Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

[Intrasinus renal hilium approach, EUREKA time for spanish urological surgical anatomy.] / Vía intrasinusal de abordaje al hilio renal, un momento E U R E K A de la investigación anatómica quirúrgica urológica española.

Historical research has allowed us to reviewand document the author of the first description of the intrasinusal route for access to the renal hilum as astrategy for accessing kidney stones through the bibliography. This new route described and published by M. Serés represented a paradigm shift in open surgery for kidney stones. We want to highlight that the Spanish urological anatomical-surgical investigation with the investigations of Manuel Serés, meant a singular contribution and of enormous importance for the History of International Urology, whose value we must claim with its indisputable and reliable references.

La investigación histórica nos ha permitido revisar y mostrar documentalmente por la bibliografía el autor de la primera descripción de la via intrasinusal para el acceso al hilio renal como estrategia de accesoa la litiasis renal. Esta nueva via descrita y publicada por M. Serés supuso un cambio de paradigma en la cirugía abierta de la litiasis renal. Queremos resaltar que la investigación anatomo-quirúrgica urológica española con las investigaciones de Manuel Serés, significó una aportación singular y de enorme trascendencia para la Historia de la Urología Internacional, cuyo valor debemos reivindicar con sus referencias indiscutibles y fehacientes.

Vía intrasinusal de abordaje al hilio renal, un momento EUREKA de la investigación anatómica quirúrgica urológica española / Intrasinus journey to kidney disease, a EUREKA moment of Spanish urological surgical anatomical research

La investigación histórica nos ha permitidorevisar y mostrar documentalmente por la bibliografíael autor de la primera descripción de la via intrasinusalpara el acceso al hilio renal como estrategia de accesoa la litiasis renal. Esta nueva via descrita y publicadapor M. Serés supuso un cambio de paradigma en lacirugía abierta de la litiasis renal. Queremos resaltarque la investigación anatomo-quirúrgica urológica es-pañola con las investigaciones de Manuel Serés, signi-ficó una aportación singular y de enorme trascendenciapara la Historia de la Urología Internacional, cuyo valordebemos reivindicar con sus referencias indiscutibles yfehacientes.(AU)

Historical research has allowed us to re-view and document the author of the first description ofthe intrasinusal route for access to the renal hilum as astrategy for accessing kidney stones through the bibli-ography. This new route described and published byM. Serés represented a paradigm shift in open surgeryfor kidney stones. We want to highlight that the Span-ish urological anatomical-surgical investigation with theinvestigations of Manuel Serés, meant a singular con-tribution and of enormous importance for the History ofInternational Urology, whose value we must claim withits indisputable and reliable references.(AU)

El "volumen" del saber urológico en el último cuarto de siglo / The volume of urological knowledge in the last 25 years

Pocas especialidades médicas y quirúrgicas han experimentado en las últimas décadas tantos y tan significativos avances terapéuticos como la Urología. Además de progresos en los conocimientos fisiopatológicos de las distintas enfermedades que conforman el corpus del saber Urológico. La cirugía laparoscópica y las ondas de choque extracorpóreas han revolucionado la especialidad en su totalidad, provocando cambios de paradigma tanto en las indicaciones terapéuticas como en la interpretación de algunos procesos patológicos. Aportamos unas reflexiones desde una mirada retrospectiva

Few specialties have gone through as many transitions in the last decades as Urology. Progressive physiology advances in several disease have become part of the urological knowledge. Laparoscopic surgery and ESWL (Extracorporeal Shock Wave Lithotripsy) wave have completely turn upside down the whole management of disease. The current text provides a back to the future sigh into Urology

[The volume of urological knowledge in the last 25 years.] / El "volumen" del saber urológico en el último cuarto de siglo.

Few specialties have gone through as many transitions in the last decades as Urology. Progressive physiology advances in several disease have become part of the urological knowledge. Laparoscopic surgery and ESWL (Extracorporeal Shock Wave Lithotripsy) wave have completely turn upside down the whole management of disease. The current text provides a back to the future sigh into Urology.

