Identification of Clinically Significant Cytokine Signature Clusters in Patients With Septic Shock.

OBJECTIVES: To identify cytokine signature clusters in patients with septic shock. DESIGN: Prospective observational cohort study. SETTING: Single academic center in the United States. PATIENTS: Adult (≥ 18 yr old) patients admitted to the medical ICU with septic shock requiring vasoactive medication support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fourteen patients with septic shock completed cytokine measurement at time of enrollment (t 1 ) and 24 hours later (t 2 ). Unsupervised random forest analysis of the change in cytokines over time, defined as delta (t 2 -t 1 ), identified three clusters with distinct cytokine profiles. Patients in cluster 1 had the lowest initial levels of circulating cytokines that decreased over time. Patients in cluster 2 and cluster 3 had higher initial levels that decreased over time in cluster 2 and increased in cluster 3. Patients in clusters 2 and 3 had higher mortality compared with cluster 1 (clusters 1-3: 11% vs 31%; odds ratio [OR], 3.56 [1.10-14.23] vs 54% OR, 9.23 [2.89-37.22]). Cluster 3 was independently associated with in-hospital mortality (hazard ratio, 5.24; p = 0.005) in multivariable analysis. There were no significant differences in initial clinical severity scoring or steroid use between the clusters. Analysis of either t 1 or t 2 cytokine measurements alone or in combination did not reveal clusters with clear clinical significance. CONCLUSIONS: Longitudinal measurement of cytokine profiles at initiation of vasoactive medications and 24 hours later revealed three distinct cytokine signature clusters that correlated with clinical outcomes.

Aortic Dissection From an Intra-aortic Balloon Pump: A Dangerous Complication to Keep in Mind.

Despite the benefits of the intra-aortic balloon pump (IABP) being a subject of debate, it remains a widely available and easy-to-use mechanical circulatory support device. Nonetheless, its use is not exempt from complications. Aortic dissection from IABP is an infrequent but deathly complication. We describe a case in which early recognition of the condition led to control through an endovascular approach. A 57-year-old male was admitted for acute decompensated heart failure requiring intravenous inotropic agents. While undergoing assessment for a heart transplant, he developed cardiogenic shock requiring initiation of mechanical circulatory support with an IABP. A few hours after device implantation, the patient developed acute tearing chest pain and was found to have an acute dissection in the descending thoracic aorta. Prompt liaison with the endovascular team led to a thoracic endovascular aortic repair to control the extent of the lesion.

Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Immediate Effect of Mechanical Ventilation Mode and Sedative Infusion on Measured Diaphragm Thickness.

Rationale: In patients who are mechanically ventilated, diaphragm thinning on ultrasound is thought to correlate with diaphragm atrophy and has been associated with prolonged intubation. Factors other than atrophy, however, may cause changes in diaphragm thickness, which may confound studies examining changes in diaphragm thickness over time. Objectives: To determine if changes in the mode of mechanical ventilation or an interruption of sedatives have immediate effects on diaphragm thickness measurements in adult patients in the intensive care unit who are mechanically ventilated. Methods: Adult patients receiving invasive mechanical ventilation for less than 48 hours were included. Diaphragm thickness was measured at end-expiration and peak inspiration using ultrasound while patients were receiving both volume assist-control and pressure-support modes in a randomized crossover fashion. In patients receiving sedatives, additional measurements were taken after an interruption of sedatives. Measurements were compared between modes and on assist-control before and after an interruption of sedatives. Results: Of 85 patients enrolled, 66 had measurements on assist-control and spontaneous modes, and 40 had measurements before and after an interruption of sedatives. End-expiratory diaphragm thickness increased by a median of 0.08 mm after an interruption of sedatives (95% confidence interval [CI], 0.002 mm to 0.164 mm; P = 0.017), corresponding to a median increase of 6.5%. No difference was seen when comparing measurements taken on volume assist-control and pressure support (median difference, 0 mm; 95% CI, -0.07 mm to 0.08 mm; P = 0.98). Conclusions: End-expiratory diaphragm thickness increased by 6.5% after an interruption of sedatives. The effect of sedatives on measured diaphragm thickness should be considered in future studies examining changes in diaphragm thickness over time. Clinical trial registered with Clinicaltrials.gov (NCT04319939).

Bedside estimates of dead space using end-tidal CO2 are independently associated with mortality in ARDS.

