Role of Gasotransmitters in Inflammatory Edema.

Significance: Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are, to date, the identified members of the gasotransmitter family, which consists of gaseous signaling molecules that play central roles in the regulation of a wide variety of physiological and pathophysiological processes, including inflammatory edema. Recent Advances: Recent studies show the potential anti-inflammatory and antiedematogenic effects of NO-, CO-, and H2S-donors in vivo. In general, it has been observed that the therapeutical effects of NO-donors are more relevant when administered at low doses at the onset of the inflammatory process. Regarding CO-donors, their antiedematogenic effects are mainly associated with inhibition of proinflammatory mediators (such as inducible NO synthase [iNOS]-derived NO), and the observed protective effects of H2S-donors seem to be mediated by reducing some proinflammatory enzyme activities. Critical Issues: The most recent investigations focus on the interactions among the gasotransmitters under different pathophysiological conditions. However, the biochemical/pharmacological nature of these interactions is neither general nor fully understood, although specifically dependent on the site where the inflammatory edema occurs. Future Directions: Considering the nature of the involved mechanisms, a deeper knowledge of the interactions among the gasotransmitters is mandatory. In addition, the development of new pharmacological tools, either donors or synthesis inhibitors of the three gasotransmitters, will certainly aid the basic investigations and open new strategies for the therapeutic treatment of inflammatory edema. Antioxid. Redox Signal. 40, 272-291.

Extubation failure and the use of noninvasive ventilation during the weaning process in critically ill COVID-19 patients.

OBJECTIVE: To assess the outcome of extubation in COVID-19 patients and the use of noninvasive ventilation in the weaning process. METHODS: This retrospective, observational, single-center study was conducted in COVID-19 patients aged 18 years or older who were admitted to an intensive care unit between April 2020 and December 2021, placed under mechanical ventilation for more than 48 hours and progressed to weaning. Early extubation was defined as extubation without a spontaneous breathing trial and immediate use of noninvasive ventilation after extubation. In patients who underwent a spontaneous breathing trial, noninvasive ventilation could be used as prophylactic ventilatory assistance when started immediately after extubation (prophylactic noninvasive ventilation) or as rescue therapy in cases of postextubation respiratory failure (therapeutic noninvasive ventilation). The primary outcome was extubation failure during the intensive care unit stay. RESULTS: Three hundred eighty-four extubated patients were included. Extubation failure was observed in 107 (27.9%) patients. Forty-seven (12.2%) patients received prophylactic noninvasive ventilation. In 26 (6.8%) patients, early extubation was performed with immediate use of noninvasive ventilation. Noninvasive ventilation for the management of postextubation respiratory failure was administered to 64 (16.7%) patients. CONCLUSION: We found that COVID-19 patients had a high rate of extubation failure. Despite the high risk of extubation failure, we observed low use of prophylactic noninvasive ventilation in these patients.

Development a Low-Cost Wireless Smart Meter with Power Quality Measurement for Smart Grid Applications.

Developing a low-cost wireless energy meter with power quality measurements for smart grid applications represents a significant advance in efficient and accurate electric energy monitoring. In increasingly complex and interconnected electric systems, this device will be essential for a wide range of applications, such as smart grids, by introducing a real-time energy monitoring system. In light of this, smart meters can offer greater opportunities for sustainable and efficient energy use and improve the utilization of energy sources, especially those that are nonrenewable. According to the 2020 International Energy Agency (IEA) report, nonrenewable energy sources represent 65% of the global supply chain. The smart meter developed in this work is based on the ESP32 microcontroller and easily accessible components since it includes a user-friendly development platform that offers a cost-effective solution while ensuring reliable performance. The main objective of developing the smart meters was to enhance the software and simplify the hardware. Unlike traditional meters that calculate electrical parameters by means of complex circuits in hardware, this project performed the calculations directly on the microcontroller. This procedure reduced the complexity of the hardware by simplifying the meter design. Owing to the high-performance processing capability of the microcontroller, efficient and accurate calculations of electrical parameters could be achieved without the need for additional circuits. This software-driven approach with simplified hardware led to benefits, such as reduced production costs, lower energy consumption, and a meter with improved accuracy, as well as updates on flexibility. Furthermore, the integrated wireless connectivity in the microcontroller enables the collected data to be transmitted to remote monitoring systems for later analysis. The innovative feature of this smart meter lies in the fact that it has readily available components, along with the ESP32 chip, which results in a low-cost smart meter with performance that is comparable to other meters available on the market. Moreover, it is has the capacity to incorporate IoT and artificial intelligence applications. The developed smart meter is cost effective and energy efficient, and offers benefits with regard to flexibility, and thus represents an innovative, efficient, and versatile solution for smart grid applications.

