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This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations. A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status. Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027). BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. The purpose of this study was to determine if patients with TNBC have a higher risk of lymph node (LN) metastases. A prospective database review identified 3,289 patients treated with a mastectomy or with breast-conserving surgery between January 2000 and May 2012. The final analysis included those patients who underwent sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND), and the following information: age at diagnosis, tumor size, grade, stage, histologic subtype, presence of lymphovascular invasion (LVI), and the status of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2). A total of 2,967 patients met the inclusion criteria. SNB was performed in 1,094 patients, ALND in 756, and both SNB and ALND in 1,117 patients. LN metastases were detected in 1,050 (35 %) patients. On univariate analysis, the LN positivity varied across subtypes with 33 % in luminal A, 42 % in luminal B, 39 % in TNBC, and 45 % in HER-2 (p = 0.0007). However, on multivariable analysis, there was no difference in LN positivity among subtypes. Age

Summary Background Hypertension (HTN) is one of the causes of cardiovascular disease (CVD) in Africa, and may be associated with lower socio-economic status (SES). The prevalence of HTN is not well established in the Gambia or in Sierra Leone. Methods A cross-sectional, population-based study of adults was conducted in the Gambia in 2000 and in Sierra Leone from 2001 to 2003 and in 2009. The study was conducted as part of the annual visit to countries in western Africa sponsored by a medical delegation from California. People from the Gambia and Sierra Leone were examined by the medical delegation and blood pressures were measured. Results A total of 2 615 adults were examined: 1 400 females and 1 215 males. The mean systolic blood pressure (SBP) of the females was 134.3 ± 29.7 mmHg, mean diastolic blood pressure (DBP) was 84.5 ± 17.5 mmHg, and 46.2% were hypertensive. The mean SBP of the males was 132.8 ± 28.5 mmHg, mean DBP was 82.8 ± 16.2 mmHg, and 43.2% were hypertensive. Overall prevalence of HTN in the subjects was 44.8%. Mean SBP, mean DBP and HTN prevalence increased with age decade, both in males and females. In addition, after age adjustment (known age), females had higher mean SBP (p = 0.042), mean DBP (p = 0.001) and rate of occurrence of HTN (p = 0.016) when compared with males. Conclusions Prevalence rates of HTN in the Gambia and Sierra Leone were higher than 40% in males and females, and may be a major contributor to CVD in both countries. Due to the association of HTN with low SES, improvements in educational, public health, economic, non-governmental and governmental efforts in the Gambia and Sierra Leone may lead to a lower prevalence of HTN. The cause of the higher prevalence in women may be due to post-menopausal hormonal changes.

We sought to investigate the magnitude and clinical importance of thrombocytopenia post transcatheter aortic valve replacement (TAVR).Thrombocytopenia has been observed after TAVR but has not been well studied.Major thrombocytopenia (platelet count100 × 10(9) /L) was studied following aortic valve interventions in a single center. Changes in platelets were compared in 246 patients undergoing balloon-expandable TAVR and a similar population of 57 cases undergoing surgical aortic valve replacement (SAVR in the US PARTNER IA trial).An early drop in platelets was seen on the day of intervention. The drop day 1 post procedure was similar but slightly greater with SAVR vs. TAVR. In both platelet counts continued to drop, reaching a nadir of approximately 50-60% of the baseline platelet count at day 2-3, starting to recover after day 5. Early major thrombocytopenia occurred post TAVR in 37% of patients but was not significantly related to major bleeding (OR 0.89, 95% CI 0.51-1.60, P = 0.69) or risk of stroke (HR 0.61, 95% CI 0.16-2.20, P = 0.45); there was a trend to greater acute kidney injury (OR 1.76, 95% CI 0.95-3.26, P = 0.073) and mortality (HR 1.47, 95% CI 0.98-2.22, P = 0.065). Major thrombocytopenia was persistent in 7.7% of patients and this was independently associated with mortality (HR 3.65, 95% CI 1.63-8.16, P = 0.002).Post-TAVR thrombocytopenia is a common phenomenon and its magnitude appears similar to that seen after SAVR. It is most often transient, not associated with adverse sequelae and, unless persistent, should be managed in an expectant fashion. © 2014 Wiley Periodicals, Inc.

Objectives: The purpose of this study was to describe the injuries sustained by displaced people returning home after a military conflict when landmines were not removed. Method: This study describes the landmine injuries to patients at the Jaffna Teaching Hospital in northern Sri Lanka over a 20-month period, from May 1, 1996, to December 31, 1997. Results: There were definite and identifiable landmine injury patterns. Patients were most often wounded in the lower extremities, had multiple wounds, and were injured together in groups. Victims were most often male, but there were unusually high numbers of women, children, and elderly injured. Mortality rates and amputation rates were high. Deaths occurred early after injury. Higher incidences of mine injuries could be associated with two important activities: returning home and agriculture. Conclusions: Civilians returning home after armed conflicts are at risk of injury when landmines are not removed. No one is spared. This problem is preventable.

Background The clinical benefits of the left internal thoracic artery–to–left anterior descending coronary artery graft are well established in coronary artery bypass graft surgery ( CABG ). However, limited data are available regarding the long‐term outcome of the radial artery ( RA ) as a secondary conduit over the established standard of the saphenous venous graft. Methods and Results We compared the 12‐year survival outcome in a set of propensity‐matched CABG patients who received either the RA or the saphenous vein as a secondary conduit. A multivariable logistic regression that included 18 baseline characteristics was used to define the propensity of receiving an RA graft. The propensity model resulted in 260 matched pairs who underwent first‐time isolated CABG from 1996 to 2001 with similar preoperative characteristics (C statistic=0.86). The cumulative 12‐year survival estimated by use of the K aplan– M eier method was higher for the RA graft patients (hazard ratio 0.76; P =0.03). This survival advantage was especially significant in diabetics ( P =0.005), in women ( P =0.02), and in the elderly ( P =0.04.) The protective effect appeared beginning at year 5 post surgical intervention. Conclusion The RA as a secondary conduit provided superior long‐term survival after CABG , especially in diabetic patients, women, and the elderly. This effect was most pronounced >5 years after surgery.

