Operational feasibility of Plasmodium vivax radical cure with tafenoquine or primaquine following point-of-care, quantitative glucose-6-phosphate dehydrogenase testing in the Brazilian Amazon: a real-life retrospective analysis.

BACKGROUND: To achieve malaria elimination, Brazil must implement Plasmodium vivax radical cure. We aimed to investigate the operational feasibility of point-of-care, quantitative, glucose-6-phosphate dehydrogenase (G6PD) testing followed by chloroquine plus tafenoquine or primaquine. METHODS: This non-interventional, observational study was done at 43 health facilities in Manaus (Amazonas State) and Porto Velho (Rondônia State), Brazil, implementing a new P vivax treatment algorithm incorporating point-of-care quantitative G6PD testing to identify G6PD status and single-dose tafenoquine (G6PD normal, aged ≥16 years, and not pregnant or breastfeeding) or primaquine (intermediate or normal G6PD, aged ≥6 months, not pregnant, or breastfeeding >1 month). Following training of health-care providers, we collated routine patient records from the malaria epidemiological surveillance system (SIVEP-Malaria) retrospectively for all consenting patients aged at least 6 months with parasitologically confirmed P vivax malaria mono-infection or P vivax plus P falciparum mixed infection, presenting between Sept 9, 2021, and Aug 31, 2022. The primary endpoint was the proportion of patients aged at least 16 years with P vivax mono-infection treated or not treated appropriately with tafenoquine in accordance with their G6PD status. The trial is registered with ClinicalTrials.gov, NCT05096702, and is completed. FINDINGS: Of 6075 patients enrolled, 6026 (99·2%) had P vivax mono-infection, 2685 (44·6%) of whom were administered tafenoquine. G6PD status was identified in 2685 (100%) of 2685 patients treated with tafenoquine. The proportion of patients aged at least 16 years with P vivax mono-infection who were treated or not treated appropriately with tafenoquine in accordance with their G6PD status was 99·7% (95% CI 99·4-99·8; 4664/4680). INTERPRETATION: Quantitative G6PD testing before tafenoquine administration was operationally feasible, with high adherence to the treatment algorithm, supporting deployment throughout the Brazilian health system. FUNDING: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Western diet consumption by host vertebrate promotes altered gene expression on Aedes aegypti reducing its lifespan and increasing fertility following blood feeding.

BACKGROUND: The high prevalence of metabolic syndrome in low- and middle-income countries is linked to an increase in Western diet consumption, characterized by a high intake of processed foods, which impacts the levels of blood sugar and lipids, hormones, and cytokines. Hematophagous insect vectors, such as the yellow fever mosquito Aedes aegypti, rely on blood meals for reproduction and development and are therefore exposed to the components of blood plasma. However, the impact of the alteration of blood composition due to malnutrition and metabolic conditions on mosquito biology remains understudied. METHODS: In this study, we investigated the impact of whole-blood alterations resulting from a Western-type diet on the biology of Ae. aegypti. We kept C57Bl6/J mice on a high-fat, high-sucrose (HFHS) diet for 20 weeks and followed biological parameters, including plasma insulin and lipid levels, insulin tolerance, and weight gain, to validate the development of metabolic syndrome. We further allowed Ae. aegypti mosquitoes to feed on mice and tracked how altered host blood composition modulated parameters of vector capacity. RESULTS: Our findings identified that HFHS-fed mice resulted in reduced mosquito longevity and increased fecundity upon mosquito feeding, which correlated with alteration in the gene expression profile of nutrient sensing and physiological and metabolic markers as studied up to several days after blood ingestion. CONCLUSIONS: Our study provides new insights into the overall effect of alterations of blood components on mosquito biology and its implications for the transmission of infectious diseases in conditions where the frequency of Western diet-induced metabolic syndromes is becoming more frequent. These findings highlight the importance of addressing metabolic health to further understand the spread of mosquito-borne illnesses in endemic areas.

