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Farid Samaan,1,2,* Áquilas Mendes,3,4,* Leonardo Carnut5,* 1Planning and Evaluation Group, São Paulo State Health Department, São Paulo, SP, Brazil; 2Research Division, Dante Pazzanese Cardiology Institute, São Paulo, SP, Brazil; 3Public Health School, University of São Paulo, São Paulo, SP, Brazil; 4Postgraduate Program, Pontifícia Universidade Católica, São Paulo, SP, Brazil; 5Center for the Development of Higher Education in Health, Federal University of São Paulo, São Paulo, SP, Brazil*These authors contributed equally to this workCorrespondence: Farid Samaan, Planning and Evaluation Group, São Paulo State Health Department, Av. Dr. Arnaldo, 351 - 5th Floor, Room 501, São Paulo, SP, 01246-903, Brazil, Tel +55 11 3066-8165, Email fsamaan@saude.sp.gov.brAbstract: Worldwide the assistance on renal replacement therapy (RRT) is carried out mainly by private for-profit services and in a market with increase in mergers and acquisitions. The aim of this study was to conduct an integrative systematic review on privatization and oligopolies in the RRT sector in the context of contemporary capitalism. The inclusion criteria were scientific articles without language restrictions and that addressed the themes of oligopoly or privatization of RRT market. Studies published before 1990 were excluded. The exploratory search for publications was carried out on February 13, 2024 on the Virtual Health Library Regional Portal (VHL). Using the step-by-step of PRISMA flowchart, 34 articles were retrieved, of which 31 addressed the RRT sector in the United States and 26 compared for-profit dialysis units or those belonging to large organizations with non-profit or public ones. The main effects of privatization and oligopolies, evaluated by the studies, were: mortality, hospitalization, use of peritoneal dialysis and registration for kidney transplantation. When considering these outcomes, 19 (73%) articles showed worse results in private units or those belonging to large organizations, six (23%) studies were in favor of privatization or oligopolies and one study was neutral (4%). In summary, most of the articles included in this systematic review showed deleterious effects of oligopolization and privatization of the RRT sector on the patients served. Possible explanations for this result could be the presence of conflicts of interest in the RRT sector and the lack of incentive to implement the chronic kidney disease care line. The predominance of articles from a single nation may suggest that few countries have transparent mechanisms to monitor the quality of care and outcomes of patients on chronic dialysis.Keywords: renal dialysis, chronic kidney failure, health facility merger, private sector, capitalism, review

Summary: This protocol presents a workflow for detecting differences in kinematics between experimental conditions. It is tailored for short-tailed opossums but can be applied to any species capable of completing the ladder rung task. There are four phases of this protocol: (1) data collection, (2) pose tracking, (3) analysis of single trials, and (4) cross-condition comparisons. This pipeline implements aspects of machine learning and signal processing, allowing for rapid data analysis that provides insight into how animals perform this task.For complete details on the use and execution of this protocol, please refer to Englund et al. (2020).

Summary: The early loss of vision results in a reorganized neocortex, affecting areas of the brain that process both the spared and lost senses, and leads to heightened abilities on discrimination tasks involving the spared senses. Here, we used performance measures and machine learning algorithms that quantify behavioral strategy to determine if and how early vision loss alters adaptive sensorimotor behavior. We tested opossums on a motor task involving somatosensation and found that early blind animals had increased limb placement accuracy compared with sighted controls, while showing similarities in crossing strategy. However, increased reliance on tactile inputs in early blind animals resulted in greater deficits in limb placement and behavioral flexibility when the whiskers were trimmed. These data show that compensatory cross-modal plasticity extends beyond sensory discrimination tasks to motor tasks involving the spared senses and highlights the importance of whiskers in guiding forelimb control.