Diagnosis of adrenal-cortisol insufficiency is often misleading in hospitalized patients, as clinical and biochemical features overlap with comorbidities. We analyzed clinical determinants associated with a biochemical diagnosis of adrenal-cortisol insufficiency in non-intensive care unit (ICU) hospitalized patients.In a retrospective cohort study we reviewed 4668 inpatients with random morning cortisol levels ≤15 μg/dL hospitalized in our center between 2003 and 2010. Using serum cortisol threshold level of 18 μg/dL 30 or 60 minutes after Cortrosyn (250 μg; Amphastar Pharmaceuticals, Inc., Rancho Cucamonga, Calif) injection to define biochemical adrenal-cortisol status, we characterized and compared insufficient (n = 108, serum cortisol ≤18 μg/dL) and sufficient (n = 394; serum cortisol18 μg/dL) non-ICU hospitalized patients.Commonly reported clinical and routine biochemical adrenal-cortisol insufficiency features were similar between insufficient and sufficient inpatients. Biochemical adrenal-cortisol insufficiency was associated with increased frequency of liver disease, specifically hepatitis C (P = .01) and prior orthotopic liver transplantation (P.001), human immunodeficiency virus (HIV; P = .005), and reported pre-existing male hypogonadism (P.001), as compared with the biochemical adrenal-cortisol sufficiency group. Forty percent of insufficient inpatients were not treated with glucocorticoids after diagnosis. Multivariable logistic analysis demonstrated that inpatients with higher cortisol levels (P = .0001) and higher diastolic blood pressure (P = .05), and females (P = .009) were more likely not to be treated, while those with previous short-term glucocorticoid treatment (P = .002), other coexisting endocrine diseases (P = .005), or who received an in-hospital endocrinology consultation (P.0001), were more likely to be replaced with glucocorticoids.Commonly reported adrenal-cortisol insufficiency features do not reliably identify hospitalized patients biochemically confirmed to have this disorder. Comorbidities including hepatitis C, prior orthotopic liver transplantation, HIV, and reported pre-existing male hypogonadism may help identify hospitalized non-ICU patients for more rigorous adrenal insufficiency assessment.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Background HER2/neu (HER2) is a significant prognostic marker for breast carcinomas. Recently, new guidelines defining HER2 genetic heterogeneity (GH) were published by the College of American Pathologists. Aims To determine the prevalence of HER2 GH as defined in primary invasive breast carcinoma, to determine its relationship with prognostic variables and to investigate its impact on concurrent axillary metastasis. Methods 235 consecutive infiltrating breast carcinomas were evaluated for GH (defined as presence of 5–50% of neoplastic cells with HER2 /CEP17 ratio >2.2) using fluorescence in situ hybridisation. Pathological features of carcinomas with GH were compared with those lacking GH. GH was also evaluated in a subset of 37 paired primary carcinomas and its concurrent axillary nodal metastases using dual in situ hybridisation. Results HER2 GH was noted in 27% of HER2 negative breast carcinomas. These carcinomas demonstrated aggressive characteristics (larger size, higher grade and greater incidence of lymph node metastasis) in comparison with HER2 negative cases without GH. Higher levels of GH were associated with the equivocal HER2 status. GH was maintained in the concurrent lymph node metastases with some variations; however, two cases with clusters of HER2 amplified cells in the primary carcinoma showed HER2 amplification in the nodal metastasis. Conclusions HER2 GH is present in 27% of breast carcinomas, portends an aggressive phenotype and contributes to the equivocal HER2 status. Evaluation of the HER2 status in nodal metastasis of select primary carcinomas with GH may be beneficial before treatment selection.

The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known.All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection.Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count 200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS).ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.

Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5-15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS.

Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient-reported outcomes of quality of life (QOL), functioning, and depressive symptom severity.Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients with severe impairments in quality of life and functioning.MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30-60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education.Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD.

Objectives This study compared cross-sectional three-dimensional (3D) transesophageal echocardiography (TEE) to two-dimensional (2D) TEE as methods for predicting aortic regurgitation after transcatheter aortic valve replacement (TAVR). Background Data have shown that TAVR sizing using cross-sectional contrast computed tomography (CT) parameters is superior to 2D-TEE for the prediction of paravalvular aortic regurgitation (AR). Three-dimensional TEE can offer cross-sectional assessment of the aortic annulus but its role for TAVR sizing has been poorly elucidated. Methods All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVR in a single center. Patients studied had both 2D-TEE and 3D imaging (contrast CT and/or 3D-TEE) of the aortic annulus at baseline. Receiver-operating characteristic curves were generated for each measurement parameter using post-TAVR paravalvular AR moderate or greater as the state variable. Results For the 256 patients studied, paravalvular AR moderate or greater occurred in 26 of 256 (10.2%) of patients. Prospectively recorded 2D-TEE measurements had a low discriminatory value (area under the curve = 0.52, 95% confidence interval: 0.40 to 0.63, p = 0.75). Average cross-sectional diameter by CT offered a high degree of discrimination (area under the curve = 0.82, 95% confidence interval: 0.73 to 0.90, p l 0.0001) and mean cross-sectional diameter by 3D-TEE was of intermediate value (area under the curve = 0.68, 95% confidence interval: 0.54 to 0.81, p = 0.036). Conclusions Cross-sectional 3D echocardiographic sizing of the aortic annulus dimension offers discrimination of post-TAVR paravalvular AR that is significantly superior to that of 2D-TEE. Cross-sectional data should be sought from 3D-TEE if good CT data are unavailable for TAVR sizing.

