Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial.

SARS-CoV-2 and its different variants caused a "wave and wave" pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI - 0.74 [- 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI - 0.28 [0.1-0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

Assessment of cardiovascular alterations and catecholamines serum concentration after oral surgery in patients receiving local anesthetics with epinephrine: a randomized, blind, controlled clinical trial.

OBJECTIVES: A randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100,000. MATERIALS AND METHODS: Twenty patients were divided into control (CG - normotensive patients) and experimental groups (EG - hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (SO2), systolic and diastolic blood pressure (SBP and DBP), serum catecholamine concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans, and final). Blood samples were taken to measure the catecholamines, and a Holter device was used to measure data from the electrocardiogram including a 24-h postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups, and the Friedman test with the adjusted Wilcoxon posttest was used for intragroup evaluation for repeated measures. RESULTS: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES was higher for the EG during the 24-h postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystole evaluation showed that the 24-h postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups. CONCLUSIONS: Teeth extraction with LAVC can be safely executed in hypertensive patients. Blood pressure should be monitored in these patients since the sysBP presented significant differences during the surgical procedures. Cardiac arrhythmia and the serum catecholamines concentration levels seem not to be altered by the surgical procedure. Also, serum catecholamines do not influence cardiovascular changes in this type of surgery. CLINICAL RELEVANCE: LAVC can be safely used in hypertensive patients and does not increase the risk of arrhythmias or cardiac ischemia.

Fracture in Irradiated Rat Femur: A Description of an Experimental Model and Evaluation of its Effectiveness.

Objective We aim to describe an experimental model for studying femoral fractures in rats after exposure to ionizing radiation, demonstrating a way to apply a substance for analysis, the method for patterning fracture and irradiation, and how to evaluate its effectiveness based on radiographic studies. Methods We used 24 rats divided into 2 groups of 12 animals each. The STUDY group was exposed to ionizing radiation and treated with saline solution, and the CONTROL group was not exposed to radiation and was treated with saline solution. All animals were subjected to standardized fracture of the right femur that was fixed with intramedullary wire. The efficiency of the bone union was assessed by radiographic exam. Results Fracture healing was more efficient in bones not exposed to ionizing radiation ( p = 0.012). All fractures met the criteria of being simple, diaphyseal, transverse or short oblique. Conclusion The experimental model presented is an efficient alternative for the study of fractures in irradiated bones in rats.

Inflammation in Coronary Atherosclerosis: Insights into Pathogenesis and Therapeutic Potential of Anti-Inflammatory Drugs.

Atherosclerosis is a lipid-driven immune-inflammatory disease that affects the arteries, leading to multifocal plaque development. The inflammatory process involves the activation of immune cells and various inflammatory pathways. Anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events in individuals with coronary disease. However, their use is still limited due to concerns about long-term follow-up, cost-effectiveness, adverse effects, and the identification of the ideal patient profile to obtain maximum benefits. This review aims to improve the understanding of inflammation in coronary atherosclerosis and explore potential therapeutic interventions, encompassing both traditional and non-traditional anti-inflammatory approaches. By addressing these concepts, we seek to contribute to the advancement of knowledge about this type of treatment for coronary artery disease.

Fracture in Irradiated Rat Femur: A Description of an Experimental Model and Evaluation of its Effectiveness / Fratura em fêmur irradiado de rato: Descrição de um modelo experimental e avaliação de sua eficácia

Abstract Objective We aim to describe an experimental model for studying femoral fractures in rats after exposure to ionizing radiation, demonstrating a way to apply a substance for analysis, the method for patterning fracture and irradiation, and how to evaluate its effectiveness based on radiographic studies. Methods We used 24 rats divided into 2 groups of 12 animals each. The STUDY group was exposed to ionizing radiation and treated with saline solution, and the CONTROL group was not exposed to radiation and was treated with saline solution. All animals were subjected to standardized fracture of the right femur that was fixed with intramedullary wire. The efficiency of the bone union was assessed by radiographic exam. Results Fracture healing was more efficient in bones not exposed to ionizing radiation (p = 0.012). All fractures met the criteria of being simple, diaphyseal, transverse or short oblique. Conclusion The experimental model presented is an efficient alternative for the study of fractures in irradiated bones in rats.

