Natural Killer Cell Dysfunction In Human Bladder Cancer Is Caused By Tissue-Specific Suppression of SLAMF6 Signaling.

NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors. Rather, TME-specific TGF-ß and metabolic perturbations such as hypoxia directly suppressed NK cell function. Specifically, an oxygen-dependent reduction in signaling through SLAMF6 was mechanistically responsible for poor NK cell function, as tumor-infiltrating NK cells cultured ex vivo under normoxic conditions exhibited complete restoration of function, while deletion of SLAMF6 abrogated NK cell cytolytic function even under normoxic conditions. Collectively, this work highlights the role of tissue-specific factors in dictating NK cell function, and implicates SLAMF6 signaling as a rational target for immuno-modulation to improve NK cell function in bladder cancer.

Characterization of renal masses with MRI-based radiomics: assessment of inter-package and inter-observer reproducibility in a prospective pilot study.

OBJECTIVES: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization. METHODS: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM. RESULTS: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM. CONCLUSION: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM. CLINICAL RELEVANCE: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization.

Stratification of Patients with Renal Cell Carcinoma by the Abundance of Sarcomatoid Features Reveals Differences in Survival and the Underlying Pathobiology.

Sarcomatoid renal cell carcinoma (sRCC) is histologically heterogeneous, with variable sarcomatoid amounts intermixed within epithelial carcinoma. However, the current classification for this aggressive disease is homogeneous and agnostic to the sarcomatoid proportion. We investigated whether sRCC subclassification has prognostic value and can reveal the biology underlying dedifferentiation and its clinical aggressiveness. On the basis of the intratumoral abundance of sarcomatoid features, cases were classified as sarcomatoid-high (≥10% sarcomatoid features) or sarcomatoid-low (<10% sarcomatoid features) in a cohort of 104 consecutive patients with sRCC undergoing nephrectomy at a single center. In comparison to sarcomatoid-low patients (n = 52), sarcomatoid-high patients (n = 52) had significantly shorter overall survival (median 14.5 vs 62.9 mo; p < 0.001), which was confirmed on multivariable analysis, and significantly shorter median metastasis-free survival among patients with clinically localized disease (10.7 vs 39.0 mo; p = 0.043). Transcriptomic analyses of 45 sRCC tumors revealed significant upregulation of nine hallmark pathways related to cell cycle/proliferation, epithelial-to-mesenchymal transition, reactive oxidative species, and interferon-α signaling among sarcomatoid-high (n = 24) versus sarcomatoid-low (n = 21) tumors. Categorization into transcriptomic clusters revealed predominance of proliferative, inflammatory, and immune effector phenotypes among sarcomatoid-high tumors, versus a hypoxia/angiogenesis phenotype among sarcomatoid-low tumors. Overall, these findings indicate prognostic value for sRCC subclassification into high versus low sarcomatoid groups and highlight key biology underlying the differences in clinical outcomes. PATIENT SUMMARY: Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of kidney cancer. The percentage of sarcomatoid features varies among tumors, but sRCC is still defined as a single kidney cancer type. Our results show that grouping patients according to their percentage of sarcomatoid features improves prediction of whether their tumors will become metastatic or lethal, and reveal molecular differences that may be important for this disease. Future assignment of sRCC to high and low sarcomatoid groups may help in guiding research and patient management.

Experiencias en implementación de rutas integrales de atención en salud en Cauca. Un estudio cualitativo

Introducción: Las dinámicas poblacionales, la carga de enfermedad y los cambios estructurales político-económicos han impulsado al estado colombiano a buscar la integralidad en los procesos de atención en salud, en tal propósito definió la implementación de rutas integrales de atención en salud (RIAS). Objetivo: Comprender la percepción de la experiencia que tienen los líderes de proceso en entidades sanitarias referente a la implementación de las RIAS en Cauca, Colombia. Método: Estudio cualitativo, inductivo, con enfoque de fenomenología interpretativa. El grupo de estudio estuvo conformado por siete líderes de proceso de entidades sanitarias. Resultados: Los entrevistados sienten que la implementación es un proceso difícil, determinado por la voluntad y compromiso de los actores sanitarios. Los cambios de administración generan discontinuidades afectando avances en las rutas de la que ellos son responsables. Perciben desarticulación en la implementación, limitados recursos, deficiencia administrativa, de infraestructura y talento humano, principalmente especialistas en salud. Discusión: La percepción de las experiencias denota lo que varios autores han descrito en relación con tensiones en procesos de implementación y gestión en salud: inaccesibilidad, discontinuidad y fragmentación de servicios; débil autoridad sanitaria, enfoque curativo e intereses económicos. Conclusiones: Desde su experiencia, los líderes del proceso perciben las RIAS como un fundamento estratégico que favorece la atención integral en salud, sin embargo, existen vacíos en la implementación originados de procesos administrativos, financieros y del propio modelo de salud, restringiendo el cumplimiento del propósito para las cuales fueron creadas. A la vez, perciben sentimientos de impotencia y desesperanza, dificultades y tensiones en el ejercicio de la implementación.

