Adhesión a dentina parte I: características del sustrato y sistemas adhesivos / Dentin bonding part I: substrate characteristics and bonding systems

La Odontología Restauradora contemporánea no puede concebirse sin la adhesión de los materiales restauradores a las estructuras dentarias. En mu-chos procedimientos restauradores, no sólo el esmal-te sino también la dentina se encuentra involucrada, por lo tanto, la adhesión a esta última juega un rol cla-ve en el éxito clínico. No obstante, todavía supone un gran desafío lograr una adhesión estable y predeci-ble en el tiempo. El propósito del presente artículo es analizar las características principales de la dentina como sustrato adhesivo y describir los sistemas ad-hesivos actuales y sus mecanismos de acción (AU)

Contemporary Restorative Dentistry cannot be conceived without the adhesion of restorative materials to dental structures. In many restorative procedures not only the enamel, but also the dentin is involved, therefore dentin bonding plays a key role in their success. However, it is still a great challenge to achieve stable and predictable dentin bonding over time. The aim of this article is to analyze the main characteristics of dentin as an adhesive substrate and to describe current adhesive systems and their bonding mechanisms (AU)

Adhesión a dentina part II: estrategias para optimizar la adhesión a dentina y protocolos adhesivos / Dentin bonding part II: strategies to optimize dentin bonding and adhesive protocols

La adhesión a dentina con sistemas adhesivos polimé-ricos representa un desafío que surge de la necesi-dad de vincular un sustrato dentario heterogéneo y variable con materiales que presentan todavía cier-tos aspectos a atender para poder conseguir el máxi-mo desempeño. El propósito del presente artículo es evaluar algunas de las estrategias propuestas para mejorar la adhesión a dentina, y sugerir un protocolo de trabajo con los diferentes tipos de sistemas adhesivos (AU)

Dentin bonding with polymeric adhesive systems represents a challenge that arises from the need to link a heterogeneous and variable dental substrate with materials that still have certain aspects to be addressed in order to achieve maximum performance. The aim of this article is to evaluate some of the proposed strategies to improve dentin bonding and to suggest a protocol for each different type of bonding systems (AU)

Cost-effectiveness analysis of treatment sequences containing tofacitinib for the treatment of rheumatoid arthritis in Spain.

OBJECTIVE: To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). METHODS: A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. RESULTS: In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. CONCLUSIONS: Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in rheumatoid arthritis.

In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0.61; 95% of confidence interval (CI)95%: 0.42, 0.88; P=0.008), remission (OR: 0.51; CI95%: 0.35, 0.75; P=0.001), LDA (OR: 0.41; CI95%: 0.24, 0.72; P=0.002) and improvement in DAS28 (B=-0.32; CI95%): -0.47, -0.17; P=7.5 × 10-5) at 12 months was lower number of previous biological therapy (BT). High baseline DAS28 was also associated with a greater decrease in DAS28 at 12 months of treatment (B=0.99; CI95%: 0.79, 1.20; P=1.5 × 10-14). Those patients who were carriers of AA genotypes for rs12083537 (OR: 13.0; CI95%: 2.31, 72.91; P=0.004) and CC for rs11265618 (OR: 12.15; CI95%: 2.18, 67.81; P=0.004) had better LDA response at 12 months of treatment with TCZ. In conclusion, RA patients treated with TCZ showed better EULAR response, remission, LDA and DAS28 improvement rates when a lower number of BT were previously administered. The AA genotype for rs12083537 and CC for rs11265618 polymorphisms for may act as predictors of good response LDA.

Dificultades en el manejo de los hemangiomas capilares retinianos asociados a enfermedad de von Hippel-Lindau / Difficulties in the management of retinal capillary haemangiomas associated with von Hippel Lindau disease

Caso clínico: Mujer de 29 años con hemangiomas capilares retinianos (HCR) bilaterales. Ante la sospecha clínica de enfermedad de von Hippel Lindau (VHL), se realizan estudios genéticos que son negativos en 2 ocasiones. Se produce progresión de los HCR del ojo izquierdo, con aparición de membrana epimacular, que son tratados con láser, ranibizumab intravítreo y vitrectomía. Finalmente, el tercer estudio genético detecta una mutación de novo en el gen VHL que permite confirmar el diagnóstico. Discusión: El síndrome de VHL causa una enfermedad ocular compleja y de difícil diagnóstico que requiere tratamiento precoz de los HCR para modificar el pronóstico visual (AU)