Resumo Objetivo Nosso objetivo é descrever um modelo experimental para estudo de fraturas de fêmur em ratos após exposição a radiação ionizante, demonstrando uma forma de aplicação de uma substância para análise, o método de padronização de fratura e irradiação e a forma de avaliação de sua eficácia com base em estudos radiográficos. Métodos Utilizamos 24 ratos divididos em dois grupos de 12 animais cada. O grupo ESTUDO foi exposto à radiação ionizante e tratado com soro fisiológico, enquanto o grupo CONTROLE não foi exposto à radiação e foi tratado com soro fisiológico. Todos os animais foram submetidos à fratura padronizada do fêmur direito e sua fixação com fio intramedular. A eficácia da consolidação óssea foi determinada por exame radiográfico. Resultados A cicatrização de fraturas foi mais eficiente em ossos não expostos à radiação ionizante (p = 0,012). Todas as fraturas atenderam aos critérios de serem simples, diafisárias, transversas ou oblíquas curtas. Conclusão O modelo experimental apresentado é uma boa alternativa para o estudo de fraturas em ossos irradiados em ratos.

Effectiveness of thiazide and thiazide-like diuretics in advanced chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thiazide diuretics are first-line drugs for the treatment of hypertension, but hypertension treatment guidelines have systematically discouraged their use in patients with advanced chronic kidney disease (CKD). For the first time, a systematic review and random-effects meta-analysis were performed to assess the effectiveness of thiazides and thiazide-like diuretics to treat hypertension in patients with stages 3b, 4, and 5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review and random-effects meta-analysis that included a literature search using the following databases were performed: MEDLINE through PubMed, Cochrane Database of Systematic Reviews (CDSR) and Cochrane Central Register of Controlled Trials (CENTRAL) through the Cochrane Library, Embase, and ISI - Web of Science (all databases). Prospective studies that evaluated the effectiveness of thiazide and thiazide-like diuretics in individuals with a GFR < 45 mL/min/1.73 m2 were included. RESULTS: Five clinical trials, totaling 214 participants, were included, and the mean GFR ranged from 13.0 ± 5.9 mL/min/1.73 m2 to 26.8 ± 8.8 mL/min/1.73 m2. There was evidence of a reduction in mean blood pressure and in GFR, as well as in fractional sodium excretion and fractional chloride excretion. CONCLUSION: Thiazide and thiazide-like diuretics seem to maintain their effectiveness in lowering blood pressure in patients with advanced chronic kidney disease. These findings should spur new prospective randomized trials and spark discussions, particularly about upcoming hypertension guidelines.

Intrinsic foot strengthening and electrostimulation in older adults - Randomized clinical trial / Fortalecimento intrínseco do pé e eletroestimulação em idosos - Ensaio clínico randomizado

Abstract Introduction Aging reduces functional capacity related to reduced toe plantar flexion strength. The exercise for strengthening the foot's intrinsic muscles can be optimized using electrostimulation. Due to the scarcity of data in the literature on these methods, further studies are necessary. Objective To evaluate and compare the effects of training to strengthen the foot's intrinsic muscles on the risk of falls in older adults. Methods This is a randomized clinical trial with 19 older patients allocated into three groups: control (CG; n = 7), exercise (EG; n = 6), and exercise+electrostimulation (EEG; n = 6). The EG received an exercise protocol for the foot's intrinsic muscles, the EEG received the same protocol with Neuromuscular electrical stimulation (NMES), and the CG received guidance regarding preventing falls. The individuals were evaluated before and after the intervention using the Single-Limb balance test (SLBT), Functional Reach Test (FRT), Timed Up and Go (TUG), and Paper Grip Test (PGT) tests. One and two-way ANOVA was used for the statistical analysis. Statistical significance was set at p < 0.05. Results There was a significant improvement in the TUG test (9.64 ± 1.78 vs. 8.20 ± 1.94) in relation to the EG. With the EEG, there was an improvement both in the TUG (12.68 ± 4.01 vs. 10.61 ± 3.70) and in the FRT (26.37 ± 7.66 vs. 33.14±9.73) with p < 0.05). Conclusion An exercise protocol associated with electrostimulation improves performance in func-tional and dynamic balance tests in older adults.