Background: Disparity in the allocation of medical services and resources based on race is present within the health care industry today, including the prescription of postoperative analgesics. The purpose of this study was to evaluate the presence of race-based disparity in the prescription of postdischarge opioids after lower extremity bypass (LEB) surgery for chronic limb-threatening ischemia (CLTI)., Methods: Retrospective analysis was conducted on adult CLTI patients who underwent LEB from 2000 to 2023 in the TrinetX database. Patients were stratified into two groups based on race: White (group I) and black or African American (AA) (group II). Primary outcomes were defined as oral opioid prescriptions at 7 days and 30 days after discharge, and mortality at 1 year postoperatively. Secondary outcomes included length of stay and 30-day postoperative outcomes, including myocardial infarction, pulmonary embolism, cerebral vascular accident, deep vein thrombosis, acute kidney injury, major amputation, minor amputation, major adverse cardiac events, and major adverse limb events. Stratified analysis was conducted based on disease stage (rest pain vs lower extremity ulcer vs gangrene). Univariate analysis was performed via two-sample t test and χ 2 test. Logistic regression was performed to estimate the association of Black or AA (vs White) race while controlling for pertinent preoperative potential confounders., Results: There were 3345 patients who met the inclusion criteria. Group I included 2661 White patients and group II included 684 Black or AA patients. Group II patients were more likely to be younger, female, present with gangrene, and have a history of hypertension, diabetes, chronic kidney disease, or diabetic neuropathy. At both 7 and 30 days after discharge, the Black or AA cohort had significantly lower rates of opioid prescriptions (33.2% vs 42.5% and 35.8% vs 47.2%, respectively) (all P < .05). Stratification by indication showed that opioid prescription disparity persisted despite black or AA patients presenting at worse stages of disease both at 7 and 30 days after discharge (7 days: rest pain 43.4% vs 33.7% [P = .013], ulcer 41.4% vs 31.7% [P = .027], gangrene, 42.7% vs 33.6% [P = .006] and 30 days: rest pain 47.8% vs 37.1% [P = .007], ulcer 45.4% vs 33.5% [P = .007], gangrene, 48.2% vs 36.1% [P < .001]). Adjusted analysis confirmed that Black or AA race was associated with lower rates of 7- (adjusted odds ratio, 0.607; P = .001) and 30-day (adjusted odds ratio, 0.56; P = .001) postdischarge opioid prescriptions., Conclusions: Black or AA patients were less likely to receive postdischarge opioid prescriptions compared with their White counterparts at 7 and 30 days after LEB for CLTI., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: This study assesses the association of preoperative use of gabapentinoids (GBPs) with postoperative risk of opioid-related disorders in peripheral artery disease patients undergoing lower extremity bypass operation., Methods: This is a retrospective propensity score-matched analysis of patients undergoing peripheral artery bypass in TriNetX, a multicenter national database. Two study groups were constituted based on the preoperative history of prescribed GBPs. Primary outcomes were opioid-related disorders and mortality. The outcomes were reported at two-time endpoints that is, at 1 and 5 y., Results: This study population included a total of 23,706 patients. After propensity score-matched analysis, each group contained 5130 patients. The primary outcomes showed a significant increase in postoperative opioid-related disorders at the 1 and 5-y time points between GBPs and no GBPs groups: 1-y outcome (2.0% versus 1.1%; adj. P = 0.007) and 5-y outcome (4.5% versus 3.5%; adj. P = 0.035). Logistic regression analysis revealed an increase in the 1-y (adjusted odds ratio= 1.664; 95% CI [1.217, 2.273], P = 0.001) and 5-y (OR = 1.353; 95% CI [1.107, 1.653], P = 0.003) odds of opioid-related disorders in patients on GBPs. A secondary analysis showed a significant dose-dependent increase in the associated risk of 5-y opioid-related disorders in patients with a history of prescribed gabapentin., Conclusions: In patients undergoing lower extremity bypass with a history of gabapentin use, there is an associated increased long-term risk of opioid-related disorders in a dose-dependent fashion. Overall, this study highlights weighing risks and benefits of prescribing GBPs for pain control versus their long-term associated risk of opioid-related disorders among other adverse outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Race-based disparities in health care have been related to a myriad of prevailing factors among minorities in the United States. This study aims to study the race-based differences in the outcomes of carotid endarterectomy (CEA)., Methods: The PROSPERO database registered the review protocol (CRD42023428253). A systematic English literature review was performed using literature databases PubMed and Scopus from inception till June 2023. The review was designed on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and included studies reporting mortality, stroke, or composite outcome of mortality and stroke after CEA for carotid artery disease, regardless of any degree of stenosis including both symptomatic and asymptomatic patients. The risk of bias was evaluated utilizing the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool. A pooled odds ratio (OR) for the overall mortality was computed, and a P value of < .05 was designated as statistically significant. Interstudy heterogeneity was evaluated by Q-metric and quantified using Higgins I 2 statistics., Results: Twelve studies were identified which included a total of 574,055 patients who underwent CEA from 1998 to 2022. Eleven of 12 studies reported 30-day mortality as an outcome for patients undergoing CEA in which 524,708 patients (92.5%) were White and 42,797 (7.5%) were non-White. The overall pooled OR indicated a statistical significance in 30-day mortality between White and non-White patients undergoing CEA (OR, 1.73; 95% confidence interval [CI], 1.37-2.18; P = .011) with substantial heterogeneity (I 2  = 56.3%). Eleven of 12 studies reported stroke as an outcome for patients undergoing CEA in which 524,708 patients (92.5%) were White and 42,801 (7.5%) were non-White. The overall pooled OR indicated no statistical significance in stroke between White and non-White patients undergoing CEA (OR, 1.46; 95% CI, 1.28-1.65; P = .111) with moderate heterogeneity (I 2  = 35.9%). Five of 12 studies reported composite mortality or stroke as an outcome for patients undergoing CEA. The overall pooled OR indicated no statistical significance in composite mortality or stroke between White and non-White patients undergoing CEA (OR, 1.40; 95% CI, 1.24-1.59; P = .467) with no heterogeneity (I 2  = 0.0%)., Conclusions: Non-White patients have a relatively higher risk of mortality; however, no significant difference was observed between the racial groups in terms of stroke or a composite outcome of mortality or stroke. The odds of mortality in non-White patients have been persistent throughout recent studies., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to evaluate quality indicators of secondary health care in chronic kidney disease (CKD). Methods: This retrospective longitudinal study was conducted in an outpatient medical nephrology clinic of the Brazilian Unified Health System (UHS) and a multidisciplinary outpatient clinic of a private health plan (PHP). The inclusion criteria were age ≥ 18 years, ≥ 3 medical appointments, and follow-up time ≥ 6 months. Results: Compared to PHP patients ( n  = 183), UHS patients ( n  = 276) were older (63.4 vs. 59.7 years, p =0.04), had more arterial hypertension (AH) (91.7% vs. 84.7%, p =0.02) and dyslipidemia (58.3 vs. 38.3%, p < 0.01), and had a lower estimated baseline glomerular filtration rate (eGFR) (29.9 [21.5-42.0] vs. 39.1 [28.6-54.8] mL/min/1.73 m 2 , p < 0.01). Compared to PHP patients, UHS patients had a lower percentage of diabetics with glycated hemoglobin < 7.5% (46.1% vs. 61.2%, p =0.03), fewer people with potassium < 5.5 mEq/L (90.4% vs. 95.6%, p =0.04), and fewer referrals for hemodialysis with functioning arteriovenous fistula (AVF) (9.1% vs. 54.3%, p < 0.01). The percentages of people with hypertension and blood pressure < 140 × 90 mmHg were similar between the UHS and PHP groups (59.7% vs. 66.7%; p =0.17), as was the percentage of people with parathyroid hormone control (85.6% vs. 84.8%; p =0.83), dyslipidemia and LDL-cholesterol < 100 mg/dL (38.3% vs. 49.3%; p =0.13), phosphorus < 4.5 mg/dL (78.5% vs. 72.0%; p =0.16), and 25-OH-vitamin-D > 30 ng/mL (28.4% vs. 36.5%; p =0.11). The crude reduction in eGFR was greater in the UHS group than in PHP (2.3 [-0.1; 5.9] vs. 1.1 [-1.9; 4.6] mL/min/1.73 m 2 ; p < 0.01). In the multivariate linear mixed-effects model, UHS patients also showed faster CKD progression over time than PHS ones (group effect, p < 0.01; time effect, p < 0.01; interaction, p < 0.01). Conclusions: Quality of care for patients with CKD can be improved through both services, and multidisciplinary care may have a positive impact on the control of comorbidities, the progression of CKD, and the planning of the initiation of hemodialysis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Farid Samaan et al.)

