Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Ovarian function, fertility and reproductive lifespan in cancer patients

INTRODUCTION: The increasing survival of girls and young women after cancer has led to a rapid growth in research into assessment of ovarian function after treatment. AREAS COVERED: This aim of this review is to discuss normal ovarian function over time, the impact of cancer treatment on ovarian function, the assessment of ovarian reserve after treatment, and pretreatment predictors of ovarian recovery. EXPERT COMMENTARY: Ovarian function damage after chemotherapy and radiotherapy will impact on fertility and reproductive lifespan, but with great variability. Age at menopause has implications for the duration of estrogen deficiency, with its own adverse health consequences. This has led to identification of the key treatment and patient factors at the time of treatment, notably age and ovarian reserve that impact on post-treatment ovarian function. However, most studies have used outcome measures such as ongoing menses, or biomarkers such as anti-mullerian hormone (AMH), with few reporting on fertility or age at menopause

Breast Carcinoma in Young Women

OBJECTIVE: To estimate the incidence of breast carcinoma and survival in patients younger than 25 years old, and to describe presenting clinical signs and symptoms of breast cancer in this age group. METHODS: A population-based descriptive study and case review in Olmsted County, Minnesota, was conducted using the resources of the Rochester Epidemiology Project. Participants were Olmsted County girls and women younger than 25 years old with histopathologically confirmed breast carcinoma diagnosed between 1935 and 2005. Nonresidents who presented to a medical facility within Olmsted County during this time period were included in some portions of the analysis. Main outcome measures were age-adjusted incidence, 5-year survival, and clinical presentation of breast carcinoma in girls and women younger than 25 years of age. RESULTS: With four breast carcinomas observed in Olmsted County residents over 1,201,539 person-years, the annual age-adjusted incidence of breast cancer in this population was 3.2 per million (95% confidence interval, 0.1-6.2). All four cancers occurred in the 20- to 24-year age group (age-specific incidence, 16.2 per million). Eight additional cases of breast carcinoma were identified in nonresidents. Delay in diagnosis was common. All had at least one feature worrisome for an aggressive neoplasm identified in their clinical history, on physical examination or by imaging. CONCLUSION: Breast carcinoma in young women is very rare, associated with delayed diagnosis, and usually associated with concerning features requiring biopsy. LEVEL OF EVIDENCE: III

Literature Review of Benign Mullerian Papilloma Contrasted With Vaginal Rhabdomyosarcoma

STUDY OBJECTIVES: Benign müllerian papillomas of the genital tract are rare and, hence, can be mistaken for vaginal rhabdomyosarcoma on initial clinical review. This review of the literature will consolidate the previous cases of müllerian papilloma reported and looks for clues to differentiate the 2 entities. DESIGN AND SETTING: We provide a case report and literature review, with patients from a pediatric adolescent gynecology clinic in a tertiary center. METHODS: We conducted a search of English-language publications from 1951 (the first case report) until January 2014 by using the search words "Müllerian papilloma" and "prepubertal bleeding." References from previous published reports were also obtained for completeness. MAIN OUTCOME: Literature review of benign müllerian papilloma. RESULTS: Since 1951, 56 cases of müllerian papilloma were reported, including 4 cases at our institution. Comorbid conditions were found in 31.5% of cases (with 3 cases associated with mesenchymal tumors). The average length of time from onset of symptoms (primarily vaginal bleeding) to diagnosis was 6.7 months (range, 1 day to 3 years), with only 1 case diagnosed incidentally. Median age of presentation was 5 years (range, 1 day to 52 years). Most cases were localized and resected with ease. Histology reveals complex papillary lesions without cytologic atypia. CONCLUSION: Benign müllerian papilloma is distinguished from the more significant diagnosis of vaginal rhabdomyosarcoma by initial length of vaginal bleeding at presentation, lack of vaginal wall extension, ease of resection, and histopathology. This is compared with vaginal rhabdomyosarcoma which commonly exhibits both localized and distant spread

Prevalence and severity of dysmenorrhoea, and management options reported by young Australian women

BACKGROUND: Little is known about the severity of dysmenorrhoea and attitudes towards its management in young females. OBJECTIVE: The aim of this study was to evaluate the prevalence and severity of dysmenorrhoea in women aged 16-25 years. METHODS: Participants were recruited via targeted Facebook advertising and asked to complete an online questionnaire covering medications, menstruation and lifestyle-related themes. A follow-up questionnaire on dysmenorrhoea was also administered. RESULTS: The prevalence of dysmenorrhoea was 88% (n = 247, mean age 21.5 years, SD 2.6). Only 34% of participants reported consulting a healthcare provider about their pain, whereas 86% consulted other sources. Pain medication was used by 58% of the participants. Dysmenorrhoea was associated with interference with daily activities (P DISCUSSION: Dysmenorrhoea is highly prevalent among these women, with most indicating moderate to severe pain and a significant adverse impact on daily activities. Most women did not obtain information about dysmenorrhoea from healthcare providers, indicating the need for general practitioners to provide accurate information about dysmenorrhoea to young females