Resumo Introdução O envelhecimento reduz a capacidade fun-cional, que está relacionada com a redução de força muscular de flexão plantar dos dedos dos pés. O exercício de fortalecimento da musculatura intrínseca do pé pode ser otimizado com o uso da eletroestimulação eletro (EENM). Devido à escassez de dados na literatura sobre a utilização desses métodos, torna-se necessário realizar novos estudos. Objetivo Avaliar e comparar os efeitos do treino de fortalecimento da musculatura intrínseca do pé no risco de queda em idosos. Métodos Trata-se de um ensaio clínico randomizado, no qual 19 idosos foram alocados em três grupos: controle (GC; n = 7), exercício (GE; n = 6) e exercício+eletroestimulação (GEE; n = 6). O GE recebeu um protocolo de exercícios para a musculatura intrínseca do pé, o GEE recebeu o mesmo protocolo seguido de EENM e o GC recebeu orientações quanto à prevenção de quedas. Os indivíduos foram avaliados antes e após a intervenção através dos testes de Apoio Unipodal , Teste de Alcance Funcional (TAF), Timed Up and Go (TUG) e Paper Grip Test (PGT). Para a análise estatística, utilizou-se ANOVA 1 e 2 vias. Considerou-se estatisticamente significante um valor de p < 0,05. Resultados Observou-se melhora significativa no teste TUG (9,64 ± 1,78 vs 8,20 ± 1,94) em relação ao GE. Em relação ao GEE, houve melhora tanto no TUG (12,68 ± 4,01 vs 10,61 ± 3,70) quanto no TAF (26,37 ± 7,66 vs 33,14 ± 9,73). Conclusão Conclui-se que um protocolo de exercício associado à eletroestimulação melhora o desempenho nos testes de equilíbrio funcional e equilíbrio dinâmico em indivíduos idosos.

Effects of Standardized Brazilian Green Propolis Extract (EPP-AF®) on Inflammation in Haemodialysis Patients: A Clinical Trial.

Background: Patients on haemodialysis (HD) present a significant inflammatory status, which has a pronounced negative impact on their outcomes. Propolis is a natural resin with anti-inflammatory and immunomodulatory properties. We assessed the safety and impact of a standardized Brazilian green propolis extract (EPP-AF®) on the inflammatory status in patients under conventional HD. Methods: Patients were assigned to receive 200 mg/day of EPP-AF® for 4 weeks followed by 4 weeks without the drug, and changes in plasma levels of interleukins (ILs), interferon gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), and high-sensitivityc-reactive protein (HsCRP) were measured. A heatmap was used to illustrate trends in data variation. Results: In total, 37 patients were included in the final analysis. Patients presented an exacerbated inflammatory state at baseline. During EPP-AF® use, there was a significant reduction in IFN-γ (p=0.005), IL-13 (p=0.04 2), IL-17 (p=0.039), IL-1ra (p=0.008), IL-8 (p=0.009), and TNF-α (p < 0.001) levels compared to baseline, and significant changes were found in Hs-CRP levels. The heatmap demonstrated a pattern of pronounced proinflammatory status at baseline, especially in patients with primary glomerulopathies, and a clear reduction in this pattern during the use of EPP-AF®. There was a tendency to maintain this reduction after suspension of EPP-AF®. No significant side effects were observed. Conclusion: Patients under haemodialysis presented a pronounced inflammatory status, and EPP-AF® was demonstrated to be safe and associated with a significant and maintained reduction in proinflammatory cytokines in this population. This trial is registered with Clinicaltrials.gov NCT04072341.

Acute kidney injury and electrolyte disorders in COVID-19.