Introduction: Southern Hemisphere countries have been underrepresented in epidemiological studies on acute kidney injury (AKI). The objectives of this study were to determine the frequency, risk factors, and outcomes of AKI in adult hospitalized patients from the emergency department of a public high-complexity teaching hospital in the city of São Paulo, Brazil., Methods: Observational and prospective study. AKI was defined by the KDIGO guidelines (Kidney Disease: Improving Global Outcomes) using only serum creatinine., Results: Among the 731 patients studied (age: median 61 years, IQR 47-72 years; 55% male), 48% had hypertension and 28% had diabetes as comorbidities. The frequency of AKI was 52.1% (25.9% community-based AKI [C-AKI] and 26.3% hospital-acquired AKI [H-AKI]). Dehydration, hypotension, and edema were found in 29%, 15%, and 15% of participants, respectively, at hospital admission. The in-hospital and 12-month mortality rates of patients with vs. without AKI were 25.2% vs. 11.1% (p<0.001) and 36.7% vs. 12.9% (p<0.001), respectively. The independent risk factors for C-AKI were chronic kidney disease (CKD), chronic liver disease, age, and hospitalization for cardiovascular disease. Those for H-AKI were CKD, heart failure as comorbidities, hypotension, and edema at hospital admission. H-AKI was an independent risk factor for death in the hospital, but not at 12 months. C-AKI was not a risk factor for death., Conclusions: AKI occurred in more than half of the admissions to the clinical emergency department of the hospital and was equally distributed between C-AKI and H-AKI. Many patients had correctable risk factors for AKI, such as dehydration and arterial hypotension (44%) at admission. The only independent risk factor for both C-AKI and H-AKI was CKD as comorbidity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Azevedo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although approximately 25% of Brazilians have private health coverage (PHC), studies on the surveillance of chronic kidney disease (CKD) in this population are scarce. The objective of this study was to estimate the prevalence of CKD in individuals under two PHC regimes in Brazil, who total 8,335,724 beneficiaries., Methods: Outpatient serum creatinine and proteinuria results of individuals from all five regions of Brazil, ≥ 18 years of age, and performed between 10/01/2021 and 10/31/2022, were analyzed through the own laboratory network database. People with serum creatinine measurements were evaluated for the prevalence and staging of CKD, and those with simultaneous measurements of serum creatinine and proteinuria were evaluated for the risk category of the disease. CKD was classified according to current guidelines and was defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73 m² estimated by the 2021 CKD-EPI equation., Results: The number of adults with serum creatinine results was 1,508,766 (age 44.0 [IQR, 33.9-56.8] years, 62.3% female). The estimated prevalence of CKD was 3.8% (2.6%, 0.8%, 0.2% and 0.2% in CKD stages 3a, 3b, 4 and 5, respectively), and it was higher in males than females (4.0% vs. 3.7%, p < 0.001, respectively) and in older age groups (0.2% among 18-29-year-olds, 0.5% among 30-44-year-olds, 2.0% among 45-59-year-olds, 9.4% among 60-74-year-olds, and 32.4% among ≥ 75-year-olds, p < 0.001) Adults with simultaneous results of creatinine and proteinuria were 64,178 (age 57.0 [IQR, 44.8-67.3] years, 58.1% female). After adjusting for age and gender, 70.1% were in the low-risk category of CKD, 20.0% were in the moderate-risk category, 5.8% were in the high-risk category, and 4.1% were in the very high-risk category., Conclusion: The estimated prevalence of CKD was 3.8%, and approximately 10% of the participants were in the categories of high or very high-risk of the disease. While almost 20% of beneficiaries with PHC had serum creatinine data, fewer than 1% underwent tests for proteinuria. This study was one of the largest ever conducted in Brazil and the first one to use the 2021 CKD-EPI equation to estimate the prevalence of CKD., (© 2024. The Author(s).)

