Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Pérdida de peso no intencionada, un diagnóstico de patología orgánica con costos a la salud.

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Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Frecuencia de hiponatremia posoperatoria en pacientes sometidos a cirugía mayor en un centro de tercer nivel

Contexto la hiponatremia posoperatoria es una complicación frecuente que se encuentra hasta en el 4 % de los pacientes sometidos a cirugía y que además es un factor independiente de mortalidad intrahospitalaria. Hasta ahora, los estudios se enfocan en las primeras horas posteriores a la cirugía, existiendo poca literatura que abarque hasta el periodo posoperatorio tardío. Objetivo evaluar la frecuencia y las características de hiponatremia en la primera semana posoperatoria. Metodología se incluyeron pacientes sometidos a cirugía mayor durante un periodo de 18 meses. Se determinó el nivel de sodio a las 24 horas, al tercer, quinto y séptimo día del procedimiento. Se clasificó de acuerdo con el tipo de cirugía realizada y se documentó la presencia de datos clínicos y desenlaces de los pacientes. Resultados 280 pacientes fueron estudiados, de los cuales 20 (7,1 %) desarrollaron hiponatremia durante el primer día posoperatorio, 34 (12,1 %) en el tercero, 30 (10,7 %) en el quinto día y 31 (11 %) en el séptimo día. En el primer día posoperatorio, los pacientes sometidos a cirugías urológicas y gastrointestinales desarrollaron hiponatremia con mayor frecuencia. Ninguno de los pacientes desarrolló complicaciones graves y no hubo relación entre la edad, el género o el tipo de soluciones y el desarrollo de hiponatremia. Conclusiones la hiponatremia es una complicación frecuente de varios tipos de procedimientos quirúrgicos que puede desarrollarse en los primeros siete días posoperatorios.

Background Postoperative hyponatremia is a frequent complication that is found in more than 4% of patients undergoing surgery. It is also an independent factor of in-hospital mortality. Until now, previous studies have focused on the first hours after surgery, so there is little information regarding hyponatremia in the late postoperative period. Purpose evaluate the frequency and characteristics of hyponatremia in the first postsurgical week. Methodology Patients undergoing major surgery over a period of 18 months were included. Sodium level was determined at 24 hours, third, fifth and seventh day of the procedure. Hyponatremia was classified according to surgery type and presence of clinical symptoms and outcomes were documented. Results 280 patients were studied. 20 (7.1%) developed hyponatremia on the first postoperative day, 34 (12.1%) on the third, 30 (10.7%) on the fifth day, and 31 (11%) on the seventh day. On the first postoperative day, patients undergoing urological and gastrointestinal surgeries developed hyponatremia more frequently. None of the patients developed serious complications. There was no relationship between age, gender or type of solutions and the development of hyponatremia. Conclusions hyponatremia is a frequent complication of surgical procedures that can develop in the first seven postoperative days.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients.

BACKGROUND: SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. METHODS: We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. RESULTS: Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPß, IRF1and FOSL2 potentially suggests the induction of trained immunity. CONCLUSIONS: Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.

Sacroilitis paraneoplásica: presentación inusual de leucemia linfoblástica aguda.

La sacroilitis es una manifestación poco común de neoplasias hematológicas. Reportamos el caso de una mujer de 40 años que presentó un cuadro de 1 mes de evolución con fiebre y sacroilitis simulando espondiloartritis, acompañado de anemia, hepatomegalia y elevación de marcadores inflamatorios. El abordaje descartó infecciones y causas inflamatorias de dolor sacroilíaco. Los hallazgos en la médula ósea llevaron al diagnóstico de leucemia linfoblástica aguda (LLA) de células B. Hasta donde sabemos, el presente es uno de los pocos casos publicados de LLA que se manifiesta con sacroilitis. La sacroilitis como manifestación inicial de LLA puede resultar en un diagnóstico erróneo, por lo que el diagnóstico diferencial es esencial cuando se encuentran presentes características atípicas.Sacroiliitis is an uncommon manifestation of hematological malignancies. We herein report the case of a 40-year-old female that presented with a one-month-old history of fever and sacroiliitis mimicking spondylarthritis, accompanied by anemia, hepatomegaly, and elevated inflammatory markers. Work-up ruled out infectious and inflammatory causes of sacroiliac pain. Bone marrow findings led to the diagnosis B-cell acute lymphoblastic leukemia (ALL). To the best of our knowledge, the current study represents one of the few published cases of ALL presenting with sacroiliitis. Sacroiliitis as an onset manifestation of ALL may result in misdiagnosis, therefore, a differential diagnosis is essential when atypical features are present.

