Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

Síndrome de choque por dengue (SCD) y embarazo: reporte de un caso / Syndrome of shock by dengue (ACD) and pregnancy: a case report

El Dengue Hemorrágico (DH) es una variante del Dengue, que cursa con alteraciones hemostáticas y vasculares potencialmente fatales. El Síndrome de Choque por Dengue (SCD) es la forma más severa del DH. A continuación, se presenta un caso de SCD en una paciente con gestación de 9 semanas, y su manejo. Actualmente no se cuenta con conocimiento suficiente acerca del comportamiento de esta enfermedad en pacientes embarazadas. Vale la pena destacar, que no hallamos ningún reporte de SDC en pacientes embarazadas, ni encontramos pautas para el manejo de las mismas, por lo que consideramos de mucha importancia la publicación y diseminación del mismo, como base para nuevas investigaciones.

Manejo de las pacientes embarazadas con HIV en el Hospital Dr. Luis Razetti de Barinas: estudio de 25 casos / Management of pregnant patients with HIV at the Hospital Dr. Luis Razetti of Barinas: study of 25 cases

Con el objetivo de dar a conocer nuestra experiencia en el manejo de pacientes embarazadas infectadas con HIV, se realizó un estudio observacional descriptivo en el Servicio de Ginecología y Obstetrica del Hospital de Barinas. Se revisaron las historias clínicas entre enero de 2001 y abril de 2007, encontrando 25 pacientes con edad promedio de 24,44 años, una media de 3,74 parejas sexuales, al 52 por ciento se les realizo el diagnóstico de HIV durante el tercer trimestre de su último embarazo, 84 por ciento cumplió el protocolo de tratamiento 076 con ZDV, al 76 por ciento se les realizó cesárea segmentaría durante su último embarazo. La infección por HIV es un riesgo latente en nuestra población de mujeres en edad fértil, en nuestro medio se hacen esfuerzos por realizar un manejo adecuado y tratar de disminuir las probabilidades de transmisión vertical.

Tumor filodes benigno de mama izquierda: a propósito de un caso / Left breast benign phylodes tumor: a purpose of a case

Femenina de 34 años de edad, quien refiere enfermedad, con una tumoración en la mama izquierda de 6 meses de evolución, que fue aumentando progresivamente de tamaño. Se diagnóstico un Tumor Filodes benigno de mama izquierda, que fue estudiado y llevado a resolución quirúrgica sin complicaciones ni recidivas hasta la actualidad. El Tumor Filodes es una patología poco frecuente que representa menos del 1 por ciento de todos los tumores mamarios, con un comportamiento biológico variable, aunque la mayoría son benignos existe una variante histológica maligna que puede dar metástasis a distancia. Debe ser resecado quirúrgicamente con márgenes adecuados para evitar recidivas y mantenerse una vigilancia clínica post-operatoria estricta durante un periodo no menor de 2 años.

Hemangioma deformante cervical derecho: a propósito de un caso / Deformans right cervical hemangioma: a purpose of a case

Masculino de 32 años de edad, con aumento de volumen progresivo en la cara lateral derecha del cuello, de 20 años de evolución. Se sometió a resolución quirúrgica sin complicaciones. La histopatología reveló un Hemangioma Cavernoso, un tumor vascular benigno poco común, que puede causar molestias estéticas y funcionales de acuerdo a su localización, así como complicaciones sistémicas relacionadas con síndromes asociados. Comúnmente aparece en etapa neonatal puede hacerlo en el adulto. No existe tendencia a la regresión. La cirugía es el tratamiento definitivo, siempre que la lesión sea circunscrita y no afecte a órganos vitales.

[Preocclusive stenosis of the extracranial vertebral artery. Treatment by percutaneous transluminal angioplasty and insertion of endoprosthesis]. / Estenosis preoclusiva de la arteria vertebral extracraneal. Tratamiento mediante angioplastia transluminal percutánea y colocación de endoprótesis.

