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Hyperuricemia is a common finding in hypertensive patients, especially among those who are on diuretic therapy. However, its clinical relevance regarding cardiovascular and chronic kidney disease (CKD) has not clearly been established. The authors assessed whether, in a population of 385 hypertensive women categorized according to diuretic therapy, the stratification in quartiles by uric acid levels would identify a gradient of changes in renal function and in risk factors for cardiovascular disease. The following were evaluated: serum uric acid, glycemia, total and fractional cholesterol, triglycerides, apolipoprotein (Apo) B, Apo A-I, and C-reactive protein. Renal function was assessed by serum creatinine, albuminuria, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation, whereas cardiovascular risk was estimated through the Framingham score. A total of 246 women were on diuretic therapy; 139 were taking other antihypertensive medications. There was a reduction in eGFR parallel to the increase in uric acid levels, regardless of diuretic use and without a concomitant increase in albuminuria. In both groups, higher uric acid levels translated into an increase in metabolic syndrome components, in markers of insulin resistance, triglyceride / high-density lipoprotein levels, and Apo B/Apo A-I ratios, as well as in Framingham scores. Hyperuricemia was associated with an increase in inflammatory markers only in patients on diuretic therapy. In a binary logistic regression, hyperuricemia (uric acid >6.0 mg/ dL) was independently associated with CKD (eGFR <60 mL/ min / 1.73 m(2)) (odds ratio, 2.63; 95% confidence interval, 1.61-4.3; P<.001). In hypertensive women, the presence of hyperuricemia indicated a substantial degree of kidney dysfunction as well as a greater cardiovascular risk profile. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play a critical role in the functional competence of sperm cells. Conversely, excessive generation of ROS can impair sperm function, including their fertilization ability. Urolithin A (UA), a gut bacteria-derived metabolite produced from the transformation of ellagitannins, with anti-aging and antioxidant properties, was investigated for the first time in bovine sperm cells in the present study. Firstly, different doses of UA (0, 1, and 10 μM; 8-16 sessions) were used during the capacitation process of frozen-thawed bovine sperm. Sperm motility was assessed using optical microscopy and CASA. Sperm vitality (eosin-nigrosin), ROS, and ATP levels, as well as mitochondrial membrane potential (JC1) and oxygen consumption were evaluated. A second experiment to test the effect of different doses of UA (0, 1, and 10 μM; 9 sessions) in both the capacitation medium, as above, and the fertilization medium, was also implemented. The embryonic development and quality were evaluated. UA, at a concentration of 1 μM, significantly improved sperm movement quality ( p < 0.03). There was a trend towards an increase in the oxygen consumption rate (OCR) of capacitated sperm with 1 μM and 10 μM UA supplementation. Moreover, an increase in ATP levels ( p < 0.01) was observed, accompanied by a reduction in ROS levels at the higher UA concentration. These results suggest that UA may enhance spermatozoa mitochondrial function, modifying their metabolic activity while reducing the oxidative stress. Also, the number of produced embryos appears to be positively affected by UA supplementation, although differences between the bulls may have mitigated this effect. In conclusion, presented results further support previous findings indicating the potential therapeutic value of UA for addressing reproductive sub/infertility problems and improving ART outcomes. In addition, our results also reinforce the important bull effect on ART and that male sperm bioenergetic parameters should be used to predict spermatozoa functionality and developmental potential.

Background: Over the last 3 decades, over 700 million individuals worldwide have been diagnosed with chronic kidney disease (CKD). In a 2017 survey in southern Brazil, 11.4% of those surveyed had CKD. Early identification and effective therapy in Brazil may reduce CKD's impact. This panel discusses the early diagnosis and treatment of CKD and the barriers and actions needed to improve the management of CKD in Brazil. A panel of Brazilian nephrologists was provided with relevant questions to address before a multiday conference. During this meeting, each narrative was discussed and edited through several rounds until agreement on the relevant topics and recommendations was achieved., Summary: Panelists highlighted hurdles to early diagnosis and treatment of CKD. These include, but are not limited to, a lack of public and patient education, updated recommendations, multidisciplinary CKD treatment, and a national CKD database. People-centered, physician-centered, and healthcare institution-centered actions can be taken to improve outcomes. Patient empowerment is needed via multiple channels of CKD education and access to health-monitoring wearables and apps. Primary care clinicians and nonspecialists must be trained to screen and manage CKD-causing illnesses, including diabetes and hypertension. The healthcare system may implement a national health data gathering system, more screening tests, automated test result reporting, and telehealth., Key Messages: Increasing access to early diagnosis can provide a path to improving care for patients with CKD. Concerted efforts from all stakeholders are needed to overcome the barriers., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The use of regional citrate anticoagulation (RCA) in liver failure (LF) patients can lead to citrate accumulation. We aimed to evaluate serum levels of citrate and correlate them with liver function markers and with the Cat/Cai in patients under intensive care and undergoing continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA). A prospective cohort study in an intensive care unit was conducted. We compared survival, clinical, laboratorial and dialysis data between patients with and without LF. Citrate was measured daily. We evaluated 200 patients, 62 (31%) with LF. Citrate was significantly higher in the LF group. Dialysis dose, filter lifespan, systemic ionized calcium and Cat/Cai were similar between groups. There were weak to moderate positive correlations between Citrate and indicators of liver function and Cat/Cai. The LF group had higher mortality (70.5% vs. 51.8%, p = 0.014). Citrate was an independent risk factor for death, OR 11.3 (95% CI 2.74-46.8). In conclusion, hypercitratemia was an independent risk factor for death in individuals undergoing CVVHDF-ARC. The increase in citrate was limited in the LF group, without clinical significance. The correlation between citrate and liver function indicators was weak to moderate., (© 2023. The Author(s).)