Introduction: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil., Methods: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves., Results: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves., Conclusions: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Samaan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chronic kidney disease (CKD) provides a worse prognosis for patients with heart disease. In Latin America, studies that analyzed the prevalence and risk stratification of CKD in this population are scarce. We aimed to evaluate CKD prevalence and risk categories in patients of a public referral cardiology hospital in São Paulo, Brazil. This was a cross-sectional study based on a laboratory database. Outpatient serum creatinine and proteinuria results performed between 1 January 2021 and 31 December 2021 were analyzed. CKD was defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 and proteinuria, by the albumin/creatinine ratio in a spot urine sample (UACR) >30 mg/g. A total of 36,651 adults were identified with serum creatinine levels (median age 72.4 [IQR, 51.0-73.6] years, 51% male). Among them, 51.9% had UACR dosage (71.5% with UACR < 30 mg/g, 22.6%, between 30-300 mg/g, and 5.9% with UACR > 300 mg/g). The prevalence of CKD was 30.9% (15.3% stage 3a, 10.2% stage 3b, 3.6% stage 4, and 1.7% stage 5), and the distribution of patients in the risk categories of the disease was: 52.0% with low-risk, 23.5%, moderate risk, 13.0%, high risk, and 11.2%, very high. In an outpatient setting, the prevalence of CKD in cardiological patients was almost three times (31%) that of the general population; about half of the individuals evaluated (48%) were not screened for an important risk marker (proteinuria), and approximately a quarter of these patients (24%) were in the high or very high CKD risk categories.

