Microglia as a cellular target of diclofenac therapy in Alzheimer's disease.

Alzheimer's disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit. More recently, protective effects of diclofenac and NSAIDs in the fenamate group have been reported. Diclofenac decreased the frequency of AD significantly compared to other NSAIDs in a large retrospective cohort study. Diclofenac and fenamates share similar chemical structures, and evidence from cell and mouse models suggests that they inhibit the release of pro-inflammatory mediators from microglia with leads to the reduction of AD pathology. Here, we review the potential role of diclofenac and NSAIDs in the fenamate group for targeting AD pathology with a focus on its potential effects on microglia.

Increased thymus weight in sudden infant death syndrome compared to controls: The role of sub-clinical infections.

OBJECTIVE: The goal of the present investigation is to analyze thymus, brain, heart, liver, and kidney weights in SIDS victims compared to controls. BACKGROUND: Epidemiologic risk factors for SIDS (eg, male gender, genetic, obstetric, environmental, smoke exposure, nonbreastfeeding, etc.) are consistent with an infectious process underlying many of these deaths. METHODS: Data from autopsy reports on 585 SIDS victims and comparison deaths (n = 294 control, n = 291 SIDS) were analyzed. Cases were obtained from Australia (n = 184 controls, n = 98 SIDS) and Russia (n = 122 controls, n = 181 SIDS). Log10 transform of thymus and other organ weights was computed because variables were skewed. Multivariate analysis of variance (MANOVA) of standardized log values were age-adjusted by multivariate analysis of covariance (MANCOVA). The standardized log10 thymus residual adjusted for age, brain and liver weights was computed for the final analysis. RESULTS: After controlling for age by MANCOVA, thymus, body, brain and liver weights were significantly higher among SIDS compared to non-SIDS victims. The largest difference as between covariate-adjusted log10 non-SIDS thymus weight differed (mean = 1.423, 95% CI: 1.393-1.452) and log10 non-SIDS thymus weight (mean = 1.269, 95% CI: 1.243-1.294) were significantly different (P < .0001). Heart weight was significantly lower in SIDS victims. DISCUSSION: When adjusted for confounders (age, body, and organ weights), SIDS victims have a significantly heavier thymus and brain compared to non-SIDS controls who died of trauma. This finding supports previously published studies that link infection to SIDS deaths.

Diclofenac reduces the risk of Alzheimer's disease: a pilot analysis of NSAIDs in two US veteran populations.

BACKGROUND: Our aim was to determine whether specific nonsteroidal anti-inflammatory (NSAID) agents are associated with a decreased frequency of Alzheimer's disease (AD). MATERIALS AND METHODS: Days of drug exposure were determined for diclofenac, etodolac, and naproxen using US Department of Veterans Affairs (VA) pharmacy transaction records, combined from two separate VA sites. AD diagnosis was established by the International Classification of Diseases, ninth revision (ICD-9)/ICD-10 diagnostic codes and the use of AD medications. Cox regression survival analysis was used to evaluate the association between AD frequency and NSAID exposure over time. Age at the end of the study and the medication-based disease burden index (a comorbidity index) were used as covariates. RESULTS: Frequency of AD was significantly lower in the diclofenac group (4/1431, 0.28%) compared with etodolac (328/14,646, 2.24%), and naproxen (202/12,203, 1.66%). For regression analyses, naproxen was chosen as the comparator drug, since it has been shown to have no effect on the development of AD. Compared with naproxen, etodolac had no effect on the development of AD, hazard ratio (HR) 1.00 [95% confidence interval (CI): 0.84-1.20, p = 0.95]. In contrast, diclofenac had a significantly lower HR of AD compared with naproxen, HR 0.25 (95% CI: 0.09-0.68, p <0.01). After site effects were controlled for, age at end of the study (HR = 1.08, 95% CI: 1.07-1.09, p <0.001) was also found to influence the development of AD, and the medication-based disease burden index was a strong predictor for AD, HR 5.17 (95% CI: 4.60-5.81) indicating that as comorbidities increase, the risk for AD increases very significantly. CONCLUSION: Diclofenac, which has been shown to have active transport into the central nervous system, and which has been shown to lower amyloid beta and interleukin 1 beta, is associated with a significantly lower frequency of AD compared with etodolac and naproxen. These results are compelling, and parallel animal studies of the closely related fenamate NSAID drug class.

