Efficacy and Safety of the Combination of Pravastatin and Sorafenib for the Treatment of Advanced Hepatocellular Carcinoma (ESTAHEP Clinical Trial).

Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response.

Correction: Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study.

[This corrects the article DOI: 10.1371/journal.pone.0184550.].

Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study.

BACKGROUND: Hepatitis B virus (HBV) reactivation in patients with resolved HBV infection (HBsAg negative, antiHBc positive) is uncommon, but potentially fatal. The role of HBV prophylaxis in this setting is uncertain. The aim of this study was to compare the efficacy of tenofovir disoproxil fumarate (TDF) prophylaxis versus close monitoring in antiHBc-positive, HBsAg-negative patients under treatment with rituximab (RTX)-based regimens for hematologic malignancy. METHODS: PREBLIN is a phase IV, randomized, prospective, open-label, multicenter, parallel-group trial conducted in 17 hospitals throughout Spain. Anti-HBc-positive, HBsAg-negative patients with undetectable HBV DNA were randomized to receive TDF 300 mg once daily (Group I) or observation (Group II). The primary endpoint was the percentage of patients showing HBV reactivation during 18 months following initiation of RTX treatment. Patients with detectable HBV DNA (Group III) received the same dose of TDF and were analyzed together with Group I to investigate TDF safety. RESULTS: Sixty-one patients were enrolled in the study, 33 in the TDF treatment group and 28 in the observation group. By ITT analysis, HBV reactivation was 0% (0/33) in the study group and 10.7% (3/28) in the observation group (p = 0.091). None of the patients in either group showed significant differences in liver function parameters between baseline and the last follow-up sample. TDF was generally well tolerated and there were no severe treatment-related adverse events. CONCLUSION: In patients with hematological malignancy and resolved hepatitis B infection receiving RTX-based regimens, HBV reactivation did not occur in patients given TDF prophylaxis.

Dermatosis ampollar por inmunoglobulina A lineal: Reporte de dos casos / Linear immunoglobulin A bullous dermatosis: Two cases report

La dermatosis ampollar por inmunoglobulina A lineal es una rara enfermedad, generalmente autolimitada, que afecta a niños de 4,5 años (edad media), con una incidencia de 0,52,3 casos/millón de habitantes/año. Es, tras la dermatitis herpetiforme, la enfermedad ampollar pediátrica más frecuente. Ocurre en brotes con lesión patognomónica en collar de perlas y afecta preferentemente la zona genital y peribucal. Su diagnóstico se basa en una alta sospecha clínica y en la biopsia de piel con observación de ampollas subepidérmicas y depósito lineal de inmunoglobulina A en inmunofluorescencia directa. Frecuentemente, el diagnóstico es tardío debido al desconocimiento de esta enfermedad.

Linear immunoglobulin A bullous dermatosis is a rare entity with frequent spontaneous resolution. It usually presents in children with average age of 4.5 years. Its incidence is about 0.5-2.3 cases/million individuals/year. It is, after dermatitis herpetiformis, the most frequent paediatric blister disorder. It usually appears in bouts with acute development of vesicles in strings of pearls; affecting the perioral area and genitalia. Diagnosis is based on the clinical signs and symptoms and biopsy of the skin with subepidermal blister and a linear band of immunoglobulin A in the direct immunofluorescence. Often, diagnosis is made late because of the unawareness of this disease.

[Linear immunoglobulin A bullous dermatosis: Two cases report]. / Dermatosis ampollar por inmunoglobulina A lineal: Reporte de dos casos.

Linear immunoglobulin A bullous dermatosis is a rare entity with frequent spontaneous resolution. It usually presents in children with average age of 4.5 years. Its incidence is about 0.5-2.3 cases/million individuals/year. It is, after dermatitis herpetiformis, the most frequent paediatric blister disorder. It usually appears in bouts with acute development of vesicles in strings of pearls; affecting the perioral area and genitalia. Diagnosis is based on the clinical signs and symptoms and biopsy of the skin with subepidermal blister and a linear band of immunoglobulin A in the direct immunofluorescence. Often, diagnosis is made late because of the unawareness of this disease.

