Hepatitis C virus point-of-care microelimination approach in a vulnerable population in the South of Spain.

Background: Since the introduction of direct-acting antivirals, thousands of chronic hepatitis C patients have been successfully treated. However, vulnerable populations have a higher prevalence of hepatitis C virus (HCV) infection and face barriers that impede their access to antivirals. We carried out an HCV microelimination program focused on vulnerable population groups in Malaga. Methods: People in drug addiction treatment centers and homeless shelters in Malaga who participated in the program between October 2020 and October 2021 were included. After providing participants with educational information on HCV, a dry drop test (DDT) was used to collect blood for subsequent screening for HCV infection. The participants who were diagnosed with HCV infection were scheduled for comprehensive healthcare assessments, including blood tests, ultrasonography, elastography, and the prescription of antivirals, all conducted in a single hospital visit. Sustained viral response (SVR) was analysed 12 weeks after end of treatment. Results: Of the 417 persons invited to participate, 271 (65%) agreed to participate in the program. These participants were screened for HCV infection and 28 of them were diagnosed with HCV infection (10%). These hepatitis C-infected patients had a mean age of 53 ± 9 years; 86% were males and 93% were or had been drug users. Among 23 patients with HCV infection, HCV genotype 1a predominated (74%). Medical exams showed that 19% (4/21) had advanced fibrosis (F3-4), and 5% (1/21) had portal hypertension. Finally, 23 infected patients received treatment with glecaprevir/pibrentasvir or sofosbuvir/velpatasvir and SVR was confirmed in 22 patients (96%). Conclusions: Drug users and homeless people have a higher prevalence of HCV infection than the general population. The microelimination program with educational activity and screening tools achieved a high participation rate, easy healthcare access, and a high rate of SVR despite the SARS-CoV-2 pandemic.

Brote epidémico de hepatitis aguda A en el área sanitaria del Hospital Universitario Virgen de la Victoria (HUVV): un cambio en la epidemiología / Outbreak of acute hepatitis A in the health area served by the Hospital Universitario Virgen de la Victoria (HUVV): a change in epidemiology

En el año 2016 se detectó en la provincia de Málaga un brote de hepatitis A en pacientes con características epidemiológicas especiales, con un predominio de sujetos del sexo masculino. Presentamos 51 casos de hepatitis A aguda con una media de edad de 35,7 años, el 90% varones, con un 55% de casos que reconocían haber mantenido relaciones sexuales con otros hombres en los últimos dos meses. La mitad de ellos requirieron ingreso hospitalario por coagulopatía significativa en el momento del diagnóstico, sin evolución a fallo fulminante, ni encefalopatía en ningún caso. Cuatro casos presentaban ascitis al diagnóstico. Este brote se suma a otros dos publicados en Reino Unido y Holanda con un número de casos similar y epidemiológicamente muy parecidos, lo cual refuerza la importancia de la vigilancia epidemiológica y la necesidad de vacunación en esta población de riesgo, así como de campañas informativas a la población para prevenir la enfermedad

In 2016, an outbreak of hepatitis A was identified in the Malaga province among patients with specific epidemiological characteristics, which were predominantly males. This is a report of 51 subjects with acute hepatitis A and a mean age of 35.7 years, 90% were male and 55% of cases were men who had had sex with other men within the last two months. Half of them required hospitalization for significant coagulopathy at diagnosis and no cases progressed to fulminant failure or encephalopathy. Four patients had ascites at the time of diagnosis. This outbreak adds to those reported in the United Kingdom and the Netherlands with a similar number of cases and epidemiology. These studies highlight the importance of epidemiological surveillance, the need for vaccination in this particular at risk population and the need for informative campaigns in order to prevent this disease

Massive splenomegaly correlates with malignancy: 180 cases of splenic littoral cell tumors in the world literature.

Littoral cell tumors (LCT) are rare primary splenic neoplasms, unique for their morphologic and immunolabeling features resembling the endothelial littoral cells lining the sinusoids of the red pulp. They include the more common and typically benign littoral cell angioma, as well as the less common, potentially malignant, littoral cell hemangioendothelioma (LCHE) and the aggressive littoral cell angiosarcoma (LCAS). The most common presentation of these neoplasms is splenomegaly, and diagnosis is made histologically following biopsy or resection. To better understand these tumors, a comprehensive, international literature search was performed. Patient and tumor data, including presenting symptoms, comorbid cancers, immunosuppressive states, splenic mass and tumor size were analyzed. Massive splenomegaly (≥ 1500 g) following splenic resection, which correlates with a splenic length of 20 cm preoperatively, was found to be significantly associated with the presence of malignancy in the LCT (P<0.05).

