Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis

Abstract Objective Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. Method A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. Results Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. Conclusion The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.

Utilidad de diversos parámetros hemodinámicos como marcadores pronósticos en la hipertensión pulmonar / Prognostic Value of Various Hemodynamic Parameters in Pulmonary Hypertension

RESUMEN Introducción . La hipertensión pulmonar (HP) se asocia con elevada morbimortalidad y su pronóstico está determinado por la función del ventrículo derecho y el acople ventrículo-arterial pulmonar. Diversos parámetros hemodinámicos han sido propuestos para caracterizar el riesgo de evolución adversa. Objetivos . Determinar la capacidad de predicción de eventos graves, de diversos parámetros hemodinámicos medidos por cateterismo derecho. Material y métodos . Estudio multicéntrico, descriptivo, de cohorte retrospectiva de pacientes con HP. Se dividió a los datos hemodinámicos en alto o bajo riesgo según lo definido por las recomendaciones europeas de 2022, o según media o mediana de nuestra población. Resultados . Fueron incluidos 324 pacientes con HP, con edad media 61,5 años y 69% de sexo femenino; 62,1 % de los pacientes del Grupo 1 y 19,2 % del Grupo 3. La tasa de eventos (muerte o internaciones) en un seguimiento mediano de 23 (RIC 14-44) meses fue 60 % y la mortalidad global 24,5 %. Los valores de corte para definir riesgo de las diferentes variables fueron. índice cardíaco (IC) 2,72 L/min/m2, índice de volumen sistólico (IVS) 33,1 mL/lat./m2, resistencia vascular pulmonar (RVP) 6 unidades Wood (UW), índice de pulsatilidad de la arteria pulmonar (IPAP) 3,76, índice de trabajo sistólico del ventrículo derecho (ITSVD) 11,6 g.m/m2, compliance vascular pulmonar 1,84 mL/mmHg. La RVP elevada se asoció a mayor frecuencia de eventos combinados, mientras que valores de alto riesgo de IC, IVS, RVP y compliance presentaron asociación con mayor mortalidad en el seguimiento. Conclusiones . Si bien el IC y el IVS presentaron una adecuada predicción de riesgo, variables como la RVP y la compliance mostraron similar, e incluso mejor predicción de eventos graves en HP. Se necesitan nuevos estudios que validen estos parámetros en el seguimiento.

ABSTRACT Background. Pulmonary hypertension (PH) is associated with high morbidity and mortality and its prognosis is determined by the right ventricular function and right ventricular-pulmonary artery coupling. Several hemodynamic parameters have been proposed to better characterize the risk for adverse disease progression. Objective. The aim of this study was to determine the predictive ability of various hemodynamic parameters that can be calculated during RHC to predict serious events. Methods. In this retrospective multicenter and descriptive cohort study of patients with PH, hemodynamic variables values were divided as high or low risk based on the 2022 European guidelines, or mean or median values in our population. Results. A total of 324 patients with PH were included; mean age was 61.5 years and 69% were women; 62.1 % of the patients were in Group 1 and 19.2 % in Group 3. In a median (IQR) follow-up of 23(14-44) months, the event rate (death or hospitalization for heart failure) was 60.6% and all-cause mortality was 24.5%. The cut-off values associated with risk for the different hemodynamic variables were: cardiac index (CI) 2.72 L/min/m2, systolic volume index (SVI) 33.1 ml/m2, pulmonary vascular resistance (PVR) 6 Wood units (WU), pulmonary artery pulsatility index (PAPI) 3.76, right ventricle systolic work index (RVSWI) 11.6 g.m/m2, and pulmonary arterial compliance 1.84 mL/mm Hg. Elevated PVR was associated with a higher rate of composite events, while high-risk CI, SVI, PVR, and compliance were associated with higher mortality at follow-up. Conclusions. While CI and SVI are adequate predictors of risk, PVR and compliance demonstrate similar or even better risk prediction in patients with PH. Additional research is necessary to validate these parameters during follow-up.

