Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients.

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system-IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII-for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFß, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19.

OBJECTIVE: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. DESIGN: An observational, analytical, retrospective cohort study with longitudinal follow-up. SETTING: Hospital Universitario Príncipe de Asturias (HUPA). PARTICIPANTS: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. MAIN OUTCOME MEASURES: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). RESULTS: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. CONCLUSIONS: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient's inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure.

A Predictive Model and Risk Factors for Case Fatality of COVID-19.

This study aimed to create an individualized analysis model of the risk of intensive care unit (ICU) admission or death for coronavirus disease 2019 (COVID-19) patients as a tool for the rapid clinical management of hospitalized patients in order to achieve a resilience of medical resources. This is an observational, analytical, retrospective cohort study with longitudinal follow-up. Data were collected from the medical records of 3489 patients diagnosed with COVID-19 using RT-qPCR in the period of highest community transmission recorded in Europe to date: February-June 2020. The study was carried out in in two health areas of hospital care in the Madrid region: the central area of the Madrid capital (Hospitales de Madrid del Grupo HM Hospitales (CH-HM), n = 1931) and the metropolitan area of Madrid (Hospital Universitario Príncipe de Asturias (MH-HUPA) n = 1558). By using a regression model, we observed how the different patient variables had unequal importance. Among all the analyzed variables, basal oxygen saturation was found to have the highest relative importance with a value of 20.3%, followed by age (17.7%), lymphocyte/leukocyte ratio (14.4%), CRP value (12.5%), comorbidities (12.5%), and leukocyte count (8.9%). Three levels of risk of ICU/death were established: low-risk level (<5%), medium-risk level (5-20%), and high-risk level (>20%). At the high-risk level, 13% needed ICU admission, 29% died, and 37% had an ICU-death outcome. This predictive model allowed us to individualize the risk for worse outcome for hospitalized patients affected by COVID-19.

Valor pronóstico del antecedente de insuficiencia cardiaca en pacientes ingresados con tromboembolia pulmonar / Prognostic value of prior heart failure in patients admitted with acute pulmonary thromboembolism

Fundamento y objetivo: El tromboembolismo pulmonar (TEP) es una entidad frecuente con una elevada morbimortalidad. Aunque algunas escalas consideran la insuficiencia cardiaca (IC) como factor de riesgo de TEP, ninguna ha analizado la contribución del tipo de IC, con fracción de eyección del ventrículo izquierdo (FEVI) reducida y preservada, al pronóstico intrahospitalario de los pacientes ingresados con un episodio de TEP. Pacientes y método: Estudio de cohortes retrospectivo que incluyó pacientes hospitalizados por TEP de manera consecutiva durante el período comprendido entre 2012-2014. Se analizaron las características epidemiológicas basales, el tratamiento durante su ingreso, así como variables pronósticas durante su estancia hospitalaria. Se definió como objetivo primario la mortalidad intrahospitalaria por cualquier causa. Resultados: Se incluyeron 442 pacientes con TEP (88 con historia de IC). Los pacientes con antecedente de IC resultaron ser mayores, con mayor porcentaje de hipertensos y diabéticos, mayor presencia de enfermedad renal crónica, pulmonar u oncológica y cardiopatía isquémica, y con menor FEVI (p<0,001). La mortalidad intrahospitalaria fue significativamente mayor en el grupo con historia previa de IC (21,6 frente a 6,8%, p<0,001). En el análisis multivariante, únicamente la IC con FEVI reducida se mostró como factor de riesgo independiente (OR 5,54; IC 95% 2,12-14,51), no así la IC con FEVI preservada (OR 1,29; IC 95% 0,72-4,44). Conclusiones: Los pacientes con antecedentes de IC ingresados con un TEP deben ser considerados como una población de alto riesgo, presentando una elevada morbimortalidad intrahospitalaria. Dentro de este grupo, son aquellos con IC y FEVI reducida los que presentan un peor pronóstico (AU)

Background and objective: Pulmonary thromboembolism (PTE) is a very common condition with high mortality. Although some scales include heart failure (HF) as a risk factor of PTE, none of them have assessed the contribution of the different kinds of HF, i. e. with reduced or preserved left ventricular ejection fraction (LVEF) to the in-hospital outcome of patients admitted with PTE. Patients and method: A retrospective study assessing a cohort of patients consecutively admitted to hospital with a PTE from 2012-2014. Baseline epidemiological characteristics, treatment during admission and prognostic variables during hospitalization were analyzed. Primary endpoint was defined as hospital mortality for any cause. Results: A total of 442 patients with PTE were included (88 with prior HF). Patients with a history of HF were older, more frequently had hypertension, diabetes mellitus, chronic kidney or pulmonary disease, cancer, and coronary artery disease, and showed less LVEF (P<.001). Hospital mortality was significantly higher in patients with prior HF (21.6 vs. 6.8%, P<.001). Multivariate analysis found that HF with reduced LVEF but not HF with preserved LVEF resulted as an independent risk factor (respectively OR 5.54; 95% CI 2.12-14.51 and OR 129; 95% CI 0.72-4.44). Conclusions: Patients with prior HF admitted to hospital with PTE should be considered a high-risk population, since they present high in-hospital mortality. In our cohort, patients with prior HF and reduced LVEF presented a poorer prognosis than those with preserved LVEF (AU)

[Prognostic value of prior heart failure in patients admitted with acute pulmonary thromboembolism]. / Valor pronóstico del antecedente de insuficiencia cardiaca en pacientes ingresados con tromboembolia pulmonar.

