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Pancreatic cancer is a leading cause of cancer mortality and is projected to become the second-most common cause of cancer mortality in the next decade. While gene-wide association studies and next generation sequencing analyses have identified molecular patterns and transcriptome profiles with prognostic relevance, therapeutic opportunities remain limited. Among the genes that are upregulated in pancreatic ductal adenocarcinomas (PDAC), the leukaemia inhibitory factor (LIF), a cytokine belonging to IL-6 family, has emerged as potential therapeutic candidate. LIF is aberrantly secreted by tumour cells and promotes tumour progression in pancreatic and other solid tumours through aberrant activation of the LIF receptor (LIFR) and downstream signalling that involves the JAK1/STAT3 pathway. Since there are no LIFR antagonists available for clinical use, we developed an in silico strategy to identify potential LIFR antagonists and drug repositioning with regard to LIFR antagonists. The results of these studies allowed the identification of mifepristone, a progesterone/glucocorticoid antagonist, clinically used in medical abortion, as a potent LIFR antagonist. Computational studies revealed that mifepristone binding partially overlapped the LIFR binding site. LIF and LIFR are expressed by human PDAC tissues and PDAC cell lines, including MIA-PaCa-2 and PANC-1 cells. Exposure of these cell lines to mifepristone reverses cell proliferation, migration and epithelial mesenchymal transition induced by LIF in a concentration-dependent manner. Mifepristone inhibits LIFR signalling and reverses STAT3 phosphorylation induced by LIF. Together, these data support the repositioning of mifepristone as a potential therapeutic agent in the treatment of PDAC.

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Objectives This study hypothesized that the presence of residual mitral regurgitation (MR) post–continuous flow (CF) left ventricular assist device (LVAD) implantation based on quantitative assessment would be negatively associated with right ventricular (RV) size and function and clinical outcomes. Background MR is associated with elevated left atrial pressure, secondary pulmonary hypertension and RV dysfunction. Implantation of a LVAD leads to mechanical unloading of the left ventricle and generally improves MR. The clinical significance of residual MR in patients supported with CF LVADs is uncertain. Most studies evaluating the presence of MR in LVAD patients have utilized predominantly qualitative assessments of MR. Methods We retrospectively identified patients implanted with CF LVADs at our institution from 2007 to 2013 who had a pre-operative transthoracic echocardiogram (TTE) within 3 months of LVAD implant and who had a post-operative TTE at least 1 month post-LVAD. MR was assessed quantitatively using the ratio of MR color jet area (CJA)/left atrial area (LAA) in apical views. We also compared quantitative RV metrics, hospitalizations, and mortality in patients with and without significant residual MR (defined as MR CJA/LAA >0.2) on post-implantation TTE. Results Sixty-nine patients were included in this study. Post-LVAD implantation, 55 patients (80%) had mild or less MR (mean MR CJA/LAA 0.08) but 14 (20%) had significant residual MR (mean MR CJA/LAA 0.34). Patients with residual MR had significantly larger RV size (right ventricular end diastolic dimension 49 mm vs. 45 mm; p = 0.04) and worse RV function (tricuspid annular plane systolic excursion 10 mm vs. 12 mm; p = 0.02; and right ventricular fractional area change 29% vs. 34%; p = 0.02). Post-implantation pulmonary artery pressures were higher in patients with residual MR (pulmonary artery systolic 43 mm Hg vs. 35 mm Hg; p = 0.05). In patients with residual MR there was slightly greater posterior displacement of the mitral coaptation point on pre-operative TTE (28 mm vs. 26 mm; p = 0.16) but this difference was not significant. Time from LVAD implantation to first hospitalization was shorter in patients with residual MR (62 days vs. 103 days; p = 0.05) as was time from LVAD implantation to death (80 days vs. 421 days; p = 0.03). Conclusions Significant residual MR post-LVAD implantation assessed by a quantitative measure is associated with persistent pulmonary hypertension, worse RV function, and significantly shorter time to hospitalization and death. MR post-LVAD implantation may serve as a surrogate for adverse outcomes post-LVAD implantation.

Background Despite improvements in pump design and durability, left ventricular assist device patients still suffer from life-threatening complications such as pump thrombosis (PT) and infection, often necessitating device exchange. Surgical exchange from HeartMate II (HM2; Abbott, Pleasanton, CA) to another HM2 is safe and associated with low mortality, but recurrent device thrombosis rates are high. Switching from axial-flow to centrifugal-flow pump, such as the HeartWare ventricular assist device (HVAD; Medtronic, Framingham, MA) may offer certain advantages due to it being a smaller, newer generation device, although there are limited data to support this strategy. Herein, we aimed to assess the surgical approach and feasibility, safety, and outcomes of surgical exchange from HM2 to HVAD. Methods We evaluated HM2 patients who underwent device exchange to HVAD due to PT or infection at 4 large-volume left ventricular assist device implant centers. Results Twenty-four patients underwent HM2 to HVAD exchange due to PT (92%) and refractory infection (8%). Patients were male (75%), white (88%), with ischemic cardiomyopathy (54%), Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale level 1-3 (90%), and destination therapy (62%). The majority underwent redo-sternotomy (79%) and the remainder underwent minimally invasive thoracotomy with subcostal approach. The existing HM2 outflow graft was maintained in 79% of cases. Recurrent PT was noted in 9% of patients. Mortality was 8% at 30 days and 33% at 1 year. Conclusions The surgical exchange from a HM2 to HVAD is safe and feasible, despite the differences in device specifications and surgical adaptation required. Newer-generation pumps are increasingly considered for exchange in the setting of HM2 device complication, and increasing experience with modified surgical approaches may be valuable in the current era.