Background: Acute kidney injury is a common complication in solid organ transplants, notably liver transplantation. The MELD is a score validated to predict mortality of cirrhotic patients, which is also used for organ allocation, however the influence of this allocation criteria on AKI incidence and mortality after liver transplantation is still uncertain., Methods: This is a retrospective single center study of a cohort of patients submitted to liver transplant in a tertiary Brazilian hospital: Jan/2002 to Dec/2013, divided in two groups, before and after MELD implementation (pre-MELD and post MELD). We evaluate the differences in AKI based on KDIGO stages and mortality rates between the two groups., Results: Eight hundred seventy-four patients were included, 408 in pre-MELD and 466 in the post MELD era. The proportion of patients that developed AKI was lower in the post MELD era (p 0.04), although renal replacement therapy requirement was more frequent in this group (p < 0.01). Overall mortality rate at 28, 90 and 365 days was respectively 7%, 11% and 15%. The 1-year mortality rate was lower in the post MELD era (20% vs. 11%, p < 0.01). AKI incidence was 50% lower in the post MELD era even when adjusted for clinically relevant covariates (p < 0.01)., Conclusion: Liver transplants performed in the post MELD era had a lower incidence of AKI, although there were more cases requiring dialysis. 1-year mortality was lower in the post MELD era, suggesting that patient care was improved during this period., (© 2022. The Author(s).)

Plants subjected to stress need to respond rapidly and efficiently to acclimatize and survive. In this paper, we investigated a selected gene set potentially involved in early cell reprogramming in two rice genotypes with contrasting salinity tolerance (Pokkali tolerant and IR29 susceptible) in order to advance knowledge of early molecular mechanisms of rice in dealing with salt stress. Selected genes were evaluated in available transcriptomic data over a short period of 24 h and involved enzymes that avoid ROS formation (AOX, UCP and PTOX), impact ATP production (PFK, ADH and COX) or relate to the antioxidant system. Higher transcript accumulation of AOX (ROS balancing), PFK and ADH (alcohol fermentation) was detected in the tolerant genotype, while the sensitive genotype revealed higher UCP and PTOX transcript levels, indicating a predominant role for early transcription of AOX and fermentation in conferring salt stress tolerance to rice. Antioxidant gene analyses supported higher oxidative stress in IR29, with transcript increases of cytosolic CAT and SOD from all cell compartments (cytoplasm, peroxisome, chloroplast and mitochondria). In contrast, Pokkali increased mRNA levels from the AsA-GSH cycle as cytosolic/mitochondrial DHAR was involved in ascorbate recovery. In addition, these responses occurred from 2 h in IR29 and 10 h in Pokkali, indicating early but ineffective antioxidant activity in the susceptible genotype. Overall, our data suggest that AOX and ADH can play a critical role during early cell reprogramming for improving salt stress tolerance by efficiently controlling ROS formation in mitochondria. We discuss our results in relation to gene engineering and editing approaches to develop salinity-tolerant crops.

The performance (development and reproduction) of generalist predators can vary greatly among the prey species that they use, and these differences can influence the ability of predatory insects to suppress pest populations. The aim of this study was to compare the performance of larvae of the green lacewing Chrysoperla rufilabris (Burmeister, 1839) by offering 16 species of aphids and by assessing the effects of each species on the survival, larval development time, prey consumption, pupal mass and egg load of adult Chr. rufilabris females taking aphid phylogeny into account. Chrysoperla rufilabris larvae preyed on individuals from all 16 aphid species, but complete development, adult emergence and egg load production were achieved only in seven species. As a general pattern, the best levels of performance were achieved for an aphid clade that includes the soybean aphid, Aphis glycines (Matsumara, 1917), and for a milkweed-feeding species, Myzocallis asclepiadis (Monell, 1879). We found significant phylogenetic clustering for most of the performance traits indicating the aspects of specialization in the diet breadth of Chr. rufilabris despite the fact that this species is considered a generalist aphid predator. These findings can help us to understand the interactions of this species in agroecological food webs, where it is commonly found, and provide insights into why natural, conservation biological control or augmentative releases may succeed or fail.

Objective: To evaluate anthropometric and clinical data, muscle mass, subcutaneous fat, spine bone mineral density, extent of acute pulmonary disease related to COVID-19, quantification of pulmonary emphysema, coronary calcium, and hepatic steatosis using chest computed tomography of hospitalized patients with confirmed diagnosis of COVID-19 pneumonia and verify its association with disease severity., Methods: A total of 123 adults hospitalized due to COVID-19 pneumonia were enrolled in the present study, which evaluated the anthropometric, clinical and chest computed tomography data (pectoral and paravertebral muscle area and density, subcutaneous fat, thoracic vertebral bodies density, degree of pulmonary involvement by disease, coronary calcium quantification, liver attenuation measurement) and their association with poorer prognosis characterized through a combined outcome of intubation and mechanical ventilation, need of intensive care unit, and death., Results: Age (p=0.013), body mass index (p=0.009), lymphopenia (p=0.034), and degree of pulmonary involvement of COVID-19 pneumonia (p<0.001) were associated with poor prognosis. Extent of pulmonary involvement by COVID-19 pneumonia had an odds ratio of 1,329 for a poor prognosis and a cutoff value of 6.5 for increased risk, with a sensitivity of 64.9% and specificity of 67.1%., Conclusion: The present study found an association of high body mass index, older age, extent of pulmonary involvement by COVID-19, and lymphopenia with severity of COVID-19 pneumonia in hospitalized patients.

