Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic alternatives in the treatment of patients with BRAF V600 mutation unresectable or metastatic melanoma. The search was carried out on four databases up to July-2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF V600 mutation (NMA-pBRAFV600) and another with a mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via sensitivity analysis. Five clinical trials were included in the NMA-pBRAFV600. In the NMA-pBRAFV600 population, dabrafenib-trametinib had a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine, and on partial response rate (PRR) and overall response rate (ORR) compared with dacarbazine and vemurafenib. In the NMA-pMixed population, dabrafenib-trametinib had a positive effect on OS vs ipilimumab 3 mg/kg and on PFS and PRR vs ipilimumab (3 and 10 mg/kg), nivolumab, and pembrolizumab. However, dabrafenib-trametinib, and vemurafenib-cobimetinib were comparable in terms of clinical efficacy. In addition, dabrafenib-trametinib was associated with less grades 3 and 4 adverse events.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.

Acceptability by sensory and visual analyses of meat from Nellore heifers fed with natural additives and finished in feedlots.

BACKGROUND: This study evaluated the acceptability (by sensorial and visual analyses) of meat from 40 Nellore heifers (finished in feedlots for 73 days) fed with different diets supplemented with essential oils (EOs) and an active principle blend. The five diets tested were: CON - a diet without essential oil and active principle blend (eugenol, thymol, and vanillin); ROS - a diet supplemented with rosemary EO; BLE - supplemented with a blend; BCL - a diet with clove EO+ blend; and BRC - a diet with rosemary, clove EOs + blend. The acceptability of diet and aging time was evaluated by consumers. RESULTS: Diet affected consumer acceptability and visual analysis (meat color). The diets with EO and the blend showed better sensory acceptance by the consumers; meat aged for 7 days received higher scores than meat aged for 1 day. Meat from heifers that received both EOs + blend (BCL, BRC) obtained the highest scores in the visual evaluation. CONCLUSION: The use of natural compounds in ruminant diets improves the sensory characteristics of meat without damaging visual acceptability and may be an alternative to the conventional additive market. © 2020 Society of Chemical Industry.

TGF-ß pro-oligodendrogenic effects on adult SVZ progenitor cultures and its interaction with the Notch signaling pathway.

Adult neural progenitor cells (NPCs) are capable of differentiating into neurons, astrocytes, and oligodendrocytes throughout life. Notch and transforming growth factor ß1 (TGF-ß) signaling pathways play critical roles in controlling these cell fate decisions. TGF-ß has been previously shown to exert pro-neurogenic effects on hippocampal and subventricular zone (SVZ) NPCs in vitro and to interact with Notch in different cellular types. Therefore, the aim of our work was to study the effect of TGF-ß on adult rat brain SVZ NPC glial commitment and its interaction with Notch signaling. Initial cell characterization revealed a large proportion of Olig2+, Nestin+, and glial fibrillary acidic protein (GFAP+) cells, a low percentage of platelet-derived growth factor receptor α (PDGFRα+) or NG2+ cells, and <1% Tuj1+ cells. Immunocytochemical analyses showed a significant increase in the percentage of PDGFRα+, NG2+, and GFAP+ cells upon four-day TGF-ß treatment, which demonstrates the pro-gliogenic effect of this growth factor on adult brain SVZ NPCs. Real-time polymerase chain reaction analyses showed that TGF-ß induced the expression of Notch ligand Jagged1 and downstream gene Hes1. Notch signaling inhibition in cultures treated with TGF-ß produced a decrease in the proportion of PDGFRα+ cells, while TGF-ß receptor II (TßRII) inhibition also rendered a decrease in the proportion of PDGFRα+ cells, concomitantly with a decrease in Jagged1 levels. These findings demonstrate the participation of Notch signaling in TGF-ß effects and illustrate the impact of TGF-ß on glial cell fate decisions of adult brain SVZ NPCs, as well as on oligodendroglial progenitor cell proliferation and maturation.

Genetic variability and physiological traits of Saccharomyces cerevisiae strains isolated from "Vale dos Vinhedos" vineyards reflect agricultural practices and history of this Brazilian wet subtropical area.