Surface magnetism in O2 dissociation-from basics to application.

First-principles calculations were performed to investigate magnetic phenomena in surface reactions involving O(2). We present two magnetized surface cases: (1) oxidation of paramagnetic Ag, and magnetic properties of the high coverage oxide phase, which correspond to a magnetic impurity superlattice on paramagnetic surfaces and (2) oxidation of ferromagnetic Pt, represented by the Pt layer on M (M = Fe and Co) relevant to the oxidation reduction reaction (ORR) on Pt, in relation to both fundamental and application interests. In the first case, we found that the dissociative adsorption of O(2), resulting in oxide phases in Ag(111), reveals interesting magnetic interactions. We note that the magnetic states are induced by the ferromagnetic superexchange interactions and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions. Specifically, the superlattice structures with short O-O distances have an effective ferromagnetic superexchange and RKKY interaction. In the second case, we found that a magnetic moment is induced on the Pt layer by the M substrate. The spin polarization of Pt-d states is due to hybridization with M-d states. The d-band center (ε(d)) of Pt (on M), is shifted downwards with respect to pure Pt. However, because of the spin polarization, the otherwise filled spin-down d(zz) orbital in paramagnetic pure Pt is shifted towards the Fermi level. This promotes π(z↑)-d(zz↓) interactions, which influences the O(2)-Pt interaction at O(2) far from the surface. Details and mechanisms of these two magnetic phenomena are discussed.

Another way of looking at bonding on bimetallic surfaces: the role of spin polarization of surface metal d states.

The nature of electronic and chemical properties of an unstrained Pt monolayer on a 3d transition metal substrate, M (M = Cr, Mn, Fe), is studied using spin-polarized density functional theory calculations. High spin polarization of Pt d states is noted, verifying the magnetization induced on Pt, which is observed to be responsible for redirecting the analysis of bond formation on a metal surface towards a different perspective. While the shift in the Pt d band center (the average energy of the Pt d band, commonly used to predict the reactivity of surfaces) does give the expected trend in adsorbate (oxygen) chemisorption energy across the bimetallic surfaces in this work, our results show that for spin-polarized Pt d states, the variation in strength of adsorption with respect to the Fermi level density of states is more predictive of Pt chemisorption properties. Hence, this study introduces a scheme for analyzing trends in reactivity of bimetallic surfaces where adsorption energies are used as reactivity parameters and where spin polarization effects cannot be neglected.

Altered expression of genes in experimentally induced myopic chick eyes.

PURPOSE: To identify a casual pathway between the alteration in visual experience, due to form deprivation and hyperopic defocus, and the increase in eye growth, we searched for candidate genes having regulatory effects on eye growth under myopic conditions. METHODS: The expression of the brain-derived neurotrophic factor, neurotrophin-3, sonic hedgehog, nerve growth factor, Six-3 and the Lh-2 group of genes in the transcriptional level after experimentally induced myopia (form-deprivation by goggles and by hyperopic defocus using negative spectacle lenses) were evaluated by semiquantitative reverse transcriptional polymerase chain reaction and Northern blot analysis. RESULTS: Results showed that only the sonic hedgehog gene was differentially expressed in the experimentally induced myopic retinal samples compared with controls. CONCLUSIONS: The sonic hedgehog gene may have regulatory functions in the signaling of the cascade of events that leads to axial elongation and vitreous enlargement of the eye under myopic conditions.

Expression of Sonic hedgehog and retinal opsin genes in experimentally-induced myopic chick eyes.