Mapping the evidence of the effects of environmental factors on the prevalence of antibiotic resistance in the non-built environment: Protocol for a systematic evidence map.

BACKGROUND: Human, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies. OBJECTIVE: This study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin. METHODS: Here, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM. We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature.

Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex.

In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes' midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite.

Influence of Sugarcane Variety on Rhizosphere Microbiota Under Irrigated and Water-Limiting Conditions.

Drought is one of the main problems linked to climate change that is faced by agriculture, affecting various globally important crops, including sugarcane. Environmentally sustainable strategies have been sought to mitigate the effects of climate change on crops. Among them, the use of beneficial microorganisms offers a promising approach. However, it is still necessary to understand the mechanisms that regulate plant-microorganism interactions, in normal situations and under stress. In this work, the rhizosphere metagenomes of two sugarcane varieties, one resistant and the other susceptible to drought, were compared under normal conditions and under water-limiting conditions. The results showed that for the drought-resistant sugarcane variety, bacteria belonging to the order Sphingomonadales and the family Xanthomonadaceae presented increased activities in terms of mobility, colonization, and cell growth. In contrast, the rhizosphere associated with the drought-sensitive variety exhibited increases of bacteria belonging to the family Polyangiaceae, and the genus Streptomyces, with modifications in DNA metabolism and ribosome binding proteins. The results pointed to variation in the rhizosphere microbiota that was modulated by the host plant genotype, revealing potential bacterial candidates that could be recruited to assist plants during water-limiting conditions.

Long-lasting infectivity of Plasmodium vivax present in malarial patient blood to Anopheles aquasalis.

Experimental studies for understanding the relationship between Plasmodium vivax and its vector hosts are difficult, because of to the lack of a long-term, in vitro continuous culture system unavailability of infected blood samples, seasonality of the disease, and the concentration of most cases in remote areas. This study evaluates the duration of the infectivity of P. vivax to Anopheles aquasalis after collecting blood from malaria-infected patients. Blood was collected from patients and stored at 4 °C and 37 °C. Every day, for 4 days, the blood was fed to An. aquasalis adult females, and a Giemsa-stained thick blood smear was mounted to account for sexual (gametocytes) and asexual (trophozoites and schizonts) stages and calculate parasitemia. Oocysts in the midgut of the mosquitoes were counted on the seventh day after feeding. Kruskal-Wallis test was used to compare the mean number of oocysts (MO) and the parasite density (PD) in each storage condition and post-infection time-points. The Mann-Whitney test was used to compare the number of oocysts for each day between temperatures. The results show that P. vivax stored at 4 °C and at 37 °C has its infectivity to An. aquasalis preserved for 2 days and 3 days, respectively. Infection rate (IR), PD and MO were higher on the day of blood collection and decreased gradually over time. The parasite density (number of parasites/µL) diminished faster at 4 °C than at 37 °C. In this study, a preservation protocol is shown for long-lasting infectivity of P. vivax in a blood sample taken from malaria-infected patients. These results show that infectivity of P. vivax stored at 4 °C and at 37 °C to An. aquasalis persist until 3 days after blood collection, but parasite density, infection rate, and mean of oocysts decreased 24h after blood collection. Since the malaria cases are increasingly far from the urban areas these results indicate that is possible, losing some infectivity, to realize experimental infections several dozen hours after the blood collection. However, it is necessary to improve the procedures for preserving P. vivax gametocytes for mosquito infection in the laboratory.

A novel technology with precise oxygen-input control: Application of the partial nitritation-anammox process.

