Occurrence of secondary insults during endovascular treatment of acute ischemic stroke and impact on outcome: the SIR-STROKE prospective observational study.

BACKGROUND: Neurological outcome after endovascular treatment (EVT) of acute ischemic stroke (AIS) may depend on both patient-specific and procedural factors. We hypothesized that altered systemic homeostasis might be frequent and affect outcome in these patients. The aim of this study was to analyze secondary insults during EVT of AIS and its association with outcome and anesthesiologic regimen. METHODS: This was a single-center prospective observational study on patients undergoing EVT for AIS under local anesthesia (LA), conscious sedation (CS), or general anesthesia (GA). Altered systemic parameters were recorded and quantified as secondary insults. The primary endpoint was to evaluate number, duration, and severity of secondary insults during EVT. Secondary endpoints were to analyze association of insults with modified Rankin Scale at 90 days and anesthesiologic regimen. RESULTS AND CONCLUSIONS: One hundred twenty patients were enrolled. Overall, 78% of patients experienced at least one episode of hypotension, 21% hypertension, 54% hypoxemia, 16% bradycardia, and 13% tachycardia. In patients monitored with capnometry, 70% experienced hypocapnia and 21% hypercapnia. LA was selected in 24 patients, CS in 84, and GA in 12. Hypotension insult was more frequent during GA than LA and CS (p = 0.0307), but intraprocedural blood pressure variation was higher during CS (p = 0.0357). Hypoxemia was more frequent during CS (p = 0.0087). Proportion of hypotension duration was higher in unfavorable outcome but secondary insults did not remain in the final model of multivariable analysis. Secondary insults occurred frequently during EVT for AIS but the main predictors of outcome were age, NIHSS at admission, and prompt and successful recanalization.

Multifocal Invasive Ductal Cancer: Distinguishing Independent Tumor Foci From Multiple Satellites.

Patients with multifocal breast cancers (MBCs) have a poorer prognosis than patients with unifocal breast cancers. Studies have attributed this to tumor size underestimation in MBC. An alternative hypothesis is that some MBCs behave in a fashion analogous to the "satellite" and "in-transit metastasis" observed in melanoma and, thereby, are more clinically aggressive. We identified 79 cases of MBC, which we classified into 2 groups: study cases defined as ≥2 morphologically similar tumor foci with ≥1 focus without in situ carcinoma (n = 21); and a control group defined as ≥2 morphologically similar or dissimilar foci with associated in situ carcinoma in all foci (n = 58). The odds of being a study case is 1.86 (95% confidence interval [CI] 1.26-2.74) times greater per unit increase in number of tumor foci (median of 4 tumor foci; P = .002). Study cases were 73.33 (95% CI = 8.91-603.16) times more likely to have lymphovascular invasion (LVI) and 14.72 (95% CI = 4.37-49.61) times more likely to have nodal metastases. Grade I/II tumors were 0.20 (95% CI = 0.07-0.59) times less likely to be study cases. There was a significant positive interaction ( P < 0.001) indicated by the relationship of LVI status and nodal status with the study case and control group. We conclude that there is a subset of MBC that presents with more numerous tumor foci and a higher rate of nodal metastasis. The aggressive behavior of these cases may be attributed to their proclivity for LVI.

Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis.

OBJECTIVES: Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. METHODS: In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in µg/puff: 2-4 years: 44, 5-11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4-12 months, 13-24 months, and >24 months. Growth and adverse effects were monitored. RESULTS: We enrolled 54 patients, 80% male, median age 6.5 years (range 2-17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4-12 months: 1.75, 13-24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4-12 months: 50, 13-24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4-12 months: 0.17, 13-24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4-12 months: 0.11, 13-24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves. CONCLUSIONS: We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

Donor-recipient height ratio and outcomes in pediatric heart transplantation.

Height matching in pediatric HTx has been proposed as a superior method of evaluating graft size, but no studies have examined survival advantage for height-matched donor-recipient pairs. We hypothesized that in pediatric patients with DCM, an oversized donor improves survival and aimed to define the optimal height ratio in this patient group. Pediatric primary HTx recipients with DCM between 10/89 and 09/12 were identified in the OPTN database. Patients were stratified into three donor-recipient height and weight ratio categories. One- and five-yr survival was compared using Kaplan-Meier analysis and HRs were computed. A total of 2133 children with DCM who underwent HTx during the study period were included. Unadjusted one-yr survival was worse for DRHR <0.87 (HR, 2.15 [95% CL, 1.30, 3.53]; p < 0.01). This difference was not present at five yr post-HTx or when stratified by weight. After adjustment for other risk factors affecting transplant survival, height matching was no longer significant. Although height matching appears to predict short-term survival better than weight in pediatric HTx recipients with DCM, other factors play a more important role as height matching loses significance in multivariate analysis.

