Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Factors associated with quality of care in inflammatory bowel diseases: a view from patient's side using the IQCARO quality of care decalogue.

BACKGROUND: Quality of care (QoC) is a highly important topic in inflammatory bowel disease (IBD). We recently elaborated a decalogue of QoC indicators (IQCARO-QoC) developed by IBD patients. The aim of the present study was to assess the factors associated with patients' evaluation of QoC in Spain using the IQCARO-QoC Decalogue recently developed by IBD patients. METHODS: A survey including patients' socio-demographic and clinical characteristics, and the IQCARO-QoC Decalogue, was completed by IBD patients. We described patients' assessment of QoC across Spanish patients. A univariable and multivariable analysis was performed to explore the associations between patients' characteristics and QoC. RESULTS: Questionnaires from 788 participant patients were analysed. Participants' mean age was 43.4 years, 63% were females and 58% had Crohn's disease. The mean QoC score was 8.1 (± 2.4 SD) points out of a maximum of 10. Items with the lowest score were related to the provision of information and the implication of the medical team throughout the entire patient care. Factors associated with better QoC scores included: being employed better disease control, fewer numbers of unscheduled visits, and being followed by a gastroenterologist specialized in IBD. CONCLUSIONS: Spanish patients' reported QoC seems to be globally good although there is room for improvement, especially in providing adequate information to patients. Care provided by specialized IBD gastroenterologists seems to be related with higher QoC scores.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Tuberculosis in Anti-Tumour Necrosis Factor-treated Inflammatory Bowel Disease Patients After the Implementation of Preventive Measures: Compliance With Recommendations and Safety of Retreatment.

BACKGROUND AND AIMS: Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. METHODS: In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. RESULTS: We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. CONCLUSIONS: Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe.

Perone distal estudio anatomico con placa de osteosintesis / Anatomical study of fibula plate location osteosynthesis

La fractura de tobillo es una patologíatraumática muy frecuente, que cuando debe ser intervenidaquirúrgicamente, lo habitual es el uso de placade osteosíntesis, la misma puede ser colocada en unade sus dos caras, externa o posterior. La externa se encuentradividida por una cresta en una superficie triangularanterior subcutánea y una pósteroexterna, diferentesautores recomiendan la colocación en una u otracara. El objetivo de este trabajo es evaluar cuál de lascaras del tercio distal del peroné, es la más adecuadaanatómicamente para la colocación de la placa deosteosíntesis.MATERIALES Y MÉTODOS: Se evaluó el tercio distal de25 perones, 15 correspondieron al lado izquierdo y 10 allado derecho las muestras fueron obtenidas de la Cátedrade Anatomía Normal. Facultad de Ciencias Médicas(UNC. Córdoba), se realizaron mediciones tanto de lacara ánteroexterna como de la pósteroexterna. Para lamedición se utilizó un calibre digital.RESULTADOS: Los resultados obtenidos indicaron unadistancia promedio de la cara ánteroexterna de 75 mmdesde el maléolo hasta el vértice de la cresta (rango 65mm a 92 mm) y una distancia promedio de 65 mm en lacara pósteroexterna desde la fosita de los peroneos hastala unión de ambas (rango 60 mm a 72.3 mm).CONCLUSIÓN: El estudio anatómico del peroné distalnos permite afirmar que ninguna de sus caras terminansiendo ideales para la colocación de una placa, estaosteosíntesis de 7 orificios puede utilizarse en ambascaras ánteroexterna y pósteroexterna, cuando se tratade una fractura transindesmal, pero no es anatómicamenteviable colocar en la cara ánteroexterna cuandohablamos de fracturas suprasindesmales. Debe colocarseen la cara pósteroexterna aunque en esta partetambién interfiera la unión de ambas caras...