Background: The mortality rate of diabetic patients on dialysis is higher than that of non-diabetic patients. Asymmetric dimethylarginine and inflammation are strong predictors of death in hemodialysis. This study aimed to evaluate asymmetric dimethylarginine and C-reactive protein interaction in predicting mortality in hemodialysis according to the presence or absence of diabetes., Methods: Asymmetric dimethylarginine and C-reactive protein were measured in 202 patients in maintenance hemodialysis assembled from 2011 to 2012 and followed for four years. Effect modification of C-reactive protein on the relationship between asymmetric dimethylarginine and all-cause mortality was investigated dividing the population into four categories according to the median of asymmetric dimethylarginine and C-reactive protein., Results: Asymmetric dimethylarginine and C-reactive protein levels were similar between diabetics and non-diabetics. Asymmetric dimethylarginine - median IQR μM - (1.95 1.75-2.54 versus 1.03 0.81-1.55 P=0.000) differed in non-diabetics with or without evolution to death (HR 2379 CI 1.36-3.68 P=0.000) and was similar in diabetics without or with evolution to death. Among non-diabetics, the category with higher asymmetric dimethylarginine and C-reactive protein levels exhibited the highest mortality (69.0% P=0.000). No differences in mortality were seen in diabetics. A joint effect was found between asymmetric dimethylarginine and C-reactive protein, explaining all-cause mortality (HR 15.21 CI 3.50-66.12 P=0.000)., Conclusions: Asymmetric dimethylarginine is an independent predictor of all-cause mortality in non-diabetic patients in hemodialysis. Other risk factors may overlap asymmetric dimethylarginine in people with diabetes. Inflammation dramatically increases the risk of death associated with high plasma asymmetric dimethylarginine in hemodialysis., (Copyright © 2021 Sociedad Española de Nefrología. All rights reserved.)

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D 2 [25(OH)D 2 ], 25-hydroxyvitamin D 3 [25(OH)D 3 ], 3-epi-25-hydroxyvitamin D 3 [3-epi-25(OH)D 3 ], and 24R,25-dihydroxyvitamin D 3 [24R,25(OH) 2 D 3 ] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D 2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH) 2 D 3 . The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH) 2 D 3 content using results from a reference measurement procedure., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Ascorbate-glutathione (AsA-GSH) cycle plays an important role in tuning beneficial ROS accumulation for intracellular signals and imparts plant tolerance to oxidative stress by detoxifying excess of ROS. Here, we present genome-wide identification of AsA-GSH cycle genes (APX, MDHAR, DHAR, and GR) in several leguminous species and expression analyses in G. max during stress, germination and tissue development. Our data revealed 24 genes in Glycine genus against the maximum of 15 in other leguminous species, which was due to 9 pars of duplicated genes mostly originated from sub/neofunctionalization. Cytosolic APX and MDHAR genes were highly expressed in different tissues and physiological conditions. Germination induced genes encoding AsA-GSH proteins from different cell compartments, whereas vegetative phase (leaves) stimulated predominantly genes related to chloroplast/mitochondria proteins. Moreover, cytosolic APX-1, 2, MDHAR-1a, 1b and GR genes were the primary genes linked to senescence and biotic stresses, while stAPX-a, b and GR (from organelles) were the most abiotic stress related genes. Biotic and abiotic stress tolerant genotypes generally showed increased MDHAR, DHAR and/or GR mRNA levels compared to susceptible genotypes. Overall, these data clarified evolutionary events in leguminous plants and point to the functional specificity of duplicated genes of the AsA-GSH cycle in G. max., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D 2 [25(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D 2 and 25(OH)D 3 ) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D 2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D 2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D 3 , was deemed non-commutable for 50% of the LC-MS/MS assays., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: The mortality rate of diabetic patients on dialysis is higher than that of non-diabetic patients. Asymmetric dimethylarginine and inflammation are strong predictors of death in hemodialysis. This study aimed to evaluate asymmetric dimethylarginine and C-reactive protein interaction in predicting mortality in hemodialysis according to the presence or absence of diabetes., Methods: Asymmetric dimethylarginine and C-reactive protein were measured in 202 patients in maintenance hemodialysis assembled from 2011 to 2012 and followed for four years. Effect modification of C-reactive protein on the relationship between asymmetric dimethylarginine and all-cause mortality was investigated dividing the population into four categories according to the median of asymmetric dimethylarginine and C-reactive protein., Results: Asymmetric dimethylarginine and C-reactive protein levels were similar between diabetics and non-diabetics. Asymmetric dimethylarginine - median IQR μM - (1.95 1.75-2.54 versus 1.03 0.81-1.55 P=0.000) differed in non-diabetics with or without evolution to death (HR 2379 CI 1.36-3.68 P=0.000) and was similar in diabetics without or with evolution to death. Among non-diabetics, the category with higher asymmetric dimethylarginine and C-reactive protein levels exhibited the highest mortality (69.0% P=0.000). No differences in mortality were seen in diabetics. A joint effect was found between asymmetric dimethylarginine and C-reactive protein, explaining all-cause mortality (HR 15.21 CI 3.50-66.12 P=0.000)., Conclusions: Asymmetric dimethylarginine is an independent predictor of all-cause mortality in non-diabetic patients in hemodialysis. Other risk factors may overlap asymmetric dimethylarginine in people with diabetes. Inflammation dramatically increases the risk of death associated with high plasma asymmetric dimethylarginine in hemodialysis., (Copyright © 2021 Sociedad Española de Nefrología. All rights reserved.)