Vale dos Vinhedos appellation of origin has a very recent history as industrial wine making region. In this study we investigated the genetic and phenotypic variability of Saccharomyces cerevisiae strains isolated from South-Brazilian vineyards in order to evaluate strain fermentation aptitude and copper and sulphites tolerance. Merlot grape bunches were collected from three vineyards and yeast isolation was performed after single bunch fermentation. High genotypic variability was found and most of the genotypes revealed to be vine-specific. No industrial strain dissemination was present in the sampled vineyards, although it has been wildly reported in traditional winemaking countries. From the phenotypic traits analysis these Brazilian native strains showed good fermentation performances, good tolerance to sulphites and, in particular, a high copper tolerance level. Copper is the most important metal in the formulation of fungicides against downy mildew (Plasmopara viticola), one of the most harmful disease of the vines, and other fungal pests. The high tolerance to copper suggests an environmental adaptation to the strong use of copper-based fungicides, requested by the wet subtropical climate.

The safety of statins in children.

UNLABELLED: Current American Academy of Pediatrics Guidelines recommended that statins should be considered as a first-line agent in children as early as 8 years of age. The aim of our work is to assess the safety of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in children with hypercholesterolaemia. CONCLUSION: Controlled studies in children show that statin monotherapy is efficacious, well tolerated and safe in the short-time. Unfortunately, these studies have relatively short-term follow-up periods, and therefore, long-term safety remains unclear.

Indica rice cultivar IRGA 424, transformed with cry genes of B. thuringiensis, provided high resistance against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Plant expression of the entomopathogenic bacteria Bacillus thuringiensis cry gene has reduced the damage created by insect pests in several economically important cultures. For this study, we have conducted genetic transformation of the indica rice "IRGA 424", via Agrobacterium tumefaciens, using the B. thuringiensis cry1Aa and cry1B genes, with the objective of obtaining rice plants resistant to the insect pests from this culture. The gene constructions harbor the promoters maize proteinase inhibitor and ubiquitin. The results showed that high concentration of the hormone 2,4-dichlorophenoxyacetic acid and agarose as the gelling agent helped the production of embryogenic calli for the analyzed cultivar. More than 80% of the obtained transformed plants revealed the integration, using polymerase chain reaction, of the cry1Aa and cry1B genes. Analysis of the expression of the heterologous protein by Western blotting revealed the expression of the Cry1B delta-endotoxin in IRGA 424 plants transformed with the ubiquitin promoter. Data showed the production and dissemination of a high number of embryogenic calli in addition to obtaining plants transformed with the cry1Aa and cry1B genes until the reproductive phase. The feed bioassays with the transformed plants and Spodoptera frugiperda (JE Smith) larvae indicated high rates of mortality to the insect target. The highest corrected mortality rate achieved under laboratory conditions with Bt-rice plants transformed with the cry1B and cry1Aa genes was 94 and 84%, respectively. Thus, our results demonstrated the great potential of transformed Bt-rice plants in controlling the damage caused by these insect pests in rice paddy fields.

Responses of wild skuas (Catharacta antarctica ssp. lonnbergi) to human cues in cooperative and competitive social contexts.

Many animals respond to and use social cues emitted by other species (e.g., head direction). In the context of human-animal communication, these capacities have been attributed to regular and longstanding exposure to humans. We presented wild brown skuas (Catharacta antarctica ssp. lonnbergi) with two versions of an object-choice paradigm. In the cooperative version (Experiment 1), one human experimenter provided a simple and salient cue indicating which of two containers covered a food reward. The cues administered consisted of touching, looking at, pointing at, or pointing and looking at the container hiding food. In Experiment 1, skuas could thus cooperate with an experimenter by using the cues provided to locate the rewarded container. In the competitive version (Experiment 2), two human experimenters presented a platform with a visible food reward. In six experimental conditions, we varied experimenters' body orientation, head orientation, eye-gaze direction, face occlusion, and mouth occlusion, as well as the platform's location, ensuring that in each case only one experimenter had visual access to the rewarded platform. Here, birds could compete with the experimenters by robbing the human who does not see the food. Skuas failed to use human-given cues spontaneously in Experiment 1, and took the reward regardless of whether the experimenters could see in Experiment 2. Our results contrast with those obtained on other wild birds with pre-experience with humans. Hopefully, our findings will stimulate further research in order to illuminate the potential role of such experience in the capacity to respond to and use human-given cues. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Evaluation of the economic benefits, administration times, and patient preferences associated with the use of biotechnological drugs administered subcutaneously and intravenously in patients with cancer: a systematic review.

INTRODUCTION: Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations. METHODOLOGY: A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively. RESULTS: 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration. CONCLUSIONS: The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.

Alectinib for treating patients with metastatic ALK-positive NSCLC: systematic review and network metanalysis.

