Liver stiffness change with HCV cure in HIV-infected patients on non-nucleoside analogues.

BACKGROUND: Liver stiffness (LS) at sustained viral response (SVR) is strongly associated with a lower incidence of subsequent hepatic events. HIV NNRTIs may have a beneficial impact on fibrogenesis. OBJECTIVES: Our aim was to analyse the influence of NNRTI-based therapy on the change in LS from starting direct-acting antiviral (DAA) therapy to achieving SVR in HIV/HCV-coinfected patients. METHODS: Three hundred and thirteen HIV/HCV-coinfected patients who fulfilled the following criteria were included: (i) had achieved SVR with an IFN-free, DAA-including regimen; (ii) LS ≥9.5 kPa before therapy; (iii) LS measurement available at SVR; (iv) seronegative for HBsAg; and (v) ART containing 2 NRTIs plus either 1 NNRTI or 1 integrase inhibitor (INI) or 1-2 NRTIs plus 1 PI. LS changes were assessed. RESULTS: Seventy-four patients received NNRTI-based combinations [53 (71.6%) rilpivirine and 16 (21.6%) efavirenz] and 239 patients received other regimens. At baseline, the median (IQR) LS was 16.7 kPa (11.8-25.6) in the NNRTI group and 17.3 kPa (11.9-27.4) in the non-NNRTI group (P = 0.278). The median (IQR) percentage of LS decrease from baseline to SVR was 35.2% (18.2%-52.3%) for NNRTI-based therapy and 29.5% (10%-45.9%) for PI- or INI-based therapy (P = 0.018). In multivariate analysis, adjusted for sex, age, HCV genotype, NRTI backbone and propensity score for HIV therapy, NNRTI-based regimen use was associated with a higher LS decrease [ß = 11.088 (95% CI = 1.67-20.51); P = 0.021]. CONCLUSIONS: Treatment with NNRTI plus 2 NRTI combinations is associated with a higher LS decline than other ART combinations in HIV/HCV-coinfected patients receiving DAA-based therapy.

Projecting Climate Dependent Coastal Flood Risk With a Hybrid Statistical Dynamical Model.

Numerical models for tides, storm surge, and wave runup have demonstrated ability to accurately define spatially varying flood surfaces. However these models are typically too computationally expensive to dynamically simulate the full parameter space of future oceanographic, atmospheric, and hydrologic conditions that will constructively compound in the nearshore to cause both extreme event and nuisance flooding during the 21st century. A surrogate modeling framework of waves, winds, and tides is developed in this study to efficiently predict spatially varying nearshore and estuarine water levels contingent on any combination of offshore forcing conditions. The surrogate models are coupled with a time-dependent stochastic climate emulator that provides efficient downscaling for hypothetical iterations of offshore conditions. Together, the hybrid statistical-dynamical framework can assess present day and future coastal flood risk, including the chronological characteristics of individual flood and wave-induced dune overtopping events and their changes into the future. The framework is demonstrated at Naval Base Coronado in San Diego, CA, utilizing the regional Coastal Storm Modeling System (CoSMoS; composed of Delft3D and XBeach) as the dynamic simulator and Gaussian process regression as the surrogate modeling tool. Validation of the framework uses both in-situ tide gauge observations within San Diego Bay, and a nearshore cross-shore array deployment of pressure sensors in the open beach surf zone. The framework reveals the relative influence of large-scale climate variability on future coastal flood resilience metrics relevant to the management of an open coast artificial berm, as well as the stochastic nature of future total water levels.

Climate-induced variability in South Atlantic wave direction over the past three millennia.

Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~ 3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Clonal complexes and diversity of exotoxin gene profiles in methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates from patients in a Spanish hospital.