Neuroendocrine tumors can present as liver metastases before discovery of the primary tumor. Islet 1 and PAX8 have recently been proposed as markers for neuroendocrine tumors of pancreatic origin. In this study, we compared the utility of Islet 1 and PAX8 in distinguishing pancreatic neuroendocrine tumors from neuroendocrine tumors of other sites and determined the usefulness of an immunohistochemical panel, including TTF1, CDX2, Islet 1 and/or PAX8, in identifying metastatic pancreatic neuroendocrine tumors. A total of 110 primary neuroendocrine tumors (33 pancreatic, 31 pulmonary, 23 ileal, 14 rectal, and 9 gastric) and 73 metastatic neuroendocrine tumors (28 pancreatic, 5 pulmonary, 37 ileal, 1 rectal, 1 colonic, and 1 duodenal) were studied. Islet 1 and PAX8 were positive in 27/33 (82%) and 29/33 (88%), respectively, of primary pancreatic neuroendocrine tumors, and in 19/28 (68%) and 15/28 (54%), respectively, of metastatic pancreatic neuroendocrine tumors. No cases of primary (0/23) or metastatic (0/37) ileal neuroendocrine tumors were positive with either Islet 1 or PAX8. There was Islet 1 positivity in 2/31 (6%) primary pulmonary, 12/14 (86%) primary rectal, and 1/1 metastatic rectal neuroendocrine tumors, and PAX8 positivity in 7/31 (23%) primary pulmonary, 11/14 (79%) primary rectal, and 2/9 (22%) primary gastric neuroendocrine tumors. ROC curve analysis incorporating sensitivity and specificity data of immunohistochemical panels for metastatic pancreatic neuroendocrine tumors showed that a four-stain panel, including Islet 1, PAX8, TTF1, and CDX2 significantly outperformed a three-stain panel composed of PAX8, TTF1, and CDX2 (P=0.019), and also showed a trend for better performance compared with a three-stain panel composed of Islet 1, TTF1, and CDX2 (P=0.072). Both Islet 1 and PAX8 are reliable immunohistochemical markers for pancreatic neuroendocrine tumors and would be useful adjuncts to other markers (TTF1, CDX2) currently used to work up a metastatic neuroendocrine tumor of unknown primary.

Objectives The purpose of this study was to examine the efficacy of nonvisualization of the fourth ventricle for first-trimester detection of spina bifida. Methods A total of 250 digitally stored sonographic examinations at gestational ages of 11 weeks to 13 weeks 6 days (245 normal and 5 randomly interspersed spina bifida cases) were retrospectively analyzed by 4 blinded reviewers for the presence or absence of the fourth ventricle followed by an anteroposterior ventricular dimension measurement. The ventricle size was related to the crown-rump length and gestational age by linear regression analysis and Pearson correlation. Results The fourth ventricle was identified in 971 of 1000 image readings (97.1%). False-negative and false-positive readings occurred in 11 of 20 (55.0%) and 20 of 980 (2.0%) cases, respectively (sensitivity, 0.45; specificity, 0.98.). False-negative and false-positive readings were evenly distributed throughout the gestational age range. When the ventricular size was measurable, its mean dimensions increased linearly with gestational age and were below the fifth percentile in 10 of 245 (4.0%) normal and 0 of 4 spina bifida cases, respectively. Intraclass correlation coefficient estimates were calculated based on the 2-way analysis of variance model and found to be 0.30 for a single rater and 0.64 for the mean of 4 raters. Conclusions Nonvisualization of the first-trimester fourth ventricle is a less robust screening parameter for spina bifida than previously published.

Transplant glomerulopathy (TG) is associated with antibody-mediated renal allograft rejection (AMR) and reduced graft survival. Histologically, TG is typically seen >1 year posttransplantation. However, ultrastructural changes including glomerular endothelial swelling, subendothelial widening and early glomerular basement membrane duplication are associated with development of TG but appear much earlier. We examined the specificity of these changes for AMR, and whether these are inevitably associated with development of TG. Of 98 for cause renal allograft biopsies carried out within 3 months of transplantation with available serologic data, 17 showed C4d-positive AMR and 16 had histologic changes of AMR and donor-specific antibodies (DSA), but no C4d. All three ultrastructural changes were seen in 11 of 17 biopsies with C4d-positive AMR, 8 of 16 with histologic changes of AMR and DSA but no C4d, and 0 of 65 without histologic changes of AMR and/or DSA (p < 0.0001 for both of the former groups vs. the latter). Twenty patients with positive DSA (18 with histologic changes of AMR and 11 C4d-positive) had ≥1 follow-up biopsy; eight developed overt TG 3.5-30 months posttransplantation. Among the 18 patients with DSA and histologic changes of AMR, 11 C4d-positive and 7 C4d-negative, treatment for AMR after the early biopsy significantly reduced subsequent development of overt TG.

Expected values of tissue Doppler imaging (TDI) velocities and myocardial performance index (MPI) after heart transplantation (HTx) have not been evaluated. This study assessed left and right ventricular (LV and RV) structure and function during the first year after HTx using these indexes.Echocardiography including MPI and TDI systolic (S'), early (E') and late (A') diastolic velocities of RV and LV were performed in 20 donors (mean age 35 ± 13 years) and serially in 20 recipients (mean age 59 ± 9 years) during the first year after HTx. Increase in LV mass occurred at 7 days, with normalisation at 3 months (p0.001). An increase in MPI (p0.001) and a decrease in E', S' velocities on TDI occurred at week 1 with gradual improvement during the first year (p0.001). Normalisation of LV and RV MPI occurred at 6 months (p0.001) and LV TDI velocities at 1 year (p0.001). TDI velocities of both ventricles, however, at 1 year remained lower than at baseline. No patient had greater than grade IA rejection during the follow-up. No significant change was found in myocyte size within the first year. However, there was a 3.3-fold increase in fibrosis.This study is the first to identify the normal changes of TDI and MPI of both ventricles during the first year after HTx. An increase in LV mass and impairment of bi-ventricular systolic and diastolic function occur early after HTx with gradual improvement during the first year. No significant changes in myocyte size were observed, but there was a substantial increase in fibrosis.

