A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial.

BACKGROUND & AIM: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum--CECT 7315 and 7316--on systemic immunity in elderly. METHODS: 50 institutionalized elderly subjects were randomized, in a double-blind fashion, to receive for 12 weeks 1) 5·10(8) cfu/day of L. plantarum CECT7315/7316 ("low probiotic dose") (n = 13), 2) 5·10(9) cfu/day of the probiotic mixture ("high probiotic dose") (n = 19), or 3) placebo (n = 15). Leukocyte subpopulations, and cytokine levels (IL-1 , IL-10, TGF-ß1) were measured in venous blood at baseline, end of treatment (week 12), and end of follow-up (week 24). Infection and survival rates were recorded. RESULTS: After treatment, high probiotic dose resulted in significant increases in the percentages of activated potentially T-suppressor (CD8+CD25+) and NK (CD56+ CD16+) cells, while low probiotic dose increased activated T-helper lymphocytes (CD4+CD25+), B lymphocytes (CD19+), and antigen presenting cells (HLA-DR+). Also, plasma TGF-ß1 concentration significantly decreased after treatment with both probiotic doses. Most of these changes remained 12 weeks after probiotic discontinuation. Incidence of infections during treatment showed a significant trend to be lower in the high probiotic dose group. In addition, there was a significant trend for mortality to be greater in the placebo group vs. both probiotic groups. CONCLUSIONS: Depending on the dose, L. plantarum CECT7315/7316 have different immune-enhancing effects in elderly subjects. These effects might result in a better clinical outcome.

Clinical outcome of newly diagnosed Crohn's disease: a comparative, retrospective study before and after infliximab availability.

BACKGROUND: Infliximab (IFX) could change the course of Crohn's disease (CD) by reducing steroid use, surgery or prompting earlier introduction of immunomodulators (IMM). AIM: To evaluate the impact of IFX availability on the course of early CD. METHODS: Two cohorts of newly diagnosed CD patients were identified: The first cohort included patients diagnosed from January 1994 to December 1997 and the second from January 2000 to December 2003. All patients were diagnosed, treated and followed up in the same centre until December 1999 (first cohort) or December 2005 (second cohort). Development of disease-related complications, steroid, IMM or IFX requirements and intestinal resections during follow-up were registered. RESULTS: A total of 328 patients were included (146 first cohort, 182 second cohort). A similar proportion of patients in both cohorts received steroids, but steroid exposure resulted significantly more intense in the first cohort (P = 0.001). In the second cohort, 14% of patients received IFX. Thiopurines were used more (P = 0.001) and earlier (P = 0.012) in the second cohort. No differences in surgical requirements or the development of disease-related complications were found. CONCLUSIONS: Following a step-up therapeutic algorithm, IFX availability did not reduce surgical requirements or the development of disease-related complications.

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice.

BACKGROUND: Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. AIM: To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. METHODS: Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. RESULTS: One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3-8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). CONCLUSIONS: Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found.

Reduced liver injury in the interleukin-6 knockout mice by chronic carbon tetrachloride administration.

BACKGROUND: Interleukin-6 has been involved in restoration of liver function after partial hepatectomy and toxic liver injury. However, normal liver regeneration in interleukin-6 knockout mice has also been reported. The aim of this work was to investigate the effect of interleukin-6 deficiency on liver injury and its regeneration in a model of long term carbon tetrachloride (CCl4) administration. DESIGN: Serum and whole livers from wild type and interleukin-6 knockout mice treated with carbon tetrachloride (0.25 mL kg(-1)) twice a week were obtained after 4, 6 and 8 weeks (n = 4-6). Sections were assessed for liver regeneration, liver injury and hepatocyte apoptosis whereas sera were assayed for aminotransferase levels. Nuclear extracts and total liver lysates were assayed for transcription factor activation and apoptosis related proteins, respectively. RESULTS: When compared to wild type, interleukin-6 knockout mice showed reduced liver damage scores, lower aminotransferase levels and diminished apoptosis, as well as reduced nuclear factor kappa B activation. Although the level of active protein was lower, activation of signal transducer and activator of transcription 3 still takes place in knockout mice. Furthermore, liver regeneration measured by bromodeoxyuridine incorporation showed no differences between wild type and knockout animals after 6 and 8 weeks of treatment. CONCLUSIONS: Compared to the wild type mice liver regeneration after chronic treatment with carbon tetrachloride proceeds at a slower rate in interleukin-6 deficient mice. However, this low recovery rate is accompanied by a reduction not only in hepatocyte apoptosis, but also in activation of nuclear factor kappa B and liver injury.