Molecular epidemiology studies have allowed the identification of the methicillin (meticillin)-resistant (MRSA) and methicillin-susceptible (MSSA) clonal complexes (CCs) and clones of Staphylococcus aureus circulating in a Spanish hospital recently. Of 81 isolates tested, 32.1% were MRSA. Most of them carried staphylococcal cassette chromosome mec (SCCmec) IVc (88.5%) and belonged to CC5 (88.5%; multilocus sequence typing types ST125 [mainly associated with spa type t067], ST5, and ST228). A higher diversity was found among MSSA isolates (67.9%). Eighty percent shared the genetic background of major MRSA lineages (CC5 [38.2%; ST125 and ST5], CC30 [25.5%; ST30], CC45 [14.5%; ST45 and ST47], and CC8 [1.8%; ST8]), but CC12, CC15, CC51, and CC59 were also detected. Many exotoxin genes were present in each of the 81 isolates, independent of whether they were involved in sepsis (11 to 22) or other types of infections (13 to 21), and they appeared in 73 combinations. The relevant data are that (i) all isolates were positive for hemolysin and leukotoxin genes (98.8% for lukED and 25.9% for lukPV); (ii) all contained an enterotoxin gene cluster (egc with or without seu), frequently with one or more genes encoding classical enterotoxins; (iii) about half were positive for tst and 95% were positive for exfoliatin-encoding genes (eta, etb, and/or etd); and (iv) the four agr groups were detected, with agrII (55.6%) and agrIII (23.5%) being the most frequent. Taken together, results of the present study suggest a frequent acquisition and/or loss of exotoxin genes, which may be mediated by efficient intralineage transfer of mobile genetic elements and exotoxin genes therein and by eventual breakage of interlineage barriers.

Diagnostic detection of Streptococcus pneumoniae PpmA in urine.

Streptococcus pneumoniae infections are often difficult to diagnose accurately, as it is not uncommon for clinical samples to be culture-negative, particularly after antibiotic administration. The rapid Binax NOW S. pneumoniae urinary antigen test lacks specificity in children, owing to pneumococcal antigen reactions in children who are nasopharyngeal carriers of S. pneumoniae. A western blot assay with a specific polyclonal antibody was developed for direct detection of the putative proteinase maturation protein A (PpmA) in urine samples from children with pneumococcal infections. The sensitivity and specificity of the assay were 66.7% and 100%, respectively. Previous antibiotic treatment or S. pneumoniae nasopharyngeal colonization did not affect PpmA antigenuria. Results also demonstrated the presence of PpmA cross-reactive epitopes in commensal bacteria that co-colonize the nasopharyngeal niche, although the non-pneumococcal cross-reactive protein(s) did not interfere with the detection assay. S. pneumoniae PpmA in the urine of children with pneumococcal infections may be a marker that has the potential to be used in the clinical diagnosis of pneumococcal infection.

Involvement of adenovirus in clinical mononucleosis-like syndromes in young children.

Although Epstein-Barr virus (EBV) commonly causes infectious mononucleosis (IM) or IM-like syndromes, other agents can be implicated. In this study, viral and parasitic screening was performed to determine the etiological agent of pediatric IM-like syndromes in 38 children. Adenovirus was the agent most frequently detected (47.3%), followed by EBV (31.5%) and cytomegalovirus (2.6%). Although the statistically significant difference between viral detection rates observed in patients who fulfilled clinical and hematological criteria and detection rates in those who presented clinical symptoms only (91.6% vs. 64.3%) indicates that hematological abnormalities are common in viral IM-like syndromes, the existence of syndromes of viral etiology without hematological criteria cannot be discarded. A further analysis showed an absence of lymphocytosis in adenovirus infections as well as a low number (14.3%) of EBV infections associated with increased neutrophils. These data suggest the usefulness of appropriate virological techniques for the detection of adenovirus in pediatric IM-like syndromes.

[Fibrillary and immunotactoid glomerulonephritis: report of a case and review of the literature]. / Glomerulonefritis fibrilar e inmunotactoide: descripción de un caso y revisión de la literatura.

We describe the case of a 67 year-old female with nephrotic syndrome and rapidly progressive renal failure. The nephropathy was characterized by deposits of randomly oriented fibrils with a diameter of about 18-20 nm on electron microscopy. Immunofluorescence microscopy was performed and there was no staining for immunoglobulins and complement. We diagnosed atypical fibrillary glomerulopathy with absence of immune deposits. The patient developed end-stage renal failure rapidly. We review in the literature new clinical and pathogenetic features related to fibrillary and immunotactoid glomerulopathy.

Septicaemia due to Corynebacterium striatum: molecular confirmation of entry via the skin.