Risk of New or Recurrent Cancer in Patients With Inflammatory Bowel Disease and Previous Cancer Exposed to Immunosuppressive and Anti-Tumor Necrosis Factor Agents.

BACKGROUND & AIMS: Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. METHODS: We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti-tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test. RESULTS: During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer (P = .14) or type of incident cancer (P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09-1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26-1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54-2.15) or time to subsequent cancer between study arms (P = .22). CONCLUSION: On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.

Time to prerandomization monthly seizure count in perampanel trials: A novel epilepsy endpoint.

OBJECTIVE: To determine whether a novel endpoint of time to prerandomization monthly seizure count could be used to differentiate efficacious and nonefficacious therapies in clinical trials of new add-on antiepileptic drugs (AEDs). METHODS: This analysis used data from 3 randomized, double-blind, placebo-controlled phase III trials of perampanel as an add-on therapy in patients with epilepsy who were experiencing refractory partial seizures: studies 304 (ClinicalTrials.gov identifier NCT00699972), 305 (NCT00699582), and 306 (NCT00700310). Time to prerandomization monthly seizure count was evaluated post hoc for each trial, and findings were compared with the original primary outcomes (median percent change in seizure frequency and 50% responder rate). Outcomes were assessed for all partial-onset seizures, secondarily generalized (SG) tonic-clonic seizures only, and complex partial plus SG (CP + SG) seizures. RESULTS: Perampanel 4-12 mg significantly prolonged median time to prerandomization monthly seizure count, generally by more than 1 week, compared with placebo, across all 3 studies, consistent with the original primary outcomes. Analysis of SG seizures only, and CP + SG seizures, also indicated a significantly prolonged median time to prerandomization monthly seizure count with perampanel 8 mg and 12 mg compared with placebo. CONCLUSIONS: Time to prerandomization monthly seizure count is a promising novel alternative to the standard endpoints of median percent change in seizure frequency and 50% responder rates used in trials of add-on AEDs. Use of this endpoint could reduce exposure to placebo or ineffective treatments, thereby facilitating trial recruitment and improving safety.

Pediatric cardiac retransplantation: Waitlist mortality stratified by age and era.

BACKGROUND: Waitlist mortality among children listed for primary heart transplant (HTx) has been well characterized, whereas limited data exist for cardiac retransplantation (CRTx) after pediatric primary HTx. We sought to characterize the population listed for CRTx and to determine the factors that affect waitlist mortality. METHODS: All individuals listed for CRTx >1 year after pediatric primary HTx between October 1, 1987, and October 14, 2012 were identified in the Organ Procurement and Transplantation Network database. Baseline characteristics and waitlist mortality were compared between age groups (< 11 years, 11-18 years, and > 18 years) and during 3 successive eras (1987-1999, 1999-2006, and 2006-2012). RESULTS: The cohort comprised 632 patients who were listed for CRTx > 1 year after pediatric primary HTx. Median age was 4 years at primary HTx and 14 years at relisting. Median time from primary HTx to relisting was 7.3 years. Median waiting time was 75.3 days. Overall mortality was 25.2% (159 of 632). The most frequent relisting diagnosis was related to graft vasculopathy (62.5%). The leading causes of death were chronic rejection and vasculopathy (52%). Waitlist mortality significantly decreased after 2006 (31% vs 17%; p < 0.01), despite a relatively constant CRTx rate (67% vs 65%). Univariate analysis showed era, age, listing status, and life support (mechanical circulatory support device, extracorporeal membrane oxygenation, mechanical ventilation) were significant predictors of mortality. Multivariate analyses showed that later era (2006-2012), ages 11 to 18 years, and United Network of Organ Sharing listing status 2 predicted decreased mortality, whereas life support increased mortality. CONCLUSIONS: Waitlist mortality for CRTx in children and young adults has decreased by almost 50% over time. Individuals relisted as adults have increased waitlist mortality.

Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma.

BACKGROUND: Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms. METHODS: This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants. RESULTS: Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p=0.005) and cough (p<0.001), episodes of rhinitis (p=0.04) and tracheitis (p=0.01), asthma attacks (p<0.001), episodes of pneumonia (p<0.001) and hospitalizations (p=0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR]=1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR=0.50; 95% CI, 0.31 -0.80). An increase of 10 µg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR]=1.08, 95% CI: 1.00-1.17 for PM10; continuous RR=1.08, 95% CI: 1.01-1.17 for NO2). CONCLUSIONS: There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

The weekend effect in patients hospitalized for upper gastrointestinal bleeding: a single-center 10-year experience.