Diffuse intestinal ganglioneuromtosis is a benign tumor of the enteric nervous system, that almost always occurs in children with systemic syndromes. Whereas isolated cases in adults are exceedingly rare., Case Presentation: A 38-year-old man presented with refractory chronic constipation. An abdominal computed tomography scan revealed a redundant sigmoid colon, then he underwent a sigmoid colectomy. Histopathologic examination showed diffuse ganglioneuromatosis. However, the patient was in good health 18 months after surgery., Clinical Discussion: Intestinal ganglioneuromas commonly occur in children with systemic syndromes such as multiple endocrine neoplasia type 2B and neurofibromatosis type 1. The most frequent symptoms are abdominal discomfort, constipation, ileus, weight loss, appendicitis, and obstruction in more severe cases. surgical resection is the standard management in diffuse ganglioneuromatosis., Conclusion: Although diffuse ganglioneuromatosis is uncommon, it should be considered in patients with refractory constipation., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report., (© 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Acute kidney injury (AKI) is a worldwide public health problem and is often treated by non-nephrologists. The objective of this study was to evaluate the knowledge of non-nephrologists, undergraduate medical students and health professionals regarding AKI., Methods: An unsupervised and closed-response electronic questionnaire was sent to sixth-year medical students and non-nephrologist health professionals working in the city of São Paulo, Brazil., Results: A total of 424 responses were returned from 650 invitations (40.1% males, 39.2% physicians, 34.0% senior medical students or resident physicians, 16.3% nurses and 10.6% pharmacists). The knowledge of medical students and health professionals about the prevalence and lethality of AKI in hospitals ranged from 40.8% to 59.2%. The most recognized susceptibilities and risk factors for AKI were sepsis/septic shock (95.0%) and diabetes mellitus (91.3%); the less-recognized susceptibilities and risk factors were exposure to gadolinium-based contrast (23.3%) and chronic liver disease (55.7%). The study participants' rate of knowledge regarding the diagnosis of AKI was 50.9-73.6%, and their rate of knowledge regarding the criteria of increased serum creatinine and reduced urine volume was 52.6%. The most-recognized nephrotoxic medications were vancomycin (82.3%) and diclofenac (80.4%), and the least-recognized were acyclovir (34.0%) and cotrimoxazole (30.4%). The indications for emergency renal replacement therapy that were recognized by the study respondents were metabolic acidosis (82.3%), uremic syndrome (81.6%), hyperkalemia unresponsive to clinical treatment (78.1%) and acute pulmonary edema (71.6%)., Conclusion: The study showed knowledge gaps that can impact patient care and can be used to guide professional training programs.

