Prospective Multicenter Observational Study of Overt Hepatic Encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (OHE) is a frequent complication of decompensated cirrhosis. AIMS: A multicenter prospective observational study was performed to assess the most commonly recorded presenting manifestations of OHE and its associated health-care burden. METHODS: Qualifying patients must have experienced ≥1 OHE episode within 30 days of enrollment (qualifying OHE) and were followed for recurrence (on-study OHE). RESULTS: Two hundred and sixty-five patients were enrolled at 30 sites and followed for up to 9 months (mean 72 days). Seventy-two patients experienced 122 on-study episodes; with 72, 23, and 13 having ≥1, ≥2, or ≥3 on-study episodes with median days to occurrence of the 1st, 2nd, and 3rd episode of 34, 19, and 11, respectively. The most frequently recorded OHE manifestations included confusion (78 %), change in mental status (57 %), disorientation (48 %), lethargy (46 %), and asterixis (45 %). West Haven grade was used inconsistently and recorded for only 28 % of episodes. Most qualifying and on-study episodes occurred on rifaximin (60 and 82 %, respectively) and were associated with hospitalization (68 and 85 %, respectively). Twenty-three patients experienced ≥2 on-study episodes within 2 months of enrollment on average (median 45 days) and accounted for 60 % of on-study episodes. CONCLUSIONS: In this prospective study, OHE's most commonly recorded presenting manifestations included confusion, altered mental status, disorientation, lethargy, and asterixis. As reflected by frequent recurrence and hospitalizations, OHE, particularly the approximately 10 % of "high-resource-utilizing" patients with frequent recurrence, continues to pose a major unmet medical need and health-care burden despite the use of rifaximin.

Chlorophyll a Covalently Bonded to Organo-Modified Translucent Silica Xerogels: Optimizing Fluorescence and Maximum Loading.

Chlorophyll is a pyrrolic pigment with important optical properties, which is the reason it has been studied for many years. Recently, interest has been rising with respect to this molecule because of its outstanding physicochemical properties, particularly applicable to the design and development of luminescent materials, hybrid sensor systems, and photodynamic therapy devices for the treatment of cancer cells and bacteria. More recently, our research group has been finding evidence for the possibility of preserving these important properties of substrates containing chlorophyll covalently incorporated within solid pore matrices, such as SiO2, TiO2 or ZrO2 synthesized through the sol-gel process. In this work, we study the optical properties of silica xerogels organo-modified on their surface with allyl and phenyl groups and containing different concentrations of chlorophyll bonded to the pore walls, in order to optimize the fluorescence that these macrocyclic species displays in solution. The intention of this investigation was to determine the maximum chlorophyll a concentration at which this molecule can be trapped inside the pores of a given xerogel and to ascertain if this pigment remains trapped as a monomer, a dimer, or aggregate. Allyl and phenyl groups were deposited on the surface of xerogels in view of their important effects on the stability of the molecule, as well as over the fluorescence emission of chlorophyll; however, these organic groups allow the trapping of either chlorophyll a monomers or dimers. The determination of the above parameters allows finding the most adequate systems for subsequent in vitro or in vivo studies. The characterization of the obtained xerogels was performed through spectroscopic absorption, emission and excitation spectra. These hybrid systems can be employed as mimics of natural systems; the entrapment of chlorophyll inside pore matrices indicates that it is possible to exploit some of the most physicochemical properties of trapped chlorophyll for diverse technological applications. The data herein collected suggest the possibility of applying the developed methodology to other active, captive molecules in order to synthesize new hybrid materials with optimized properties, suitable to be applied in diverse technological fields.

