Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease.

Purpose of the Review: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings: Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary: Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

Correlation between eye lens doses and over apron doses in interventional procedures.

Measurements of eye lens dose using over apron dosimeters with a geometric correction factor is an international accepted practice. However, further knowledge regarding geometric correction factors in different contexts is required. The authors studied the correlation between eye lens dose and over apron dosimetry for different medical specialties in eleven hospitals, using a standardized protocol, two independent over apron dosimeters (worn at chest and at neck levels) and a dedicated calibration procedure. The results show good correlation between subjects working on the same medical specialty for 5 specialties: Interventional Radiology, Vascular Surgery, Vascular Radiology, Hemodynamics and Neuroradiology. The geometric correction factors resulting from this study could be used to estimate eye lens dose using over apron dosimeters, which are more comfortable than eye lens dosimeters, as reported by the study subjects, as long as the increased uncertainty of the over apron dosimetry compared to the dedicated eye lens dosimetry is acceptable.

Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock. A prospective pilot study

Objective: To evaluate procalcitonin clearance as a prognostic biomarker in septic shock. Design: Prospective, observational pilot study. Setting: Intensive care unit. Patients: Patients admitted to the ICU due to septic shock and multiorgan dysfunction. Interventions: Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived. Data collected: Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality). Results: Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h. Conclusions: ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker (AU)

Objetivo: Evaluar el aclaramiento de procalcitonina como biomarcador pronóstico del shock séptico. Diseño: Estudio piloto, observacional y prospectivo. Ámbito: Servicio de Medicina Intensiva. Pacientes: Enfermos ingresados en el Servicio de Medicina Intensiva por shock séptico y disfunción multiorgánica. Intervenciones: Determinación de las concentraciones séricas de procalcitonina en las primeras 12h de evolución del shock séptico (coincidiendo con el ingreso en el Servicio de Medicina Intensiva) y posteriormente a las 24 horas, 48 horas y a las 72 horas en los pacientes supervivientes. Variables recogidas: datos demográficos, score Acute Physiology and Chronic Health Evaluation II, score Sequential Organ Failure Assessment, datos relativos al foco de sepsis y al resultado del paciente (mortalidad en el Servicio de Medicina Intensiva). Resultados: El aclaramiento de procalcitonina fue mayor en los pacientes supervivientes respecto a los no supervivientes, con diferencias significativas a las 24 horas (73,9 [56,4-83,8]% vs 22,7 [-331-58,4], p<0,05) y las 48 horas (81,6 [71,6-91,3]% vs -7,29 [-108,2-82,3], p<0,05). El área por debajo de la curva ROC fue 0,74 (IC del 95%, 0,54 a 0,95, p<0,05) para el aclaramiento de procalcitonina a las 24 horas y 0,86 (IC del 95%, 0,69 a 1,0, p<0,05) para el aclaramiento de procalcitonina a las 48 horas. Conclusiones: La persistencia de concentraciones elevadas de procalcitonina se asoció a una mayor mortalidad. El aclaramiento de procalcitonina realizado a las 48h puede ser de utilidad como biomarcador pronóstico (AU)

The sounds of cardiac arrest: innovating to obtain an accurate record during in-hospital cardiac arrest.

BACKGROUND: To obtain an accurate audit during in-hospital cardiac arrest, following recommendations of the Utstein style and measuring time intervals between the different interventions, is difficult. OBJECTIVE: To assess whether the use of an audio recording system during in-hospital cardiac arrest resuscitation allows the register of more items during cardiopulmonary resuscitation. MATERIAL AND METHODS: Prospective observational study between January 2008 and December 2009. The population that were included, were hospitalized patients and non-hospitalized patients assisted by a cardiac arrest team, except for critical areas. An audio recording system with a timer was turned on when cardiac arrest team was alerted. Recordings were reviewed to fill in the items recommended by the Utstein style. Time intervals were calculated. Mean number of completed items per patient were compared between recorded and non-recorded cardiac arrest. RESULTS: 119 CA team alerts took place. 64 (53.7%) cases were real CA and 37 (57.8%) of them were properly recorded. A mean number of items per patient in recorded cardiac arrest cases were 18.18 (±3.2) vs. 15.96 (±4.1) in non-recorded cardiac arrest cases (p<0.05). In the recorded cases, mean times were: alert - arrival: 1.23 (±0.95)min; arrival - cardiopulmonary resuscitation initiation: 0.63 (±0.38)min; arrival - first defibrillation: 2.06 (±1.33)min; arrival - intubation: 8.42 (±4.64)min; arrival - first adrenaline: 3.30 (±1.98)min. CONCLUSIONS: The audio recording system permits the register of a larger number of items per patient during in-hospital cardiac arrest and allows measurement of time intervals between the different interventions during cardiopulmonary resuscitation.

Usefulness of procalcitonin clearance as a prognostic biomarker in septic shock. A prospective pilot study.

OBJECTIVE: To evaluate procalcitonin clearance as a prognostic biomarker in septic shock. DESIGN: Prospective, observational pilot study. SETTING: Intensive care unit. PATIENTS: Patients admitted to the ICU due to septic shock and multiorgan dysfunction. INTERVENTIONS: Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived. DATA COLLECTED: Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality). RESULTS: Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h. CONCLUSIONS: ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker.