In addition to playing a major role in tumor cell biology, p53 generates a microenvironment that promotes antitumor immune surveillance via tumor-associated macrophages. We examined whether increasing p53 signaling in the tumor microenvironment influences antitumor T cell immunity. Our findings indicate that increased p53 signaling induced either pharmacologically with APR-246 (eprenetapopt) or in p53-overexpressing transgenic mice can disinhibit antitumor T cell immunity and augment the efficacy of immune checkpoint blockade. We demonstrated that increased p53 expression in tumor-associated macrophages induces canonical p53-associated functions such as senescence and activation of a p53-dependent senescence-associated secretory phenotype. This was linked with decreased expression of proteins associated with M2 polarization by tumor-associated macrophages. Our preclinical data led to the development of a clinical trial in patients with solid tumors combining APR-246 with pembrolizumab. Biospecimens from select patients participating in this ongoing trial showed that there was a suppression of M2-polarized myeloid cells and increase in T cell proliferation with therapy in those who responded to the therapy. Our findings, based on both genetic and a small molecule-based pharmacological approach, suggest that increasing p53 expression in tumor-associated macrophages reprograms the tumor microenvironment to augment the response to immune checkpoint blockade.

Objective: To determine the supply/demand ratio for procedures related to diagnosis and treatment for chronic kidney disease in the Brazilian National Health System (SUS), in the state of São Paulo, Brazil, 2019., Methods: This was a descriptive study, using data from the SUS outpatient and hospital information systems. The numbers of medical consultations, diagnostic and chronic kidney disease monitoring tests, performed in the period, were compared with the demand estimation, obtained through ministerial guidelines., Results: Exclusive SUS users were 28,791,244, and individuals with arterial hypertension and/or diabetes mellitus, 5,176,188. The number of procedures performed and the ratio between this number and the needs of the population were 389,414 consultations with nephrologists (85%); 11,540,371 serum creatinine tests (223%); 705,709 proteinuria tests (14%); 438,123 kidney ultrasounds (190%); and 1,045 kidney biopsies (36%)., Conclusion: In the chronic kidney disease care in the SUS it could be seen simultaneous existence of lack of supply, waste and inadequate screening of important procedures.

Background: The number of nephrologists has risen slowly, compared with the prevalence of chronic kidney disease (CKD) in Brazil. Data on patients referred to nephrology outpatient clinics remains scarce., Objective: To determine the demographic and kidney function characteristics of patients at their first appointment with a nephrologist., Design and Setting: Retrospective study conducted at three nephrology outpatient clinics (public and private services), in São Paulo, Brazil., Methods: From December 2019 to February 2020, we collected patient data regarding demographics, kidney function parameters and comorbidities. We then analyzed data on 394 patients who met a nephrologist for their first appointment., Results: The main comorbidities were hypertension (63.7%), diabetes (33.5%) and nephrolithiasis (22.3%). Regarding CKD stages, 24.1%, 9.1%, 13.7%, 15.2%, 15.2% and 2.3% of the patients were in stages 1, 2, 3a, 3b, 4 and 5, respectively. Proteinuria was absent or mild, moderate and high in 17.3%, 15.2% and 11.7%, respectively; and 16.2% had not undergone previous investigation of serum creatinine or proteinuria (55.8%). For 17.5%, referral to a nephrologist occurred late. Patients in public services were older than those in private services (59 years versus 51 years, respectively; P = 0.001), more frequently hypertensive (69.7% versus 57.5%; P = 0.01) and reached a nephrologist later (22.4% versus 12.4%; P = 0.009)., Conclusion: Referrals to a nephrologist were not being made using any guidelines for CKD risk and many cases could have been managed within primary care. Late referral to a nephrologist happened in one-fifth of the cases and more frequently in the public service.