Asociación de los índices neutrófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19 / Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality

Resumen Introducción: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. Objetivo: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. Método: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. Resultados: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. Conclusión: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Abstract Introduction: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. Objective: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. Method: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. Results: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002] with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. Conclusion: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19.

Prone position in non-intubated patient with COVID-19 as a maneuver to avoid intubation. / Posición prono en paciente no intubado con COVID-19 como maniobra para evitar la intubación.

BACKGROUND: The COVID-19 (from Coronavirus Disease 2019) is a disease that has generated a pandemic that has affected the world, Mexico included. The spectrum of the disease ranges from asymptomatic infection to severe acute respiratory distress syndrome (ARDS). The objective of the case is to demonstrate the usefulness of the prone position in non-intubated patients. CLINICAL CASE: We present the case of a woman without comorbidities with COVID-19 and moderate ARDS, in whom intubation was avoided after improvement with the prone position, as determined by arterial oxygen saturation by pulse oximetry and by the relationship of arterial oxygen pressure and the fraction of inspired oxygen (PaO2/FiO2). CONCLUSION: There is scarce evidence of this therapeutic maneuver in awake patients. However, it can help to improve oxygenation and to avoid intubation in these patients.

INTRODUCCIÓN: la COVID-19 (del inglés Coronavirus Disease 2019) es una enfermedad que ha generado una pandemia, la cual ha afectado a todo el mundo, incluido México. Esta enfermedad puede presentarse desde una infección asintomática hasta síndrome de distrés respiratorio agudo (SDRA) grave. El objetivo del reporte de caso es mostrar la utilidad de la posición prono en pacientes no intubados. CASO CLÍNICO: presentamos el caso de una mujer sin comorbilidades con COVID-19 y SDRA moderado, en quien se evitó la intubación tras la mejoría con la posición prono, evaluada por la saturación arterial de oxígeno por pulsioximetría y por la relación de la presión arterial de oxígeno y la fracción inspirada de oxígeno (PaO2/FiO2). CONCLUSIÓN: existe poca evidencia sobre esta maniobra terapéutica en pacientes despiertos. Sin embargo, puede ser de ayuda para mejorar la oxigenación y evitar la intubación en estos pacientes.

Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality.

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. OBJECTIVE: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. METHOD: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. RESULTS: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002) with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. CONCLUSION: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19. INTRODUCCIÓN: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. OBJETIVO: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. MÉTODO: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. RESULTADOS: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. CONCLUSIÓN: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Síndrome autoinmune/inflamatorio inducido por adyuvante que debuta con manifestaciones pulmonares y articulares / Adjuvant induced autoimmune/inflammatory syndrome presenting as joint and lung manifestations

Mujer de 59 años de edad, la cual cuenta con antecedente de aplicación de material oleoso en los glúteos hace 11 años; posteriormente hace 18 meses comienza con cuadro de poliartritis aditivas simétricas, así como afección en las vías aéreas superior e inferior, sin evidencia de alteración por granulomatosis con poliangitis (Wegener). Presenta en suero autoanticuerpos, y se toma biopsia de piel donde se observa granuloma por cuerpo extraño. Se concluye con síndrome autoinmune/inflamatorio inducido por adyuvante, en el que la afección pulmonar es una manifestación atípica en la presentación inicial de la enfermedad (AU)

A 59-year-old female with a history of injection of an oily material in the buttocks 11 years ago. She developed symmetric additive polyarthritis as well as superior and inferior airways involvement. There was no evidence of granulomatosis with polyangiitis (Wegener). She had several serum autoantibodies and a skin biopsy showed a foreign body granuloma. The diagnosis of adjuvant induced autoimmune/inflammatory syndrome was made. The pulmonary involvement was an atypical manifestation at the onset of disease (AU)

Adjuvant induced autoimmune/inflammatory syndrome presenting as joint and lung manifestations.