[Value of the use of the geometric mean to calculate the relative renal function in 99mTc-DMSA renal scintigraphy]. / Valor del uso de la media geométrica en el cálculo de la función renal relativa en la gammagrafía renal con 99mTc-DMSA.

Determining the relationship of DMSA uptake of the left versus right kidney is theoretically one of the easiest quantitative procedures in nuclear medicine. The quantification can be performed on the posterior view, with or without a lateral view for correction of kidney depth. The geometric mean can also be determined by using both the anterior and the posterior views. This study has aimed to evaluate if there are significant differences in the quantification of the renal function percentage using only the posterior view and the geometric mean. Furthermore, we evaluated to what extent the patient's age and diagnosis influenced these differences. We have proposed a work protocol in which we indicate which cases the geometric mean should be calculated in order to minimize the possible errors occurring when only the posterior view is used.A total of 328 renal scintigraphies with 99mTc-DMSA performed at our Department in the last six months were studied. The mean and standard deviation of the differences as well as the correlation coefficient between both methods were calculated. The difference between the right renal function in posterior view and the right renal function obtained using the geometric mean was calculated for all the patients. The Student's T test was applied to determine whether the differences between both methods were statistically different from zero. Statistical differences were found in patients older than 9 years and in patients with genitourinary malformations.

[Value of 123I-MIBG scanning, neuron-specific enolase and serum ferritin in the diagnosis and follow-up of patients with neuroblastoma]. / Valor del rastreo con 123I-MIBG, enolasa neuronal específica y ferritina sérica en el diagnóstico y seguimiento de pacientes con neuroblastoma.

INTRODUCTION: The neuroblastoma (NB) is one of the most common pediatric malignant neoplasms. The most commonly used tumor markers in the diagnosis and follow-up of this tumor are the serum neuron-specific enolase (NSE), ferritin and lactic dehydrogenase and urinary vanillymandelic and homovanillic acid. The common imaging modalities are CT, MRI and 123I or 131I-meta-iodobenzylguanidine scintigraphy. AIM: The aim of this study is to assess the value of 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and serum determinations of NSE and ferritin in the diagnosis and evolution of NB patients. MATERIAL AND METHODS: 20 patients (8 female, 12 male) whose ages ranged from 2 months to 9 years with a mean age of 2.64 years diagnosed of NB. 47 123I-MIBG scans, 47 NSE determinations and 47 ferritin ones were selected. RESULTS: At the time of diagnosis, 100% of the 123I-MIBG scans were positive. 65% of NSE determinations presented clearly pathological levels and 15% were very near to the cut-off point. Only 45% of the ferritin levels were increased. The differences between the lesions visible by 123I-MIBG scanning before and 3 months after treatment as well as NSE and ferritin levels were studied. When the Student's T test was applied, we found statistically significant pre and post-treatment differences in 123I-MIBG scanning and NSE. In the case of ferritin, there was no statistical significance in spite of the decrease in the values. The direct correlation and Spearman correlation between laboratory data and 123I-MIBG scanning as well as correlation between NSE and ferritin were also studied. There was a good correlation between 123I-MIBG and NSE and between NSE and ferritin. We have also studied the data in 7 relapses. CONCLUSIONS: 123I-MIBG scintigraphy and serum determination of NSE are two successful diagnostic tools for the diagnosis and evolution of NB patients.

[Radioimmunometric assay of neuron specific enolase in aqueous humor and serum in patients with retinoblastoma]. / Determinación radioinmunométrica de la enolasa neuronal específica en humor acuoso y suero, en pacientes con retinoblastoma.

INTRODUCTION: Retinoblastomas (RB) are the most common malignant intraocular tumors in childhood. The neuron specific enolase (NSE) is used as a tumor marker in different malignant diseases (mainly in neuroblastomas and lung carcinoma of small cells). In this work we report our experience using NSE and the role we consider that it plays in the determination of this enzyme in RB cases. MATERIALS AND METHODS: NSE determinations in aqueous humor (AH) and serum were carried out in 17 RB by means of a radioimmunometric assay and were compared with those values obtained in a control group composed of 8 subjects in whom the RB diagnosis as well as other diseases that could alter its determination had been ruled out. The possible correlation between NSE levels and different tumor stages (Reese-Elsworth and histological-clinical), as well as the tumor type (exophytic and mixed) were also studied. RESULTS: NSE levels were increased in AH and serum in 88% of RB patients and were normal in all the subjects in the control group (when a sample which was considered to be non-valid due to the presence of red cells in AH was excluded). No correlation between NSE levels in AH and serum and the different tumor stages was found. Nevertheless, the RB group of mixed tumor type showed a significantly higher mean in AH (p<0.01) than the RB exophytic group. CONCLUSION: NSE determination in AH is of value in the differential diagnosis in patients in whom RB is suspected but difficult to diagnose as well as in the diagnosis of relapses. Serum determinations are mainly useful in the follow-up and in the early diagnosis of possible metastases.