The purpose of this study was to evaluate changes in the expression of different genes in chick retinal tissues after induction of experimental myopia and to evaluate the roles of these genes in the regulation of postnatal eye growth and myopia. Form-deprivation using occlusive goggles and hyperopic defocus by negative spectacle lenses were used to induce myopia in hatched chicks. Expression levels of Sonic hedgehog, its receptor complex, and other retinal cell genes were evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Levels of Sonic hedgehog protein were further evaluated by Western blot analysis. The induction of myopia caused significant increase in expression of Sonic hedgehog mRNA and protein and increased expression of blue and red opsin mRNA. In contrast, the expression of mRNA for Sonic hedgehog receptor complex (Patched-Smoothened), rhodopsin, vimentin, green opsin, violet opsin, and HPC-1 were unaffected by the induction of myopia. The increase in expression of Sonic hedgehog in chick retinas in experimentally-induced myopia suggests involvement in the retina control of postnatal eye growth. Furthermore, Sonic hedgehog may influence the expression of blue and red opsins under myopic conditions.

Chronic liver injury related to use of bentazepam: an unusual instance of benzodiazepine hepatotoxicity.

Liver injury induced by benzodiazepines is rare and is classified as an unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that in most cases the pattern of liver injury was cholestatic. We describe three patients with persistent increases in liver transaminase levels after several weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for anxiety disorders. In all cases withdrawal of the drug was followed by resolution of transaminase level abnormalities. A liver biopsy (done in one patient only) showed histological evidence of severe chronic active hepatitis. In conclusion, these findings, together with two previously published case reports, suggest that a benzodiazepine can cause chronic hepatitis and argue in favor of using liver function tests to monitor all patients taking bentazepam.

Indocyanine green videoangiography in macular variant of idiopathic polypoidal choroidal vasculopathy.

BACKGROUND: Fifty patients diagnosed with choroidal neovascularization in age-related macular degeneration were examined by indocyanine green videoangiography. Results were correlated with fundus photographs and fluorescein angiograms. Two patients were diagnosed with the macular variant of idiopathic polypoidal choroidal vasculopathy. CASES: Two middle-aged hypertensive women were diagnosed with macular idiopathic polypoidal choroidal vasculopathy. Throughout the follow-up period, both cases showed improved signs and symptoms without worsening of visual acuity, and despite the absence of definitive therapy. OBSERVATIONS: Indocyanine green videoangiography demonstrated the characteristic polypoidal lesions in idiopathic polypoidal choroidal vasculopathy better than fluorescein angiography, particularly when blood, exudates, or pigment epithelial detachments blocked visualization of the lesions. CONCLUSIONS: Incidence of idiopathic polypoidal choroidal vasculopathy may not be as low as reported, as its presentation mimics choroidal neovascularization in age-related macular degeneration. Differentiation can be made only through indocyanine green videoangiography. Conservative management may be beneficial, as visual prognosis is good.

Effects of interferon-beta on plasma lipid and lipoprotein composition and post-heparin lipase activities in patients with chronic hepatitis C.

BACKGROUND: Interferon therapy has been shown to induce lipid abnormalities. AIM: We assessed the effects of interferon-beta on the lipoprotein profile and post-heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C. METHODS: Interferon-beta was administered subcutaneously at doses of 6 x 106 U (units) three times a week, over 6 months, and lipoproteins and post-heparin lipases were measured at baseline and at the end of therapy. RESULTS: Plasma triglycerides increased by 21% due to preferential enrichment in those contained in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The concentration of cholesterol decreased slightly in the high density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic lipase activity decreased by a 36%, and this change showed a significant negative correlation with changes in plasma triglycerides. Five patients (19.5%) responded to interferon-beta therapy. The lipoprotein profile was no different between responders and non-responders to therapy. CONCLUSIONS: Interferon-beta treatment in normolipaemic patients with chronic hepatitis C induced moderate disturbances in plasma lipoproteins, associated with inhibition of lipoprotein lipase activity.

Differential expression of neuroendocrine-specific protein in form-deprived chick eyes.