Background/aims: Continuous renal replacement therapies (CRRT) are initially employed in patients with acute kidney injury (AKI) in ICU setting. After the period of serious illness, hemodialysis is usually used as a mode of transition from CRRT. Intermittent hemodiafiltration (HDF) is not commonly applied in this scenario., Objectives: To evaluate the feasibility of using HDF as transition therapy after CVVHDF in critically patients with AKI., Methods: An observational and prospective pilot study was conducted in ICU patients with dialysis-requiring AKI. Patients were initially treated with CVVHDF and, after medical improvement, those who still needed renal replacement therapy were switched to HDF treatment., Results: Ten Patients underwent 53 HDF sessions (mean of 5.3 sessions/patient). The main cause of renal dysfunction was sepsis ( N = 7; 70%). The APACHE II mean score was 27.6 ± 6.9. During HDF treatment, the urea reduction ratio was 64.5 ± 7.5%, for β-2 microglobulin serum levels the percentage of decrease was 42.0 ± 7.8%, and for Cystatin C was 36.2 ± 6.9%. Five episodes of arterial hypotension occurred (9.4% of sessions). There were 20 episodes of electrolytic disturbance (37.7% of sessions), mainly hypophosphatemia. No pyrogenic or suggestive episode of bacteremia was observed., Conclusion: Hemodiafiltration was safe and efficient to treat critically ill patients with acute kidney injury during the transition phase from continuous to intermittent dialysis modality. Special attention should be paid regarding the occurrence of electrolytic disturbance, mainly hypophosphatemia.

Background: Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients., Methods: We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission., Results: 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33-4.69], p = 0.005), diuretic use (OR 4.14 [1.27-13.49], p = 0.019), and IMV (OR 7.60 [1.37-42.05], p = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16-4.33], p = 0.023). Overall 60-day mortality was 14.4% {23.8% (n = 24) in the AKI group versus 5% (n = 5) in the non-AKI group (HR 2.79 [1.04-7.49], p = 0.040); and 35.3% (n = 12) in the RRT group versus 10.2% (n = 17) in the non-RRT group, respectively (HR 2.21 [1.01-4.85], p = 0.047)}., Conclusions: AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients., (© 2020 S. Karger AG, Basel.)

The authors conducted a subanalysis of the ReHOT (Resistant Hypertension Optimal Treatment) study to evaluate the association between endothelial dysfunction and resistant hypertension in a population of patients treated in a staged fashion for hypertension. One hundred and three hypertensive patients were followed for 6 months and participated in seven visits (V0-V6) 28 days apart. There was a first phase (V0-V3) of antihypertensive adjustment with three drugs and determination of resistant hypertension and a second randomized phase (V3-V6) of treatment with a fourth drug (clonidine or spironolactone) in the hypertensive patients characterized as resistant. Of the 103 patients included, 86 (83.5%) underwent the randomization visit (V3), 71 were characterized as non-resistant hypertensives (82.5%), and 15 as resistant hypertensives (17.5%). Serum asymmetric dimethylarginine (ADMA) was shown to be an independent predictor of resistant hypertension after adjustment for multiple variables (OR: 11.42, 95% CI: 1.02-127.71, P = .048), and in addition, there was a reduction in blood pressure levels and ADMA values during follow-up with a positive correlation in both groups and a greater reduction in the group of resistant hypertensives. We demonstrated that ADMA was an independent predictor of resistant hypertension, and we observed that the improvement in blood pressure levels obtained with the treatment was proportional to the reduction in ADMA values, suggesting a complementary role of ADMA not only as a stratification tool for the occurrence of resistant hypertension, but also as a possible therapeutic target in this population., (© 2020 Wiley Periodicals LLC.)

Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL.

BACKGROUND Cocaine abuse is a globally recognized problem with great socioeconomic and health impacts on society. We report a case of dissection of vertebral arteries and right renal artery after cocaine abuse that clinically presented as atypical headache and hypertension. CASE REPORT A 36-year-old male sought emergency care due to cervical pain after cocaine abuse. The pain was located to the right cervical side with irradiation to the homolateral temporal region. He had no previous comorbidities, except for cocaine abuse on a weekly basis. Angiotomography showed alterations compatible with recent arterial dissection of the right vertebral artery, confirmed on angioresonance. The patient received double anti-aggregation and antihypertensive drugs and was discharged. He was readmitted 5 days later due to hypertensive crisis and mild abdominal pain. Abdominal ultrasound with a Doppler of renal arteries showed signs right renal artery stenosis. Magnetic resonance angiography confirmed dissection of the same vessel. The patient underwent arteriography with stent implantation in the right renal artery. During outpatient follow-up, he progressed with gradual reduction of antihypertensive drugs. CONCLUSIONS There is only 1 case report correlating renal artery dissection with cocaine use and none with concomitant presentation of dissection in the vertebral and renal arterial beds. The scarcity of reports is a consequence of many problems. Therefore, young patients presenting with new-onset hypertension or abdominal pain and cocaine abuse history should raise suspicion for renal artery dissection.