Acute kidney injury (AKI) and electrolyte disorders are important complications of hospitalized coronavirus disease 2019 (COVID-19) patients. AKI is thought to occur due to multiple pathophysiological mechanisms, such as multiple organ dysfunction (mainly cardiac and respiratory), direct viral entry in the renal tubules, and cytokine release syndrome. AKI is present in approximately one in every ten hospitalized COVID-19 patients. The incidence rates of AKI increase in patients who are admitted to the intensive care unit (ICU), with levels higher than 50%. Additionally, renal replacement therapy (RRT) is used in 7% of all AKI cases, but in nearly 20% of patients admitted to an ICU. COVID-19 patients with AKI are considered moderate-to-severe cases and are managed with multiple interdisciplinary conducts. AKI acts as a risk factor for mortality in severe acute respiratory syndrome coronavirus 2 infection, especially when RRT is needed. Electrolyte disorders are also common manifestations in hospitalized COVID-19 patients, mainly hyponatremia, hypokalemia, and hypocalcemia. Hyponatremia occurs due to a combination of syndrome of inappropriate secretion of antidiuretic hormone and gastrointestinal fluid loss from vomiting and diarrhea. When it comes to hypokalemia, its mechanism is not fully understood but may derive from hyperaldosteronism due to renin angiotensin aldosterone system overstimulation and gastrointestinal fluid loss as well. The clinical features of hypokalemia in COVID-19 are similar to those in other conditions. Hypocalcemia is the most common electrolyte disorder in COVID-19 and seems to occur because of vitamin D deficiency and parathyroid imbalance. It is also highly associated with longer hospital and ICU stay.

Avaliação dos padrões cardiovasculares e da concentração sérica de catecolaminas em pacientes submetidos à exodontias por via alveolar, sob anestesia local com epinefrina: um ensaio clínico controlado, cego e randomizado / Assessment of cardiovascular patterns and serum catecholamine concentration in patients undergoing alveolar extraction under local anesthesia with epinephrine: a controlled, blind and randomized clinical trial

Objetivos: Um ensaio clínico controlado, cego e randomizado foi desenvolvido para avaliar os efeitos cardiovasculares em pacientes saudáveis e com hipertensão submetidos à exodontia por via alveolar utilizando lidocaína com epinefrina 1:100.000. Materiais e métodos: Vinte pacientes foram divididos em grupos experimental (GE ­ pacientes hipertensos) e controle (GC ­ pacientes normotensos). As variáveis analisadas foram a frequência cardíaca (FC), saturação de oxigênio (SO2), pressão arterial sistólica e diastólica (PAsis e PAdias), concentração sérica de catecolaminas (dopamina, epinefrina e norepinefrina), extrassístoles ventriculares e supraventriculares (ESV e ESSV respectivamente) e depressão do segmento do ST. Os dados foram colhidos em três momentos distintos: inicial, transoperatório (trans) e final. Amostras de sangue foram coletadas para a mensuração das catecolaminas, e um aparelho de Holter foi utilizado para coleta de dados do eletrocardiograma incluindo um período de avaliação de 24 horas pós-operatório. Foram utilizados o teste de Mann-Whitney para identificar diferenças entre os grupos e o teste de Friedman com o pós-teste de Wilcoxon ajustado para a avaliação intragrupos das amostras repetidas. Resultados: O GE apresentou menor SO2 no momento inicial (p = 0,001) enquanto a PAsis apresentou diferença estatística para os três momentos de avaliação com o GE apresentando os maiores valores. As ESV foram maiores para o GE no período de avaliação pós-operatória de 24 horas (p = 0,041). As ESSV e as catecolaminas séricas foram similares nos dois grupos. A análise intragrupo revelou diferença significativa na avaliação da PAsis para o GE com o período trans operatório apresentando os maiores valores. Já avaliação das extrassístoles demonstrou que o período pós-operatório de 24 horas teve a maioria dos eventos sendo que apenas o GC não apresentou diferença significativa para a variável ESV durante esse período (p = 0,112). Não houve depressão do segmento ST para nenhum dos grupos, ou seja, a isquemia do miocárdio não foi observada durante o estudo. Conclusões: As exodontias por via alveolar, com o uso de ALVC com epinefrina podem ser realizadas de forma segura em pacientes hipertensos. A pressão arterial sistêmica deve ser monitorada durante todo o procedimento, sobretudo nos pacientes hipertensos, devido à tendência de aumento da pressão arterial nesses pacientes. Já o nível sérico de catecolaminas não sofre alteração nas condições estudadas assim como o uso de ALVC parecem não influenciar os padrões cardiovasculares nesse tipo de cirurgia (AU).

