Nanoplasmonic Single-Tumoroid Microarray for Real-Time Secretion Analysis.

Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine as such 3D structures grown from tumor cells recapitulate better tumor characteristics, making these tumoroids unique for personalized cancer research. Assessment of their functional behavior, particularly protein secretion, is of significant importance to provide comprehensive insights. Here, a label-free spectroscopic imaging platform is presented with advanced integrated optofluidic nanoplasmonic biosensor that enables real-time secretion analysis from single tumoroids. A novel two-layer microwell design isolates tumoroids, preventing signal interference, and the microarray configuration allows concurrent analysis of multiple tumoroids. The dual imaging capability combining time-lapse plasmonic spectroscopy and bright-field microscopy facilitates simultaneous observation of secretion dynamics, motility, and morphology. The integrated biosensor is demonstrated with colorectal tumoroids derived from both cell lines and patient samples to investigate their vascular endothelial growth factor A (VEGF-A) secretion, growth, and movement under various conditions, including normoxia, hypoxia, and drug treatment. This platform, by offering a label-free approach with nanophotonics to monitor tumoroids, can pave the way for new applications in fundamental biological studies, drug screening, and the development of therapies.

Predictors of autosomal dominant polycystic kidney disease progression: a Brazilian single-center cohort.

INTRODUCTION: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. METHODS: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. RESULTS: The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome. CONCLUSIONS: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.

Association between chronic kidney disease stages and changes in ambulatory blood pressure monitoring parameters.

INTRODUCTION: Blood pressure (BP) assessment affects the management of arterial hypertension (AH) in chronic kidney disease (CKD). CKD patients have specific patterns of BP behavior during ambulatory blood pressure monitoring (ABPM). OBJECTIVES: The aim of the current study was to evaluate the associations between progressive stages of CKD and changes in ABPM. METHODOLOGY: This is a cross-sectional study with 851 patients treated in outpatient clinics of a university hospital who underwent ABPM examination from January 2004 to February 2012 in order to assess the presence and control of AH. The outcomes considered were the ABPM parameters. The variable of interest was CKD staging. Confounding factors included age, sex, body mass index, smoking, cause of CKD, and use of antihypertensive drugs. RESULTS: Systolic BP (SBP) was associated with CKD stages 3b and 5, irrespective of confounding variables. Pulse pressure was only associated with stage 5. The SBP coefficient of variation was progressively associated with stages 3a, 4 and 5, while the diastolic blood pressure (DBP) coefficient of variation showed no association. SBP reduction was associated with stages 2, 4 and 5, and the decline in DBP with stages 4 and 5. Other ABPM parameters showed no association with CKD stages after adjustments. CONCLUSION: Advanced stages of CKD were associated with lower nocturnal dipping and greater variability in blood pressure.

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .

Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Executive Summary of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management.

The Airway section of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) present the Guidelines for the integral management of difficult airway in adult patients. This document provides recommendations based on current scientific evidence, theoretical-educational tools and implementation tools, mainly cognitive aids, applicable to the treatment of the airway in the field of anesthesiology, critical care, emergencies and prehospital medicine. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations and optimization in the progression of the application of strategies to preserve adequate alveolar oxygenation in order to improve safety and quality of care.

Integrase strand transfer inhibitor resistance mediated by R263K plus E157Q in a patient with HIV infection treated with bictegravir/tenofovir alafenamide/emtricitabine: case report and review of the literature.

OBJECTIVES: The in vivo selection of E157Q plus R263K has not been reported in patients treated with coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). To the best of our knowledge, we hereby report the first case of high-grade INSTI resistance associated with the presence of these aminoacidic substitutions in a treatment-experienced HIV patient treated with BIC/FTC/TAF. METHODS: Clinical case report and review of the literature. RESULTS: A heavily treatment-experienced patient was switched to BIC/FTC/TAF due to drug-drug interactions after being diagnosed with disseminated Mycobacterium avium-intracellulare disease. He had been treated before with raltegravir with poor adherence. No mutations in the integrase gene were detected 1 year after finishing treatment with raltegravir. Months after being switched to BIC/FTC/TAF, and again with poor adherence documented, virological failure (VF) was detected. The polymorphic substitution E157Q and the resistance mutation R263K in the integrase gene were detected, as well as M184V, among other mutations in the reverse transcriptase gene. The patient is currently being treated with dolutegravir q12h plus boosted darunavir along with directly observed treatment, and for the first time in 20 years, plasmatic viral load values are below 100 copies/mL. CONCLUSIONS: This case illustrates that the combination of E157Q and R263K plus M184V can be selected in vivo in a clinical scenario of poor adherence with BIC/FTC/TAF, although it is a very rare phenomenon. Previous VF with first-generation integrase strand transfer inhibitors (INSTIs) should be kept in mind when switching patients to second-generation INSTIs.