Complications of chronic kidney disease (CKD) can be avoided when promptly diagnosed and treated. The objective was to describe quality indicators of CKD detection and health care in the primary care public service of a city in the State of São Paulo, Brazil. This retrospective study analyzed charts of patients who attended primary care in the public service between November 2019 and February 2020. We selected 10 health quality indicators based on their scientific relevance and availability from the medical records that could express how CKD was identified and managed in primary health care. We estimated the adequate percentage of health indicators with data from 1,066 individuals who had ≥ one risk factor for CKD: hypertension, diabetes, or > 60 years old. Among patients, 79.4% had information on serum creatinine, whereas 58.8% were investigated for proteinuria. Blood pressure data were found in 98.9% of the records. The percentage of patients with blood pressure < 140x90mmHg, glycosylated hemoglobin < 6.5% and LDL-cholesterol < 100mg/dL was 79.2%, 49.2%, and 33.3%, respectively. Renin-angiotensin system blockers were prescribed to 82.8% of the patients with hypertension and CKD. Serum potassium was measured in 35.7% for those who were using renin-angiotensin system blockers. Among those people with CKD, 16.7% had CKD assigned in the medical records as a diagnose. Among those participants at higher risk for CKD, the referral rate to a nephrologist was 31.6%. This study confirmed some missed quality indicators of CKD in primary healthcare. Our results may help administrators develop public policies that improve health care for individuals at high risk for CKD. Long-term follow-up of the health indicators we proposed here will be useful to assess the impact of policy intervention.

Introduction: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil., Methods: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included., Results: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency., Conclusion: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%)., Competing Interests: The authors have declared that no competing interests exist.

Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β 2 -adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (β 2 V 2 R). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling.

Chronic abdominal pain of unknown origin is a challenging diagnosis encountered by clinicians. Patients often undergo an extensive workup and long periods of uncertainty without the establishment of a definitive diagnosis. Diagnostic laparoscopy is a relatively safe procedure that can be used as an effective diagnostic and therapeutic tool in treating this disease. This was a retrospective, single-institution study exploring the efficacy of diagnostic laparoscopy in treating chronic abdominal pain of unknown origin. More than 90 per cent of laparoscopies resulted in a positive finding, with adhesions being the most common. A total of 50 per cent of patients experienced resolution of symptoms on follow-up. Patients were overwhelmingly satisfied with their postoperative outcomes and willing to undergo the procedure again with their outcomes in mind.

Objective: The role of vitamin D supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD) is controversial. The objective of this study was to evaluate the effects of long-term cholecalciferol supplementation on VC in nondialysis patients with CKD stages 3-4 with hypovitaminosis D., Design and Methods: Eighty patients aged 18-85 years with creatinine clearance between 15 and 60 mL/min/1.73 m 2 and serum 25(OH)D level < 30 ng/mL were enrolled in a 18-month prospective study. Individuals with vitamin D insufficiency (25-hydroxyvitamin D [25(OH)D] level between 16 and 29 ng/mL) were included in a randomized, double-blind, two-arm study to receive cholecalciferol or placebo. Patients with vitamin D deficiency [25(OH)D < 15 ng/mL] were included in an observational study and mandatorily received cholecalciferol. The coronary artery calcium score was obtained by multislice computed tomography at baseline and the 18th month., Results: During the study, VC did not change in the treated insufficient group (418 [81-611] to 364 [232-817] AU, P = 0.25) but increased in the placebo group (118 [37-421] to 199 [49-490] AU, P = 0.01). The calcium score change was inversely correlated with 25(OH)D change (r = -0.45; P = 0.037) in the treated insufficient group but not in the placebo group. Renal function did not change in the insufficient, treated, and placebo groups. In multivariate analysis, there was no difference in VC progression between the treated and placebo insufficient groups (interaction P = 0.92). In the deficient group, VC progressed (265 [84-733] to 333 [157-745] AU; P = 0.006) and renal function declined (33 [26-43] to 23 [17-49] mL/min/1.73 m 2 ; P = 0.04). The calcium score change was inversely correlated with cholecalciferol cumulative doses (r = -0.41; P = 0.048) and kidney function change (r = -0.43; P = 0.033) but not with 25(OH)D change (r = -0.08; P = 0.69)., Conclusion: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D., Conclusion: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)