Introduction: Population dynamics, disease burden and political-economic structural changes have prompted the Colombian state to seek comprehensiveness in health care processes, and to this end it defined the implementation of Integrated Health Care Routes (RIAS). Objective: To understand the perception of the experience of process leaders in health entities regarding the implementation of the RIAS in Cauca, Colombia. Method: Qualitative, inductive study with an interpretative phenomenology approach. The study group consisted of seven process leaders of health entities. Results: The interviewees feel that implementation is a difficult process, determined by the willingness and commitment of the health stakeholders. Changes in administration generate discontinuities affecting progress on the routes for which they are responsible. They perceive disarticulation in implementation, limited resources, administrative deficiencies, infrastructure and human talent, mainly health specialists. Discussion: The perception of the experiences denotes what several authors have described in relation to tensions in implementation and management processes in health: inaccessibility, discontinuity and fragmentation of services; weak health authority, curative approach and economic interests. Conclusions: From their experience, process leaders perceive the RIAS as a strategic foundation that favors comprehensive health care; however, there are gaps in the implementation caused by administrative and financial processes and the health model itself, restricting the fulfillment of the purpose for which they were created. At the same time, they perceive feelings of helplessness and hopelessness, difficulties and tensions in the implementation exercise.

Itinerarios terapéuticos de mujeres migrantes con hipertensión arterial: miradas desde el proceso salud-enfermedad-atención / Therapeutic itineraries of migrant women with arterial hypertension: views from the health-disease-care process

Introducción: La hipertensión arterial (HTA) es un factor de riesgo de morbilidad y mortalidad a nivel global y la principal causa de muerte prematura, afecta en buena parte a mujeres. El propósito del estudio fue comprender cómo las mujeres migrantes (MM) con HTA configuran sus itinerarios terapéuticos (IT) en la búsqueda de atención sanitaria en Colombia, desde el proceso salud-enfermedad-atención. Métodos: Estudio cualitativo con enfoque de teoría fundamentada. Se realizaron 16 entrevistas y 2 grupos focales a MM con HTA en Popayán Colombia. Se realizó muestreo teórico intencionado hasta alcanzar la saturación teórica y la abstracción de categorías emergentes a través de codificación abierta, axial y selectiva. Resultados: La codificación abierta generó 1.135 códigos. La categoría principal emergente fue que los IT en la atención de la HTA están determinados por dinámicas sociales, culturales, políticas y económicas. Como subcategorías relacionadas emergieron: riesgos de enfermar por HTA configuran IT; surge heterogeneidad de recursos terapéuticos formales e informales para atender la enfermedad; existen determinantes de acceso al sistema sanitario; y movilización de diversas prácticas para el seguimiento y control del padecimiento. Conclusión: Las mujeres en situación de migración con HTA configuran IT para lograr la atención en salud no solo desde el sistema sanitario estatal, sino a partir de diversos elementos del orden social, cultural, político y económico. En esta medida, la HTA supera nominaciones mórbidas exclusivas de la biomedicina y de la relación médico-paciente, para abocarse y trascender hacia un padecimiento que exige resolver contingencias del contexto. (AU)

Introduction: Arterial hypertension (AH) is a global risk factor for morbidity and mortality and the main cause of premature death, largely affecting women. The purpose of the study was to understand how migrant women (MW) with AH configure their therapeutic itineraries (TI) in the search for health care in Colombia, from the health-disease-care process. Methods: Qualitative study with a grounded theory approach. 16 interviews and two focus groups were conducted with MW with AH in Popayán Colombia. Intentional theoretical sampling was carried out until reaching theoretical saturation and the abstraction of emerging categories through open, axial and selective coding. Results: Open coding generated 1,135 codes. The main emerging category was that TI in AH care are determined by social, cultural, political, and economic dynamics. As related subcategories emerged: the risks of getting sick from AH configure TI; heterogeneity of formal and informal therapeutic resources arises to attend to the disease; there are determinants of access to the health system; and mobilization of various practices for monitoring and control of the disease. Conclusion: Women in a situation of migration with AH configure TI to achieve health care not only from the state health system, but from various elements of the social, cultural, political and economic order. To this extent, AH goes beyond morbid nominations exclusive to biomedicine and the doctor-patient relationship, to address and transcend towards a condition that requires resolving contingencies of the context. (AU)

Risk Factors for Liver Fibrosis in Diabetic Patients with End-stage Renal Disease

