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Trigger finger is the second cause of consultation with the hand surgeon. In 2009, Kerrigan published a strategy for the treatment of this pathology, which consists of two infiltrations with corticosteroids in the sheath of the flexor tendons at the level of the A1 pulley, followed by percutaneous or open surgical release, following the algorithm described by the author. 140 files that met the inclusion criteria were analyzed. It was found that the female gender is the most frequently affected during the sixth decade of life in 46%. The most frequently affected finger is the third, affects the right hand in 44% and both hands in 29%. 91% of the patients received a first infiltration and only 31% of these received a second infiltration. The surgical procedure was decided in 33% of the patients. The longest follow-up was 180 months and the shortest was 3 months with 100% of asymptomatic patients. The algorithm proposed by Kerrigan in the treatment of this pathology is a good strategy that has a high success rate without having to perform a surgical procedure as the first treatment option.

Introduction: The incidence of dermatological malignancies increases with age and a considerable percentage of older adults will require radical surgeries and adjuvant treatments, microsurgery allows repair and coverage of major defects with success rates of up to 90%. Case Report: We present the case of an elderly patient with an ulcer in the left clavicular region without evidence of healing. Histological and imaging studies were performed, a basal cell carcinoma subtype morphea was found. A wide excision and axillary lymph node dissection were performed, subsequently covering the defect with a free flap. There is an 11-year follow-up. Conclusion: Complications in microsurgical reconstructions are more associated with comorbidities than with the age of the patient. The same success rates can be obtained in elderly patients.

Immune response plays a dual role in COVID-19 infection. On the one hand virus activates innate and adaptative immune responses that most of the times achieve antiviral control. On the other hand in a minority of patients uncontrolled inflammatory response may lead to harmful tissue damage. Here we summarize the current state of knowledge of the factors that contribute to disease severity and death and the rationale of the posible therapeutic strategies.

Cardiac resynchronization therapy (CRT) with left ventricular (LV) MultiPoint™ pacing (MPP) has been shown to improve CRT response by pacing two LV sites (LV1, LV2). While an additional LV pacing site reduces battery longevity, this cost can be minimized by leveraging an existing device-based capture management algorithm (LVCap™ Confirm). The purpose of this study was to evaluate the MPP battery longevity improvement achieved by configuring LV pacing sites to properly leverage LVCap Confirm. Patients previously enrolled in the MORE-CRT MPP trial with existing MPP-enabled CRT-D devices (Abbott Quadra Assura MP™ CD3371-40QC, Quartet™ LV lead) underwent device interrogation. Device electrical characteristics and estimated battery longevities were compared for various MPP settings. At 2.1 ± 1.1 years post-implant, the estimated remaining battery longevity in 65 patients was 70 ± 14 months with MPP Off (LV pacing from minimum capture threshold). Enabling MPP with maximal anatomical separation between LV1 and LV2 cathodes reduced longevity by 15 ± 14%. However, swapping the LV1 and LV2 cathodes, such that the LV1 threshold was the higher of the two, allowed the device to take full advantage of the LVCap™ Confirm capture management algorithm, resulting in significantly lower longevity reduction of 9 ± 11% (p

Introduction: Vascular malformations are anomalies of the vascular system, constituted by a network of vessels with mature endothelium, with normal cell replacement without proliferation capacity. Case Report: We report the clinical case of a 25-year-old man who came to the hospital for left pelvic limb edema and lumbar pain. An ultrasonography (USG) and positron emission tomography-computed tomography (PET-CT) revealed deep vein thrombosis of the inferior vena cava (IVC) and left iliac vein and a 9.5 cm × 5 cm retroperitoneal nometabolic tumor compatible with perivascular lymphadenopathies. Exploratory laparotomy was performed, transperitoneum exploration of the retroperitoneum and resection of the tumor arising from the IVC and left iliac vein. Pathological examination revealed a 10 cm retroperitoneal tumor filled with venous vessels and fibrotic septa. Postoperative diagnosis was venous malformation of the IVC. Conclusion: Cavernous hemangiomas are not true vascular tumors, but rather a congenital vascular anomaly. It is classified by International Society for the Study of Vascular Anomalies as venous malformation. This tumor is present from birth, and it grows with the child, they do not involute spontaneously. A differential diagnosis of vena cava tumors is leiomyosarcoma. This is the first case in literature of a vascular malformation (formerly called cavernous hemangioma) involving the IVC. It is important to know that this benign pathology has an excellent prognosis and survival after a successful surgery.

Background Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. Methods We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls. Results The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P Conclusions Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.

Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.

OBJECTIVES The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. BACKGROUND Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. METHODS A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 +/- 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. RESULTS Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p = 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p = 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p = 0.25). CONCLUSIONS Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects. (C) 2021 by the American College of Cardiology Foundation.