Systemic hypotension is a well documented predictor of increased mortality following traumatic brain injury (TBI). Hypotension is traditionally defined as systolic blood pressure (SBP)90 mmHg. Recent evidence defines hypotension by a higher SBP in injured (non-TBI) trauma patients. We hypothesize that hypotension threshold requires a higher SBP in isolated moderate to severe TBI.A retrospective database review of all adults (≥ 15 years) with isolated moderate to severe TBI (head abbreviated injury score (AIS)≥ 3, all other AIS ≤ 3), admitted from five Level I and eight Level II trauma centres (Los Angeles County), between 1998 and 2005. Several fit statistic analyses were performed for each admission SBP from 60 to 180 mmHg to identify the model that most accurately defined hypotension for three age groups: 15-49 years, 50-69 years, and ≥ 70 years. The main outcome variable was mortality, and the optimal definition of hypotension for each group was determined from the best fit model. Adjusted odds ratios (AOR) were then calculated to determine increased odds in mortality for the defined optimal SBP within each age group.A total of 15,733 patients were analysed. The optimal threshold of hypotension according to the best fit model was SBP of 110 mmHg for patients 15-49 years (AOR 1.98, CI 1.65-2.39, p0.0001), 100 mmHg for patients 50-69 years (AOR 2.20, CI 1.46-3.31, p=0.0002), and 110 mmHg for patients ≥ 70 years (AOR 1.92, CI 1.35-2.74, p=0.0003).Patients with isolated moderate to severe TBI should be considered hypotensive for SBP110 mmHg. Further research should confirm this new definition of hypotension by correlation with indices of perfusion.

BACKGROUND: This analysis explored the association between gender and systolic blood pressure (SBP) in trauma patients and then established how gender influenced outcomes in those with elevated SBP. METHODS: Demographics and outcomes were compared using the Los Angeles County Trauma System Database and multivariable modeling determined predictors for SBP, pneumonia, and mortality. RESULTS: Age and male sex were significant predictors for increased SBP, whereas the Injury Severity Score (ISS) 16 was a significant predictor for decreased SBP. In both male and female TBI patients, SBP 160 mmHg was associated with increased pneumonia (Adjusted odds ratio [AOR] 1.74, P .002 and AOR 2.37, P .046, respectively), whereas SBP 160 mmHg was a predictor for mortality only among male TBI patients (AOR 1.48, P .03). In non-TBI patients, SBP 160 mmHg was not a predictor for pneumonia or mortality in either sex. CONCLUSIONS: In this retrospective review of trauma registry data, men presented with higher SBP. In patients with TBI, regardless of gender, increased SBP was associated with increased pneumonia, and in men with TBI increased SBP was associated with increased mortality. The cause and relevance of these epidemiological findings require further investigation. Crown Copyright © 2011 Published by Elsevier Inc. All rights reserved.

Background This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery. Methods Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests. Results Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was

Objective: Our aim was to compare the long-term outcomes between drug-eluting stents and bare-metal stents for saphenous vein graft stenosis. Background: The ideal type of stent to treat saphenous vein graft stenosis has not been clearly established. Short-term randomized controlled trial results comparing drug-eluting stents with bare-metal stents for saphenous vein graft stenosis are conflicting, intermediate-term retrospective studies and meta-analyses at two years suggest no difference in outcomes, and there are no long term follow-up studies. The need for long term follow-up data has become emerged with concern over late stent thrombosis. Methods: 246 saphenous vein graft patients undergoing stenting from August 2002–December 2008 were studied. Overall survival and event-free survival were compared by Kaplan-Meier method. Hazard ratios (HR) were calculated by Cox-proportional hazards models. Results: We treated 133 patients with DES (median follow-up four years) and 113 patients with BMS (median follow-up four years) for SVG stenosis. Overall survival (77.0% ± 3.9% vs. 70.6% ± 4.6%, log-rank P = 0.60) and MACE-free survival (57.5% ± 4.6% vs. 56.8% ± 4.9, log-rank P = 0.70) were not significantly different between the DES and BMS groups. Although BMS was associated with increased risk of target lesion revascularization (TLR) (freedom from TLR 85.2% ± 3.5% vs. 90.0% ± 3.0%, HR 2.07, 95% CI 0.97–4.42, log-rank P = 0.05), there was no significant difference in the freedom from myocardial infarction (86.7% ± 3.3% vs. 88.7% ± 3.2%, log-rank P = 0.39) or target vessel revascularization (77.1% ± 4.2% vs. 76.1% ± 4.2%, log-rank P = 0.33) between the two groups. Conclusions: Although mortality is not statistically different between DES and BMS for SVG stenosis, BMS is associated with increased risk of revascularization, thus suggesting the superiority of DES over BMS in the long term. © 2011 Wiley Periodicals, Inc.

Hypotension, defined as systolic blood pressure less than 90 mm Hg, is recognized as a sign of hemorrhagic shock and is a validated prognostic indicator. The definition of hypotension, particularly in the elderly population, deserves attention. We hypothesized that the systolic blood pressure associated with increased mortality resulting from hemorrhagic shock increases with increasing age. The Los Angeles County Trauma Database was queried for all moderate to severely injured patients without major head injuries admitted between 1998 and 2005. Several fit statistic analyses were performed for each systolic blood pressure from 50 to 180 mm Hg to identify the model that most accurately defined hypotension for three age groups. The optimal definition of hypotension for each group was determined from the best fit model. A total of 24,438 patients were analyzed. The optimal definition of hypotension was systolic blood pressure of 100 mm Hg for patients 20 to 49 years, 120 mm Hg for patients 50 to 69 years, and 140 mm Hg for patients 70 years and older. The optimal systolic blood pressure for improved mortality in hemorrhagic shock increases significantly with increasing age. Elderly trauma patients without major head injuries should be considered hypotensive for systolic blood pressure less than 140 mm Hg.