Background Stroke and transient ischemic attack after transcatheter aortic valve replacement results in significantly higher morbidity and mortality. Severe carotid artery disease may be a contributing factor to this increased risk. We report our technique and outcomes of combined carotid endarterectomy (CEA) with transcatheter aortic valve replacement (TAVR). Methods From March 2013 to November 2017 a total of 753 TAVRs were performed at our institution for symptomatic severe aortic stenosis. Of this group, 16 patients underwent concomitant TAVR and CEA. A retrospective review was performed to assess risk, outcomes, and short-term survival. Results Sixteen patients underwent concomitant CEA/TAVR procedures for severe carotid and severe aortic stenosis. The mean Society of Thoracic Surgeons (STS) Risk Score was 7.0 ± 4.7. All patients had severe carotid artery stenosis and aortic stenosis. Nine patients had a transfemoral TAVR approach and eight patients had a transapical TAVR approach. The mean length of stay was 6.4 ± 3.7 days. At 30 days there were no cerebrovascular events and no mortalities. Conclusions The use of concomitant CEA and TAVR in patients with severe aortic stenosis and severe carotid stenosis can be done safely without increased risk of complications. This approach may reduce the risk of stroke associated with TAVR in appropriately selected patients.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Calcific aortic stenosis (CAS) is the most common valvular disease in Western countries. Histological findings in patients with CAS extremely resemble those of atherosclerosis and include accumulation and modification of lipoproteins, inflammation, extracellular matrix remodeling, and calcification. Angiogenesis is another prominent feature of CAS; however, there is only a limited amount of data available regarding the mechanisms behind the pathological neovascularization of a structure that is originally avascular. The present study aims to identify the molecular basis that regulates blood vessel growth in stenotic aortic valves, focusing on the role of HIF-1α and VEGF pathway. A total of 19 native degenerating aortic valves obtained at valve replacement surgery have been processed for Western blot, immunohistochemical, morphometric, and ultrastructural analyses. First, we have demonstrated the adverse ECM remodeling and the significant thickening of the leaflet also showing that HIF-1α and VEGF are significantly upregulated in the stenotic valves, are locally produced and colocalize with angiogenesis and areas of calcification. Next, we have characterized, for the first time to the best of our knowledge, the morphological features of the neovasculature evidencing the presence of intact blood vessels in close proximity to the mineralized zones. These results suggest that the complex structural remodeling of the matrix might reduce oxygen availability in the valve cusp contributing to the stabilization of HIF-1α that in turn induces a metabolic adaptation through the upregulation of VEGF and the formation of new blood vessels not only to overcome the hypoxic state but also to sustain the calcification process.

Management for continuous flow left ventricular assist device (LVAD) thrombosis often relies on speculation of individual clinical risk factors and integration of indirect evidence for device dysfunction. There are no comprehensive guidelines for treatment of this serious complication, and most of our current knowledge comes from anecdotal experience or observational study. More data on effective treatment, both with aggressive pharmacologic and device-based interventions, are needed for improving our understanding of mechanisms driving device thrombosis and for preventing future events. We present a case of LVAD thrombosis with emphasis on recognition and treatment of acute pump thrombosis, and discuss a potentially novel strategy using percutaneous mechanical circulatory support for pump salvage.

Background Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Methods Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. Results and conclusions In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada.

Objectives: Acute refractory cardiogenic shock with early multisystem organ failure has a poor outcome without mechanical circulatory support. We review our experience with emergent peripheral cardiopulmonary support as a bridge to decision in these patients. Methods: A retrospective review from January 2009 through December 2010 was conducted of 26 consecutive adult patients at a single institution with acute refractory cardiogenic shock who underwent salvage peripheral cardiopulmonary support. Results: There were 18 men and 8 women with a mean age of 54 years (range 18 to 76). Indications for support: acute myocardial infarction (n = 16), decompensated chronic heart failure (n = 2), refractory arrhythmic arrest (n = 3), acute valvular pathology (n = 4), and unknown (n = 1). Patients with primary postcardiotomy shock were excluded. Median duration of support was 3 days (range 1 to 14). Decisions included: withdraw of support (n = 4), recovery (n = 5), and bridge to a procedure (n = 17). The procedures were percutaneous coronary intervention (n = 4), left ventricular assist device (n = 9), heart transplantation (n = 1), and miscellaneous cardiac surgery (n = 3). Overall survival to discharge was 65%. In the recovery and bridge to a procedure group, 78% were discharged from the hospital and survival at three months was 72%. Conclusions: Salvage peripheral cardiopulmonary support is a useful tool to rapidly stabilize acute refractory cardiogenic shock permitting an assessment of neurologic and end-organ viability. (J Card Surg 2012;27:521-527)