Mortalidad en neumonía bacteriémica por neumococo / Mortality in bacterial pneumonia due to pneumococcus

Resumen Introducción : A pesar de las mejoras en los cuidados de la salud, la mortalidad asociada a neumonía continúa siendo alta. El objetivo de este estudio fue analizar los factores asociados a mortalidad en neumonía bacterié mica por neumococo. Métodos : Estudio de cohorte retrospectiva en pacien tes adultos con diagnóstico de neumonía y neumococo aislado en hemocultivos, entre enero 2012 y mayo 2021. Se analizaron: variables clínicas y de laboratorio, com promiso radiológico, evolución y mortalidad durante la internación. Se comparó el grupo de pacientes fallecidos con el de sobrevivientes. Resultados : Se incluyeron 152 pacientes. La mediana de edad fue de 58 años y el 58.9% fueron hombres. El 33% presentó un CURB-65 mayor a 2 al momento de internación. La mortalidad global fue 34% (n=52). Los pacientes fallecidos se encontraban más frecuente mente taquipneicos al ingreso (frecuencia respiratoria 26 vs. 22; p=0.003), presentaban más frecuentemente alteración del sensorio (58% vs. 14%; p< 0.001), PaO2/ fracción inspirada de oxígeno (PAFI) < 250 (58% vs. 22%; p<0.001), compromiso radiológico bilateral (50% vs. 32%; p=0.03), necesidad de asistencia respiratoria mecánica (ARM) (50% vs. 12%; p< 0.001), mayor valor de creati nina en sangre (1.6 vs. 1.15; p=0.01), menor recuento de glóbulos blancos (10 900 vs. 17 400; p=0.002), menor valor de glucemia (111 vs. 120; p=0.01) y menos días de estancia hospitalaria (6 vs. 9; p=0.015). En el análisis de regresión logística multivariable se mantuvieron diferen cias significativas en los siguientes factores asociados a mortalidad: ventilación mecánica (OR=3.54), confusión (OR=5.95), radiografía con compromiso bilateral (OR= 3.20) y PAFI < 250 (OR=3.62). Conclusión : Los factores relacionados con mortalidad, a pesar de la presencia de bacteriemia, no difieren de los publicados en la literatura y forman parte de los scores pronósticos de práctica habitual.

Abstract Introduction : Despite improvements in health care, pneumonia-associated mortality remains high. The ob jective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus. Methods : Retrospective cohort study in adult pa tients with pneumonia diagnosis and isolation of pneu mococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory vari ables, radiological involvement, evolution and mortal ity during hospitalization were analyzed. The group of deceased patients was compared with that of survivors. Results : 152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respira tory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62). Conclusion : In our series, the factors related to mor tality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.

Study of serum ferritin as diagnostic and prognostic biomarker for severity of sepsis: a hospital-based study

Background: The objective of the study was to evaluate serum ferritin levels to define it as a diagnostic and prognostic biomarker for severity of sepsis.Methods: In this hospital-based descriptive type of observational study, conducted at the Department of Pediatrics, NIMS Medical College; 80 children of age group 6 months to 18 years with diagnosis of pediatric sepsis were included. Children were divided into grades of sepsis (sepsis, severe sepsis, septic shock, MODS). Progress of sepsis, severe sepsis, septic shock, and sepsis with MODS was followed with serum ferritin levels on day 1, day 3, day 7, or more than 7 days and one week post recovery.Results: Pneumonia was identified as the most common source of infection. The blood culture positivity rate was 32.5%. E. coli was the most common organism grown on blood culture. Median serum ferritin levels increased as sepsis severity worsened. A significant association was discovered between sepsis severity and CRP levels at the time of admission.Conclusions: There is a consistent pattern of Serum ferritin levels with increasing severity of pediatric sepsis. Routine use of serum ferritin levels in diagnosis and prognostication is both feasible and simple. CRP level correlate well with serum ferritin level for diagnosis of sepsis.

Exploring human mammaglobin: as a possible diagnostic and prognostic indicator in breast cancer tissue

Breast cancer is a major global health issue, with high diagnosis rates worldwide, especially in less developed areas, leading to significant mortality rates. This review focuses on the molecular characteristics of breast cancer, emphasizing the role of human mammaglobin-A (hMAM-A) as a diagnostic and prognostic marker. hMAM-A, a dimeric protein from the secretoglobin family, is produced exclusively by breast tissue and shows elevated levels in breast cancer cases, making it a highly accurate marker for disease detection. The review also examines various factors influencing breast cancer, such as age, tobacco use, menopausal status, and hormone replacement therapy (HRT). Younger age at diagnosis is associated with poorer outcomes, highlighting the importance of early detection. Tobacco smoke increases mortality rates in breast cancer patients. Menopausal status affects molecular subtypes and risk factors, impacting treatment and prognosis. HRT has a complex relationship with breast cancer risk. The review concludes by discussing the need for novel biomarkers, including hMAM-A, to improve breast cancer diagnosis and management.