INTRODUCTION: Atherosclerotic occlusive disease of the extracranial portion of the vertebral artery is relatively frequent and is usually related to vertebrobasilar ischemia. Due to the lack of a noninvasive diagnostic technique, at present it is often not diagnosed. Surgical treatment is difficult and risky. Percutaneous transluminal angioplasty (PTA) is only partly useful due to a high rate of restenosis. The recent development of stenting has led to an evident improvement of PTA results, reducing restenosis and offering an effective treatment with low morbidity and mortality. CLINICAL CASE: Sixty year old male patient, smoker and moderate drinker, who is hospitalized due to repeated ischemic strokes (cerebellar stroke in the left posterior and interior inferior cerebellar arteries, and cerebral stroke at occipito-parietal and ipsilateral capsulo-thalamic levels) in spite of antithrombotic treatment. Angiography showed: a) occlusion of the left vertebral artery; b) preocclusive stenosis of the right vertebral artery in the ostium; c) fetal origin of the right posterior cerebral artery, and d) left hypoplasic posterior communicating artery. PTA and stent placement at the right vertebral artery is performed with an excellent angiographic result, a partial recovery of neurological symptomatology and absence of new episodes of cerebral ischemia during a three-month follow-up. CONCLUSION: Percutaneous transluminal angioplasty and stent placement is an effective low morbidity-mortality treatment in occlusive atherosclerosis of the vertebral artery, although further randomized multicenter studies are required in order to validate this conclusion.

[Prisoners and tuberculosis. Rejection of chemoprophylaxis]. / Reclusos y tuberculosis. Rechazo a la quimioprofilaxis.

Inmates under age 25 held in prisons who manifest first degree level health problems demonstrate a degree of rejection towards preventive treatment which periodically requires reconsideration of the methods employed by the interdisciplinary teams in these centers. Our main objective is to evaluate the degree of rejection that these inmates demonstrate towards preventive campaigns against tuberculosis and to try to relate their lack of collaboration to such negative psychosociological factors as drug addiction, immunodeficiency due to HIV, and prolonged prison stays. For this study, a total of 50 inmates having similar characteristics were selected. A high rate of a negative attitude was shown in these circumstances: towards preventive treatment with Isoniacide, in relationship to the degree of immunodeficiency, a rejection of treatment with antiretroviruses and length of prison stay. Nursing programs for penitentiary inmates must take into consideration psychological and sociological aspects.

[Bacterial origin of acute diarrhea in Merida, Venezuela]. / Origen bacteriano de la enfermedad diarreica aguda en Mérida, Venezuela.

464 stool specimens from children under 5 with acute diarrheal disease and other 149 specimens from the control group were studied from July, 1993, to May, 1995. The specimens were collected at the Pediatric Emergency Department of the Autonomous Institute of the Teaching Hospital of Los Andes, Mérida, Venezuela. The presence of the internationally recommended bacterial, parasitary and viral agents was investigated. The commonest bacteria isolated as unique pathogens were: Shigella (42.85%), Shigella sonnei, the most found, (66.67%), and the thermotolerant Campylobacter, Aeromonas sp. and enteropathogenous Escherichia coli, with 15; 15 and 13.5%, respectively. 6.5% of parasites and 24.12% of Rotavirus were also found. It was concluded that in the period of time under study the infectious and mainly, the bacterial origin is an important cause of acute diarrheal disease in Mérida.

Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells.