[Greenlight-XPS laser vaporization, the new standard of treatment in men with myasthenia gravis and benign prostatic obstruction]? / La fotovaporización prostática con laser (PVPL) podría constituir una alternativa eficaz y segura a la resección transurethral (RTUP) en pacientes con miastenia gravis.

UNLABELLED: Patients with Benign Prostatic Obstruction (BPO) and Myasthenia Gravis (MG) treated with Transurethral Resection of the prostate (TURP) show a high incidence of urinary incontinence due to unnoticed damage to muscle fibres of the external sphincter. Photoselective laser vaporization could be an alternative treatment based on the hypothesis that using Laser as energy source in the treatment of BPH prevents sphincter damage because the energy is not transmitted outside the fiber tip. METHODS: We report the case of a man diagnosed of MG and symptomatic BPO treated satisfactorily with photoselective laser vaporization (GreenLight-XPS). RESULTS: Patient did not experienced postoperative secondary incontinence. CONCLUSIONS: Laser photoselective vaporization (GreenLight-XPS) could be the standard treatment for men with MG and BPO, whose prostate volume is less than 60 cc who are candidates for surgical treatment. Despite the extremely low incidence of these cases, further investigations are needed to confirm this affirmation.

Dried blood as an alternative to plasma or serum for Trypanosoma cruzi IgG detection in screening programs.

Trypanosoma cruzi serological screening is recommended for people potentially exposed to this parasite in countries where Trypanosoma cruzi is endemic and those where it is not endemic. Blood samples on filter paper may be a practical alternative to plasma/serum for antibody detection. Using the Architect Chagas assay, we detected the presence of IgG against T. cruzi in matched serum and dried blood spots (DBS) collected from 147 patients residing in Madrid, Spain, who had potential previous exposure to T. cruzi. The κ statistic for the DBS/serum proportion of agreement for the detection of antibodies against T. cruzi was 0.803, considering an S/CO (assay result unit; chemiluminescent signal from the sample [S] divided by the mean chemiluminescent signal for the three calibrators used in the test [CO]) cutoff value of ≥1.00. The relative sensitivity of the Architect test using DBS increased from 95.2% to 98.8% when the cutoff was lowered from ≥1.00 to ≥0.88, while the relative specificity decreased from 84.1% to 71.6%. Overall, the median S/CO values for DBS were significantly lower than those for serum (2.6 versus 6.5; P < 0.001). Discrepancies that occurred with the use of DBS included 10 false positives (with low S/CO values in 9 cases [median, 2.13]) and 4 false negatives, with mean S/CO values of 0.905 (gray zone). Using DBS plus a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) may be a simple and reliable method for detecting IgG against T. cruzi when blood sampling by venipuncture is not feasible. This method may also reduce the false-negative rates observed with some rapid diagnostic tests. The lower relative sensitivity compared to the reference method may be increased by lowering the optical density threshold.

Application of Pediatric Appendicitis Score on the emergency department of a secondary level hospital.