Clinical case: A 29-year-old female with bilateral retinal capillary haemangiomas (RCH). A genetic analysis was carried out due to the suspicion of von Hippel-Lindau (VHL) disease, with negative results on 2 occasions. There was progression of the RCH in the left eye, leading to a macular epiretinal membrane. The patient was treated with laser, intravitreal ranibizumab, and vitrectomy. Finally, a third genetic test detected a de novo mutation in the VHL gene, and led to the genetic diagnosis. Discussion: VHL syndrome causes a complex ocular disease with a difficult diagnosis that requires early treatment of the RCH in order to modify its visual prognosis (AU)

Biomarker responses of Cu-induced toxicity in European seabass Dicentrarchus labrax: Assessing oxidative stress and histopathological alterations.

A comprehensive approach to chemical accumulation and biological effects of short-term Cu exposure in juveniles of European seabass (Dicentrarchus labrax) has been achieved. Fish were exposed to 0.01-10mgL-1 nominal Cu concentrations for 24-96h. Metal concentrations in water and gills, liver, muscle and brain tissues were studied along with oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation). Induction of oxidative damage was observed in all the organs with differential antioxidant responses; gills appearing as the most sensitive from low environmentally water Cu concentrations as 0.01mgL-1. Histopathological alterations were also observed in liver and gills, even without a significant Cu accumulation. The results show that the combination of oxidative stress parameters, particularly lipid peroxidation and glutathione peroxidase activities, and histopathological alterations provide a good model fish and reliable early biomarkers for monitoring Cu pollution in seawater and might call for the protection agencies to revise the Cu environmental standards.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Difficulties in the management of retinal capillary haemangiomas associated with von Hippel Lindau disease. / Dificultades en el manejo de los hemangiomas capilares retinianos asociados a enfermedad de von Hippel-Lindau.

CLINICAL CASE: A 29-year-old female with bilateral retinal capillary haemangiomas (RCH). A genetic analysis was carried out due to the suspicion of von Hippel-Lindau (VHL) disease, with negative results on 2occasions. There was progression of the RCH in the left eye, leading to a macular epiretinal membrane. The patient was treated with laser, intravitreal ranibizumab, and vitrectomy. Finally, a third genetic test detected a de novo mutation in the VHL gene, and led to the genetic diagnosis. DISCUSSION: VHL syndrome causes a complex ocular disease with a difficult diagnosis that requires early treatment of the RCH in order to modify its visual prognosis.

IV Spanish Consensus Conference on Helicobacter pylori infection treatment / IV Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended

La infección por Helicobacter pylori afecta aproximadamente al 50% de la población española y es causante de la gastritis crónica, la úlcera péptica y el cáncer gástrico. Se han llevado a cabo hasta el momento, en nuestro país, 3 reuniones de Consenso sobre el manejo de la infección por H. pylori (la última de ellas en 2012). Los cambios en los esquemas de tratamiento y la creciente evidencia disponible al respecto han justificado la organización de esta IV Conferencia Española de Consenso en marzo de 2016, centrada en el tratamiento de esta infección. Participaron 19 expertos sobre el tema, que realizaron una búsqueda sistemática de la evidencia científica y elaboraron una serie de recomendaciones que fueron sometidas a un proceso de interacción de votaciones anónimas seriadas mediante metodología Delphi. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Este consenso establece, como punto de partida, un aumento de la exigencia en la eficacia de los tratamientos recomendados, que deben alcanzar, o preferiblemente superar, el 90% de curación al ser administrados de forma empírica. De este modo, tanto en primera como en segunda línea se recomiendan tratamientos cuádruples con o sin bismuto, generalmente prescritos durante 14 días. El tratamiento cuádruple sin bismuto concomitante, que incluye un inhibidor de la bomba de protones, claritromicina, amoxicilina y metronidazol, se recomienda como primera línea. En el presente consenso se revisan también con detalle otras alternativas de tratamiento tanto de primera línea como de rescate.

Clinical Relevance of ASC-H Cytologies: Experience in a Single Tertiary Hospital.