Coronavirus Disease 2019 Catheterization Laboratory Survey.

Background The coronavirus disease 2019 pandemic is expected to affect operations and lifestyles of interventional cardiologists around the world in unprecedented ways. Timely gathering of information on this topic can provide valuable insight and improve the handling of the ongoing and future pandemic outbreaks. Methods and Results A survey instrument developed by the authors was disseminated via e-mail, text messaging, WhatsApp, and social media to interventional cardiologists between April 6, 2020, and April 11, 2020. A total of 509 responses were collected from 18 countries, mainly from the United States (51%) and Italy (36%). Operators reported significant decline in coronary, structural heart, and endovascular procedure volumes. Personal protective equipment was available to 95% of respondents; however FIT-tested N95 or equivalent masks were available to only 70%, and 74% indicated absence of coronavirus disease 2019 pretesting. Most (83%) operators expressed concern when asked to perform cardiac catheterization on a suspected or confirmed coronavirus disease 2019 patient, primarily because of fear of viral transmission (88%). Although the survey demonstrated significant compliance with social distancing, high use of telemedicine (69%), and online education platforms (80%), there was concern over impending financial loss. Conclusions Our survey indicates significant reduction in invasive procedure volumes and concern for viral transmission. There is near universal adoption of personal protective equipment; however, coronavirus disease 2019 pretesting and access to FIT-tested N95 masks is suboptimal. Although there is concern over impending financial loss, substantial engagement in telemedicine and online education is reported.

Randomized control trial comparing the effect of cilostazol and aspirin on changes in carotid intima-medial thickness.

Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetes (T2D) patients. However, the efficacy and usefulness of antiplatelet drugs on the progression of carotid intima-media thickness (IMT), a marker for evaluating early atherosclerotic vascular disease, has not been analyzed. We conducted a prospective, randomized, open, 36-month trial comparing cilostazol vs. aspirin. A total of 415 T2D patients (age range 38-83 years; 206 females) without macrovascular complications were randomized to either an aspirin (100 mg/day) or cilostazol (200 mg/day) treatment. Patients underwent B-mode ultrasonography annually to assess the IMT and serum levels of inflammatory markers were measured before and after each treatment. Potential confounders were statistically adjusted, and included lipid profiles, HbA1c, body mass index, waist circumference, anti-hypertensive and statin medications. The decrease in mean left, maximum left, mean right and maximum right IMT were significantly greater with cilostazol compared with aspirin (- 0.094 ± 0.186 mm vs. 0.006 ± 0.220 mm, p < 0.001; - 0.080 ± 0.214 mm vs. 0.040 ± 0.264 mm, p < 0.001; - 0.064 ± 0.183 mm vs. 0.004 ± 0.203 mm, p = 0.015; - 0.058 ± 0.225 mm vs. 0.023 ± 0.248 mm, p = 0.022, respectively). And these differences remained significant after adjustment of potential confounders. Compared with aspirin, cilostazol treatment was associated with significantly increased HDL cholesterol (p = 0.039) and 25-hydroxy vitamin D levels (p = 0.001). Cilostazol treatment was associated with significantly lowered IMT in T2D patients compared to aspirin, independent of conventional cardiovascular risk factors. Cilostazol may inhibit plaque formation and have beneficial effects on atherosclerosis through vasodilatory and antiplatelet effects.

Geographic variation in the growth status of indigenous school children and youth in Mexico.

OBJECTIVE: To analyze variation in the growth status of indigenous children and youth attending bilingual schools, escuelas albergues, for the indigenous population in México. MATERIALS AND METHODS: The children and youth attended escuelas albergues in 1,009 localities in 21 Mexican states in 2012. Heights and weights of 31,448 boys and 27,306 girls 6-18 years of age were measured by trained staff at each school; the BMI was calculated. The students were divided into five geographic regions for analysis: North, Central, South-Gulf, South-Pacific, and South-Southeast. Growth status was compared to United States reference percentiles (P). RESULTS: Mean heights of children and youth from the five regions varied between P10 and P5 of the reference until about 13 years (girls) and 14 years (boys); subsequently, heights were ≤P5. Mean weights in both sexes were at P25 of the reference between 6 and 12 years, and then varied between P25 and P10 in boys and were ≥P25 in girls. Given the elevated weights relative to heights compared to the reference, mean BMIs of indigenous boys and girls were at or above the reference medians. Children and youth in the North and Central regions were, on average, taller than those in the South-Pacific and South-Southeast regions, while heights of those in the South-Gulf region were generally intermediate. In contrast, mean weights and BMIs differed negligibly among the regions. CONCLUSIONS: The geographic gradient in heights of indigenous children and youth was consistent with a north-to-south pattern noted among indigenous adults in studies spanning 1898 through 2013. Variation in height among children and youth likely reflected ethnic-specific and geographic variation interacting with economic and nutritional factors.