The fibula is a long thin bone thatarticulates with the tibia at both ends. A study wasconducted over 25 perones anatomical and analyzed thedistal third. Our goal is to evaluate which of the faces ofthe distal fibula is the most appropriate anatomically tothe placement of the osteosynthesis plate.MATERIALS AND METHODS: Was evaluated peronesdistal third of 25, 15 corresponded to the left and rightside 10 samples were obtained from plants of NormalAnatomy Chair Faculty of Medical Sciences (UNCCordoba), were measured both as the anterolateral theposterolateral was used for measuring a digital caliper.RESULTS: The results showed an average distance of75 mm anterolateral from the malleolus to the apex of theridge (range 65 to 92 mm) and an average distance of 65mm in the posterolateral from the pit of the peroneal tothe junction of two (range 60 to 72.3 mm).CONCLUSION: We conclude that none of its faces endup being suitable for placement of a plate, theosteosynthesis plate of holes 7 may be used on both sidesanterolateral and posterolateral when dealing with fractureanatomically syndesmotic but not feasible to placeon the face when speaking of fractures anterolateralsuprasindesmales. Should be placed in the posterolateralbut also interfere in this part of the union of both sides...

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

BACKGROUND: Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. METHODS: A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. RESULTS: Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. CONCLUSIONS: IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients.

Post-treatment bone marrow residual disease > 5% by flow cytometry is highly predictive of short progression-free and overall survival in patients with Waldenström's macroglobulinemia.

To assess the value of bone marrow (BM) assessment by flow cytometry FCM after therapy in the clinical outcome of WM patients, we analyzed 42 WM patients who were evaluated before and after therapy. Patients were studied with a panel that always included the CD19, CD22, CD25, and κ/λ light chain immunoglobulin monoclonal antibodies. The mean of abnormal B-cells in the pre-therapeutic BM was 17.8% ± 12.1%, which decreased was after therapy to 5.4% ± 0.7% (P = .049). A linear correlation was seen between the better quality of response and the reduction in the tumor B-lymphocyte counts at the BM, since the ratio of abnormal B cells between pre and posttherapy BM was 1172.17, 221.64, 3.37, 1.03, and 0.56 for responses complete, partial, minor, stable disease and progression, respectively (P < .001). Intensive and rituximab-containing therapies correlated with deeper tumor cell reductions. Finally, the B-cell decrease correlated with the better overall and progression-free survival.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

[Bariatric surgery in patients with focal segmental glomerulosclerosis secondary to obesity]. / Cirugía bariátrica en pacientes con glomeruloesclerosis focal y segmentaria secundaria a obesidad.

2 cases of proteinuria in obese non-diabetic young males, both corresponding to focal segmental glomerulosclerosis are presented. Effective reduction of body weight by bariatric surgery was followed by sustained remission of proteinuria allowing significant reduction or total removal of blockers of the reninangiotensin- system.

Cirugía bariátrica en pacientes con glomeruloesclerosisfocal y segmentaria secundaria a obesidad / No disponible

Se presentan dos casos de proteinuria en jóvenes obesos no diabéticos, con histología de Glomeruloesclerosis Focaly Segmentaria (GFS). La efectiva reducción de peso corporal mediante cirugía bariátrica se siguió de una remisión sostenida de la proteinuria, permitiendo una significativa reducción o suspensión de las dosis de fármacos bloqueadores del sistema renina-angiotensina (AU)

2 cases of proteinuria in obese non-diabetic youngmales, both corresponding to focal segmental glomerulosclerosis are presented. Effective reduction of bodyweight by bariatric surgery was followed by sustained remission of proteinuria allowing significant reduction or total removal of blockers of the renin-angiotensinsystem (AU)

Evaluación de los efectos antioxidante, antibacteriano y antifúngico de Calophyllum Brasilense Cambes (Lagarto Caspi) / Evaluation of antioxidant effects, antibacterial and antifungal Brasilense Calophyllum Cambes (Caspi Lizard)