Association of cardiovascular risk factors and myocardial hypertrophy in women with preeclampsia history.

AIMS: A historic of preeclampsia (PE) has been associated with cardiovascular disease (CVD) in women. There are substantial evidences that cardiovascular changes resulting from PE can persist even after pregnancy end. Therefore, the aims was to evaluate the prevalence of myocardial hypertrophy in young women 12 months after PE event as well as try to identify risk factors for these changes. MATERIALS AND METHODS: Single-center observational prospective cross-sectional study that included 118 consecutive patients after 12 months of PE. Clinical and laboratory evaluations, echocardiogram were performed. Myocardial hypertrophy (LVH) was defined as an index myocardial mass ≥ 45 g/m2.7, for women. Classical risk factors for CVD were considered. Analysis included linear or logistic regression and Spearman's correlation coefficient. Significance level of 5 %. KEY FINDINGS: Systemic arterial hypertension (SAH) was identified in 52 patients (44 %), overweight/obesity (OOB) in 82 (69 %), dyslipidemia in 68 (57 %) and metabolic syndrome in 47 patients (40 %). LVH was present in 35 cases (29 %) and associated with OOB (OR = 4.51; CI95%:1.18-17.17, p < 0.001), in a model corrected for age and SAH diagnosis. When only the metabolic syndrome components were analyzed, in the multiple logistic regression model, the abdominal circumference was the only clinical variable associated with LVH (OR = 17.65; CI95%:3.70-84.17; p < 0.001). SIGNIFICANCE: It was observed a high prevalence of ventricular hypertrophy in young women with a history of pre-eclampsia. This condition was associated with the presence of obesity.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis / Avaliação dos fatores de risco de aterosclerose e disfunção endotelial em pacientes com glomerulopatias primárias

Abstract Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Impact of ChAdOx1 or DNA Prime Vaccination on Magnitude, Breadth, and Focus of MVA-Boosted Immunogen-Specific T Cell Responses.

The efficacy of anti-viral T-cell vaccines may greatly depend on their ability to generate high-magnitude responses targeting a broad range of different epitopes. Recently, we created the HIV T-cell immunogen HTI, designed to generate T-cell responses to protein fragments more frequently targeted by HIV controllers. In the present study, we aim to maximize the breadth and magnitude of the T-cell responses generated by HTI by combining different vaccine vectors expressing HTI. We evaluated the ability to induce strong and broad T-cell responses to the HTI immunogen through prime vaccination with DNA plasmid (D) or Chimpanzee Adenovirus Ox1 (ChAdOx1; C) vectors, followed by a Modified Virus Ankara (MVA; M) vaccine boost (DDD, DDDM, C, and CM). HTI-specific T-cell responses after vaccination were measured by IFN-γ-ELISpot assays in two inbred mice strains (C57BL/6 and BALB/c). CM was the schedule triggering the highest magnitude of the response in both mice strains. However, this effect was not reflected in an increase in the breadth of the response but rather in an increase in the magnitude of the response to specific immunodominant epitopes. Immunodominance profiles in the two mouse strains were different, with a clear dominance of T-cell responses to a Pol-derived peptide pool after CM vaccination in C57BL/6. Responses to CM vaccination were also maintained at higher magnitudes over time (13 weeks) compared to other vaccination regimens. Thus, while a ChAdOx1 prime combined with MVA booster vaccination generated stronger and more sustained T-cell responses compared to three DNA vaccinations, the ChAdOx1 primed responses were more narrowly targeted. In conclusion, our findings suggest that the choice of vaccine vectors and prime-boost regimens plays a crucial role in determining the strength, duration, breadth, and focus of T-cell responses, providing further guidance for selecting vaccination strategies.

Climate change increases threat to plant diversity in tropical forests of Central America and southern Mexico.