Secular trends are associated with the demographic and epidemiologic transitions in an indigenous community in Oaxaca, Southern Mexico.

OBJECTIVE: To test the hypothesis that secular changes in body size and age at menarche are related to the demographic and epidemiologic transitions in an indigenous community in Oaxaca, southern Mexico. METHODS: Data were derived from surveys of a Zapotec-speaking community conducted between 1968 and 2000. Segmented linear regressions of height, weight, BMI and recalled age at menarche on year of birth in cohorts of adults born before and after the demographic transition were used to evaluate secular changes. Corresponding comparisons of body size (MANCOVA controlling for age) and age at menarche (status quo, probit analysis) were done for samples of children and adolescents born before and after the epidemiological transition. RESULTS: Height and weight increased in adults born after the demographic transition (mid-1950s), and especially in children and adolescents born after the epidemiological transition (mid-1980s). Age at menarche also decreased significantly in women born after the demographic transition, but at a more rapid estimated rate in adolescents born after the epidemiological transition. Secular gains in body weight were proportional to those for height among children and adolescents, but adults, males more so than females, gained proportionally more weight. CONCLUSIONS: The secular trend in height in adults of both sexes was associated with the decade of the demographic transition in the mid-1950s. Significant secular gains in size attained and age at menarche occurred in children and youth born after the epidemiologic transition which likely reflected improved health and nutritional conditions since the mid-1980s.

Natural selection and type 2 diabetes-associated mortality in an isolated indigenous community in the valley of Oaxaca, southern Mexico.

OBJECTIVE: This study tests the hypothesis that natural selection is associated with type 2 diabetes (T2D)-associated mortality and fertility in a rural isolated Zapotec community in the Valley of Oaxaca, southern Mexico. PARTICIPANTS AND METHODS: Mortality data and related demographic and genealogic information were linked with data for fertility, prereproductive mortality and family history of mortality attributed to T2D. Physician verified T2D mortality (n = 27) between 1980 and 2009 and imputed T2D (n = 70) from cardiovascular mortality (68% random sample) and renal failure (44% random sample). Bootstrapping was used to obtain a robust variance estimate in survival analysis and multivariate analysis of variance. RESULTS: Estimated maximum natural selection by Crow's Index occurred circa 1930 and was relaxed after this time in the study population. Cox-regression survival analysis of T2D mortality with covariates (family history of T2D, cardiovascular disease, renal failure) indicated a significant hazard ratio (HR = 5.95, 95% CI: 1.38-25.67, p < .008) for the increase in T2D in 2000 to 2009. Survival analysis of imputed T2D resulted in a significant HR of 2.03 (95% CI: 1.08-3.85, p = .01) for the increase in T2D in the 2000 to 2009 cohort (reference group: 1980-1989). Mean number of live born offspring was lower among T2D (n = 27, 4.04 ± 3.85 SD) compared to non-T2D (n = 199, 5.30 ± 3.48) groups (p < .08). Mean number of live born offspring was lower (p = .003) among imputed T2D compared to non-T2D groups (4.10 ± 3.44 vs. 5.62 + 3.50). DISCUSSION: T2D-associated mortality increased in frequency as natural selection decreased, and favored offspring survival of non-T2D descedants. The results indicated statistically significant directional selection against T2D and imputed T2D to this population isolate.

Stent and Non-Stent Based Outcomes of Infrainguinal Peripheral Artery Interventions From the Multicenter XLPAD Registry.