INTRODUCTION AND OBJECTIVES: The ADVANCE III trial showed that a delayed-detection strategy reduces implantable cardioverter-defibrillator (ICD) therapies. Here, we describe the adherence to and predictors of ADVANCE adoption and compare ICD therapy rates between patients with and without ADVANCE programming. METHODS: This observational retrospective study analyzed patients implanted with Medtronic ICDs included from 2005 to 2016 in a Spanish national multicenter registry (UMBRELLA database; ClinicalTrials.gov, NCT01561144). Changes in ADVANCE programming adoption were described in relation to a) publication of the ADVANCE trial, b) implementation of an "ADVANCE awareness" campaign, and c) publication of an expert consensus statement. Multivariate logistic regression identified predictors of adoption. Therapy incidence rates were compared between groups by estimating the adjusted incidence rate ratio (aIRR) using negative binomial regression. RESULTS: A total of 3528 patients were included. An ADVANCE strategy was used in 20% overall and in 44% at the end of the study. ADVANCE III adoption increased after trial publication, with less growth after an "ADVANCE awareness" campaign and after expert consensus statement publication. Predictors of ADVANCE adoption were as follows: ICD device with a nominal number of intervals to detect 30/40 (aOR, 4.4; 95%CI, 3.5-5.4), implantation by an electrophysiologist (aOR, 1.7; 95%CI, 1.4-2.2), and secondary prevention (aOR, 3.2; 95%CI, 2.6-3.9). Dual-chamber ICDs (aOR, 0.6; 95%CI, 0.5-0.8) and cardiac resynchronization-defibrillators (aOR, 0.5; 95%CI, 0.4-0.7) were associated with lower adoption. ADVANCE programming was associated with reduced total therapy burden (aIRR, 0.77; 95%CI, 0.69-0.86) and fewer inappropriate shocks (aIRR, 0.66; 95%CI, 0.52-0.85). CONCLUSIONS: ADVANCE adoption remains modest and can be improved through evidence-driven selection of nominal ICD settings. ADVANCE programming is associated with reduced therapy rates in real-world ICD recipients.

Background Large‐scale studies describing modern populations using an implantable cardioverter‐defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real‐world ICD patients with different heart disorders. Methods and Results The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29–1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07–1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43–2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54–0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14–0.45) showed a lower risk. All‐cause death was 13.4% at follow‐up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58–5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18–5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25–6.99) had the worst prognoses. Delayed high‐rate detection was enabled in 39.7% of patients, and single‐zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow‐up was low (6%) and did not differ among type of ICD but was lower in SmartShock‐capable devices. Conclusions Irrespective of the cause, contemporary ICD patients with heart failure–related disorders had a similar risk of ICD life‐saving interventions and death. Current ICD programming recommendations still need to be implemented. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NTC01561144.

Abstract/Introduction Decompensated congestive heart failure (CHF) is a main and increasing health problem worldwide, which leads to patients’ bad outcomes and high money expenditure. Direct relationship between Brain Natriuretic Peptides (NT-proBNP) increasing levels and adverse clinical outcomes have been demonstrated in patients with CHF. SonR signal sensor, a micro-accelerometer embedded in the tip of the atrial lead in patients implanted with devices, picks up cardiac muscle vibration. Its amplitude is a surrogate for cardiac contractility, which is found to be further reduced in patients with decompensated CHF. Purpose We sought to find a significant inverse correlation between SonR signal and NT-proBNP levels, in order to use SonR as a surrogate of NT-proBNP to anticipate worsening CHF leading to hospital admission. Methods AVCs SONR trial is a pilot, prospective, observational, multicentre study, in which patients with dilated cardiomyopathy, any aetiology, LV ejection fraction ≤ 30%, at least one recent (< 1 year) hospital admission due to CHF, and implanted with CRT-D devices (used as dual-chamber, no left ventricular (LV) lead implanted) with SonR sensor feature, were enrolled. During a year, NT-proBNP and SonR values were obtained every month, and both levels compared (Pearson’s test) Results This an interim analysis of our data, 18 months after the first patient was enrolled. Twenty two patients and 116 data pairs were analysed. Most patients were men (91%) and had ischemic dilated cardiomyopathy (59%). Mean age was 61 (range 34-82) and mean LV ejection fraction was 27% (range 15-30). The mean Pearson’s correlation coefficient of the NT-proBNP values and the SonR signal was r = - 0.36 (95% CI -0.51 to -0.19), p < 0.00006 (Figure) Conclusions The interim analysis of this study shows an inverse and very significant relationship between SonR signal and NT-proBNP values. This suggests SonR signal might be used as predictor of worsening CHF. Abstract Figure

Early and moderate Parkinson’s disease patients seem to have attention dysfunctions manifested differentially in separate attention streams: top-down and bottom-up. With a focus on the neurophysiological underpinnings of such differences, this study evaluated source-localized regional activity and functional connectivity of regions in the top-down and bottom-up streams as well as any discordance between the two streams. Resting state electroencephalography was used for 36 Parkinson’s disease patients and 36 healthy controls matched for age and gender. Parkinson’s disease patients showed disproportionally higher bilateral gamma activity in the bottom-up stream and higher left alpha2 connectivity in the top-down stream when compared to age-matched controls. An additional cross-frequency coupling analysis showed that Parkinson’s patients have higher alpha2-gamma coupling in the right posterior parietal cortex, which is part of the top-down stream. Higher coupling in this region was also associated with lower severity of motor symptoms in Parkinson’s disease. This study provides evidence that in Parkinson’s disease, the activity in gamma frequency band and connectivity in alpha2 frequency band is discordant between top-down and bottom-up attention streams.

