Citations

ABSTRACTIntroductionOver the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE.AimDevelop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts.MethodReview of the literature.ResultsThis article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients.ConclusionDevelopment of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.

Abstract The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype–phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes.

Background— Proposed advantages to the Ross procedure included presumed increased freedom from reoperation and simpler reoperation for pulmonary conduit replacement if needed. It is increasingly apparent, however, that reoperations are frequent after the Ross procedure and that when required, they may be more complex than previously thought. Methods and Results— Between September 1991 and August 2008, 56 patients underwent reoperation at our institution after a Ross procedure performed by ourselves (n=13) or elsewhere (n=43). Median age at first reoperation at our institution was 26 years (range 1 to 69 years). The 4 most common indications for reoperation were isolated autograft (neoaortic) regurgitation in 11 cases (20), isolated pulmonary conduit regurgitation/stenosis in 9 (16), combined autograft regurgitation/dilatation in 8 (14), and combined autograft regurgitation and pulmonary conduit regurgitation/stenosis in 6 (11). A total of 144 procedures were performed in these 56 patients during first reoperation at our institution. The autograft valve required replacement in 21 cases (38) and aortic root replacement in 21 (38), with ascending aortic/arch reconstruction in 13 (23) and mitral valve surgery in 5 (9). The pulmonary valve was replaced in 33 cases (59) and the tricuspid valve was repaired/replaced in 10 (18). Early mortality was 1.8 (1 of 56 patients), and morbidity included 6 patients with respiratory failure and 3 who required postcardiotomy extracorporeal membrane oxygenation. There were 4 late deaths during the median follow-up of 8 months (range 1 to 179 months). Conclusions— A broad spectrum of complex reoperations may be required after the Ross procedure. Patients and family members considering the procedure should be informed of the potential for associated morbidity should reoperation be necessary.

Abstract Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow, which evolves from a premalignant stage called monoclonal gammopathy of undetermined significance (MGUS). In some patients, an intermediate stage referred to as smoldering multiple myeloma (SMM) is clinically recognized, with the full-bore malignancy termed MM. We conducted a study to assess differential CpG methylation at 1,500 genic loci during MM progression and profiled CD138+ plasma cells from MGUS, SMM, and MM specimens; human myeloma cell lines; and normal plasma cell (NPC) samples. We showed that the number of differentially methylated loci (DML) increased with tumor grade, and the vast majority were due to hypomethylation. Hierarchical clustering analysis revealed samples that coclustered tightly with NPC. These cases, referred to as “normal-like,” contained significantly fewer DML when compared with their non–normal-like counterparts and displayed overall methylation levels resembling NPC. This study represents one of the first methylome interrogation studies in MM and points toward global hypomethylation at genic CpG loci as an important and early mechanism driving myelomagenesis. Determining the set of critical genes and pathways based on the myeloma methylome is expected to lead to an improved understanding of biological mechanisms involved in myelomagenesis. Cancer Res; 70(17); 6934–44. ©2010 AACR.

Abstract Zosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp–mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomized placebo-controlled double-blind trial (Eastern Cooperative Oncology Group 3999). Overall survival was compared between patients receiving conventional-dose cytarabine and daunorubicin and either zosuquidar (550 mg; 212 patients) or placebo (221 patients). Median and 2-year overall survival values were 7.2 months and 20% on zosuquidar and 9.4 months and 23% on placebo, respectively (P = .281). Remission rate was 51.9% on zosuquidar and 48.9% on placebo. All cause mortality to day 42 was not different (zosuquidar 22.2% vs placebo 16.3%; P = .158). In vitro modulation of P-gp activity by zosuquidar and expression of P-gp, multidrug resistance-related protein 1, lung resistance protein, and breast cancer resistance protein, were comparable in the 2 arms. Poor-risk cytogenetics were more common in P-gp+ patients. P-gp expression and cytogenetics were correlated, though independent prognostic factors. We conclude that zosuquidar did not improve outcome in older acute myeloid leukemia, in part, because of the presence P-gp independent mechanisms of resistance. This trial is registered at www.clinicaltrials.gov as #NCT00046930.

