299 research outputs found
Therapeutic variability in the treatment of Candida colonization/infection in non-neutropenic critically ill patients
Satellite monitoring of surface phytoplankton functional types in the Atlantic Ocean over 20 years (2002–2021)
An analysis of multi-satellite-derived products of four major phytoplankton functional types (PFTs – diatoms, haptophytes, prokaryotes and dinoflagellates) was carried out to investigate the PFT time series in the Atlantic Ocean between 2002 and 2021. The investigation includes the 2-decade trends, climatology, phenology and anomaly of PFTs for the whole Atlantic Ocean and its different biogeochemical provinces in the surface layer that optical satellite signals can reach. The PFT time series over the whole Atlantic region showed mostly no clear trend over the last 2 decades, except for a small decline in prokaryotes and an abrupt increase in diatoms during 2018–2019, which is mainly observed in the northern Longhurst provinces. The phenology of diatoms, haptophytes and dinoflagellates is very similar: at higher latitudes bloom maxima are reached in spring (April in the Northern Hemisphere and October in the Southern Hemisphere), in the oligotrophic regions in winter time and in the tropical regions during May to September. In general, prokaryotes show opposite annual cycles to the other three PFTs and present more spatial complexity. The PFT anomaly (in percent) of 2021 compared to the 20-year mean reveals mostly a slight decrease in diatoms and a prominent increase in haptophytes in most areas of the high latitudes. Both diatoms and prokaryotes show a mild decrease along coastlines and an increase in the gyres, while prokaryotes show a clear decrease at mid-latitudes to low latitudes and an increase on the western African coast (Canary Current Coastal Province, CNRY and Guinea Current Coastal Province, GUIN) and southwestern corner of North Atlantic Tropical Gyral Province (NATR). Dinoflagellates, as a minor contributor to the total biomass, are relatively stable in the whole Atlantic region. This study illustrated the past and current PFT state in the Atlantic Ocean and acted as the first step to promote long-term consistent PFT observations that enable time series analyses of PFT trends and interannual variability to reveal potential climate-induced changes in phytoplankton composition on multiple temporal and spatial scales
Sarcopenic Obesity and Myosteatosis Are Associated with Higher Mortality in Patients with Cirrhosis
Background and aims Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.
Methods We analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender-and body mass index-specific cutoffs.
Results Patients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non-alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P = 0.04) were associated with mortality.
Conclusions Sarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long-term mortality in cirrhosis
Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients
BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study
Objectives: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent. Methods: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18. Results: 53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): –1.03 (–1.66 to –0.40) vs –0.58 (–1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement. Conclusions: Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA. Trial registration number: NCT04991753
Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis
Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH.
Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC.
Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal.
Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF
Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes
BACKGROUND: HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists. METHODS: Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained. RESULTS: Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative. CONCLUSION: The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region
Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis
Pre-heated dual-cured resin cements: analysis of the degree of conversion and ultimate tensile strength
Incentive or Habit Learning in Amphibians?
Toads (Rhinella arenarum) received training with a novel incentive procedure involving access to solutions of different NaCl concentrations. In Experiment 1, instrumental behavior and weight variation data confirmed that such solutions yield incentive values ranging from appetitive (deionized water, DW, leading to weight gain), to neutral (300 mM slightly hypertonic solution, leading to no net weight gain or loss), and aversive (800 mM highly hypertonic solution leading to weight loss). In Experiment 2, a downshift from DW to a 300 mM solution or an upshift from a 300 mM solution to DW led to a gradual adjustment in instrumental behavior. In Experiment 3, extinction was similar after acquisition with access to only DW or with a random mixture of DW and 300 mM. In Experiment 4, a downshift from DW to 225, 212, or 200 mM solutions led again to gradual adjustments. These findings add to a growing body of comparative evidence suggesting that amphibians adjust to incentive shifts on the basis of habit formation and reorganization
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