Background Arteriovenous fistulas (AVFs) for hemodialysis frequently fail to mature because of inadequate dilation or early stenosis. The pathogenesis of AVF nonmaturation may be related to ...pre-existing vascular pathologic states: medial fibrosis or microcalcification may limit arterial dilation, and intimal hyperplasia may cause stenosis. Study Design Observational study. Setting & Participants Patients with chronic kidney disease (N = 50) undergoing AVF placement. Predictors Medial fibrosis, microcalcification, and intimal hyperplasia in arteries and veins obtained during AVF creation. Outcome & Measurements AVF nonmaturation. Results AVF nonmaturation occurred in 38% of patients despite attempted salvage procedures. Preoperative arterial diameter was associated with upper-arm AVF maturation ( P = 0.007). Medial fibrosis was similar in patients with nonmaturing and mature AVFs (60% ± 14% vs 66% ± 13%; P = 0.2). AVF nonmaturation was not associated with patient age or diabetes, although both variables were associated significantly with severe medial fibrosis. Conversely, AVF nonmaturation was higher in women than men despite similar medial fibrosis in both sexes. Arterial microcalcification (assessed semiquantitatively) tended to be associated with AVF nonmaturation (1.3 ± 0.8 vs 0.9 ± 0.8; P = 0.08). None of the arteries or veins obtained at AVF creation had intimal hyperplasia. However, repeated venous samples obtained in 6 patients during surgical revision of an immature AVF showed venous neointimal hyperplasia. Limitations Single-center study. Conclusion Medial fibrosis and microcalcification are frequent in arteries used to create AVFs, but do not explain AVF nonmaturation. Unlike previous studies, intimal hyperplasia was not present at baseline, but developed de novo in nonmaturing AVFs.
Background Arteriovenous fistulas (AVFs) often fail to mature, but the mechanism of AVF nonmaturation is poorly understood. Arterial microcalcification is common in patients with chronic kidney ...disease (CKD) and may limit vascular dilatation, thereby contributing to early postoperative juxta-anastomotic AVF stenosis and impaired AVF maturation. This study evaluated whether preexisting arterial microcalcification adversely affects AVF outcomes. Study Design Prospective study. Setting & Participants 127 patients with CKD undergoing AVF surgery at a large academic medical center. Predictors Preexisting arterial microcalcification (≥1% of media area) assessed independently by von Kossa stains of arterial specimens obtained during AVF surgery and by preoperative ultrasound. Outcomes Juxta-anastomotic AVF stenosis (ascertained by ultrasound obtained 4-6 weeks postoperatively), AVF nonmaturation (inability to cannulate with 2 needles with dialysis blood flow ≥ 300 mL/min for ≥6 sessions in 1 month within 6 months of AVF creation), and duration of primary unassisted AVF survival after successful use (time to first intervention). Results Arterial microcalcification was present by histologic evaluation in 40% of patients undergoing AVF surgery. The frequency of a postoperative juxta-anastomotic AVF stenosis was similar in patients with or without preexisting arterial microcalcification (32% vs 42%; OR, 0.65; 95% CI, 0.28-1.52; P = 0.3). AVF nonmaturation was observed in 29%, 33%, 33%, and 33% of patients with <1%, 1% to 4.9%, 5% to 9.9%, and ≥10% arterial microcalcification, respectively ( P = 0.9). Sonographic arterial microcalcification was found in 39% of patients and was associated with histologic calcification ( P = 0.001), but did not predict AVF nonmaturation. Finally, among AVFs that matured, unassisted AVF maturation (time to first intervention) was similar for patients with and without preexisting arterial microcalcification (HR, 0.64; 95% CI, 0.35-1.21; P = 0.2). Limitations Single-center study. Conclusions Arterial microcalcification is common in patients with advanced CKD, but does not explain postoperative AVF stenosis, AVF nonmaturation, or AVF failure after successful cannulation.