Reliable and accurate oxygen-input control, which is critical to maintaining efficient nitrogen removal performance for partial nitritation-anammox (PN-A) process, remains one of the main operational difficulties. In this study, a novel, yet simple system (a simple process for autotrophic nitrogen-removal, SPAN) with precise oxygen-input control was developed to treat ammonium-rich wastewater via PN-A process. SPAN brings oxygen to biomass by circulating water and creating water spray (shower) at the water-air interface, and effectively balances the activities of core functional microorganisms through precise oxygen-input control. The oxygen-input rate is decided by the water circulation rate and shower rate and is measurable and predictable. Therefore, the required amount of oxygen for ammonium oxidation can be precisely delivered to the biomass by adjusting the circulation rate and shower rate. The results of two parallel SPAN reactors demonstrated that during long-term operation, the required oxygen input was precisely and reliably controlled. More than 99% of NH4+-N and 81% - 85% of total nitrogen were stably removed, with anammox bacteria contributing to more than 96% of total nitrogen removal. Anammox bacteria were efficiently enriched to the highest level among the key nitrogen-converting microbial groups, both in terms of abundance (8.17%) and nitrogen-conversion capacity, while ammonium oxidizing bacteria were well controlled to provide sufficient ammonium-oxidizing capacity. Nitrite oxidizing bacteria were maintained stable (relative abundance of 1.08%-1.88%) and their activity was effectively suppressed. This study provided a novel technology, SPAN, to precisely control oxygen input in PN-A system, and proved that SPAN was effective and reliable in achieving long-term high-efficiency nitrogen removal.

Geographical location influences the composition of the gut microbiota in wild house mice (Mus musculus domesticus) at a fine spatial scale.

The composition of the mammalian gut microbiota can be influenced by a multitude of environmental variables such as diet and infections. Studies investigating the effect of these variables on gut microbiota composition often sample across multiple separate populations and habitat types. In this study we explore how variation in the gut microbiota of the house mouse (Mus musculus domesticus) on the Isle of May, a small island off the east coast of Scotland, is associated with environmental and biological factors. Our study focuses on the effects of environmental variables, specifically trapping location and surrounding vegetation, as well as the host variables sex, age, body weight and endoparasite infection, on the gut microbiota composition across a fine spatial scale in a freely interbreeding population. We found that differences in gut microbiota composition were significantly associated with the trapping location of the host, even across this small spatial scale. Sex of the host showed a weak association with microbiota composition. Whilst sex and location could be identified as playing an important role in the compositional variation of the gut microbiota, 75% of the variation remains unexplained. Whereas other rodent studies have found associations between gut microbiota composition and age of the host or parasite infections, the present study could not clearly establish these associations. We conclude that fine spatial scales are important when considering gut microbiota composition and investigating differences among individuals.

Impact of Prosthesis-Patient Mismatch on 1-Year Outcomes after Transcatheter Aortic Valve Implantation: Meta-analysis of 71,106 Patients.

OBJECTIVES: This study sought to evaluate the impact of prosthesis-patient mismatch (PPM) on the risk of early-term mortality after transcatheter aortic valve implantation (TAVI). METHODS: Databases (Medical Literature Analysis and Retrieval System Online [MEDLINE], Excerpta Medica dataBASE [EMBASE], Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Latin American and Caribbean Literature on Health Sciences [LILACS], and Google Scholar) were searched for studies published until February 2019. PPM after TAVI was defined as moderate if the indexed effective orifice area (iEOA) was between 0.85 cm2/m2 and 0.65 cm2/m2 and as severe if iEOA ≤ 0.65 cm2/m2. RESULTS: The search yielded 1,092 studies for inclusion. Of these, 18 articles were analyzed, and their data extracted. The total number of patients included who underwent TAVI was 71,106. The incidence of PPM after TAVI was 36.3% (25,846 with PPM and 45,260 without PPM). One-year mortality was not increased in patients with any PPM (odds ratio [OR] 1.021, 95% confidence interval [CI] 0.979-1.065, P=0.338) neither in those with moderate PPM (OR 0.980, 95% CI 0.933-1.029, P=0.423). Severe PPM was separately associated with high risk (OR 1.109, 95% CI 1.041-1.181, P=0.001). CONCLUSION: The presence of severe PPM after TAVI increased early-term mortality. Although moderate PPM seemed harmless, the findings of this study cannot not rule out the possibility of it being detrimental, since there are other registries that did not address this issue yet.