Septicaemia due to Corynebacterium striatum occurs infrequently. A case of C. striatum septicaemia with a known skin focus is reported in a 69-year-old male with ischaemia, refractory anaemia and treated for thyroid cancer. The characterization and typing of blood and cutaneous isolates was carried out using biochemical and DNA molecular typing methods to analyse the isolates. This is the first reported case with a documented source.

[Collagenous colitis and small intestinal villous atrophy: manifestations of the same disorder?]. / Colitis colágena y atrofia vellositaria del intestino delgado: manifestaciones de una misma enfermedad?

We describe the case of a 64-year-old woman with a previous diagnosis of celiac sprue and no clinical or histological response to gluten withdrawal. The patient presented a history of longstanding recurrent watery diarrhea and was found to have collagenous colitis after further investigation of her diarrhea. Immunological study was incompatible with celiac disease and no other cause of villous atrophy was found. We suggest that this patient may have a separate disease entity unrelated to celiac sprue and consisting of a pan-intestinal inflammatory disorder characterized by the combination of a chronic inflammatory infiltrate in the small and lower bowel together with a subepithelial collagenous band in the colon.

Boric acid susceptibility testing of non-C. albicans Candida and Saccharomyces cerevisiae: comparison of three methods.

To establish the best method for boric acid susceptibility testing, we compared two agar dilution methods (high and low inoculum) and a standard broth microdilution method (from the National Commitee for Clinical Laboratory Standards document NCCLS M-27A). Saccharomyces cerevisiae (37) and non-C. albicans Candida (39) isolates, as well as one isolate of Trichosporon sp., were included. All were isolated from female workers with vulvovaginitis. Good agreement within a fourfold dilution range was found between the three methods, and only the broth microdilution method versus the agar dilution method with high inoculum showed significant discrepancies. Reading results was easier with the broth microdilution method than with the agar dilution methods because of partial growth inhibition in the latter. In conclusion, broth microdilution is a suitable method for testing yeast susceptibility to boric acid.

A specific and ultrasensitive chemiluminescent sandwich ELISA test for the detection and quantitation of pneumolysin.

A chemiluminescent sandwich ELISA test has been developed for the detection and quantitation of pneumolysin. The test is based on a mouse monoclonal as the capture antibody and on rabbit polyclonal IgGs as detection antibodies, in combination with an anti-rabbit IgG alkaline phosphatase conjugate. The estimated detection limit of the purified recombinant toxin in phosphate-buffered saline with 0.05% Triton X-100 is around 5 pg ml(-1), with averaged intra- and inter-assay variation coefficients of 7% and 13.5%, respectively. The assay has been applied to the quantitation of pneumolysin in pneumococcal isolates, providing, for the first time, a direct measurement of the amount of the toxin produced by different strains, a variation has been found in their pneumolysin content. The test is highly specific as no other purified toxins or human pneumonia- or meningitis-associated bacteria yielded false-positive results. This specific and highly sensitive method could help in the diagnosis of human infections.

Postural hygiene program to prevent low back pain.

STUDY DESIGN: A quasi-experimental study with 3 x 4 design was performed. OBJECTIVE: To improve the level of knowledge and motor skills and thereby avert the development of painful symptoms. SUMMARY OF BACKGROUND DATA: Despite the fact that low back pain affects a high percentage of the population, little research has been carried out to prevent low back pain through health education. METHODS: The participants in this study were 106 third-grade (9-year-old) students. The program included 11 sessions. The teacher attended the placebo group sessions. No intervention was used with the control group. RESULTS: The level of knowledge and motor skills in the experimental group showed a significant increase immediately after the intervention finished, and at 6- and 12-month intervals after completion of the postural hygiene program (P = 0.00). Some positive changes were generalized to natural situations (P = 0.00). In an independent health check carried out by the local school health services 4 years after application of the postural hygiene program, the results tended slightly to favor the experimental condition over the control conditions (placebo + no intervention). A greater number of the control subjects required medical treatment for low back pain, although this difference was only marginally significant (P = 0.07). CONCLUSIONS: The findings from this study support the hypothesis that programs involving practice and motivating strategies impart health knowledge and habits more efficiently than those restricted to the mere transmission of information.