Abstract Background The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association ...cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation PCE) is untested. Objectives This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle–brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis). Methods The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell’s C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease–related death, or fatal or nonfatal stroke. Results Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell’s C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell’s C statistic when added to the cPCE. Conclusions CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.
Abstract Objectives The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe ...symptomatic aortic stenosis who were contraindicated or high risk for surgery. Background The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation. Methods A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria. Results Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm2. Conclusions At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.
Background Arteriovenous grafts (AVGs) are prone to neointimal hyperplasia leading to AVG failure. We hypothesized that pre-existing pathologic abnormalities of the vessels used to create AVGs ...(including venous intimal hyperplasia, arterial intimal hyperplasia, arterial medial fibrosis, and arterial calcification) are associated with inferior AVG survival. Study Design Prospective observational study. Setting & Participants Patients with chronic kidney disease undergoing placement of a new AVG at a large medical center who had vascular specimens obtained at the time of surgery (n = 76). Predictor Maximal intimal thickness of the arterial and venous intima, arterial medial fibrosis, and arterial medial calcification. Outcome & Measurements Unassisted primary AVG survival (time to first intervention) and frequency of AVG interventions. Results 55 patients (72%) underwent interventions and 148 graft interventions occurred during 89.9 years of follow-up (1.65 interventions per graft-year). Unassisted primary AVG survival was not associated significantly with arterial intimal thickness (HR, 0.72; 95% CI, 0.40-1.27; P = 0.3), venous intimal thickness (HR, 0.64; 95% CI, 0.37-1.10; P = 0.1), severe arterial medial fibrosis (HR, 0.58; 95% CI, 0.32-1.06; P = 0.6), or severe arterial calcification (HR, 0.68; 95% CI, 0.37-1.31; P = 0.3). The frequency of AVG interventions per year was associated inversely with arterial intimal thickness (relative risk RR, 1.99; 95% CI, 1.16-3.42; P < 0.001 for thickness <10 vs >25 μm), venous intimal thickness (RR, 2.11; 95% CI, 1.39-3.20; P < 0.001 for thickness <5 vs >10 μm), arterial medial fibrosis (RR, 3.17; 95% CI, 1.96-5.13; P < 0.001 for fibrosis <70% vs ≥70%), and arterial calcification (RR, 2.12; 95% CI, 1.31-3.43; P = 0.001 for <10% vs ≥10% calcification). Limitations Single-center study. Study may be underpowered to demonstrate differences in unassisted primary AVG survival. Conclusions Pre-existing vascular pathologic abnormalities in patients with chronic kidney disease may not be associated significantly with unassisted primary AVG survival. However, vascular intimal hyperplasia, arterial medial fibrosis, and arterial calcification may be associated with a decreased frequency of AVG interventions.
Objectives The study sought a prospective multicenter nonrandomized evaluation of the Direct Flow Medical (DFM) system for the treatment of severe aortic stenosis. Background The DFM transcatheter ...aortic valve system is a nonmetallic design with a pressurized support structure that allows precise positioning, retrieval, and assessment of valve performance prior to permanent implantation. Methods One hundred high surgical risk patients with severe aortic stenosis were evaluated for the primary endpoint. There were 75 patients in the group evaluable for the secondary endpoints and 25 in the pre-specified roll-in training phase. Echocardiographic and angiographic data were evaluated by an independent core laboratory and adverse events adjudicated by clinical event committee and classified according to Valve Academic Research Consortium (VARC) criteria. Results There was 99% freedom from all cause mortality at 30 days (primary endpoint). VARC criteria defined 30 day combined freedom from patient safety event rate was 91% and overall device success was 93%. The post-implantation echocardiography results demonstrated mild or no aortic regurgitation in 99% (73 of 74) with a mean gradient of 12.6 ± 7.1 mm Hg (n = 72) and effective orifice area of 1.50 ± 0.56 cm2 and New York Heart Association functional class was I or II in 92% of cases. Conclusions The present study demonstrates the safety and efficacy of the DFM system in surgical high risk patients with severe aortic stenosis and complex anatomy aortic regurgitation was less than moderate in 99% of patients.