BACKGROUND: Acute appendicitis is the most common surgical emergency during childhood. Accurate early diagnosis is important to avoid complications and unnecessary interventions. In 2002, Samuel developed the Pediatric Appendicitis Score (PAS) based on a series of data obtained from anamnesis, physical examination, and laboratory tests. The main purpose of this study was to check the validity of PAS and its applicability to our population. METHODS: Prospective observational study, carried out at Hospital Río Hortega (Valladolid, Spain), between June 2009 and May 2010. Data from 101 patients who presented to the emergency department experiencing abdominal pains were recovered. RESULTS: A total of 101 patients were included in the study: 55 were boys and 46 girls. The mean age was 9.51 (2.76) years. Diagnosis was acute appendicitis in 28 patients, adenitis in 8 patients, nonspecific abdominal pain in 51 patients, and other diagnoses in 14 patients. The mean (SD) PAS for children with and without appendicitis was 7.43 (1.79) and 4.97 (1.67), respectively (P < 0.001). CONCLUSIONS: With a cutoff PAS of 3 or lower, there were no patients diagnosed with acute appendicitis; hence, these patients could be discharged without any image studies. If all the patients with a PAS of 8 or higher undergo surgery, we would find in our sample a 4.95% rate of negative appendicectomy, less than other studies have shown. The application of this score in the emergency department could help in the decision making process, aiding in the identification of patients with a low risk of having appendicitis and enabling a better use of resources by avoiding unnecessary diagnostic tests.

Prostatic nephrogenic adenoma. Case report.

OBJECTIVE: We present a case of prostatic urethra nephrogenic adenoma as an incidental finding following transurethral resection of the prostate. METHOD/RESULT: It is an incidental diagnosis of nephrogenic adenoma of prostatic urethra in a 50-year-old male operated for benign prostatic hyperplasia by means of transurethral resection. CONCLUSIONS: Nephrogenic adenoma is an infrequent and benign lesion of the urinary tract, associated with a previous history of trauma or irritation on the urothelium. Predisposing factors include infections, calculi, surgery, trauma and kidney transplantation.

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry.

BACKGROUND AND AIM: Esophageal motility abnormalities, as measured by conventional manometry (CM), are non-specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high-resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction. METHODS: All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed. RESULTS: HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan-esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan-esophageal pressurization in controls. Nine of 10 patients with pan-esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings. CONCLUSIONS: The most frequent esophageal motor abnormality measured by HRM was a pan-esophageal pressurization. Bolus impaction in patients with EoE was associated with pan-esophageal pressurization.

Adrenal myelolipoma. Contribution of a case and bibliographic review.

OBJECTIVE: We report the case of adrenal gland myelolipoma. METHODS/RESULTS: The patient was a 29 year old who is diagnosed with an adrenal adenoma during an endocrinology review. He underwent laparoscopic adrenalectomy. The pathological study confirmed the diagnosis of adrenal myelolipoma. CONCLUSIONS: The myelolipoma is a rare tumor composed of hematopoietic elements in different maturation stages and without histological changes, combined with mature adipose tissue in varying proportions. Most of them are incidental findings during radiologic complementary tests. Treatment should be tailored to each particular case. Surgery is indicated when the mass exceeds the size 4-6 cm or when it is a functioning mass.

Prospective evaluation of a clinical guideline recommending early patients discharge in bleeding peptic ulcer.

BACKGROUND AND AIM: To validate an early discharge policy in patients admitted with upper gastrointestinal bleeding (UGIB) due to ulcers. METHODS: Patients with gastroduodenal ulcer or erosive gastritis/duodenitis were included in a previous study aiming to develop a practice guideline for early discharge of patients with UGIB. Variables associated with unfavorable evolution were analyzed in order to identify patients with low-risk of re-bleeding. After that, a one-year prospective analysis of all UGIB episodes was carried out. RESULTS: A total of 341 patients were identified in the retrospective study. Variables associated with unfavorable evolution were: systolic blood pressure < or = 100 mmHg, heart rate > or = 100 bpm, and a Forrest endoscopic classification of severe. 10% of patients were immediately discharged; however, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 34% of patients. A total of 77 patients were included in the prospective analysis. Although only 19.5% of patients were immediately discharged without complications, 29 patients (37.7%) were theoretically suitable for early discharge. CONCLUSIONS: Patients with UGIB who have clean-based ulcers and are stable on admission can be safely discharged immediately after endoscopy. Implementation of the clinical practice guideline safely reduced hospital admission for those patients.