Global biodiversity is negatively affected by anthropogenic climate change. As species distributions shift due to increasing temperatures and precipitation fluctuations, many species face the risk of extinction. In this study, we explore the expected trend for plant species distributions in Central America and southern Mexico under two alternative Representative Concentration Pathways (RCPs) portraying moderate (RCP4.5) and severe (RCP8.5) increases in greenhouse gas emissions, combined with two species dispersal assumptions (limited and unlimited), for the 2061-2080 climate forecast. Using an ensemble approach employing three techniques to generate species distribution models, we classified 1924 plant species from the region's (sub)tropical forests according to IUCN Red List categories. To infer the spatial and taxonomic distribution of species' vulnerability under each scenario, we calculated the proportion of species in a threat category (Vulnerable, Endangered, Critically Endangered) at a pixel resolution of 30 arc seconds and by family. Our results show a high proportion (58-67%) of threatened species among the four experimental scenarios, with the highest proportion under RCP8.5 and limited dispersal. Threatened species were concentrated in montane areas and avoided lowland areas where conditions are likely to be increasingly inhospitable. Annual precipitation and diurnal temperature range were the main drivers of species' relative vulnerability. Our approach identifies strategic montane areas and taxa of conservation concern that merit urgent inclusion in management plans to improve climatic resilience in the Mesoamerican biodiversity hotspot. Such information is necessary to develop policies that prioritize vulnerable elements and mitigate threats to biodiversity under climate change.

To what extent does frailty mediate the association between age and the outcomes of brain reperfusion following acute ischemic stroke?

Objective: We evaluated the extent to which frailty mediated the association between age, poor functional outcomes, and mortality after acute ischemic stroke when patients were treated with brain reperfusion (thrombolytic therapy and/or thrombectomy). Materials and methods: This retrospective cohort study included patients diagnosed with ischemic stroke who had undergone intravenous cerebral reperfusion therapy and/or mechanical thrombectomy. We created a mediation model by analyzing the direct natural effect of an mRS score > 2 and death on age-mediated frailty according to the Frailty Index. Results: We enrolled 292 patients with acute ischemic stroke who underwent brain reperfusion. Their mean age was 67.7 ± 13.1 years. Ninety days after the stroke ictus, 54 (18.5%) participants died, and 83 (28.4%) lived with moderate to severe disability (2 < mRS < 6). In the mediation analysis of the composite outcome of disability (mRS score > 2) or death, frailty accounted for 28% of the total effect of age. The models used to test for the interaction between age and frailty did not show statistically significant interactions for either outcome, and the addition of the interaction did not significantly change the direct or indirect effects, nor did it improve model fit. Conclusion: Frailty mediated almost one-third of the effect of age on the composite outcome of disability or death after acute ischemic stroke.

Different methods for assessing glomerular filtration rate in the elderly.

OBJECTIVE: The objective of this study was to identify the best method to replace cystatin C in the evaluation of glomerular filtration in the elderly. METHODS: Individuals over 60 years of age from a primary care center were studied. Blood was collected to determine creatinine and cystatin C and 24-h urine. Three methods were compared to determine glomerular filtration: Creatinine clearance, Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine, considering as a reference the determination of glomerular filtration using the cystatin-based Chronic Kidney Disease Epidemiology Collaboration equation. The statistical methods used were linear regression, Bland-Altman curve, and receiver operating characteristic. RESULTS: A total of 180 elderly people were evaluated, but 14 patients were lost from the sample, resulting in a total of 166 patients. The average age of patients was 66.9±6.1 years, and 69.8% were females. Regarding the number of patients eligible for the study, there were 12 black, 108 brown, and 46 white, 42.77% hypertensive, and 38.3% diabetic. Glomerular filtration was less than 60 mL/min in 22.28% of patients. Regarding the evaluation of the different equations, the correlation coefficient was lower for creatinine clearance and progressively higher for Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine. The Bland-Altman diagram and the receiver operating characteristic curve showed similar performance to the correlation coefficient for the different equations evaluated. CONCLUSION: Collaboration Epidemiology of Chronic Kidney Disease based on creatinine presented the best performance. Creatinine debug had the worst performance, which reinforces the idea that 24-h urine collection is unnecessary in these patients.

Open, Observational, Single-Arm, Multicenter Study Assessing the Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine for Osteoarthritis Pain Reduction.