Pocas especialidades médicas y quirúrgicas han experimentado en las últimas décadas tantos y tan significativos avances terapéuticos como la Urología. Además de progresos en los conocimientos fisiopatológicos de las distintas enfermedades que conforman el corpus del saber Urológico. La cirugía laparoscópica y las ondas de choque extracorpóreas han revolucionado la especialidad en su totalidad, provocando cambios de paradigma tanto en las indicaciones terapéuticas como en la interpretación de algunos procesos patológicos. Aportamos unas reflexiones desde una mirada retrospectiva.

Shorter hepatitis B immunoglobulin administration is not associated to hepatitis B virus recurrence when receiving combined prophylaxis after liver transplantation.

BACKGROUND & AIMS: The combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens. METHODS: Retrospective multicentre analysis of hepatitis B virus-related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short-term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation. RESULTS: Three hundred and thirty-eight patients were analysed. After a median follow-up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival. CONCLUSIONS: Liver transplantation is an effective treatment for hepatitis B virus-related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence.

Aportaciones al conocimiento de la hepatitis fulminante realizadas por la Unidad de Cuidados Intensivos Hepática del Hospital Clínic de Barcelona: revisión histórica / Contributions to our understanding of fulminant hepatitis from the Liver ICU of Hospital Clínic Barcelona: Historical review

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Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.

Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. METHODS: We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. RESULTS: The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. CONCLUSION: Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.

Extracorporeal liver support in severe alcoholic hepatitis.

The severity of alcoholic hepatitis (AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation.

Impact of chronic liver disease in intensive care unit acquired pneumonia: a prospective study.

PURPOSE: To assess the impact of chronic liver disease (CLD) on ICU-acquired pneumonia. METHODS: This was a prospective, observational study of the characteristics, microbiology, and outcomes of 343 consecutive patients with ICU-acquired pneumonia clustered according to the presence of CLD. RESULTS: Sixty-seven (20%) patients had CLD (67% had liver cirrhosis, LC), MELD score 26 ± 9, 20% Child-Pugh class C). They presented higher severity scores than patients without CLD both on admission to the ICU (APACHE II, LC 19 ± 6 vs. other CLD 18 ± 6 vs. no CLD 16 ± 6; p < 0.001; SOFA, 10 ± 3 vs. 8 ± 4 vs. 7 ± 3; p < 0.001) and at onset of pneumonia (APACHE II, 19 ± 6 vs. 17 ± 6 vs. 16 ± 5; p = 0.001; SOFA, 11 ± 4 vs. 9 ± 4 vs. 7 ± 3; p < 0.001). Levels of CRP were lower in patients with LC than in the other two groups (day 1, 6.5 [2.5-11.5] vs. 13 [6-23] vs. 15.5 [8-24], p < 0.001, day 3, 6 [3-12] vs. 16 [9-21] vs. 11 [5-20], p = 0.001); all the other biomarkers were higher in LC and other CLD patients. LC patients had higher 28- and 90-day mortality (63 vs. 28%, p < 0.001; 72 vs. 38%, p < 0.001, respectively) than non-CLD patients. Presence of LC was independently associated with decreased 28- and 90-day survival (95% confidence interval [CI], 1.982-17.250; p = 0.001; 95% confidence interval [CI], 2.915-20.699, p = 0.001, respectively). CONCLUSIONS: In critically ill patients with ICU-acquired pneumonia, CLD is associated with a more severe clinical presentation and poor clinical outcomes. Moreover, LC is independently associated with 28- and 90-day mortality. The results of this study are important for future trials focused on mortality.

A multicolor fluorescence in situ hybridization assay: A monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: A prospective study.