An observational study of association of thyroid dysfunction and heart failure in a tertiary care centre

Background: Heart failure (HF) is becoming leading problem in world now a days. Thyroid hormone has been proven to influence physiologic functions of cardiovascular system in many ways. HF presents a clinical challenge, with thyroid dysfunction emerging as a significant comorbidity, affecting prognosis and management. Approximately 22% of patients with HF have been demonstrated to have thyroid dysfunction. Clinical studies were confirmed that the patients with sub-clinical hypothyroidism had high risk of cardiovascular disease due to increased low density lipoprotein, elevated homocystein, hypercoagulative blood. In this study, we aim to evaluate association between sub-clinical hypothyroidism and HF to know its clinical significance. Methods: An observational study conducted over three months on 70 diagnosed HF patients admitted in tertiary care hospital, evaluating history, clinical profile and demographics, HF types, comorbidity, and screened for thyroid function. Results: Thyroid dysfunction prevalence among HF patients was 27.14%, with subclinical hypothyroidism being most common. Treatment led to significant improvements in symptoms and cardiac function. Conclusions: There is significant correlation between thyroid dysfunction and HF with Subclinical hypothyroidism can be independent risk factor for HF. Timely and early recognition and management of thyroid dysfunction in HF patients are crucial for prognosis enhancement. Early intervention holds promise for improved outcomes in HF management.

Survival analysis and associated factors of high-grade glioma patients / Análisis de supervivencia y factores asociados de pacientes con glioma de alto grado

ABSTRACT Introduction. High-grade gliomas are the most common primary brain tumors in adults, and they usually have a quick fatal course. Average survival is 18 months, mainly, because of tumor resistance to Stupp protocol. Objective. To determine high-grade glioma patient survival and the effect of persuasion variables on survival. Materials and methods. We conducted a longitudinal descriptive study in which 80 untreated recently diagnosed high-grade glioma patients participated. A survey was conducted regarding their exposure to some risk factors, degree of genetic instability in peripheral blood using micronucleus quantification on binuclear lymphocytes, micronuclei in reticulocytes and sister-chromatid exchanges in lymphocytes. In the statistical analysis, this study constructed life tables, used the Kaplan-Meier, and the log-rank test, and in the multivariate analysis, a Cox proportional hazards model was constructed. Results. Eighty patients' clinical, demographic and lifestyle characteristics were analyzed, as well as their survival rates and the average survival time is 784 days (interquartile range: 928). Factors like age, exposure at work to polycyclic hydrocarbons and the number of sister-chromatid exchanges in lymphocytes in the first sampling was significantly survival-related in the multivariate analysis. Conclusion. We determined that only three of the analyzed variables have an important effect on survival time when it comes to high-grade glioma patients.

RESUMEN Introducción. Los gliomas de alto grado son los tumores cerebrales primarios más comunes en adultos y, por lo general, tienen un curso mortal rápido. La supervivencia media es de 18 meses, principalmente, como consecuencia de la resistencia del tumor al protocolo Stupp. Objetivo. Determinar la supervivencia de los pacientes con glioma de alto grado y el efecto de las variables de persuasión en la supervivencia. Materiales y métodos. Se llevó a cabo un estudio descriptivo longitudinal en el que participaron 80 pacientes con diagnóstico reciente de glioma de alto grado no tratados. Se hizo una encuesta sobre su exposición a algunos factores de riesgo, grado de inestabilidad genética en sangre periférica mediante cuantificación de micronúcleos en linfocitos binucleares, micronúcleos en reticulocitos e intercambios de cromátidas hermanas en linfocitos. En el análisis estadístico, se construyeron tablas de vida, se utilizó Kaplan-Meier y la prueba de rangos logarítmicos, y en el análisis multivariado, se construyó un modelo de riesgos proporcionales de Cox. Resultados. Se analizaron las características clínicas, demográficas y de estilo de vida de 80 pacientes, así como sus tasas de supervivencia y el tiempo medio de supervivencia fue de 784 días (rango intercuartílico: 928). Factores como la edad, la exposición laboral a hidrocarburos policíclicos y el número de intercambios de cromátidas hermanas en linfocitos en el primer muestreo se relacionaron significativamente con la supervivencia en el análisis multivariante. Conclusión. Según los resultados, el estudio determinó que solo tres de las variables analizadas tienen un efecto importante en el tiempo de supervivencia cuando se trata de pacientes con glioma de alto grado.