A 59 year-old female with a history of injection of an oily material in the buttocks 11 years ago. She developed symmetric aditive polyarthritis as well as superior and inferior airways involvement. There was no evidence of granulomatosis with polyangiitis (Wegener). She had several serum autoantibodies and a skin biopsy showed a foreign body granuloma. The diagnosis of adjuvant induced autoimmune/inflammatory syndrome was made. The pulmonary involvement was an atypical manifestation at the onset of disease.

La valoración preoperatoria en el adulto / Preoperative evaluation in adults

Este trabajo pretende reconsiderar la utilidad y las indicaciones de la valoración preoperatoria en el adulto. Se estudió de manera prospectiva una cohorte de 791 pacientes candidatos a tratamiento quirúrgico, mayores de 40 años, que contaban con citología hemática, glucosa en sangre, urea, creatinina, sodio y potasio séricos, tiempo de protrombina, tiempo de tromboplastina parcial, cuenta de plaquetas, pruebas de funcionamiento hepático, telerradiografía de tórax en posteroanterior y electrocardiograma. Se buscaron complicaciones postoperatorias cardiovasculares, renales, hepáticas, pulmonares, hemorrágicas trans y postoperatorias, infecciosas y alteraciones metabólicas, mediante una visita diaria que se continuó hasta el egreso hospitalario. Se calculó el riesgo relativo (RR) de cada una de la variables, para predecir cada una de las complicaciones, valorando las diferencias con X² y prueba exacta de Fisher. Las variables estadísticamente significativas se sometieron a regresión logística. Se estudiaron 751 pacientes, 335 hombres (44 por ciento) y 416 mujeres (56 por ciento), con edad promedio de 63.9 años. Las complicaciones más frecuentes fueron las alteraciones metabólicas (16.9 por ciento) y las infecciones postoperatorias (7.0). La hemorragia trans o postoperatoria tuvo una frecuencia de 2.2 por ciento. Hubo 17 defunciones (2.2 por ciento) relacionadas directamente con la magnitud del suceso quirúrgico, la presencia de enfermedades subyacentes y la suma de complicaciones postoperatorias. La selección de pruebas de laboratorio y gabinetes, para llevar a cabo la valoración clínica, la cual debe enfocarse a la búsqueda de factores de riesgo para complicaciones del acto quirúrgico

Acidosis tubular renal tipo I y parálisis periódica hipopotasémica / Tubular acidosis type 1 with hypotassemic periodic paralysis

Mujer de 25 años de edad con el diagnóstico de acidosis tubular renal distal o tipo 1 con acidosis metabólica hiperclorémica o de brecha aniónica normal persistente, pH urinario mayor de 6.5, excreción urinaria de calcio elevada a hipopotasemia. La frecuencia de la acidosis tubular renal distal tipo 1 asociada a parálisis periódica hipopotasémica es rara. En la literatura los reportes con escasos

Lambert-Eaton en un hombre con cáncer de páncreas / Lambert-Eaton in a men with pancreas cancer

El síndrome de Lambert-Eaton (L-E) es un padecimiento autoinmunitario descrito por Eaton y Lambert en 1957. Afecta con mayor frecuencia a hombres y se caracteriza por debilidad, mialgias y fatiga en extremidades inferiores e hiporeflexia. Se pueden presentar ptósis y son frecuentes las alteraciones de tipo disautonómico como sequedad de boca y ojos, impotencia, disminución de la sudoración y sintomatología ortostática. En la mayoría de los casos está asociado a neoplasias, principalmente a cáncer de células pequeñas de pulmón; también se ha asociado a enfermedades autoinmunes y en un porcentaje de los casos no es posible demostrar enfermedad subyacente. El propósito de este escrito es informar el caso de un paciente que presentó como manifestación inicial un Síndrome de Lambert-Eaton en el que se descartó cáncer de pulmón y otras enfermedades autoinmunes. Seis meses después se encontró cáncer de páncreas