Epidemiological Profile of Hospitalized Patients with Cystic Fibrosis in Brazil Due to Severe Acute Respiratory Infection during the COVID-19 Pandemic and a Systematic Review of Worldwide COVID-19 in Those with Cystic Fibrosis.

Since the onset of the coronavirus disease, COVID-19 pandemic, concern arose for those who might be at higher risk of a worse COVID-19 prognosis, such as those with cystic fibrosis (CF). In this context, we evaluated the features of hospitalized patients with CF due to severe acute respiratory infection (SARI) in Brazil and we also performed a systematic review including all the studies published from the beginning of the first case of COVID-19 (17 November 2019) to the date of this search (23 May 2022) which included, concomitantly, patients with CF and COVID-19 in the worldwide population. In our Brazilian data, we evaluated the period from December 2019 to March 2022, and we included 33 demographical and clinical patients' features. We classified the patients into groups: (G1) SARI due to another viral infection than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (23; 5.4%), (G2) SARI due to an unknown etiological agent (286; 67.1%), and (G3) SARI due to SARS-CoV-2 infection (117; 27.5%). The individuals in G3 tended to be older, especially over 50 years old, and presented a higher prevalence of dyspnea, peripheral capillary oxygen saturation (SpO2) <95%, and cardiopathy. The highest prevalence for intensive care unit (ICU) treatment (52; 44.4%) and invasive mechanical ventilation (29; 24.8%) was for patients in G3. Almost half of the patients in G3 died (51; 43.6%); in contrast, none in G1 died. However, we observed 43 (15.0%) deaths in G2. In addition, 12 (4.2%) and one (0.9%) death not associated with SARI occurred, respectively, in the G2 and G3. The patients who died due to SARS-CoV-2 infection had a higher frequency of SpO2 <95% (46; 90.2%), ICU treatment (34; 66.7%), and invasive mechanical ventilation (27; 52.9%) when compared to those who recovered. The systematic review comprised a total of 31 papers published as observational studies. These studies comprised 661,386 patients in total, including children, adults, and elderly age groups. However, only 19,150 (2.9%) patients were diagnosed with CF and, from these patients, 2523 (0.4%) were diagnosed with both CF and COVID-19. It was observed that the most common outcome was the need for hospitalization (n = 322 patients with CF), and the need for oxygen support (n = 139 patients with CF). One hundred patients with CF needed intensive care units, fifty patients needed non-invasive mechanical ventilation support, and only three patients were described as receiving invasive mechanical ventilation support. Deaths were described in 38 patients with CF. Importantly, lung-transplanted patients with CF represented an increased risk of death in one publication; in accordance, another study described that lung transplantation and moderate to severe lung disease were independent risk factors for severe outcomes after SARS-CoV-2 infection. In contrast with the literature, in conclusion, Brazilian patients in G3 presented a severe phenotype, even though most of the other studies did not observe worse outcomes in patients with CF and COVID-19.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study.

BACKGROUND: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. METHODS: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. RESULTS: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. CONCLUSIONS: SMS could assist patients in adhering to prescribed antimalarials.

Mechanical Power in Prone Position Intubated Patients with COVID-19-Related ARDS: A Cohort Study.