Osteoarthritis (OA) is an age-related degenerative joint disease with a great impact on patients' well-being and quality of life. This is an observational, open, single-arm multicenter study aimed to evaluate the effectiveness of a nutritional supplement in patients with knee and/or hip OA. A total of 186 patients were recruited from Spanish centers and received a supplement containing hydrolyzed collagen (3000 mg), chondroitin sulfate (800 mg), glucosamine sulfate (700 mg), turmeric extract (250 mg) and devil's claw (150 mg), once daily during 6 months. The primary outcome was the patients' self-perceived pain in the affected joints measured with a visual analogue scale (VAS). Secondary outcome was the patient's functioning, measured with the Lequesne Functional Index and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Participants showed a significant reduction in self-perceived pain after 3 (mean reduction ± standard deviation, 1.99 ± 1.05) and 6 months (3.57 ± 1.39) of treatment (p < 0.0001 in both comparisons). Lequesne Functional Index score was significantly reduced at 3 months (3.86 ± 2.94) and at 6 months (6.73 ± 4.30) of treatment (p < 0.0001 in both comparisons). The WOMAC index was also significantly reduced after 3 (14.24 ± 10.04) and 6 months (26.43 ± 17.35) of treatment (p < 0.0001 in both comparisons). Significant reductions in WOMAC subdomains (p < 0.0001 in all comparisons) were observed. No severe adverse events were reported during the study. The main results arising from this study show that this nutritional supplementation can improve OA-related symptoms and physical function with a good safety profile in patients with hip and/or knee OA.

Clonal spread of fluconazole-resistant C. parapsilosis in patients admitted to a referral hospital located in Burgos, Spain, during the COVID-19 pandemic.

BACKGROUND: Fluconazole-resistant Candida parapsilosis (FRCP) is a matter of concern in Spain. OBJECTIVES: We here report a FRCP spread across a 777-bed referral hospital located in Burgos, Spain, during the COVID-19 pandemic. PATIENTS/METHODS: In April 2021, an FRCP isolate (MIC = 64 mg/L, E-test®) from a hospitalised patient was detected. Up to June 2022, all C. parapsilosis isolates (n = 35) from hospitalised patients (n = 32) were stored and genotyped using microsatellite markers, and their antifungal susceptibilities were studied (EUCAST); FRCP isolates were molecularly characterised. RESULTS: We detected 26 FRCP isolates collected between 2021 (n = 8) and 2022 (n = 18); isolates were susceptible to amphotericin B, echinocandins and ibrexafungerp. FRCP isolates were grouped into three genotypes: CP-707 and CP-708 involved isolates harbouring the Y132F + R398I ERG11p substitutions (n = 24) and were clonally related; the remaining CP-675 genotype involved isolates harbouring the G458S ERG11p substitution (n = 2). FRCP genotypes were genetically related to the FRCP genotypes found in Madrid and were unrelated to fluconazole-susceptible ones. Patients harbouring FRCP were mainly (n = 22/23) admitted to intensive care units. Most patients had received broad-spectrum antibiotics (n = 22/23), and/or antifungal therapy with azoles (n = 14/23) within the 30 days prior to FRCP isolation. Thirteen patients were colonised, 10 of whom were infected and presented candidaemia (n = 8/10), endovascular infection (n = 1/10) or complicated urinary infection (n = 1/10). Overall nonattributable 30-day mortality was 17% (n = 4/23). CONCLUSIONS: We report an outbreak caused by FRCP affecting patients admitted to the ICU of a referral hospital located in Burgos. Patients harbouring FRCP had a higher fluconazole use than those carrying susceptible isolates.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis.

INTRODUCTION: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. HYPOTHESIS: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. OBJECTIVE: To evaluate the main markers of atherosclerosis in patients with PG. METHOD: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. RESULTS: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. DISCUSSION AND CONCLUSION: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Different methods for assessing glomerular filtration rate in the elderly

SUMMARY OBJECTIVE: The objective of this study was to identify the best method to replace cystatin C in the evaluation of glomerular filtration in the elderly. METHODS: Individuals over 60 years of age from a primary care center were studied. Blood was collected to determine creatinine and cystatin C and 24-h urine. Three methods were compared to determine glomerular filtration: Creatinine clearance, Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine, considering as a reference the determination of glomerular filtration using the cystatin-based Chronic Kidney Disease Epidemiology Collaboration equation. The statistical methods used were linear regression, Bland-Altman curve, and receiver operating characteristic. RESULTS: A total of 180 elderly people were evaluated, but 14 patients were lost from the sample, resulting in a total of 166 patients. The average age of patients was 66.9±6.1 years, and 69.8% were females. Regarding the number of patients eligible for the study, there were 12 black, 108 brown, and 46 white, 42.77% hypertensive, and 38.3% diabetic. Glomerular filtration was less than 60 mL/min in 22.28% of patients. Regarding the evaluation of the different equations, the correlation coefficient was lower for creatinine clearance and progressively higher for Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine. The Bland-Altman diagram and the receiver operating characteristic curve showed similar performance to the correlation coefficient for the different equations evaluated. CONCLUSION: Collaboration Epidemiology of Chronic Kidney Disease based on creatinine presented the best performance. Creatinine debug had the worst performance, which reinforces the idea that 24-h urine collection is unnecessary in these patients.