PURPOSE: In acute respiratory distress syndrome (ARDS), dead space fraction has been independently associated with mortality. We hypothesized that early measurement of the difference between arterial and end-tidal CO2 (arterial-ET difference), a surrogate for dead space fraction, would predict mortality in mechanically ventilated patients with ARDS. METHODS: We performed two separate exploratory analyses. We first used publicly available databases from the ALTA, EDEN, and OMEGA ARDS Network trials (N = 124) as a derivation cohort to test our hypothesis. We then performed a separate retrospective analysis of patients with ARDS using University of Chicago patients (N = 302) as a validation cohort. RESULTS: The ARDS Network derivation cohort demonstrated arterial-ET difference, vasopressor requirement, age, and APACHE III to be associated with mortality by univariable analysis. By multivariable analysis, only the arterial-ET difference remained significant (P = 0.047). In a separate analysis, the modified Enghoff equation ((PaCO2-PETCO2)/PaCO2) was used in place of the arterial-ET difference and did not alter the results. The University of Chicago cohort found arterial-ET difference, age, ventilator mode, vasopressor requirement, and APACHE II to be associated with mortality in a univariate analysis. By multivariable analysis, the arterial-ET difference continued to be predictive of mortality (P = 0.031). In the validation cohort, substitution of the arterial-ET difference for the modified Enghoff equation showed similar results. CONCLUSION: Arterial to end-tidal CO2 (ETCO2) difference is an independent predictor of mortality in patients with ARDS.

Temperature Trajectory Subphenotypes Correlate With Immune Responses in Patients With Sepsis.

OBJECTIVES: We recently found that distinct body temperature trajectories of infected patients correlated with survival. Understanding the relationship between the temperature trajectories and the host immune response to infection could allow us to immunophenotype patients at the bedside using temperature. The objective was to identify whether temperature trajectories have consistent associations with specific cytokine responses in two distinct cohorts of infected patients. DESIGN: Prospective observational study. SETTING: Large academic medical center between 2013 and 2019. SUBJECTS: Two cohorts of infected patients: 1) patients in the ICU with septic shock and 2) hospitalized patients with Staphylococcus aureus bacteremia. INTERVENTIONS: Clinical data (including body temperature) and plasma cytokine concentrations were measured. Patients were classified into four temperature trajectory subphenotypes using their temperature measurements in the first 72 hours from the onset of infection. Log-transformed cytokine levels were standardized to the mean and compared with the subphenotypes in both cohorts. MEASUREMENTS AND MAIN RESULTS: The cohorts consisted of 120 patients with septic shock (cohort 1) and 88 patients with S. aureus bacteremia (cohort 2). Patients from both cohorts were classified into one of four previously validated temperature subphenotypes: "hyperthermic, slow resolvers" (n = 19 cohort 1; n = 13 cohort 2), "hyperthermic, fast resolvers" (n = 18 C1; n = 24 C2), "normothermic" (n = 54 C1; n = 31 C2), and "hypothermic" (n = 29 C1; n = 20 C2). Both "hyperthermic, slow resolvers" and "hyperthermic, fast resolvers" had high levels of G-CSF, CCL2, and interleukin-10 compared with the "hypothermic" group when controlling for cohort and timing of cytokine measurement (p < 0.05). In contrast to the "hyperthermic, slow resolvers," the "hyperthermic, fast resolvers" showed significant decreases in the levels of several cytokines over a 24-hour period, including interleukin-1RA, interleukin-6, interleukin-8, G-CSF, and M-CSF (p < 0.001). CONCLUSIONS: Temperature trajectory subphenotypes are associated with consistent cytokine profiles in two distinct cohorts of infected patients. These subphenotypes could play a role in the bedside identification of cytokine profiles in patients with sepsis.

Presentación clínico-patológica del adenocarcinoma prostático en un Hospital de tercer nivel en Colombia / Clinical-pathological Presentation of Prostatic Adenocarcinoma in a Tertiary Hospital in Colombia

Objetivo Mundialmente, el cáncer de próstata es la segunda neoplasia maligna más frecuente en hombres a nivel mundial y la primera en Colombia. Se determinaron las características clínico-patológicas de los casos de cáncer de próstata diagnosticados en un hospital de la región caribe colombiana. Métodos Se realizó un estudio retrospectivo en la Facultad de Medicina de la Universidad de Cartagena, Colombia. Se analizaron las características clínicas y patológicas de todos los pacientes diagnosticados con cáncer de próstata en el Hospital Universitario del Caribe durante los años 2007 a 2014. Resultados Se documentaron 394 casos, con edad promedio de 71,13 años (DE ± 8,25). El puntaje de Gleason fue mayor o igual a 8 en el 31,7%. En biopsias hubo localización bilateral del tumor en un 73,5% y compromiso tumoral mayor al 40% del tejido en el 73,2% de los casos. En un 5,8% de los pacientes, hubo valores de PSA normales. Se dio una asociación estadísticamente significativa entre el PSA y el examen digital rectal (p = 0,0009), puntaje de Gleason (p < 0,0001) y porcentaje de compromiso tumoral en biopsias (p < 0,0012). La combinación PSA más examen digital rectal obtuvo una sensibilidad del 96%. Conclusiones Gran parte de los casos de cáncer de próstata se diagnostican en estadios avanzados. La mayor sensibilidad para el diagnóstico clínico la tiene el uso del PSA más el examen digital rectal, sin dejar de lado la experiencia clínica que permite diagnosticarlo aún con PSA o examen digital rectal normales. Esos hallazgos deben promover la educación de la población.