PURPOSE: To identify genes that are highly expressed in form-deprived retina-retinal pigment epithelium-choroid tissues. Neuroendocrine-specific proteins were found to be highly expressed. METHODS: mRNAs enriched in retina-retinal pigment epithelium-choroid tissues from 3-, 7-, and 14-day form-deprived chick eyes were isolated by differential display technique with cDNA library screening. Neuroendocrine-specific protein A and C were cloned in control and form-deprived eyes. mRNA and protein levels, with respective regional localizations, were examined by Northern blot, Western blot, and immunohistochemical analyses, respectively. RESULTS: The isolated clone included an insert with a sequence homologous to both chick neuroendocrine-specific proteins A and C. The increases in mRNA and protein levels were confirmed by Northern and Western blot analyses, respectively. Immunohistochemical localization of neuroendocrine-specific proteins A and C was detected in the layer of photoreceptor inner segments, presumably in the cone cells. Northern blot analysis using negative lenses showed that levels of neuroendocrine-specific protein A and C mRNAs were not altered using negative lenses. CONCLUSIONS: The expression of both neuroendocrine-specific proteins A and C mRNAs in cone photoreceptor cells was upregulated within 14 days of form deprivation, but not in response to negative spectacle lenses. These data suggest that the increase in induction of neuroendocrine-specific proteins is not a secondary consequence of ocular elongation or myopic refraction. Induction of neuroendocrine-specific proteins in form-deprived eyes may be causally related to the development of myopia or may be an unrelated effect of form deprivation.

Up-regulation of crystallin mRNAs in form-deprived chick eyes.

Form-deprivation of chicks during early postnatal development results in ocular enlargement and great myopic refractive error (form-deprivation myopia). Previous studies have indicated that the retina, RPE and choroid play important roles in ocular enlargement in form-deprivation myopia. We aimed to isolate genes up-regulated in the retina-RPE-choroid of form-deprived chick eyes. A suppression subtractive hybridization method was used to compare mRNA expression in the retina-RPE-choroid of form-deprived and control eyes. One up-regulated cDNA was isolated and identified as part of chick delta1-crystallin cDNA. Northern blot and RT-PCR analyses demonstrated that delta1-crystallin mRNA was up-regulated in the retina-RPE at day 7 after form-deprivation treatment. Semi-quantitative RT-PCE analysis of the expression of several transcription factors indicated that Sox1 and Sox3 were upregulated in parallel with delta1-crystallin mRNA in form-deprived eyes. Northern blot analysis demonstrated that alphaA-, betaA3/A1-, betaB1-, and betaB2-crystallin mRNAs were also up-regulated in form-deprived eyes. Although the detailed mechanisms and functions of the crystallin family genes in the retina-RPE-choroid of form-deprived eyes remain unclear, results of our study suggests that form-deprivation affects the expression of these genes in chick eyes.

Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist.

BACKGROUND/AIM: Ebrotidine is a new H2-receptor antagonist marketed in Spain in early 1997 and withdrawn in July 1998. We report 11 cases of acute liver injury related to ebrotidine and submitted to a Regional Registry of Hepatotoxicity between June 1997 and August 1998. METHODS: In all cases a structured protocol was used to ascertain the role of ebrotidine and to exclude other causes (viral, immunologic, metabolic) of liver injury. RESULTS: All patients showed clinical symptoms of acute hepatitis, with a marked increase in aminotransferase activities (ALT values ranging from 15 to 91 times the upper limit of normal). Total bilirubin values were also greatly increased (mean 16 mg/dl), and the liver injury was defined as hepatocellular. Features of hypersensitivity were absent. Liver biopsy was done in three patients. Histopathological examination revealed mainly centrozonal necrosis (two cases) or massive necrosis (one patient). Withdrawal of the drug was followed by a gradual improvement in liver dysfunction, except in one patient who developed fulminant hepatic failure and died. There was a positive response to rechallenge in one patient after an inadvertent drug administration. CONCLUSION: Ebrotidine therapy seems to be associated with severe acute liver injury, and therefore its benefit/risk ratio is unfavorable. The relative rareness and unpredictability of the injury, the lack of dose-relationship and the absence of hallmarks of drug allergy are suggestive of an idiosyncratic metabolic mechanism.

[Chronic cholestasis as a presentation form of portal cavernoma]. / Colestasis crónica como forma de presentación de una cavernomatosis portal.

A 37 year-old-woman was evaluated in 1993 for a chronic asymptomatic cholestasis. An endoscopic retrograde cholangiopancreatography showed the biliary tract compressed, and a mesenteric angiogram disclosed that the cause of biliary obstruction was a portal cavernoma. In addition, large esophageal varices with "red spots" were observed at endoscopy. Propranolol and ursodeoxicolic acid were started and the patient has remained asymptomatic to date. The biliary features of portal cavernoma are reviewed, as well as its pathogenesis, diagnosis and management. Portal cavernoma should be considered in the differential diagnosis of chronic cholestasis.