OBJECTIVES: To review the cases of atypical squamous cells (ASC), cannot exclude squamous intraepithelial lesion (ASC-H) diagnosed at a single institution and to discuss the interpretation challenges and clinical management of these cases. STUDY DESIGN: The ASC-H cases diagnosed at our institution from 2006 to 2015 were studied retrospectively; of 159,000 Pap smears, there were 959 cases of ASC of undetermined significance (ASC-US) and 148 cases of ASC-H. We have reviewed the clinical records of the ASC-H cases, and data have been analyzed using SPSS 20.0. RESULTS: Median age was 43.1 years; 49.6% of the patients had previous cervical cytologies, and 55.9% of them were negative. Following ASC-H diagnosis, another smear was obtained in 97.1% of the cases and in 67.6% a biopsy was performed. Biopsy revealed low-grade dysplasia in 18.8% of the cases, high-grade dysplasia in 27.8%, and infiltrating carcinoma in 2.3%. Patients with significant lesions in histology were younger than patients with negative results (p = 0.08). A diagnosis of ASC-H/squamous intraepithelial lesion in the repeated cytology had a sensitivity of 74.2%, specificity of 39.6%, positive predictive value of 44.8%, and negative predictive value of 70% for the diagnosis of dysplasia. CONCLUSIONS: ASC-H diagnosis is associated with a high incidence of histological high-grade lesions. A repeat cytology can aid in the selection of high-risk patients, but there may be false-negative results.

Analysis of expression of PTEN/PI3K pathway and programmed cell death ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM).

BACKGROUND: Malignant pleural mesothelioma (MPM) frequently express elevated AKT/mTOR activity. Previous reports in gliomas, colon, breast and prostate cancer suggest that PTEN/PI3K pathway may be important for the induction of PD-L1 expression. This study explored the expression of PTEN/PI3K pathway and PD-L1 in MPM and its relationship with the patient́s prognosis MATERIAL AND METHODS: Twenty seven consecutive MPM patients were reviewed. Formalin-fixed, paraffin-embedded tissue biopsies were used for immunohistochemical analysis of PTEN/PI3K pathway and PD-L1 RESULTS: Expression of PTEN, mTOR, pAKT, p4EBP1, peif4E, pS6 and FOXO3a was found in 88.5%, 92.3%, 78.3%, 38.5%, 100%, 52.2% and 100% of tumors and PD-L1 in 23%. We found a significant correlation between pAKT, FOXO3a and PD-L1 expression and longer overall survival (p <0.05). We did not identify significant association between the level of PD-L1 expression and alterations in PI3K pathway CONCLUSIONS: This study shows PTEN/PI3K pathway and PD-L1 in MPM are frequently activated. Our results suggests that there is not association between PD-L1 and the involvement of the PI3K pathway in MPM.

Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group.

BACKGROUND: Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM: To develop an evidence-based clinical practice guide on MC current concepts. METHODS: Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS: Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS: This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.

Juvenile, adult and late-onset systemic lupus erythematosus: a long term follow-up study from a geographic and ethnically homogeneous population.

OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.

Intervención en la sarcopenia con entrenamiento de resistencia progresiva y suplementos nutricionales proteicos / Sarcopenia intervention with progressive resistance training and protein nutritional supplements

Introducción: El envejecimiento viene acompañado de cambios en la composición corporal entre los que se encuentra una reducción progresiva de la masa muscular, que puede contribuir al desarrollo de limitaciones funcionales en las personas mayores, y donde el estilo de vida juega un papel de especial relevancia. Objetivos: Comprobar la efectividad del entrenamiento de resistencia progresiva, los suplementos nutricionales proteicos y ambas intervenciones combinadas en el tratamiento de la sarcopenia. Método: Revisión de la literatura en las bases de datos Medline, ScienceDirect, CINAHL, ISI WOK y PEDro, mediante la combinación de los descriptores del Medical Subjects Headings (MeSH) referentes a sarcopenia, entrenamiento de fuerza progresiva, suplementos proteicos y personas mayores. Resultados: Un total de 147 estudios fueron encontrados los cuales realizaban ejercicio de resistencia, mediante sesiones de 45-60 minutos, 2-3 veces por semana, y 3-4 series de 8 repeticiones, a una intensidad creciente. Este ejercicio produjo un aumento de la masa muscular y la fuerza, así como incremento en la síntesis de proteínas musculoesqueléticas y tamaño de la fibra muscular. Los suplementos nutricionales tales como el beta-hidroxi-beta-metilbutirato, la leucina y los aminoácidos esenciales produjeron beneficios en la masa muscular. Todos los suplementos aumentaron la fuerza, especialmente cuando se combinaron con el ejercicio de resistencia. Conclusión: La combinación del entrenamiento de resistencia progresiva y las proteínas incluidas en la dieta, o bien en forma de suplementos nutricionales, refuerza los efectos que cada una de estas intervenciones puede tener en el tratamiento de la sarcopenia en las personas mayores (AU)