Objective Worldwide, prostate cancer is the second most common malignant neoplasm diagnosed in men, in Colombia is the most common. The objective was to determine clinical and histopathological characteristics based upon the cases of prostate cancer diagnosed in a hospital of the Colombian Caribbean coast. Methods A retrospective study was conducted in the Faculty of Medicine at the University of Cartagena, Colombia. Clinical and pathological characteristics were analyzed in all patients diagnosed with prostate cancer at the Hospital Universitario del Caribe between January 2007 and December 2014. Results A total of 394 cases were documented. Mean presentation age was 71,1 years (SD ± 8,25). A Gleason score greater than 8 was reported in 31.7% of the cases. Biopsies showed bilateral tumor localization in 73.5% and percent tumor involvement greater than 40% in 73.2% of cases. 5.8% of patients presented with normal PSA values. A statistically significant difference was found between PSA and: digital rectal exam (p = 0.0009), Gleason Score (p < 0.0001) and percent tumor involvement in biopsies (p < 0.0012). PSA and digital rectal examination had a sensitivity of 96%. Conclusions A large proportion of prostate cancer cases are diagnosed in advanced stages. The highest sensitivity for the clinical diagnosis is made by the combined use of PSA and digital rectal examination, without ignoring the clinical experience that allows the diagnosis of cancer even in cases with normal PSA and/or digital rectal examination. These findings may increase awareness for the early diagnosis of the disease in the population.

Factores de riesgo presentes en pacientes con lesiones intraepiteliales escamosas del cérvix en la Clínica Maternidad Rafael Calvo en la ciudad de Cartagena(Colombia): estudio descriptivo / Risk factors in patients with cervical squamous intraepithelial lesions in Clínica Maternidad Rafael Calvo in Cartagena (Colombia): descriptive study

Objetivo: describir los factores de riesgo presentes en un grupo de pacientes con lesiones intraepiteliales escamosas (LIE) de cérvix en una entidad de referencia para mujeres del régimen subsidiado en la ciudad de Cartagena entre los años 2007 y 2012. Materiales y métodos: estudio descriptivo. La población de estudio la conformaron pacientes con diagnóstico histológico de lesiones intraepiteliales escamosas, que asistieron a la Unidad de Patología Cervical y Colposcopia de la Clínica Maternidad Rafael Calvo, de Cartagena (Colombia). La muestra fueron 150 mujeres mayores de 18 años. Resultados: el promedio de edad fue 35,5 años, el62% del grupo estudio se encontró entre los 20 y 39 años. El 78% presentó LIE debajo grado y el 22% LIE de alto grado. El 74% tuvo dos o más embarazos, 44,1% su primer embarazo fue antes de los 20 años, 64% tuvieron dos o más partos, 94.66% de la población no era fumadora, 4% refirió consumir alcohol regularmente, 54% afirmó haber tenido dos o más compañeros sexuales, 62% inició su vida sexual entrelos 16-20 años, 22% usa anticonceptivos hormonales y 38% no utiliza métodos de planificación familiar. Conclusiones: la multiparidad, la cantidad de embarazos, la sexarquia temprana, el múltiple número de parejas sexuales y los métodos hormonalesde anticoncepción, fueron los factores de riesgo con mayor frecuencia encontrados en las pacientes con lesiones intraepiteliales escamosas del cerviz en Cartagena.

Introduction: the squamous intraepithelial lesions are an indispensable condition for the occurrence of cervical cancer, one of the leading causes of death from gynecological cancer. The aim of this study is to show the risk factors more frequently found inpatients with squamous intraepithelial lesions of the cervix in this population. Materials and methods: a descriptive study of patients with squamous intraepithelial lesions, who attended the unit of cervical pathology and colposcopy in Clínica Maternidad RafaelCalvo. Results: the average age was 35.5 years, 62% of the study group was between20 and 39 years. 78% had LSIL and 22% HSIL. 74% had two or more pregnancies,44,1% had their first pregnancy before age 20, 64% had two or more deliveries, 62%the age of first intercourse was between 16-20 years, 54% had two or more sexual partners, 22% use hormonal contraceptives. 94.66% of the population didn’t smokeand 78.66% deny alcohol. Conclusions: multiparity, early onset of sexual intercourse, multiple sexual partners and use hormonal contraceptives were the factors most frequently found in the population of patients with squamous intraepithelial lesions of the cervix in Cartagena.