Background: Respiratory monitoring of mechanical ventilation (MV) is relevant and challenging in COVID-19. Mechanical power (MP) is a novel and promising monitoring tool in acute distress respiratory syndrome (ARDS), representing the amount of energy transferred from the ventilator to the patient. It encompasses several setting parameters and patient-dependent variables that could cause lung injury. MP can therefore be an additional tool in the assessment of these patients. Objective: This study aims to evaluate respiratory monitoring through MP and its relationship with mortality in patients with COVID-19-related ARDS (CARDS) under mechanical ventilation (MV) and prone position (PP) strategies. Methods: Retrospective, unicentric, and cohort studies. We included patients with CARDS under invasive MV and PP strategies. Information regarding MP, ventilation, and gas exchange was collected at 3 moments: (1) prior to the first PP, (2) during the first PP, and (3) during the last PP. We tested the relationship between MP and VR with in-hospital mortality. Results: We included 91 patients. There was a statistically significant difference in MP measurements between survivors and nonsurvivors only in the last prone position (p < 0.001). This is due to the significant increase in MP measurements in nonsurvivors (difference from the baseline: 3.63 J/min; 95% CI: 0.31 to 6.94), which was not observed in the group that survived (difference from the baseline: 0.02 J/min; 95% CI: -2.66 to 2.70). In multivariate analysis, MP (p=0.009) was associated with hospital death when corrected for confounder variables (SAPS 3 score, mechanical ventilation time, age, and number of prone sessions). Conclusions: MP is an independent predictor of mortality in PP patients with CARDS.

Influence of radiologic pattern and the presence of diffuse parenchymal lung disease on outcome in ventilated patients with COVID-19 pneumonia: impact on prognosis.

BACKGROUND: Suspected organising pneumonia (OP) is a common finding in patients with severe coronavirus disease 2019 (COVID-19), but the impact on outcomes of the radiological patterns of diffuse parenchymal lung disease on outcome of these patients is still uncertain. AIMS: Investigate the presence of radiological images compatible with OP and its association with clinical outcomes in patients with COVID-19 submitted to invasive mechanical ventilation (IMV). METHODS: Retrospective, unicentric cohort study composed of patients who required IMV and underwent chest computerized tomography to investigate secondary complications of COVID-19. We compared patients with radiological findings characteristic of suspected OP with those without this condition. The main outcome was hospital mortality. RESULTS: Two hundred and ten patients were included, and 65 had signals compatible with OP. All patients with suspected OP were treated with corticosteroids. There was no difference in IVM-free days until day 28 between the groups (median, 0 days; interquartile range [IQR], 0-14.8) in the group with suspected OP vs 0 days (IQR, 0-11) in the group without suspected OP (P = 0.14). In univariate analysis, the presence of suspected OP was associated with lower hospital mortality; however, after correction for potential confounding variables, it was not associated with the outcome, even after matching by propensity score in patients without this condition. CONCLUSION: OP radiologic pattern in patients with severe COVID-19 is not associated with worse outcomes.

Extubation failure and the use of noninvasive ventilation during the weaning process in critically ill COVID-19 patients / Falha de extubação e uso de ventilação não invasiva durante o processo de desmame em pacientes críticos com COVID-19

ABSTRACT Objective: To assess the outcome of extubation in COVID-19 patients and the use of noninvasive ventilation in the weaning process. Methods: This retrospective, observational, single-center study was conducted in COVID-19 patients aged 18 years or older who were admitted to an intensive care unit between April 2020 and December 2021, placed under mechanical ventilation for more than 48 hours and progressed to weaning. Early extubation was defined as extubation without a spontaneous breathing trial and immediate use of noninvasive ventilation after extubation. In patients who underwent a spontaneous breathing trial, noninvasive ventilation could be used as prophylactic ventilatory assistance when started immediately after extubation (prophylactic noninvasive ventilation) or as rescue therapy in cases of postextubation respiratory failure (therapeutic noninvasive ventilation). The primary outcome was extubation failure during the intensive care unit stay. Results: Three hundred eighty-four extubated patients were included. Extubation failure was observed in 107 (27.9%) patients. Forty-seven (12.2%) patients received prophylactic noninvasive ventilation. In 26 (6.8%) patients, early extubation was performed with immediate use of noninvasive ventilation. Noninvasive ventilation for the management of postextubation respiratory failure was administered to 64 (16.7%) patients. Conclusion: We found that COVID-19 patients had a high rate of extubation failure. Despite the high risk of extubation failure, we observed low use of prophylactic noninvasive ventilation in these patients.