In response to fibroblast growth factor (FGF), FGF receptor-1 (FGFR-1) (flg) becomes tyrosine phosphorylated and associates with phospholipase C gamma (PLC gamma) and a 90 kDa protein. We report here that in cells transformed by v-Src, FGFR-1 becomes phosphorylated on tyrosine; however, neither PLC gamma nor p90 was found to be associated with tyrosine-phosphorylated FGFR-1. Instead, there was a strong constitutive association of FGFR-1 with the adaptor proteins Shc and Grb2 and the Ras guanine nucleotide exchange factor Sos. Association with Shc and Grb2 and Sos was not observed in response to FGF. Suramin did not prevent either tyrosine phosphorylation or Shc/Grb2/Sos association, indicating a non-autocrine mechanism. Thus, in cells transformed by v-Src, tyrosine phosphorylation of FGFR-1 results not in the expected association with PLC gamma and p90, but rather in the recruitment of the Ras activating Shc/Grb2/Sos complex. These data suggest a mechanism for Ras activation by v-Src involving phosphorylation of novel tyrosine(s) on FGFR-1.

Activation of gene expression by a non-transforming unmyristylated-SH3-deleted mutant of Src is dependent upon Tyr-527.

v-Src transcriptionally induces gene expression by activating several transcriptional response elements such as the serum response element (SRE), the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE), and the c-AMP response element (CRE) found in the promoters of several proliferation-related immediate early genes. We report here that a Src protein, with a deletion in the SH3 domain and lacking a membrane localization signal, strongly activates gene expression mediated by SRE, TRE and CRE transcriptional control elements. This mutant was unable to cause cellular transformation, suggesting that activation of these transcriptional control elements is not sufficient for the induction of a transformed phenotype by Src. Interestingly, the ability of the membrane localization and SH3 deletion mutant to activate gene expression was abolished upon conversion of the C-terminal inhibitory Tyr-527 to Phe. These data suggest the existence of previously unreported Tyr-527-dependent activation of intracellular signals that activate gene expression. These data raise the possibility that Src may exert physiological effects via an interaction between Tyr-527 and an SH2-containing protein that would interact with the phosphorylated form of Tyr-527.

[Yield of ultrasound-guided transrectal biopsy in the diagnosis of prostatic cancer in symptomatic patients]. / Rendimiento de la biopsia transrectal ecodirigida en el diagnóstico del cáncer de próstata en los pacientes sintomáticos.

OBJECTIVE: The aim of this retrospective study was to evaluate the utility of US-guided transrectal biopsy of the prostate in the diagnosis of prostatic cancer in symptomatic patients and its correlation with the digital rectal examination (DRE), PSA levels and ultrasound findings. METHODS: From 1994 to 1995, 427 patients with prostatic symptomatology underwent prostatic biopsy. The mean age was 69.1 +/- 8.3 years (range 44 - 89). The criteria for biopsy were abnormal DRE, PSA > 10 ng/ml, abnormal US findings and/or PSA density > 0.15. RESULTS: Prostate cancer was confirmed in 42% of the patients. The incidence of cancer when DRE was abnormal was 73%, 46% when PSA was > 10 ng/ml and 55% when the US findings were abnormal; 82% for abnormal DRE and PSA > 10 ng/ml, and 84% when the criterion of abnormal US was included. The incidence of cancer when DRE was normal was 16%, 18% when combined with PSA > 10 ng/ml and remained unchanged when combined with the US findings. In patients with normal DRE and PSA between 10 - 30 ng/ml, the incidence of cancer was 14% and 41% for those with PSA > 30 ng/ml. CONCLUSION: DRE was the best independent predictor of prostate cancer and the combination of abnormal DRE, PSA > 10 ng/ml and abnormal US findings gave the highest detection rate. The incidence of prostate cancer was very low in patients with normal DRE and PSA between 10 - 30 ng/ml, which may be due to the fact that the PSA levels are raised by the non neoplastic changes in the transitional zone in symptomatic patients.

[Variability of rectal examination of the prostate among various groups of observers]. / Variabilidad del tacto rectal de la próstata entre distintos groupos de observadores.

