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Objective: To evaluate the diagnostic performance of FENa (Fractional excretion of sodium), FEK (fractional excretion of potassium) and uSID (urinary strong ion difference) in predicting pAKI in sepsis and septic shock., Design: Retrospective cohort study., Setting: Two intensive care units in Argentina., Patients: Adult patients with a confirmed diagnosis of sepsis or septic shock and AKI, and had a urinary biochemistry within 24h of the AKI diagnosis., Interventions: None., Main Variables of Interest: We evaluated the diagnostic accuracy of FENa, FEK and uSID through a ROC (Receiver Operating Characteristic) curve analysis., Results: 80 patients were included. 40 patients presented pAKI. pAKI group had higher APACHE, SOFA score, and mortality rate. In the ROC curve analysis, uSID had no diagnostic utility (AUC=0.52, p=0.69). FENa presented moderate accuracy showing an AUC of 0.71 (95% CI 0.60-0.83; p=0.001), while FEK presented low accuracy with an AUC of 0.69 (95% CI 0.57-0.80; p=0.04). The optimal Youden point for identifying pAKI was at a FENa higher than 0.51 % with a specificity of 72.5% and a sensitivity of 65.0%. In the case of FEK, a value higher than 21.9 % presented the best relation, with a specificity of 67.5% and a sensitivity of 65.0%., Conclusions: urine biochemistry interpretation in septic patients must be revised. FENa and FEK are related to the severity of AKI and could be helpful complementary tools for diagnosing pAKI., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Background: In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer. Toll-like receptors (TLRs) ligands, such as poly(I:C) or resiquimod (R848) are able to reprogram TAMs towards M1-like antitumor effector cells. The objective of our work has been to develop and evaluate polymeric nanocapsules (NCs) loaded with poly(I:C)+R848, to improve drug stability and systemic toxicity, and evaluate their targeting and therapeutic activity towards TAMs in the TME of solid tumors., Methods: NCs were developed by the solvent displacement and layer-by-layer methodologies and characterized by dynamic light scattering and nanoparticle tracking analysis. Hyaluronic acid (HA) was chemically functionalized with mannose for the coating of the NCs to target TAMs. NCs loaded with TLR ligands were evaluated in vitro for toxicity and immunostimulatory activity by Alamar Blue, ELISA and flow cytometry, using primary human monocyte-derived macrophages. For in vivo experiments, the CMT167 lung cancer model and the MN/MCA1 fibrosarcoma model metastasizing to lungs were used; tumor-infiltrating leukocytes were evaluated by flow cytometry and multispectral immunophenotyping., Results: We have developed polymeric NCs loaded with poly(I:C)+R848. Among a series of 5 lead prototypes, protamine-NCs were selected based on their physicochemical properties (size, charge, stability) and in vitro characterization, showing good biocompatibility on primary macrophages and ability to stimulate their production of T-cell attracting chemokines (CXCL10, CCL5) and to induce M1-like macrophages cytotoxicity towards tumor cells. In mouse tumor models, the intratumoral injection of poly(I:C)+R848-protamine-NCs significantly prevented tumor growth and lung metastasis. In an orthotopic murine lung cancer model, the intravenous administration of poly(I:C)+R848-prot-NCs, coated with an additional layer of HA-mannose to improve TAM-targeting, resulted in good antitumoral efficacy with no apparent systemic toxicity. While no significant alterations were observed in T cell numbers (CD8, CD4 or Treg), TAM-reprogramming in treated mice was confirmed by the relative decrease of interstitial versus alveolar macrophages, having higher CD86 expression but lower CD206 and Arg1 expression in the same cells, in treated mice., Conclusion: Mannose-HA-protamine-NCs loaded with poly(I:C)+R848 successfully reprogram TAMs in vivo , and reduce tumor progression and metastasis spread in mouse tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Anfray, Varela, Ummarino, Maeda, Sironi, Gandoy, Brea, Loza, León, Calvo, Correa, Fernandez-Megia, Alonso, Allavena, Crecente-Campo and Andón.)