Aim: To compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. Methods: A systematic literature review was conducted up to November 2021. Network meta-analyses were performed using the frequentist method (random effects). GRADE evidence profile was conducted. Results: 13 RCTs were selected. For overall survival, alectinib was found to reduce the risk of death compared with crizotinib. In progression-free survival, alectinib reduced the risk of death or progression compared with crizotinib and ceritinib. Subgroup analysis by brain metastasis at baseline showed the superiority of alectinib over crizotinib and a similar effect compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors.

This article reports the results of a systematic literature review with network meta-analysis (NMA) that aimed to compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. The results show that alectinib reduces the risk of death and the risk of progression compared with crizotinib. For progression-free survival, further significant reductions were observed when compared with ceritinib. For the other ALK inhibitors, no statistically significant differences were found. Subgroup analysis according to the presence of CNS metastases at baseline were consistent in showing the superiority of alectinib over crizotinib and the absence of statistically significant differences compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors, reducing the frequency of adverse events (AEs) compared with ceritinib, and with no statistically significant differences compared with lorlatinib, brigatinib, ensartinib and crizotinib for the frequency of serious AEs or discontinuation of treatment due to AEs. The results of this study suggest clinically relevant insights in decision-making based on patient survival and progression-free survival. Furthermore, considering the importance of reducing the risk of intracranial progression and the need for available therapies for patients who will inevitably progress, alectinib could be considered as a first-line treatment for patients with ALK-positive NSCLC.

The Design, Development, and Usability Testing of an eHealth Program for Youths With Osteogenesis Imperfecta: Protocol for a 2-Phase User-Centered Mixed Methods Study.

BACKGROUND: Innovative approaches are needed to address the self-management needs of youths with osteogenesis imperfecta (OI) transitioning into adult-oriented health care systems. Using a sequentially phased research approach, the goal is to design, develop, and test the usability of an innovative eHealth program called "Teens Taking Charge: Managing OI Online," hereafter named "Teens OI." This program seeks to optimize self-management, facilitate a successful transition to adult care, and address a critical gap in the quality of care for youths with OI. OBJECTIVE: The study objectives are to (1) design and develop an English and French version of the Teens OI and (2) test the usability of the Teens OI in terms of efficiency, effectiveness, and satisfaction from the perspectives of youths with OI and their parents. METHODS: A user-centered design is presently in progress to design and develop Teens OI. A "Website Design and Development Council" (ie, Council) has been convened, with 20 youths and parent dyads recruited and global experts surveyed at an international meeting. With unanimous support from the Council, usability testing of the Teens OI will ensue in 4 iterative cycles with 32 youth-parent dyads. All sociodemographic and usability metrics will be descriptively analyzed. All recorded interview and focus group data are analyzed using content analysis techniques involving an iterative process of data reduction, data display, conclusion drawing, and verification. RESULTS: As of December 2022, an 8-person, interdisciplinary Teens OI council, comprising 4 health care professionals, 3 youths and young adults with OI, and 1 parent, has been convened to oversee the design and development of Teens OI. Two cycles of interviews have been conducted with 10 youths with OI with or without their parents (n=6) from December 2021 to September 2022. Data analysis has been in progress since April 2022. Aim 2 is ethically approved and will commence following the completion of content development, expected by late July 2023. Preliminary analysis indicates that the following topics need to be prioritized for the youths: mental health, pain, accessibility, medical care, education, community, and parental care. CONCLUSIONS: The proposed study will design and develop a self-management and transitional care program for youths with OI in partnership with patients, caregivers, and health care professionals. This study leverages youths' openness to adopt eHealth technologies to meet their needs and has the potential to actively engage them to autonomously manage their lifelong conditions, and facilitate a successful transition to adult health care. Finally, the proposed study will also address a critical gap in the quality of care and the growing concern that the OI population transitioning from pediatric to adult care is at risk of various adverse events associated with the transition. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47524.

Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity.