Rectal examination (RE) of the prostate gland is compulsory to rule out the presence of prostate cancer (PC). Empirically, it is defined as an examination burdened with a high degree of subjectivity and difficult to reproduce. The objective of this retrospective study is to evaluate RE concordance between different groups of researchers. In 133 patients referred to our Centre with suspected PC, RE was performed by three groups of experimented urologists (2 in-hospital and 1 out-hospital). Concordance between the different groups was evaluated using Kappa's index (K). Kappa's index between out- and in-hospital urologists was 70%, 71% and 78%. Concordance of RE findings between the different groups of urologists can be considered good, since no significant differences were found relative to ER positive predictive value.

[Performance+ of transrectal ultrasonography in the diagnosis of prostatic cancer in patients with abnormal digital examination]. / Rendimiento de la ecografía transrectal en el diagnóstico del cáncer de próstata en los pacientes con tacto rectal anormal.

OBJECTIVES: To determine the incidence of prostatic cancer in patients with abnormal digital rectal examination (DRE) and its correlation with PSA levels and US findings. METHODS: A retrospective study was conducted on 167 patients with abnormal DRE that had been evaluated by PSA, US and prostate biopsy from January, 1994 to September, 1995. The 95% confidence interval was estimated (C195) for the differences observed. RESULTS: Biopsy demonstrated cancer in 73% of the patients; 67.7% of the patients with DRE classification of T2 versus 88.4% of those with T3 (C195 = 8%-33.3%); 81.4% of patients with PSA > 10 ng/ml had cancer versus 60.5% of patients with PSA > 4 and < 10 ng/ml (CI95 = 3%-37.9%); 79.5% of the cases with ultrasound nodes had cancer vs 43.3% of those without (CI95 = 17.3%-55.2%). In patients with PSA > 4 and < or = 10 ng/ml, 71% of the cases with ultrasound nodes had cancer versus 14.3% with no nodal involvement (CI95 = 26.2%-87.1%). In patients with PSA > 10 ng/ml, 83.2% of the patients with ultrasound evidence of node involvement had cancer versus 70.6% of the patients with no node involvement (CI95 = -10.3%-35.4%). CONCLUSIONS: The incidence of prostatic cancer in patients with abnormal DRE was 73%; 81.4% of patients with PSA > 10 ng/ml and 79.5% of patients with ultrasound evidence of node involvement and 83.2% of those with both of the foregoing characteristics. Biopsy of both prostatic lobes should be performed routinely in all patients with abnormal DRE.

[Subcapsular renal hematoma following shock wave lithotripsy]. / Hematomas renales subcapsulares tras litofragmentación por ondas de choque.

OBJECTIVES: The present study analyzed the incidence of subcapsular hematoma of the kidney (SH) following extracorporeal shock wave lithotripsy (ESWL), its management and the possible risk factors that influence the development of this condition. METHODS: We received the records of 1600 patients submitted to 2250 ESWL sessions. SH was evaluated according to the following parameters: clinical features, diagnostic methods, management, follow up and the patient -and ESWL- related factors that influence the development of this condition. RESULTS: Five cases of SH were found (0.22% incidence), which had been diagnosed by ultrasound (US). Eighty per cent had sustained lumbar pain and a fall in hemoglobin values. The patients were managed conservatively and US follow up evaluation was done. At six months, resolution was almost complete with no sequelae. No patient had any of the risk factors described in the literature (hypertension, concomitant urinary tract infection or coagulation disorders) or changes in the ESWL unit standards. CONCLUSIONS: Although SH following ESWL is uncommon, sustained lumbar pain and a fall in hemoglobin values are risk factors that should be taken into account and corroboration and follow up by US should be done. Unless complications present, the patients should be managed conservatively.

[Gangrenous cystitis induced by giant bladder calculus]. / Cistitis gangrenosa inducida por un cálculo vesical gigante.

Presentation of one case of gangrenous cystitis or vesical gangrene induced by the presence of a large vesical calculus in a patient with neurogenic bladder. Remarks on the patho-etiology, symptoms and treatment of this rare entity entailing a truly surgical emergence.