Differential cytokine expression and regulatory cells in patients with primary and secondary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The aim of the study was to characterize and compare the presence of diverse cytokines and regulatory T and B cells in lip minor salivary gland (MSG) biopsies from patients with primary Sjögren's syndrome (pSS), secondary SS (sSS), and patients with connective tissue disease (CTD) without (w/o) SS. We included samples of MSG from 15 pSS, 24 sSS (six scleroderma, nine rheumatoid arthritis and nine lupus patients) and 15 patients with CTD w/o SS. Tissues were examined by an indirect immunoperoxidase technique (goat polyclonal anti-human IL-19, goat polyclonal anti-human IL-22 or mouse monoclonal anti-human IL-24). To determine the subpopulation of CD4(+)/IL-17A(+)-, CD4(+)/IL-4(+)-, CD4(+)/IFN-É£(+)-expressing T cells, CD25(+)/Foxp3(+) Treg cells and CD20(+)/IL-10(+)-producing B cell subset, a double-staining procedure was performed. We estimated the mean percentage of positively staining cells in two fields per sample. CD4(+)/IFN-É£(+), CD4(+)/IL-4(+) and IL-22(+) cell percentages were elevated in both SS varieties; however, the cells were more prevalent in pSS. Patients with pSS had a high number of CD4(+)/IL-17A(+) and IL-19(+) T cells and a lower percentage of IL-24(+) cells (P < 0.05). The Treg and IL-10-producing B cells were increased in pSS (P < 0.05). Concluding, in our patients, a pro-inflammatory and regulatory balance coexists in SS, being both responses more intense in pSS. The explanation of these differences may be related to disease activity, disease duration and treatment.

Prevalence and clinical-epidemiologic characteristics of a Mexican population with metabolic (dysfunction) associated fatty liver disease: An open population study.

INTRODUCTION AND AIMS: The risk factors for fatty liver disease are frequent in the Mexican population and the available studies appear to underestimate its prevalence. Our aims were to know the prevalence of metabolic (dysfunction) associated fatty liver disease (MAFLD) in an open population and determine the clinical and sociodemographic characteristics, nutritional status, physical activity level, and prevalence of metabolic syndrome, in the affected population. MATERIALS AND METHODS: Volunteers from the general public were invited to take part in the study. Three separate questionnaires were applied to 1) determine the sociodemographic characteristics and health status of the participants, 2) evaluate the quality of their diet, and 3) to evaluate their level of physical activity. The participants underwent somatometry, laboratory tests, liver ultrasound, and FIB-4 index determination, and transition elastography (FibroScan®) was carried out on all subjects with signs suggestive of liver fibrosis that agreed to undergo the procedure. The statistical analysis was carried out using SPSS for Windows, version 22, software. RESULTS: A total of 585 volunteers were studied, resulting in a prevalence of MAFLD of 41.3%, a predominance of men above 50 years of age, poor dietary habits, and sedentary lifestyle. Male sex, obesity, metabolic syndrome, and elevated ALT were risk factors for the disease and 40% of those affected had advanced fibrosis. CONCLUSIONS: The prevalence of MAFLD in our population is one of the highest in the world. The conditioning factors of the disease can be modified. Therefore, public policies that redirect the current trend are required.

Evaluation of clinical and functional sequels of central serous chorioretinopathy. A case series analysis.

OBJECTIVE: To evaluate the clinical and functional sequelae of patients with a diagnosis of resolved CSC, through macular OCT, contrast sensitivity test, visual field 10-2 and Farnsworth D-15 color test. METHODS: 27 eyes of 26 individuals with CSC resolved by macular OCT were included and evaluated; the patients underwent a contrast sensitivity test with the Optec 6500 equipment, a 10-2 visual field with an Octopus 900 Haag-Streit, and a Farnsworth D-15 color test. RESULTS: Sequelae were observed in 20 eyes (74.1%) by macular OCT and in 21 (77.8%) in contrast sensitivity, predominantly type 2 defect. Also 27 (100%) had a visual field 10-2 altered corresponding to reduced foveal sensitivity, 11 eyes (40.7%) corresponded to central and paracentral scotomas. The color test showed alteration in 11 (40.7%) of the total eyes evaluated, finding tritanomaly in 9 of them (81.8%). No significant differences were observed in the studies between observation group vs the treatment group. CONCLUSIONS: CSC can leave sequelae in the visual quality of patients despite treatment in the acute phase. Visual acuity before and after treatment in the intervention group had no significant difference.

