Clinical characteristics and outcomes of 1,331 patients with COVID-19: HM Spanish Cohort.

OBJECTIVE: Spain is one of the European countries most affected by the COVID-19 pandemic. Epidemiologic studies are warranted to improve the disease understanding, evaluate the care procedure and prepare for futures waves. The aim of the study was to describe epidemiologic characteristics associated with hospitalized patients with COVID-19. METHODS: This real-world, observational, multicenter and retrospective study screened all consecutive patients admitted to 8 Spanish private hospitals. Inclusion criteria: hospitalized adults (age≥18 years old) with clinically and radiologically findings compatible with COVID-19 disease from March 1st to April 5th, 2020. Exclusion criteria: patients presenting negative PCR for SARS-CoV-2 during the first 7 days from hospital admission, transfer to a hospital not belonging to the HM consortium, lack of data and discharge against medical advice in emergency departments. RESULTS: One thousand and three hundred thirty-one COVID-19 patients (medium age 66.9 years old; males n= 841, medium length of hospital stayed 8 days, non-survivors n=233) were analyzed. One hundred and fifteen were admitted to intensive care unit (medium length of stay 16 days, invasive mechanical ventilation n= 95, septic shock n= 37 and renal replacement therapy n= 17). Age, male gender, leukocytes, platelets, oxygen saturation, chronic therapy with steroids and treatment with hydroxychloroquine/azithromycin were independent factors associated with mortality. The proportion of patients that survive and received tocilizumab and steroids were lesser and higher respectively than those that die, but their association was not significant. CONCLUSIONS: Overall crude mortality rate was 17.5%, rising up to 36.5% in the subgroup of patients that were admitted to the intensive care unit. Seven factors impact in hospital mortality. No immunomodulatory intervention were associated with in-hospital mortality.

Does Rapid Drug Desensitization to Chemotherapy Affect Survival Outcomes?

BACKGROUND AND OBJECTIVE: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. Objective: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. METHODS: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). RESULTS: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). CONCLUSIONS: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.

Does rapid drug desensitization to chemotherapy affect survival outcomes?

BACKGROUND: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. OBJECTIVE: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. METHODS: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). RESULTS: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). CONCLUSIONS: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients

ANTECEDENTES: Las reacciones de hipersensibilidad al oxaliplatino podrían afectar al pronóstico vital cuando fuerzan a los pacientes a cambiar de tratamiento o cuando impiden que lo finalicen. La desensibilización rápida medicamentosa permite que estos pacientes reciban sus tratamientos de primera elección. Sin embargo, no existen datos sobre si la desensibilización rápida medicamentosa podría tener algún efecto sobre la eficacia del oxaliplatino. OBJETIVO: El objetivo de este estudio es evaluar los efectos que la desensibilización rápida medicamentosa al oxalipatlino pudiera tener sobre la eficacia del tratamiento en los pacientes alérgicos al oxaliplatino sometidos a desensibilización. MÉTODOS: Estudio retrospectivo comparando datos de supervivencia, durante un periodo de 7 años, de pacientes alérgicos al oxaliplatino (recibiendo oxaliplatino mediante desensibilización rápida medicamentosa) y controles no alérgicos (recibiendo administraciones estándar de oxaliplatino). La supervivencia global se seleccionó como el criterio de valoración de la eficacia principal y se analizó con el estimador Kaplan-Meier utilizando comparaciones mediante la prueba de log-ran. RESULTADOS: La supervivencia global de los 67 casos fue de 23,7 meses (IC95%, 15,3-30,9), que se sometieron a 337 desensibilizaciones rápidas medicamentosas. Para los 143 controles la supervivencia global fue 34,5 meses (IC95%, 21,7-55,5). No se encontraron diferencias significativamente estadísticas entre ambos grupos (HR, 1,42; IC95%, 0,93-2,17;P=0,104). CONCLUSIONES: Los resultados de supervivencia de los pacientes sometidos a desensibilización no fueron significativamente distintos a los de los controles que recibieron oxaliplatino de forma estándar. La desensibilización se presenta como una alternativa para recibir oxaliplatino de forma eficaz en pacientes alérgicos

Chemotherapy in mastocytosis: administration issues, hypersensitivity, and rapid drug desensitization

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Calibration of a low background gas-flow proportional counter to estimate 234Th activity in coastal waters.

This paper relates the calibration of a low background gas-flow proportional counter. This calibration has been used to determine low activity of 234Th in coastal water samples. Two methods were used to prepare calibration samples: Evaporation and Electrodeposition. First method was rejected due to the lack of reproducibility because the different geometry adopted by the drops of tracer once dried on the disk. On the contrary, through the second method, similar efficiencies were obtained in all detectors with an average of 0.401±0.004. In this paper, the whole procedure to obtain 234Th activity in dissolution as well as in particulate matter has been detailed, and all the algorithms needed to calculate activities and efficiencies are shown. Finally, two experiments have been designed in order to validate the calibration of the beta counter and the method to determine 234Th in coastal waters with high concentration of particulate matter.

Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.