Summary Background Available drugs against cytomegalovirus have adverse effects that compromise their prophylactic use in recipients of allogeneic stem-cell transplants. We assessed the safety, ...tolerability, and antiviral activity of oral maribavir in such patients. Methods In this placebo-controlled, randomised, double-blind, multicentre phase 3 study, we enrolled adult patients recipient-seropositive or donor-seropositive for cytomegalovirus who had undergone allogeneic stem-cell transplantation. Patients were recruited from 90 centres in Canada, Europe, and the USA. After engraftment, patients were stratified by recipient cytomegalovirus serostatus and conditioning regimen (myeloablative or reduced-intensity) and assigned (2:1) by masked computer-generated randomisation sequence to receive maribavir 100 mg twice daily or placebo for up to 12 weeks, with weekly blood cytomegalovirus surveillance. If the virus was detected, administration of study drug was stopped and pre-emptive anticytomegalovirus treatment started. The primary endpoint was cytomegalovirus disease within 6 months of transplantation. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov , NCT00411645. Findings Between December, 2006, and May, 2008, 681 patients were enrolled and assigned to receive maribavir (454) or placebo (227). The incidence of cytomegalovirus disease within 6 months was 20 of 454 (4%) for the maribavir group and 11 of 227 (5%) for the placebo group (OR 0·90; 95% CI 0·42–1·92). During the 100 days following transplantation, cytomegalovirus infection rates as measured by pp65 antigenaemia were lower in the maribavir group (26·4%) than in the placebo group (34·8%; OR 0·67; 0·47–0·95), but not when measured by plasma cytomegalovirus DNA PCR (27·8% vs 30·4%; OR 0·88; 0·62–1·25), nor by initiation of treatment against cytomegalovirus (30·6% vs 37·4%; OR 0·73, 0·52–1·03). Maribavir was well tolerated: most adverse events, including incident acute graft-versus-host disease and neutropenia, affected both groups equally, except for taste disturbance (15% maribavir, 6% placebo). Interpretation Compared with placebo, maribavir prophylaxis did not prevent cytomegalovirus disease when started after engraftment. Cytomegalovirus disease as a primary endpoint might not be sufficient to show improvements in cytomegalovirus prevention in recipients of allogeneic stem-cell transplants in the setting of pre-emptive antiviral treatment. Clinical and virological composite endpoints should be used in future trials. Funding ViroPharma Incorporated.
Background Atopic dermatitis (AD) is characterized by epidermal barrier failure and immune-mediated inflammation. Evidence on AD as a potential risk factor for inflammatory comorbidities is scarce. ...Objectives We sought to test the hypothesis that prevalent AD is a risk factor for incident rheumatoid arthritis (RA) and inflammatory bowel disease (IBD; Crohn disease CD, ulcerative colitis UC) and is inversely related to type 1 diabetes (T1D) and to investigate established RA, IBD, and T1D susceptibility loci in AD. Methods This cohort study used data from German National Health Insurance beneficiaries aged 40 years or younger (n = 655,815) from 2005 through 2011. Prevalent AD in the period 2005 to 2006 was defined as primary exposure , and incident RA, IBD, and T1D in the period 2007 to 2011 were defined as primary outcomes . Risk ratios were calculated with generalized linear models. Established RA, IBD, and T1D loci were explored in high-density genotyping data from 2,425 cases with AD and 5,449 controls. Results Patients with AD (n = 49,847) were at increased risk for incident RA (risk ratio RR, 1.72; 95% CI, 1.25-2.37) and/or IBD (CD: RR, 1.34; 95% CI, 1.11-1.61; UC: RR, 1.25; 95% CI, 1.03-1.53). After adjusting for health care utilization, there was a nominally significant inverse effect on T1D risk (RR, 0.72; 95% CI, 0.53-0.998). There was no disproportionate occurrence of known RA, CD, UC, or T1D risk alleles in AD. Conclusions AD is a risk factor for the development of RA and IBD. This excess comorbidity cannot be attributed to major known IBD and RA genetic risk factors.
