Outcomes of Roux-en-Y gastric bypass surgery for severely obese patients with type 1 diabetes: a case series report

Roux-en-Y gastric bypass surgery (RYGB) reverses type 2 diabetes (DM2) in approximately 83% of patients with morbid or severe obesity. This procedure has been performed in small numbers of severely obese patients with type 1 diabetes (DM1), but the impact on glycemic control and insulin requirement in this population has not been widely described. We report three patients with DM1 and severe obesity that underwent RYGB. Weight, glycemic control, and insulin requirements before and one year after the procedure were compared. Significant weight loss was achieved by all three patients but insulin requirements decreased in only 2 patients. In contrast, glycemic control (A1C) remained suboptimal in all three patients up to one year after the surgery. These findings suggest that RYGB leads to important weight loss and positively affects insulin sensitivity. However, reaching optimal glycemic control in patients with DM1 diabetes remains challenging due to persisting insulin deficiency

EU Cohesion policy 2007-13 and the implications for Spain : who gets what, when and how?

The recent negotiation of the EU budget and the associated reform of EU Cohesion policy have had major policy implications for Spain, the country in receipt of most Cohesion policy support in the current programming period (2000-06). EU enlargement, combined with relatively rapid growth in Spain, impacted on the eligibility of Spanish regions for Cohesion support while also taking the country as a whole beyond the eligibility threshold for the Cohesion Fund. As a result, based on the original Commission budget proposals of February 2004, Spain was facing a reduced Cohesion policy budget of at least a half (to below €30 billion). This paper first reviews the budget negotiations from a Spanish (Cohesion policy) perspective, identifying the key negotiating goals and the extent to which they were achieved. It then looks at the outcome of the negotiations for Spain, initially at the national level and then in the regions. It highlights the significant differential impacts of the cutbacks in Cohesion policy allocations at the regional level and the pressures on the Spanish government to modulate the regional impact of the budgetary changes. Having considered the direct funding implications of the new Cohesion policy, the second half of the paper is concerned with the regulatory, institutional and economic impacts of the new policy regime. Many of the reform proposals fit with Spanish priorities, not least the new rationale for Cohesion policy (with its stress on the Lisbon and Gothenburg agendas) and the new policy architecture (with all regions eligible for some form of support and with a related shift from a geographic to more of a thematic focus). The retention of the key Structural Funds principles has also been welcomed in Spain, unsurprising given the wealth of experience and expertise built up over three (high-spending) programming cycles. As in most Member States, the main regulatory concern relates to the extent to which a more simplified and devolved approach to Funds' implementation will be achieved in practice. As regards policy and institutional impacts, the paper brings together regional views on the new budgetary and regulatory frameworks and reviews how the new regulations are being implemented in practice. A discussion of the developing National Strategic Reference Framework and the related Operational Programmes makes clear that the strong emphasis on the Lisbon agenda is not viewed as a constraint in Spain; rather, it is felt to fit well with recent Spanish developments and goals. Finally, the paper considers the economic implications of the reductions in Cohesion policy support. On the basis of evaluation studies, it highlights the positive impact the Funds have had in the past and the potentially quite varied regional impacts the reductions in funding may have in the future

Familial chylomicronemia syndrome: A family case report in U.S./Mexico border by CEDIAMET