Background. Angiotensin type 1 receptor (AT1R) mediates most physiologic and pathophysiologic actions of its endogenous ligand, angiotensin II, with overactivity leading to vascular remodeling and hypertension. Antibodies to AT1R are implicated in several vascular pathologies. The aim of our study was to determine the impact of antibody to AT1R on clinical outcomes including antibody mediated rejection (AMR), with or without C4d deposition, in patients whose sera contained no donor human leukocyte antigen (HLA)-specific antibody (HLA-DSA). Methods. Pretransplant sera from 97 recipients and sera obtained at the time of acute rejection (AR) were tested by Luminex-based single-antigen bead assays to determine HLA-DSA and antibodies to major histocompatibility class I chain-related gene A (MICA). The presence of antibody to AT1R was determined by a cell-based ELISA method using a cutoff of 17 units to distinguish high from low binding. Results. Sera from 63 recipients were determined to have no HLA-DSA and no donor-specific MICA antibodies pretransplantandatthetimeofAR,and16oftheserecipientswerediagnosedwithARincluding7withAMRand9with cellular AR (cell-mediated rejection). High-binding AT1R antibodies were identified for six of seven in the AMR group and zero of nine in the cell-mediated rejection group (P0.0009). Conclusions.A strong association was observed between the presence of high binding to AT1R and AMR in recipients whose sera contained no antibody to donor HLA or MICA. Assessing the AT1R antibody status along with the HLADSA provides additional information to determine the immunologic risk for recipients.

Background Baseline left ventricular ejection fraction (LVEF) has been shown to be associated with likelihood of recovery in patients with peripartum cardiomyopathy (PPCM). The clinical relevance of this association for individual patients is unclear. Methods and Results We analyzed baseline parameters of LVEF in 187 PPCM patients with ≥6 months follow-up data in an attempt to detect the value of baseline LVEF as a predictor of early recovery or persistence of severe LV dysfunction. Recovery of LV function (LVEF ≥50%) at 6 months after diagnosis was found in 115 patients (61%). Multivariate analysis identified baseline LVEF >30% as a significant predictor for recovery (odds ratio 5.2, 95% confidence interval 1.96–7.70; P > .0001). Recovery of LV function was 6.4-fold higher in women with baseline LVEF ≥ 30% (group III) and 3.9-fold higher in women with LVEF 20%–29% (group II) compared with those with LVEF 10%–19% (group I). Failure to achieve full recovery was seen in 63% of group I patients, 32% of group II ( P = .03), and 21% of group III ( P = .02 vs group I). Failure to achieve LVEF ≥30% was seen in 30% of group I patients and 13% of group II ( P = .09). Conclusions Early recovery in patients with PPCM is significantly related to the degree of myocardial insult at time of diagnosis. Baseline LVEF however, has a limited sensitivity for prediction of failure to improve in individual patients and can not be used as an indication for premature use of aggressive therapy including devices or cardiac transplantation.

Desensitization with IVIG and rituximab followed by transplantation with alemtuzumab or daclizumab induction is an effective clinical protocol. Here, we examined the effects of this protocol on immune cell number, T cell function by Cylex ImmuKnow®, CMV-specific CD8+ T cell (CMV-Tc) activity, total and viral-specific immunoglobulin levels and viral infections. In 17 highly HLA-sensitized (HS) patients who received desensitization, CD19+ cells were undetectable immediately after desensitization, while other immune cells were unchanged. No alteration in Cylex or CMV-Tc levels was seen. In separate 14 HS patients who were desensitized followed by transplantation, T cell numbers were near zero after alemtuzumab, while NK cell reduction was minimal. Early B cell recovery was not a risk for antibody-mediated rejection. Total IgG, IgM, and IgA remained in the normal range up to 12.6 months post-transplant, and CMV IgG level did not change. CMV-Tc activity was eliminated post-transplant in some patients, but recovered by 4 months post-transplant. None of them developed CMV infection. In conclusion, IVIG-rituximab-desensitization does not significantly alter T cell function pre-transplant, or reduce Ig levels below the normal range post-transplant. Although post-transplant induction therapy is associated with a transient depletion of viral-specific CD8+ memory cells, it does not increase risks for viral infections.

Introduction: Irritable bowel syndrome (IBS) is a chronic disorder often subdivided into constipation-predominant and diarrhea-predominant forms. Earlier studies have shown that IBS patients with methane detected on lactulose breath test (LBT) are more likely to have constipation. The goal of this study was to conduct a factor analysis to determine whether there is a cluster of symptoms associated with methane production. Methods: Patients with IBS referred for a LBT completed a questionnaire assessing 31 symptoms. The degree of each symptom was graded on a visual analog scale of 0 to 5. Exploratory factor analysis was carried out separately in methane and nonmethane patients. A score was determined for each symptom cluster by summing across the related variables. The cluster scores were compared between the 2 groups by the Wilcoxon rank-sum test. Results: A total of 459 IBS patients (72 with methane, 387 with nonmethane) were evaluated. On the basis of factor analysis results, 3 symptom clusters (bloating weighted, pain weighted, and constipation weighted) were created in methane-producing patients. Two symptom clusters (bloating weighted and diarrhea weighted) were created in the nonmethane group. The groups did not differ significantly on the methane-derived bloating score (P=0.24) or the pain score (P=0.15). However, the methane-derived constipation score was significantly higher in the methane group, 15.3 ± 4.9 versus 13.4 ± 4.9, P = 0.002. The constipation-weighted cluster included the following symptoms: constipation, lack of milk intolerance, lack of weight loss, small bowel movements, and straining. The diarrhea cluster score was significantly higher in the nonmethane group, 14.2 ± 8.0 versus 11.3 ± 6.5, P=0.005. The diarrhea cluster included the following symptoms: diarrhea, pain with bowel movements, pain after bowel movements, foul-smelling bowel movements, and large bowel movements. The groups did not differ significantly on the nonmethane-derived bloating cluster, P=0.11. Conclusions: Methane-producing IBS patients have a unique cluster of symptoms related to constipation.

Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994-2008 with follow-up time ranging from 1-15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissue-specific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p

Background Pregnant women, who have significantly elevated levels of estrogen and progesterone, might benefit from the neuroprotective effect of steroid hormones. Methods Pregnant patients were identified and compared with their nonpregnant counterparts with respect to demographics and outcome. Results Of the 18,800 female, moderate to severe TBI patients, 71 were pregnant. Similar mortalities were noted in pregnant and nonpregnant TBI patients (9.9% vs 9.3%, P = .84). Adjusting for confounding variables, pregnant TBI patients had a trend toward increased mortality (adjusted odds ratio [AOR] = 2.2; 95% confidence interval [CI], .9–5.1; P = .07). In patients aged 15 to 47 years (n = 8,854), similar mortalities were noted in pregnant and nonpregnant TBI patients (9.9% vs 6.8%, P = .34). After adjusting for risk factors, again there was a trend toward increased mortality in the pregnant TBI group (AOR = 2.0; 95% CI, .8–4.6; P = .12). Conclusions Pregnant patients with moderate to severe TBI show no statistically significant difference in mortality compared with their nonpregnant counterparts.

Introduction: Pleural effusions are a frequent occurrence in critically ill patients, but there is little agreement regarding the benefit of their drainage in mechanically ventilated patients. We determined the effects of thoracentesis upon gas exchange and hemodynamics in intubated patients with di

Background: The inability to mount tachycardia (T) after trauma-related hypotension is labeled relative bradycardia (RB). The objective of this study was to examine RB incidence and prognosis in a large cohort of patients. Methods: The Los Angeles County Trauma System database, consisting of five Level I and eight Level II trauma centers, was queried for all adult (> 14 years) hypotensive (systolic blood pressure [SBP] ≤90) trauma patients admitted between 1998 and 2005. RB was defined as SBP ≤90 with heart rate (HR) ≤90, and T was defined as SBP ≤90 with HR >90. Demographics, injury severity, mechanism, and outcomes were compared between the RB and T groups. Multivariate logistic regression was used to determine significant risk factors for mortality. Results: Of 130,906 adult trauma patients, 7,123 (5.4%) were hypotensive. After excluding patients dead on arrival and those with missing data, 3,727 patients were identified. RB was observed in 1,630 (44%) of patients, whereas T was observed in 2,097 patients (56%). RB patients were older (39.8 ± 18.6 years vs. 35.3 ± 17.0 years, p < 0.0001), less severely injured (injury severity score 18.0 ± 14.2 vs. 20.5 ± 15.3, p < 0.0001), more hypotensive (SBP 64.7 ± 31.6 vs. 76.2 ± 15.1, p < 0.0001), and had less abdominal trauma (abdomen abbreviated injury score 2.9 ± 1.2 vs. 3.2 ± 1.1, p < 0.0001) than their tachycardic counterparts. In addition, the mortality was significantly higher in the RB group compared with the T group (30.1% vs. 22.6%, p < 0.0001). Overall, RB had a higher mortality among all subgroups except older patients (age ≥55; 27.7% vs. 35.2%, p = 0.045) and patients with a higher Glasgow coma scale score (≥12; 5.3% vs. 11.2%, p < 0.0001). Logistic regression identified RB as an independent risk factor for mortality (odds ratio, 1.60; 95% confidence interval, 1.33―1.94; p < 0.0001). When RB was further divided into two groups, observed mortality for HR

Objective We sought to review the surgical outcomes of our initial 120 robotic mitral valve repairs from June 2005 through April 2009. Methods The initial 74 repairs were performed with the first-generation da Vinci robot (Intuitive Surgical, Inc, Sunny Vale, Calif), and the last 46 were performed with the da Vinci Si HD model. All patients received an annuloplasty band and 1 or more of the following: leaflet resection; annuloplasty; basal chord transposition, polytetrafluoroethylene neochordal replacement, or both; and edge-to-edge repair. Results The overall mean age was 58.4 ± 10.5 years, and 64% were male. There was 1 (0.8%) hospital mortality. Five patients required mitral valve replacement for a failed repair. Another patient had mitral valve rerepair on postoperative day 2. Except for 2 early reoperations for postoperative bleeding, all of the complications and failed repairs requiring operative revision occurred with the original robot. Postdischarge transthoracic echocardiographic follow-up was available on 107 (93%) of 115 patients, with a median follow-up of 321 days. None to mild mitral regurgitation was seen in 102 (89%) patients, moderate mitral regurgitation was seen in 9 (8.4%) patients, and severe mitral regurgitation was seen in 3 (2.8%), with 1 patient undergoing mitral valve replacement and 2 patients being medically managed. Conclusions The majority of complications and all the repeat operations for failed mitral valve repair occurred with the older-model da Vinci robot. The newer da Vinci Si HD system, with the addition of an adjustable left atrial roof retractor, improves mitral valve exposure, enhancing the surgeon's ability to repair and test the valve. We have progressed to successful repair of all types of degenerative mitral valve pathology and have found the approach reproducible.

Background Clinical profile and predictors of major adverse events (MAE) associated with peripartum cardiomyopathy (PPCM) have not been characterized. Methods and Results A retrospective review and analysis of clinical data of 182 patients with PPCM. Forty-six patients had ≥1 MAE, including death (13), heart transplantation (11), temporary circulatory support (4), cardiopulmonary arrest (6), fulminant pulmonary edema (17), thromboembolic complications (4), and defibrillator or pacemaker implantation (10). Diagnosis of PPCM was delayed ≥1 week in 48% of patients with MAE that preceded the diagnosis in 50% of these patients. Seven (32%) of the surviving patients who had MAE and did not undergo heart transplantation had residual brain damage. Significant predictors of MAE were: left ventricular ejection fraction ≤25% (HR 4.20, CI 2.04–8.64) and non-Caucasian background(HR 2.16, CI 1.17– 3.97). These predictors in addition to diagnosis delay (HR 5.51, CI 1.21–25.04) were also associated with death or heart transplantation. Conclusions 1. PPCM may be associated with mortality or severe and lasting morbidity. 2. Incidence of MAE is higher in non-Caucasians and in women with left ventricular ejection fraction ≤25%. 3. Diagnosis of PPCM is often delayed and preceded by MAE. 4. Increased awareness of PPCM is required for early diagnosis and aggressive therapy in an attempt to prevent complications.