Background When permanent pacemaker implantation is not possible or advisable via superior venous access (i.e., axillary or subclavian veins), safe and feasible surgical alternatives are required. The femoral approach is relatively unknown and seldom studied. This single-center study analyzed 10-year outcomes of a femoral implantation approach. Methods Data about the implantation procedure (indication, approach, lead and pacemaker models, complications), patient characteristics (age, sex, medications, comorbidities), and follow-up were analyzed for all permanent pacemaker implantations using the femoral approach between June 2001 and June 2011. Results A permanent pacemaker was implanted with the femoral approach in 50 patients (mean age, 76 years [range: 45-96], 31 [61%] men). The most frequent indication was atrioventricular block, associated with sinus rhythm in 30 patients and with atrial fibrillation in eight patients. Overall, 20 patients (40%) were treated with oral anticoagulants postimplantation. Mean implantation time was 64 minutes (range: 20-210) and mean fluoroscopy time was 6.7 minutes (range: 0.2-50). Minimum follow-up window was 1 year (June 2012), with a mean of 50 months [range: 1-113]). No deaths, septic episodes, or severe complications were associated with the procedure, acute or long-term. Follow-up data were available for 46 patients, of who 21 (46%) died during follow-up (mean age, 87 years [range: 73-101]). No cause of death was associated with the femoral technique. Conclusion Permanent pacemaker implantation through femoral access is not difficult for an experienced implant surgeon. Outcomes were comparable to systems implanted by superior venous approach, and no severe complications were observed at 10-year follow-up.

Microsurgical reconstruction of complex midfacial and maxillectomy defects is among the most challenging procedures in plastic surgery, and it often requires composite flaps to improve functional and aesthetic results. Various factors have been identified as having influence in the outcome of microsurgical reconstruction. In this article, the authors present their experience with immediate and delayed reconstruction of complex maxillectomy defects in a tertiary center in Mexico. The authors present a total of 37 patients with microsurgical reconstruction of a complex maxillectomy defect; 13 patients had immediate and 24 had delayed reconstructions. The authors recommend doing immediate reconstruction when feasible.

Facial paralysis has a profound impact on the brow, and currently static procedures are the mainstay of treatment. The deep temporal branches of the trigeminal nerve, given their proximity to the brow, may serve as possible donor nerves for both potential innervation of a free muscle transfer in patients with prolonged facial palsy or nerve transfers in acute or subacute palsy. As such, the authors present the detailed surgical anatomy of the deep temporal nerve, assessing feasibility for both functional muscle and nerve transfers, including a proposed surgical technique.Thirty cadaver hemifaces were dissected to establish deep temporal nerve anatomy and perform axonal analysis.Two (53 percent) or three (47 percent) divisions of the deep temporal nerve were noted, with the most consistent division being the middle division (30 of 30 specimens). This division was consistently found approximately 4.1 cm (range, 3.7 to 4.5 cm) anterior to the tragus at the level of the zygomatic arch. For each 1 cm cranial to the arch, the nerve courses approximately 1 mm posteriorly. The number of axons in the proposed temporal branch is 1469 as it emerges from behind the zygomatic arch, 889 at 1 cm, 682 at 2 cm, 534 at 3 cm, 355 at 4 cm, 377 at 5 cm, and 256 at 6 cm.Given its anatomical consistency, and expendability, the middle division of the deep temporal nerve is a viable donor nerve for dynamic upper facial reanimation with either nerve transfer or functional muscle transfer, depending on the length of facial palsy.Therapeutic, V.

Background Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence. Although RRP is available in all current implantable cardioverter defibrillators (ICDs), the outcomes of this pacing mode in ICD patients are unknown. The aim is to evaluate the relationship between atrial RRP and atrial arrhythmias in ICD recipients. Methods Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed. Results Data from 415 patients and 80,707 AT/AF episodes (median duration: 0.4 hours) were collected after a 21.3 ± 14.1-month follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated with a higher atrial pacing percentage in the overall study population (51.2 ± 33.8% vs 18.4 ± 25.7%, P 23 hours) were previous AF (odds ratio [OR]: 7.98; 95% confidence interval [CI]: 4.11–15.47; P < 0.001) and atrial RRP (OR: 3.58; 95% CI: 1.82–7.03; P < 0.001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with a history of AF (43% vs 70%, P = 0.035) and without a history of AF (82% vs 97%, P = 0.004) at 2 years. Conclusions Atrial RRP in ICD patients was related to a higher incidence of sustained atrial arrhythmias. This pacing mode may have an atrial proarrhythmic effect on ICD patients, especially among those with a history of AF.

This paper analyses the influence of the presence of polypropylene fibres in the microstructure of a high-strength self-compacting concrete by X-ray computed tomography and its consequences on the mechanical and fracture properties. The addition of PP fibres alters the pore structure of the concrete matrix, and this affects the macroscopic response (i.e., mechanical and fracture behaviour). A microstructural analysis of an unreinforced concrete, used as reference mix, and two polypropylene fibre-reinforced mixes with two fibre length (6 and 24 mm) were experimentally carried out. Complementary, a comprehensive experimental study of the mechanical and fracture properties of each concrete were performed. Finally, it was established a correlation between the microscopic response (pore morphology and pore distribution) and the macroscopic behaviour of high-strength self-compacting concrete.

Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. Summary Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of 75 years and intracranial malignancy.

BACKGROUND A left ventricular (LV) endocardial lead implant to achieve cardiac resynchronization therapy (CRT) is feasible when a conventional implant failed due to anatomical or technical issues or when the venous implant was performed but the patient did not respond to the therapy. METHODS Data about the implantation procedure (age, sex, clinical characteristics, anticoagulant use, and previous devices), patient characteristics (indication, technique used, lead model, complications), and follow-up (clinical and echocardiographic outcome, LV lead electrical measurements) were analyzed for all CRT systems implanted using LV endocardial lead, due to failed conventional implant or nonresponse, between April 2011 and November 2016. RESULTS Thirty-five patients were implanted with an active fixation LV endocardial lead during the study period, without significant complications. There were no dislodgements or severe complications related to the implant procedure in the follow-up period (36 ± 20 months) and a high percentage of patients responded to therapy, as assessed by several indicators. CONCLUSIONS An LV endocardial lead implant was feasible when the conventional technique had previously failed or was not effective. A high rate of response was achieved without any significant complications.

