Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Gas hold-up and oxygen mass transfer in three pneumatic bioreactors operating with sugarcane bagasse suspensions.

Sugarcane bagasse is a low-cost and abundant by-product generated by the bioethanol industry, and is a potential substrate for cellulolytic enzyme production. The aim of this work was to evaluate the effects of air flow rate (QAIR), solids loading (%S), sugarcane bagasse type, and particle size on the gas hold-up (εG) and volumetric oxygen transfer coefficient (kLa) in three different pneumatic bioreactors, using response surface methodology. Concentric tube airlift (CTA), split-cylinder airlift (SCA), and bubble column (BC) bioreactor types were tested. QAIR and %S affected oxygen mass transfer positively and negatively, respectively, while sugarcane bagasse type and particle size (within the range studied) did not influence kLa. Using large particles of untreated sugarcane bagasse, the loop-type bioreactors (CTA and SCA) exhibited higher mass transfer, compared to the BC reactor. At higher %S, SCA presented a higher kLa value (0.0448 s−1) than CTA, and the best operational conditions in terms of oxygen mass transfer were achieved for %S < 10.0 g L−1 and QAIR > 27.0 L min−1. These results demonstrated that pneumatic bioreactors can provide elevated oxygen transfer in the presence of vegetal biomass, making them an excellent option for use in three-phase systems for cellulolytic enzyme production by filamentous fungi.

Paediatric interventional radiology: it's not child's play.

Pediatric interventional radiology is a dynamic and growing subspecialty. The new training pathways in interventional radiology, the maintenance of skills with a small volume of cases or complex procedures, the limited availability of specific pediatric equipment and materials pose significant challenges and opportunities.

Computed tomography of complicated Meckel's diverticulum in adults. / Tomografía computarizada del divertículo de Meckel complicado en adultos.

OBJECTIVE: To review the embryology, the clinical findings and the appearance in multidetector computed tomography (MDCT) of complicated Meckel's diverticulum (DM) in adults. CONCLUSION: The presence of an MD in a MDCT should be suspected when a blind tubular structure connected to the terminal ileum by a neck of variable size is observed. Multiplanar 2D reconstructions images and CT enterography can help in the diagnosis. In patients with symptoms of obstruction or intestinal inflammation, the possibility of a complication secondary to a MD should be considered, especially when the terminal ileum and the vermiform appendix are normal. MDCT angiography, in cases of acute gastrointestinal bleeding, can identify contrast extravasation and accumulation of blood in the MD, and could demonstrate the persistent omphalomesenteric artery, which is diagnostic of MD. Other MDCT findings such as the presence of enteroliths or associated inflammatory changes around the MD can facilitate the preoperative diagnosis of MD complications.

[Recommendations of antimicrobial treatment in patients allergic to beta-lactam antibiotics]. / Recomendaciones del tratamiento antimicrobiano en pacientes alérgicos a antibióticos betalactámicos.

Beta-lactam antibiotics are the cornerstone of most of the severe bacterial infections. However, their use can be limited by resistances and allergic reactions. Allergic reactions to beta-lactam antibiotics account for only a small proportion of reported adverse drug reactions, but they are related with an important morbidity, mortality and increase of the health care costs. Drug-specific IgE antibodies cause early reactions, whereas T cells play a predominant role in delayed hypersensitivity reactions. For penicillin a major antigenic determinant and several minor determinants have been identified. Clinical assessment is mandatory by medical history, skin and other testing, including provocation. If the beta-lactam should be avoided or a desensitization procedure should be performed depends on the nature and severity of the reaction. Several new antibiotics are currently available (tigecycline, linezolid, daptomycin, etc.) that are as effective and safe as beta-lactams. In this article we have developed a few recommendations for the management of patients with allergy to beta-lactams on the basis of evidence and expert opinion.

[Recommendations of antifungal treatment in patients with low grade immunosuppression]. / Recomendaciones de tratamiento antifúngico en pacientes con bajo grado de inmunodepresión.

Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, the treatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts' panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

Potential of Mangrove-Associated Endophytic Fungi for Production of Carbohydrolases with High Saccharification Efficiency.