Introduction: Liver cirrhosis is the fourth cause of death in the world. Fatty liver disease is the most common cause of chronic liver disease (CKD) in most countries. Identifying risk factors for liver fibrosis in a population with end-stage renal disease (ESRD) may facilitate early diagnosis of this complication and allow the activation of follow-up protocols to reduce morbidity and mortality in these patients. Materials and methods: A cross-sectional and analytical study was carried out. Patients on hemodialysis, older than 18 years with a diagnosis of diabetes mellitus and ESRD were included. The hypotheses were contrasted through the chi-square test and Student's T-test, as appropriate. Statistical significance was established at a p-value = 0.05. Results: A prevalence of significant liver fibrosis and cirrhosis of 17% was found. Factors associated with liver fibrosis were a history of cerebrovascular disease, peripheral vascular disease, body mass index (BMI), total cholesterol, glycosylated hemoglobin, sodium, and aspartate aminotransferase (AST). No relationship was observed between the NAFLD (non-alcoholic fatty liver disease) score, the APRI index (AST to Platelet Ratio Index), and fibrosis. Conclusion: The prevalence of significant liver fibrosis in patients with diabetes and ESRD is similar to that reported in other populations of patients with diabetes. However, some factors, such as BMI, could behave differently and favor the appearance of liver injury with lower degrees of obesity than previously reported in the literature.

Introducción: la cirrosis hepática es la cuarta causa de muerte en el mundo. Actualmente, la enfermedad hepática por depósito de grasa es la causa más frecuente de hepatopatía crónica en la mayoría de los países. La identificación de factores de riesgo para la presencia de fibrosis hepática en una población con enfermedad renal crónica terminal puede facilitar el diagnóstico temprano de esta complicación y permitir la activación de protocolos de seguimiento para disminuir la morbimortalidad en estos pacientes. Metodología: se realizó un estudio de corte transversal y analítico. Se incluyeron pacientes en hemodiálisis, mayores de 18 años con diagnóstico de diabetes mellitus y de enfermedad renal crónica terminal. El contraste de hipótesis se realizó a través de la prueba de chi cuadrado y la T de Student, según correspondiera. La significación estadística se estableció con un valor p = 0,05. Resultados: se observó una prevalencia de fibrosis hepática significativa y cirrosis del 17%. Los factores asociados a la presencia de fibrosis hepática fueron los antecedentes de enfermedad cerebrovascular, la enfermedad vascular periférica, el índice de masa corporal (IMC), el colesterol total, la hemoglobina glicosilada, el sodio y el aspartato-aminotransferasa (AST). No se observó relación entre el puntaje de NAFLD (enfermedad del hígado graso no alcohólico), el índice APRI (AST to Platelet Ratio Index) y la presencia de fibrosis. Conclusión: la prevalencia de fibrosis hepática significativa en pacientes con diabetes y ERCT es similar a la reportada en otras poblaciones de pacientes con diabetes. Sin embargo, algunos factores, como el IMC, podrían comportarse de forma diferente y favorecer la aparición de lesión hepática con grados menores de obesidad a los reportados previamente en la literatura.

Coinfections and Superinfections Associated with COVID-19 in Colombia: A Narrative Review.

The COVID-19 pandemic has had significant impacts on healthcare systems around the world, including in Latin America. In Colombia, there have been over 23,000 confirmed cases and 100 deaths since 2022, with the highest number of cases occurring in females and the highest number of deaths in males. The elderly and those with comorbidities, such as arterial hypertension, diabetes mellitus, and respiratory diseases, have been particularly affected. Coinfections with other microorganisms, including dengue virus, Klebsiella pneumoniae, and Mycobacterium tuberculosis, have also been a significant factor in increasing morbidity and mortality rates in COVID-19 patients. It is important for surveillance systems to be improved and protocols to be established for the early detection and management of coinfections in COVID-19. In addition to traditional treatments, alternatives such as zinc supplementation and nanomedicine may have potential in the fight against COVID-19. It is also crucial to consider the social, labor, educational, psychological, and emotional costs of the pandemic and to address issues such as poverty and limited access to potable water in order to better prepare for future pandemics.

Quality and Content Concordance of International Clinical Guidelines on Hypertensive Disorders of Pregnancy Using the AGREE II Instrument: An Updated Systematic Review.

Utilization of high-quality clinical practice guidelines has the potential to positively impact health outcomes. This study aimed to assess the quality and content concordance of national and international recommendations on hypertensive disorders of pregnancy (HDPs). Searches were conducted of the MEDLINE database and reference lists generated from national and international agencies. Covidence software was used for the management of the systematic review process, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used to assess guidelines for quality, and three reviewers independently screened records. The research team identified and screened a total of 399 records of which 10 were deemed high quality. Guidelines were assessed and compared regarding the treatment, prevention, and categorization of disorders. The quality of guidelines varied across different domains, with significant variation in domain scores even within individual guidelines. Not all recommendations showed a high level of methodologic rigor, and the highest-rated guidelines were from the American Heart Association, the World Health Organization, and South Africa national guidelines. Classification of hypertension differed among the guidelines, particularly in defining chronic hypertension, severe hypertension, and preeclampsia. Prevention modalities varied across guidelines, with recommendations for aspirin, calcium supplementation, and against the use of certain approaches. Treatment modalities highlighted the importance of delivery as the definitive way to terminate hypertensive disorders of pregnancy, with other management strategies provided for symptom control. The variability in guidelines and consensus statements across different contexts may reflect regional differences in healthcare practices, available resources, and research evidence. There is potential to harmonize guidelines for HDP globally while considering the unique needs of individual countries. Where guidelines may be synthesized and condensed into an accessible format, doing so could improve their use in clinical decision-making.