Introduction: Aging is accompanied by changes in body composition among which is a progressive reduction in muscle mass, which may contribute to the development of functional limitations in older people, and where the lifestyle plays a particularly important role. Objectives: To test the effectiveness of progressive resistance training, protein nutritional supplements and both interventions combined in the treatment of sarcopenia. Methods: Review of literature in Medline, ScienceDirect, CINAHL, ISI WOK and PEDro data by combining the descriptors of Medical Subject Headings (MeSH) concerning sarcopenia, progressive resistance training, protein supplements and seniors. Results: A total of 147 studies were found which resistance exercise performed by sessions 45-60 minutes, 2-3 times a week, and 3-4 sets of 8 repetitions, to an increasing intensity. This exercise resulted in increased muscle mass and strength, and increased skeletal muscle protein synthesis and muscle fiber size. Nutritional supplements such as beta-hydroxy-beta-methylbutyrate, leucine and essential amino acids produced gains in muscle mass. All supplements increased strength, especially when combined with resistance exercise. Conclusion: The combination of progressive resistance training and protein included in the diet, either in the form of nutritional supplements, strengthens the impact that each of these interventions can have on the treatment of sarcopenia in the elderly (AU)

[Sarcopenia intervention with progressive resistance training and protein nutritional supplements]. / Intervención en la sarcopenia con entrenamiento de resistencia progresiva y suplementos nutricionales proteicos.

INTRODUCTION: Aging is accompanied by changes in body composition among which is a progressive reduction in muscle mass, which may contribute to the development of functional limitations in older people, and where the lifestyle plays a particularly important role. OBJECTIVES: To test the effectiveness of progressive resistance training, protein nutritional supplements and both interventions combined in the treatment of sarcopenia. METHODS: Review of literature in Medline, ScienceDirect, CINAHL, ISI WOK and PEDro data by combining the descriptors of Medical Subject Headings (MeSH) concerning sarcopenia, progressive resistance training, protein supplements and seniors. RESULTS: A total of 147 studies were found which resistance exercise performed by sessions 45-60 minutes, 2-3 times a week, and 3-4 sets of 8 repetitions, to an increasing intensity. This exercise resulted in increased muscle mass and strength, and increased skeletal muscle protein synthesis and muscle fiber size. Nutritional supplements such as beta-hydroxy-beta-methylbutyrate, leucine and essential amino acids produced gains in muscle mass. All supplements increased strength, especially when combined with resistance exercise. CONCLUSION: The combination of progressive resistance training and protein included in the diet, either in the form of nutritional supplements, strengthens the impact that each of these interventions can have on the treatment of sarcopenia in the elderly.