Background: Jehovah's Witnesses (JW) are a Christian faith, with an estimated 1.1 million members in the United States, well recognized for their refusal of blood and blood products. JW may not be considered for cardiac surgery due to perceived higher risks of morbidity and mortality. This study reviews our contemporary strategies and experience with JW undergoing routine and complex cardiac surgery. Methods: From November 2001 to April 2010, 40 JW were referred for cardiac surgery at a single quaternary referral institution. A retrospective analysis of demographic data, perioperative management, and clinical outcomes was examined. Published validated clinical risk calculator and model for prediction of transfusion were used to identify high-risk patients (risk of mortality >6% or probability of transfusion >0.80). Results: The mean age was 70 (± 9.5) years with 21 men and 19 women. Patients were classified as high risk (45%, n = 18) and low risk (55%, n = 22) with demographics and comorbidities listed in Table 2. Operative procedures included: isolated coronary artery bypass grafting (CABG) (n = 19), isolated valve replacement/repair (n = 7), valve/CABG (n = 7), reoperative valve replacement (n = 4), reoperative CABG (n = 2), valve/ascending aorta replacement (n = 1), and CABG/ascending aorta replacement (n = 1). All JW were evaluated by The Department of Bloodless Medicine to individually define acceptable blood management strategies. The mean preoperative hemoglobin was 14.1 g/dL (±1.6). Overall mortality was 5% (n = 2) all of which were in the high-risk group. Discussion: Using a multidisciplinary approach to blood management, JW can safely undergo routine and complex cardiac surgery with minimal morbidity and mortality. (J Card Surg 2011;26:135-143) Table 2. Patient Demographics Variables Total (n = 40) Low Risk (n = 22) High Risk (n = 18) p value AGH = Allegheny General Hospital; NS = not significant; TRUST score = transfusion risk understanding scoring tool. Age (years) 70 (+9.5) 66.7 (+10) 74.1 (+6.2) 0.01 Women 48% 27 % 72% 0.01 Body surface area (m2) 2.0 (+0.3) 2.3 (+0.2) 2.0 (+0.4) 0.01 Congestive heart failure 32% 27 % 38% NS Cerebral vascular accident 7.5% 9% 5% NS Chronic obstructive pulmonary disease 10% 0 % 22% 0.03 Diabetes mellitus 32% 32% 33% NS Hypertension 75% 77% 77% NS Peripheral vascular disease 15% 5% 27% NS Renal insufficiency (serum creatinine > 1.3) 25% 32% 17% NS History myocardial infarction 18% 18% 17% NS Urgent operation 18% 14% 22% NS Previous cardiac surgery 15% 5% 27% NS Preoperative hemoglobin 14.1 (+1.6) 14.1 (+1.5) 14.3 (+1.6) NS AGH clinical risk score 6.0 (+3.5) 3.9 (+1.9) 8.6 (+3.5) 0.001 TRUST score 2.7 (+1.2) 2.0 (+0.8) 3.6 (+1) 0.001

Background The association between malnutrition and worse outcomes as pressure ulcers and mortality is well established in a variety of setting. Currently none investigation was conducted in patients with long-term consequences of the acquired brain injury in which recovery from brain injury could be influenced by secondary complications. The aim of this study was to investigate the association between various nutritional status parameters (in particular albumin) and pressure ulcers formation and short-term mortality in minimal conscious state patients. Methods In this prospective, observational study of 5-months duration, a 30 patients sample admitted to a Neurological Institute was considered. All patients underwent a complete medical examination. Anthropometric parameters like mid-arm circumference and mid-arm muscle circumference and nutritional parameters as serum albumin and blood hemoglobin concentration were assessed. Results At univariate and logistic regression analysis, mid-arm circumference (p = 0.04; beta = −0.89), mid-arm muscle circumference (p = 0.050; beta = −1.29), hemoglobin (p = 0.04, beta −1.1) and albumin (p = 0.04, beta −7.91) were inversely associated with pressure ulcers. The area under the ROC curve for albumin to predict sores was 0.76 (p = 0.02) and mortality was 0.83 (p = 0.03). Patient with lower albumin had significantly higher short-term mortality than those with higher serum albumin (p = 0.03; χ2 test = 6.47). Conclusion Albumin, haemoglobin and mid-arm circumference are inversely associated with pressure ulcers. Albumin is a prognostic index in MCS patients. Since albumin and haemoglobin could be affected by a variety of factors, this association suggests to optimize nutrition and investigate on other mechanism leading to mortality and pressure ulcers.

BackgroundCognitive dysfunction and cerebral vascular accidents remain some of the most devastating problems related to cardiac surgery. Despite the major advances in perioperative care and operative technique in coronary artery bypass, this cohort of patients appears to have poor cerebral physiologic reserve. The aim of this study was to describe regional cerebral perfusion of patients with coronary artery disease referred for coronary artery bypass grafting.MethodsEighty-two consecutive patients with coronary artery disease referred for coronary artery bypass grafting were enrolled after providing informed consent in an institutional review board–approved study. Patients with prior cerebral vascular accident, transient ischemic attacks, head trauma, or other neurologic afflictions were excluded from the study. We prospectively measured preoperative regional cerebral perfusion using single photon emission computed tomography (SPECT) imaging of 12 regions. Patients were determined to have an abnormal SPECT if regional cerebral perfusion was less than 2 standard deviations below the mean of age-matched controls.ResultsThe mean age was 67.5 (range, 34-89) years. The study group comprised 22% women and 78% men with known risk factors for atherosclerosis: current tobacco use (30%), hypertension (69%), and diabetes (27%). Seventy-five percent of the SPECT scans demonstrated abnormal regional cerebral perfusions, which were associated with older age (P < .008), current tobacco use (P < .005), and diabetes mellitus (P < .005). The incidence of postoperative cerebral vascular accident was 5% and only occurred in patients with abnormal regional cerebral perfusion.ConclusionSeventy-five percent of patients undergoing coronary bypass grafting have a significant impairment in regional cerebral perfusion compared with published age-matched controls, which may contribute to their proclivity for cerebral complications.