Objectives: A blind, randomized controlled clinical trial was developed to evaluate the cardiovascular effects of local anesthetics with vasoconstrictors (LAVC) containing epinephrine in healthy and hypertensive patients undergoing teeth extraction with lidocaine 2% with epinephrine 1:100.000. Materials and methods: 20 patients were divided into control (CG ­ normotensive patients) and experimental groups (EG ­ hypertensive patients). The variables analyzed were heart rate (HR), oxygen saturation (O2S), systolic and diastolic blood pressure (sysBP and diasBP), serum catecholamines concentration (dopamine, epinephrine, and norepinephrine), ventricular and supraventricular extrasystoles (VES and SVES respectively), and ST segment depression. Data was obtained in three different moments (initial, trans and final). Blood samples were taken to measure the catecholamines and a Holter device was used to measure data from the electrocardiogram including a 24-hour postoperative evaluation period. The Mann-Whitney test was used to identify differences between the two groups and the Friedman test with the adjusted Wilcoxon post-test were used for intragroup evaluation for repeated measures. Results: The EG presented a lower O2S in the initial period (p = 0,001) while the sysBP showed a statistical difference for the three evaluation periods with the EG presenting the highest values. The VES where higher for the EG during the 24-hour postoperative evaluation period (p = 0,041). The SVES and the serum catecholamines showed were similar between the groups. The intragroup analysis revealed significant statistical difference for the sysBP in the EG with the trans period presenting the highest measurements. The extrasystoles evaluation showed that the 24- hour postoperative period presented most events with only the CG not presenting statistical difference for the variable VES during this period (p = 0,112). No ST segment depression was noticed for both groups, ie, Myocardial ischemia was not observed. Conclusions: Teeth extraction with LAVC containing epinephrine can be safely executed in hypertensive patients. Blood pressure should be monitored during the entire procedure, especially in hypertensive patients due to a tendency to high blood pressure within these patients. Serum catecholamines concentration levels are not altered in the conditions seen in this study and the use of LAVC seem not to influence cardiovascular changes in this type of surgery (AU).

The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. METHODS: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). DISCUSSION: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

High frequency transcutaneous electrical stimulation in the immediate postoperative period of anterior cruciate ligament reconstruction: a randomized clinical trial / Estimulação elétrica transcutânea de alta frequência no pós operatório imediato de reconstrução do ligamento cruzado anterior: um ensaio clínico randomizado

INTRODUCTION: The anterior cruciate ligament (ACL) is an important structure for knee stability. Transcutaneous electrical nerve stimulation (TENS) is an electrical current applied for significant pain relief. OBJECTIVE: To evaluate the effects of high-frequency TENS on the immediate postoperative period of ACL reconstruction. METHODS: 46 patients in the postoperative period of ACL reconstruction were randomly assigned to a control group (CG=23) and a TENS group (TG=23). Knee range of motion (ROM), pain, muscle strength, and drug intake were assessed before surgery and 24 and 48 hours after surgery. The TENS intervention protocol started in the recovery room, shortly after surgery, and was maintained continuously for the first 48 hours after surgery. RESULTS: The TENS group (TG) significantly controlled the increased level of postoperative pain (p<0.05) and significantly increased flexion ROM (p<0.05). When compared to the Control group (CG), the TENS group had a lower intake of ketoprofen (48.27%), diazepam (256.98%), and dipyrone (121.21%), morphine (320.77%), and tramadol (437.46%). CONCLUSION: Continuous high-frequency TENS significantly reduced pain intensity and significantly improved ROM, muscle strength, and drug intake in the postoperative period of ACL reconstruction.

Risk Factors for Acute Kidney Injury and Death in Patients Infected With the Yellow Fever Virus During the 2018 Outbreak in São Paulo, Brazil.

