Lateralized deficit of response inhibition in early-onset schizophrenia

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence OF executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few Studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS). Methods. Twenty-one adolescents with (lie onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized Lis paranoid (n= 10) and Undifferentiated subtypes (n= 11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response. Results. The Undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT. Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients With Undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and Supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement.

Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into ""early"" and ""late"" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

Prognostic Value of Dobutamine Stress Echocardiography With Early Injection of Atropine With Versus Without Chronic Beta-Blocker Therapy in Patients With Known or Suspected Coronary Heart Disease

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with P blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1291-1295)

Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease - A meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials

Background-Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results-We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P = 0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions-In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.

Surgical Treatment of Morbid Obesity: Mid-term Outcomes of the Laparoscopic Ileal Interposition Associated to a Sleeve Gastrectomy in 120 Patients

The aim of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition associated to a sleeve gastrectomy (LII-SG) for the treatment of morbid obesity. The procedure was performed in 120 patients: 71 women and 49 men with mean age of 41.4 years. Mean body mass index (BMI) was 43.4 +/- 4.2 kg/m(2). Patients had to meet requirements of the 1991 NIH conference criteria for bariatric operations. Associated comorbidities were observed in all patients, including dyslipidemia in 51.7%, hypertension in 35.8%, type 2 diabetes in 15.8%, degenerative joint disease in 55%, gastroesophageal reflux disease in 36.7%, sleep apnea in 10%, and cardiovascular problems in 5.8%. Mean follow-up was 38.4 +/- 10.2 months, range 25.2-61.1. There was no conversion to open surgery nor operative mortality. Early major complications were diagnosed in five patients (4.2%). Postoperatively, 118 patients were evaluated. Late major complications were observed in seven patients (5.9%). Reoperations were performed in six (5.1%). Mean postoperative BMI was 25.7 +/- 3.17 kg/m(2), and 86.4% were no longer obese. Mean %EWL was 84.5 +/- 19.5%. Hypertension was resolved in 88.4% of the patients, dyslipidemia in 82.3%, and T2DM in 84.2%. The LII-SG provided an adequate weight loss and resolution of associated diseases during mid-term outcomes evaluation. There was an acceptable morbidity with no operative mortality. It seems that chronic ileal brake activation determined sustained reduced food intake and increased satiety over time. LII-SG could be regularly used as a surgical alternative for the treatment of morbid obesity.

Electromyographic Study of the Masseter Muscle after Lower Third Molar Surgery

Third molar extraction surgery is one of the most frequently performed procedures in the areas of buccal-maxillofacial traumatology and surgery. The post-surgery evolution was evaluated based on the clinical evidence obtained so far. The objective of this study was to analyze the post-surgery clinical evolution of the masseter muscle by means of surface electromyography, to evaluate muscle activity. Four analyses were performed: one pre-surgery, to register the normal activity, and three in post-surgery: on the 7(th), 14(th) and 21(st) postoperative days, in a sample of 30 patients. On the 21(st) day, there was near normal recovery of the electrical signal of the masseter in women, but in men this activity did not reach normal levels. Surface electromyography is a safe and reliable tool for post-surgery evolution control of masseter function.

When Should Renal Replacement Therapy be Initiated for Acute Kidney Injury?

Acute kidney injury (AKI) is now well recognized as an independent risk factor for increased morbidity and mortality particularly when dialysis is needed. Although renal replacement therapy (RRT) has been used in AKI for more than five decades, there is no standard methodology to predict which AKI patients will need dialysis and who will recover renal function without requiring dialysis. The lack of consensus on what parameters should guide the decision to start dialysis has led to a wide variation in dialysis utilization. A contributing factor is the lack of studies in the modern era evaluating the relationship of timing of dialysis initiation and outcomes. Although listed as one of the top priorities in research on AKI, timing of dialysis initiation has not been included as a factor in large, randomized controlled trials in this area. In this review we will discuss the criteria that have been used to define early vs. late initiation in previous studies on dialysis initiation. In addition, we propose a patient-centered approach to define early and late initiation that could serve as framework for managing patients and for future studies in this area.

Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

Thirty-Day Morbidity and Mortality of the Laparoscopic Ileal Interposition Associated with Sleeve Gastrectomy for the Treatment of Type 2 Diabetic Patients with BMI < 35: An Analysis of 454 Consecutive Patients

Background The objective of this study was to evaluate the early results of the laparoscopic interposition of a segment of ileum associated with a sleeve gastrectomy (LII-SG) in order to treat patients with type 2 diabetes mellitus (T2DM) and BMI <35. Data regarding morbidly obese diabetic patients subjected to surgery has consistently been validated. To date, there is scarce information about morbidity and mortality related to the surgical treatment of a ""true"" typical diabetic population with BMI <35. Methods The procedures were performed in 454 patients (322 male, 132 female). Mean age was 53.6 +/- 8 years (range = 27-75). Mean BMI was 29.7 +/- 3.6 kg/m(2) (range = 19-34.8). All patients had the diagnosis of T2DM for at least 3 years. Insulin therapy was used by 45.6% of patients. Mean duration of T2DM was 10.8 +/- 5.9 years (range = 3-35). Mean hemoglobin A(1c) was 8.8 +/- 1.9%. Dyslipidemia was observed in 78.4%, hypertension in 64.8%, nephropathy in 28.6%, retinopathy in 32.6%, neuropathy in 34.6%, and coronary heart disease in 13%. Results There was no conversion to open surgery. All patients were evaluated postoperatively. Mortality was 0.4%. There were 29 major complications (6.4%) in 22 patients (4.8%) and 51 minor complications (11.2%). Reoperations were performed on 8 patients (1.7%). Twenty patients (4.4%) were readmitted to the hospital. Mean postoperative BMI was 25.8 +/- 3.5 kg/m(2). Mean fasting plasma glucose decreased from 198 +/- 69 to 128 +/- 67 mg/dl and mean postprandial plasma glucose decreased from 262 +/- 101 to 136 +/- 43 mg/dl. Conclusions The laparoscopic ileal interposition associated with a sleeve gastrectomy was considered a safe operation with low rates of morbidity and mortality in a diabetic population with BMI < 35. An early control of postprandial glycemia was observed.

Bariatric Surgery Reverses Natural Killer (NK) Cell Activity and NK-Related Cytokine Synthesis Impairment Induced by Morbid Obesity

Background Obesity is related to a higher rate of infections and some types of cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en-Y gastric bypass (RYGB) on immunological parameters, i.e., cytokine productions and natural killer cell function. Methods We analyzed 28 morbidly obese patients before and 6 months after RYGB. Biochemical parameters were analyzed in plasma. The percent of natural killer (NK) cells, their cytotoxicity, and the production of cytokines by peripheral blood mononuclear cells were analyzed. The percent of NK cells was determined by flow cytometry and cytokine production determined by enzyme-linked immunosorbent assay. NK cytotoxicity was determined by the lactate dehydrogenase release assay. Results The weight loss 6 months following surgery was 35.3 +/- 4.5 kg. RYGB also improves biochemical parameters. No significant difference was found in the percent of NK cells after surgery. We found an increase in the production of interferon-gamma, interleukin (IL)-12 and IL-18, but not in IL-2, 6 months after RYGB. Cytotoxic activity of NK cells was significantly enhanced 6 months after RYGB [17.1 +/- 14.7% before RYGB vs 51.8 +/- 11.3% at 6 months after, at 40: 1 effector to target cell ratio; p<0.001]. We observed significant post-surgical improvement in the cytotoxic activity curve in 22 out of 28 patients (78.6%), irrespective of the target to effector cell ratio. Conclusions The weight loss induced by RYGB modifies the production of cytokines related with NK cell function and improves its activity.

Online monitoring of pulse pressure variation to guide fluid therapy after cardiac surgery