Multivariate analysis of histopathological features as prognostic factors in fifty cases of thyroid neoplasm: a retrospective study done at tertiary care centre

Background: Number of prognostic factors for thyroid carcinoma have been identified including age, gender and tumor characteristics, such as histology and stage. The importance of these factors as independent predictors of survival for patients with differentiated thyroid carcinoma has been extensively studied but remains uncertain. Methods: A retrospective analysis of 50 thyroid carcinomas was made to assess prognostic factors including histological variants from September 2019 to February 2022 at our centre. The surgical and histopathological data were studied. Results: 72% patients had papillary thyroid cancer. Multivariate analysis was done and factors showing prognostic significance were tumour size, extrathyroid extension, extranodal extension, lymphovascular, perineural invasion, histological type, necrosis, focality, capsular invasion were found to have poor prognosis. Conclusions: There are histopathological factors which can modify the course and influence the line of treatment of thyroid neoplasms.

Hiperglicemia al ingreso hospitalario como predictor de mala evolución en pacientes hospitalizados por COVID-19 / Hyperglycemia on hospital admission as a predictor of poor outcome in patients hospitalized for COVID-19

RESUMEN Introducción : La hiperglicemia al ingreso hospitalario podría ser una buena herramienta para predecir evolución desfavorable en pacientes con COVID-19. Objetivo : Determinar si la hiperglicemia al ingreso hospitalario constituye un factor pronóstico de evolución desfavorable. Métodos : Se realizó un estudio observacional, analítico, de cohorte retrospectivo en el Hospital Regional de Moquegua. Se revisaron de manera aleatoria historias clínicas de 640 pacientes hospitalizados con COVID-19 confirmado durante las primeras dos olas de la pandemia. Las variables incluyeron evolución desfavorable, secuelas respiratorias, ingreso a la Unidad de Cuidados Intensivos (UCI), y fallecimiento. La hiperglicemia al ingreso se definió como glicemia >140 mg/dL. Se realizaron análisis bivariados y multivariados utilizando modelos de regresión de Poisson con varianzas robustas para hallar el riesgo relativo crudo y ajustado (RRa) con sus respectivos IC95%. Resultados : El 36,9% tuvo 60 o más años, el 58,9% fue del sexo masculino y el 10,2% tuvo diabetes mellitus. El 34,7% de los pacientes presentaron hiperglicemia al ingreso. La hiperglicemia se asoció significativamente con una evolución desfavorable (RRa = 5,65; IC95%: 3,72-8,62; p < 0,001), secuelas respiratorias (RRa = 1,96; IC95%: 1,74-2,21; p < 0,001), ingreso a UCI (RRa = 3,68; IC95%: 2,03-6,69; p < 0,001), y fallecimiento (RRa = 1,57; IC95%: 1,22-2,02; p = 0,001). Conclusión : La hiperglicemia al ingreso es un factor pronóstico significativo para evolución desfavorable en pacientes con COVID-19. Es esencial monitorear cuidadosamente a estos pacientes.

ABSTRACT Introduction: Hyperglycemia on hospital admission may be a useful tool to predict poor outcomes in COVID-19 patients. Objective: To determine if hyperglycemia on hospital admission constitutes a prognostic factor for poor outcomes. Methods: An observational, analytical, retrospective cohort study was conducted at the Hospital Regional de Moquegua. Medical records of 640 randomly selected patients hospitalized with confirmed COVID-19 during the first two waves of the pandemic were reviewed. Variables included poor outcomes, respiratory sequelae, admission to the Intensive Care Unit (ICU), and death. Hyperglycemia on admission was defined as blood glucose >140 mg/dL. Bivariate and multivariate analyses were performed using Poisson regression models with robust variances to find the crude and adjusted relative risks (RRa) with their respective 95% confidence intervals (CI95%). Results: Of the patients, 36.9% were 60 years or older, 58.9% were male, and 10.2% had diabetes mellitus. Hyperglycemia on admission was present in 34.7% of the patients. Hyperglycemia was significantly associated with poor outcomes (RRa = 5.65; CI95%: 3.72-8.62; p < 0.001), respiratory sequelae (RRa = 1.96; CI95%: 1.74-2.21; p < 0.001), ICU admission (RRa = 3.68; CI95%: 2.03-6.69; p < 0.001), and death (RRa = 1.57; CI95%: 1.22-2.02; p = 0.001). Conclusion: Hyperglycemia on admission is a significant prognostic factor for poor outcomes in COVID-19 patients. Careful monitoring of these patients is essential.