BACKGROUND: There are limited data regarding contemporary use of stent and non-stent based treatment strategies of infrainguinal peripheral artery disease (PAD). METHODS: We analyzed data from the ongoing multicenter XLPAD registry between July 2005 and October 2013 to report on the use of non-stent (atherectomy ± balloon angioplasty) and stent-based treatment of superficial femoral artery (SFA), popliteal, and below-the-knee (BTK) vessels in contemporary clinical practice. RESULTS: A total of 584 interventions (SFA, 82.5%; popliteal, 7.2%; BTK, 9.9%) were performed in 372 patients (mean age, 63.2 years; diabetes mellitus, 57.7%; Rutherford category 1-3, 73.5%; Rutherford category 4-6, 20.1%). Stents were deployed in 389 lesions (66.6%; SFA, 90.5%; popliteal, 5.1%; BTK, 4.1%) and non-stent strategy (atherectomy, 49%) in 195 lesions (33.4%; SFA, 66.7%; popliteal, 11.3%; BTK, 21.5%). In the stent and non-stent groups, mean lesion lengths were 133.9 mm and 86.0 mm (P<.001), chronic total occlusions (CTOs) constituted 63.0% and 49.7% (P<.01), and restenotic lesions were 12.6% and 32.3% (P<.001), respectively. At a mean follow-up of 260 ± 130 days, in the stent and non-stent treated patients, all-cause mortality was 4.3% and 3.5% (P=.65), clinically indicated repeat revascularization was 17.5% and 14.9% (P=.42), and amputation was 4.6% and 9.2% (P<.01), respectively. SFA lesion location, long lesion length, and CTO were associated with the use of stents. Advanced Rutherford class was associated with a non-stent treatment strategy. CONCLUSION: The majority of endovascular peripheral arterial interventions are performed in the SFA; most include a CTO and in patients with diabetes mellitus. Operators use stents to primarily treat complex SFA lesions with overall similar outcomes, except for fewer amputations compared to a non-stent strategy.

Greater sensitivity to drought accompanies maize yield increase in the U.S. Midwest.

A key question for climate change adaptation is whether existing cropping systems can become less sensitive to climate variations. We use a field-level data set on maize and soybean yields in the central United States for 1995 through 2012 to examine changes in drought sensitivity. Although yields have increased in absolute value under all levels of stress for both crops, the sensitivity of maize yields to drought stress associated with high vapor pressure deficits has increased. The greater sensitivity has occurred despite cultivar improvements and increased carbon dioxide and reflects the agronomic trend toward higher sowing densities. The results suggest that agronomic changes tend to translate improved drought tolerance of plants to higher average yields but not to decreasing drought sensitivity of yields at the field scale.

Significance of an abnormal ankle-brachial index in patients with established coronary artery disease with and without associated diabetes mellitus.

An abnormal ankle-brachial index (ABI) is associated with higher risk for future cardiovascular (CV) events; however, it is unknown whether this association is true in patients with established coronary artery disease (CAD) and associated diabetes mellitus (DM). We evaluated 679 patients with stable CAD enrolled in the Excellence in Peripheral Arterial Disease and Veterans Affairs North Texas Healthcare System peripheral arterial disease databases. ABI and 12-month major adverse CV events (MACEs, a composite of all-cause death, nonfatal myocardial infarction, need for repeat coronary revascularization, and ischemic stroke) were assessed. Cox proportional hazard models were used to assess the association of ABI and DM with subsequent CV events. An abnormal ABI (<0.9 or >1.4) was present in 72% of patients with stable CAD and 68% had DM. Using patients without DM and normal ABI as reference, the adjusted hazard ratio for 12-month MACE was 1.7 (95% confidence interval [CI] 0.71 to 4.06) for patients with DM and normal ABI; 2.03 (95% CI 0.83 to 4.9) for patients without DM with abnormal ABI; and 4.85 (95% CI 2.22 to 10.61) for patients with DM and abnormal ABI. In conclusion, in patients with stable CAD, an abnormal ABI confers an incremental risk of MACE in addition to DM and traditional CV risk factors.

Thinness, overweight and obesity in indigenous youth in Oaxaca, 1970 and 2007.

OBJECTIVE: To evaluate change in body mass index (BMI) and weight status of indigenous youth in Oaxaca between the 1970s and 2007. MATERIALS AND METHODS: Heights and weights were measured in cross-sectional samples of school children 6-14 years in the 1970s (2 897) and 2007 (4 305); BMI was calculated. International Obesity Task Force cutoffs for weight status were used. BMI and prevalence of severe and moderate thinness, overweight and obesity were compared by year. RESULTS: BMI increased significantly across time. Primary change in weight status occurred in overweight, 1970s, <2%; 2007, 7 to 12%. Little change occurred in thinness (<2%) and obesity (≤ 1%) in both surveys, except in children 6-9 years (obesity=4% in 2007). CONCLUSION: BMI and prevalence of overweight increased across all ages from the 1970s to 2007, but children 6-9 years appeared to be more at risk for obesity than youth 10-14 years. Prevalence of thinness was unchanged.