Does testosterone replacement therapy increase the risk of conversion to treatment in patients with prostate cancer on active surveillance?

PURPOSE: We aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer (CaP) who elected active surveillance (AS). METHODS: A retrospective review of our CaP database was performed. Patients who received TRT while on AS were identified and were matched to a cohort of patient on AS while not on TRT (1:3) using propensity score matching. Treatment-free survival (TFS) was computed using Kaplan Meier method. Multivariable Cox regression model was used to evaluate variables associated with treatment. RESULTS: Twenty-four patients in the TRT group were matched to 72 patients without TRT. Median follow-up was 5.82 years (IQR 3.27-9.30). There was no significant difference in conversion to treatment (24% vs. 21%, P = 1.00) There was no significant difference in TFS (log rank P = 0.87). Prostate specific antigen (PSA) density was the only variable associated TFS (HR 1.08, 95%CI 1.03-1.13, P = 0.001). CONCLUSION: TRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS.

Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer.

BACKGROUND: Data on Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) have shown that follow-up cystoscopies are normal in 82% and 67% of patients with single and multiple tumors, respectively. OBJECTIVE: To develop a predictive model associated with recurrence-free survival (RFS) at 6, 12, 18 and 24 months in TaLG cases that consider the patients' risk aversion. MATERIALS AND METHODS: Data from a prospectively maintained database of 202 newly diagnosed TaLG NMIBC patients treated at Scandinavian institutions were used for the analysis. To identify risk groups associated with recurrence, we performed a classification tree analysis. Association between risk groups and RFS was evaluated by Kaplan Meier analysis. A Cox proportional hazard model selected significant risk factors associated with RFS using the variables defining the risk groups. The reported C index for the Cox model was 0.7. The model was internally validated and calibrated using 1000 bootstrapped samples. A nomogram to estimate RFS at 6, 12, 18, and 24 months was generated. The performance of our model was compared to EUA/AUA stratification using a decision curve analysis (DCA). RESULTS: The tree classification found that tumor number, tumor size and age were the most relevant variables associated with recurrence. The patients with the worst RFS were those with multifocal or single, ≥ 4cm tumors. All the relevant variables identified by the classification tree were significantly associated with RFS in the Cox proportional hazard model. DCA analysis showed that our model outperformed EUA/AUA stratification and the treat all/none approaches. CONCLUSION: We developed a predictive model to identify TaLG patients that benefit from less frequent follow-up cystoscopy schedule based on the estimated RFS and personal recurrence risk aversion.

Urine supernatant reveals a signature that predicts survival in clear-cell renal cell carcinoma.

OBJECTIVE: To profile the cell-free urine supernatant and plasma of a small cohort of clear-cell renal cell carcinoma (ccRCC) patients by measuring the relative concentrations of 92 proteins related to inflammation. Using The Cancer Genome Atlas (TCGA), we then performed a targeted mRNA analysis of genes encoding the above proteins and defined their effects on overall survival (OS). SUBJECTS/PATIENTS AND METHODS: Samples were collected prospectively from ccRCC patients. A multiplex proximity extension assay was used to measure the concentrations of 92 inflammation-related proteins in cell-free urine supernatants and plasma. Transcriptomic and clinical information from ccRCC patients was obtained from TCGA. Unsupervised clustering and differential protein expression analyses were performed on protein concentration data. Targeted mRNA analysis on genes encoding significant differentially expressed proteins was performed using TCGA. Backward stepwise regression analyses were used to build a nomogram. The performance of the nomogram and clinical benefit was assessed by discrimination and calibration, and a decision curve analysis, respectively. RESULTS: Unsupervised clustering analysis revealed inflammatory signatures in the cell-free urine supernatant of ccRCC patients. Backward stepwise regressions using TCGA data identified transcriptomic risk factors and risk groups associated with OS. A nomogram to predict 2-year and 5-year OS was developed using these risk factors. The decision curve analysis showed that our model was associated with a net benefit improvement compared to the treat-all/none strategies. CONCLUSION: We defined four novel biomarkers using proteomic and transcriptomic data that distinguish severity of prognosis in ccRCC. We showed that these biomarkers can be used in a model to predict 2-year and 5-year OS in ccRCC across different tumour stages. This type of analysis, if validated in the future, provides non-invasive prognostic information that could inform either management or surveillance strategies for patients.