AbstractBackground: Supplement use among cancer patients is high, and folic acid intake in particular may adversely affect the progression of colorectal cancer. Few studies have evaluated the use of folic acid–containing supplements (FAS) and its predictors in colorectal cancer patients.Objective: To assess the use of FAS, change in use, and its predictors after colorectal cancer diagnosis.Design: We used logistic regression models to investigate predictors of FAS use and its initiation after colorectal cancer diagnosis in 1,092 patients recruited through the Colon Cancer Family Registry.Results: The prevalence of FAS use was 35.4% before and 55.1% after colorectal cancer diagnosis (P = 0.004). Women were more likely than men to use FAS after diagnosis [odds ratio (OR), 1.47; 95% confidence interval (95% CI), 1.14-1.89], as were those consuming more fruit (Ptrend < 0.0001) or vegetables (Ptrend = 0.001), and U.S. residents (P < 0.0001). Less likely to use FAS after diagnosis were nonwhite patients (OR, 0.66; 95% CI, 0.45-0.97), current smokers (OR, 0.67; 95% CI, 0.46-0.96), and those with higher meat intake (Ptrend = 0.03). Predictors of FAS initiation after diagnosis were generally similar to those of FAS use after diagnosis, although associations with race and vegetable intake were weaker and those with exercise stronger.Conclusions: Our analysis showed substantial increases in the use of FAS after diagnosis with colorectal cancer, with use or initiation more likely among women, Caucasians, U.S. residents, and those with a health-promoting life-style.Impact: Studies of cancer prognosis that rely on prediagnostic exposure information may result in substantial misclassification. Cancer Epidemiol Biomarkers Prev; 19(8); 2023–34. ©2010 AACR.

Purpose The purposes of this study was to better understand the utilization of anterior acromioplasty over time, in the absence of rotator cuff repair; to examine the relation to patient characteristics (age, sex) and types of rotator cuff pathology (inflammation or fibrosis, partial‐thickness tearing, full‐thickness tearing undergoing debridement); and to assess the utilization of arthroscopy in this procedure. Methods Using the resources of the Rochester Epidemiology Project, cataloging medical records of residents in Olmsted County, Minnesota, we identified 246 patients who underwent anterior acromioplasty between 1980 and 2005. It has previously been shown that rarely does a resident of Olmsted County undergo an orthopaedic procedure at a facility outside the county. Results The incidence of anterior acromioplasty increased over time ( P < .001), with crude rates of 3.3 per 100,000 persons in 1980 to 1985 and 19.0 per 100,000 persons in 2000 to 2005. Sex, age, and types of rotator cuff pathology did not significantly change over the 26‐year period. There was a dramatic shift from use of the open approach to the arthroscopic approach over this time period ( P < .001) and a decrease in the concomitant performance of distal clavicle resection ( P < .001). Conclusions The frequency of anterior acromioplasty has dramatically increased over time. Increasing knowledge about this syndrome, including better imaging, has facilitated patient treatment for a stable spectrum of rotator cuff pathology (inflammation or fibrosis, partial‐thickness tearing, full‐thickness tearing undergoing debridement), as has the application of endoscopic surgery. Level of Evidence Level III, epidemiologic study.

Abstract The purpose of this Consensus Statement is to focus on implantable cardioverter-defibrillator (ICD) deactivation in patients with irreversible or terminal illness. This statement summarizes the opinions of the Task Force members, convened by the European Heart Rhythm Association (EHRA) and the Heart Rhythm Society (HRS), based on ethical and legal principles, as well as their own clinical, scientific, and technical experience. It is directed to all healthcare professionals who treat patients with implanted ICDs, nearing end of life, in order to improve the patient dying process. This statement is not intended to recommend or promote device deactivation. Rather, the ultimate judgement regarding this procedure must be made by the patient (or in special conditions by his/her legal representative) after careful communication about the deactivation's consequences, respecting his/her autonomy and clarifying that he/she has a legal and ethical right to refuse it. Obviously, the physician asked to deactivate the ICD and the industry representative asked to assist can conscientiously object to and refuse to perform device deactivation.