New Records of Ticks of Genus Amblyomma Koch, 1844 (Acari: Ixodidae) for Ecuador.

PURPOSE: In Ecuador, knowledge of the diversity and geographic distribution of ticks, as well as their importance as vectors, is scarce. Within the family Ixodidae, the genus Amblyomma is the most diverse and parasitizes wild and domestic animals. This genus is represented by 19 species in Ecuador, 12 of which occur in the continental territory and 7 in the Galapagos Islands. In this way, the objective of this work was to update the diversity of ticks reported for Ecuador on wild and domestic animals. METHODS: The specimens were collected manually on mammals and birds, in four localities belonging to the Sierra and Amazon of Ecuador and were kept in tubes with 96% ethyl alcohol. After that, all specimens were separated into immatures, males and females and were identified using their morphological characters. RESULTS: This study records Amblyomma coelebs Neumann, 1899, Amblyomma longirostre (Koch, 1844) Neumann, 1905 and Amblyomma varium Koch, 1844 for the first time in Ecuador. Thus, the genus Amblyomma is currently represented by 22 species. In addition, their hosts, distribution, and importance are also discussed. CONCLUSIONS: Knowing the diversity of ticks that wildlife possesses, its interrelation with the domestic fauna, and the possible pathogens that could be transmitting could significantly contribute to wildlife's conservation.

Daptomycin-Induced Posterior Reversible Encephalopathy Syndrome (PRES).

AIMS: To present a 60-year-old female patient who manifested clinical and radiological features of posterior reversible encephalopathy syndrome (PRES) following the administration of Daptomycin for glycopeptide-resistant Enterococcal urinary tract infection. MATERIAL: Case report. METHOD: Posterior reversible encephalopathy syndrome was diagnosed in our patient following the administration of Daptomycin based on clinical suspicion as well as brain CT and MRI imaging. RESULTS: The temporal association between the initiation of Daptomycin and the onset of PRES is highly suggestive of causality, and this is further supported by clinical and radiological resolution after Daptomycin was withdrawn. CONCLUSION: This is the first report of Daptomycin-induced posterior reversible encephalopathy syndrome.

Enhanced resonance light scattering properties of gold nanoparticles due to cooperative binding.

The interaction of 11-mercaptoundecanoic acid capped gold nanoparticles (MUA-GNPs) with europium ions and aminoacids has been studied by UV-Vis spectrophotometry, fluorescence, confocal fluorescence microscopy, resonance light scattering and TEM. Results demonstrated that hyper-Rayleigh scattering emission occurs upon the addition of lysine to the MUA-GNPs-Eu(III) system, thus providing an inherently sensitive method for lysine determination. The effects of geometrical factors of the gold nanoparticles (aspect ratio, particle size, cluster formation) and the surrounding medium (pH) on this behavior are discussed. The cooperative binding interactions of Eu(3+) and lysine with gold nanoparticles permitted the discrimination of lysine from other amino acids. The probable mechanism for the spectral changes and the enhanced resonance light scattering observed is outlined.

Cost-effectiveness of suppressing hepatitis B virus DNA in immune tolerant patients to prevent hepatocellular carcinoma and cirrhosis.