[Associated factors in the intention of vaccination against COVID-19, in POPAYÁN, Cauca Colombia]. / FACTORES ASOCIADOS A LA INTENCIÓN DE VACUNACIÓN CONTRA EL COVID-19, EN POPAYÁN, CAUCA COLOMBIA.

Vaccination against the Covid-19 pandemic, decreed by the WHO in 2020, has shown in the initial trials an admissible efficacy for the scientific community, but with many doubts and concerns for the communities, developing the phenomenon known as vaccine hesitancy. Objective: to understand the factors associated with the intention or rejection of vaccination against COVID-19 in the city of Popayán in the year 2022. Methodology: Cross-sectional descriptive-analytical study, carried out between August 2021 and March 2022; with a non-probabilistic sampling, for convenience, with a sample size of 993 people; A questionnaire-type survey was applied in person and virtually to know the intention of vaccination, knowledge and perceptions. Results: The surveyed population was characterized as 56.19% female, 49.24% between 18 and 28 years old; 23.16% state that they do not intend to be vaccinated against COVID-19, the main reasons being: not being well informed 56.29%, ineffective vaccine 54.8% and that the vaccine weakens the immune system 27,5%; as well as the low confidence with the Vaccination Plan and with the pharmaceutical companies that produce the vaccine. Conclusion: The intention to vaccinate against COVID-19 is determined not only by the technical-administrative dynamics of the immunization program and the health system, variables of the context and the perception of risk, add up to explain the vaccination processes.

Desigualdades en salud en mortalidad perinatal durante el Plan Decenal de Salud Pública 2012-2021. Cauca, Colombia

Objetivo: identificar desigualdades en salud asociadas a la mortalidad perinatal durante el Plan Decenal de Salud Pública 2012-2021 en los 42 municipios del Departamento de Cauca Colombia. Métodos: estudio ecológico que abordó el periodo 2012-2021 a partir de datos de fuentes secundarias procedentes del Departamento Administrativo Nacional de Estadística. La población de estudio fueron mujeres entre los 12 y 49 años residentes en Cauca. Se calcularon desigualdades por rangos y modelos de regresión de acuerdo con el Índice de Desigualdad de la Pendiente, el Índice de Desigualdad Relativa y el Índice de Concentración. Resultados: 42 municipios reportaron 3 110 muertes perinatales. La edad media de las mujeres afectadas fue de 25,3 años con predominio del grupo de 20 a 24 años. La región Pacifico reportó la mayor tasa de mortalidad. La pertenencia étnica, el analfabetismo y el Índice de Pobreza Multidimensional, se asociaron estadísticamente con la mortalidad. Se observó una desigualdad más pronunciada en la tasa de mortalidad perinatal en los municipios con condiciones socioeconómicas más desfavorables. Conclusiones: a pesar de la operacionalización del Plan Decenal de Salud Pública, la mortalidad perinatal en el Cauca continúa siendo un reto en el proceso salud/enfermedad. Existe disparidad en la mortalidad perinatal en relación con el nivel socioeconómico; aunque se ha observado disminución en la desigualdad en el transcurso de los años, aún persisten brechas significativas. Los hallazgos subrayan la necesidad de monitorear y dar cuenta de las desigualdades en salud al diseñar, implementar y evaluar las políticas públicas de prevención de la mortalidad perinatal.

Objective: to identify health inequalities associated with perinatal mortality during the Ten-Year Public Health Plan 2012-2021 in the 42 municipalities of the Department of Cauca, Colombia. Methods: ecological study that addressed the period 2012 - 2021 based on data from secondary sources from the National Administrative Department of Statistics. The study population was women between 12 and 49 years of age residing in Cauca. Rank inequalities and regression models were calculated according to the Slope Inequality Index, the Relative Inequality Index and the Concentration Index. Results: 42 municipalities reported 3 110 perinatal deaths. The mean age of the affected women was 25,3 years with a predominance of the 20-24 years age group. The Pacific region reported the highest mortality rate. Ethnicity, illiteracy and the Multidimensional Poverty Index were statistically associated with mortality. There was greater inequality in perinatal mortality in municipalities with worse socioeconomic status. Conclusions: despite the operationalization of the Ten-Year Public Health Plan, perinatal mortality in Cauca continues to be a challenge in the health/disease process. There is disparity in perinatal mortality in relation to socioeconomic level, and although a decrease in inequality has been observed over the years, significant gaps still persist. The findings underscore the need to monitor and account for health inequalities in the design, implementation and evaluation of public policies to prevent perinatal mortality.

Tumor-Infiltrating Myeloid Cells Confer De Novo Resistance to PD-L1 Blockade through EMT-Stromal and Tgfß-Dependent Mechanisms.

SIGNIFICANCE: Most patients with bladder cancer do not respond to ICB targeting of the PD-L1 signaling axis. Our modeling applied a de novo resistance signature to show that tumor-infiltrating myeloid cells promote poor treatment response in a TGFß-dependent mechanism.

NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer.

Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1)-blockade immunotherapies have limited efficacy in the treatment of bladder cancer. Here, we show that NKG2A associates with improved survival and responsiveness to PD-L1 blockade immunotherapy in bladder tumors that have high abundance of CD8+ T cells. In bladder tumors, NKG2A is acquired on CD8+ T cells later than PD-1 as well as other well-established immune checkpoints. NKG2A+ PD-1+ CD8+ T cells diverge from classically defined exhausted T cells through their ability to react to human leukocyte antigen (HLA) class I-deficient tumors using T cell receptor (TCR)-independent innate-like mechanisms. HLA-ABC expression by bladder tumors is progressively diminished as disease progresses, framing the importance of targeting TCR-independent anti-tumor functions. Notably, NKG2A+ CD8+ T cells are inhibited when HLA-E is expressed by tumors and partly restored upon NKG2A blockade in an HLA-E-dependent manner. Overall, our study provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of HLA-E.

Recomendaciones sobre la vacunación contra SARS-CoV-2 en pacientes en diálisis y lista de espera de trasplante renal

Contexto las personas con diálisis se consideran una población de alto riesgo de infección por SARS-CoV-2, complicaciones y muerte. En Colombia, cerca del 44 % de la población en diálisis es menor de 60 años, adicionalmente, por los mismos retos que ha impuesto la pandemia a los programas de trasplantes, se ha incrementado notoriamente la población joven que debe seguir en diálisis al no tener opción a corto plazo de un trasplante renal, por lo tanto, las limitaciones en el acceso temprano a la vacunación contra SARS-CoV-2 agudizarían los problemas de esta población, provocando pérdidas considerables en años de vida que la vacuna podría salvar. Objetivo el objetivo del presente documento es sintetizar los principales motivos por los que se recomienda la priorización de la vacunación de los pacientes en diálisis crónica y lista de espera para trasplante renal. Metodología se realizó una búsqueda rápida de información sobre la vacunación en pacientes con ERC en diálisis o en espera de trasplante renal. La información resultante fue analizada críticamente por expertos en nefrología para la formulación de recomendaciones. Los resultados de la búsqueda se presentan a manera de síntesis narrativa. Resultados a partir de la información revisada y discutida por los expertos en nefrología se proponen 4 recomendaciones para la vacunación contra el virus SARS-Cov-2. Conclusiones la Asociación Colombiana de Nefrología e Hipertensión Arterial, la Asociación Colombiana de Nefrología Pediátrica y la Asociación Colombiana de Trasplante de Órganos, comprometidos con la salud de los pacientes con enfermedad renal en diálisis y listas de espera de trasplantes en Colombia, se unen a la solicitud mundial de generar recomendaciones para la vacunación contra SARS-CoV-2.

Background People on dialysis are considered a high-risk population for SARS-CoV-2 infection, complications, and death. In Colombia, about 44% of the population on dialysis is under 60 years of age. In addition, due to the same challenges that the pandemic has imposed on transplant programs, the young population that must continue on dialysis has increased markedly, as they have no option in the short term of a kidney transplant, therefore, the limitations in early access to vaccination against SARS-CoV-2 would exacerbate the problems of this population, causing considerable losses in years of life that the vaccine could save. Purpose The objective of this document is to summarize the main reasons why the prioritization of vaccination of patients on chronic dialysis and on the kidney transplant waiting list is recommended. Methodology A rapid search for information on vaccination in patients with CKD on dialysis or awaiting kidney transplantation was performed. The resulting information was critically analyzed by experts in nephrology for the formulation of recommendations. The search results are presented as a narrative synthesis. Results Based on the information reviewed and discussed by nephrology experts, 4 recommendations are proposed for vaccination against the SARS-Cov-2 virus. Conclusions The Colombian Association of Nephrology and Arterial Hypertension (ASOCOLNEF), the Colombian Association of Pediatric Nephrology (ACONEPE) and the Colombian Association of Organ Transplantation (ACTO), committed to the health of patients with kidney disease on dialysis and transplant waiting lists in Colombia, join to generate recommendations for prioritization and vaccination against SARS-CoV-2.

Recommendations of high-quality clinical practice guidelines related to the process of starting dialysis: A systematic review.