Systemic mastocytosis is a hematologic disorder with important perioperative implications. A variety of stimuli and medications can cause severe anaphylaxis in these patients. We report successful preoperative, intraoperative, and postoperative management of a patient with systemic mastocytosis who underwent an aortic valve replacement and review the literature pertaining to cardiac surgery in these patients.

Background:There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families.Methods:This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community.Results:The societal burden of AD, composed of public, patient, and informal care costs, was about €20,000/yr. Out of this, the cost borne by the public sector was €4,534/yr. The main driver of public cost was the national cash-for-care allowance (€2,324/yr), followed by drug prescriptions (€1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at €13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure.Conclusion:The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556).

Background— Moderate, regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce. We evaluated the relations between wine consumption, health status, circulating biomarkers, and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial. Methods and Results— A brief questionnaire on dietary habits was administered at baseline to 6973 patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial. The relations between wine consumption, fatal and nonfatal clinical end points, quality of life, symptoms of depression, and circulating biomarkers of cardiac function and inflammation (in subsets of patients) were evaluated with simple and multivariable-adjusted statistical models. Almost 56% of the patients reported drinking at least 1 glass of wine per day. After adjustment, clinical outcomes were not significantly different in the predefined 4 groups of wine consumption. However, patients with more frequent wine consumption had a significantly better perception of health status (Kansas City Cardiomyopathy Questionnaire score, adjusted P P =0.01), and lower plasma levels of biomarkers of vascular inflammation (osteoprotegerin and C-terminal proendothelin-1, adjusted P P =0.01) after adjusting for possible confounders. Conclusions— We show for the first time in a large cohort of patients with chronic heart failure that moderate wine consumption is associated with a better perceived and objective health status, lower prevalence of depression, and less vascular inflammation, but does not translate into more favorable clinical 4-year outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT0033633.

The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs.We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables-education, social class, and the availability of a care allowance-and three outcomes-employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers).The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW.Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems.

Objective Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients. Design and methods We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index ≥ 30 kg/m 2 ), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index ≤ 25 kg/m 2 ). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radioimmunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and β-actin, were performed. 32 P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the β-actin expression level. Results Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5 ± 7 versus 43.2 ± 6 pg/ml, P< 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03). Conclusions Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.

Traditionally aortic arch anomalies have been viewed as a "normal" and clinically insignificant; therefore, they are often overlooked by radiologists and go unreported. Arch anomalies have been reported to occur in 7% to 15% of patients without thoracic aortic aneurysm or dissection. This study aims to define the incidence of aortic arch anomalies in patients with a thoracic aortic dissection (TAD).We retrospectively reviewed all patients from 2006 to 2010 with a TAD admitted to a single institution. Thoracic computed tomography images of 176 patients with dissected thoracic aortas and 179 consecutive, unselected age-matched patients without dissection as controls were reviewed to determine the incidence of bovine arch and other arch anomalies. Statistical analysis of demographic data and clinical outcomes was performed to evaluate significant differences between the groups.Arch anomalies occurred in 34% of patients with TAD compared to controls (19%, p = 0.0017). The most common variant was a common origin of the innominate and left common carotid arteries ("bovine" arch) found in 31% of dissection patients compared to 15% in the control group (p = 0.0004). Overall arch anomalies occurred in 27% of all Type A dissections and 39% (p = 0.1409) of all Type B dissections. The association was statistically significant in patients ages 50 to 79 with TAD (36.4%, p = 0.0011) and in African Americans collectively (43.2%, p = 0.0033).Aortic arch anomalies occur frequently in patients with TAD and therefore may represent a proclivity for this life threatening condition.

Background Drugs not commonly considered to be cardioactive agents may cause prolongation of the QT interval with resultant torsades de pointes and ventricular fibrillation. This form of drug toxicity often causes cardiac arrest or sudden death. Case presentation After accidental ingestion of tosylchloramide a caucasian 77-year-old woman, with a family history of cardiovascular disease and hypertension, was admitted to the intensive care unit following episodes of torsades de pointes with a prolonged QT/QTc interval (640/542 ms). The patient received an implantable cardioverter-defibrillator, was discharged from the hospital with normal QT/QTc interval and did not experience additional ventricular arrhythmias during one year of follow-up. Conclusion This is the first report concerning an unusual case of torsades de pointes after accidental intoxication by ingestion of tosylchloramide. The pronounced impact of the oxidyzing agent tosylchloramide on the activity of some of the ion channels regulating the QT interval was identified as a probable cause of the arrhythmia.

Background In the past decade, there has been an increase in the amount of patients with medical co-morbidities referred for coronary artery bypass surgery (CABG). Significant carotid artery disease in patients undergoing CABG procedures increases the risk of neurological complications. We review the results of routine carotid screening in patients undergoing CABG to determine the contemporary incidence and risk factors for carotid artery disease. Methods Between 2008 through 2010, 673 patients were referred for isolated coronary artery bypass surgery at a single institution. Patients were identified through a systematic review of The Department of Cardiothoracic Surgery Society of Thoracic Surgery Outcomes Database. A retrospective analysis of prospectively collected demographic, clinical data and outcomes were performed. All patients with screening preoperative carotid duplex were reviewed. We defined the degree of carotid disease as: none to mild stenosis ( Results 559 (83%) patients underwent screening preoperative carotid ultrasonography prior to CABG. The incidence of carotid artery disease (>50% stenosis) was 36% with 18% unilateral moderate disease, 10% bilateral moderate and 8% severe disease. Risk factors associated with carotid artery disease included: advanced age, renal failure, previous stroke, peripheral vascular disease, left main coronary artery disease, and previous myocardial infarction. Conclusions There is a significant incidence of carotid artery stenosis in patients referred for CABG. Routine screening will identify patients with carotid artery disease and may reduce the risk of postoperative stroke.