Estudio comparativo entre remifentanilo y propofol para la sedación en anestesia subaracnoidea / Sedation in spinal anesthesia. Comparison of remifentanil and propofol

OBJETIVOS. Evaluar la eficacia y seguridad de remifentanilo para proporcionar analgesia y sedación durante la anestesia subaracnoidea y compararlo con propofol.MÉTODO. En este estudio prospectivo se incluyó a 90 pacientes ASA I-III sometidos a cirugía ortopédica y traumatológica bajo anestesia subaracnoidea. Los pacientes fueron distribuidos aleatoriamente en dos grupos de tratamiento. El grupo propofol (n = 45) recibió un bolo de 0,5 mg/kg seguido de una perfusión a 3 mg/kg/h. El grupo remifentanilo (n = 45) recibió un bolo de 0,5 µg/kg seguido de una perfusión a 0,1 µg/kg/min. Valoramos la calidad de la sedación, la intensidad del dolor durante el bloqueo nervioso, los parámetros hemodinámicos y respiratorios y los tiempos de recuperación. RESULTADOS. En el grupo remifentanilo se observó menos dolor moderado-intenso (13 por ciento) que en el grupo propofol (63 por ciento; p < 0,01). Se consiguió un nivel de sedación adecuado en ambos grupos. Éste era fácilmente controlable ajustando el ritmo de infusión. Los tiempos de recuperación del nivel de conciencia y de la frecuencia respiratoria desde que se interrumpieron las perfusiones hasta que se alcanzaron los valores basales previos fueron de 7,87 ñ 3,54 min y 5,22 ñ 2,49 min en el grupo remifentanilo y 8,72 ñ 4,59 min y 5,36 ñ 2,49 min en el grupo propofol, respectivamente. Los pacientes en el grupo remifentanilo experimentaron un significativo descenso de SpO2 comparado con el grupo propofol (un 20 y un 4 por ciento, respectivamente; p < 0,05). En los pacientes tratados con remifentanilo la presión arterial media era mayor. La incidencia de náuseas fue mayor en el grupo remifentanilo que en el propofol (el 9 frente al 0 por ciento). CONCLUSIÓN. Remifentanilo es más efectivo para disminuir el dolor asociado al bloqueo nervioso con menores niveles de sedación; sin embargo, se asocia a mayor incidencia de depresión respiratoria y náuseas (AU)

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Epidemiological study of Streptococcus pneumoniae carriers in healthy primary-school children.

To obtain information on the Streptococcus pneumoniae carrier state in Spanish children, 332 healthy 6-year-old children from nine primary schools in northern Spain were screened. Thirty-six percent of the children had positive cultures yielding 128 strains. Seventy-one strains belonged to 14 serogroup/serotypes, the most frequent being 19, 23, 3, 24 and 11. Fifty-seven strains were nontypeable. The identification of strains with equivocal results was confirmed at species level by means of hybridisation with a specific probe, pneumolysin-mediated agglutination and a pathogenicity test in mice. Sixty-four percent of strains showed resistance to penicillin, 22% of these also being resistant to cefotaxime. More than 40% of the strains were resistant to trimethoprim-sulfamethoxazole, tetracycline and erythromycin. Twenty percent of the erythromycin-resistant strains were susceptible to clindamycin. Two strains were resistant to rifampicin and one strain was resistant to ofloxacin. All strains were susceptible to vancomycin. Previous antibiotic administration and having siblings under the age of 2 years correlated with the carriage of pneumococcus. There was no correlation with the carriage of antibiotic-resistant strains, or a record of previous infections, previous hospital admissions or having relatives with chronic respiratory disease.

The conserved undecapeptide shared by thiol-activated cytolysins is involved in membrane binding.

Thiol-activated cytolysins share a conserved hydrophobic, Trp-rich undecapeptide that is suggested to be involved in membrane binding and intercalation. The neutralizing monoclonal antibody PLY-5 recognizes all members of this toxin family and peptide mapping assigned its epitope to the undecapeptide motif. This antibody inhibited binding of the toxins to host cell membranes and the epitope was no longer available for binding when a preformed toxin/membrane complex was tested. These results confirm the model of cytolysin binding suggested by structural data.

Rapid and reliable identification of Streptococcus pneumoniae isolates by pneumolysin-mediated agglutination.

A pneumolysin-based agglutination test which allows an easy, rapid, cost-effective, and accurate (100% specific and 95% sensitive) discrimination between pneumococci and other related human and animal pathogenic bacterial strains has been assayed.