Understanding into acerola (Malpighia emarginata) molecular and biochemical bases is still obscure, despite it is one of the most important natural source of vitamin C for humans. Recently, our research group published the first data on acerola transcriptome generating valuable information to identify reference genes for RT-qPCR in this species. Hence, this study aimed to identify the most stably expressed genes based on acerola transcriptome data, and further to evaluate the suitability of F-box, U3, Merad50-ATPase, TGD4, NOB1, PA-RNA, RCC1, RBL and PGAL candidates for accurate gene expression normalization in leaf, flower and fruit at 12, 16 and 20 days after anthesis using RT-qPCR analysis. Three algorithms, geNorm, NormFinder, and BestKeeper confirmed the expression stability of all nine candidate reference genes, whereas RefFinder consensually summarized a comprehensive gene ranking. Based on geNorm, the combination of the most stable reference genes RBL and U3 for leaf/flower group, TGD4, F-box and PGAL (fruit developmental stages or fruit/leaf), RCC1, PGAL and RBL (fruit/flower) and RCC1, RBL, TGD4 and PGAL (total samples) were required for accurate normalization. Moreover, the use of these reference genes to assess the expression profile of GMP1 and NAT3 genes confirmed the reliability of ranking and defined the best combination of genes recommended by geNorm and RefFinder. This work will benefit further RT-qPCR studies in these acerola organs by offering a foundation for accurate normalization of gene expression profiling.

Key Message: The first transcriptome coupled to metabolite analyses reveals major trends during acerola fruit ripening and shed lights on ascorbate, ethylene signalling, cellular respiration, sugar accumulation, and softening key regulatory genes. Acerola is a fast growing and ripening fruit that exhibits high amounts of ascorbate. During ripening, the fruit experience high respiratory rates leading to ascorbate depletion and a quickly fragile and perishable state. Despite its growing economic importance, understanding of its developmental metabolism remains obscure due to the absence of genomic and transcriptomic data. We performed an acerola transcriptome sequencing that generated over 600 million reads, 40,830 contigs, and provided the annotation of 25,298 unique transcripts. Overall, this study revealed the main metabolic changes that occur in the acerola ripening. This transcriptional profile linked to metabolite measurements, allowed us to focus on ascorbate, ethylene, respiration, sugar, and firmness, the major metabolism indicators for acerola quality. Our results suggest a cooperative role of several genes involved in AsA biosynthesis (PMM, GMP1 and 3, GME1 and 2, GGP1 and 2), translocation (NAT3, 4, 6 and 6-like) and recycling (MDHAR2 and DHAR1) pathways for AsA accumulation in unripe fruits. Moreover, the association of metabolites with transcript profiles provided a comprehensive understanding of ethylene signalling, respiration, sugar accumulation and softening of acerola, shedding light on promising key regulatory genes. Overall, this study provides a foundation for further examination of the functional significance of these genes to improve fruit quality traits.

Objective: To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay., Methods: Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study., Results: Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease., Conclusion: Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.

Vitamin D possesses renoprotective effects beyond mineral metabolism, potentially reducing arterial blood pressure and inflammation and vitamin D enzymes (CYP24A1 and CYP27B1) as well as vitamin D receptor (VDR) contribute to its homeostasis. In the present study, we aimed to determine vitamin D association with kidney volume, blood pressure parameters and inflammatory markers in ADPKD. This cross-sectional study, conducted from August 2011 through May 2016, evaluated 25(OH)D, 1,25(OH)2D and other hormonal/biochemical serum and urinary parameters, inflammatory markers and monocyte expression of VDR, CYP24A1, CYP27B1 in 74 ADPKD patients. The height-adjusted total kidney volume (htTKV) was determined by MRI and blood pressure (BP) measured through 24-h ambulatory BP monitoring (ABPM).Vitamin D insufficiency was present in 62% of patients and CYP24A1 was overexpressed in this group, raising a hypothesis of 25(OH)D increased catabolism. Serum 25(OH)D levels and VDR expression were negatively correlated with htTKV as was VDR with IL-6, IL-10, CRP, and NFκB. A multiple linear regression analysis with htTKV as dependent variable, including hypertension, CRP, eGFR, age, time since diagnosis, VDR, and 25(OH)D adjusted for season of the year showed that only the first three parameters were independent predictors of the former. There has been no association of serum 25(OH)D and VDR expression with ABPM parameters. Present findings suggested that low levels of serum 25(OH)D and VDR expression are associated with a higher kidney volume in ADPKD patients, but do not represent independent risk factors for htTKV.