Expression and Clinical Significance of CLCA2 in Pan-Cancer / Expresión y Significado Clínico de CLCA2 en Pan-Cáncer

SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.

El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.

Frailty does not affect prognostic markers in patients with acute coronary syndrome: results from a Brazilian university hospital

OBJECTIVE: To evaluate frailty and its relationship with prognostic markers in hospitalized patients with acute coronary syndrome. METHODS: This cross-sectional study with a prospective variable analysis (prognostic markers) involved adults of both sexes aged ≥ 50 years with acute coronary syndrome. Patients with ≥ 3 of the following criteria were considered frail: 1) unintentional weight loss; 2) exhaustion (assessed by self-reported fatigue); 3) low handgrip strength; 4) low physical activity level; and 5) low gait speed. The included prognostic markers were: metabolic changes (lipid and glycemic profile), changes in inflammatory status (C-reactive protein), thrombolysis in myocardial infarction risk score, troponin level, angioplasty or surgery, hospitalization in the intensive care unit, length of hospital stay, and hospital outcome. RESULTS: The sample consisted of 125 patients, whose mean age was 65.5 (SD, 8.7) years. The prevalence of frailty was 48.00%, which was higher in women (PR = 1.55; 95%CI 1.08­2.22; p = 0.018) and patients with systemic arterial hypertension (PR = 2.18; 95%CI 1.01­5.24; p = 0.030). Frailty was not associated with age, cardiac diagnosis, or prognostic markers (p > 0.05). CONCLUSIONS: Frailty was highly prevalent in patients with acute coronary syndrome, affecting almost half of the sample, particularly women and patients with hypertension, irrespective of age. However, despite its high prevalence, frailty was not associated with markers of metabolic change or poor prognosis.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Cociente neutrófilos/linfocitos preoperatorio como factor pronóstico en el cáncer epitelial de ovario / Preoperative neutrophil/lymphocyte ratio as prognostic factor in epithelial ovarian cancer

RESUMEN Objetivos: evaluar si hay asociación entre los valores del cociente plasmático neutrófilos/ linfocitos (NLR) y el pronóstico en pacientes con cáncer epitelial de ovario (CEO) diagnosticadas y tratadas en una población española. Materiales y métodos: cohorte retrospectiva de pacientes con cáncer epitelial de ovario que tuvieran un recuento de neutrófilos y linfocitos en hemograma previo al diagnóstico histopatológico en un hospital de nivel medio de complejidad y posterior sobrevida de, al menos, 3 meses. Muestreo por conveniencia. Se midieron: edad, estado menopáusico, paridad, estadio Federacion International de Ginecología y Obstetricia (FIGO), tipo de tratamiento, tumor residual, afectación ganglionar, presencia de ascitis, citología, tipo histológico, grado de diferenciación y cifras de CA-125; como desenlaces, sobrevida global y sobrevida libre de enfermedad o progresión. Análisis inferencial bivariado y por regresión de Cox. Resultados: de 78 candidatas, ingresaron 60 mujeres con CEO. De ellas, 24 (40%) presentaron un NLR bajo (< 2,9) y 36 (60 %) elevado (> 2,9). Se encontró asociación entre los niveles altos de NLR y cirugía citoreductora subóptima. Los niveles altos de NLR se asociaron a menor sobrevida global (Hazard ratio (HR): 4,1; IC 95%: 1,4-11,8) y menor sobrevida libre de enfermedad a los 5 años (HR:2,6; IC 95 %: 1,2-5,7). Conclusiones: un cociente plasmático neutrófilos/ linfocitos mayor de 2,9 se asoció a un mal pronóstico en pacientes con cáncer epitelial de ovario en nuestro medio. Se necesita determinar el punto de corte óptimo y realizar estudios prospectivos con mayor número de pacientes que avalen esta información.