Introduction: There have been few studies investigating acute kidney injury (AKI) in patients with yellow fever (YF). The objective of this study was to identify the risk factors for AKI and death in such patients. Methods: We evaluated 95 consecutive critically ill adult patients with the sylvatic form of YF, as confirmed by reverse-transcriptase polymerase chain reaction, in Brazil. The outcome measures were AKI (as defined by Kidney Disease: Improving Global Outcomes [KDIGO] criteria) and in-hospital death. Results: Of the 95 patients, 73 (76.8%) had AKI and 59 (62.1%) died from it. A total of 70 patients (73.7%) required dialysis because of AKI. After adjusting for age, sex, and the Simplified Acute Physiology Score 3 (SAPS 3), we found that elevated fractional excretion of sodium and requiring dialysis were independent risk factors for in-hospital mortality and that proteinuria correlated with AKI-associated mortality. Conclusion: Our findings indicate that, in patients with sylvatic YF, AKI is common and is associated with significant mortality. The data presented here could prove useful for improving understanding of the pathogenesis of AKI in YF and informing decisions regarding the care of the affected patients.

Distal Renal Tubular Acidosis Associated with Autoimmune Diseases: Reports of 3 Cases and Review of Mechanisms.

BACKGROUND Distal renal tubular acidosis (dRTA) is a defect in the urinary acidification process that limits the elimination of protons [H+] by alpha intercalated cells in the collecting tubules, with consequent metabolic acidosis with a normal plasma anion gap. The relationship between this tubulopathy and immune-mediated diseases like Sjögren syndrome, rheumatoid arthritis, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus, and thyroiditis is well known. Further, the pathophysiological mechanisms are diverse, but, unfortunately, many are not yet fully understood. We report 3 cases of dRTA in patients with different autoimmune diseases and review the pathophysiological mechanisms already described. CASE REPORT The first case involved a 29-year-old woman with autoimmune hepatitis. She had metabolic acidosis with persistent hypokalemia, and a kidney stone was also identified. The second case involved a 67-year-old woman diagnosed with rheumatoid arthritis. She had metabolic acidosis with hypokalemia. The third case involved a 30-year-old woman with Sjögren syndrome and persistent metabolic acidosis. In addition to the presence of metabolic acidosis with a normal plasma anion gap, all 3 patients exhibited urine with a supraphysiologic pH (above 5.3). CONCLUSIONS Autoimmune diseases may be associated with deficits in urinary acidification with consequent metabolic acidosis and, therefore, systemic repercussions. This association must be remembered and researched because correct diagnosis and treatment will serve to reduce complications.

Prediction of hemodynamic tolerance of intermittent hemodialysis in critically ill patients: a cohort study.

The evaluation and management of fluid balance are key challenges when caring for critically ill patients requiring renal replacement therapy. The aim of this study was to assess the ability of clinical judgment and other variables to predict the occurrence of hypotension during intermittent hemodialysis (IHD) in critically ill patients. This was a prospective, observational, single-center study involving critically ill patients undergoing IHD. The clinical judgment of hypervolemia was determined by the managing nephrologists and critical care physicians in charge of the patients on the basis of the clinical data used to calculate the ultrafiltration volume and rate for each dialysis treatment. Seventy-nine (31.9%) patients presented with hypotension during IHD. Patients were perceived as being hypervolemic in 109 (43.9%) of the cases by nephrologists and in 107 (43.1%) by intensivists. The agreement between nephrologists and intensivists was weak (kappa = 0.561). Receiver operating characteristic curve analysis yielded an AUC of 0.81 (95% CI 0.75 to 0.84; P < 0.0001), and a cutoff value of 70 mm for the vascular pedicle width (VPW) had the highest accuracy for the prediction of the absence of hypotension. The clinical judgment of hypervolemia did not predict hypotension during IHD. The high predictive ability of the VPW may assist clinicians with critical thinking.

Early recovery after surgery protocol in orthognathic surgery: a randomized, blind clinical study.

