A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse ...transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.
We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.
We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.
There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).
Protocol available on the OSF website: https://tinyurl.com/vvbgqya.
Scope
Dysbiosis of gut microbiota is involved in metabolic syndrome (MetS) development, which has a different incidence between men (M) and women (W). The differences in gut microbiota in MetS ...patients are explored according to gender, and whether consuming two healthy diets, Mediterranean (MED) and low‐fat (LF), may, over time, differentially shape the gut microbiota dysbiosis according to gender is evaluated.
Materials and Methods
All the women from the CORDIOPREV study whose feces samples were available and a similar number of men, matched by the main metabolic variables (N = 246, 123 women and 123 men), and categorized according to the presence or not of MetS are included. Gut microbiota is analyzed at baseline and after 3 years of dietary intervention.
Results
Higher abundance of Collinsella, Alistipes, Anaerotruncus, and Phascolarctobacterium genera is observed in MetS‐W than in MetS‐M, whereas the abundance of Faecalibacterium and Prevotella genera is higher in MetS‐M than in MetS‐W. Moreover, higher levels of Desulfovibrio, Roseburia, and Holdemania are observed in men than in women after the consumption of the LF diet.
Conclusion
The results suggest the potential involvement of differences in gut microbiota in the unequal incidence of metabolic diseases between genders, and a sex‐dependent effect on shaping the gut microbiota according to diet.
Dysbiosis of gut microbiota is involved in the development of metabolic syndrome, whose incidence is different between men and women. This work provides evidence of a different gut microbiota composition in metabolic syndrome, according to gender. Moreover, the study shows a differential shaping of the gut microbiota according to the gender in metabolic syndrome patients after the consumption of a Mediterranean or a low‐fat diet for three years.
Old and new challenges in Chagas disease Pérez-Molina, Jose A, Dr; Perez, Angela Martinez, MD; Norman, Francesca F, MBBS ...
The Lancet infectious diseases,
11/2015, Letnik:
15, Številka:
11
Journal Article
Recenzirano
Summary Chagas disease, caused by the parasite Trypanosoma cruzi , is a neglected disease, which can lead to cardiomyopathy, arrhythmias, megaviscera, and more rarely, polyneuropathy in up to 30–40% ...of patients around 20 to 30 years after acute infection. Although it is endemic in the Americas, global population movements mean that it can be located wherever migrants from endemic areas settle. The disease was first described 100 years ago and still challenges clinicians worldwide, since diagnostic, therapeutic, and prognostic methods remain insufficient. Furthermore, factors such as HIV co-infection, immunosuppressive drugs, transplantation, and neoplastic disease can alter the natural course of the infection. We present the case of a Bolivian woman with chronic T cruzi infection diagnosed at our clinic in Madrid, Spain, who subsequently developed non-Hodgkin lymphoma. Our report illustrates the challenges of an increasingly common infection seen in non-endemic countries, and highlights both daily management dilemmas and associated difficulties that arise.
Graft-versus-host disease (GvHD) was first described in 1959, since then major efforts have been made in order to understand its physiopathology and animal models have played a key role. Three steps, ...involving different pathways, have been recognised in either acute and chronic GvHD, identifying them as two distinct entities. In order to reduce GvHD incidence and severity, prophylactic measures were added to transplant protocols. The combination of a calcineurin inhibitor (CNI) plus an antimetabolite remains the standard of care. Better knowledge of GvHD pathophysiology has moved this field forward and nowadays different drugs are being used on a daily basis. Improving GvHD prophylaxis is a major goal as it would translate into less non-relapse mortality and better overall survival. As compared to CNI plus methotrexate the combination of CNI plus mycophenolate mophetil (MMF) allows us to obtain similar results in terms of GvHD incidence but a lower toxicity rate in terms of neutropenia or mucositis. The use of ATG has been related to a lower risk of acute and chronic GvHD in prospective randomized trials as well as the use of posttransplant Cyclophosphamide, with no or marginal impact on overall survival but with an improvement in GvHD-relapse free survival (GRFS). The use of sirolimus has been related to a lower risk of acute GvHD and significantly influenced overall survival in one prospective randomized trial. Other prospective trials have evaluated the use of receptors such as CCR5 or α4β7 to avoid T-cells trafficking into GvHD target organs, cytokine blockers or immune check point agonists. Also, epigenetic modifiers have shown promising results in phase II trials. Attention should be paid to graft-versus-leukemia, infections and immune recovery before bringing new prophylactic strategies to clinical practice. Although the list of novel agents for GvHD prophylaxis is growing, randomized trials are still lacking for many of them.