Prosthesis-Patient Mismatch after Surgical Aortic Valve Replacement: Neither Uncommon nor Harmless.

Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) is an issue that has been overlooked (not to say neglected). Cardiac surgeons must bear in mind that this is a real problem that we must tackle. The purpose of this paper is to be a wake-up call to the surgical community by giving a brief overview of what PPM is, its incidence and impact on the outcomes. We also discuss the increasing role played by imaging for predicting and assessing PPM after SAVR (with which surgeons must become more acquainted) and, finally, we present some options to avoid PPM after the surgical procedure.

Prosthesis-patient mismatch after surgical aortic valve replacement: neither uncommon nor harmless

Abstract Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) is an issue that has been overlooked (not to say neglected). Cardiac surgeons must bear in mind that this is a real problem that we must tackle. The purpose of this paper is to be a wake-up call to the surgical community by giving a brief overview of what PPM is, its incidence and impact on the outcomes. We also discuss the increasing role played by imaging for predicting and assessing PPM after SAVR (with which surgeons must become more acquainted) and, finally, we present some options to avoid PPM after the surgical procedure.

Impact of prosthesis-patient mismatch on 1-year outcomes after transcatheter aortic valve implantation: meta-analysis of 71, 106 patients

Abstract Objectives: This study sought to evaluate the impact of prosthesis-patient mismatch (PPM) on the risk of early-term mortality after transcatheter aortic valve implantation (TAVI). Methods: Databases (Medical Literature Analysis and Retrieval System Online [MEDLINE], Excerpta Medica dataBASE [EMBASE], Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Latin American and Caribbean Literature on Health Sciences [LILACS], and Google Scholar) were searched for studies published until February 2019. PPM after TAVI was defined as moderate if the indexed effective orifice area (iEOA) was between 0.85 cm2/m2 and 0.65 cm2/m2 and as severe if iEOA ≤ 0.65 cm2/m2. Results: The search yielded 1,092 studies for inclusion. Of these, 18 articles were analyzed, and their data extracted. The total number of patients included who underwent TAVI was 71,106. The incidence of PPM after TAVI was 36.3% (25,846 with PPM and 45,260 without PPM). One-year mortality was not increased in patients with any PPM (odds ratio [OR] 1.021, 95% confidence interval [CI] 0.979-1.065, P=0.338) neither in those with moderate PPM (OR 0.980, 95% CI 0.933-1.029, P=0.423). Severe PPM was separately associated with high risk (OR 1.109, 95% CI 1.041-1.181, P=0.001). Conclusion: The presence of severe PPM after TAVI increased early-term mortality. Although moderate PPM seemed harmless, the findings of this study cannot not rule out the possibility of it being detrimental, since there are other registries that did not address this issue yet.

Prosthesis-patient mismatch negatively affects outcomes after mitral valve replacement: meta-analysis of 10, 239 patients

Abstract Objective: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long-term mortality after mitral valve replacement. Methods: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. Results: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis-patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194-1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280-1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. Conclusion: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis-patient mismatch in order to decrease mortality rates.

Prosthesis-Patient Mismatch Negatively Affects Outcomes after Mitral Valve Replacement: Meta-Analysis of 10,239 Patients.

OBJECTIVE: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long-term mortality after mitral valve replacement. METHODS: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. RESULTS: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis-patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194-1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280-1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. CONCLUSION: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis-patient mismatch in order to decrease mortality rates.

Current Practice of State-of-the-Art Coronary Revascularization in Patients with Heart Failure.