BACKGROUND: The optimal time for initiation of dialysis and which modality to choose as the starting therapy is currently unclear. This systematic review aimed to assess the recommendations across high-quality clinical practice guidelines (CPGs) related to the start of dialysis. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, LILACS, and databases of organisations that develop CPGs between September 2008 to August 2021 for CPGs that addressed recommendations on the timing of initiation of dialysis, selection of dialysis modality, and interventions to support the decision-making process to select a dialysis modality. We used the Appraisal of Guidelines for Research and Evaluation instrument to assess the methodological quality of the CPGs and included only high-quality CPGs. This study is registered in PROSPERO, number CRD42018110325. RESULTS: We included 12 high-quality CPGs. Six CPGs addressed recommendations related to the timing of initiating dialysis, and all agreed on starting dialysis in the presence of symptoms or signs. Six CPGs addressed recommendations related to the selection of modality but varied greatly in their content. Nine CPGs addressed recommendations related to interventions to support the decision-making process. Eight CPGs agreed on recommended educational programs that include information about dialysis options. One CPG considered using patient decision aids a strong recommendation. LIMITATIONS: We could have missed potentially relevant guidelines since we limited our search to CPGs published from 2008, and we set up a cut-off point of 60% in domains of the rigour of development and editorial independence. CONCLUSION: High-quality CPGs related to the process of starting dialysis were consistent in initiating dialysis in the presence of symptoms or signs and offering patients education at the point of decision-making. There was variability in how CPGs addressed the issue of dialysis modality selection. CPGs should improve strategies on putting recommendations into practice and the quality of evidence to aid decision-making for patients. REGISTRATION: The protocol of this systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD CRD42018110325. https://clinicaltrials.gov/ct2/show/CRD42018110325.

Clinical and histopathological characteristics of diabetic patients with nephrotic proteinuria. A case series / Características clínicas e histopatológicas de pacientes diabéticos con proteinuria nefrótica. Una serie de casos

Abstract Objective: to describe the clinical and histopathological characteristics of diabetic patients with nephrotic-range proteinuria. Materials and methods: the kidney biopsies of diabetic patients with nephrotic proteinuria were reviewed. Descriptive analyses were performed along with a comparison of three groups according to the histopathological findings. Results: the medical charts of 19 patients from 2018 through 2020 were collected, most of whom (94.7%) were diagnosed with type 2 diabetes mellitus (DM), with an average age of 58 years, and an average duration of DM of 9.9 years (SD: ±7.3). The findings from biopsies performed throughout the years prior to data collection showed that 26.3% had diabetic nephropathy as the only finding, 31.6% had a nephropathy other than diabetic nephropathy, and 42.1% had findings of both diabetic and nondiabetic nephropathy. A comparison of the groups showed a significant difference in the duration of DM, which was greater in patients with diabetic nephropathy (16.4 vs. 5 vs. 9.5 years, respectively, p: 0.024). Conclusions: we present a case series of diabetic patients with nephrotic-range proteinuria in Colombia, showing that kidney biopsy lesions other than diabetic nephropathy may be a cause of proteinuria. We found that patients with a report of DN alone had a much longer duration of diabetes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2231).

Resumen Objetivo: describir las características clínicas e histopatológicas de pacientes diabéticos con proteinuria en rango nefrótico. Material y métodos: se revisaron biopsias renales de pacientes diabéticos con proteinuria ne frótica, se realizaron análisis descriptivos y comparación entre tres grupos de acuerdo con hallazgos histopatológicos. Resultados: se recolectaron historias de 19 pacientes, entre los años 2018 y 2020, la mayoría (94.7%) con diagnóstico de diabetes mellitus (DM) tipo 2, edad promedio de 58 años, con un tiempo de evolución de la DM en promedio de 9.9 años (DE: ±7.3). En los hallazgos de la biopsia, practica das a lo largo de años anteriores a la recolección, se encontró que 26.3% tenían nefropatía diabética como único hallazgo, el 31.6% otra nefropatía diferente a la diabética y 42.1% hallazgos tanto de nefropatía diabética como no diabética. Al comparar los grupos se encontró diferencia significativa en el tiempo de evolución de la DM, siendo mayor en pacientes con nefropatía diabética (16.4 vs 5 vs 9.5 años respectivamente, p: 0.024). Conclusiones: se presenta una serie de casos de pacientes diabéticos con proteinuria en rango nefrótico en Colombia, mostrando que existen lesiones diferentes a la nefropatía diabética en la biopsia renal como posible causa de la proteinuria. Se encontró que los pacientes en quienes se reportó ND únicamente, tenían un tiempo de evolución de la diabetes mucho mayor. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2231).

Implementación de la Política Atención Integral en Salud en el Cauca: Un estudio de caso 2016-2019 / Implementation of the comprehensive health care policy in Cauca: a case study 2016-2019 / Implementação da política atenção integral em saúde no Cauca: um estudo de caso 2016-2019