Altitude effects on growth of indigenous children in Oaxaca, Southern Mexico.

The effect of altitude of residence on the growth status of 11,454 indigenous school children 6-14 years of age in Oaxaca, southern Mexico, was examined. Indicators of living conditions (human development index [HDI], index of community nutritional risk [INR], index of marginalization [IM], index of relative isolation [II]) were regressed on z-scores for height, weight and BMI, and the residuals were regressed on altitude of residence (km). Independent of other environmental conditions, altitude negatively affected height by approximately -0.07 z-scores per kilometer altitude above sea level. The estimated average decrease in stature was 0.92 cm per kilometer elevation. BMI was significantly increased, 1.2 units per kilometer elevation, consistent with earlier studies of growth status and altitude. In contrast, weight was not affected by altitude of residence. Approximately 36% of the reduction in height and 54% of the increase in BMI were due to altitude effects; the remaining changes in height and BMI were associated with environmental factors reflected in the indices of community well-being considered.

Thinness, overweight and obesity in indigenous youth in Oaxaca, 1970 and 2007 / Delgadez, sobrepeso y obesidad en jóvenes indígenas en Oaxaca, 1970 y 2007

Objective. To evaluate change in body mass index (BMI) and weight status of indigenous youth in Oaxaca between the 1970s and 2007. Materials and methods. Heights and weights were measured in cross-sectional samples of school children 6-14 years in the 1970s (2 897) and 2007 (4 305); BMI was calculated. International Obesity Task Force cutoffs for weight status were used. BMI and prevalence of severe and moderate thinness, overweight and obesity were compared by year. Results. BMI increased significantly across time. Primary change in weight status occurred in overweight, 1970s, <2%; 2007, 7 to 12%. Little change occurred in thinness (<2%) and obesity (≤1%) in both surveys, except in children 6-9 years (obesity=4% in 2007). Conclusion. BMI and prevalence of overweight increased across all ages from the 1970s to 2007, but children 6-9 years appeared to be more at risk for obesity than youth 10-14 years. Prevalence of thinness was unchanged.

Objetivo. Evaluar el cambio en el índice de masa corporal (IMC) y el estatus de peso entre 1970 y 2007 en jóvenes indígenas de Oaxaca. Material y métodos. Se midieron estatura y peso de series transversales de escolares indígenas en edades de 6 a 14 años en 1970 (2 897) y en 2007 (4 305), se calculó el IMC y se emplearon los puntos de corte del International Obesity Task Force para el estatus de peso. El IMC y la prevalencia de delgadez, sobrepeso y obesidad en 1970 y 2007 fueron comparados. Resultados. El IMC aumentó de manera significativa entre 1970 y 2007. Los cambios más importantes fueron en sobrepeso, <2% en 1970 a 7-12% en 2007. Hubo poco cambio en la delgadez (<2%) y la obesidad (≤1%) en ambas investigaciones, excepto en niños de 6 a 9 años (4% en 2007). Conclusión. El IMC y la prevalencia de sobrepeso aumentaron a través de todas las edades de los años 1970 a 2007, pero los niños de 6 a 9 años parecen tener un mayor riesgo para la obesidad que los jóvenes de 10 a 14 años. La frecuencia de la delgadez fue igual.

Weight status of indigenous youth in Oaxaca, southern Mexico: concordance of IOTF and WHO criteria.

PURPOSE: To compare the prevalence of thinness, overweight and obesity with IOTF and WHO criteria among indigenous school youth from the state of Oaxaca, southern Mexico. METHODS: The sample included 11 454 indigenous youth (6216 boys, 5238 girls) 6-14 years of age. Heights and weights were measured in 2007 by trained staff. BMIs were calculated and classified as severely thin, moderately thin, normal, overweight or obese using age- and sex-specific IOTF and WHO cut-offs. Prevalence, percentage agreement between classifications, Spearman rank order correlations and Kappa coefficients were calculated. RESULTS: Prevalence of overweight and obesity was higher with WHO than IOTF criteria, while prevalence of severe and moderate thinness did not appreciably differ between criteria. Weight status with the two criteria was discordant in 839 boys (13.5%) and 383 girls (7.3%) and more often for overweight and obesity than thinness. Percentage agreement, correlations and Kappa coefficients were moderate-to-high and were higher in girls than boys. CONCLUSION: Prevalence of overweight and obesity among indigenous youth in Oaxaca was higher with WHO than IOTF criteria, whereas prevalence of severe and moderate thinness was similar. Differences in estimates for overweight and obesity have implications for surveillance.