Background: Left heart mechanical circulatory support (MCS) through the left chest via the pulmonary vein and descending thoracic aorta is a good option for patients with an inaccessible anterior mediastinum and/or poor peripheral access. Materials and Methods: We report the case of a 19-year-old small female with a newly discovered bulky primary mediastinal diffuse large B-cell lymphoma (PMBL) who developed refractory inverted Takotsubo cardiomyopathy (TC) with cardiogenic shock. Results: Temporary MCS was implemented in order to stabilize the patient and proceed with a chemotherapy treatment. Given the patient's oncologic “frozen” mediastinum and the presence of poor peripheral arterial access, the left heart temporary MCS was successfully implanted through a left mini-thoracotomy via the left inferior pulmonary vein and descending thoracic aorta. Conclusions: This is the first report of temporary MCS to treat inverted TC and diffuse PMBL. (J Card Surg 2012;27:119–121)

Schwannomas are degenerate peripheral nerve sheath tumors that very rarely occur in the retroperitoneum. They are usually benign than malignancy is very rare and is usually observed in patients with von Recklinghausen disease. We report a case of female adult patient who presented with vague abdominal discomfort. The preoperative diagnosis was difficult and the treatment was complete surgical excision. The patient is with no evidence of recurrence more than four years after surgery.

Accidental or intentional chloroform poisoning is rare, but a few such cases have been reported in literature. We report here a successful management of acute chloroform toxicity in a 33-year-old white female who attempted suicide by injecting one half milliliter of chloroform, followed by drinking half a cup the next morning. Plasma chloroform levels, measured by headspace gas chromatography declined rapidly. Sequential measurement of biomarkers in serum for liver cell necrosis, liver function, and liver regeneration indicated the presence of initial liver damage followed by recovery. These results suggest that in addition to biomarkers for liver cell necrosis, serial determinations of markers for liver regeneration provide objective evidence for recovery from chloroform poisoning and possibly other hepatotoxins.

Background: Aberrant right subclavian artery (ARSA) is the most common congenital arch anomaly, which can be complicated by aneursymal dilation at its ostium. We describe a successful repair of an ARSA with a three-stage operative procedure using a left carotid to subclavian bypass, coiling of the ARSA, and thoracic endovascular aortic repair with long-term clinical and radiographic follow-up. (J Card Surg 2010;25:390-393)

Background Statins are widely prescribed to patients with atherosclerosis. A retrospective database analysis was used to examine the role of preoperative statin use in hospital mortality, for patients undergoing isolated coronary artery bypass grafting (CABG.) Methods The study population comprised 2377 patients who had isolated CABG at Allegheny General Hospital between 2000 and 2004. Mean age of the patients was 65 ± 11 years (range 27 to 92 years). 1594 (67%) were male, 5% had previous open heart procedures, and 4% had emergency surgery. 1004 patients (42%) were being treated with a statin at the time of admission. Univariate, bivariate (Chi2, Fisher's Exact and Student's t-tests) and multivariate (stepwise linear regression) analyses were used to evaluate the association of statin use with mortality following CABG. Results Annual prevalence of preoperative statin use was similar over the study period and averaged 40%. Preoperative clinical risk assessment demonstrated a 2% risk of mortality in both the statin and non-statin groups. Operative mortality was 2.4% for all patients, 1.7% for statin users and 2.8% for non-statin users (p < 0.07). Using multivariate analysis, lack of statin use was found to be an independent predictor of mortality in high-risk patients (n = 245, 12.9% vs. 5.6%, p < 0.05). Conclusions Between 2000 and 2004 less than 50% of patients at this institution were receiving statins before admission for isolated CABG. A retrospective analysis of this cohort provides evidence that preoperative statin use is associated with lower operative mortality in high-risk patients.

We have previously shown that interleukin-2 (IL-2) is able to induce the generation of natural killer (NK) activity in bone marrow (BM) cell cultures from mice pretreated with 5-fluorouracil (5-FU). Cell fractionation experiments to analyze the nature of BM precursors indicate that MAC-1 − , NK1-1 − noncytotoxic precursors are induced by IL-2 to proliferate and generate cytolytic NK cells. These data demonstrate that the phenotype and functional characteristics of the IL-2-responsive cells in the FUBM are different from those of mature NK cells in that they are MAC-1 + , NK1.1 + , CD3 − and susceptible to boosting by IFN-α.