Neurodegenerative diseases (NDs) are characterized by a progressive deterioration of neuronal function, leading to motor and cognitive damage in patients. Astrocytes are essential for maintaining brain homeostasis, and their functional impairment is increasingly recognized as central to the etiology of various NDs. Such impairment can be induced by toxic insults with palmitic acid (PA), a common fatty acid, that disrupts autophagy, increases reactive oxygen species, and triggers inflammation. Although the effects of PA on astrocytes have been addressed, most aspects of the dynamics of this fatty acid remain unknown. Additionally, there is still no model that satisfactorily explains how astroglia goes from being neuroprotective to neurotoxic. Current incomplete knowledge needs to be improved by the growing field of non-coding RNAs (ncRNAs), which is proven to be related to NDs, where the complexity of the interactions among these molecules and how they control other RNA expressions need to be addressed. In the present study, we present an extensive competing endogenous RNA (ceRNA) network using transcriptomic data from normal human astrocyte (NHA) cells exposed to PA lipotoxic conditions and experimentally validated data on ncRNA interaction. The obtained network contains 7 lncRNA transcripts, 38 miRNAs, and 239 mRNAs that showed enrichment in ND-related processes, such as fatty acid metabolism and biosynthesis, FoxO and TGF-ß signaling pathways, prion diseases, apoptosis, and immune-related pathways. In addition, the transcriptomic profile was used to propose 22 potential key controllers lncRNA/miRNA/mRNA axes in ND mechanisms. The relevance of five of these axes was corroborated by the miRNA expression data obtained in other studies. MEG3 (ENST00000398461)/hsa-let-7d-5p/ATF6B axis showed importance in Parkinson's and late Alzheimer's diseases, while AC092687.3/hsa-let-7e-5p/[SREBF2, FNIP1, PMAIP1] and SDCBP2-AS1 (ENST00000446423)/hsa-miR-101-3p/MAPK6 axes are probably related to Alzheimer's disease development and pathology. The presented network and axes will help to understand the PA-induced mechanisms in astrocytes, leading to protection or injury in the CNS under lipotoxic conditions as part of the intricated cellular regulation influencing the pathology of different NDs. Furthermore, the five corroborated axes could be considered study targets for new pharmacologic treatments or as possible diagnostic molecules, contributing to improving the quality of life of millions worldwide.

Burden of disease of spinal muscular atrophy linked to chromosome 5q (5q-SMA) in Colombia.

OBJECTIVE: This article estimates the disease burden of 5q-SMA in Colombia by using the disability-adjusted life years (DALYs) metric. METHODS: Epidemiological data were obtained from local databases and medical literature and were adjusted in the DisMod II tool. DALYs were obtained by adding years of life lost due to premature death (YLL) and years lived with disability (YLD). RESULTS: The modeled prevalence of 5q-SMA in Colombia was 0.74 per 100,000 population. The fatality rate for all types was 14.1%. The disease burden of 5q-SMA was estimated at 4,421 DALYs (8.6 DALYs/100,000), corresponding to 4,214 (95.3%) YLLs and 207 (4.7%) YLDs. Most of the DALYs were accounted in the 2-17 age group. Of the total burden, 78% correspond to SMA type 1, 18% to type 2, and 4% to type 3. CONCLUSIONS: Although 5q-SMA is a rare disease, it is linked to a significant disease burden due to premature mortality and severe sequelae. The estimates shown in this article are important inputs to inform public policy decisions on how to ensure adequate health service provision for patients with 5q-SMA.

Natural photosensitizer-loaded in micellar copolymer to prevent bovine mastitis: A new post-dipping protocol on milking.

Good management practices such as post-dipping applications (post-milking immersion bath) contribute to the dairy cattle health during lactation and minimize the appearance of mastitis (an infection in the mammary gland). The post-dipping procedure is performed conventionally using iodine-based solutions. The search for therapeutic modalities that are not invasive and do not cause resistance to the microorganisms that cause bovine mastitis instigates the interest of the scientific community. In this regard, antimicrobial Photodynamic Therapy (aPDT) is highlighted. The aPDT is based on combining a photosensitizer (PS) compound, light of adequate wavelength, and molecular oxygen (3O2), which triggers a series of photophysical processes and photochemical reactions that generate reactive oxygen species (ROS) responsible for the inactivation of microorganisms. The present investigation explored the photodynamic efficiency of two natural PS: Chlorophyll-rich spinach extract (CHL) and Curcumin (CUR), both incorporated into the Pluronic® F127 micellar copolymer. They were applied in post-dipping procedures in two different experiments. The photoactivity of formulations mediated through aPDT was conducted against Staphylococcus aureus, and obtained a minimum inhibitory concentration (MIC) of 6.8 mg mL-1 for CHL-F127 and 0.25 mg mL-1 for CUR-F127. Only CUR-F127 inhibited Escherichia coli growth with MIC 0.50 mg mL-1. Concerning the count of microorganisms during the days of the application, a significant difference was observed between the treatments and control (Iodine) when the teat surface of cows was evaluated. For CHL-F127 there was a difference for Coliform and Staphylococcus (p < 0.05). For CUR-F127 there was a difference for aerobic mesophilic and Staphylococcus (p < 0.05). Such application decreased bacterial load and maintained the milk quality, being evaluated via total microorganism count, physical-chemical composition, and somatic cell count (SCC).

Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort.

BACKGROUND: Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. METHODS: This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. RESULTS: Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P = .04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. CONCLUSIONS: Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.

Bacillus thuringiensis monogenic strains: screening and interactions with insecticides used against rice pests.

The screening of Bacillus thuringiensis (Bt) Cry proteins with high potential to control insect pests has been the goal of numerous research groups. In this study, we evaluated six monogenic Bt strains (Bt dendrolimus HD-37, Bt kurstaki HD-1, Bt kurstaki HD-73, Bt thuringiensis 4412, Bt kurstaki NRD-12 and Bt entomocidus 60.5, which codify the cry1Aa, cry1Ab, cry1Ac, cry1Ba, cry1C, cry2A genes respectively) as potential insecticides for the most important insect pests of irrigated rice: Spodoptera frugiperda, Diatraea saccharalis, Oryzophagus oryzae, Oebalus poecilus and Tibraca limbativentris. We also analyzed their compatibility with chemical insecticides (thiamethoxam, labdacyhalothrin, malathion and fipronil), which are extensively used in rice crops. The bioassay results showed that Bt thuringiensis 4412 and Bt entomocidus 60.5 were the most toxic for the lepidopterans, with a 93% and 82% mortality rate for S. frugiperda and D. saccharalis, respectively. For O. oryzae, the Bt kurstaki NRD-12 (64%) and Bt dendrolimus HD-37 (62%) strains were the most toxic. The Bt dendrolimus HD-37 strain also caused high mortality (82%) to O. poecilus, however the strains assessed to T. limbativentris caused a maximum rate of 5%. The assays for the Bt strains interaction with insecticides revealed the compatibility of the six strains with the four insecticides tested. The results from this study showed the high potential of cry1Aa and cry1Ba genes for genetic engineering of rice plants or the strains to biopesticide formulations.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro.

BACKGROUND: Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. AIM OF THE STUDY: To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). METHODS: Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. RESULTS: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR = 26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR = 15.00 [95% CI: 2.30-631.47]). CONCLUSION: Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Integrated Maternal Care Strategies in Low- and Middle-Income Countries: A Systematic Review.

Background and aim: Ineffective organisation of care leads to increased morbidity and mortality in neonates and their mothers. We aimed to identify and describe strategies used in low- and middle-income countries that attempt to deliver coherent, coordinated, and continuous services (i.e., integrated care) and how the various strategies affect the organisation of care. Methods: We conducted a systematic literature review to identify, appraise, and synthesise relevant evidence about strategies for integrating maternal care in low- and middle-income countries, searching multiple electronic databases. Results: Fourteen studies met our inclusion criteria. We identified five types of integration strategies: 1) organisational, 2) service/professional, 3) functional, 4) organisational combined with normative strategies, and 5) clinical combined with functional integration strategies. The most frequent types of strategies were organisational, and service/professional integration strategies. We did not identify any publications describing systemic integration strategies implemented in low- and middle-income countries. Conclusions: Most types of strategies described in theory have been implemented and studied in low- and middle-income countries. Our findings suggest that different types of strategies may lead to comparable organisational outcomes. For example, organisational integration strategies and professional or service integration strategies may similarly influence inter-organisational collaboration. Inter-organisational collaboration may play a particularly important role in the context of maternal care integration.

Pregnant patient with prune belly syndrome: case report.

Prune belly syndrome is a rare congenital disease of unknown etiology that is present in one in every 40 thousand live births, and predominantly affects males, at a ratio of 4:1. In males, it presents with anomalies in the urinary system, absence of abdominal muscles, bilateral cryptorchidism, and infertility. In women, the syndrome has variable presentations, but fertility is preserved. Searching the medical literature, we found only one case of prune belly syndrome in pregnant women. Therefore, the patient in this report is the second case. She was primiparous, 25-years-old, with no abdominal muscles, severe congenital kyphoscoliosis, and pulmonary restriction. Elective cesarean section was performed at 37 weeks of gestation due to maternal risk of uterine rupture by transverse presentation and fetal risk of intrauterine growth restriction. The pre-anesthetic approach defined that general anesthesia might have more risks for the patient due to severe maternal lung disease compared to ultrasound-guided locoregional anesthesia. During prenatal care, there were some maternal complications, such as asthma exacerbations, abdominal pain, and constipation. The newborn was born small for gestational age and this can possibly be explained by maternal restrictive lung capacity. The newborn presented with Apgar score 8/9 and tachypnea, but improved after two hours of life.