Immune treatment in COVID-19.

Current immune treatment directed to avoid viral replication relies mainly in convalescent plasma and monoclonal antibodies (mAbs). No clinical benefit for convalescent plasma has been reported in a meta-analysis and systematic review compared to standard of care. MAbs are recombinant proteins capable to bind with SARS-CoV-2 preventing its entrance into cells. Several mAbs have shown reduction in viral load and/or progression of the disease such as casirivimab-imdevimab, bamlanivimab-etesevimab and sotrovimab. After the apparition of Omicron variant, it has been reported that sotrovimab retained its activity whereas the other two combinations exhibited loss of neutralizing activity. Several aspects as the target population, timing and doses, serological patient status and evolution of variants still require attention, monitorization and further studies for knowledge gaps.

[Pharmacological treatment of COVID-19: Narrative review of the Working Group in Infectious Diseases and Sepsis (GTEIS) and the Working Groups in Transfusions and Blood Products (GTTH)]. / Tratamiento farmacológico de la COVID-19: revisión narrativa de los Grupos de Trabajo de Enfermedades Infecciosas y Sepsis (GTEIS) y del Grupo de Trabajo de Transfusiones Hemoderivados (GTTH).

Infection by the SARS-CoV-2 virus, known as COVID-19 (COronaVIrus Disease-19) was initially detected in China in December 2019, and has subsequently spread rapidly throughout the world, to the point that on March 11 the World Health Organization (WHO) reported that the outbreak could be defined as a pandemic. COVID-19 disease ranges from mild flu-like episodes to other serious and even life-threatening conditions, mainly due to acute respiratory failure. These patients are frequently admitted to our Intensive Care Units in relation to acute respiratory distress syndrome. The lack of a treatment based on scientific evidence has led to the use of different management guidelines, in many cases with rapid changes in the applied protocols. Recent reviews in reputed journals have underscored the lack of proven therapies and the need for clinical trials to establish clear and objective treatment guidelines. The present study provides an update on the currently applied treatment, and intends to offer help in relation to daily care, without seeking to replace the protocols adopted in each individual center.

Guidelines for the management of community-acquired pneumonia in the elderly patient.

The incidence of community-acquired pneumonia (CAP) increases with age and is associated with an elevated morbimortality due to the physiological changes associated with aging and a greater presence of chronic disease. Taking into account the importance of this disease from an epidemiological and prognostic point of view, and the enormous heterogeneity described in the clinical management of the elderly, we believe a specific consensus document regarding this patient profile is necessary. The purpose of the present work was to perform a review of the evidence related to the risk factors for the etiology, the clinical presentation, the management and the treatment of CAP in elderly patients with the aim of elaborating a series of specific recommendations based on critical analysis of the literature. This document is the fruit of the collaboration of different specialists representing the Spanish Society of Emergency Medicine and Emergency Care (SEMES), the Spanish Society of Geriatrics and Gerontology (SEGG), the Spanish Society of Chemotherapy (SEQ), the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Home Hospitalization (SEHAD).

Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia.

Neutrophil activation state and its relationship with an inflammatory environment in community-acquired pneumonia (CAP) remain insufficiently elucidated. We aimed to evaluate the neutrophil apoptosis and cytokine pattern in CAP patients after 72 h of treatment, and their impact on infection resolution. Apoptosis of blood and bronchoalveolar lavage (BAL) neutrophils was measured in nonresponding CAP (NCAP), in responding CAP (blood only) and in patients without infection (control). Pro-inflammatory (interleukin (IL)-6, IL-8) and anti-inflammatory (IL-10) cytokines were measured. Main outcomes were clinical stability and days of hospitalisation. Basal neutrophil apoptosis was higher in the BAL and blood of NCAP, whereas spontaneous apoptosis (after 24 h culture) was lower. Cytokines in NCAP were higher than in responding CAP and control: IL-6 was increased in BAL and blood, IL-8 in BAL and IL-10 in blood. An increased basal apoptosis (≥20%) in BAL of NCAP was associated with lower systemic IL-10 (p<0.01), earlier clinical stability (p=0.05) and shorter hospital stay (p=0.02). A significant correlation was found for systemic IL-6 and IL-10 with days to reach stability and length of stay. After 72 h of treatment, an increased basal alveolar neutrophil apoptosis might contribute to downregulation of inflammation and to faster clinical stability.

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia.

Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p = 0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium < 130 mEq·L⁻¹, pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg and glycaemia ≥ 250 mg·dL⁻¹. The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure < 90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.

Macrophage activation in exacerbated COPD with and without community-acquired pneumonia.