Resumen La Política de Atención Integral en Salud (PAIS) con sus marcos estratégico y operativo, busca ser garante del derecho a la salud en Colombia. Dado que la fase de implementación de toda política es considerada como crítica para el cumplimiento de los objetivos, resulta válida la mirada de actores en la cotidianidad laboral en salud de un territorio. Objetivo: describir el proceso de implementación de la PAIS percibido desde sus actores y las particularidades territoriales del departamento del Cauca. Materiales y métodos: investigación de perspectiva cualitativa que adopta el estudio de caso y como referente, el modelo analítico de Subirast. Se realizaron 14 entrevistas semiestructuradas a líderes de procesos, se revisaron 47 documentos de planeación y se complementó información con un diario de campo. Resultados: el proceso de implementación de la PAIS permitió avances desde algunos elementos del marco estratégico y operativo, sin embargo, los participantes vivencian limitaciones en la adopción de la atención primaria, la autoridad sanitaria y la articulación de actores. El talento humano en salud es fundamental en la política, sin embargo, su permanencia en territorio es discontinua. Conclusiones: el limitado trabajo interinstitucional, las prácticas clientelares, la débil autoridad sanitaria y la falta de estructuras de gestión acorde a la PAIS, conducen a pensar en la necesidad de acrecentar capacidades y recursos para nivelar la comprensión y operación de estrategias contemplados en la política. Se insiste en la debilidad estatal para hacer efectiva la regulación, el control y la vigilancia de los actores en salud.

Abstract With its strategic and operational frameworks, the Comprehensive Health Care Policy (PAIS for its acronym in Spanish) seeks to guarantee the right to health in Colombia. Given that the implementation phase of any policy is considered critical for the fulfillment of its objectives, the perspective of actors in the daily health work of a territory is valid. Objective: To describe the process of implementation of PAIS as perceived by its actors and the territorial particularities of the Department of Cauca. Materials and methods: Research from a qualitative perspective adopting the case study and, as a reference, the Subirast analytical model. Fourteen semi-structured interviews were conducted with process leaders, 47 planning documents were reviewed and information was complemented with a field diary. Results: The PAIS implementation process allowed progress from some elements of the strategic and operational framework. However, participants experience limitations in the adoption of primary care, the health authority and the articulation of actors. Human talent in health is fundamental in politics. However, its permanence in territory is discontinuous. Conclusions: The limited inter-institutional work, the clientelist practices, the weak health authority and the lack of management structures according to PAIS, lead to think about the need to increase capacities and resources to level the understanding and operation of strategies contemplated in the policy. The weakness of the State to make effective regulation, control and surveillance of health actors is emphasized.

Resumo A Política de Atenção Integral em Saúde (PAIS) com seus marcos estratégico e operativo, procura ser garante do direito à saúde na Colômbia. Já que a fase de implementação de toda política é considerada como crítica para o cumprimento dos objetivos, resulta válida a olhada de atores na cotidianidade laboral em saúde de um território. Objectivo: descrever o processo de implementação da PAIS percebendo desde seus atores as particularidades territoriais do departamento do Cauca. Materiais e métodos: pesquisa de perspectiva qualitativa que adota o estudo de caso e como referente, o modelo analítico de Subirast. Analisaram-se 14 entrevistas semi-estruturadas a líderes de processos, se revisaram 47 documentos de planejamento e se complementou informação com um diário de campo. Resultados: o processo de implementação da PAIS permitiu avanços desde alguns elementos do marco estratégico e operativo, porém, os participantes têm limitações na adopção da atenção primaria, a autoridade sanitária e a articulação de atores. O talento humano em saúde é fundamental na política, contudo, sua permanência no território é descontínua. Conclusões: o limitado trabalho interinstitucional, as práticas clientelistas, a fraca autoridade sanitária e a falta de estruturas de gestão acorde com PAIS, conduzem a pensar na necessidade de acrescentar capacidades e recursos para nivelar a compreensão e operação de estratégias contemplados na política. Insiste-se na fraqueza estatal para fazer efetiva a regulação, o controle e a vigilância dos atores em saúde.

The role of RENAL score in predicting complications after robotic partial nephrectomy.

BACKGROUND: The aim of this study was to evaluate the association between tumor complexity based on RENAL nephrometry score and complications. METHODS: We retrospectively identified 2555 patients who underwent RPN for renal cell carcinoma. Major complication was defined as Clavien Grade ≥3. The relationship between baseline demographic, clinical characteristics, perioperative and postoperative outcomes, and tumor complexity were assessed using χ2 test of independence, Fisher's Exact Test and Kruskal Wallis Test. An unadjusted and adjusted logistic regression model was used to assess the relationship between major complication and demographic, clinical characteristics, and perioperative outcomes. RESULTS: There was a significant relationship between tumor complexity and WIT (P<0.001), operative time (P<0.001), estimated blood loss (P<0.001), and major complication (P=0.019). However, there was no relationship with overall complications (P=0.237) and length of stay (LOS) (P=0.085). In the unadjusted model, higher tumor complexity was associated with major complication (P=0.009). Controlling for other variables, there was no significant difference between major complication and tumor complexity (low vs. moderate, P=0.142 and high, P=0.204). LOS (P<0.001) and operative time (P=0.025) remained a significant predictor of major complication in the adjusted model. CONCLUSIONS: Tumor complexity is not associated with an increase in overall or major complication rate after RPN. Experience in high-volume centers is demonstrating a standardization of low complications rates after RPN independent of tumor complexity.