The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the “Practice ...parameter for the diagnosis and management of primary immunodeficiency.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
Acute right upper quadrant pain is a common presenting symptom in patients with acute cholecystitis. When acute cholecystitis is suspected in patients with right upper quadrant pain, in most clinical ...scenarios, the initial imaging modality of choice is ultrasound. Although cholescintigraphy has been shown to have slightly higher sensitivity and specificity for diagnosis, ultrasound is preferred as the initial study for a variety of reasons, including greater availability, shorter examination time, lack of ionizing radiation, morphologic evaluation, confirmation of the presence or absence of gallstones, evaluation of bile ducts, and identification or exclusion of alternative diagnoses. CT or MRI may be helpful in equivocal cases and may identify complications of acute cholecystitis. When ultrasound findings are inconclusive, MRI is the preferred imaging test in pregnant patients who present with right upper quadrant pain. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Objective This report presents the 30-day results of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial and evaluates the safety ...and efficacy of ENROUTE Transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcarotid neuroprotection system that provides direct surgical common carotid access and cerebral embolic protection via high-rate flow reversal during carotid artery stenting (CAS). Methods A prospective, single-arm, multicenter clinical trial was performed to evaluate the use of the ENROUTE Transcarotid NPS during CAS procedures performed in patients considered to be at high risk for complications from carotid endarterectomy. Symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥70% stenosis were eligible to be treated with any U.S. Food and Drug Administration-approved carotid artery stent. The primary end point was the composite of all stroke, myocardial infarction (MI), and death at 30 days postprocedure as defined in the Food and Drug Administration-approved study protocol. Secondary end points included cranial nerve injury; 30-day stroke, death, stroke/death, and MI; acute device, technical, and procedural success; and access site complications. All major adverse events were adjudicated by an independent clinical events committee. Results Between November 2012 and July 2014, 208 patients were enrolled at 18 sites. Sixty-seven patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase. In the pivotal cohort, 26% were symptomatic and 75% were asymptomatic. Acute device and technical success were 99% (140 of 141). By hierarchical analysis, the all-stroke rate in the pivotal group was 1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness from potential Xth cranial nerve injury, which completely resolved at the 6-month follow-up visit. Conclusions The results of the ROADSTER trial demonstrate that the use of the ENROUTE Transcarotid NPS is safe and effective at preventing stroke during CAS. The overall stroke rate of 1.4% is the lowest reported to date for any prospective, multicenter clinical trial of CAS.
Abstract Multiple myeloma remains an incurable neoplasm of plasma cells that affects more than 20,000 people annually in the United States. There has been a veritable revolution in this disease ...during the past decade, with dramatic improvements in our understanding of its pathogenesis, the development of several novel agents, and a concomitant doubling in overall survival. Because multiple myeloma is a complex and wide-ranging disorder, its management must be guided by disease- and patient-related factors; emerging as one of the most influential factors is risk stratification, primarily based on cytogenetic features. A risk-adapted approach provides optimal therapy to patients, ensuring intense therapy for aggressive disease and minimizing toxic effects, providing sufficient but less intense therapy for low-risk disease. This consensus statement reflects recommendations from more than 20 Mayo Clinic myeloma physicians, providing a practical approach for newly diagnosed patients with myeloma who are not enrolled in a clinical trial.