Metabolic acid-base disorders, especially metabolic acidosis, are common in critically ill patients who require renal replacement therapy. Continuous veno-venous hemodiafiltration (CVVHDF) achieves profound changes in acid-base status, but metabolic acidosis can remain unchanged or even deteriorate in some patients. The objective of this study is to understand the changes of acid-base variables in critically ill patients with septic associated acute kidney injury (SA-AKI) during CVVHDF and to determine how they relate to clinical outcome.Observational study of 200 subjects with SA-AKI treated with CVVHDF for at least 72 hours. Arterial blood gases and electrolytes and other relevant acid-base variables were analyzed using quantitative acid-base chemistry.Survivors and nonsurvivors had similar demographic characteristics and acid-base variables on day one of CVVHDF. However, during the next 48 hours, the resolution of acidosis was significantly different between the 2 groups, with an area under the ROC curve for standard base excess (SBE) and mortality of 0.62 (0.54-0.70), this was better than APACHE II score prediction power. Quantitative physicochemical analysis revealed that the majority of the change in SBE was due to changes in Cl and Na concentrations.Survivors of SA-AKI treated with CVVHDF recover hyperchloremic metabolic acidosis more rapidly than nonsurvivors. Further study is needed to determine if survival can be improved by measures to correct acidosis more rapidly.

Anemia is a common feature in critically ill patients. Serum soluble-Fas (sFas) levels are associated with anemia in chronic kidney disease. It is possible that sFas levels are also associated with anemia in acute kidney injury (AKI) patients. The study aims to investigate the relationship between serum levels of sFas, erythropoietin (Epo), inflammatory cytokines, and hemoglobin (Hb) concentration in critically ill patients with AKI. We studied 72 critically ill patients with AKI (AKI group; n = 53) or without AKI (non-AKI group; n = 19), and 18 healthy volunteers. Serum sFas, Epo, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, iron status, and Hb concentration were analyzed in all groups. We also investigated the correlation between these variables in the AKI group. Critically ill patients (AKI and non-AKI groups) had higher serum levels of Epo than healthy volunteers. Hb concentration was lower in the AKI group than in the other groups. Serum sFas, IL-6, TNF-α, and ferritin levels were higher in the AKI group. Hb concentration correlated negatively with serum IL-6 (r = -0.37, P = 0.008), sFas (r = -0.35, P = 0.01), and Epo (r = -0.27, P = 0.04), while serum sFas correlated positively with iron levels (r = 0.36, P = 0.008) and IL-6 (r = 0.28, P = 0.04) in the AKI group. In multivariate analysis, after adjusting for markers of inflammation and iron stores, only serum sFas levels (P = 0.03) correlated negatively with Hb concentration in the AKI group. Serum Epo and inflammatory cytokine levels are elevated in critically ill patients with or without AKI. Serum levels of sFas are elevated and independently associated with anemia in critically ill patients with AKI., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: The use of point-of-care testing (POCT) in different clinical applications is justified by the fact that the time to release the result is shortened, allowing the physician to define the diagnosis and most appropriate therapy in a shorter time. However, the negative aspects must also be highlighted and studied so that we can move forward with the use of these devices. These negative aspects include greater analytical imprecision compared to laboratory automation, the variability between different equipment from different manufacturers, the risk of inappropriate use, a low level of global regulation, higher costs compared with laboratory testing and cost ineffectiveness in terms of health care. Methods and., Results: This review presents some clinical applications of POCT in different scenarios, such as for diabetes mellitus, infectious diseases, pediatrics, and chronic kidney disease, among others., Conclusions: We hope to see a global consensus on an acceptable quality standard for performing POCT that is adaptable, practical, and cost effective in primary care settings, ensuring patient safety, and minimizing the risk of harm.

Background: Bone metabolism involves many complex pathways that are disturbed by several bone diseases. The literature shows some limitations concerning pediatric reference intervals to bone markers, mainly because of the low number of patients included in the studies, the heterogeneity of methods, beyond the fact that it is time-consuming and expensive. The aim of this study was to determine reference values for β-isomerized carboxy-terminal telopeptides collagen type I (β-CTX), a marker of bone resorption, for children and adolescents., Methods: Blood samples from 246 patients were collected and β-CTX was measured using an electrochemiluminescence immunoassay (ECLI)., Results and Conclusions: We propose reference ranges for β-CTX concentration from the 2.5 percentile and 97.5 percentile for each age group. The reference values obtained, concerning children and adolescents, might be useful in the evaluation of diseases such as osteosarcoma and anorexia in both childhood as adolescence.

Asymmetric dimethylarginine (ADMA), which is the main endogenous inhibitor of nitric oxide synthase, plays a critical role in the process of endothelial dysfunction. The authors evaluated the association between high plasma ADMA levels in patients with hypertension and the presence of cardiovascular risk factors and the development of type 2 diabetes mellitus (DM) and cardiovascular outcomes, including death. The authors evaluated 191 patients with hypertension who were stratified into two groups according to the median value of basal ADMA: those with high levels of plasma ADMA (>0.55 μmol/L) and low levels of plasma ADMA (≤0.55 μmol/L) who were prospectively evaluated over 5.8 years. High ADMA levels were seen in patients with higher weight, body mass index, waist circumference, triglycerides, uric acid, and high-sensitivity C-reactive protein, and lower levels of high-density lipoprotein cholesterol and in patients with type 2 DM. There was an association between high plasma ADMA levels and the occurrence of cardiovascular death. In a subgroup of patients with hypertension free from metabolic syndrome and DM at baseline, there was an association between high ADMA levels and the development of type 2 DM. This study confirms the association of high plasma ADMA levels and the presence of cardiovascular risk factors in patients with hypertension and suggests a positive predictive value of high plasma ADMA levels for cardiovascular death in patients with hypertension and also for the development of type 2 DM in a subgroup of patients with hypertension free from metabolic abnormalities., (©2018 Wiley Periodicals, Inc.)