RESUMO Objetivo: Avaliar o desfecho da extubação em pacientes com COVID-19 e o uso da ventilação não invasiva no processo de desmame. Métodos: Este estudo retrospectivo, observacional e unicêntrico foi realizado em pacientes com COVID-19 com 18 anos ou mais, internados em uma unidade de terapia intensiva entre abril de 2020 e dezembro de 2021, colocados sob ventilação mecânica por mais de 48 horas com progressão para o desmame. A extubação precoce foi definida como a extubação sem um teste de ventilação espontânea e com uso imediato de ventilação não invasiva após a extubação. Em pacientes submetidos a um teste de ventilação espontânea, a ventilação não invasiva poderia ser usada como assistência ventilatória profilática, quando iniciada imediatamente após a extubação (ventilação não invasiva profilática), ou como terapia de resgate em casos de insuficiência respiratória pós-extubação (ventilação não invasiva terapêutica). O desfecho primário foi falha de extubação durante a internação na unidade de terapia intensiva. Resultados: Foram incluídos 384 pacientes extubados. A falha de extubação foi observada em 107 (27,9%) pacientes. Quarenta e sete (12,2%) pacientes receberam ventilação não invasiva profilática. Em 26 (6,8%) pacientes, a extubação precoce foi realizada com o uso imediato de ventilação não invasiva. A ventilação não invasiva para o manejo da insuficiência respiratória pós-extubação foi administrada em 64 (16,7%) pacientes. Conclusão: Os pacientes com COVID-19 apresentaram alta taxa de falha de extubação. Apesar do alto risco de falha de extubação, observamos baixo uso de ventilação não invasiva profilática nesses pacientes.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study

ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.

Reconstrução escrotal após gangrena de Fournier / Scrotal reconstruction after Fournier's gangrene

Introdução: Gangrena de Fournier é uma infecção polibacteriana, geralmente causada por bactérias anaeróbias e aeróbias, sendo caracterizada por fasciite necrosante escrotal e perineal. Seu tratamento é embasado em intervenção cirúrgica com excisão da área necrótica e antibioticoterapia precoces. Diversas são as estratégias de reconstrução do defeito resultante do desbridamento, devendo ser salientado que perdas teciduais maiores do que 50% costumam ser reconstruídas com retalhos. Métodos: Análise retrospectiva da série de casos de reconstrução escrotal após gangrena de Fournier procedidos pelos autores ao longo de 2020, totalizando oito pacientes. Resultados: O retalho mais utilizado foi o fasciocutâneo de coxa, que apresentou taxa de necrose parcial de 14,29%, sem necrose total. Em um dos casos foi possível reconstruir uma uretra esponjosa com músculo grácil sem fistulização, evitando que o paciente fosse submetido a uma uretrostomia definitiva. Quanto às complicações, foi comum a ocorrência de intercorrências menores que necessitaram de procedimentos revisionais simples. Destaca-se a prevalência de 75% de diabetes mellitus em nossa casuística, o que pode ter interferido negativamente no processo cicatricial. Conclusão: A reconstrução escrotal com retalhos é importante para acelerar a cicatrização da ferida proveniente do desbridamento de gangrena de Fournier e para manter o aspecto de bolsa necessário para a termorregulação do testículo. Nossa opção primária foi o retalho fasciocutâneo de coxa, que se mostrou seguro. Pequenas intercorrências foram frequentes nesta série, sem comprometimento do resultado final.

Introduction: Fournier's gangrene is a polybacterial infection, usually caused by anaerobic and aerobic bacteria, characterized by scrotal and perineal necrotizing fasciitis. Its treatment is based on surgical intervention by excision of the necrotic area and early antibiotic therapy. There are several strategies to reconstruct the defect resulting from debridement, and it should be noted that tissue losses greater than 50% are usually reconstructed with flaps. Methods: Retrospective analysis of the series of cases of scrotal reconstruction after Fournier's gangrene performed by the authors throughout 2020, totaling eight patients. Results: The most used flap was thigh fasciocutaneous flap, which presented a partial necrosis rate of 14.29%, without total necrosis. In one of the cases, it was possible to reconstruct a spongy urethra with gracilis muscle without fistulization, preventing the patient from undergoing a definitive urethrostomy. As for complications, the occurrence of minor complications that required simple revision procedures was common. The prevalence of 75% of diabetes mellitus in our series is highlighted, which may have negatively interfered with the healing process. Conclusion: Scrotal reconstruction with flaps is important to accelerate wound healing from Fournier gangrene debridement and to maintain the pouch aspect necessary for testicular thermoregulation. Our primary option was thigh fasciocutaneous flap, which proved to be safe. And minor complications were frequent in this series, without compromising the final result.