Introducción: El envejecimiento viene acompañado de cambios en la composición corporal entre los que se encuentra una reducción progresiva de la masa muscular, que puede contribuir al desarrollo de limitaciones funcionales en las personas mayores, y donde el estilo de vida juega un papel de especial relevancia. Objetivos: Comprobar la efectividad del entrenamiento de resistencia progresiva, los suplementos nutricionales proteicos y ambas intervenciones combinadas en el tratamiento de la sarcopenia. Método: Revisión de la literatura en las bases de datos Medline, ScienceDirect, CINAHL, ISI WOK y PEDro, mediante la combinación de los descriptores del Medical Subjects Headings (MeSH) referentes a sarcopenia, entrenamiento de fuerza progresiva, suplementos proteicos y personas mayores. Resultados: Un total de 147 estudios fueron encontrados los cuales realizaban ejercicio de resistencia, mediante sesiones de 45-60 minutos, 2-3 veces por semana, y 3-4 series de 8 repeticiones, a una intensidad creciente. Este ejercicio produjo un aumento de la masa muscular y la fuerza, así como incremento en la síntesis de proteínas musculoesqueléticas y tamaño de la fibra muscular. Los suplementos nutricionales tales como el beta-hidroxi-beta-metilbutirato, la leucina y los aminoácidos esenciales produjeron beneficios en la masa muscular. Todos los suplementos aumentaron la fuerza, especialmente cuando se combinaron con el ejercicio de resistencia. Conclusión: La combinación del entrenamiento de resistencia progresiva y las proteínas incluidas en la dieta, o bien en forma de suplementos nutricionales, refuerza los efectos que cada una de estas intervenciones puede tener en el tratamiento de la sarcopenia en las personas mayores.

Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding.

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Long-term durability of response to adalimumab in Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. AIMS: To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. METHODS: CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. RESULTS: In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4-75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naïve and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naïve patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02-2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2-5.3) were associated with higher risk of loss of efficacy. CONCLUSIONS: A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naïve patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy.

Pre-pregnancy weight and excess weight gain are risk factors for macrosomia in women with gestational diabetes.

OBJECTIVE: To determine whether women with gestational diabetes mellitus (GDM) whose weight gain exceeded the 2009 Institute of Medicine (IOM) recommendations were more likely to have macrosomia. STUDY DESIGN: Retrospective cohort study of the association of weight gain in women with Class A1 GDM, with term (≥37 weeks) singleton liveborns and macrosomia (birthweight ≥4000 g). Multivariate logistic regression models were used to adjust for covariates and test for interactions. RESULT: Of 1502 women studied, pre-pregnancy body mass index (BMI) categories were: normal (39.6%), overweight (28.5%) and obese (31.9%). The mean (±standard deviation ) weight gain (lbs) for these groups was: 27.6±10.9, 24.2±13.0 and 18.8±16.3 (P<0.0001), whereas the occurrence of macrosomia was 7.4, 11.4 and 19.0%, respectively. Women with an obese BMI were twice as likely to have a macrosomic infant compared with women in the normal BMI group (odds ratio, OR 2.0; 95% CI 1.4-3.0; P=0.0005). Independently, women who exceeded the IOM guidelines were three times more likely to have a macrosomic infant (OR 3.0, 95% CI 2.2-4.2, P<0.0001). CONCLUSION: Maternal pre-pregnancy weight and weight gain during pregnancy appear to be significant and independent risk factors for macrosomia in women with GDM.

Risk factors for intestinal ischaemia among patients registered in a UK primary care database: a nested case-control study.

BACKGROUND: Intestinal ischaemia, including ischaemic colitis and acute mesenteric ischaemia, causes significant morbidity and mortality. Few population-based studies have estimated incidence and potential risk factors for this disease. AIMS: To estimate the incidence of intestinal ischaemia and identify the associated risk factors in cohorts: (i) patients with irritable bowel syndrome and/or chronic constipation (IBS/CC/both), (ii) individuals free of these conditions. METHODS: Population-based case-control analysis nested in a cohort of patients with first ever recorded diagnosis of IBS/CC/both and a cohort free of these conditions from general population using the General Practice Research Database. RESULTS: Of 78 cases of intestinal ischaemia, 71 were from general population, seven from the IBS/CC/both cohort. Incidence rate of intestinal ischaemia in IBS/CC/both patients vs. general population was 4.49:1.09 per 100,000 person-years; age- and gender-adjusted incidence rate ratio (95% CI) was 2.7 (1.2-5.9). Inflammatory bowel disease and heart failure showed an association with ischaemic colitis [OR (95% CI): 4.2 (0.5-38.4) and 5.6 (2.2-14.1)], but none with acute mesenteric ischaemia. Diabetes and prior cardiovascular surgery were associated with higher risk of acute mesenteric ischaemia, but showed no association with ischaemic colitis. CONCLUSIONS: Results suggest that different risk factors are associated with acute mesenteric ischaemia and ischaemic colitis. However, due to small number of patients, associations should be carefully interpreted.