ResumenAntecedentesEl desarrollo y aplicación de imágenes tridimensionales en cirugía laparoscópica ha brindado los beneficios de la percepción de profundidad, de la que la laparoscopia tradicional carecía. Existen estudios al respecto en poblaciones con experiencia quirúrgica previa y para limitar este sesgo de selección realizamos este estudio en población sin experiencia previa.Material y métodosEstudio experimental, abierto, transversal y comparativo en el que se evaluaron los logros obtenidos con un equipo 2D de cirugía laparoscópica y un equipo 3D, siendo cada sujeto su propio control. Se evaluaron 6 destrezas realizadas en 2D y 3D.ResultadosSe incluyó a un total de 40 participantes, de los cuales 20 comenzaron los ejercicios en 2D y 20 en 3D. En el 72%, de 118 destrezas se mejoró el tiempo de realización con 3D, contra solo 37% en 2D (p=0.000). El porcentaje al final de los ejercicios en el grupo de 3D tanto en el primero como en el segundo ejercicio fue mayor de manera estadísticamente significativa y se observaron menores tiempos al realizar los ejercicios en 3D. Un 52.5% de los participantes prefirieron el equipo 3D, el 15% el 2D y el 32.5% no tuvieron preferencia por ninguno.DiscusiónComo se ha encontrado en diversos estudios, existió mejoría en el desempeño en el grupo 3D. Al ser población sin experiencia quirúrgica previa, se elimina este sesgo del estudio.ConclusionesLa realización de destrezas laparoscópicas en 3D mostró ventajas en comparación con 2D, con mayor porcentaje de finalización, menores tiempos para realizarlas y menor curva de aprendizaje.AbstractBackgroundThe development and application of 3D images in laparoscopic surgery has brought the benefit of in-depth perception that traditional laparoscopic surgery lacked. Previous studies in surgical populations have demonstrated the advantages of 3D technology. To limit bias of the previous experiences of participants, this study was performed in a population without any experience in this area.Material and methodsAn experimental, open, cross-sectional, comparative study between surgical skills achievements using 2D and a 3D laparoscopy equipment, using each subject as their own control. Six skills were evaluated in 2D and 3D modalities.ResultsOf the 40 participants included, 20 began the skills in the 2D modality and then performed them in 3D, and the other 20 began in 3D. Of the 118 skills evaluated there was a time improvement in 72% in the 3D group compared to 37% in the 2D modality (P=.000). The accomplishment percentage using the 3D laparoscopy was greater for both groups. There was a statistically significant difference in the better time for the 3D performed tasks. Just over half (52.5%) of participants preferred 3D laparoscopy, 15% preferred 2D, and 32.5% had no preferences.DiscussionAs other studies have demonstrated, there was improvement in the overall performance using the 3D laparoscope. Bias was limited by using a population without surgical experience.Conclusions3D laparoscopic surgical skills showed superior to 2D, with higher percentages of tasks completion, less time in performing them, and a shorter learning curve.

Importance Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers in Asia, Africa, Europe, and North, Central, and South America between August 2010 and November 2013. Adult patients with active cancer (defined as histologic diagnosis of cancer and receiving anticancer therapy or diagnosed with, or received such therapy, within the previous 6 months) and objectively documented proximal deep vein thrombosis (DVT) or pulmonary embolism, with a life expectancy greater than 6 months and without contraindications for anticoagulation, were followed up for 180 days and for 30 days after the last study medication dose for collection of safety data. Interventions Tinzaparin (175 IU/kg) once daily for 6 months vs conventional therapy with tinzaparin (175 IU/kg) once daily for 5 to 10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio within the therapeutic range (2.0-3.0) for 6 months. Main Outcomes and Measures Primary efficacy outcome was a composite of centrally adjudicated recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality. Results Nine hundred patients were randomized and included in intention-to-treat efficacy and safety analyses. Recurrent VTE occurred in 31 of 449 patients treated with tinzaparin and 45 of 451 patients treated with warfarin (6-month cumulative incidence, 7.2% for tinzaparin vs 10.5% for warfarin; hazard ratio [HR], 0.65 [95% CI, 0.41-1.03]; P = .07). There were no differences in major bleeding (12 patients for tinzaparin vs 11 patients for warfarin; HR, 0.89 [95% CI, 0.40-1.99]; P = .77) or overall mortality (150 patients for tinzaparin vs 138 patients for warfarin; HR, 1.08 [95% CI, 0.85-1.36]; P = .54). A significant reduction in clinically relevant nonmajor bleeding was observed with tinzaparin (49 of 449 patients for tinzaparin vs 69 of 451 patients for warfarin; HR, 0.58 [95% CI, 0.40-0.84]; P = .004). Conclusions and Relevance Among patients with active cancer and acute symptomatic VTE, the use of full-dose tinzaparin (175 IU/kg) daily compared with warfarin for 6 months did not significantly reduce the composite measure of recurrent VTE and was not associated with reductions in overall mortality or major bleeding, but was associated with a lower rate of clinically relevant nonmajor bleeding. Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk of recurrent VTE. Trial Registration clinicaltrials.gov Identifier:NCT01130025

ICD Programming in Ischemic and Nonischemic Cardiomyopathy Introduction The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. Methods and Results First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11–0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. Conclusion High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy.