ABSTRACT Objectives: To determine if there is an association between the neutrophil to lymphocyte ratio (NLR) and prognosis in patients with epithelial ovarian cancer (EOC) diagnosed and treated in a Spanish population. Material and methods: Retrospective cohort of patients with epithelial ovarian cancer who had neutrophil and lymphocyte values in complete blood count before the histopathological diagnosis and survival of at least three months, in an intermediate complexity hospital. Convenience sampling. Measured variables included age, menopausal stage, parity, International Federation of Gynecology and Obstetrics (FIGO) stage, treatment type, residual tumor, lymph node involvement, presence of ascites, cytology, histologic type, differentiation grade, and CA-125 values. Additionally, outcomes, overall survival, disease/progression-free survival were also measured. Bivariate inferential and Cox regression analyses were performed. Results: Out of 78 candidates, 60 women with EOC were included. Of them, 24 (40%) had a low NLR (< 2,9) while 36 (60%) had a high NLR (> 2,9). An association was found between high NLR levels and suboptimal cytoreductive surgery. High NLR ratios were associated with lower overall survival (Hazard ratio (HR): 4.1; 95% CI: 1.4-11.8) and lower 5-year disease-free survival (HR: 2.6; 95% CI: 1.2-5.7). Conclusions: A plasma neutrophil to lymphocyte ratio of more than 2.9 was associated with poor prognosis in patients with epithelial ovarian cancer in our setting. There is a need to establish the optimal cut-off point and conduct prospective studies with larger patient numbers in order to support this information.

Consenso colombiano para el diagnóstico molecular del cáncer de endometrio / Colombian consensus for the molecular diagnosis of endometrial cancer

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ABSTRACT Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and non-regulatory document.

Análise do perfil clínico e epidemiológico das internações por asma no período de 2020 a 2021 em um hospital do sul de Santa Catarina / Analysis of the clinical and epidemiological profile of hospitalizations due to asthma in the period 2020­2021 in a hospital in southern Santa Catarina, Brazil

INTRODUÇÃO: A asma brônquica é uma doença crônica inflamatória de alta frequência mundialmente, e em especial no Brasil, onde ocorreram mais de 100.000 internações por ano, segundo dados do DATASUS. Identificar pacientes em admissão hospitalar que poderão necessitar de leito em UTI ou uso de ventilação mecânica por conta de crises asmáticas é um desafio ao profissional de saúde, portanto, faz-se importante analisar variáveis clínicas que possam predispor agravos e avaliar pacientes mais vulneráveis, para que as condutas realizadas sejam efetivas e rápidas. OBJETIVO: Analisar o perfil clínico e epidemiológico de pacientes internados em um hospital do sul do Brasil e avaliar os preditores relacionados ao maior tempo de internação. MÉTODOS: Estudo epidemiológico observacional, do tipo transversal, que utilizou como fonte de informação dados secundários, os quais foram obtidos através de prontuários de pacientes internados em um hospital do sul do Brasil. RESULTADOS: Foram analisados 261 prontuários. Verificou-se que a população menor de 40 anos de idade teve maior prevalência, representando 57% das internações. Além disso, em relação a gênero e etnia, mulheres e caucasianos foram as populações com maiores taxas de hospitalização, sendo 63% e 87% das admissões hospitalares, respectivamente.A necessidade de internação em UTI foi encontrada em 1,1% dos casos (3 pacientes), cerca de 6,9% tiveram internações prolongadas (maiores de 3 dias), e 0,8% vieram à óbito (2 pacientes). Identificou-se que a baixa saturação de oxigênio e a alta frequência cardíaca tiveram relação significativa com internação prolongada. CONCLUSÃO: É importante analisar sinais vitais no momento das admissões hospitalares e o perfil epidemiológico dos pacientes para que as populações mais prevalentes e os fatores preditivos de desfechos mais graves possam ser acompanhados e a conduta a ser tomada seja adequada e efetiva.

INTRODUCTION: Bronchial asthma is a chronic inflammatory disease with a high worldwide frequency, especially in Brazil, where more than 100,000 asthma-related hospitalizations occur annually according to DATASUS data. Identifying patients upon hospital admission who may require an ICU bed or mechanical ventilation due to an asthma attack is a challenge for healthcare professionals. It is important to analyze clinical variables that may predispose to deterioration and evaluate more vulnerable patients to ensure that effective interventions are instituted promptly. OBJECTIVE: To analyze the clinical and epidemiological profile of patients admitted due to asthma in a hospital in southern Brazil and evaluate predictors of longer hospital stay. METHODS: Observational epidemiological study with a cross-sectional design.The source of information were secondary data obtained from medical records of patients admitted to a hospital in southern Brazil. RESULTS: Overall, 261 medical records were analyzed.Patients were predominantly under the age of 40, representing 57% of hospitalizations. In terms of gender and ethnicity, most patients were female (63%) and white (87%).Three patients (1.1%) required ICU admission, approximately 6.9% had prolonged hospitalizations (>3 days), and 2 (0.8%) died. Low oxygen saturation and elevated heart rate correlated significantly with prolonged hospitalization. CONCLUSION: Vital signs at the time of hospital admission and the epidemiological profile of patients should be analyzed, so that the most prevalent populations and predictors of severe outcomes can be monitored, and appropriate and effective measures can be taken.