Farmers in the State of Piauí in northeastern Brazil reported nervous signs in ruminants and donkeys after ingestion of Brunfelsia uniflora at the start of the rainy season when the plant is flowering. Leaves of the plant, collected at the start or at the end of the rainy season, were administered in single doses of 5-20 g/kg body weight to 8 sheep and 3 donkeys. Two sheep and 1 donkey that ingested 10 g/kg of the plant in November at the start of the rainy season, when the plant was flowering, developed severe convulsions and diarrhea. One sheep was euthanized and autopsied, and no significant lesions were found. The other sheep and the donkey recovered. Four sheep and one donkey that ingested 10 or 20 g/kg of leaves collected in April, at the end of the rainy season, did not show clinical signs. One donkey that ingested 5 g/kg of leaves collected in November developed diarrhea and recovered. These results demonstrate the toxicity of B. uniflora for livestock and suggest that the plant is toxic at these doses only during the start of the rainy season.

TLR expression in neutrophils and monocytes is associated with increased cytokine synthesis, resulting in increased inflammation. However, the inflammatory pathway related to TLR and cathelicidin expression in these cells from CKD patients is unclear. To evaluate TLR4, cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 expression in neutrophils and monocytes from HD and CKD patients. Blood samples were drawn from 47 CKD and 43 HD patients and 71 age and gender-matched healthy volunteers (CONT). TLR4 was analyzed using flow cytometry. Cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 were analyzed via ELISA.TLR4 expression in neutrophils was higher in HD patients than in stage 3 and 4 CKD patients. In these cells, we observed a positive correlation between TLR4 and cathelicidin, TNF-α, IL-6, IL-10 and MCP-1 levels. In monocytes, TLR4 expression was significantly higher in CKD 3 and 4 groups than in the control and HD groups and positively and negatively correlated with IL-6 and MCP-1 and cathelicidin, respectively. TNF-α, IL-6 and MCP-1 serum levels were higher in HD and CKD patients than in control. Cathelicidin and IL-10 levels were only higher in HD patients. IL-6 serum levels were positively correlated with all cytokines, and cathelicidin was negatively correlated with MCP-1 (r = - 0.35; p < 0.01) and positively correlated with IL-10 (r = 0.37; p = 0.001). These results suggest that a uremic environment induces high TLR4, cathelicidin and cytokine expression and may increase inflammation. Thus, future studies should be conducted to evaluate whether TLR4 and cathelicidin should be targets for anti-inflammatory therapeutic strategies., (Copyright © 2018. Published by Elsevier Inc.)

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P =1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434., (© 2018 American Heart Association, Inc.)

Objective: To describe and standardize an original protocol for fractional flow reserve (FFR) pre and postangioplasty in an initial series of patients with clinically manifested transplant renal artery stenosis (TRAS)., Background: There is no data in the literature about the use of FFR in TRAS., Methods: Patients with TRAS detected in a noninvasive study were referred to diagnostic angiography and stenosis considered visually severe (≥ 60%) were included. After selective cannulation, a PressureWire 0.014" (Certus™-St. Jude Medical) was advanced to the distal portion of the vessel. Resting Pd/Pa ratio (ratio of mean distal to lesion and mean proximal pressures) and translesional systolic pressure gradient were obtained and FFR and hyperemic translesional systolic and mean pressure gradients (HSG and HMG) were registered after papaverine induced maximum hyperemia-pre and poststent implantation. Creatinine levels and office blood pressure measurements were registered at the baseline, 6 and 12 months after intervention., Results: Ten consecutive patients had successful stent implantation and were included. After treatment, significant increase in FFR (0.76 ± 0.09 vs. 0.96 ± 0.04, P < 0.001) and reduction in systolic hyperemic gradients (-41.40 ± 19.18, P < 0.001) and mean (-24.00 ± 11.65, P < 0.001) were observed. A strong negative correlation was observed between FFR and percent stenosis diameter-%SD (r = -0.89, P < 0.001) and HSG (r = -0.9, P < 0.001) as well as a strong positive correlation between FFR and baseline Pd/Pa ratio (r = 0.9, P < 0.001)., Conclusion: FFR was a well-tolerated, valid and reproducible tool during percutaneous intervention for TRAS. Good correlation was observed between FFR and others hemodynamic parameters of lesion severity., (© 2018 Wiley Periodicals, Inc.)

Point-of-Care Testing (POCT) has been highlighted in the health care sector in recent decades. On the other hand, due to its low demand, POCT is at a disadvantage compared to conventional equipment, since its cost is inversely proportional to the volume of use. In addition, for the implementation of POCT to succeed, it is essential to rely on the work of a multidisciplinary team. The awareness of health professionals of the importance of each step is perhaps the critical success factor. The trend towards the continuous advancement of the use of POCT and the great potential of its contributions reinforce the need to implement quality management tools, including performance indicators, to ensure their results. This review presents some advantages and disadvantages concerning POCT and the real need to use it. A worldwide call for the availability of easy-to-use health technologies that are increasingly closer to the final user is one of the main reasons for this focus.

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery.