Quantitative G6PD Deficiency Screening in Routine Malaria Diagnostic Units in the Brazilian Amazon (SAFEPRIM): An Operational Mixed-Methods Study.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most Plasmodium vivax endemic areas, despite the risk of primaquine-associated hemolysis. This is due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed. METHODS AND FINDINGS: This mixed-methods operational study was aimed at implementing the quantitative point-of-care StandardTM G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286 P. vivax cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients. INTERPRETATION: Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.

Translation and Cross-Cultural Adaptation of the "Early Support Monitoring Protocol".

Parents are required to make various decisions after a child's hearing loss diagnosis. With that in mind, one of the researchers of this study, the father of a child with deaf, did not find any available instrument in the Brazilian literature to support was found to the decision-making process for parents. Considering the importance of assisting parents, caretakers, and professionals who work with Deaf and Hard of Hearing children to monitor and assess the child's development, this work aims to translate and adapt a monitoring protocol for professionals and parents. For this, we translated and cross-culturally adapted 452 items of the Early Support instrument. The items corresponded to the domains of communication, attention, listening, and vocalization. We selected 25% of the items to be assessed by specialists, which were divided into the categories: (1) cultural adequacy; (2) concept presented; and (3) target audience adequacy. A reverse translation was conducted in this stage of the research. After compiling the data and correcting the probable translation errors, it was possible to analyze the items that were not included in the specialists' assessment and propose an assessment with new items. Afterward, the translated items were compared with the reviewed version of the instrument (Success From the Start), which comprises 347 items of the two development domains.

Epidemiological profile of dog attacks to patients under 14 years old assisted at the pediatric referral emergency unit of a tertiary hospital in Campinas, Brazil.

Introduction: Accidents involving dog attacks are very common, which makes this type of accident a global public health issue. The estimates point to 20% of the victims of such accidents seeking care in health units, and half of them being children. In addition to acute injuries, dog attacks might result in fractures, infections, scars, and psychological traumas. This study aimed to describe the epidemiological profile of dog attacks to children under 14 years old assisted in a pediatric emergency service in Brazil. Methods: The database of the Information and Toxicological Assistance Center of Campinas was surveyed to identify cases of children under 14 years old assisted after a dog attack in a 9-years period. Demographic data, number and type of lesions, type of exposure, part of the body affected, dog origin and condition, and the accident location and cause were analyzed. The data were presented in a descriptive way, and the age groups were classified as follows: 0-3 years old, 4-6 years old, and 7-14 years old. The different age groups were compared one to another regarding the markers evaluated using the chi-square test and the Fisher's exact test. A 0.05 alpha was adopted in all analyses. Results: The number of children assisted in the study period totaled 1,012. The 7-14-year-old group was the most affected (n = 498; 49.2%), male patients were also majority (n = 660; 65.2%). Most injuries were found on the head/neck area (n = 378; 37.4%). However, the older the patients were, the higher the frequency of lesions on upper and lower limbs was, as well as attacks occurred in external environments, thus involving animals that could not be observed. A significant increase in accidents with provoked causes was observed in younger patients. Conclusion: Accidents involving dog attacks are more likely to happen among boys. Younger children run higher risks of becoming victims of these accidents inside homes, being attacked by pets, and showing a greater incidence of head and neck lesions. Older children present more injuries on their limbs, which are caused by dogs that cannot be observed.

Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil.

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.

An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches.

Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia, inflammation and oxidative stress as important factors for MS establishment and progression. Alterations in adipokine levels may favour glucotoxicity and lipotoxicity which, in turn, contribute to inflammation and cellular stress responses within the adipose, pancreatic and liver tissues, in addition to hepatic steatosis. The multiple mechanisms of MS make its clinical management difficult, involving both non-pharmacological and pharmacological interventions. Transient receptor potential (TRP) channels are non-selective calcium channels involved in a plethora of physiological events, including energy balance, inflammation and oxidative stress. Evidence from animal models of disease has contributed to identify their specific contributions to MS and may help to tailor clinical trials for the disease. In this context, the oxidative stress sensors TRPV1, TRPA1 and TRPC5, play major roles in regulating inflammatory responses, thermogenesis and energy expenditure. Here, the interplay between these TRP channels and oxidative stress in MS is discussed in the light of novel therapies to treat this syndrome.