BACKGROUND: The arterial pulse pressure variation induced by mechanical ventilation (Delta PP) has been shown to be a predictor of fluid responsiveness. Until now, Delta PP has had to be calculated offline (from a computer recording or a paper printing of the arterial pressure curve), or to be derived from specific cardiac output monitors, limiting the widespread use of this parameter. Recently, a method has been developed for the automatic calculation and real-time monitoring of Delta PP using standard bedside monitors. Whether this method is to predict reliable predictor of fluid responsiveness remains to be determined. METHODS: We conducted a prospective clinical study in 59 mechanically ventilated patients in the postoperative period of cardiac surgery. Patients studied were considered at low risk for complications related to fluid administration (pulmonary artery occlusion pressure <20 mm Hg, left ventricular ejection fraction >= 40%). All patients were instrumented with an arterial line and a pulmonary artery catheter. Cardiac filling pressures and cardiac output were measured before and after intravascular fluid administration (20 mL/kg of lactated Ringer`s solution over 20 min), whereas Delta PP was automatically calculated and continuously monitored. RESULTS: Fluid administration increased cardiac output by at least 15% in 39 patients (66% = responders). Before fluid administration, responders and nonresponders were comparable with regard to right atrial and pulmonary artery occlusion pressures. In contrast, Delta PP was significantly greater in responders than in nonresponders, (17% +/- 3% vs 9% +/- 2%, P < 0.001). The Delta PP cut-off value of 12% allowed identification of responders with a sensitivity of 97% and a specificity of 95%. CONCLUSION: Automatic real-time monitoring of Delta PP is possible using a standard bedside rnonitor and was found to be a reliable method to predict fluid responsiveness after cardiac surgery. Additional studies are needed to determine if this technique can be used to avoid the complications of fluid administration in high-risk patients.

Use of an Inflatable Silicone Balloon Improves the Success Rate of Bladder Autoaugmentation at Long-Term Followup

Purpose: Most groups have reported disappointing results with autoaugmentation or detrusor myectomy for low capacity/compliance neuropathic bladders. Failure may be due to an ischemic diverticulum or mucosal shrinkage. We investigated whether a Silimed (R) silicone balloon placed in the bladder after autoaugmentation could prevent these problems, improving surgical results. Materials and Methods: We compared the results of standard bladder autoaugmentation in 12 children (group 1) with those in 10 (group 2) who underwent the same surgery using a bladder conformer. The conformer was a silicone balloon filled with saline that remained in the bladder for 2 weeks. All patients had a neuropathic bladder with poor capacity and compliance, resulting in urinary leakage between catheterizations. Preoperative and postoperative evaluation included a voiding diary, ultrasound, voiding cystourethrogram and urodynamics. Results: In group 1 only 1 patient became dry, 4 had little improvement in continence, 4 remained unchanged and 3 became worse. In group 2, 6 patients (60%) become continent without medication, 2 (20%) become continent with oxybutynin and 2 remained unchanged. Bladder capacity and compliance did not change significantly in group 1. However, in group 2 capacity changed from a mean of 140 to 240 ml and mean +/- SD compliance increased from 15.6 +/- 16.8 to 34.3 +/- 22.8 ml/cm H(2)O (p = 0.02). Conclusions: The inflatable balloon improved our long-term results of bladder auto-augmentation. A larger series may be necessary to confirm procedure efficacy and safety.

Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery

Pulmonary hypertension represents an important cause of morbidity and mortality in patients with mitral stenosis who undergo cardiac surgery, especially in the postoperative period. The aim of this study was to test the hypothesis that inhaled nitric oxide (iNO) would improve the hemodynamic effects and short-term clinical outcomes of patients with mitral stenosis and severe pulmonary hypertension who undergo cardiac surgery in a randomized, controlled study. Twenty-nine patients (4 men, 25 women; mean age 46 2 years) were randomly allocated to receive iNO (n = 14) or oxygen (n = 15) for 48 hours immediately after surgery. Hemodynamic data, the use of vasoactive drugs, duration of stay, and short-term complications were assessed. No differences in baseline characteristics were observed between the groups. After 24 and 48 hours, patients receiving iNO had a significantly greater increase in cardiac index compared to patients receiving oxygen (p < 0.0001). Pulmonary vascular resistance was also more significantly reduced in patients receiving iNO versus oxygen (-117 dyne/s/cm(5), 95% confidence interval 34 to 200, vs 40 dyne/s/cm5, 95% confidence interval 34 to 100, p = 0.005) at 48 hours. Patients in the iNO group used fewer systemic vasoactive drugs.(mean 2.1 +/- 0.14 vs 2.6 +/- 0.16, p = 0.046) and had a shorter intensive care unit stay (median 2 days, interquartile range 0.25, vs median 3 days, interquartile range 7, p = 0.02). In conclusion, iNO immediately after surgery in patients with mitral stenosis and severe pulmonary hypertension improves hemodynamics and may have short-term clinical benefits. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1040-1045)

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T 19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T 19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.