Chronic ventricular pressure overload states, such as hypertension, and elevated levels of neurohormones (norepinephrine, angiotensin II, endothelin-1) initiate cardiac hypertrophy and dysfunction and share the property of being able to bind to Gq-coupled 7-transmembrane receptors. The goal of the current study was to determine the role of endogenous cardiac myocyte Gq signaling and its role in cardiac hypertrophy and dysfunction during high blood pressure (BP). We induced renal artery stenosis for 8 weeks in control mice and mice expressing a peptide inhibitor of Gq signaling (GqI) using a 2 kidney, 1 clip renal artery stenosis model. 8 weeks following chronic high BP, control mice had cardiac hypertrophy and depressed function. Inhibition of cardiomyocyte Gq signaling did not reverse cardiac hypertrophy but attenuated increases in a profile of cardiac profibrotic genes and genes associated with remodeling. Inhibition of Gq signaling also attenuated the loss of cardiac function. We determined that Gq signaling downstream of angiotensin II receptor stimulation negatively impacted beta-adrenergic receptor (AR) responses and inhibition of Gq signaling was sufficient to restore betaAR-mediated responses. Therefore, in this study we found that Gq signaling negatively impacts cardiac function during high BP. Specifically, we found that inhibition of AT1-Gq signaling augmented betaAR mediated effects in a renal artery stenosis model of hypertension. These observations may underlie additional, beneficial effects of angiotensinogen converting enzyme (ACE) inhibitors and angiotensin receptor antagonists observed during times of hemodynamic stress.

Background The purpose of this study was to compare operative mortality and long-term outcome of patients undergoing tricuspid valve replacement versus tricuspid valve repair. Methods From February 1986 to July 2006, 315 patients underwent tricuspid valve surgery including 93 replacements (72 biologic, 21 mechanical) and 222 repairs. To control for selection bias and varying comorbidities, a matched cohort of patients undergoing repair versus replacement was selected using propensity score analysis (68 patients in each group). Results In the propensity-matched cohorts, operative mortality was similar for tricuspid valve replacement (13% ± 4%) and repair (18% ± 5%; p = 0.64). Intensive care unit length of stay was similar between cohorts (replacement, 4 days; repair, 3 days; p = 0.45), but the replacements had a significantly longer hospital lengths of stay (9 days versus 6 days; p = 0.01). In the replacement cohort, survival was 85% at 1 year, 79% at 5 years, and 49% at 10 years. In the repair cohort, survival rates were similar with 80% at 1 year, 72% at 5 years, and 66% at 10 years ( p = 0.66 versus replacement). Conclusions Surgical treatment of tricuspid valve disease, regardless of the operative approach, is associated with significant early and late mortality. However, there is no difference favoring tricuspid valve repair over replacement. Thus, we should not hesitate to consider tricuspid valve replacement for patients in whom we believe there is a reasonable chance for recurrence of regurgitation after repair.

Hypothesis The reported morbidity and mortality associated with esophagectomy for high-grade dysplasia (HGD) and intramucosal cancer (IMC) have led asymptomatic patients to consider less invasive and possibly less effective treatments. This study provides a critical assessment of outcomes and health-related quality of life (HRQL) after esophagectomy for HGD and IMC. Design Cohort analytic study. Setting Section of thoracic surgery at a tertiary referral center. Patients All patients who presented between May 1991 and February 2003 with a biopsy-proven diagnosis of Barrett esophagus with HGD or IMC were assessed. Main Outcome Measures Prospective analysis of postoperative morbidity, mortality, HRQL, and gastrointestinal symptoms. Results Follow-up was complete in 36 patients. Mean follow-up was 4.9 years (range, 0.5-12.0 years). The incidence of postoperative invasive cancer was 39%, with stages ranging from I to IIB. There were 4 major complications (11%) and no operative mortality. Twenty-eight patients were alive, with a cancer-free survival of 85%. The HRQL outcomes (Medical Outcomes Study 36-Item Short-Form Health Survey) were comparable with those of age- and sex-matched controls. Significant differences in postesophagectomy gastrointestinal symptoms were seen with a decreased incidence of heartburn ( P ≤.001) and increased requirement for a slower speed of eating. Twenty-two (79%) of the 28 patients described their current eating pattern as “normal or insignificantly impacted.” Conclusions Esophagectomy for HGD and IMC can be accomplished with low morbidity and mortality. Furthermore, most patients are able to resume a normal eating pattern, and postoperative HRQL can be equivalent to that of the general population.

The dimensions of the entire aorta at different anatomic levels were measured by transthoracic 2-dimensional echocardiography in 162 consecutive patients with isolated bicuspid aortic valves (BAVs) without significant aortic valve dysfunction. Aortic dilation involved the aortic root and the ascending aorta but was not present in the descending and abdominal aorta. A significant increase in the dimensions of the aortic arch was found in patients with BAVs aged >40 years. Ascending aortic diameter and the extension of aortic dilation were significantly correlated with age, but no correlation was found between aortic dimensions and aortic valve morphology.

Hypothesis Normal biliary function can be achieved after reconstruction for major bile duct injuries using either hepaticoduodenostomy (HD) or Roux-en-Y hepaticojejunostomy (HJ). Design Retrospective analysis of consecutive patients requiring biliary enteric reconstructions from February 1, 1993, through January 1, 2002, for bile duct injuries. Setting Academic multispecialty referral clinic. Patients Twenty-seven consecutive patients were evaluated who underwent biliary enteric reconstruction for bile duct injury caused during cholecystectomy. Patients were reconstructed either by HD (18 patients) or HJ (9 patients). Interventions Patients' medical records were reviewed and long-term evaluations were obtained via telephone questionnaire by 2 separate observers (R.J.M. and F.T.L.). Biliary function was evaluated in all using symptoms and liver function test results. Cholangiography was obtained, if indicated clinically. These were reviewed for stricture or dilatation. Any biliary interventions were recorded. Main Outcome Measures Comparison of long-term biliary function after HD vs HJ reconstructions. Results All patients were contacted after a median postoperative time of 54 months. Excellent or good results were observed for biliary function in 25 (92%) of the 27 patients. These results were obtained regardless of the type of reconstruction—HD (18 patients) or HJ (9 patients). Conclusions We found biliary function to be normal at more than 4 years after biliary-enteric reconstruction for bile duct injury. When surgically feasible, we prefer HD to HJ.