Objetivo: Evaluar el efecto antibacteriano, antifúngico y antioxidante de diferentes extractos del Calophyllum brasiliense Cambess. Material y Métodos: El efecto antioxidante fue determinado por captación de radicales libres, midiendo la decoloración de una solución de 2,2-difenil-1-picril hidrazilo (DPPH); La actividad antibacteriana y antifúngica, in Vitro, se determinó mediante la prueba de dilución. El efecto antibacteriano se evaluó en cepas de E. coli ATCC25922 y Staphylococcus aureus ATCC25923, utilizando medios de cultivo: Caldo y Agar Mueller Hinton. Para evaluar el efecto antifúngico, se utilizó cepas de Cándida albicans en medio de Agar Sabouraud. Resultados: La actividad antioxidante de los extractos acuoso, metanólico y etanólico fue muy satisfactoria, siendo de 110.56 por ciento, 99.17 por ciento y 99.57 por ciento, respectivamente, a una concentración de 100 ug/mL, en comparación con la Vitamina C que presentó 86,5 por ciento. Asimismo, observamos un buen efecto antifúngico para los extractos acuoso y etanólico al 20 por ciento p/v a los volúmenes de 3, 3.5 y 4mL. y en el caso del extracto etanólico también presentó un buen efecto a una concentración del 10 por ciento a un volumen de 1.6mL. Conclusiones: Los extractos: acuoso, metanólico y etanólico, presentaron un buen efecto antioxidante y antifúngico, en las cepas estudiadas.

Objetive: To evaluate, in vitro, the antibacterial, antifungal andantioxidant effects of different extracts of Calophyllum brasiliense Cambess. Material and Methods: The antioxidant effect was tested by free radicals capture, measuring discoloration of the 2,2-diphenyl-1-pycryl hydrazyle solution (DPPH). We used a dilution to measure antibacterial and antifungal in vitro activity. Strains of E. coli ATCC25922 and Staphylococcus aureus ATCC25923 were used to evaluate antibacterial effect; using Broth and Mueller Hinton Agar as culture medium. Strains of Candida albicans and Agar Sabouraud as culture medium were usedto evaluate antifungal effect. Results: Aqueous, methanolic and ethanolic extracts, showed good antioxidant activity having 110.56 per cent, 99.17 per cent and 99.57 per cent of antioxidant activity at 100 ug/mL concentration, respectively. This is superior to the vitamin C referencepattern that showed 86,5 per cent activity. Good antifungal effect for aqueous and ethanol extracts at a 20 per cent concentration for 3, 3.5 and 4 ml of volume was determined. Ethanol extracts had the same antifungal effect at a 10 per cent concentration for 1.6mL. of volume. Conclusions: The aqueous, methanolic and ethanolic extracts showed a good antioxidant and antifungal activity on the strains studied.

Gremlin: a novel mediator of epithelial mesenchymal transition and fibrosis in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the most frequent cause of chronic dysfunction and late loss of renal allografts. Epithelial mesenchymal transition (EMT) has been identified as responsible for the presence of activated interstitial fibroblasts (myofibroblasts) and transforming growth factor beta (TGF-beta)/Smad is the key signaling mediator. It has been proposed that the bone morphogenetic protein 7 (BMP-7) antagonist, Gremlin, could participate in EMT, as a downstream mediator of TGF-beta. METHODS: We evaluated 33 renal allograft biopsies, 16 of which showed CAN, versus 17 controls. By in situ hybridization we studied the expression of TGF-beta and Gremlin mRNA. Gremlin, BMP-7, E-cadherin, and alpha-smooth muscle actin (alpha-SMA) proteins were evaluated by immunohistochemistry and Smad3 activation by Southwestern. In cultured human tubuloepithelial cells (HK2 cell line), Gremlin induction by TGF-beta was studied by confocal microscopy. RESULTS: Among renal biopsies of transplanted patients with CAN, we detected up-regulation of TGF-beta in colocalization with Gremlin (RNA and protein), mainly in areas of tubulointerstitial fibrosis. In the same tubules, we observed decreased expression of E-cadherin and induction of vimentin and alpha-SMA. BMP-7 was significantly decreased in the CAN biopsies. In addition, HK2 stimulated with TGF-beta (1 ng/mL) induced Gremlin production at 72 hours. CONCLUSION: We postulated that Gremlin is a downstream mediator of TGF-beta, suggesting a role for Gremlin in EMT observed in CAN.