Background Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation. Methods and Results The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7±7.5% at baseline to 50.3±8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53±6% (P not significant versus LVEF at discharge). Conclusions Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population.

Objective: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS. Methods: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables. Results: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003). Conclusions: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.

The association between the severity of arteriosclerosis in the thoracic aorta in patients with isolated aortic stenosis (AS) and with concomitant coronary artery disease (CAD) has been not evaluated. Therefore, the aim of our study was to compare the thoracic aortic atheroma extent and severity in patients with severe AS alone and with concomitant CAD by intraoperative transesophageal echocardiography.We retrospectively evaluated echocardiograms of 105 consecutive patients with severe degenerative AS who underwent aortic valve replacement. Sixty patients had concomitant CAD (AS/CAD) on coronary angiography and 45 had no CAD (AS alone). These patients were compared with 54 sex- and age-matched patients without AS or CAD. Aortic atheroma (localized intimal thickening of3 mm) prevalence and morphology in three segments of aorta were assessed with echocardiography.There were 62 men, mean age 75.3 +/- 9.4 years. No difference was observed in age, sex, and risk factors for arteriosclerosis other than hypercholesterolemia among AS/CAD, AS alone, and control groups (88%, 67%, 41%, respectively; p0.0001). The AS/CAD group had a significantly higher rate of aortic root calcification (68%, 36%, 26%, respectively; p0.0001) and aortic atheroma (ascending aorta [26%, 20%, 14%, respectively; p = 0.03]; aortic arch [78%, 36%, 30%, respectively; p0.0001]; descending aorta [72%, 42%, 29%, respectively; p0.0001]) than AS alone or control subjects. Patients with AS/CAD also had more complex atheromas in the aortic arch (48%, 20%, 7%, respectively; p0.0001). Significant differences in extension of aortic arteriosclerosis (presence of plaques in two or three segments) were observed among the groups (70%, 31%, 18%, respectively; p0.0001).Patients with severe AS and coexisting CAD have more extensive arteriosclerotic changes in the thoracic aorta compared with those with AS alone and control subjects. Preoperative evaluation of the thoracic aorta and more aggressive lipid therapy should be considered in these patients.

Objectives: The aim of this study was to compare the procedural characteristics and outcomes of patients with acute myocardial infarction treated with drug-eluting stents (DES) vs. bare metal stents (BMS). Background: DES have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) in clinical randomized studies when compared with BMS in patients undergoing elective percutaneous intervention. Limited data are available with the use of DES in patients with acute ST-segment elevation myocardial infarction. Methods: Two hundred and sixty-one consecutive patients who presented with myocardial infarction between 7/2001 and 8/2005 were studied. The procedural characteristics, 30-day and 12-month outcomes of 131 patients treated with DES were compared with 130 patients treated with BMS. Results: At 12-months follow-up DES therapy was associated with a substantial decrease in major adverse cardiovascular events (MACE) (HR 0.33; P =0.002), TVR (HR 0.19; P =0.002), and recurrent myocardial infarction (HR 0.23; P =0.051) vs. BMS therapy. Coronary interventions utilizing DES were characterized by a marked increase in the number of stent per target vessel (DES: 1.9 ± 0.9 vs. BMS: 1.38 ± 0.6, P < 0.0001), treatment of bifurcation (DES: 21% vs. BMS: 5%, P =0.0004), and multivessel intervention (DES: 22% vs. BMS: 8%, P =0.003). Conclusion: The routine use of DES in acute myocardial infarction is associated with reduced rates of MACE at 12 months vs BMS, despite a higher rate of complex procedures in the DES treated patients. In addition to its anti-restenosis effect, the improved outcome of patients treated with DES may be linked to a more complete revascularization in association with prolonged clopidogrel therapy. © 2007 Wiley-Liss, Inc.

Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding “organic” conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P

Poor outcomes after thoracic transplantation with concurrent renal dysfunction are well described: without transplantation or with thoracic-only transplantation, patients face unacceptably high mortality. Outcomes after combined lung-kidney transplantation (LKT) remain largely uninvestigated. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was queried to identify all LKTs, lung transplantations (LTs), and kidney transplantations (KTs) performed in the United States from 1995 to 2013. Survival was calculated using the Kaplan-Meier method and compared using log-rank tests or Cox regression models. Thirty-one LKTs were performed. Mean recipient age was 45.4 ± 13.5 years; 48.3 per cent were male. Retransplantation for graft failure was the leading indication for LT (n = 13) and the most common renal indication was calcineurin inhibitor nephrotoxicity (n = 11). Mean lung allocation score was 46.6 ± 14.4, mean creatinine was 3.7 ± 2.8 g/dL, and glomerular filtration rate was 23.1 (interquartile range 11.9, 38.3) mL/min/1.7 m2, and 11 (35.5%) were dialysis dependent. Patient survival after LKT was 92.9 per cent, 71.0 per cent, and 71.0 per cent at one month, six months, and one year, with a median survival of 95.2 months. One- and five-year survival after LKT, 71.0 per cent and 59.9 per cent, were similar to LT (n = 23,913), 81.7 per cent and 51.4 per cent ( P = 0.061 and 0.55), and inferior to KT (n = 175,269), 94.9 per cent and 82.8 per cent ( P < 0.0001), respectively. Patient survival after LKT was similar to isolated LT, and these results suggest that LKT is a feasible therapeutic option for LT candidates with significant renal dysfunction.

of these patients had fasting FGF19 measured. Alanine transaminase (ALT) and appearance of fatty liver on imaging (ultrasound, CT or MR) were retrospectively added to the database. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Patients with known chronic liver disease or alcohol abuse were excluded from the final analysis. Results: Of 578 SeHCAT values on the database, 303 (52%) were positive with a value 31IU/L (36% v 21%, p 31IU/L (21% v 7%, p 31IU/L (43% v 22%, p 31IU/L (23% v 7%, p 40 IU/L (40% vs 12%, p