Ten-year institutional experience in nasopharyngeal carcinoma: a comprehensive retrospective analysis

Background: Nasopharyngeal carcinoma (NPC) is relatively rare worldwide but exhibits a higher prevalence in specific geographic regions, particularly Southeast Asia and the North-Eastern states of India. In this study, we present a comprehensive analysis of a decade抯 worth of data involving 117 patients with NPC at the Regional Institute of Medical Sciences, Imphal, Manipur, India. Methods: We retrospectively reviewed data from 117 newly diagnosed NPC patients spanning from 2012 to 2022. Key demographic parameters such as age, gender, presenting symptoms, and disease stage were meticulously documented. Survival outcomes were assessed using Kaplan-Meier survival curves. Results: Our analysis encompassed 117 patients. The median age at presentation was 54 years. Undifferentiated carcinoma emerged as the predominant histological subtype. Notably, patients with type 1 keratinizing carcinoma, cranial nerve involvement, and advanced disease stages exhibited significantly poorer overall survival outcomes. Conclusions: This retrospective analysis of nasopharyngeal carcinoma in the North-Eastern region of India highlights the critical significance of implementing early detection and intervention strategies for NPC in this specific geographical area, with the potential to improve patient outcomes.

RESISTIN GENE POLYMORPHISMS: POTENTIAL BIOMARKER FOR ORAL SQUAMOUS CELL CARCINOMA

Objective: The objective of the work is to study the association between Resistin Gene polymorphisms and susceptibility of Oral Squamous Cell carcinoma.Methods: In the present study, we scrutinize the connection between four genetic polymorphisms present in RETN gene with the susceptibility, progression, and clinical outcome of OSCC among 200 OSCC patients and 200 healthy controls.Results: The results of the study reveal that among 260 smokers, the risk of developing OSCC is significantly more among the subjects having history of using betel quid in comparison to those who are not habitual users of betel quid.Conclusion: The study reveals that patients with OSCC exhibiting G/A heterozygous genotype of RETN rs3219175 polymorphism have lesser risk for developing high-grade tumor compared to the patients with G/G homozygotes in North Indian population.

Utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer / Usefulness of the qSOFA score for predicting hospital mortality in cancer patients

Resumen Antecedentes: El quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) es una puntuación propuesta para identificar de forma rápida a pacientes con mayor probabilidad de morir. Objetivo: Describir la utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer. Material y métodos: Estudio transversal realizado entre enero de 2021 y diciembre de 2022. La mortalidad hospitalaria fue la variable dependiente. Se calculó el área bajo la curva ROC (ABC) para determinar la capacidad discriminativa de qSOFA para predecir mortalidad hospitalaria. Resultados: Se incluyeron 587 pacientes con cáncer. La puntuación qSOFA < 1 obtuvo una sensibilidad de 57.2 %, una especificidad de 78.5 %, un valor predictivo positivo de 55.4 % y un valor predictivo negativo de 79.7 %. El ABC de qSOFA para predecir mortalidad hospitalaria fue de 0.70. La mortalidad hospitalaria de los pacientes con qSOFA de 2 y 3 puntos fue de 52.7 y 64.4 %, respectivamente. La mortalidad hospitalaria fue de 31.9 % (187/587). Conclusión: qSOFA mostró capacidad discriminativa aceptable para predecir mortalidad hospitalaria en pacientes con cáncer.

Abstract Background: The quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) is a score that has been proposed to quickly identify patients at higher risk of death. Objective: To describe the usefulness of the qSOFA score to predict in-hospital mortality in cancer patients. Material and methods: Cross-sectional study carried out between January 2021 and December 2022. Hospital mortality was the dependent variable. The area under the ROC curve (AUC) was calculated to determine the discriminative ability of qSOFA to predict in-hospital mortality. Results: A total of 587 cancer patients were included. A qSOFA score higher than 1 obtained a sensitivity of 57.2 %, specificity of 78.5 %, a positive predictive value of 55.4 % and negative predictive value of 79.7 %. The AUC of qSOFA for predicting in-hospital mortality was 0.70. In-hospital mortality of patients with qSOFA scores of 2 and 3 points was 52.7 and 64.4 %, respectively. In-hospital mortality was 31.9 % (187/587). Conclusions: qSOFA showed acceptable discriminative ability for predicting in-hospital mortality in cancer patients.