Resumen Introduccion y objetivos Se ha demostrado que los desfibriladores automaticos implantables reducen la mortalidad de ciertos pacientes con cardiopatia. El recambio de su bateria es una situacion frecuente en la practica clinica, hasta un 30% de los implantes. El beneficio/riesgo del desfibrilador no es constante en el tiempo, y debe revaluarse en el momento del recambio. El objetivo del estudio es conocer las caracteristicas clinicas y la incidencia de terapias del desfibrilador en los pacientes sometidos a un recambio de generador. Metodos Se realizo un estudio retrospectivo multicentrico basado en los pacientes del registro nacional UMBRELLA, sometidos a recambio por agotamiento de la bateria del desfibrilador. Se analizo la incidencia de arritmias ventriculares mediante monitorizacion a distancia. Se analizaron los factores de riesgo de arritmia ventricular sostenida tras el recambio. Resultados Se incluyo a 354 pacientes (media de edad, 61,8 ± 14,5 anos; varones, 80%; prevencion secundaria, 42%; arritmias ventriculares en el generador explantado, 62%). Tras un seguimiento de 25 meses, 70 pacientes (20%) presentaron terapias apropiadas y 8 (2,3%) tuvieron descargas inapropiadas. El sexo masculino, la presencia de cardiopatia estructural, la insuficiencia cardiaca y la ausencia de resincronizacion fueron predictores independientes de la aparicion de arritmias ventriculares. Conclusiones Una quinta parte de los pacientes tiene terapias apropiadas de desfibrilador en los primeros 2 anos desde el recambio de generador. El conocimiento de los factores asociados a la aparicion de arritmias tras el recambio puede ser util para optimizar el rendimiento de la terapia.

Introduction and objectives Implantable cardioverter-defibrillators reduce mortality in some patients with heart disease. Battery replacement is a frequent occurrence in clinical practice and is required in up to 30% of implants. The benefit/risk ratio of defibrillators varies over time and should be reevaluated at the time of replacement. The aim of this study was to determine the clinical characteristics and incidence of defibrillator therapies in patients who underwent generator replacement. Methods This multicenter retrospective study involved patients from the UMBRELLA national registry who underwent replacement due to defibrillator battery depletion. The incidence of ventricular arrhythmias was determined via remote monitoring. Risk factors for sustained ventricular arrhythmia after replacement were analyzed. Results A total of 354 patients were included (mean age [standard deviation], 61.8 [14.5] years; men, 80%; secondary prevention, 42%; ventricular arrhythmias in the explanted generator, 62%). After a 25-month follow-up, 70 patients (20%) received appropriate therapies and 8 (2.3%) received inappropriate discharges. Male sex, structural heart disease, heart failure, and the absence of resynchronization were independent predictors of ventricular arrhythmia occurrence. Conclusions One-fifth of patients had appropriate defibrillator therapies in the first 2 years after generator replacement. Determination of the factors associated with arrhythmia occurrence after replacement may be useful to optimize implantable cardioverter-defibrillator treatment.

Resumen Introduccion y objetivos La insuficiencia cardiaca cronica es una enfermedad con elevada mortalidad y consumidora de recursos sanitarios y sociales. El objetivo del estudio es cuantificar la utilizacion de los recursos sanitarios y no sanitarios e identificar variables que ayuden a explicar la variabilidad de su coste en Espana. Metodos Estudio multicentrico, prospectivo y observacional con 12 meses de seguimiento. Se incluyo a 374 pacientes con insuficiencia cardiaca sintomatica de consultas especificas de cardiologia, y se recogio informacion sobre caracteristicas socioeconomicas de pacientes y cuidadores, estado de salud, recursos sanitarios y cuidados profesionales y no profesionales. Los recursos empleados en el cuidado de la salud se valoraron monetariamente, diferenciando entre clases funcionales. Resultados El coste total estimado durante ese ano oscilo entre 12.995 y 18.220 euros, dependiendo del escenario elegido (ano base, 2010). La mayor partida fue para los cuidados no profesionales (59,1-69,8% del coste total), seguido del gasto sanitario (26,7-37,4%) y los cuidados profesionales (3,5%). Dentro de los costes sanitarios, el coste hospitalario tuvo el mayor peso, seguido de la medicacion. Hubo diferencias estadisticamente significativas en los costes totales entre los pacientes en clase funcional II y los de clases III - IV . Conclusiones La insuficiencia cardiaca es una enfermedad que requiere la movilizacion de un importante volumen de recursos. La partida mas importante del gasto es la del cuidado informal del paciente. Tanto el gasto sanitario como el no sanitario son mayores en la poblacion con enfermedad mas avanzada.

A B S T R A C T Introduction and objectives: Chronic heart failure is associated with high mortality and utilization of health care and social resources. The objective of this study was to quantify the use of health care and nonhealth care resources and identify variables that help to explain variability in their costs in Spain. Methods: This prospective, multicenter, observational study with a 12-month follow-up period included 374 patients with symptomatic heart failure recruited from specialized cardiology clinics. Information was collected on the socioeconomic characteristics of patients and caregivers, health status, health care resources, and professional and nonprofessional caregiving. The monetary cost of the resources used in caring for the health of these patients was evaluated, differentiating among functional classes. Results: The estimated total cost for the 1-year follow-up ranged from s 12 995 to s 18 220, depending on the scenario chosen (base year, 2010). The largest cost item was informal caregiving (59.1%-69.8% of the total cost), followed by health care costs (26.7%- 37.4%), and professional care (3.5%). Of the total health care costs, the largest item corresponded to hospital costs, followed by medication. Total costs differed significantly between patients in functional class II and those in classes III or IV. Conclusions: Heart failure is a disease that requires the mobilization of a considerable amount of resources. The largest item corresponds to informal care. Both health care and nonhealth care costs are higher in the population with more advanced disease.