Treatment of acute retinal necrosis Tibbetts, Michael D; Shah, Chirag P; Young, Lucy H ...
Ophthalmology (Rochester, Minn.),
04/2010, Letnik:
117, Številka:
4
Journal Article
Recenzirano
To compare outcomes from patients with acute retinal necrosis (ARN) treated in the acyclovir-only era with those treated in the era of newer antiviral therapies, identify variables affecting outcomes ...in ARN, and evaluate strategies for fellow eye prophylaxis.
Multicenter, nonrandomized, retrospective, interventional series.
A cohort of 58 patients diagnosed with ARN by a retina specialist at 1 of 4 referral centers between 1981 and 2008. The cohort was divided into 2 subgroups: patients treated during the acyclovir-only era (n = 36) and patients treated during the current era of newer antiviral medications (n = 22).
Intravenous, oral, or intravitreal antiviral medications, including acyclovir, valacyclovir, famciclovir, valganciclovir, ganciclovir, and foscarnet; prophylactic laser retinopexy; aspirin; oral steroids.
Visual acuity, retinal detachment, and fellow eye involvement.
A wide range and combination of antiviral agents are currently used for initial and long-term treatment of ARN. Outcomes from the newer antivirals era were similar to those achieved during the acyclovir-only era. In both groups, the incidence of 20/200 or worse visual acuity was 24% per person-year (P = 0.91). The prevalence of retinal detachment was approximately 50% in each group (P = 0.59). No variables, including prophylactic laser retinopexy, were associated with risk of retinal detachment. Two patients (3.4%) developed ARN in the initially unaffected eye.
Current treatment trends vary widely, including single agents or combinations of oral, intravenous, and intravitreal agents. Differing strategies did not affect outcomes. The final visual acuity in ARN was generally poor. Retinal detachment was common and could neither be predicted nor prevented. Development of ARN in the unaffected fellow eye occurred rarely. Long-term oral antiviral treatment strategies varied with unclear relative efficacy.
Proprietary or commercial disclosure may be found after the references.
Background Mirizzi syndrome (MS) is characterized by extrinsic compression of the common hepatic duct by stones impacted in the cystic duct or gallbladder neck. Open cholecystectomy (OC) has been the ...standard treatment; however, laparoscopy has challenged this approach. Study Design The objective of this study was to review our clinical experience with MS since the introduction of laparoscopic cholecystectomy (LC) and determine the impact of alternative approaches. We conducted a retrospective review of patients with MS from January 1987 to December 2009. Results There were 36 patients with MS among 21,450 cholecystectomies (frequency 0.18%). Seventeen were women. The most common presenting symptoms were abdominal pain (n = 23) and jaundice (n = 19). Preoperative diagnostic studies included ultrasonography (n = 27), CT (n = 24), and endoscopic retrograde cholangiopancreatography (n = 32). Cholecystectomy was performed in 35 patients; LC was initiated in 15 and OC in 21. Conversion rate from LC to OC was 67%. Five patients who had successful LC had type I MS. Of the patients who underwent LC with conversion or OC, 14 had type I and 16 had type II MS. The cystic duct for type I and the bile duct for type II MS were managed diversely according to surgeon's preference. There was no operative mortality. Morbidity was 31% with Clavien class I in 2, IIIa in 4, IIIb in 1, and IV in 3 patients. Mean hospitalization was 9 days (range 2 to 40 days). Mean follow-up was 37 months (range 1 to 187 months). Conclusions Low incidence and nonspecific presentation of MS precludes referral and substantive individual experience. Although LC may be applicable in selected patients with type I MS, OC remains the standard of care.
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