OBJECTIVE: This study was conducted to assess the possible weekend effect in patients with upper gastrointestinal bleeding (UGIB) on the basis of a 10-year single-center experience in Serbia. MATERIALS AND METHODS: A retrospective analysis of hospital records in the University Clinic 'Dr Dragisa Misovic-Dedinje', Belgrade, Serbia, from 2002 to 2012 was conducted. Patients admitted for UGIB were identified, and data on demographic characteristics, symptoms, drug use, alcohol abuse, diagnosis and treatment were collected. Univariate and multivariate logistic regression were used to assess the association between weekend admission and the occurrence of rebleeding and in-hospital mortality. RESULTS: Analyses included 493 patients. Rebleeding occurred significantly more frequently on weekends (45.7 vs. 32.7%, P=0.004). Weekend admission [odds ratio (OR)=1.78; 95% confidence interval (CI): 1.15-2.74], older age (OR=1.02; 95% CI: 1.00-1.03), and the presence of both melaena and hematemesis (OR=2.29; 95% CI: 1.29-4.07) were associated with the occurrence of rebleeding. No difference between weekend and weekday admissions was observed for the in-hospital mortality rate (6.9% vs. 6.0%, P=0.70). Older age (OR=1.14; 95% CI: 1.08-1.20), presentation with melaena and hematemesis (OR=4.12; 95% CI: 1.56-10.90) and need for surgical treatment (OR=5.16; 95% CI: 1.61-16.53) were significant predictors of all-cause mortality. Patients with nonvariceal bleeding had significantly higher rebleeding rates on weekends (44 vs. 32.3%, P=0.013). CONCLUSION: There was no significant weekend effect in the mortality of patients admitted for UGIB, irrespective of the source of bleeding. Increased attention to older patients presenting with a more severe clinical picture is needed to prolong survival and prevent rebleeding.

A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases.

Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.

Dietary glycemic index, glycemic load, and the risk of endometrial cancer: a case-control study and meta-analysis.

Carbohydrates and the dietary glycemic index (GI) influence insulin secretion and insulin-like growth factors, and may exert relevant effects on obesity and diabetes, both of which are important risk factors for endometrial cancer. We studied the association between dietary GI and glycemic load (GL) and endometrial cancer using data from an Italian case-control study. This included 454 women with histologically confirmed endometrial cancer and 908 controls admitted to the same hospitals for acute, non-neoplastic conditions. Multivariate odds ratios were obtained after allowance for major potential confounding factors, including noncarbohydrate energy intake. We updated a meta-analysis on this issue, including a recent US cohort study, which contributed about a quarter of all cases, besides our case-control study. In the case-control study, the odds ratios of endometrial cancer for the highest versus the lowest quintile were 1.03 [95% confidence interval (CI): 0.67-1.58] for GI and 1.01 (95% CI: 0.64-1.61) for GL. No heterogeneity was found across the strata of diabetes and other selected covariates. The summary risk estimate of endometrial cancer for the highest versus the lowest GI level, obtained from the meta-analysis, was 1.09 (95% CI: 0.92-1.29). The corresponding risk estimate for GL was 1.19 (95% CI: 1.06-1.34). The case-control study showed no association between dietary GI and GL and the risk of endometrial cancer overall and in the strata of relevant covariates, whereas the meta-analysis supported an increased risk for high GL, but not GI.

A meta-analysis of coffee and tea consumption and the risk of glioma in adults.

BACKGROUND: Coffee contains many compounds, including antioxidants, which could prevent cancerogenesis, and coffee has been related with lower incidence of cancer at several sites. Tea is also rich in antioxidants, mainly polyphenols. To provide a quantitative overall estimate on the relation between coffee and tea consumption and glioma, we combined all published data, using a meta-analytic approach. METHODS: In September 2012, a bibliography search was carried out in both PubMed and Embase to identify observational studies providing quantitative estimates on the issue. Pooled estimates of the relative risks (RR) and the corresponding 95 % confidence intervals (CI) were calculated using random-effects models. RESULTS: Six studies (four cohort and two case-control studies) were available for meta-analysis, for a total of about 2100 cases. The summary RRs and 95 % CIs of glioma for drinkers versus non/occasional drinkers were 0.96 (95 % CI: 0.81-1.13) for coffee and 0.86 (95 % CI: 0.78-0.94) for tea, with no heterogeneity between studies. When we compared the highest versus the lowest categories of consumption, the RRs were 1.01 (95 % CI: 0.83-1.22) for coffee, 0.88 (95 % CI: 0.69-1.12) for tea, and 0.75 (95 % CI: 0.54-1.05) for coffee plus tea. CONCLUSIONS: This meta-analysis, although based on few studies, suggests a lack of association between coffee intake and glioma risk, and a tendency, if any, to a lower risk for tea and coffee plus tea drinkers.