Diferencias individuales en adicciones: perfiles psicosociales asociados al consumo de cocaína / Individual differences in addictions: associated psychosocial profiles to cocaine use

En las últimas décadas se ha encontrado evidencia acerca de la existencia de dos perfiles claramente distinguibles en los pacientes alcohólicos. Estos perfiles incluyen diferencias que van desde la edad de comienzo, gravedad y estilo de consumo, hasta características diferenciales de personalidad. Diferentes grupos de investigación han denominado a dichos patrones como Tipo I y II, o Tipo A y B. En los últimos años se ha intentado probar si dichos hallazgos son generalizables a otras adicciones. En el presente trabajo se hará una revisión de esas investigaciones, centrando el análisis en aquellas que han sido realizadas con personas adictas a la cocaína, con resultados positivos hasta el momento.

[Hematuria of papillary or medullar origin: a difficult diagnosis entity]. / Hematuria de origen papilar o medular: entidad de difícil diagnóstico.

OBJECTIVES: Renal haemangiomas of renal papillary or medullar origin are a difficult diagnosis entity, being one of the most frequent processes of chronic episodes of hematuria, secondary to benign disease, mainly in young patients. The objective of this paper is to show the difficulty of this diagnosis and the need to suspect it in cases with clinical history similar to the ones described in these cases. METHODS: We report 4 cases of spontaneous hematuria of renal origin, with clinical presentation as renal colic, from the historical case series of the Fundacion Jimenez Díaz-Capio, the last two from the years 2005-6. We present the diagnostic and therapeutic methodology employed, including angio-CT and flexible ureterorenoscopy (URS) as well as various treatment options. RESULTS: Hematuria was identified as "essential" when any relation with tumor or lithiasic pathologies was ruled out, and of renal origin when the source was clearly pointed. We interpreted it was related to angiomas or microangiomas of papillary or medullar origin. In one case, the vascular malformation was interpreted as an arterial venous fistula (AVF) at that level. Hematuria stopped spontaneously in two cases after exploratory URS. The eldest historical case required surgical expiration of the caliceal structures. CONCLUSION: Years ago, following the professional development of Urology as speciality, conventional surgery was carried out in all these cases, of very difficult diagnosis, with a very small number of cases undergoing a conservative approach based on the examination of renal cavities trying to observe and find the bleeding point. Most cases underwent complete or partial nephrectomy. Currently, the possibility of exploration of all renal cavities with the flexible ureterorenoscope enables a better diagnosis of the lesions and a more conservative treatment. The ultimate diagnosis of renal papillary angioma is the pathologic diagnosis, without pathognomonic data in the imaging tests. This pathology is thought of at the end of the diagnostic workup, and when the papillary area is identified as the source of bleeding. The historical case series, with the pathologic findings from nephrectomy specimens, permits us to point out this entity as papillary angioma, in patients with similar clinical presentation.

Neuroimmunomodulation during exercise: role of catecholamines as 'stress mediator' and/or 'danger signal' for the innate immune response.

Exercise-induced neuroimmunomodulation is clearly accepted today. The present article reviews the main literature concerning the immunomodulatory capacity of catecholamines on the innate immune response during physical exercise, and presents our laboratory's latest results on this topic. It is well known that the effects of exercise on the immune system are mediated by the 'stress hormones and mediators'. Although catecholamines have usually been regarded as immunosuppressors, they may stimulate innate immune response mechanisms (such as phagocytic function) during exercise-induced stress, even without previous antigenic stimulation. The exercise-induced stimulation of the phagocytic response in particular and the innate responses in general have been considered as a prevention strategy of the athlete's organism in order to prevent the entry and/or maintenance of antigens in a situation where the adaptive immune response seems to be depressed, and thus it has been suggested that catecholamines participate as a 'stress mediator' of these effects. Given this hypothesis, it is also suggested here that catecholamines may be the first 'danger signal' to the immune system during exercise-induced stress.