Summary Background Protease inhibitors have improved treatment of infection with hepatitis C virus (HCV), but dosing, a low barrier to resistance, drug interactions, and side-effects restrict their ...use. We assessed the safety and efficacy of sofosbuvir, a uridine nucleotide analogue, in treatment-naive patients with genotype 1–3 HCV infection. Methods In this two-cohort, phase 2 trial, we recruited treatment-naive patients with HCV genotypes 1–3 from 22 centres in the USA. All patients were recruited between Aug 16, 2010, and Dec 13, 2010, and were eligible for inclusion if they were aged 18–70 years, had an HCV RNA concentration of 50 000 IU/mL or greater, and had no cirrhosis. We randomly allocated all eligible patients with HCV genotype 1 (cohort A) to receive sofosbuvir 200 mg, sofosbuvir 400 mg, or placebo (2:2:1) for 12 weeks in combination with peginterferon (180 μg per week) and ribavirin (1000–1200 mg daily), after which they continued peginterferon and ribavirin for an additional 12 weeks or 36 weeks (depending on viral response). Randomisation was done by use of a computer-generated randomisation sequence and patients and investigators were masked to treatment allocation until week 12. Patients with genotypes 2 or 3 (cohort B) received open-label sofosbuvir 400 mg plus peginterferon and ribavirin for 12 weeks. Our primary outcomes were safety and tolerability. Secondary efficacy analyses were by intention to treat and endpoints included sustained virological response, defined as undetectable HCV RNA at post-treatment weeks 12 and 24. This study is registered with ClinicalTrials.gov , number NCT01188772. Findings In cohort A, 122 patients were assigned 200 mg sofosbuvir (48 patients), 400 mg sofosbuvir (48), or placebo (26). We enrolled 25 patients into cohort B. The most common adverse events—fatigue, headache, nausea, and chills—were consistent with those associated with peginterferon and ribavirin. Eight patients discontinued treatment due to adverse events, two (4%) receiving sofosbuvir 200 mg, three (6%) receiving sofosbuvir 400 mg, and three (12%) receiving placebo. In cohort A, HCV RNA was undetectable at post-treatment week 12 in 43 (90%; 95% CI 77–97) of 48 patients in the 200 mg sofosbuvir group; 43 (91%; 80–98) of 47 patients in the 400 mg sofosbuvir group, and 15 (58%; 37–77) of 26 patients in the placebo group. In cohort B, 23 (92%) of 25 patients had undetectable HCV RNA at post-treatment week 12. Interpretation Our findings lend support to the further assessment, in phase 2 and 3 trials, of sofosbuvir 400 mg plus peginterferon and ribavirin for 12 weeks in treatment-naive patients with HCV genotype-1. Funding Gilead Sciences.
Background The recombination-activating gene (RAG) 1/2 proteins play a critical role in the development of T and B cells by initiating the VDJ recombination process that leads to generation of a ...broad T-cell receptor (TCR) and B-cell receptor repertoire. Pathogenic mutations in the RAG1/2 genes result in various forms of primary immunodeficiency, ranging from T− B− severe combined immune deficiency to delayed-onset disease with granuloma formation, autoimmunity, or both. It is not clear what contributes to such heterogeneity of phenotypes. Objective We sought to investigate the molecular basis for phenotypic diversity presented in patients with various RAG1 mutations. Methods We have developed a flow cytometry–based assay that allows analysis of RAG recombination activity based on green fluorescent protein expression and have assessed the induction of the Ighc locus rearrangements in mouse Rag1−/− pro-B cells reconstituted with wild-type or mutant human RAG1 (hRAG1) using deep sequencing technology. Results Here we demonstrate correlation between defective recombination activity of hRAG1 mutant proteins and severity of the clinical and immunologic phenotype and provide insights on the molecular mechanisms accounting for such phenotypic diversity. Conclusions Using a sensitive assay to measure the RAG1 activity level of 79 mutations in a physiologic setting, we demonstrate correlation between recombination activity of RAG1 mutants and the severity of clinical presentation and show that RAG1 mutants can induce specific abnormalities of the VDJ recombination process.
Background Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients ...with symptomatic disease. Objective To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. Methods This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least 1 of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. Results A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least 1 dose of immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to immunotherapy than those receiving placebo (17/126 13.5% vs 32/122 26.2%; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance immunotherapy dose (110 87.3% vs 88 72.1%, respectively; P = .004). Conclusion Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific immunotherapy and enabled more patients to achieve the target immunotherapy maintenance dose.
Purpose Correlation exists between people who engage in academic dishonesty as students and unethical behavior once in practice. Previously, we assessed the attitudes of general surgery residents and ...ethical practices in test taking at a single institution. Most residents had not participated in activities they felt were unethical, yet what constituted unethical behavior was unclear. We sought to verify these results in a multi-institutional study. Methods A scenario-based survey describing potentially unethical activities related to the American Board of Surgery In-training Examination (ABSITE) was administered. Participants were asked about their knowledge of or participation in the activities and whether the activity was unethical. Program directors were surveyed about the use of ABSITE results for resident evaluation and promotion. Results Ten programs participated in the study. The resident response rate was 67% (186/277). Of the respondents, 43% felt that memorizing questions to study for future examinations was unethical and 50% felt that using questions another resident memorized was unethical. Most felt that buying (86%) or selling (79%) questions was unethical. Significantly more senior than junior residents have memorized (30% vs 16%; p = 0.04) or used questions others memorized (33% vs 12%; p = 0.002) to study for future ABSITE examinations and know of other residents who have done so (42% vs 20%; p = 0.004). Most programs used results of the ABSITE in promotion (80%) and set minimum score expectations and consequences (70%). Conclusion Similar to our single-institution study, residents had not participated in activities they felt to be unethical; however the definition of what constitutes cheating remains unclear. Differences were identified between senior and junior residents with regard to memorizing questions for study. Cheating and unethical behavior is not always clear to the learner and represents an area for further education.