Abstract Background Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is ...associated with high toxicity. Objective To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile. Design, setting, and participants Patients from the outpatient clinics of the participating centres with high-risk non–muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007. Intervention Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm). Outcome measurements and statistical analysis Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ2 and log-rank tests. Results and limitations A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration HR 0.83; 95% CI 0.61–1.13; p = 0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50–1.26; p = 0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%). Conclusions In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone. Patient summary Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment. Trial registration CUETO 98013
There are several pathologies, syndromes, and physiological processes in which autophagy is involved. This process of self‐digestion that cells trigger as a survival mechanism is complex and tightly ...regulated, according to the homeostatic conditions of the organ. However, in all cases, its relationship with oxidative stress alterations is evident, following a pathway that suggests endoplasmic reticulum stress and/or mitochondrial changes. There is accumulating evidence of the beneficial role that melatonin has in the regulation and restoration of damaged autophagic processes. In this review, we focus on major physiological changes such as aging and essential pathologies including cancer, neurodegenerative diseases, viral infections and obesity, and document the essential role of melatonin in the regulation of autophagy in each of these different situations.
Electrons feed into the mitochondrial electron transport chain (mETC) from NAD- or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate ...the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To prevent this, the mETC superstructure can be reconfigured through the degradation of respiratory complex I, liberating associated complex III to increase electron flux via FAD at the expense of NAD. Here, we demonstrate that this adaptation is driven by the ratio of reduced to oxidized CoQ. Saturation of CoQ oxidation capacity induces reverse electron transport from reduced CoQ to complex I, and the resulting local generation of superoxide oxidizes specific complex I proteins, triggering their degradation and the disintegration of the complex. Thus, CoQ redox status acts as a metabolic sensor that fine-tunes mETC configuration in order to match the prevailing substrate profile.
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•High CoQH2/CoQ ratio induces reverse electron transport under physiological conditions•RET-generated ROS induces partial complex I degradation•Increase in the CIII fraction detached of CI optimizes mETC to consume fatty acids•The CoQH2/CoQ ratio serves as a sensor of respiratory chain efficiency
Guarás et al. show how the mitochondrial electron transport chain (mtETC) is optimized to better oxidize different nutrients or fuels using the reducing status of ubiquinone as a metabolic sensor and ROS generated by complex I by reverse electron transport as an executor.
Background and objectives
Nonalcoholic fatty liver disease (NAFLD) management is focused on lifestyle modifications, but long‐term maintenance is a challenge for many individuals. This study aimed to ...evaluate the long‐term effects of two personalized energy‐restricted dietary strategies on weight loss, metabolic and hepatic outcomes in overweight/obese subjects with NAFLD.
Methods
Ninety‐eight subjects from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were randomly assigned to the American Heart Association (AHA) or the FLiO dietary group in a 2‐year controlled trial. Anthropometry, body composition (DXA), biochemical parameters and hepatic status (ultrasonography, Magnetic Resonance Imaging, and elastography) were assessed at baseline, 6, 12 and 24 months.
Results
Both the AHA and FLiO diets significantly reduced body weight at 6 (−9.7% vs −10.1%), 12 (−6.7% vs −9.6%), and 24 months (−4.8% vs −7.6%) with significant improvements in body composition, biochemical and liver determinations throughout the intervention. At the end of the follow‐up, the FLiO group showed a greater decrease in ALT, liver stiffness and Fatty Liver Index, among others, compared to AHA group, although these differences were attenuated when the analyses were adjusted by weight loss percentage. The FLiO group also showed a greater increase in adiponectin compared to AHA group.
Conclusions
The AHA and FLiO diets were able to improve body weight and body composition, as well as metabolic and hepatic status of participants with overweight/obesity and NAFLD within a 2‐year follow‐up. These findings show that both strategies are suitable alternatives for NAFLD management. However, the FLiO strategy may provide more persistent benefits in metabolic and hepatic parameters.
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