The best treatment for patients with ischemic heart failure (HF) is still on debate. There is growing evidence that coronary artery bypass graft (CABG) benefits these patients. The current recommendations for revascularization in this context are that CABG is reasonable when it comes to decreasing morbidity and mortality rates for patients with severe left ventricular dysfunction (ejection fraction <35%), and significant coronary artery disease (CAD) and should be considered in patients with operable coronary anatomy, regardless whether or not there is a viable myocardium (class IIb). Percutaneous coronary intervention (PCI) does not have enough data to allow the panels to reach a conclusion. The Korean Acute Heart Failure registry (KorAHF) had its data released recently, showing that patients with acute HF who underwent CABG had lower death rates, more complete revascularization and less adverse outcomes compared with patients treated with PCI. Recent ESC/EACTS guidelines on myocardial revascularization clearly recommended CABG as the first choice of revascularization strategy in patients with multivessel disease and acceptable surgical risk to improve prognosis in this scenario of left ventricular dysfunction. However, a high peri-procedural risk must be compared with the benefit of late mortality, and pros and cons of each strategy (either PCI or CABG) must be weighed in the decision-making process. Spurred on by the publication of the above-mentioned article and the release of new guidelines, we went on to write an overview of the current practice of state-of-the-art coronary revascularization options in patients with HF.

Current practice of state-of-the-art coronary revascularization in patients with heart failure

Abstract The best treatment for patients with ischemic heart failure (HF) is still on debate. There is growing evidence that coronary artery bypass graft (CABG) benefits these patients. The current recommendations for revascularization in this context are that CABG is reasonable when it comes to decreasing morbidity and mortality rates for patients with severe left ventricular dysfunction (ejection fraction <35%), and significant coronary artery disease (CAD) and should be considered in patients with operable coronary anatomy, regardless whether or not there is a viable myocardium (class IIb). Percutaneous coronary intervention (PCI) does not have enough data to allow the panels to reach a conclusion. The Korean Acute Heart Failure registry (KorAHF) had its data released recently, showing that patients with acute HF who underwent CABG had lower death rates, more complete revascularization and less adverse outcomes compared with patients treated with PCI. Recent ESC/EACTS guidelines on myocardial revascularization clearly recommended CABG as the first choice of revascularization strategy in patients with multivessel disease and acceptable surgical risk to improve prognosis in this scenario of left ventricular dysfunction. However, a high peri-procedural risk must be compared with the benefit of late mortality, and pros and cons of each strategy (either PCI or CABG) must be weighed in the decision-making process. Spurred on by the publication of the above-mentioned article and the release of new guidelines, we went on to write an overview of the current practice of state-of-the-art coronary revascularization options in patients with HF.

Impact of surgical aortic root enlargement on the outcomes of aortic valve replacement: a meta-analysis of 13 174 patients.

OBJECTIVES: This study sought to evaluate the impact of surgical aortic root enlargement (ARE) on the perioperative outcomes of aortic valve replacement (AVR). METHODS: Databases were searched for studies published until April 2018 to carry out a systematic review followed by meta-analysis of results. RESULTS: The search yielded 1468 studies for inclusion. Of these, 10 articles were analysed and their data extracted. A total of 13 174 patients (AVR with ARE: 2819 patients; AVR without ARE: 10 355 patients) were included from studies published from 2002 to 2018. The total rate of ARE was 21.4%, varying in the studies from 5.7% to 26.3%. The overall odds ratio (OR) [95% confidence interval (CI)] for perioperative mortality showed a statistically significant difference between the groups (among 10 studies), with a higher risk in the 'AVR with ARE' group (OR 1.506, 95% CI 1.209-1.875; P < 0.001), but not when adjusted for isolated AVR + ARE without any concomitant procedures such as mitral valve surgery, coronary artery bypass surgery, etc. (OR 1.625, 95% CI 0.968-2.726; P = 0.066-among 6 studies). The 'AVR with ARE' group showed an overall lower risk of significant patient-prosthesis mismatch among 9 studies (OR 0.472, 95% CI 0.295-0.756; P = 0.002) and a higher overall difference in means of indexed effective orifice area among 10 studies (random-effect model: 0.06 cm2/m2, 95% CI 0.029-0.103; P < 0.001). CONCLUSIONS: Surgical ARE seems to be associated with increased perioperative mortality but with lower risk of patient-prosthesis mismatch.