Variáveis Clínicas e Laboratoriais na Admissão Hospitalar são Preditores de Fibrilação Atrial Nova em Pacientes Internados com Pneumonia por COVID-19 / Clinical and Laboratory Data Up on Hospital Admission are Predictors of New-Onset Atrial Fibrillation in Patients Hospitalized Due to COVID-19 Pneumonia

Resumo Fundamento Fibrilação atrial nova (FAN) ocorre em pacientes internados por COVID-19. Há controvérsias quanto ao valor preditivo de dados clínicos e laboratoriais à admissão hospitalar para ocorrência de FAN. Objetivos Analisar, à admissão hospitalar, variáveis com potencial preditivo para ocorrência de FAN em pacientes com pneumonia por COVID-19. Método Estudo observacional, retrospectivo, caso-controle. Foram avaliados prontuários eletrônicos de pacientes consecutivos ≥ 60 anos, hospitalizados com pneumonia por COVID-19 entre 1º de março e 15 de julho de 2020. Comparações feitas pelos testes `t' de Student ou qui-quadrado. Foi empregado modelo de risco proporcional de Cox para identificação de preditores de FAN. Considerou-se o valor de p < 0,05 como estatisticamente significativo. Resultados Entre 667 pacientes internados por COVID-19, 201 (30,1%) foram incluídos. FAN foi documentada em 29 pacientes (14,4%) (grupo 1). Grupo 2 foi composto por 162 pacientes que não apresentaram FAN. Dez pacientes excluídos por estarem em FA na admissão hospitalar. Houve diferenças entre os grupos 1 e 2, respectivamente, no tempo de permanência em UTI (11,1±10,5 dias vs. 4,9±7,5 dias; p=0,004), necessidade de ventilação invasiva (82,9% e 32,7%; p<0,001) e mortalidade hospitalar (75,9% vs. 32,1%; p<0,001). No modelo de Cox, idade > 71 anos (hazard ratio [HR]=6,8; p<0,001), leucometria ≤ 7.720 cels.μL-1 (HR=6,6; p<0,001), natremia ≤ 137 mEq.L-1 (HR=5,0; p=0,001), escore SAPS3 > 55 (HR=5,6; p=0,002) e desorientação (HR=2,5; p=0,04) foram preditores independentes de FAN. Conclusões FAN é uma arritmia comum em idosos hospitalizados com pneumonia por COVID-19. Parâmetros clínicos e laboratoriais avaliados na admissão são preditores de FAN durante internação.

Abstract Background New-onset atrial fibrillation (NOAF) occurs in patients hospitalized due to COVID-19. It is still unknown whether clinical and laboratory data assessed upon hospital admission have predictive value for NOAF. Objectives To analyze, upon hospital admission, variables with predictive potential for the occurrence of NOAF in patients with COVID-19 pneumonia. Methods Observational, retrospective, case-control study. Electronic medical reports of consecutive patients, 60 years of age or older, hospitalized due to COVID-19 pneumonia between March 1st and July 15th, 2020, were reviewed. Non-paired Student or chi-squared tests compared variables. A Cox proportional hazard model was employed to identify independent predictors of NOAF. P value < 0.05 was considered statistically significant. Results Among 667 patients hospitalized due to COVID-19, 201 (30.1%) fulfilled the inclusion criteria. NOAF was documented in 29 patients (14.4%), composing group 1. Group 2 was composed of 162 patients without NOAF. Ten patients were excluded due to the AF rhythm upon hospital admission. In groups 1 and 2, there were differences in overall in-hospital survival rate (24.1 % vs. 67.9%; p<0.001), length of stay in ICU (11.1 ± 10.5 days vs. 4.9 ± 7.5 days; p=0.004) and need for mechanical ventilation rate (82.9% vs. 32.7%; p<0.001). In the Cox model, age > 71 y/o (HR=6.8; p<0.001), total leukocyte count ≤ 7,720 cels.μL-¹ (HR=6.6; p<0.001), serum [Na+] ≤ 137 mEq.L-¹ (HR=5.0; p=0.001), SAPS3 score > 55 (HR=5.6; p=0.002), and disorientation (HR=2.5; p=0.04) on admission were independent predictors of NOAF. Conclusion NOAF is a common arrhythmia in elderly hospitalized patients with COVID-19 pneumonia. Clinical and laboratory parameters evaluated on admission have a predictive value for the occurrence of NOAF during hospitalization.