A 3 year old intact male pygmy goat developed progressive weakness and eventual recumbancy over the course of 1 week, while maintaining its ability to eat and drink. The animal died and at necropsy, the parietal pleural surfaces and the pericardial surface were noted to be covered with firm, white, variably sized nodules that often formed linear arrays or coalesced into larger clumped aggregates. The visceral pleural surfaces of the ventral lung lobes were also covered with similar nodules. Histopathological and immunohistochemical evaluation of the submitted tissues revealed a diagnosis of mesenchymal chondrosarcoma with extensive seeding throughout the thoracic cavity.

Sin financiación 4.391 JCR (2015) Q1, 25/124 Cardiac and cardiovascular systems UEM

Background: Peroral endoscopic myotomy has recently been developed and performed on patients with good results. Aims: To evaluate the technical feasibility of peroral endoscopic full-thickness and partial thickness myotomy in a porcine model. Material and methods: Eighteen criollo pigs were randomly assigned to 2 groups: group A (partial-thickness myotomy) and group B (full-thickness myotomy). The mucosal defect proximal to the myotomy site was left open. On the seventh postoperative day the pig was euthanized and follow-up surgical exploration was performed. The duration of each procedure, postoperative progression of the animal, complications, and anatomopathologic findings were registered. Results: The procedure was viable in all the pigs. The mean surgery duration was 81 ± 35.3 min (group A 51.11 ± 11.12, group B 111 ± 22.61; P

Background The Quartet™ quadripolar lead (St. Jude Medical Inc., St. Paul, MN, USA) offers 10 different left ventricle pacing configurations that may further influence hemodynamic parameters compared to traditional bipolar pacing configurations. The purpose of this study was to evaluate whether pacing from additional quadripolar lead vectors could enhance cardiac output (CO). Methods For each patient, CO was measured in “no-pacing” and in all the 10 configurations available, within 7 days of implantation of the device. Tip-ring, tip-right ventricular coil (RVC), and ring-RVC vectors were considered as traditional vectors. The seven additional configurations available in the quadripolar lead were considered as nontraditional vectors. CO was measured by ECHO. The best configuration was defined as the one presenting the highest CO measurement within configurations, which have a capture threshold

Surgical management of complete rectal prolapse is challenging. We present our results with the novel technique stapled transanal longitudinal posterior proctectomy (STALPP) in patients with complete rectal prolapse. We performed a retrospective study in two hospitals from January 2005 to December 2012. Twenty-one patients with complete rectal prolapse were included. In all patients, STALPP was performed. The study variables were operative time, intraoperative bleeding, number of cartridges used, length of rectum prolapsed through the anus, length of rectal wall resected, length of hospital stay and preoperative and postoperative Wexner continence score and manometric measurement of anal canal resting tone and squeeze pressure. The median length of prolapsed tissue was 13 cm; the mean Wexner score in the preoperative and postoperative period was 15.95 and 4.95, respectively (p = 0.025). The mean resting tone improved from 23.3 to 32.85 mmHg postoperatively (p = 0.03), as did maximal squeeze pressure from 31 to 62.7 mmHg (p = 0.003). Median operative time was 65 min; median intraoperative bleeding was 12 ml; there was no postoperative bleeding, and no reinterventions were required. The median number of cartridges used was 4. The median length of resected wall in the right posterolateral sector was 8 and 6 cm in the left. The median length of hospital stay was 4 days, and the mean follow-up period was 2 years. No mortality was reported. Stapled transanal longitudinal posterior proctectomy is a safe and feasible surgical alternative for patients with complete rectal prolapse.

Los aneurismas del tronco comun de la coronaria izquierda (TCCI) son muy infrecuentes (0,1%) y la mayoria de ellos esta relacionada con lesiones obstructivas ateroscleroticas. Sin lesiones coronarias asociadas se han publicado hasta el momento solo unos pocos casos aislados. El manejo de estos pacientes no esta bien establecido y se ha postulado tanto el manejo quirurgico como el conservador. Presentamos un caso de un aneurisma gigante del TCCI de diametro 27,7 x 18,6 mm (el mayor publicado hasta la fecha) sin estenosis coronarias asociadas, el cual fue tratado de forma conservadora solamente con anticoagulacion oral, presentando en el seguimiento a 5 anos una evolucion muy favorable.

Overweight and obesity are two of the most important public health problems in Mexico. There is a clear association between lifestyle and obesity. This relationship means that unhealthy lifestyles can modify people's physiological response through adipocytokines, proinflammatory factors which are closely related to chronic degenerative diseases. Obesity causes low-grade chronic inflammation. Adipose tissue, in addition to its function of storing energy reserves in the form of triglycerides, has important functions as an endocrine organ, producing a variety of molecules called adipocytokines such as IL-1, IL-6, IL-8, IFNγ, TNFα, leptin and resistin. The production of these molecules by adipocytes, coupled with the destruction of these cells, induces the inflammation to become chronic, and influences other systems by altering their functions, which leads to different diseases. Understanding the relationship between the different components of lifestyle and the production of adipocytokines involved in the development of chronic degenerative diseases, will allow us to address the problem and hence reduce the morbidity and mortality caused by these diseases.