[Clinical aspects and endoscopic management of gastrointestinal bleeding from Dieulafoy's lesion]. / Aspectos clínicos y tratamiento endoscópico de la hemorragia digestiva por lesión de Dieulafoy.

OBJECTIVE: the aim of the study was to assess the incidence, clinical presentation, location, and response to endoscopic therapy of gastrointestinal bleeding from Dieulafoy's lesion. MATERIAL AND METHOD: ALL consecutive episodes of gastrointestinal bleeding due to Dieulafoy's lesion seen between 2000 and 2006 were retrospectively reviewed. All main clinical and endoscopic data were collected: type and effectiveness of endoscopic therapy, rebleeding, complications, and mortality during hospitalization. RESULTS: WE found 41 patients, 26 males and 15 females, median age of 71.19 years. Dieulafoy's lesion accounted for 1.55% of all gastrointestinal bleeding episodes during the study period. The incidence of Dieulafoy's lesion was 2.2 cases/100.000 inhabitants/year. Active bleeding at endoscopy was present in 85.36%, and comorbidity in 92.68%. The stomach was the most frequent location (60.97%), followed by duodenum (29.26%). Endoscopic therapy achieved initial hemostasis in all cases. Three patients (7.31%) initially treated with epinephrine injection showed rebleeding and properly responded to a second session of endoscopic therapy. No surgery was needed. The mortality rate during hospitalization was 4.87%. CONCLUSIONS: Dieulafoy's lesion is an uncommon, but potentially severe cause of gastrointestinal bleeding. It may be found in any location within the gastrointestinal tract. Endoscopic therapy is effective and safe. Injected epinephrine alone is associated with a higher risk of rebleeding.

Aspectos clínicos y tratamiento endoscópico de la hemorragia digestiva por lesión de Dieulafoy / Clinical aspects and endoscopic management of gastrointestinal bleeding from Dieulafoy's lesion

Objetivo: conocer la incidencia, forma de presentación, localizacióny resultados del tratamiento endoscópico en la hemorragiadigestiva causada por lesión de Dieulafoy.Material y métodos: se revisaron de forma retrospectiva todoslos casos de hemorragia digestiva por lesión de Dieulafoy entrelos años 2000 y 2006. Se recogieron los principales datos clínicosy endoscópicos, tipo de tratamiento empleado, eficacia delmismo, recidiva, complicaciones y mortalidad durante el ingreso.Resultados: se encontraron 41 pacientes, 26 varones y 15mujeres, con edad media de 71,19 años. La lesión de Dieulafoyfue la causa del 1,55% de los casos de hemorragia digestiva agudaen el periodo estudiado. La incidencia de hemorragia digestivapor lesión de Dieulafoy fue de 2,2 casos por cada 100.000 habitantesy año. La mayoría de los pacientes presentaban hemorragiaactiva en el momento de la endoscopia (85,36%) y comorbilidad(92,68%). La localización más frecuente fue el estómago(60,97%), seguida del duodeno (29,26%). El tratamiento endoscópicologró la hemostasia inicial en el 100% de los casos. Trespacientes (7,31%) presentaron recidiva hemorrágica, todos elloshabían sido tratados inicialmente con esclerosis con adrenalina yrespondieron adecuadamente a un segundo tratamiento endoscópico.Ningún paciente precisó cirugía. La mortalidad durante elingreso fue del 4,87%.Conclusiones: la lesión de Dieulafoy es una causa poco frecuente,pero potencialmente grave, de hemorragia digestiva ypuede aparecer en cualquier punto del tracto gastrointestinal. Eltratamiento endoscópico es eficaz y presenta pocas complicaciones.La esclerosis única con adrenalina se asocia a un mayor riesgode recidiva hemorrágica