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI).

Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

Vasorelaxant Activity of AP39, a Mitochondria-Targeted H2S Donor, on Mouse Mesenteric Artery Rings In Vitro.

Mitochondria-targeted hydrogen sulfide (H2S) donor compounds, such as compound AP39, supply H2S into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery. Protein and gene expressions of the H2S-producing enzymes (CBS, CSE, and 3MPST) were respectively analyzed by Western blot and qualitative RT-PCR, as well the in vitro production of H2S by mesenteric artery homogenates. Gene expression of CSE and 3MPST in the vessels has been evidenced by RT-PCR experiments, whereas the protein expression of all the three enzymes was demonstrated by Western blotting experiments. Nonselective inhibition of H2S-producing enzymes by AOAA abolished H2S production, whereas it was partially inhibited by PAG (a CSE selective inhibitor). Vasorelaxation promoted by AP39 and its H2S-releasing moiety (ADT-OH) were significantly reduced after endothelium removal, specifically dependent on NO-cGMP signaling and SKCa channel opening. Endogenous H2S seems to participate in the mechanism of action of AP39, and glibenclamide-induced KATP blockade did not affect the vasorelaxant response. Considering the results of the present study and the previously demonstrated antioxidant and bioenergetic effects of AP39, we conclude that mitochondria-targeted H2S donors may offer a new promising perspective in cardiovascular disease therapeutics.

Fever is associated with earlier antibiotic onset and reduced mortality in patients with sepsis admitted to the ICU.

To evaluate the association of body temperature with mortality in septic patients admitted to the ICU from the ward. In addition, we intend to investigate whether the timing of antibiotic administration was different between febrile and afebrile patients and whether this difference contributed to mortality. This is a retrospective cohort study that included sepsis patients admitted to the ICU from the ward between July 2017 and July 2019. Antibiotic administration was defined as the initiation of antimicrobial treatment or the expansion of the antimicrobial spectrum within 48 h prior to admission to the ICU. Regarding vital signs, the most altered vital sign in the 48 h prior to admission to the ICU was considered. Two hundred and eight patients were included in the final analysis. Antibiotic administration occurred earlier in patients with fever than in patients without fever. Antibiotic administration occurred before admission to the ICU in 27 (90.0%) patients with fever and in 101 (64.7%) patients without fever (p = 0.006). The mortality rate in the ICU was 88 in 176 (50.0%; 95% CI 42.5-57.5%) patients without fever and 7 in 32 (21.9%; 95% CI 6.7-37.0%) patients with fever (p = 0.004). In the multivariate analysis, absence of fever significantly increased the risk of ICU mortality (OR 3.462; 95% CI 1.293-9.272). We found an inverse association between body temperature and mortality in patients with sepsis admitted to the ICU from the ward. Although antibiotic administration was earlier in patients with fever and precocity was associated with reduced mortality, the time of antibiotic administration did not fully explain the lower mortality in these patients.

Understanding UX Better: A New Technique to Go beyond Emotion Assessment.

User experience (UX) is a quality aspect that considers the emotions evoked by the system, extending the usability concept beyond effectiveness, efficiency, and satisfaction. Practitioners and researchers are aware of the importance of evaluating UX. Thus, UX evaluation is a growing field with diverse approaches. Despite various approaches, most of them produce a general indication of the experience as a result and do not seek to capture the problem that gave rise to the bad UX. This information makes it difficult to obtain relevant results to improve the application, making it challenging to identify what caused a negative user experience. To address this gap, we developed a UX evaluation technique called UX-Tips. This paper presents UX-Tips and reports two empirical studies performed in an academic and an industrial setting to evaluate it. Our results show that UX-Tips had good performance in terms of efficiency and effectiveness, making it possible to identify the causes that led to a negative user experience, and it was easy to use. In this sense, we present a new technique suitable for use in both academic and industrial settings, allowing UX evaluation and finding the problems that may lead to a negative experience.