The endophytic fungi represent a potential source of microorganisms for enzyme production. However, there have been only few studies exploiting their potential for the production of enzymes of industrial interest, such as the (hemi)cellulolytic enzymatic cocktail required in the hydrolysis of lignocellulosic biomass. Here, a collection of endophytic fungi isolated from mangrove tropical forests was evaluated for the production of carbohydrolases and performance on the hydrolysis of cellulose. For that, 41 endophytic strains were initially screened using a plate assay containing crystalline cellulose as the sole carbon source and the selected strains were cultivated under solid-state fermentation for endoglucanase, ß-glucosidase, and xylanase enzyme quantification. The hydrolysis of a cellulosic material with the enzymes from endophytic strains of the Aspergillus genus resulted in glucose and conversion values more than twofold higher than the reference strains (Aspergillus niger F12 and Trichoderma reesei Rut-C30). Particularly, the enzymes from strains A. niger 56 (3) and A. awamori 82 (4) showed a distinguished saccharification performance, reaching cellulose conversion values of about 35% after 24 h. Linking hydrolysis performance to the screening steps played an important role towards finding potential fungal strains for producing enzymatic cocktails with high saccharification efficiency. These results indicate the potential of mangrove-associated endophytic fungi for production of carbohydrolases with efficient performance in the hydrolysis of biomass, thus contributing to the implementation of future biorefineries.

Addition of metal ions to a (hemi)cellulolytic enzymatic cocktail produced in-house improves its activity, thermostability, and efficiency in the saccharification of pretreated sugarcane bagasse.

High activity and stability are essential for (hemi)cellulolytic enzymes used in biomass conversion, while non-productive binding of cellulases to lignin reduces saccharification efficiency and needs to be avoided. One potential strategy is the addition of inexpensive metal ions. This paper describes the influence of divalent metal ions on the activity, thermostability, and saccharification efficiency of (hemi)cellulolytic enzymes produced in-house by Aspergillus niger under solid-state fermentation (SSF). The use of Mn(2+) provided the best (hemi)cellulolytic activity and stability, with an increase in endoglucanase activity of up to 57%. The use of Mn(2+) was then investigated in the saccharification of sugarcane bagasse submitted to acid, steam-explosion, and hydrothermal pretreatments. The addition of Mn(2+) ions at 10mM in the saccharification of acid-pretreated bagasse resulted in a 34% increase in glucose release. These positive effects appeared to be due to a reduction in non-productive enzyme adsorption. The findings suggest that the addition of inexpensive metal ions can help to improve activity, thermostability, and saccharification efficiency of (hemi)cellulolytic enzymes.

Validation of a novel sequential cultivation method for the production of enzymatic cocktails from Trichoderma strains.

The development of new cost-effective bioprocesses for the production of cellulolytic enzymes is needed in order to ensure that the conversion of biomass becomes economically viable. The aim of this study was to determine whether a novel sequential solid-state and submerged fermentation method (SF) could be validated for different strains of the Trichoderma genus. Cultivation of the Trichoderma reesei Rut-C30 reference strain under SF using sugarcane bagasse as substrate was shown to be favorable for endoglucanase (EGase) production, resulting in up to 4.2-fold improvement compared with conventional submerged fermentation. Characterization of the enzymes in terms of the optimum pH and temperature for EGase activity and comparison of the hydrolysis profiles obtained using a synthetic substrate did not reveal any qualitative differences among the different cultivation conditions investigated. However, the thermostability of the EGase was influenced by the type of carbon source and cultivation system. All three strains of Trichoderma tested (T. reesei Rut-C30, Trichoderma harzianum, and Trichoderma sp INPA 666) achieved higher enzymatic productivity when cultivated under SF, hence validating the proposed SF method for use with different Trichoderma strains. The results suggest that this bioprocess configuration is a very promising development for the cellulosic biofuels industry.

Allogeneic BMT in a patient with CML and prior disseminated infection by mycobacterium avium complex.

A patient with chronic myeloid leukemia (CML) who developed a disseminated infection by mycobacterium avium complex (MAC) was successfully treated with rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was proven by histologic examination of hepatic biopsy and culture of the liver biopsy material. Two years later the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given throughout the immediate post-transplant period. On day +25 post-BMT secondary prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic toxicity. Treatment was maintained until day 100 without side effects. There was no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is well, with a good performance status and chronic graft-versus-host disease (GVHD) limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a contraindication to successful BMT.

An unusual form of pneumatosis intestinalis associated with appendicitis.

A rare case of pneumatosis intestinalis is described in a patient with appendicitis. Gas in the colonic wall, epiploic appendices and mesentery caused a new appearance not previously reported on plain radiography or CT. The relevance of an associated redundant right colon is also discussed.

Anemia in HIV disease.

AIDS: HIV infection is associated with a number of blood abnormalities. Anemia is a frequent consequence, affecting 15 percent of asymptomatic HIV-positive individuals and 85 percent of those with AIDS. Anemia is defined by a decreased number of red blood cells. Individuals with anemia have a diminished capacity to carry oxygen in their blood and suffer from fatigue, difficulty breathing, increased heart rate, pallor, and occasionally heart murmurs. Treatment depends on the underlying cause of anemia.^ieng

Liquefaction of sugarcane bagasse for enzyme production.