In large series of nonresponding community-acquired pneumonia (CAP) patients, chronic obstructive pulmonary disease (COPD) was observed to be a protective factor for nonresponse to initial antibiotics. This intriguing fact may be linked to changes in the phenotype of inflammatory cells and, in particular, to the induction of classical-M1 or alternative-M2 activation of macrophages, which result in different inflammatory profiles. We evaluated the effect of sputum obtained from patients with acute exacerbation of COPD (AECOPD), CAP and COPD+CAP on the phenotypic changes in macrophages. Human THP1 cells differentiated to macrophages were incubated with sputum from patients with AECOPD, CAP or COPD+CAP, and expression of tumour necrosis factor-alpha, interleukin-6, mannose receptor and arginase was measured to evaluate the phenotype acquired by macrophages. We found that sputum from CAP patients induced the M1 phenotype and that from AECOPD patients induced an M2-like phenotype. Sputum from CAP+COPD patients did not present a clear M1 or M2 phenotype. These results indicate that the microenvironment in the lung modulates the activation of macrophages, resulting in different phenotypes in AECOPD, CAP and COPD+CAP patients. This different type of activation induces different inflammatory responses and may be involved in the different outcome observed when COPD and CAP present simultaneously.

Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.

BACKGROUND: Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. METHODS: The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. RESULTS: The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. CONCLUSIONS: Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

The role of neutropenia on outcomes of cancer patients with community-acquired pneumonia.

Although the presence of neutropenia may predispose cancer patients to develop community-acquired pneumonia, the role of neutropenia on their outcomes has not been investigated. The purpose of the present study was to compare clinical outcomes of cancer community-acquired pneumonia patients with and without neutropenia. Patients with cancer, identified in the Community-Acquired Pneumonia Organization database, were divided into two groups according to the type of cancer and the presence of neutropenia: patients with solid cancer without neutropenia versus those with functional or absolute neutropenia. Among the 3,106 community-acquired pneumonia patients enrolled, 135 had cancer without neutropenia and 75 had cancer with neutropenia. No significant difference was found between patients with and without neutropenia regarding mean time to clinical stability (5.4+/-2.7 versus 4.9+/-2.7 days, respectively), mean length of hospital stay (9.2+/-7.7 versus 9.9+/-9.6 days) and in-hospital mortality (18 versus 15%, respectively). Using a multiple logistic regression model, neutropenia was not associated with mortality in cancer patients when adjusting for significant covariates (odds ratio 1.30). Lack of neutropenia, during the initial evaluation of a cancer community-acquired pneumonia patient, should not be considered an indicator of better clinical outcome.

Potential hepatoprotective effects of new Cuban natural products in rat hepatocytes culture.

The protective effects of five Cuban natural products (Mangifera indica L. (MSBE), Erythroxylum minutifolium, Erythroxylum confusum, Thalassia testudinum and Dictyota pinnatifida extracts and mangiferin) on the oxidative damage induced by model toxicants in rat hepatocyte cultures were studied. Cells were pre-incubated with the natural products (5-200 microg/mL) for 24 h. Then hepatotoxins (tert-butyl hydroperoxide, ethanol, carbon tetrachloride and lipopolysaccharide) were individually added and post-incubated for another 24 h. After treatments, cell viability was determined using the MTT assay. Mangiferin and MSBE exhibited the highest cytoprotective potential (EC50 between 50 and 125 microg/mL), followed by T. testudinum and Erythroxylum extracts, whereas no significant protective effects was produced by Dictyota extract treatment. Antioxidant properties of the natural products against lipid peroxidation and GSH depletion induced by tert-butyl hydroperoxide were then investigated. The results show that at 36 h pre-treatment of cells with mangiferin or MSBE, concentrations of T. testudinum and Erythroxylum extracts ranging from 25 to 100 microg/mL significantly inhibited lipid peroxidation induced by tert-butyl hydroperoxide (100 and 250 microM) and increased the GSH levels reduced by the toxicant. D. pinnatifida inhibited lipid peroxidation, but did not preserve GSH levels. In conclusion, MSBE, E. minutifolium, E. confusum and T. testudinum extracts and mangiferin showed hepatoprotective activity against induced damage in all the experimental series, where mangiferin and the extracts of MSBE and T. testudinum were the best candidates to inhibit "in vitro" damage to rat hepatocytes. This hepatoprotective effect found could be associated with the antioxidant properties observed for the products.

[Recommendations of antifungal treatment in patients with low grade immunosuppression]. / Recomendaciones de tratamiento antifúngico en pacientes con bajo grado de inmunodepresión.

Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, the treatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts' panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

Markers of treatment failure in hospitalised community acquired pneumonia.

BACKGROUND: Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor alpha, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure. METHODS: A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (< or = 72 h) or late failure. RESULTS: 453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (> or = 169 pg/ml), IL8 (> or = 14 pg/ml) and CRP (> or = 21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure. CONCLUSIONS: Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.