Although the etiology of multiple sclerosis (MS) is unknown, it is generally believed that genetic, immunologic, and environmental factors are involved. The objectives of this study were: 1. to analyze if a genetic control could explain why HHV-6 would be able to actively replicate in a subset of MS patients but not in controls; 2. to study if MS patients with HHV-6 active replication are clinically different from those without HHV-6 active replication. A total of 195 MS patients and 195 controls were analyzed for two SNPs at the MHC2TA locus and two SNPs at the CD46 locus. Furthermore, the MS cohort was analyzed by PCR for the detection of HHV-6 genomes in five serum samples collected every six months along two-year follow-up. We found that 59/195 (30.2%) MS patients had at least one HHV-6 positive serum sample. No statistical significant difference was found for the two genes when the comparison was made between MS patients and controls; however, a statistical significance was found for the two polymorphisms of MHC2TA when we compared MS patients with active replication and controls (p=0.0000004 for rs4774C and p=0.011 for rs3087456G). Furthermore, increased significant differences were found for MHC2TA and CD46 when we compared interferon beta responders and non-responders within MS patients. In conclusion, we describe a gene-environment interaction in MS patients between HHV-6 and MHC2TA and CD46 that should be further studied to clarify if that interaction could be a genetic control. The results show that MS patients without HHV-6 active replication are better responders to interferon beta treatment than those with HHV-6 active replication.

The group of major histocompatibility complex (MHC) alleles known as shared epitope (SE) is to date the strongest rheumatoid arthritis (RA) genetic risk factor. Many studies have shown that the measurement of anti-citrullinated peptides antibodies would be useful in the diagnosis and follow-up of RA. Our aim is to determine the magnitude of the association between the possession of SE alleles and serum positive titres of antibodies against citrullinated peptides. Our selection criteria included case–control or cohort studies, where data involving antibodies against citrullinated peptides and SE in RA patients were available. No date or language restrictions were imposed. Bibliographical databases MEDLINE, Cochrane Database of Systematic Reviews and EMBASE were searched for pertinent literature. Two reviewers independently identified relevant citations and extracted data. Data extraction was then checked by two different reviewers. Five published and one unpublished (own data) studies were included in the final meta-analysis. Overall, 2700 European descent RA patients were included in this meta-analysis. A significant association between SE and positive titres of serum antibodies against citrullinated peptides [OR(95% CI) = 3.19 (2.21–4.60)] was found. Positive titres for antibodies against citrullinated peptides are threefold more frequent in RA patients who carry SE alleles than in those patients lacking them.

To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO. Genotyping of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 and signal transducers and activators of transcription 4 (STAT4) rs7574865 polymorphism was performed using fast real-time PCR System. Shared epitope, antibodies directed against cyclic citrulinated peptide (anti-CCP) antibodies and a higher level of education were associated with a younger age at disease onset (P = 0.033, P = 0.004 and P < 0.0001, respectively). Neither carriers of the minor allele of PTPN22 rs2476601 nor STAT4 rs7574 polymorphisms showed a significant association with a younger age at disease onset (P = 0.355, P = 0.065, respectively). We found an additive effect of the three genetic markers in the age at onset: subjects with three markers were associated with a disease onset 9.56, 8.61, and 6.41 years before than those with none, one, or two genetic markers (P = 0.004, P = 0.006 and P = 0.043, respectively). We also described the additive effect of shared epitope, anti-CCP antibodies, educational level, PTPN22, and STAT4 polymorphisms in age at onset. Patients with two, three, four, or five variables were associated with a significant younger age of disease onset (4.72 [0.05–9.38] years (P = 0.048), 9.56 [4.72–14.40] years (P < 0.0001), 12.74 [6.84–18.64] years (P < 0.0001), and 20.87 [10.40–37.17] years (P < 0.0001)). Risk factors for the development of rheumatoid arthritis are also associated, with an additive effect, with a younger age at disease onset.

Idiopathic achalasia is an esophageal motor disorder of unknown etiology. A wealth of evidence supports the concept that achalasia is an immune-mediated disease. According to this evidence, achalasia has been significantly associated with specific alleles of the human leukocyte antigen class II, PTPN22 and IL23R. Several studies have demonstrated association of the IL10 gene with different inflammatory disorders. Our aim was to evaluate the role of functional IL10 promoter polymorphisms in susceptibility to idiopathic achalasia. A case-control study was performed with the -1082, -819, and -592 IL10 promoter polymorphisms in 282 patients and 529 controls and in an independent replication set of 75 patients and 575 controls. The GCC haplotype of the IL10 promoter was reported to be associated with a lower risk of achalasia in the discovery sample (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64-0.98, p = 0.029). This association was validated in a replication set (OR = 0.69, 95% CI = 0.48-1.00, p = 0.04). In the combined analysis no heterogeneity was observed between the 2 sample sets and the GCC haplotype was significantly associated with the disease (OR(MH) = 0.76, 95% CI = 0.63-0.91, p = 0.003). Our results provide the first evidence for an association between IL10 promoter polymorphisms and idiopathic achalasia, suggesting that the interleukin-10 cytokine may contribute to the pathogenesis of this disease.

BACKGROUND. With Dental Caries being the most common disease amongst children in the world today, there is a need to fully understand risk factors that may be related to caries prevalence and how they could be best addressed. AIM. The aim of this study was to evaluate soda, juice, sugared-beverage intake, brushing habits, and community water source availability as they relate to the prevalence of both noncavitated and cavitated caries lesions in small rural villages in Mexico. DESIGN. The International Caries Detection and Assessment System (ICDAS) was used in children from small, isolated, villages in Mexico. Risk factors were assessed via questionnaires. RESULTS. Caries prevalence in the villages was very high, ranging from 94.7% to 100% of the children studied. The mean number of surfaces with lesions per child (D1MFS + d1mfs) having scores ≥1 (noncavitated and cavitated) ranged from 15.4 ± 11.1 to 26.6 ± 15.2. Many of the children reported drinking beverages containing sugar. CONCLUSIONS. Drinking sugared beverages, poor oral hygiene habits, and lack of access to tap water were identified as risk factor for caries in this sample of residents of rural Mexico.