Objective: the aim of the study was to assess the incidence,clinical presentation, location, and response to endoscopic therapyof gastrointestinal bleeding from Dieulafoy’s lesion.Material and methods: all consecutive episodes of gastrointestinalbleeding due to Dieulafoy’s lesion seen between 2000 and2006 were retrospectively reviewed. All main clinical and endoscopicdata were collected: type and efectiveness of endoscopictherapy, rebleeding, complications, and mortality during hospitalization.Results: we found 41 patients, 26 males and 15 females, medianage of 71.19 years. Dieulafoy’s lesion accounted for 1.55%of all gastrointestinal bleeding episodes during the study period.The incidence of Dieulafoy’s lesion was 2.2 cases/100.000 inhabitants/year. Active bleeding at endoscopy was present in85.36%, and comorbidity in 92.68%. The stomach was the mostfrequent location (60.97%), followed by duodenum (29.26%). Endoscopictherapy achieved initial hemostasis in all cases. Threepatients (7.31%) initially treated with epinephrine injectionshowed rebleeding and properly responded to a second session ofendoscopic therapy. No surgery was needed. The mortality rateduring hospitalization was 4.87%.Conclusions: Dieulafoy’s lesion is an uncommon, but potentiallysevere cause of gastrointestinal bleeding. It may be found inany location within the gastrointestinal tract. Endoscopic therapyis effective and safe. Injected epinephrine alone is associated witha higher risk of rebleeding

Trisomía 22 en mosaico como causa de disgenesia ovárica asociada a un fenotipo Turner-Ullrich / Trisomy 22 mosaicism as a cause of ovarian dysgenesis associated with Turner-Ullrich phenotype

Se presenta un caso clínico de una paciente de 25 años con disgenesia ovárica debida a una trisomía 22 en mosaico. El cariotipo en sangre periférica resultó ser 46 XX. Las biopsias de ambas cintillas ováricas revelaron una trisomía 22 en mosaico, que se confirmó en fibroblastos cutáneos. Su hermana gemela es fenotípica y genotípicamente normal. La paciente fue diagnosticada en su infancia de enanismo tipo Russell-Silver. En la exploración clínica se apreció una hemiatrofia del hemicuerpo derecho, talla baja, cúbito valgo y amenorrea primaria, hallazgos clínicos compatibles con las características del síndrome de Ullrich-Turner. No se confirmó la presencia de disomía uniparental en sus progenitores como causa de la trisomía. Concluimos que la causa de la trisomía 22 en mosaico pudiera ser un error mitótico posfertilización

We report the case of a 25-year-old woman with ovarian dysgenesis due to trisomy 22 mosaicism. Karyotype in peripheral blood showed a normal 46 XX female. Biopsy of both ovarian streaks revealed trisomy 22 mosaicism in gonads. Cultured skin fibroblasts confirmed the alteration. The patient was born to a twin delivery. Although her sister was phenotypically normal, our patient was diagnosed with Russell-Silver dwarfism in childhood. Physical examination revealed significant right-side hemiatrophy, short stature, cubitus valgus, and absence of normal menarche. These findings are compatible with Ullrich-Turner syndrome. Uniparental disomy as a cause of the trisomy was investigated but was not confirmed in the parents' blood samples. We propose a postfertilization mitotic error as the cause of the trisomy 22 mosaicism

7-day rescue therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure.

BACKGROUND: Quadruple rescue therapy requires a complex scheme with four drugs. AIM: To evaluate the efficacy of ranitidine bismuth citrate-tetracycline-metronidazole rescue regimen, and to compare two different metronidazole dose schemes. METHODS: Prospective multicentre study including proton-pump inhibitor + clarithromycin + amoxicillin failures. Rescue regimen included two 7-day treatment: (i) ranitidine bismuth citrate (400 mg b.d.)-tetracycline (500 mg q.d.s.)-metronidazole (500 mg t.d.s.; RTM1); or (ii) the same regimen but with metronidazole 250 mg q.d.s. (RTM2). Eradication was confirmed with (13)C-urea breath test. RESULTS: A total of 150 patients were included (58 RTM1, 92 RTM2). All patients but two (one in each group) returned after treatment. About 86% in group RTM1 and 95% in RTM2 correctly took all the medications (P = 0.076). Per-protocol eradication rates with RTM1 and RTM2 were 74 (95% CI: 60-84) and 69% (59-78). The intention-to-treat eradication rates were 64 (51-75) and 70% (59-78; P > 0.05). The type of regimen was not associated with eradication in the multivariate analysis. Adverse effects were more frequent with RTM1 (41%) than with RTM2 (30%; P > 0.05). CONCLUSION: Seven-day triple rescue therapy with ranitidine bismuth citrate-tetracycline-metronidazole is effective for Helicobacter pylori eradication, and represents an encouraging alternative to quadruple therapy, with the advantage of simplicity. The administration of metronidazole every 6 h (together with tetracycline), and at a low dose (250 mg), achieves similar efficacy and is probably associated with a better compliance and a lower incidence of adverse effects.