Enfermedad hemolítica perinatal por dos aloanticuerpos: presentación de un caso / Alloantibody linked perinatal hemolytic disease: case report

La etiopatogenia de la enfermedad hemolítica del recién nacido está basada en la incompatibilidad de grupo sanguíneo entre la madre y el recién nacido. Los neonatos con enfermedad hemolítica por incompatibilidad ABO usualmente tienen madres de grupo O porque la IgG anti-A y anti-B puede atravesar la placenta y sensibilizar los eritrocitos neonatales. Otros anticuerpos además de los ABO han sido reportados como causa de enfermedad hemolítica del recién nacido, ejemplo: anti-D, anti-C, anti-K, anti-Jk, anti-Fy, anti-S, etc. Presentamos el caso de una mujer de 33 años de edad, que en el segundo trimestre de su segunda gestación presentó una hemorragia que motivó la transfusión de una unidad de concentrado de eritrocitos. No se reportó reacción transfusional. El producto de dicha gestación fue un neonato masculino de 2,5 Kg de peso y apgar 6-8 que presentó íctero a las 24 horas después del parto. El fenotipaje ABO de los eritrocitos maternos y del neonato arrojó que la madre era de grupo O y el neonato de grupo B. La prueba de Coombs directa fue positiva 2+ en el neonato y la prueba de Coombs indirecta resultó positiva 3+ en la madre. Dos aloanticuerpos fueron detectados en el suero materno como causa del íctero neonatal, un anti-A y un anti-Jk b. Los eritrocitos maternos fueron fenotipados como Jk b negativos. El tratamiento con fototerapia al neonato se inició a las 40 horas de edad y se prolongó hasta los 10 días de nacido. Una transfusión simple de concentrado de eritrocitos fenotipados fue administrada al neonato a los 8 días de edad.

Terapéutica psiquiátrica integral / Comprehensive psychiatric therapy

El manual pretende contribuir a la actualización de los recursos biológicos, psicológicos y sociales apoprtados hasta hoy para el tratamiento de las afecciones psiquiátricas mayores y menores.

Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: a 24 months study.

D-003 is a mixture of high molecular weight sugarcane wax aliphatic primary acids with cholesterol-lowering, anti-platelet and antioxidant effects. This study investigated the long-term oral toxicity and carcinogenicity of D-003 in Sprague Dawley rats of both sexes, randomly distributed into four groups: a control group, treated only with the vehicle, and three treated with D-003 (50, 500 and 1500 mg/kg). All treatments were given orally for 24 months. Mortality (survival analysis), clinical symptoms, weight gain, food consumption, organ weights, time-to-tumour or tumour incidence data were not shown between group differences or trends. With the exception of serum cholesterol levels, lower in D-003-treated groups (500 and 1500 mg/kg) than in the controls, no other difference in blood indicators was found. D-003 did not increase the frequency of neoplastic and non-neoplastic lesions compared with the controls. The occurrence of all malignant and mammary tumours in D-003-treated females was lower than in the controls. The lesions observed were consistent with spontaneous lesions reported in this species. In conclusion, D-003 is not toxic or carcinogenic when given orally to Sprague Dawley rats up to 1500 mg/kg for 2 years, and 1500 mg/kg was a not-observable effect dose.

Oral acute and subchronic toxicity of D-004, a lipid extract from Roystonea regia fruits, in rats.

D-004 is a lipid extract obtained from Cuban royal palm (Rosytonea regia) fruits, consisting of a mixture of fatty acids and esters. D-004 has shown protective effects on prostate hyperplasia induced by testosterone in rodents. We report the results of two studies investigating the acute and subchronic oral toxicity of D004 in rats. Oral acute toxicity of D-004 (2,000 mg/kg) was investigated in Sprague Dawley rats according to the acute toxic class method, and the results showed that D-004 oral acute toxicity was practically absent, being defined as unclassified. In the subchronic study, rats were orally treated with D-004 at 500, 1,000 and 2,000 mg/kg for 90 days. No evidence of treatment-related toxicity was detected. Thus, analysis of body weight gain, clinical observations, blood biochemistry, hematology, organ weight ratios and histopathological data did not show significant differences between control and treated groups. We conclude that D-004 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest dose investigated in both acute and subchronic (2,000 mg/kg) studies. Thus, this dose can be considered as a nonobservable-effect dose in rats.

[Intra-abdominal desmoid tumor]. / Tumor desmoide intraabdominal.

Aggressive fibromatosis (desmoid tumor) are rare connective tissue tumors that occur sporadically or in association with familial adenomatous polyposis. The etiology is unknown and clinical findings depend on growth into neighboring structures. Biopsy is required to establish the diagnosis. The treatment of choice is surgery. We report a case with unusual localization in this form of presentation. The patient remains asymptomatic 15 months after surgery.