patterns in similar patterns regardless of their BMI at baseline. There was low participation in strength training among all women. Mean BMI decreased by 0.12 kg/m 2 in obese women and increased by 1.63 kg/m 2 in normal BMI women at 5 years ( p < 0.0001). Conclusion: These data suggest that women can increase their level of physical activity regardless of BMI and that overweight or obese status is not a barrier to initiating an aerobic, nonaerobic, or strength training exercise routine.