The objective of this paper is to report liquefaction of pretreated and sterilized sugarcane bagasse for enhancing endoglucanase production through submerged fermentation by Aspergillus niger. After initial solid state fermentation of steam pretreated bagasse solids by A. niger, fed-batch addition of the substrate to cellulase in buffer over a 12h period, followed by 36h reaction, resulted in a liquid slurry with a viscosity of 0.30±0.07Pas at 30% (w/v) solids. Addition of A. niger for submerged fermentation of sterile liquefied bagasse at 23% w/v solids resulted in an enzyme titer of 2.5IUmL(-1) or about 15× higher productivity than solid-state fermentation of non-liquefied bagasse (final activity of 0.17IUmL(-1)). Bagasse not treated by initial solid-state fermentation but liquefied with enzyme gave 2IUmL(-1). These results show the utility of liquefied bagasse as a culture medium for enzyme production in submerged fermentations.

Sequential solid-state and submerged cultivation of Aspergillus niger on sugarcane bagasse for the production of cellulase.

Sequential solid-state and submerged cultivation with sugarcane bagasse as substrate for cellulase production by Aspergillus niger A12 was assessed by measuring endoglucanase activity. An unconventional pre-culture with an initial fungal growth phase under solid-state cultivation was followed by a transition to submerged fermentation by adding the liquid culture medium to the mycelium grown on solid substrate. For comparison, control experiments were conducted using conventional submerged cultivation. The cultures were carried out in shake flasks and in a 5-L bubble column bioreactor. An endoglucanase productivity of 57 ± 13 IU/L/h was achieved in bubble column cultivations prepared using the new method, representing an approximately 3-fold improvement compared to conventional submerged fermentation. Therefore, the methodology proposed here of a sequential fermentation process offers a promising alternative for cellulase production.

The presynaptic cell determines the number of synapses in the Drosophila optic ganglia.

The role of the pre- and postsynaptic cells in determining the number of synapses has been investigated in retina mosaics of the gigas (gig) mutant of Drosophila. Mutant photoreceptors are two to three times larger than those of the wild type, while adjacent cells in the mosaic retina and the lamina are normal in size. Serial electron microscope reconstructions of mosaic lamina cartridges show that gig photoreceptors establish more synapses upon lamina neurons than the normal photoreceptors do. By contrast, the number of feedback synapses that lamina neurons make onto gig photoreceptors does not increase. The increment in the number of synapses correlates positively with the increment of presynaptic cell membrane, resulting in constancy of synapse density. The phototactic response of flies bearing a gig eye is abnormal, indicating that the extra synapses are functional.

Increased erythrocyte calcium pump activity in a kindred with familial benign hypercalcaemia.

The hypothesis that a global defect in cellular calcium transport may be critical in the development of familial benign hypercalcaemia (FBH) was investigated. Nine hypercalcaemic patients from a kindred with FBH and nine normal subjects were evaluated. Our results indicate that calcium pump activity in the FBH kindred was significantly higher (28%, P < 0.005) when compared to normal subjects. These findings suggest that alterations in calcium pump activity in target tissues may play a role in the development of FBH.

[Normative data for the neuropsychological evaluation of intravenous drug users]. / Datos normativos para la exploración neuropsicológica de usuarios de drogas por vía parenteral.

BACKGROUND: There are many recent epidemiological studies that find that intravenous drug users' (IDU's) performance in several measures of neuropsychological function are not the same than that of the general population, whether they are seropositive to HIV-1 infection or not. Consequently, it has been stated the need to establish appropriate norms for this population. The purpose of this study is to provide normative data on a battery of neuropsychological tests from a IDU group. SUBJECTS AND METHODS: This report provide normative data from a group of 116 IDU, on a battery of neuropsychological tests stratified by age group (mean = 30.9; SD = 4.5), and educational level (mean = 8; SD = 2.4). Comparisons between the means of the different groups according to age and education, and also with respect to sex are made. The analysis includes estimation of partial correlations between neuropsychological test scores and age and education. RESULTS: The analysis demonstrates that education is an important determinant of performance for most of these tests, while there are no differences in performance between the two age-groups. With respect to sex, females out-performed men on a measure of motor speed and coordination. CONCLUSIONS: This report provides norms that may be of use as a reference for clinical evaluation and research in drug user populations. It also emphasizes the need to establish normative data controlling for variables like educational level, from a population with special characteristics such as IDU population.