BACKGROUND: For patients with hepatitis B virus (HBV) infection in the immune tolerant phase, the current standard of care is to not offer treatment. However, the recent Risk Evaluation of the Viral Load Elevation and Associated Liver Disease/Cancer-In study results show a striking relationship between high HBV DNA levels and risk for hepatocellular carcinoma and cirrhosis. AIM: In a cost effectiveness analysis, to assess whether immune tolerant patients with high HBV DNA levels should undergo treatment. METHODS: We created a lifetime Markov model to evaluate the cost-effectiveness of two strategies for immune tolerant hepatitis B: (i) HBV DNA suppression with lamivudine, (ii) no treatment. Patients cycled between the following health states: viral suppression, ongoing viremia, seroconversion, hepatocellular carcinoma, cirrhosis and death. RESULTS: Compared with the no treatment strategy, lamivudine therapy was more expensive but more cost-effective with an additional cost of $5784 and $12 584 per quality adjusted life year gained in males and females, respectively. Treatment resulted in a gain in life expectancy and a decrease in lifetime risk of hepatocellular carcinoma and cirrhosis. CONCLUSIONS: Suppressing HBV DNA to prevent hepatocellular carcinoma and cirrhosis in immune tolerant patients is very cost-effective, and treatment of these patients may be considered. Future prospective clinical trials will need to be undertaken to confirm our findings.

[Diagnostic value of the gonadal biopsy in the disorders of sex development]. / Valor de la biopsia gonadal en el diagnóstico de los desórdenes del desarrollo sexual.

The gonadal biopsy provides essential information for the identification, classification and early detection of neoplasias in patients with disorders of sex development. Histopathological findings in these cases must be analysed together with clinical, hormonal, genetic and molecular information before deciding a therapeutic option. Sexual differentiation is the result of multiple and complex genetic and endocrinal mechanisms; therefore, we first present the events taking place during gonadal embryonic development, focusing on the genetic mechanisms involved in sexual determination and the differentiation of the testis and the urogenital tract. In second place, we describe the different gonads in the intersexual states -in testicular regression syndrome, fibrous streak, testicular dysgenesis, streak testes, ovotestes and microscopically normal testes and ovaries-, highlighting the histological features and the differential findings that allow the pathologist to distinguish between these entities with the aid of clinical, genetic, hormonal and molecular information that are characteristic for each situation. In third place, we studied the incidence of neoplasias in gonadal dysgenesis, male pseudohermaphroditism and true hermaphroditism. Finally, we discuss the limitations of gonadal biopsy to achieve a correct diagnosis in the disorders of sex development.

Islet transplantation in spontaneously diabetic BB/Wor rats.

We investigated the effectiveness of islet transplantation as therapy in an animal model of spontaneous type I (insulin-dependent) diabetes mellitus. Grafting MHC-matched and -mismatched islets with the spontaneously diabetic BB rat as a model has been previously reported to result in recurrence of the disease in the grafted tissue. When transplanted with nonimmunogenic islets isolated by nonenzymatic culture, we found that MHC-matched grafts proved to be susceptible to disease recurrence when allowed to remain in situ until ketosis developed in the host. Conversely, the MHC-mismatched grafts did not succumb to the disease process despite the destruction of the beta-cell population of the endogenous pancreas. Four manifestly hyperglycemic BB/Wor rats received sufficient islet mass by allotransplantation to reverse this state. All four animals had ameliorated conditions, and three of the four were restored to a normoglycemic state. Recurrence of diabetes in the BB rat was not observed.

Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

Randomised controlled trial of cisapride in feed intolerance in preterm infants.

AIM: To assess the efficacy of cisapride in reducing the time required to establish enteral feeds in preterm infants. METHODS: A randomised, double blind, placebo controlled trial was conducted of 34 infants of < or = 32 weeks of gestation, assigned to receive either cisapride 0.2 mg/kg/dose four times daily (n = 18) or placebo (n = 16). RESULTS: The time taken by the babies to tolerate full enteral feeds was not significantly different between the groups (median 9.5 days vs 10 days). There was a significantly lower incidence of large gastric residuals and regurgitation in the treated group compared with the placebo group. The number of episodes of large gastric residuals per infant was also significantly less. No adverse effects were noted. CONCLUSION: The routine use of cisapride in preterm infants cannot be recommended to decrease the time to establish enteral feeds. Its use may be justified for clinically significant gastric stasis or regurgitation.