Surgical aortic valve replacement and patient-prosthesis mismatch: a meta-analysis of 108 182 patients.

OBJECTIVES: This study sought to evaluate the impact of patient-prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. METHODS: Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. RESULTS: The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total number of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve replacement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302-1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277-1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218-1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290-1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. CONCLUSIONS: Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.

Updated Meta-analysis on the Closure of Patent Foramen Ovale in Reduction of Stroke Rates: the DEFENSE-PFO Trial Does not Change the Scenario.

OBJECTIVE: We aimed to analyze whether patent foramen ovale (PFO) closure reduces the risk of stroke, assessing also some safety outcomes after the publication of a new trial. INTRODUCTION: The clinical benefit of closing a PFO has been an open question, so it is necessary to review the current state of published medical data in regards to this subject. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant articles were used to search for randomized controlled trials (RCTs) that reported any of the following outcomes: stroke, death, major bleeding or atrial fibrillation. Six studies fulfilled our eligibility criteria and included 3560 patients (1889 for PFO closure and 1671 for medical therapy. RESULTS: The risk ration (RR) for stroke in the "closure" group compared with the "medical therapy" showed a statistically significant difference between the groups, favouring the "closure" group (RR 0.366; 95%CI 0.171-0.782, P=0.010). There was no statistically significant difference between the groups regarding the safety outcomes, death and major bleeding, but we observed an increase in the risk of atrial fibrillation in the "closure" group (RR 4.131; 95%CI 2.293-7.443, P<0.001). We also observed that the larger the proportion of effective closure, the lower the risk of stroke. CONCLUSION: This meta-analysis found that stroke rates are lower with percutaneously implanted device closure than with medical therapy alone, being these rates modulated by the rates of hypertension, atrial septal aneurysm and effective closure. The publication of a new trial did not change the scenario in the medical literature.

Opportunistic Bacteria Dominate the Soil Microbiome Response to Phenanthrene in a Microcosm-Based Study.

Bioremediation offers a sustainable approach for removal of polycyclic aromatic hydrocarbons (PAHs) from the environment; however, information regarding the microbial communities involved remains limited. In this study, microbial community dynamics and the abundance of the key gene (PAH-RHDα) encoding a ring hydroxylating dioxygenase involved in PAH degradation were examined during degradation of phenanthrene in a podzolic soil from the site of a former timber treatment facility. The 10,000-fold greater abundance of this gene associated with Gram-positive bacteria found in phenanthrene-amended soil compared to unamended soil indicated the likely role of Gram-positive bacteria in PAH degradation. In contrast, the abundance of the Gram-negative PAHs-RHDα gene was very low throughout the experiment. While phenanthrene induced increases in the abundance of a small number of OTUs from the Actinomycetales and Sphingomonadale, most of the remainder of the community remained stable. A single unclassified OTU from the Micrococcaceae family increased ~20-fold in relative abundance, reaching 32% of the total sequences in amended microcosms on day 7 of the experiment. The relative abundance of this same OTU increased 4.5-fold in unamended soils, and a similar pattern was observed for the second most abundant PAH-responsive OTU, classified into the Sphingomonas genus. Furthermore, the relative abundance of both of these OTUs decreased substantially between days 7 and 17 in the phenanthrene-amended and control microcosms. This suggests that their opportunistic phenotype, in addition to likely PAH-degrading ability, was determinant in the vigorous growth of dominant PAH-responsive OTUs following phenanthrene amendment. This study provides new information on the temporal response of soil microbial communities to the presence and degradation of a significant environmental pollutant, and as such has the potential to inform the design of PAH bioremediation protocols.