Efficacy and safety of short-term adalimumab treatment in patients with active Crohn's disease who lost response or showed intolerance to infliximab: a prospective, open-label, multicentre trial.

BACKGROUND: The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease. AIM: To determine response and remission rates associated with the 4-week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab. METHODS: In this multicentre, prospective, open-label, observational, 52-week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2). RESULTS: Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [> or =70-point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score <150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (> or =50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred. CONCLUSIONS: Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab.

Review article: the intestinal lumen as a therapeutic target in inflammatory bowel disease.

Undigested carbohydrates reaching the colon can act as competitors for epithelial bacterial receptors, making it difficult for noncommensal bacteria to adhere to them. On the contrary, fermentation of these carbohydrates by anaerobic flora produces - among other substrates - butyrate that is involved in numerous important metabolic processes. These include the provision of energy to the colonocytes, the enhancement of sodium and water absorption and the synthesis of mucus and cell membranes. In addition, butyrate inhibits the nuclear translocation of the transcription factor NFkappaB, which exerts a potent anti-inflammatory activity. Clinical experience with probiotics in inflammatory bowel disease (IBD) is controversial. Whereas some probiotic preparations appear to be useful in ulcerative colitis (UC) and pouchitis, most attempts to use probiotics for treating or preventing recurrence in Crohn's disease have failed. It should be pointed out that - unlike in the small bowel - the colon and ileal pouches are well-established microbiological ecosystems with increasing amounts of a wide variety of bacterial strains. These bacterial strains have a high degree of metabolic interaction with luminal nutrients and a greater probability of developing dysbiosis. With this in mind, the rationale for using pre- and probiotics appears to be stronger for colonic IBD (UC or Crohn's colitis) and pouchitis than for IBD mostly involving the small bowel.

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Recomendaciones sobre tuberculosis y tratamiento de la enfermedad inflamatoria intestinal con infliximab. Actualización 2006 / Recommendations on tuberculosis and treatment of inflammatory bowel disease with infliximab. 2006 update

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Presentación atípica de metástasis a distancia de hepatocarcinoma / Atypical presentation of distant metastases from hepatocarcinoma

El hepatocarcinoma (HCC) es el tumor primario maligno de hígado más frecuente. Habitualmente asienta sobre un hígado cirrótico, lo que justifica su cribado mediante determinación de las concentraciones de alfafetoproteína y ecografía abdominal de forma semestral en todo paciente cirrótico con función hepatocelular preservada. Esto permite la detección precoz de tumores, lo que incrementa la proporción de casos potencialmente curables. La diseminación metastásica más frecuente del HCC es la trombosis de la vena porta, mientras que es poco frecuente la diseminación a distancia. Presentamos 3 casos de HCC con metástasis de localización infrecuente y síntomas inespecíficos, que motivaron una orientación diagnóstica inicial errónea. Dada la mayor supervivencia actual de este tipo de pacientes, debe considerarse la posibilidad de metástasis a distancia ante la aparición de síntomas inespecíficos en pacientes portadores de HCC

Hepatocarcinoma (HCC) is the most frequent primary malignant hepatic tumour. These tumours usually develop in cirrhotic liver; for this reason, periodic screening using alphafetoprotein determination and abdominal ultrasonography is considered in cirrhotic patients with preserved hepatocellular function. This strategy allows early detection of HCC, increasing the proportion of curable tumours. The most frequent metastasic dissemination is portal vein neoplasic thrombosis, being unusual the occurrence of spread metastases in other organs. We present 3 cases of atypical HCC metastasis with non specific clinical manifestations which initial diagnosis was wrong. Because of a longer survival of these patients in recent years, spread metastasis might be considered in patients with known HCC and non specific symptoms

Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated?

BACKGROUND: Few data are available regarding the evolution of Crohn's disease after discontinuing a successful course of infliximab. AIM: To evaluate clinical outcome of Crohn's disease after induction of remission with three infliximab infusions (luminal disease) and after maintenance of remission with 1-year course of infliximab every 8 weeks (luminal and perianal). METHODS: Twenty-three patients with active luminal Crohn's disease who responded to three infusions of infliximab (0, 2, and 6 weeks), and 23 patients with sustained response to infliximab every 8 weeks during 1 year, were included. Patients were followed-up until relapse or for at least 6 months after infliximab discontinuation. Clinical outcomes and factors associated to relapse were evaluated. RESULTS: In luminal Crohn's disease, a three-infusion infliximab regimen achieved a sustained response in most patients, especially if a complete response occurred at the time of the third infusion. In patients treated for 1-year, infliximab discontinuation was also successful, with a cumulative probability of being free of relapse of 69% at 12 months. In perianal disease, early relapse was the rule after stopping infliximab treatment, with only 34% of patient maintaining remission at 1 year. CONCLUSIONS: Short regimens of infliximab might be evaluated in patients with luminal Crohn's disease. However, infliximab discontinuation is not recommended in perianal Crohn's disease, because of a high rate of early relapse.

