Abstract
Background
Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence ...exists in our setting, where diagnosis and treatment are carried out in different contexts.
Methods
An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen.
Results
One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load (<50 copies/mL) at 48 weeks from starting ART. No serious adverse effects associated with the strategy were observed. In total, 101 participants continued care at 48 weeks with retention in HIV care rate of 93.5% (101/108).
Conclusions
Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.
Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the ...metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis.
Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the ...characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia.
A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared.
Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group.
MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.
The purpose of this investigation was to explore patients' and oncologists' preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC).
...Cross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference.
A total of 105 patients with aRCC (77.1% male, mean age 65.9 years SD: 10.4, mean time since RCC diagnosis 6.3 years SD: 6.1) and 67 oncologists (52.2% male, mean age 41.9 years SD: 8.4, mean duration of experience in RCC 10.2 years SD: 7.5) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists).
Patients' and oncologists' preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.
The Mediterranean diet is a dietary pattern typical of the populations living in the Mediterranean basin during the 50s-60s of the last century. This diet has demonstrated beneficial effects in the ...prevention of several pathologies such as cardiovascular diseases, metabolic syndrome, or several cancer types, at least in part, due to its antioxidant compounds. Since the COVID-19 pandemic started, different authors have been studying the effects of certain dietary habits on the presence of COVID-19 and its severity, and the Mediterranean diet is one of them. This review gathers data from studies supporting the potential usefulness of the main phenolic compounds present in the Mediterranean diet, based on their antioxidant and anti-inflammatory effects, as preventive/therapeutic agents against COVID-19. The current evidence supports the potential benefits that hydroxytyrosol, resveratrol, flavonols such as quercetin, flavanols like catechins, and flavanones on the order of naringenin could have on COVID-19. This is due to the increase in the synthesis and translocations of Nrf-2, which increases the activity of antioxidant enzymes and thus reduces ROS production, the scavenging of free radicals, and the suppression of the activity of MMP-9, which is involved in the cytokine storm, and the inhibition of NF-κB.
Studies examining occupational exposures and cancer risk frequently report mixed findings; it is thus imperative for researchers to synthesize study results and identify any potential sources that ...explain such variabilities in study findings. However, when synthesizing study results using meta-analytic techniques, researchers often encounter a number of practical and methodological challenges. These challenges include (1) an incomparability of effect size measures due to large variations in research methodology; (2) a violation of the independence assumption for meta-analysis; (3) a violation of the normality assumption of effect size measures; and (4) a variation in cancer definitions across studies and changes in coding standards over time. In this paper, we first demonstrate these challenges by providing examples from a real dataset collected for a large meta-analysis project that synthesizes cancer mortality and incidence rates among firefighters. We summarize how each of these challenges has been handled in our meta-analysis. We conclude this paper by providing practical guidelines for handling challenges when synthesizing study findings from occupational cancer literature.
To determine the incidence of ALK translocations in patients with advanced/metastatic NSCLC in Spain, to describe the clinical characteristics of these patients, and to evaluate the effectiveness and ...safety of treatment with crizotinib in a real-world setting.
This is an observational prospective and retrospective cohort study to determine the incidence of ALK translocations and to analyze the effectiveness and safety of crizotinib in a real-world setting. Patient characteristics, treatment patterns, time to best overall response, duration of treatment, objective response rates (ORR), rates of adverse events (AE), progression free survival (PFS) and overall survival (OS) were evaluated in the ALK study cohort of patients treated with crizotinib (prospective and retrospective). ALK incidence and quality of life (QoL) questionnaires were measured from patients included in the prospective cohort.
The incidence of ALK translocations was 5.5 % (31 of 559 patients). Compared with ALK-negative patients, ALK-positive patients were significantly younger, predominantly female, and non-smokers. In the crizotinib effectiveness and safety study, 91 patients (42 prospective, 49 retrospective) with ALK-positive NSCLC (43.9 % in first-line, 56.1 % in second or more lines) were included. The ORR was 59.3 % and the median duration of response was 13.5 months (IQR, 5.3–26.2). The median PFS was 15.8 months (95 % CI, 11.8–22.3) and the median OS was 46.5 months, with 53 patients (58.2 %) still alive at data cut-off date. Frequently reported AEs included elevated transaminases, gastrointestinal disorders, and asthenia. Most patients (76.5 %) reported improved or stable scores for global QoL during treatment.
The observed incidence of ALK translocations in NSCLC patients is aligned with published reports. This analysis of the real-world clinical experience in Spain confirms the therapeutic benefit and safety of crizotinib in advanced/metastatic ALK-positive NSCLC. Clinicaltrials.gov: NCT02679170.
We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to ...the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.
Synopsis
A novel drug‐screening platform compatible with patient‐derived samples identifies effective therapies to prevent brain metastasis.
METPlatform is a novel drug‐screening strategy to identify vulnerabilities of metastasis while colonizing organs ex vivo.
METPlatform identified hits that were confirmed in vivo as effective against brain metastasis.
METPlatform allows to dissect the molecular mechanisms downstream of target inhibition using omic approaches.
METPlatform has a potential value as a patient "avatar".
A novel drug‐screening platform compatible with patient‐derived samples identifies effective therapies to prevent brain metastasis.
ABSTRACT
Consumption of high-energy-yielding diets, rich in fructose and lipids, is a factor contributing to the current increase in non-alcoholic fatty liver disease prevalence. Gut microbiota ...composition and short-chain fatty acids (SCFAs) production alterations derived from unhealthy diets are considered putative underlying mechanisms. This study aimed to determine relationships between changes in gut microbiota composition and SCFA levels by comparing rats featuring diet-induced steatohepatitis with control counterparts fed a standard diet. A high-fat high-fructose (HFHF) feeding induced higher body, liver and mesenteric adipose tissue weights, increased liver triglyceride content and serum transaminase, glucose, non-HDL-c and MCP-1 levels. Greater liver malondialdehyde levels and glutathione peroxidase activity were also observed after feeding the hypercaloric diet. Regarding gut microbiota composition, a lowered diversity and increased abundances of bacteria from the
Clostridium
sensu stricto 1,
Blautia
,
Eubacterium coprostanoligenes
group,
Flavonifractor
, and UBA1819 genera were found in rats featuring diet-induced steatohepatitis, as well as higher isobutyric, valeric and isovaleric acids concentrations. These results suggest that hepatic alterations produced by a hypercaloric HFHF diet may be related to changes in overall gut microbiota composition and abundance of specific bacteria. The shift in SCFA levels produced by this unbalanced diet cannot be discarded as potential mediators of the reported hepatic and metabolic alterations.
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