Background: Many controversies exist regarding the management of dialysis-requiring acute kidney injury (D-AKI). No clear evidence has shown that the choice of dialysis modality can change the survival rate or kidney function recovery of critically ill patients with D-AKI., Methods: We conducted a retrospective study investigating patients (≥16 years old) admitted to an intensive care unit with D-AKI from 1999 to 2012. We analyzed D-AKI incidence, and outcomes, as well as the most commonly used dialysis modality over time. Outcomes were based on hospital mortality, renal function recovery (estimated glomerular filtration rate-eGFR), and the need for dialysis treatment at hospital discharge., Results: In 1,493 patients with D-AKI, sepsis was the main cause of kidney injury (56.2%). The comparison between the three study periods, (1999-2003, 2004-2008, and 2009-2012) showed an increased in incidence of D-AKI (from 2.56 to 5.17%; p = 0.001), in the APACHE II score (from 20 to 26; p < 0.001), and in the use of continuous renal replacement therapy (CRRT) as initial dialysis modality choice (from 64.2 to 72.2%; p < 0.001). The mortality rate (53.9%) and dialysis dependence at hospital discharge (12.3%) remained unchanged over time. Individuals who recovered renal function (33.8%) showed that those who had initially undergone CRRT had a higher eGFR than those in the intermittent hemodialysis group (54.0 × 46.0 ml/min/1.73 m2, respectively; p = 0.014). In multivariate analysis, type of patient, sepsis-associated AKI and APACHE II score were associated to death. For each additional unit of the APACHE II score, the odds of death increased by 52%. The odds ratio of death for medical patients with sepsis-associated AKI was estimated to be 2.93 (1.81-4.75; p < 0.001)., Conclusion: Our study showed that the incidence of D-AKI increased with illness severity, and the use of CRRT also increased over time. The improvement in renal outcomes observed in the CRRT group may be related to the better baseline kidney function, especially in the dialysis dependence patients at hospital discharge.

American cutaneous leishmaniasis (ACL) is a chronic infectious disease caused by different protozoan species of Leishmania, and it is endemic in both tropical and subtropical countries. Using immunohistochemistry, we investigate the density of CD68 + , lysozyme + , CD1a + , factor XIIIa + , CD4 + , CD8 + , CD56 + , interferon (IFN)-γ + , and inducible NO synthase (iNOS + ) cells. These cells were analyzed from 22 biopsy samples obtained from the lesions of ACL patients, whose infection was caused by Leishmania (Viannia) spp. Histopathological analysis showed dense mononuclear inflammatory infiltration in the dermis, which was composed of lymphocytes, macrophages, plasma cells, and discrete tissue parasitism. Granulomatous reactions were also present in the majority of cases. The density of the activated macrophages was higher than that of inactivated macrophages in the lesions. The density of Langerhans cells (CD1a + ) was lower than that of dermal dendrocytes (factor XIIIa + ). The density of CD8 + T lymphocytes was higher than that of CD4 + T lymphocytes. The cellular density of these immunological markers in relation to the species of Leishmania demonstrated that L. (Viannia) sp. lesions had higher IFN-γ expression than that Leishmania (Viania) braziliensis lesions. The evaluation of these markers, according to disease progression, did not reveal any significant differences. L. (Viannia) sp. infection leads to a favorable immune response in the host, as predominantly represented by lysozyme + , factor XIIIa + , CD8 + T cells, and the expression of (IFN)-γ + at the lesion site.

Background: Several factors influence the outcomes in acute kidney injury (AKI), especially in intensive care unit (ICU) patients. In this scenario, continuous renal replacement therapies (CRRT) are used to control metabolic derangements and blood volume. Knowing this fact, it may be possible to change the course of the disease and decrease the high mortality rate observed. Thus, we aimed to evaluate the main risk factors for death in AKI patients needing CRRT., Results: This was a prospective, observational cohort study of ICU patients (N = 183) with AKI who underwent continuous venovenous hemodiafiltration (CVVHDF) as their initial dialysis modality choice. The patients were predominantly male (62.8%) and their median age was 65 (55-76) years. The most frequent comorbidities were cardiovascular disease (39.3%), hypertension (32.8%), diabetes (24%), and cirrhosis (20.7%). The main cause of AKI was sepsis (52.5%). At beginning of CVVHDF, 152 patients (83%) were using vasopressors. The median SAPS 3 and SOFA score at ICU admission was 61 (50-74) and 10 (7-12), respectively. The dialysis dose delivered was 33.2 (28.9-38.7) ml/kg/h. The median time between ICU admission and CVVHDF initiation was 2 (1-4) days. The median cumulative fluid balance during the CVVHDF period was -1838 (-5735 +2993) ml. The mortality rate up to90 days was 58%. The independent mortality risk factors in propensity score model were: chronic obstructive pulmonary disease (OR = 3.44[1.14-10.4; p = 0.028]), hematologic malignancy (OR = 5.14[1.66-15.95; p = 0.005]), oliguria (OR = 2.36[1.15-4.9; p = 0.02]), positive daily fluid balance during CVVHDF (OR = 4.55[2.75-13.1; p<0.001]), and total SOFA score on first dialysis day (OR = 1.27[1.12-1.45; p<0.001])., Conclusions: Dialysis-related factors may influence the outcomes. In our cohort, positive daily fluid balance during CRRT was associated with lower survival. Multicenter, randomized studies are needed to assess fluid balance as a primary outcome to define the best strategy in this patient population.