Primary familiar hyperchylomicronemia syndrome (FHS) is an extremely rare autosomal recessive condition. In 80% of cases is a result of a mutation in lipoprotein lipase, meanwhile, the 20% is a malfunctioning enzyme due to APOC2, APOA5, LMF1, or GP1HBP1. It is estimated FHS affects 3000 to 5000 individuals globally, with no correlation by sex or race. We are presenting a family with FHS in Reynosa, Mexico. The index patient was a male 36 years old who attended the CEDIAMET clinic after his 6th episode of acute pancreatitis. He has triglycerides 1300 mg/dl and CT scan with Balthazar C score. He suffered other five episodes of acute pancreatitis since 20 years old with serum triglycerides between 1,000 and 3,000 mg/dL. Each episode progressed in pain intensity and Balthazar score from A to C. The patient received treatment with bezafibrate and captopril because of hypertension. The physical exam shows eruptive xanthomas on his back, otherwise no other clinical relevant findings. He has a family history of recurrent pancreatitis in his father, and two older sisters (from a total of 3 sisters). This is the first case of FHS presented in RGV. To our knowledge, only one mutation in lipoprotein lipase had been described in Guanajuato, Mexico (Colima-Fausto 2017). The p.Gly188Glu mutation affects the lipid-binding region, leading to a complete loss of LPL function. We will research this case to determine if they have a mutation on any of the known genes and if negative, to sequence the regions for seeking new mutation on the U.S.-Mexico border. The common treatment for lowering triglycerides works small or not at all. Other conditions like hypothyroidism or Cushing were ruled out. A specialized exam is the post-heparin activation of lipoprotein lipase inadequate release of the enzyme. The dietary treatment includes a very low-fat diet (no more than 20 to 30 g fat/day), and avoiding alcohol. Plasmapheresis is an option for avoiding acute pancreatitis treatment. Recently, tiparvovec was discontinued in Europe (2007), and was the first gene therapy approved. Volanesorsen is another option that reduces triglycerides by 50 to 80%, currently in phase II and III trials

Monte Carlo simulation method for Laughlin-like states in a disk geometry

We discuss an alternative accurate Monte Carlo method to calculate the ground-state energy and related quantities for Laughlin states of the fractional quantum Hall effect in a disk geometry. This alternative approach allows us to obtain accurate bulk regime (thermodynamic limit) values for various quantities from Monte Carlo simulations with a small number of particles (much smaller than that needed with standard Monte Carlo approaches).Comment: 13 pages, 6 figures, 2 table

Integrating the STOP-BANG Score and Clinical Data to Predict Cardiovascular Events After Infarction A Machine Learning Study

BACKGROUND: OSA conveys worse clinical outcomes in patients with coronary artery disease. The STOP-BANG score is a simple tool that evaluates the risk of OSA and can be added to the large number of clinical variables and scores that are obtained during the management of patients with myocardial infarction (MI). Currently, machine learning (ML) is able to select and integrate numerous variables to optimize prediction tasks. RESEARCH QUESTION: Can the integration of STOP-BANG score with clinical data and scores through ML better identify patients who experienced an in-hospital cardiovascular event after acute MI? STUDY DESIGN AND METHOD: This is a prospective observational cohort study of 124 patients with acute MI of whom the STOP-BANG score classified 34 as low (27.4%), 30 as intermediate (24.2%), and 60 as high (48.4%) OSA-risk patients who were followed during hospitalization. ML implemented feature selection and integration across 47 variables (including STOP-BANG score, Killip class, GRACE score, and left ventricular ejection fraction) to identify those patients who experienced an in-hospital cardiovascular event (ie, death, ventricular arrhythmias, atrial fibrillation, recurrent angina, reinfarction, stroke, worsening heart failure, or cardiogenic shock) after definitive MI treatment. Receiver operating characteristic curves were used to compare ML performance against STOP-BANG score, Killip class, GRACE score, and left ventricular ejection fraction, independently. RESULTS: There were an increasing proportion of cardiovascular events across the low, intermediate, and high OSA risk groups (P = .005). ML selected 7 accessible variables (ie, Killip class, leukocytes, GRACE score, c reactive protein, oxygen saturation, STOP-BANG score, and N-terminal prohormone of B-type natriuretic peptide); their integration outperformed all comparators (area under the curve, 0.83 [95% CI, 0.74-0.90]; P <.01). INTERPRETATION: The integration of the STOP-BANG score into clinical evaluation (considering Killip class, GRACE score, and simple laboratory values) of subjects who were admitted for an acute MI because of ML can significantly optimize the identification of patients who will experience an in-hospital cardiovascular event

Global gene expression profiling of oral cavity cancers suggests molecular heterogeneity within anatomic subsites