[Gasometric alterations in hospitalized cirrhotic patients]. / Alteraciones gasométricas en pacientes cirróticos hospitalizados.

BACKGROUND AND OBJECTIVES: Gas exchange alterations have been described in cirrhotic patients; but by the moment, a few prospective studies have focused in them. The aim of this study was to describe the frequency and severity of gasometric alterations in hospitalized cirrhotic patients, a their correlation with hepatocellular disfunction. PATIENTS AND METHODS: 50 consecutive cirrhotic patients (41 males) admitted for liver decompensation (ascites, liver encephalopathy, alcoholic hepatitis and upper gastrointestinal bleeding) without acute or chronic cardiopulmonary disfunction were included in the study. Patients were classified according with Child-Pugh score (A, n = 13; B, n = 21; C, n = 16). Severe alcoholic hepatitis (SAH) was confirmed in 7 patients. Arterial gasometry was performed in all patients before discharge. Contrast echocardiography was performed in any case of suspicion of hepatopulmonary syndrome (HPS). RESULTS: Light hypoxemia was observed (80.9 mmHg), without differences with Child-Pugh. Hypocapnia was significantly more evident in Child C than in A and B (31.2 +/- 3.1 vs. 38.1 +/- 4.3 y 36.3 +/- 5 mmHg; p < 0,05), respectively. Cirrhotic patients with SAH showed a significantly higher hypocapnia by comparison with others (31.2 +/- 3.1 vs. a 36.3+/-5 mmHg; p < 0.05). In multivariate analysis, independent prognostic variables for hypocapnica were plasmatic levels of protrombin time, albumin and sodium. HPS was confirmed in 8 patients (16%). CONCLUSIONS: The most prevalent gas exchange abnormality in cirrhosis was the alteration of alveolar-arterial oxygen tension gradient, directly correlated with hepatocellur disfunction. Hypocapnia could be a compensatory mechanism or the result of the activation of central respiratory centres by non-depurated substances by the liver.

[Autoimmune hemolytic anemia associated with ulcerative colitis]. / Anemia hemolítica autoinmunie asociada a colitis ulcerosa.

The incidence of immunological disorders has been reported to be greater in patients with inflammatory bowel disease than among the general population. The association of ulcerative colitis (UC) and autoimmune hemolytic anemia (AIHA) was first described in the early 1950s but no more than 50 cases have been described in the international literature. Detailed description of the pathogenic mechanisms involved in this association is lacking. The clinical course of AIHA and treatment response in these patients seems to be independent of UC, sometimes requiring immunosuppressive treatment and even surgery. We present 2 cases of AIHA associated with UC with distinct response to conventional treatment. We also review the literature on the subject.

Anemia hemolítica autoinmunie asociada a colitis ulcerosa / Autoimmune hemolytic anemia associated with ulcerative colitis

En pacientes con enfermedad inflamatoria intestinal se ha descrito una incidencia de enfermedades de base inmunológica mayor que la de la población general. La asociación de colitis ulcerosa (CU) y anemia hemolítica autoinmune (AHAI) se describió por primera vez a principios de la década de los cincuenta; sin embargo, no se han publicado más de 50 casos en la bibliografía mundial. Se desconoce cuáles son los mecanismos patogénicos detallados que se hallan implicados en esta asociación. La evolución clínica de la AHAI y la respuesta al tratamiento en estos pacientes parece cursar de forma independiente a la propia CU, requiriendo en ocasiones tratamiento inmunomodulador e incluso tratamiento quirúrgico. Se presentan 2 casos de AHAI asociada a CU, con distinta respuesta al tratamiento convencional, y se revisa la bibliografía al respecto

The incidence of immunological disorders has been reported to be greater in patients with inflammatory bowel disease than among the general population. The association of ulcerative colitis (UC) and autoimmune hemolytic anemia (AIHA) was first described in the early 1950s but no more than 50 cases have been described in the international literature. Detailed description of the pathogenic mechanisms involved in this association is lacking. The clinical course of AIHA and treatment response in these patients seems to be independent of UC, sometimes requiring immunosuppressive treatment and even surgery. We present 2 cases of AIHA associated with UC with distinct response to conventional treatment. We also review the literature on the subject