Patients with a left atrial thrombus are considered as being at high risk for thromboembolic events. Although embolization may be asymptomatic, embolic events related to large thrombi are usually clinically manifest and tend to be associated with a worse prognosis. We describe the very unusual case of a patient with atrial fibrillation in whom two-dimensional echocardiography revealed a large, pedunculated, highly mobile left atrial thrombus attached by a thin stalk to the interatrial septum. Because of the high risk of embolism the patient was submitted to urgent surgery. At surgery, only the stalk was found. No mass was visualized at intraoperative transesophageal echocardiography. The patient had an uneventful postoperative course without signs of embolism. Computed tomography of the brain did not reveal any cerebral infarction.

Acquired inhibitors to FVIII (anti-FVIII) are uncommon in children. An acquired anti-FVIII developed in a previously healthy 4-year-old boy treated with penicillin for streptococcal pharyngitis. Aspirin prophylaxis begun for suspected rheumatic fever led to compartment syndromes of all four extremities, which resolved with high-dose FVIII and surgical decompression. Anti-FVIII in this patient, and the five additional cases identified in a survey of 160 haemophilia treatment centres, occurred at a median age of 8 years, with median initial and peak titres of 4.6 and 6.9 Bethesda Units (BU), respectively. All six presented with bleeding, including haematomas (three intramuscular, one intracranial), and ecchymoses in three. The median baseline FVIII was 0.05 U mL(-1), and the median baseline activated partial thromboplastin time (APTT) was 79.8 s. The inhibitor resolved completely in five patients (83%) within a median 5 months, after treatment with FVIII concentrate, steroids, cytoxan, methotrexate, and no treatment. The inhibitor persisted in the patient with Goodpasture's disease, despite steroids, cytoxan, cyclosporin, and intravenous gamma globulin. Aspirin therapy, in two, worsened ongoing bleeding. The association of penicillin-like drugs in this and three other cases in the literature suggest that to avoid potential catastrophic bleeding, it is prudent to obtain an APTT prior to initiating aspirin for suspected rheumatic fever. In conclusion, acquired anti-FVIII inhibitors in children may cause severe bleeding, and remit in the majority after FVIII and/or immunosuppressive therapy.

Acute toxic hepatic necrosis is common and may be fatal. Predicting clinical outcome may be aided by following serum markers that could indicate recovery or may signify massive (substantial) destruction of functional liver mass. Previously, in a published case of chloroform poisoning, we serially assayed serum biomarkers of hepatocellular necrosis (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) and markers of hepatocellular regeneration (alpha-fetoprotein, retinol-binding protein, gamma-glutamyl transferase, and des-gamma-carboxyprothrombin). We noted a decline in necrotic markers and a synchronous elevation in regenerative markers, which could be suggestive of a favorable outcome in similar cases. We now report 6 Amanita mushroom poisonings with favorable outcome and 2 fatal acetaminophen poisonings in which the same markers were observed. Our results further support our hypothesis that a sustained decline in serum markers of hepatocyte necrosis with a concurrent elevation in regenerative markers could aid in prediction of favorable outcome in patients with acute liver injury.

The aim of this study was to assess the importance of paraneoplastic syndromes as an early sign of non-small cell lung cancer (NSCLC). A procedure for searching paraneoplastic syndromes, based on 40 years of reports in the literature, was established and the prevalence of paraneoplastic syndromes estimated in 68 patients with resectable NSCLC. Stages I and II were considered eligible for surgery straight away. Patients in Stage IIIA underwent surgery if partially or completely responsive to three courses of neo-adjuvant chemotherapy. Paraneoplastic syndromes were assessed and confirmed in nine patients (13%). Motor-sensory neuropathy, arthritis and arthralgias to the knees, periarthritis to the shoulder, hypertrophic osteopathy, clubbing, pruritus were observed. Only three patients with painful osteoar-thropathies were diagnosed with NSCLC by tracing their paraneoplastic syndrome, whereas most of them (36/68) were diagnosed incidentally through a chest radiograph taken for tumour-unrelated symptoms. A careful research of paraneoplastic syndromes in high risk patients may guide the doctor to a resectable NSCLC diagnosis. Recent onset arthritis and arthralgias, which cannot be explained otherwise, should be considered to be early clues of lung cancer.

In the Institute of Medical Pathology of Ancona University, 53 cases of fever of unknown origin (FUO) were reviewed. In 44 cases (83%) the diagnosis was certainly stated. The diagnostic spectrum of the diagnosed cases was: 31 infectious (58%), 3 neoplastic (6%), 8 autoimmune (15%), 2 miscellaneous diseases (4%). Nine cases (17%) were undiagnosed. The mortality rate of the diagnosed cases was 16% within 16 months. The diagnostic spectrum, compared with the FUO series from nine countries, is unlike because of a higher rate of infectious diseases and a lower rate of neoplastic diseases. The methods, successfully used to achieve the final diagnosis were: laboratory tests, including bacteriologic studies, in 39%, evaluation of the clinical course and follow-up in 25%, imaging scan tests, including radionuclide, ultrasound, magnetic resonance, computed tomography, in 23%, and anatomopathological studies in 13%. A three years' follow-up was successfully carried out in 7 out of the 9 undiagnosed patients: 5 were healed without any treatment, 1 healed through a course of non steroid anti-inflammatory drugs and only one died because of the FUO carrying disease. None was persistently sick. The data are discussed through a comparison with the series of FUO bearing patients from other 9 countries.