Objective The Nellix EndoVascular Aneurysm Sealing system (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) endovascular repair whereby biocompatible polymer is ...employed to exclude and to seal the AAA sac. We report 30-day results of the U.S. pivotal trial. Methods Consecutive, eligible, consenting patients were enrolled at 29 sites in the United States and Europe. Inclusion criteria required an asymptomatic infrarenal AAA, with aortic neck length ≥10 mm and angle to the sac ≤60 degrees, aortic neck diameter of 18 to 32 mm, aneurysm blood lumen diameter ≤6 cm, common iliac artery lumen diameter of 9 to 35 mm, access artery diameter ≥6 mm, and serum creatinine level ≤2 mg/dL. Follow-up at 30 days included clinical assessment and computed tomography angiography evaluation of endoleaks and device integrity as assessed by a core laboratory. The primary safety end point is the incidence of independently adjudicated 30-day major adverse events (MAEs), with success defined as superiority with reference to the Society for Vascular Surgery open repair control group (56%). Results Between January and November 2014, 150 trial patients having a mean AAA diameter of 5.8 cm were enrolled and treated with the Nellix system with 100% procedural success. One early death (0.7%) occurred secondary to multisystem organ failure. All 149 surviving patients completed 30-day follow-up. There were no aneurysm ruptures, conversions, limb thromboses, stent fractures, or stent kinking. Five early MAEs occurred in four patients (2.7%) and included one death, bowel ischemia (1), renal failure (2), and respiratory failure (1). One (0.7%) secondary intervention to treat inadvertent coverage of a renal artery was performed. The core laboratory identified nine (6%) endoleaks (one type I, eight type II) on 30-day computed tomography angiography. Freedom from MAE was 97.3% (95% confidence interval, 93.3%-99.0%). Conclusions In selected patients, perioperative outcomes with the Nellix system for endovascular aneurysm sealing are encouraging, with very low 30-day morbidity and mortality and high procedural success. The primary safety end point has been achieved. Longer term follow-up is in progress.
Thymic Carcinoma: Outcomes After Surgical Resection Okereke, Ikenna C., MD; Kesler, Kenneth A., MD; Freeman, Richard K., MD ...
The Annals of thoracic surgery,
05/2012, Letnik:
93, Številka:
5
Journal Article
Recenzirano
Background Thymic carcinoma is a rare malignancy with little information regarding outcomes after therapy with curative intent. We undertook a retrospective analysis of all patients who underwent ...resection of thymic carcinoma at 2 hospitals. Methods From 1990 to 2011, 16 patients (9 men, 7 women) underwent surgical resection of thymic carcinoma at a mean age of 52 years. Patient demographics, extent of surgical resection, and outcomes were compiled. Results The distribution of Masaoka stages at presentation was I in 3 (19%), II in 4 (25%), III in 8 (50%), and IV in 1 (6%). Neoadjuvant chemotherapy was administered to 6 patients (38%) whose tumors were deemed to be more locally invasive. Surgical resection included en bloc extrapleural pneumonectomy in 1, lobectomy in 2, and superior vena cava resection and reconstruction in 4. There were no perioperative deaths. Complete resection was achieved in 14 (88%), and of these patients, only 1 experienced local recurrence. At last follow-up, 10 patients were alive and well, 1 patient was alive with disease, and 5 patients had died. Mean survival was 4.2 years. Conclusions Although considered to have greater malignant potential, long-term survival can be achieved in patients with thymic carcinoma who are amenable to surgical therapy. With increased use of computed tomography imaging, patients with early-stage disease are being identified more frequently, and complete surgical resection appears to have favorable cure rates in these patients. Select patients with locally advanced disease can experience long-term survival with a multimodality approach.
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