Objective: The aim of this study was to evaluate prognostic factors associated with advanced chronic kidney disease (ACKD) in a cohort of patients with ANCA-associated vasculitis and renal involvement., Methods: Observational retrospective study. We included patients with biopsy-proven ANCA glomerulonephritis (GN) diagnosed between 2001 and 2016, with at least 1-year follow-up. Data were recorded at diagnosis, end of induction, after 12 months of treatment, and at the end of follow-up. We analysed clinical-analytical data and renal histopathology, as well as treatments, dialysis requirement, relapses and death. Univariate analysis was performed to identify factors associated with long-term ACKD (eGFR < 30 ml/min). Multivariate analysis using an alternative outcome (eGFR at the end of follow-up) was performed. Diagnostic accuracy for ACKD of each predictor variable was compared using AUC of ROC curves., Results: Sixty patients were included: 17 GPA, 14 MPA, 5 EGPA, and 24 RLV. Forty-six patients were women (76.7%). Mean age at diagnosis was 67.8 years (SD 13.1), and median follow-up time was 4.2 years (IQR 2.2-6.8). At the end of follow-up, 12 patients (20.0%) had an eGFR < 30 ml/min. Univariate analysis showed a statistically significant association of ACKD with sclerotic class biopsy (OR 7.17, 95% CI 1.34-38.31), 12-month proteinuria (OR 5.16, 95% CI 1.16-22.87), and creatinine at diagnosis (OR 1.24, 95% CI 1.02-1.52), end of induction (OR 15.40, 95% CI 2.41-98.28), and after 12 months (OR 19.25, 95% CI 2.75-134.92). In the multivariate analysis, eGFR at baseline (< 0.001), after 6 months (< 0.001) and 12 months of treatment (< 0.001), remained statistically associated with eGFR at the end of follow-up. The best diagnostic accuracy in ROC curves was shown by serum creatinine at the end of induction treatment (AUC 0.93) and after 12 months (AUC 0.94)., Conclusion: In this cohort of patients with ANCA GN, creatinine and eGFR at baseline and after 6 and 12 months of treatment were the best predictors of ACKD at the end of follow-up., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity., Methods: Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD., Results: The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036)., Conclusion: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age., Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Method: Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. Suggested explanation A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. How to use these guidelines: Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. It is not assumed to change the coexistence conditions of the disease process. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. Summary of recommendations For patients with suspected amyloidosis, it is recommended: Measured value of creatinine be used as a preliminary assessment for the diagnosis of renal involvement in patients with suspected renal amyloidosis. 24-hour proteinuria be measured and characterized to diagnose renal involvement in patients with suspected renal amyloidosis. Immunohistochemical staining of skin biopsy for patients genetically diagnosed with ATTR, for early diagnosis of neuropathy. The signs or symptoms of these patients suggest the presence of fine fiber neuropathy. Skin biopsy and immunohistochemical staining for early diagnosis of neuropathy. These patients show signs or symptoms suggesting fine fiber neuropathy. Conduct nerve conduction studies on motor and sensory fibers to diagnose total fiber neuropathy in patients who are diagnosed or suspected of having amyloidosis. Test (Sudoscan) is recommended for the early diagnosis of peripheral autonomic neuropathy (even in asymptomatic patients) in patients with suspected autonomic neuropathy due to amyloidosis. Ewing's standard to measure heart rate variability to diagnose autonomic hypofunction in patients with autonomic neuropathy suspected of having amyloidosis. Measure orthostatic hypotension to diagnose early autonomic hypotension for patients with amyloidosis or systemic amyloidosis suspected of autonomic neuropathy. It is suggested: QST test to diagnose neuropathy early for patients genetically diagnosed with ATTR, if they show signs or symptoms suggesting fine fiber neuropathy Measure alkaline phosphatase to initially assess liver involvement in patients with amyloidosis., (Universidad Nacional de Córdoba)

We conducted a retrospective cohort study to report the clinical characteristics, incidence and outcomes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.

A novel series of Lu 3 Al 5- x Fe x O 12 :Ce 3+ (0.00 ≤ x ≤ 0.45) garnets were obtained by the solid-state reaction method at 1200 °C. The obtained materials were characterized by X-ray diffraction, Rietveld refinement, UV-Vis diffuse reflectance spectroscopy, absorption spectroscopy, and photoluminescence spectroscopy. Fe 3+ doping allowed obtaining pure-phase materials at temperatures and times below those reported up to now. On the other hand, the materials reached an improved blue absorption and a tunable emission from green to orange. These optical properties are attributable to a red-shift phenomenon due to an increase of the crystal field splitting in the Ce 3+ energy-levels. Moreover, the obtained phosphors exhibited a high quantum yield (55-67%), excellent thermal photoluminescence stability (up to 200 °C), and high color conversion, making the obtained phosphors promising candidates for w-LEDs., Competing Interests: The authors declare that there are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS., Methods: A panel of 4rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for the document elaboration, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network, SIGN levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques)., Results: Forty-six recommendations were drawn up, addressing 5main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the last 25, referring to the areas of: obstetric APS and special situations. The document provides a table of recommendations and treatment algorithms., Conclusions: Update of SER recommendations on APS is presented. This document corresponds to part II, related to obstetric SAF and special situations. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A part I has also been prepared, which addresses aspects related to diagnosis, evaluation and treatment., (Publicado por Elsevier España, S.L.U.)