The mechanisms by which glucocorticoids suppress immune responses have not yet been clearly defined. In steroid-sensitive pathological conditions, an increase in gamma delta T cells can occur in certain untreated systemic autoimmune disorders and seems to be a peristent feature in most cases of systemic lupus erythematosus (SLE). Our previously published data demonstrated that immunosuppressive therapy normalized this expanded SLE T cell subset in parallel with clinical remission of the symptoms. To establish how corticosteroid treatment determines the disappearance of peripheral blood gamma delta T lymphocytes, circulating alpha beta and gamma delta T lymphocytes from seven SLE subjects with active disease and seven healthy individuals were cultured in the presence or absence of 10(-7) M Dexamethasone (DEX). Cell suspensions were then analysed for DNA fragmentation, characteristic of apoptotic cell death, by a new cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T cell populations was carried out for comparison. Regular follow-ups for 6 months revealed in vivo steroid treatment determined a dramatic fall in SLE blood gamma delta T cells, and in vitro experiments seem to indicate that DEX-triggered apoptotic signals are confined to the double negative (CD4-CD8-) gamma delta T cell subpopulation which disappears after in vivo immunosuppressive therapy. Clinical and pathological remission of some autoimmune diseases is often obtained by corticosteroids. Our results offer new insights on the mechanisms through these hormones exert their potent inhibitory activities on immune system cells postulated to play a role in the generation of autoimmune responses.

Gas chromatography is considered to be the reference method for ethyl alcohol determination. However, enzymatic ethanol assays have been developed for use in the clinical laboratory by several commercial vendors. Essentially, these assays utilize the oxidation of ethyl alcohol to acetaldehyde with concurrent reduction of nicotinamide adenine dinucleotide (NAD) to NADH while monitoring the increase in absorbance at 340 nm. The increase in absorbance is theoretically proportional to the ethanol concentration in the sample. Previously, several authors reported that increased concentrations of lactate and lactate dehydrogenase (LDH) can cause false-positive results with certain enzymatic ethyl alcohol assays. In the present investigation, we further studied the interference of lactate and LDH in three enzymatic assays. Apparent ethyl alcohol concentrations in serum spiked with lactate and LDH, as well as patient and autopsy samples, were determined by the Syva, Abbott, and Roche enzymatic assays and by gas chromatography. The effect of coenzyme depletion on the rate of reaction and the interference of hemolysis were also investigated. Based on our results we suggest that coenzyme depletion plays a major role in the severity of the false-positive ethyl alcohol result, and the interference from hemolysis has a negligible effect on these results. We also confirm the previous studies in showing that elevated serum-lactate and LDH concentrations can result in varying degrees of false-positive ethyl alcohol concentrations in the three enzymatic assays. This should be taken into consideration in the management of patients in a tertiary care medical center.

We present the case history of a 30-yr-old woman who suffered a cerebral haemorrhage toward the end of pregnancy (at 35 wk). The pregnancy was terminated by Caesarean section because aggravation of cerebral bleeding was feared. Extensive studies revealed that the patient was suffering from a multiple endocrine neoplasia syndrome (type 2A or Sipple's syndrome) with bilateral pheochromocytomas and a medullary thyroid carcinoma. She made an uneventful recovery. The relevant literature is discussed.

A study of the urinary steroid profile during puerperium has been undertaken in order to supplement the knowledge gained from our previous investigations of the urinary determinations of pregnanolone, pregnanediol, pregnanetriol, and total estrogens during pregnancy. Seventeen patients with normal and abnormal pregnancies were studied. The results obtained indicate that pregnanolone and pregnanetriol originate mainly from fetoplacental precursors and confirm the similar origin of pregnanediol and total estrogens. This investigation suggests that a puerperium study can also give additional information in regard to the kidney function of the mother and the presence or absence of a functional ovary of pregnancy.

A study of the urinary steroid profile in early pregnancy has been undertaken in order to re-evaluate the usefulness of the urinary determinations of pregnanolone, pregnanediol, pregnanetriol, and total estrogens in cases of threatened abortion. This investigation incorporates an enzymatic hydrolysis with gas-liquid chromatographic analysis for the pregnane metabolites and an automated assay for total estrogens. The results obtained in 62 patients confirm the value of the urinary determinations of pregnanediol and pregnanolone. They also suggest that the prognosis is good in cases which present clinical symptoms of threatened abortion but have normal urinary excretion of pregnanediol and pregnanolone. When the “biochemical progestational activity,” as evaluated by the analysis of pregnanolone and pregnanediol remains normal, abortion does not occur in the first trimester.

Sodium nitroprusside in 0.01 per cent solution was used to induce arterial hypotension in twenty-four consecutive craniotomies for cerebral aneurysm and arteriovenous malformations. The mortality and morbidity for patients with arteriovenous malformation and grade I and II aneurysm compared favourably with previous experience in this Institute using other methods. The results in patients with grade HI and grade IV aneurysms were not improved. It is considered that further support is given to the value of sodium nitroprusside as a safe agent for use in controlled hypotensive anaesthesia