Growth and weight status of rural Texas school youth.

CONTEXT: Evidence indicates higher prevalence of obesity in rural American youth. The present study evaluates the growth status and estimates the prevalence of overweight and obesity among rural school children in Texas. METHODS: Heights and weights were measured in a sample of 1,084 school youth (545 males, 539 females) 5-19 years of age, in rural north central Texas in 2010. body mass index (BMI) was calculated. Growth status was plotted relative to US reference data. Weight status (underweight/thin, overweight, and obesity) was classified relative to age- and sex-specific Centers for Disease Control (CDC) and International Obesity Task Force (IOTF) criteria. Concordance of classifications was evaluated. RESULTS: Mean heights of the rural children approximated reference medians, while median weights exceeded reference medians and approximated 75th percentiles with increasing age. Median BMIs of boys and girls were below the 75th percentiles except among late adolescent girls. Prevalence of underweight/thinness was low (<4%). Overweight approximated 20% among boys 6-11 years and 16% among boys 12-19 years with CDC criteria; the opposite was apparent for obesity, 6-11 years, 16%, and 12-19 years, 20%. Approximately, equal percentages of boys in both age groups were classified overweight (∼21-22%) with IOTF criteria, but almost twice as many older (15%) than younger (8%) boys were classified obese. Overweight was less prevalent (∼5%) but obesity more prevalent (∼5%) with CDC compared to IOTF criteria, but both were less prevalent among younger than older girls. CONCLUSION: Prevalence of overweight and obesity among rural Texas school youth was comparable to national estimates for 2007-2008. The results highlight a need for programs aimed at preventing unhealthy weight gain and/or weight reduction given the tendency of obesity to track from childhood into adulthood and potentially negative health consequences of obesity. Am. J. Hum. Biol., 2013. © 2012 Wiley Periodicals, Inc.

Influence of chronic total occlusions on coronary artery bypass graft surgical outcomes.

BACKGROUND: Presence of epicardial coronary artery chronic total occlusion (CTO) predicts higher referral rates for coronary bypass graft surgery (CABG). However, the impact of coronary artery CTO on CABG outcomes has never been systematically studied. METHOD: We examined one-year outcomes in 605 consecutive Veterans, discharged post-CABG between June 2005 and December 2008. RESULTS: A coronary CTO was present in 256 patients (42%), predominantly (48.3%) in the right coronary artery distribution. Baseline clinical characteristics and medical therapy were similar in patients with and without a coronary CTO. A single CTO was present in 73.8%, and 26.2% patients had multiple CTO. All left anterior descending coronary artery CTO were successfully bypassed, as were >92% in left circumflex and right coronary arteries and 85% CTO in multiple coronary artery distributions. During the mean follow-up of 348.9 ± 4.5 days, incidence of all-cause death and myocardial infarction were similar in both groups (7.1% in CTO group and 7.4% in non-CTO group; p = 0.97). CTO >20 mm in length constituted 74.9% and >40 mm 37.8%. One-year survival post-CABG was significantly lower in patients with CTO lengths >40 mm compared to ≤20 mm (p = 0.04). CTO >40 mm was an independent predictor of post-CABG mortality controlling for age, number of CTO, comorbid diseases, clopidogrel use, severity of coronary artery disease, renal failure, and left ventricular ejection fraction. CONCLUSION: CABG achieves high success in grafting epicardial coronary vessels with CTO; however, presence of long coronary CTO (>40 mm) is an independent predictor of post-CABG survival.

Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents for revascularization of peripheral arterial segments: the COBRA trial.