Introduction: Epidemiology of acute kidney injury (AKI) is highly dependent on patient characteristics, context and geography. Considering the limited information in Latin America and the Caribbean, we performed a study with the aim to contribute to improve its better understanding., Methods: Observational, prospective, longitudinal, multinational cohort study addressed to determine risk factors, clinical profile, process of care and outcomes of AKI in the region. Patients meeting KDIGO AKI definition were included over a 9-month period and designated community or hospital-acquired. De-identified clinical and lab data were entered in a specifically designed on-line platform. Co-variables potentially linked to AKI onset, in-hospital and 90-days mortality, were recorded and correlated using a multiple logistic regression model., Results: Fifty-seven physicians from 15 countries provided data on 905 patients, most with acceptable basic needs coverage. Median age 64 (50-74) yrs; most of them were male (61%) and mestizos (42%). Comorbidities were present in 77%. AKI was community-acquired in 62%. Dehydration, shock and nephrotoxic drugs were the commonest causes. During their process of care, 77% of patients were assessed by nephrologists. Kidney replacement therapy (KRT) was performed in 29% of cases. In-hospital mortality was 26.5% and independently associated to older age, chronic liver disease, hypotension, shock, cardiac disturbances, hospital-acquired sepsis, KRT and mechanical ventilation. At 90-days follow up partial or complete renal recovery was 81% and mortality 24%., Conclusions: AKI was mainly community-acquired, in patients with comorbidities and linked to fluid loss and nephrotoxic drugs. Mortality was high and long-term follow up poor. Notwithstanding, the study shows partially the situation in the participant countries rather than the actual epidemiology of AKI in Latin America and Caribbean, a pending and needed task., Competing Interests: The authors have declared that no competing interests exist.

Background: Heart transplantation (HT) is regarded as the treatment of choice for end-stage heart failure (ESHF) patients. Severe acute kidney injury (AKI) after HT is a frequent clinical problem with devastating consequences for HT recipients., Methods: Data from 112 ESHF patients undergoing HT in 2010-2015 were retrospectively reviewed. The primary end point was the development of AKI stage III, and secondary outcomes were in-hospital and 1-year mortality according to Kidney Disease Improving Global Outcomes criteria., Results: In total, 81 patients (72.3%) developed AKI, of which 33 (29.4%) developed AKI stage I, 18 (16%) stage II, and 30 (26.7%) stage III; within this group, 27 recipients (24%) required renal replacement therapy (RRT). Overall hospital mortality was 14%. However, when stratifying by AKI stage, hospital mortality increased from 0% to 46% comparing recipients without AKI and those with AKI stage III, respectively (P = .001). In the same way, 1-year mortality increased from 6% to 53% for recipients without AKI compared with those who developed AKI stage III (log-rank test for trend: P = .001). Recipients that required RRT had a 1-year mortality of 59.2% compared with 5.8% in those without RRT requirement., Conclusions: The findings indicate that AKI stage III is common after HT and adversely affects early and late mortality. Clinical variables together with perioperative hemodynamic assessment could add more powerful prognostic information to predict severe AKI before HT and therefore evaluate potential heart-kidney recipients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN., Methods: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded., Results: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036)., Conclusions: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS., Methods: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24 h following CS, were assessed., Results: We included 66 patients (26% female) aging 68 ± 11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89 ± 0.67% vs. 34.22 ± 0.58%; p < 0.05) 6 h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p = NS)., Conclusion: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.

Objectives: Renal flares are common in lupus nephritis (LN), and class switch is thought to be characteristic. There is no agreement on indications for performing a repeat renal biopsy. Our objective was to retrospectively review patients who had more than one renal biopsy performed on clinical indications, and analyse clinical, pathological and treatment changes after successive biopsies., Methods: Forty-five patients with LN and one or more repeat renal biopsies were included, with a total of 116 biopsies., Results: Of the 71 repeat biopsies, pathological transition occurred in 39 (54.9%). When having a previous biopsy with a proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into non-proliferative classes. When previous biopsy was class V, transition to other classes occurred in 58.3% and changes were all into proliferative classes. Conversion from one pure proliferative form to another (class III to class IV or vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%) leading to a change in the treatment regimen., Conclusions: Histological transformations were common, and they occurred when the previous biopsy had non-proliferative lesions as well as when lesions were proliferative. Treatments were modified after repeat renal biopsy in the majority of patients. In this experience, kidney repeat biopsies were useful in guiding treatment of LN flares.