The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D). This result was confirmed by a follow-up study that pointed to new independent signals within the region. However, both studies were performed in patients with an early-onset T1D. We aimed at replicating the previous results and studying the influence of these polymorphisms in the age at T1D debut. We genotyped 439 T1D Spanish subjects (age at onset, 1 to 65 years) and 861 controls for two PTPN2 single nucleotide polymorphisms (SNPs), rs2542151 and rs478582, and studied the effect of both polymorphisms in age at onset through stratified and continuous analyses. The frequency of rs2542151*G carriers was significantly higher in the early-onset group compared with late-onset patients (p = 0.023) and with controls (OR = 1.61 [1.14–2.26]; p = 0.005). No significant differences were found between controls and late-onset patients. The log-rank chi-square test for the Kaplan–Meier plots (carriers of susceptibility allele vs non carriers) was statistically significant (χ 1df 2 = 4.485; p = 0.034), yielding an earlier disease debut for G carriers. The analysis of the SNP rs478582 did not reach statistical significance. In summary, we replicate the association detected by the WTCCC and propose that the rs2542151*G allele confers risk to an earlier onset of T1D.

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replicationTNFRSF6B-rs4809330 A: P=0.028, OR1.13; TNFRSF14-rs6684865 A: overall P=0.0008, OR=1.2; and HHV6-positive patients vs controls: P=0.017, OR=1.69. © 2011 Macmillan Publishers Limited All rights reserved.

Objective Genetic variants located close to 2 genes codifying for members of the tumor necrosis factor receptor superfamily (TNFRSF), TNFRSF14 and TNFRSF6B, have recently been associated with rheumatoid arthritis (RA) and with inflammatory bowel disease susceptibility, respectively. The TNFRSF6B protein has been related to osteoclastic activity, apoptosis inhibition, and modulation of T cell activation and differentiation. Interestingly, peptides encoded by both genes bind a common ligand called LIGHT, which is overexpressed in RA synovium. The aim of this study was to investigate the combined effect of the TNFRSF14 rs6684865 and TNFRSF6B rs4809330 polymorphisms in RA predisposition. Methods TaqMan genotyping of these polymorphisms was conducted in 649 patients with RA and 553 ethnically matched control subjects (first study). To validate the results, an independent replication cohort with 211 patients and 255 control subjects was additionally studied (replication study). Results The frequency of the rs6684865 G allele in the RA subgroup with the rs4809330 GG susceptibility genotype was significantly higher than that in the other patients with RA (74% versus 65%; P = 0.002) or in control subjects (74% versus 67%; P = 0.003). Because no significant differences between the control and patient groups in the first and replication studies were observed, the data were pooled. When compared with control subjects overall, the effect of the rs6684865 G allele in the group with the rs4809330 GG genotype (odds ratio [OR] 1.49) was significantly different from the effect observed in the group carrying the rs4809330 A allele (OR 0.97; P = 0.0015 by Breslow-Day test of homogeneity). Conclusion We have identified and replicated a novel gene–gene interaction between 2 polymorphisms of TNFRSF members in Spanish patients with RA, based on the hypothesis of shared pathogenic pathways in complex diseases.

Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (PMantel-Haenszel, odds ratio (OR) M-H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65-0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06-1.34); for rs41295061: 0.03, 0.77 (0.60-0.98)); showed a trend for association of the IL2/IL21 rs6822844 (P M-H 0.07, OR M-H (95% CI)0.86 (0.73-1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation. © 2010 Macmillan Publishers Limited All rights reserved., Concepción Núñez holds a research contract from Fondo Investigaciones Sanitarias (CA06/0163) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This study was supported by grants from: Alfonso Martín Escudero Foundation and Fondo Investigaciones Sanitarias FIS PI07/0353, FIS PI07/0369, PI08/1636 and Plan Nacional PN-SAF2006-02023.

Background: Thr300Ala polymorphism in ATG16L1 was reported as a susceptibility factor to Crohn's disease (CD). Inconsistently replicated associations with ulcerative colitis (UC) and specifically with ileal CD were also reported. Our aims were: to replicate the ATG16L1 Thr300Ala association with inflammatory bowel disease (IBD) in the Spanish population, to perform a meta-analysis to determine the risk conferred to the different IBD subgroups, and to test for the interaction with CARD15 or IL23R risk loci. Methods: Thr300Ala (rs2241880) single nucleotide polymorphism (SNP) was genotyped in 712 IBD patients and 745 controls by TaqMan technology. Genetic frequencies were compared with chi-square tests. Our findings were pooled in a meta-analysis. Results: In Spain, we observed an association of rs2241880 with CD (P = 0.008; odds ratio [OR, 95% confidence interval, CI] = 1.28 [1.06–1.54]), but not with UC. No significant differences emerged when patients were stratified by clinical features. Similarly, the meta-analysis demonstrated a significant association only with CD (P < 10−4; OR [95% CI] = 1.33 [1.28–1.38]). A significant difference between ileal CD patients and controls was observed, but heterogeneity was found in comparisons involving colonic CD patients and definite conclusions cannot be drawn. No interaction between rs2241880 and the established CARD15 or IL23R susceptibility variants was observed. Conclusions: The Thr300Ala polymorphism is associated with CD, regardless of the CARD15 or IL23R status, but not with UC. Stratification by clinical phenotypes did not show definitive results because of the existing heterogeneity among studies. (Inflamm Bowel Dis 2009;)