OBJECTIVES: The purpose of this study is to compare post-dilation strategies of nitinol self-expanding stents implanted in the superficial femoral artery of diabetic patients with peripheral arterial disease. BACKGROUND: Endovascular treatment of superficial femoral artery disease with nitinol self-expanding stents is associated with high rates of in-stent restenosis in patients with diabetes mellitus. METHODS: We conducted a prospective, multicenter, randomized, controlled clinical trial of diabetic patients to investigate whether post-dilation of superficial femoral artery nitinol self-expanding stents using a cryoplasty balloon reduces restenosis compared to a conventional balloon. Inclusion criteria included diabetes mellitus, symptomatic peripheral arterial disease, and superficial femoral artery lesions requiring implantation of stents>5 mm in diameter and >60 mm in length. Primary endpoint was binary restenosis at 12 months, defined as ≥2.5-fold increase in peak systolic velocity by duplex ultrasonography. RESULTS: Seventy-four patients, with 90 stented superficial femoral artery lesions, were randomly assigned to post-dilation using cryoplasty (n=45 lesions) or conventional balloons (n=45 lesions). Mean lesion length was 148±98 mm, mean stented length was 190±116 mm, mean stent diameter was 6.1±0.4 mm, and 50% of the lesions were total occlusions. Post-dilation balloon diameters were 5.23±0.51 mm versus 5.51±0.72 mm in the cryoplasty and conventional balloon angioplasty groups, respectively (p=0.02). At 12 months, binary restenosis was significantly lower in the cryoplasty group (29.3% vs. 55.8%, p=0.01; odds ratio: 0.36, 95% confidence interval: 0.15 to 0.89). CONCLUSIONS: Among diabetic patients undergoing implantation of nitinol self-expanding stents in the superficial femoral artery, post-dilation with cryoplasty balloon reduced binary restenosis compared to conventional balloon angioplasty. (Study Comparing Two Methods of Expanding Stents Placed in Legs of Diabetics With Peripheral Vascular Disease [COBRA]; NCT00827853).

Proton pump inhibitors increase the incidence of bone fractures in hepatitis C patients.

BACKGROUND: While proton pump inhibitors (PPI) may increase the risk of bone fractures, the incidence of new bone fractures in a chronic hepatitis C virus (HCV) infected cohort, with or without PPI exposure, has not been explored. METHODS: A retrospective cohort study of the incidence of bone fractures over 10 years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C Registry was performed. The study endpoint was the incidence of verified new bone fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI use was defined as those taking a PPI for ≥360 days. Pt-yrs of exposure for PPI users began on the first PPI prescription date, and pt-yrs of exposure for non-PPI users began with first date of any non-PPI prescription. For both HCV groups, the final date of patients' study duration was defined by end of PPI exposure, bone fracture occurrence, death or end of study evaluation period. Exclusion criteria included use of bone health modifying medications ≥30 days. Statistical differences in fracture incidence between groups were determined by multivariate regression analysis. RESULTS: Among the total study population analyzed (n = 2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were 13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively. The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p < 0.001) in PPI users. CONCLUSIONS: In patients with chronic HCV, use of PPI for >1 year increased the risk of new bone fractures by more than threefold.

Short-term secular variation in menarche and blood lead concentration in school girls in the Copper Basin of southwestern Poland: 1995 and 2007.

OBJECTIVES: To evaluate short-term secular change in menarche and associations with blood lead level in Polish girls between 1995 and 2007. METHODS: Menarcheal status of school girls 7-16 years from villages in southwestern Poland was surveyed in 1995, 2001, 2004, and 2007. Blood lead was sampled in 1995 and 2007. Median ages and variance statistics for menarche were estimated with probit analysis. Associations between blood lead level and menarcheal status in 1995 and 2007 were analyzed with logistic regression using blood lead level as an independent binary variable: 2.00-5.00 and ≥5.10 µg/dl. RESULTS: Median ages at menarche declined slightly from 1995 (13.36 ± 0.06 years) to 2001 (13.20 ± 0.04 years), was stable in 2004 (13.20 ± 0.05 years), and declined to 2007 (12.81 ± 0.05 years). Blood lead levels declined from 6.57 ± 0.13 µg/dl in 1995 to 4.24 ± 0.14 µg/dl in 2007. With age, height, and BMI controlled, probability of attaining menarche was not associated with blood lead in 1995, but was decreased with increased blood lead in 2007 (OR 0.31, 95% CI 0.09-1.06, P = 0.057). CONCLUSION: Ages at menarche and blood lead levels declined between 1995 and 2007. Higher blood lead levels were not associated with menarche in 1995, suggesting that nutritional and health conditions and perhaps somewhat unstable social and economic conditions in the 1980s and early 1990s may have masked the influence of lead on sexual maturation. Elevated blood lead was associated with the probability of later menarche in 2007, although the association was of borderline (P = 0.06).