BACKGROUND: Non-muscle-invasive urothelial cell carcinoma (NMIUCC) has a high tendency to recur and affected patients must be monitored regularly using invasive cystoscopies. The aim of the current study was to compare a multicolor fluorescence in situ hybridization (FISH) assay (UroVysion) with routine follow-up (cystoscopy and cytology) in the monitoring of patients with a previous history of NMIUCC. METHODS: An unselected cohort of patients under surveillance for a previous history of NMIUCC was prospectively studied. A total of 248 examinations in 223 patients were analyzed. Each exploration was comprised of cytological and FISH microscopic examination of voided urine samples and cystoscopy. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for tumor recurrence of all 3 techniques were determined. RESULTS: The sensitivities of FISH and cystoscopy were not found to be significantly different (92.9% and 82.1%, respectively). The specificities of FISH and cystoscopy were 92.7% and 89.7%, respectively. The PPV and NPV of FISH were 53.5% and 97.2%, respectively, whereas those of cystoscopy were 63.4% and 98.9%, respectively. No significant differences were found between these 2 tests. In contrast, the sensitivity and specificity of cytology were 14.3% and 99.5%, respectively. CONCLUSIONS: Given the lack of statistically significant differences with regard to FISH and cystoscopy results, the authors propose that FISH could be a useful monitoring tool in the surveillance of patients with a previous history of NMIUCC.

Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series.

BACKGROUND: Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. METHODS: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. RESULTS: In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4). CONCLUSIONS: Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

Multicentric reticulohistiocytosis with elevated cytokine serum levels.

Multicentric reticulohistiocytosis (MRH) is an uncommon non-Langerhans cell histiocytosis of unknown etiology. It is a multisystem disorder characterised by a papulonodular skin eruption, mainly in the extensor surfaces, and destructive polyarthritis. Histologically, either cutaneous lesions or the synovium show a dense dermal infiltrate of histiocytes and multinucleated giant cells with an eosinophilic granular material in the cytoplasm. In the immunohistochemical analysis these cells stain positively with monocyte/macrophage markers (CD68 and CD45), as well as with certain cytokines (tumor necrosis factor-α, interleukin 1ß and interleukin 6). Moreover, recent reports suggest an osteoclastic nature of the infiltrating cells, as they stain strongly with osteoclast tissue lytic markers including tartrate-resistant acid phosphatase and cathepsin K. We report a case of MRH presenting with clinical features of dermatomyositis. Furthermore, the patient showed elevated cytokine serum levels that lowered after therapy.

Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension.

UNLABELLED: Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors. Although terlipressin is also a partial agonist of renal vasopressin V2 receptors, its effects on serum sodium concentration have not been specifically investigated. To examine the effects of terlipressin on serum sodium concentration in patients with acute portal-hypertensive bleeding, 58 consecutive patients with severe portal-hypertensive bleeding treated with terlipressin were investigated. In the whole population, serum sodium decreased from 134.9 ± 6.6 mEq/L to 130.5 ± 7.7 mEq/L (P = 0.002). Thirty-nine patients (67%) had a decrease in serum sodium ≥ 5 mEq/L during treatment: in 18 patients (31%), between 5 and 10 mEq/L and in 21 patients (36%), greater than 10 mEq/L. In this latter group, serum sodium decreased from 137.2 ± 5 to 120.5 ± 5 mEq/L (P < 0.001). In multivariate analysis, the reduction in serum sodium was related to baseline serum sodium and Model for End-Stage Liver Disease (MELD) score; patients with low MELD and normal or near-normal baseline serum sodium had the highest risk of hyponatremia. Serum sodium returned to baseline values in most patients shortly after cessation of therapy. Three of the 21 patients with marked reduction in serum sodium developed neurological manifestations, including osmotic demyelination syndrome in one patient due to a rapid recovery of serum sodium (serum sodium in these three patients decreased from 135, 130, and 136 to 117, 114, and 109 mEq/L, respectively). CONCLUSION: An acute reduction in serum sodium concentration is common during treatment with terlipressin for severe portal-hypertensive bleeding. It develops rapidly after start of therapy, may be severe in some patients and is associated with neurological complications, and is usually reversible after terlipressin withdrawal.