BACKGROUND AND OBJECTIVE: Pulmonary thromboembolism (PTE) is a very common condition with high mortality. Although some scales include heart failure (HF) as a risk factor of PTE, none of them have assessed the contribution of the different kinds of HF, i. e. with reduced or preserved left ventricular ejection fraction (LVEF) to the in-hospital outcome of patients admitted with PTE. PATIENTS AND METHOD: A retrospective study assessing a cohort of patients consecutively admitted to hospital with a PTE from 2012-2014. Baseline epidemiological characteristics, treatment during admission and prognostic variables during hospitalization were analyzed. Primary endpoint was defined as hospital mortality for any cause. RESULTS: A total of 442 patients with PTE were included (88 with prior HF). Patients with a history of HF were older, more frequently had hypertension, diabetes mellitus, chronic kidney or pulmonary disease, cancer, and coronary artery disease, and showed less LVEF (P<.001). Hospital mortality was significantly higher in patients with prior HF (21.6 vs. 6.8%, P<.001). Multivariate analysis found that HF with reduced LVEF but not HF with preserved LVEF resulted as an independent risk factor (respectively OR 5.54; 95% CI 2.12-14.51 and OR 129; 95% CI 0.72-4.44). CONCLUSIONS: Patients with prior HF admitted to hospital with PTE should be considered a high-risk population, since they present high in-hospital mortality. In our cohort, patients with prior HF and reduced LVEF presented a poorer prognosis than those with preserved LVEF.

Effectiveness of botulinum toxin (type-A) administered by the fixed-site dosing approach versus the muscle area identification.

INTRODUCTION: Botulinum toxin is widely used in glabellar musculature. The authors express the need to individualize the approach by means of muscular identification to improve effectiveness. Despite these guidelines, the fixed-point technique is still used. OBJECTIVE: Comparison of effectiveness of botulinum toxin administration in the glabellar zone by using fixed-site application versus objective-muscle-identification. MATERIALS AND METHODS: Prolective dynamic cohort study. Patients (after previous informed consent) were assessed on their facial expressions, level of satisfaction, re-interventions, adverse effects, dosage, dilution, and number of injections. All patients who experienced either of both techniques of botulinum toxin administration (fixed-site or objective-muscle-identification) were subjected to followup by the following parameters: statistical analysis: student's t Test (inter-group mean comparisons), paired student's t test (intra-group mean comparisons), χ (2) with Fisher exact text. RESULTS: Sixty-two patients were evaluated (31 fixed-site approach, 31 objective-muscle-identification). No patient abandoned the trial during followup. Fixed-site injections required larger doses (16 vs 12 U, p = 0.001), greater volume (0.48 vs. 0.37 ml, p = 0.001), and more application sites (4 vs 2, p = 0.001), compared to the objective-muscle-identification approach. Under the objective-muscle-identification technique, facial expressions were better attenuated (52 vs 65%, p = 0.001), with a higher initial satisfaction level (6 vs 9, p = 0.001) and final satisfaction level (9 vs 9.9, p = 0.001). CONCLUSIONS: Botulinum toxin application is more effective when administered through the objective-muscle-identification approach (less frowning, lower doses, less fixed sites injected, and patients more satisfied at the end). LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Leech hirudo medicinalis: a therapeutic alternative available in Mexico]. / Sanguijuela Hirudo medicinalis: una alternativa terapéutica disponible en México.

Throughout history a diversity of therapeutic properties have been attributed to the leech Hirudo medicinalis, however, during the past twenty years its use has proven to be a practical and effective method for the relief of venous engorgement in reconstructive surgery. In Mexico this practice has been limited due to the lack of supply and to the time-consuming process of importation. Based on this need, the animal facilities of the Occidental Biomedical Research Center-IMSS in Guadalajara, Jalisco, has initiated a breeding and reproduction program of this species with the aim at improving its availability as a therapeutic device. The salivary gland of Hirudo medicinalis contains one of the most potent natural anticoagulants, known as hirudin, a histamine-like vasodilator, platelet aggregation inhibitors and highly specific proteases, all of which favor venous flow and turn this species into the most useful in the clinical setting. Nevertheless, it is important to know the potential risks of leech therapy since it has been associated with considerable morbidity when adequate precautions are not taken. This review exposes relevant aspects of the medicinal leech, the indications, mechanism of action and the protocol for this therapy.

Clinical experience using the dorsal reverse metacarpal flap for the treatment of congenital syndactyly: report of four cases.

Skin grafts and local flaps are conventional methods of repair for simple complete syndactyly, but the results obtained are not always as functional and aesthetic as desired and frequently leave postoperative scars and residual syndactyly. In this article, we describe a new surgical technique for the correction of syndactyly that utilizes a metacarpal dorsal reverse flap to provide skin coverage to the interdigital space and also to 1 side of the finger, therefore avoiding the use of skin grafts and resulting postoperative scar contracture. We report 4 cases using this procedure, with a 12-month follow up. The technique is safe, easily performed, and reproducible and requires a single surgical procedure. It uses donor tissue identical in color, texture, and thickness, which renders acceptable cosmesis and good hand function.