BACKGROUND: Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). METHODS: Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. RESULTS: A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. CONCLUSIONS: These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans.

Active multispectral imaging system for photodiagnosis and personalized phototherapies.

The proposed system has been designed to identify dermatopathologies or to apply personalized phototherapy treatments. The system emits electromagnetic waves in different spectral bands in the range of visible and near infrared to irradiate the target (skin or any other object) to be spectrally characterized. Then, an imaging sensor measures the target response to the stimulus at each spectral band and, after processing, the system displays in real time two images. In one of them the value of each pixel corresponds to the more reflected wavenumber whereas in the other image the pixel value represents the energy absorbed at each band. The diagnosis capability of this system lies in its multispectral design, and the phototherapy treatments are adapted to the patient and his lesion by measuring his absorption capability. This "in situ" absorption measurement allows us to determine the more appropriate duration of the treatment according to the wavelength and recommended dose. The main advantages of this system are its low cost, it does not have moving parts or complex mechanisms, it works in real time, and it is easy to handle. For these reasons its widespread use in dermatologist consultation would facilitate the work of the dermatologist and would improve the efficiency of diagnosis and treatment. In fact the prototype has already been successfully applied to pathologies such as carcinomas, melanomas, keratosis, and nevi.

Desensitizing Oxaliplatin-Induced Fever: A Case Report

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Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

BACKGROUND: Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. METHODS: Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. RESULTS: Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. CONCLUSIONS: In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

BACKGROUND: For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. METHODS: This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. RESULTS: Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. CONCLUSION: Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

Microscopic magnetic resonance imaging of the thoracic venous system in rats with congenital diaphragmatic hernia.

BACKGROUND/AIM: Infants and rats with congenital diaphragmatic hernia (CDH) have malformations of the heart and the great arteries caused by neural crest (NC) dysregulation during embryogenesis. Abnormally narrow jugular veins have been found in babies during cannulation for ECMO. However, the venous system has not been examined in depth so far. We hypothesized that abnormal patterning and/or size of the thoracic veins could occur in rats with CDH. This hypothesis was tested by microscopic magnetic resonance imaging (MMRI), a high-resolution tool able to detect subtle changes of vessels in small animals. MATERIAL/METHODS: Fetuses from pregnant rats fed either 100 mg i.g. nitrofen or vehicle on E9.5 were recovered near term. A 7 T MMRI system with a coronal multislice fast spin echo sequence allowed diagnosis of CDH (n = 19), and T2 SE high-resolution sequences made assessment of the pattern and width of cervico-thoracic veins possible. Values were corrected for body size by dividing them by the length of thoracic vertebrae T3-T5. The results in nitrofen and control (n = 11) groups were compared by non-parametric tests (*p < 0.05). RESULTS: Congenital diaphragmatic hernia fetuses were smaller than controls (4.5 ± 0.26 vs. 5.3 ± 0.2 g*). The widths (corrected for body size) of left external, both innominate, right superior vena cava and azygos veins were significantly smaller in CDH rats than in controls. CONCLUSIONS: The cervico-thoracic veins are normally patterned but abnormally narrow (except the internal jugulars) in rats with CDH. The same embryonic NC dysregulation that accounts for cardiovascular malformations could also explain these venous anomalies in CDH.

Pielonefritis aguda con absceso corticomedular renal en una mujer embarazada: imagen ecográfica y por resonancia magnética / No disponible

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Anaphylaxis associated with the ingestion of gold kiwifruit

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Sublingual immunotherapy with a standardized cat dander extract: evaluation of efficacy in a double blind placebo controlled study.

BACKGROUND: Little information is available on the clinical efficacy of sublingual immunotherapy (SLIT) using extracts derived from mammalian epithelia. OBJECTIVES: To assess clinical efficacy of cat SLIT based on natural exposure challenge test (NCT). MATERIAL AND METHODS: Fifty cat allergic patients with rhinoconjunctivitis with or without asthma were included in a randomized double blind placebo controlled clinical trial of cat SLIT during 1 year. Twenty-five patients received active treatment and 25 placebo. Sublingual immunotherapy efficacy was assessed by natural exposure challenge to a cat in a cat-room and by skin tests. Airborne Fel d 1 levels, symptom scores and peak expiratory flow (PEF) values were monitored. RESULTS: Thirty-three (66%) out of 50 patients completed the treatment. Fel d 1 content of the maximum concentration was 0.51 microg per ml. During the build up phase, the accumulated dose was 1.7 mug of Fel d 1 and during the entire length of the study was 17.1. No adverse reports were reported. The active group showed a marked reduction (62%) in symptoms during the NCT (P < 0.001) with no changes in placebo group. Active group also showed a reduced PEF response to cat exposure (P < 0.05), and an improvement in skin test reactivity to a standardized cat extract (P < 0.05), without significant changes in placebo group. Mean Fel d 1 exposure during the NCT was 6.2 +/- 2.21 ng/m(3). CONCLUSIONS: The results suggest that the cat SLIT used in this study was able to improve cat allergy based on natural exposure challenge.