<p>Abstract</p> <p>Background</p> <p>Oral squamous cell carcinoma (OSCC) is a frequent neoplasm, which is usually aggressive and has unpredictable biological behavior and unfavorable prognosis. The comprehension of the molecular basis of this variability should lead to the development of targeted therapies as well as to improvements in specificity and sensitivity of diagnosis.</p> <p>Results</p> <p>Samples of primary OSCCs and their corresponding surgical margins were obtained from male patients during surgery and their gene expression profiles were screened using whole-genome microarray technology. Hierarchical clustering and Principal Components Analysis were used for data visualization and One-way Analysis of Variance was used to identify differentially expressed genes. Samples clustered mostly according to disease subsite, suggesting molecular heterogeneity within tumor stages. In order to corroborate our results, two publicly available datasets of microarray experiments were assessed. We found significant molecular differences between OSCC anatomic subsites concerning groups of genes presently or potentially important for drug development, including mRNA processing, cytoskeleton organization and biogenesis, metabolic process, cell cycle and apoptosis.</p> <p>Conclusion</p> <p>Our results corroborate literature data on molecular heterogeneity of OSCCs. Differences between disease subsites and among samples belonging to the same TNM class highlight the importance of gene expression-based classification and challenge the development of targeted therapies.</p

Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer

Fil: Cura, Jorge E. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Blanzaco, Daniel P. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Brisson, Cecilia. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Cura, Marco A. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Cabrol, Rosa. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Larrateguy, Luis. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Mendez, Carlos. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Sechi, Jose Carlos. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Silveira, Jorge Solana. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: Theiller, Elvira. Hospital San Martín. Departamento de Medicina Oncológica, Paraná; Entre Ríos.Fil: de Roodt, Adolfo R. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.Fil: Vidal, Juan Carlos. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Producción de Biológicos; Argentina.A Phase I clinical trial was performed on patients with solid tumors refractory to conventional therapy. Crotoxin was administered i.m. for 30 consecutive days at doses ranging from 0.03 to 0.22 mg/m(2). Patients entered the study after providing a written informed consent. Although 26 patients were entered only 23 were evaluated. Reversible, nonlimiting neuromuscular toxicity evidenced as diplopia because of pareses of the external ocular muscles was present in 13 patients. It started at doses of 0.18 mg/m(2) and lasted from 2 to 6 h. These episodes did not require dose adjustment and disappeared in 1-3 weeks of treatment. Three patients experienced palpebral ptosis, nystagmus (grade 2), and anxiety (grade 2-3) at the dose-limiting toxicity of 0.22 mg/m(2). Also at dose-limiting toxicity, 1 patient showed nystagmus (grade 2) and anxiety (grade 3) without evidence of palpebral ptosis. Transient increases (grades 1-3) in the levels of creatinine kinase, aspartate aminotransferase, and alanine transaminase attributed to crotoxin myotoxicity were observed but returned to normal by the last week of treatment. At 0.21 mg/m(2) there was a case of grade-3 anaphylactic reaction on day 31, which required treatment. Hypersensitivity was regarded as an adverse drug-related reaction, and the patient was removed from the protocol. Two patients at different doses (0.12 mg/m(2) and 0.22 mg/m(2)) had sialorrhea. Four patients had asymptomatic transient increase in blood pressure (up to 20 mm Hg) 12 h after the first injection, which lasted 24 h. No treatment was required and toxicity did not reappear. Six patients experienced slight eosinophilia during the first 2 weeks. The maximum tolerated dose was set at 0.21 mg/m(2). Objective measurable partial responses (>50% reduction of tumor mass) were noted in 2 patients treated at 0.21 mg/m(2) and 1 at 0.12 mg/m(2). One patient (at 0.21 mg/m(2)) presented a complete response on day 110. Crotoxin pharmacokinetics showed rapid absorption from the injection site to blood (t(1/2 A) = 5.2 +/- 0.6 min). Plasma concentration reached a peak (C(max) = 0.79 +/- 0.1 ng/ml) at tau(max) = 19 +/- 3 min. The half-life of the distribution (alpha) phase is 22 +/- 2 min. Starting at 1.5 h after injection, the decrease in plasma concentration becomes slower, reaching 14 +/- 3 pg/ml 24 h after injection. The profile is dominated by the elimination (beta) phase with a half-life of 5.2 +/- 0.6 h. Consequently, 24 h after the injection ( approximately 5 half-life) 97% of the product was eliminated. The area under plasma concentration versus time curve was 0.19 +/- 0.05 microg/min/ml. Assuming availability (F) approximately 1, the clearance is C(L) = 26.3 +/- 7 ml/min, and the apparent volume of distribution is V(d) = 12 +/- 3 liter/kg. The recommended dose for a Phase II study is 0.18 mg/m(2)