El cerclaje de urgencia en la incompetencia istimicocervical con membranas protruyentes. Nuestra experiencia / Emergency cerclage of the incompetent cervicalisthmus with bulging membranes. Our experience

Presentamos nuestra experiencia en el cerclaje cervical en gestantes con cérvix uterino dilatado y membranas protruyentes. Nuestra supervivencia fetal es del 25 por ciento. La ecografía transvaginal es la técnica aceptada para la valoración de la competencia cervical durante el embarazo. Existe evidencia para afirmar que el cerclaje de urgencia en casos con dilatación avanzada proporciona mayor supervivencia fetal que el tratamiento médico con reposo en cama. Persiste la controversia en los casos con cambios cervicales tempranos diagnosticados mediante ecografía, en los que el cerclaje cervical no ha demostrado ser superior al tratamiento conservador en los trabajos realizados (AU)

An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells.

Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized by induction of an inflammatory response. In contrast, cells dying by apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes of cell death in inducing inflammation are not known. Here we show that necrotic cells, but not apoptotic cells, activate NF-kappaB and induce expression of genes involved in inflammatory and tissue-repair responses, including neutrophil-specific chemokine genes KC and macrophage-inflammatory protein-2, in viable fibroblasts and macrophages. Intriguingly, NF-kappaB activation by necrotic cells was dependent on Toll-like receptor 2, a signaling pathway that induces inflammation in response to microbial agents. These results have identified a novel mechanism by which cell necrosis, but not apoptosis, can induce expression of genes involved in inflammation and tissue-repair responses. Furthermore, these results also demonstrate that the NF-kappaB/Toll-like receptor 2 pathway can be activated both by exogenous microbial agents and endogenous inflammatory stimuli.

Helicobacter pylori "test-and-scope" strategy for dyspeptic patients. Is it useful and safe?

AIM: To evaluate outcome of test-and-scope strategy using 13C-urea breath test, Helicobacter pylori IgG serology, and CagA serology. PATIENTS AND METHODS: A series of 100 dyspeptic patients were studied. Biopsies were obtained for histology and rapid urease test (gold standard). Serum samples were obtained for Helicobacter pylori IgG and CagA serology, and 13C-urea breath test was carried out. RESULTS: If endoscopy had not been performed in Helicobacter pylori patients based on 13C-urea breath test, <45 years, without alarm symptoms, and without non-steroidal anti-inflammatory drug use, 15% of endoscopies would have been saved, and one gastric ulcer and two oesophagitis would have been missed. Based on Helicobacter pylori IgG serology, 21% of endoscopies would have been saved. Finally, if endoscopy had been performed only in CagA+ patients, 31% of endoscopies would have been saved, missing one gastric ulcer and two cases of oesophagitis. CONCLUSIONS: In our geographical area, the test-and-scope strategy based on 13C-urea breath test or Helicobacter pylori IgG serology would have saved only 15-20% of endoscopies. Although some relevant pathology would have been missed, it is not of a malignant type. 13C-urea breath test is the preferred non-invasive method to be used in this strategy, while Helicobacter pylori IgG serology is of limited value due to its low accuracy. With the use of CagA serology a larger number of unnecessary endoscopic examinations can be avoided.