Alteraciones gasométricas en pacientes cirróticos hospitalizados / Gasometric alterations in hospitalized cirrhotic patients

Introducción y objetivos: Aunque se ha descrito la existencia de diversas alteraciones del intercambio gaseoso en la cirrosis, existen pocos estudios que las hayan estudiado de forma prospectiva. El objetivo de este trabajo fue conocer la frecuencia y gravedad de dichas alteraciones en los pacientes cirróticos hospitalizados, correlacionándolas con el grado de disfunción hepática. Pacientes y métodos: Se estudiaron 50 pacientes cirróticos consecutivos (41 varones) que requirieron ingreso hospitalario por descompensación de su hepatopatia (ascitis, encefalopatía hepática, hepatitis alcohólica y hemorragia digestiva alta), y que no presentaban procesos pulmonares ni cardiacos agudos o crónicos que pudiesen producir hipoxemia. Los pacientes fueron agrupados según su estadio de Child-Pugh (A, n = 13; B, n = 21; C, n = 16). En siete pacientes se constató la presencia de una hepatitis alcohólica sobre añadida grave (HAAG). En todos ellos se realizó una gasometría arterial basal antes de ser dados de alta, y se efectuó un ecocardiograma transtorácico con contraste en caso de sospecha de síndrome hepatopulmonar (SHP). Resultados: Se observó una discreta hipoxemia global (80,9 mmHg) sin diferencias según el grado de Child-Pugh. La hipocapnia fue significativamente más marcada en los pacientes con estadio Child C que en aquellos con estadios A y B (31,2 ± 3,1 frente a 38,1 ± 4,3 y 36,3 ± 5mmHg; p < 0,05), respectivamente. En cambio, los pacientes cirróticoscon HAAG presentaron un hipocapnia significativamente menor que aquellos otros sin HAAG (31,2 ± 3,1 frente a 36,3 ± 5 mmHg; p < 0,05). En el análisis multivariante, las variables con valor pronóstico independiente para la presencia de hipocapnia fueron la protrombina, la albúmina y el sodio plasmáticos. Se constató la presencia de SHP en 8 pacientes (16%). Conclusiones: La alteración gasométrica más frecuentes de la cirrosis es la alteración del gradiente alvéolo-arterial de oxígeno, que se acentúa conforme empeora la función hepática. La hipocapnia, aunque supatogenia no es bien conocida, podría constituir una mecanismo compensador de la hipoxemia o bien ser el resultado de la activación de los centros respiratorios centrales por sustancias no aclaradas en el hígado

Background and objectives: Gas exchange alterations have been described in cirrhotic patients; but by the moment, a few prospective studies have focused in them. The aim of this study was to describe the frequency and severity of gasometric alterations in hospitalized cirrhotic patients, a their correlation with hepatocellular disfunction. Patients and methods: 50 consecutive cirrhotic patients (41 males) admited for liver decompensation (ascites, liver encephalopathy, alcoholichepatitis and upper gastrointestinal bleeding) without acute or chronic cardiopulmonary disfunction were included in the study. Patients were classificated according with Child-Pugh score (A, n = 13; B, n =21; C, n = 16). Severe alcoholic hepatitis (SAH) was confirmed in 7 patients. Arterial gasometry was performed in all patients before discharge. Contrast echocardiography was performed in any case of suspicion of hepatopulmonary syndrome (HPS). Results: Light hypoxemia was observed (80.9 mmHg), without differences with Child-Pugh. Hypocapnia was significantly more evident in Child C than in A and B (31.2 ± 3.1 vs. 38.1 ± 4.3 y 36.3 ± 5 mmHg; p <0,05), respectively. Cirrhotic patients with SAH showed a significantly higher hypocapnia by comparison with others (31.2 ± 3.1 vs. a 36.3 ± 5mmHg; p < 0.05). In multivariate analysis, independent prognostic variables for hypocapnica were plasmatic levels of protrombin time, albumin and sodium. HPS was confirmed in 8 patients (16%). Conclusions: The most prevalent gas exchange abnormality in cirrhosis was the alteration of alveolar-arterial oxygen tension gradient, directly correlated with hepatocellur disfunction. Hypocapnia could be a compensatory mechanism or the result of the activation of central respiratory centres by non-depurated substances by the liver