Ultrasonic blood flow measurements in arteriovenous fistulas: an experimental study.

Femoral arteriovenous fistulas (AVF) were constructed in dogs. Fistulas blood flow was measured simultaneously with standard Doppler equipment, with electromagnetic flow probes and by direct timed blood collection. A good correlation was observed between Doppler and direct timed blood collection (r = 0.822, p less than 0.001) and also between Doppler and electromagnetic determinations (r = 0.747, p less than 0.001). These results lead us to suggest that transcutaneous measurement of AVF flow is possible with standard Doppler equipment and we recommend this technique for the management of AVF constructed in uremic patients.

Nutritional support in critically ill patients with cancer.

Nutritional depletion is a common problem seen in critically ill patients with cancer and is associated with increased morbidity and mortality. Infection and injury activate a cascade of metabolic events that leads to a poor nutritional state and wasteful energy consumption. The goals of nutritional support entail minimizing starvation, preventing nutrient deficiencies, supporting or improving immune function, and facilitating tissue repair and wound healing. Further understanding of the metabolic changes of illness will improve effective regulation of the inflammatory events occurring in critically ill patients. Multiple clinical parameters are available to assess the nutritional status in critically ill patients, but no standard recommendations can be made at this time. The use of these parameters can be appropriate, provided that their limitations are understood clearly. The development and standardization of objective parameters to identify patients at risk or with subclinical malnutrition are needed. Enteral and parenteral feedings are safe and effective methods to deliver nutrients to critically ill patients with cancer who are unable to ingest adequate amounts orally. Early nutritional support should be instituted in the appropriate clinical setting. Specialized nutritional solutions and supplements require careful consideration in patients with renal, hepatic, cardiac, or pulmonary disorders. The unselective use of nutritional support is not indicated in well-nourished patients with cancer undergoing surgery, chemotherapy, or radiotherapy in whom adequate oral intake is anticipated. Nutritional support remains an important adjunctive therapy in the overall management of critically ill patients. Continued clinical investigations in nutrition are necessary to identify other groups of patients who can benefit from nutritional interventions.

[Three cases of imported dermatomycosis by Scytalidium dimidiatum]. / Dermatomicosis de importación por Scytalidium dimidiatum: a propósito de tres casos.

Scytalidium dimidiatum dermatomycosis are usually reported in tropical and subtropical countries. Some cases in Spain have been diagnosed due to the increasing number of immigrants from these areas. We herein describe three new cases of S. dimidiatum infections detected in Madrid. Two patients were from Guinea Ecuatorial and the third from Angola. We also report the first case of S. dimidiatum infection in a HIV patient in Spain. Clinical and epidemiological characteristics of S. dimidiatum infections reported in Spain are discussed.

Hand exercise effect in maturation and blood flow of dialysis arteriovenous fistulas ultrasound study.

With the help of the Doppler Ultrasound we have measured the radial artery blood flow of 20 healthy volunteers and the fistula flow of 40 uraemic patients. The measurements were made at rest and repeated one, three and five minutes after initiation of hand exercise, and one minute after the exercise had finished. Radial artery mean flow increased significantly with the exercise (p less than 0.001); radial arteries with greater baseline flow had less flow increase (p less than 0.002). However, we were not able to demonstrate any fistula flow increase with the hand exercise. Therefore, we conclude that there is no benefit in advising uraemic patients to squeeze a rubber ball which, otherwise, supposes an unnecessary preoccupation for these patients.

Aortico-left ventricular tunnel: a case report and review of the literature.

A 5-year-old child was operated on for aortico-left ventricular tunnel (ALVT). Postoperative cardiac catheterization revealed obliteration of the aortic end of the tunnel, normalization of systemic pressure and mild residual aortic valvular insufficiency. A review of the literature carefully considers the anatomical and clinical findings from previous reports involving 27 other patients, along with suggestions for appropriate surgical management of ALVT.