Background Alterations in gut flora may be important in the pathophysiology of the irritable bowel syndrome (IBS). Objective To determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS. Design Double-blind, randomized, placebo-controlled study. Setting 2 tertiary care medical centers. Participants 87 patients who met Rome I criteria for IBS and were enrolled from December 2003 to March 2005. Interventions Participants who met enrollment criteria were randomly assigned to receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n = 44). Eighty participants completed rifaximin therapy or placebo, and follow-up data were available for at least 34 participants per study group at any time point thereafter. Measurements A questionnaire was administered before treatment and 7 days after treatment. The primary outcome was global improvement in IBS. Patients were then asked to keep a weekly symptom diary for 10 weeks. Results Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating score after treatment. Limitations The major limitations of the study were its modest sample size and short duration and that most patients were from 1 center. Conclusions Rifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.

The purpose of this investigation was to determine the influence of pre-existing pulmonary hypertension (PHT) on outcome and to assess the pulmonary hemodynamic changes after heart transplantation (HT).A total of 410 patients were studied before and after (1 month and 1 year) HT: Group 1 (n = 266) had no PHT (PVR3 Wood units [WU], TPG10 mm Hg); Group 2 (n = 112) had mild-moderate PHT (PVR 3 to 6 WU, TPG 10 to 20 mm Hg); and Group 3 (n = 32) had severe PHT (PVR6 WU, TPG20 mm Hg).Mean (+/- SD) follow-up was 5.2 +/- 4.1 years, mean recipient age was 57 +/- 11, and mean donor age was 30 +/- 12 years. Baseline characteristics were similar in all groups, except donor/recipient weight ratio, which was higher in patients with PHT (p = 0.002). There was a significant (p0.0001) decrease in mean TPG to 11.0 within the first month and to 9.5 mm Hg after the first year. Decreases in PVR to 2.2 and 2.0 WU at 1 month and 1 year, respectively (p0.0001 for both) were also found. Reversibility (after vasodilation) of PHT was obtained in 85% of patients in Group 2 and in 84% in Group 3. Patients' PHT did not show a significant difference in 30-day mortality (p = 0.9) and long-term survival (p = 0.8). Patients with residual post-transplant PHT (PVRor = 3 WU) had reduced long-term survival (p = 0.03). Multivariate analysis showed no evidence that elevated PVR was associated with death.Pre-existing elevated PVR that responds to vasodilator challenge does not have a negative influence on short- and long-term survival after HT. We found that residual post-transplant PHT is associated with decreased long-term survival.

The Akt pathway, an important regulator of cell proliferation and survival, is deregulated in many cancers. The pathway has achieved considerable importance due to the development of kinase inhibitors that are able to successfully reduce tumor growth. This study was conducted to determine the status of the Akt pathway in human breast cancers and to study the relationship between the different component proteins. Expression levels of PTEN, phosphorylated forms of the constituent proteins (Akt, FKHR, mTOR, and S6) and cyclin D1 were evaluated by immunohistochemistry, on consecutive sections from a tissue microarray containing 145 invasive breast cancers and 140 pure ductal carcinomas in-situ. Aberrant expression was correlated statistically with tumor characteristics and disease outcome. The Akt pathway was found to be activated early in breast cancer, in the in-situ stage. In all, 33, 15, 32, and 60% of ductal carcinoma in-situ showed overexpression of Akt, FKHR, mTOR, and cyclin D1. PTEN loss did not correlate statistically with expression of AKT or any of the other proteins with the exception of S6, indicating that Akt activation was not a result of PTEN loss. Expression levels of PTEN and S6 were significantly different in in-situ and invasive cancers, indicating association with disease progression. Loss of PTEN was noted in 11% of in-situ as compared to 26% of invasive cancers, while S6 overexpression was seen in 47% in-situ and in 72% invasive cancers. High-grade carcinomas were associated with PTEN loss, while low-grade carcinomas with good prognostic features showed cyclin D1 overexpression and were associated with longer disease free survival. Additionally, cancers with mTOR overexpression showed a three times greater risk for disease recurrence. Overall, a large proportion of in-situ and invasive breast cancers overexpressed cyclinD1 and S6. Our results may have significant implications in the development and application of targeted therapy.

Purpose Induction therapy (IND) after heart transplant (HTx) remains controversial despite its use in over 50% of programs. No randomized trials exist to suggest benefit. African Americans (AA) are at high risk for allograft rejection. We sought to explore whether the use of Antithymocyte globulin (ATG) or Basiliximab improved survival in AA, using the UNOS database. Methods and Materials We reviewed 2,523 consecutive adult AA HTx patients from the UNOS database from 1/2000 to 3/2011. Data were analyzed using two age groups; younger ages 21-59 years (n=2,037) and older ≥60 years (n=486). Five-year (5-yr) survival was estimated by Kaplan-Meier method. Survival was compared across groups by Log-Rank test. Cox proportion hazards models were used to assess factors related to 5-yr survival and to obtain hazard ratios and their 95% confidence intervals. Results Univariable analysis found younger AA who received ATG had better 5-yr survival compared to Basiliximab (P=0.002) or no IND (P=0.016). Older AA with Basiliximab experienced better 5-year survival than ATG recipients (P=0.019). In multivariable models, adjusting for Creatinine>2mg/dL and PRA>10%, younger AA, had a trends for ATG to be protective vs Basilximab (HR=0.74, P=0.075) and no IND (HR=0.78, P=.076). In older AA, Basiliximab was protective vs ATG (HR=0.46, P=0.022) and there was a trend for no IND to be protective vs ATG(HR=0.72, P=0.16). [ figure 1 ] Conclusions ATG may confer protection in the young AA but worsen survival in AA age 60 and older. For AA of age ≥60 Basiliximab appears protective vs ATG. Age-related differences in immune activation may explain these findings. Randomized trials to assess efficacy of induction therapy are indicated.