A randomized, blind and prospective clinical trial was conducted to compare two clinical rehabilitation protocols in patients submitted to orthognathic surgery, during the first 60 days after surgery. Pain, edema, mandibular movement, masticatory efficiency and quality of life were evaluated. Nineteen (19) patients were separated into control and experimental groups. The control group consisted of 10 patients followed by oral and maxillofacial surgeons and submitted to a rehabilitation protocol that involved active and passive mouth opening exercises. The experimental group had 9 patients and followed the surgeons' protocol, in addition to an Early Recovery After Surgery (ERAS) protocol performed by speech therapists, and involving specific motricity exercises and lymphatic drainage. The Student's t-test was applied to compare the results, and the Fisher's exact test of independence, to analyze the quality of life and the masticatory efficiency variables. The statistical significance was set at 5% (p < 0.05) for all the tests. The results showed that the ERAS protocol made a positive difference in pain perception in the first 14 days. However, it did not improve the other variables. Although many variables showed no significant difference, it was concluded that the surgeons can delegate patient rehabilitation to qualified professionals, so that they can optimize their postoperative clinical time.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. METHODS: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®ï¸) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. RESULTS: We enrolled 124 patients; 40 were assigned to EPP-AF®ï¸ 400 mg/day, 42 to EPP-AF®ï¸ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. CONCLUSIONS: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Evaluation of urine SARS-COV-2 RT-PCR as a predictor of acute kidney injury and disease severity in patients with critical COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began as an outbreak in Wuhan, China and has spread rapidly across the globe. Although most infections are mild, patients with severe and critical COVID-19 infections face deterioration of respiratory function and may also have extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart, and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material using reverse-transcription polymerase chain reaction in urine samples obtained from patients with COVID-19 receiving critical care. Among 51 included patients, we found higher serum creatinine levels, a longer hospital stay, and more frequent need for dialysis in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.

Using the Cecal Ligation and Puncture Model of Sepsis to Induce Rats to Multiple Organ Dysfunction.

Sepsis is a dysregulated hyperinflammatory disease caused by infection. Sepsis leads to multiple organ dysfunction syndrome (MODS), which is associated with high rates of mortality. The cecal ligation and puncture (CLP) model has been widely used in animals and has become the gold-standard method of replicating features of sepsis in humans. Despite several studies and modified CLP protocols, there are still open questions regarding the multifactorial determinants of its reproducibility and medical significance. In our protocol, which is also aimed at mimicking the sepsis observed in clinical practice, male Wistar rats are submitted to CLP with adequate fluid resuscitation (0.15 M NaCl, 25 ml/kg BW i.p.) immediately after surgery. At 6 h after CLP, additional fluid therapy (0.15 M NaCl, 25 ml/kg BW s.c.) and antibiotic therapy with imipenem-cilastatin (single dose of 14 mg/kg BW s.c.) are administered. The timing of the fluid and antibiotic therapy correspond to the initial care given when patients are admitted to the intensive care unit. This model of sepsis provides a useful platform for simulating human sepsis and could lay the groundwork for the development of new treatments.

Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis.

Sepsis is the leading cause of acute kidney injury (AKI) and lung injury worldwide. Despite therapeutic advances, sepsis continues to be associated with high mortality. Because Brazilian green propolis (GP) has promising anti-inflammatory, antioxidant, and immunomodulatory properties, we hypothesized that it would protect kidneys and lungs in rats induced to sepsis by cecal ligation and puncture (CLP). Male Wistar rats were divided into groups-control (sham-operated); CLP (CLP only); and CLP + GP (CLP and treatment with GP at 6 h thereafter)-all receiving volume expansion and antibiotic therapy at 6 h after the procedures. By 24 h after the procedures, treatment with GP improved survival, attenuated sepsis-induced AKI, and restored renal tubular function. Whole-blood levels of reduced glutathione were higher in the CLP + GP group. Sepsis upregulated the Toll-like receptor 4/nuclear factor-kappa B axis in lung and renal tissues, as well as increasing inflammatory cytokine levels and macrophage infiltration; all of those effects were attenuated by GP. Treatment with GP decreased the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells in renal and lung tissue, as well as protecting the morphology of the renal mitochondria. Our data open the prospect for clinical trials of the use of GP in sepsis.