Avatrombopag plus fostamatinib combination as treatment in patients with multirefractory immune thrombocytopenia.

Immune thrombocytopenia (ITP) refractory to multiple therapies may require a combination of drugs targeting different mechanisms and targets. In this retrospective, multicentre, international study, we report the safety and effectiveness of avatrombopag and fostamatininb in combination administered to 18 patients with multirefractory ITP. Overall, the combination response was achieved in 15 patients (83.3%), with a median time from combination start to best response of 15 days (IQR: 8-35 days). After a median follow-up of 256 days (IQR: 142.8-319), 5 patients relapsed (26.7%), all during tapering or stopping one drug. Adverse events were described in 6 of 18 patients (33%).

Cirrosis en una lactante como manifestación de un defecto congénito de la glicosilación

Se presenta el caso de una recién nacida a término valorada en el servicio de urgencias por ictericia sin criterios de fototerapia. En los controles analíticos posteriores se detecta hipertransaminasemia y dislipemia con aumento de LDL-colesterol. Tras no objetivar alteraciones en los diferentes parámetros estudiados se realiza biopsia hepática que muestra hallazgos compatibles con cirrosis. Se amplía el estudio metabólico y presenta un perfil alterado de sialotransferrinas lo que lleva a realizar un diagnóstico de defecto congénito de la glicosilación. Bajo este nombre se incluye un grupo amplio de enfermedades relacionadas con alteraciones en el proceso de unión de glicanos a las cadenas proteicas. Este defecto, de origen genético, implica cambios en la estructura y funcionalidad de las glicoproteínas. Las manifestaciones clínicas son heterogéneas, en función del gen afecto y del tipo de glicoproteínas alteradas, siendo lo más común la afectación hepática, neurológica y hematológica. (provisto por Infomedic International)

We present the case of a full-term newborn girl evaluated in the emergency department for jaundice without phototherapy criteria. Subsequent laboratory tests showed hypertransaminasemia and dyslipidemia with increased LDL-cholesterol. After finding no alterations in the different parameters studied, a liver biopsy was performed showing findings compatible with cirrhosis. The metabolic study was extended and the patient presented an altered sialotransferrin profile, which led to a diagnosis of congenital defect of glycosylation. This name includes a broad group of diseases related to alterations in the process of glycan binding to protein chains. This defect, of genetic origin, involves changes in the structure and functionality of glycoproteins. The clinical manifestations are heterogeneous, depending on the gene affected and the type of glycoproteins altered, the most common being hepatic, neurological and hematological involvement. (provided by Infomedic International)

Hepatitis autoinmune y enfermedad celiaca en una paciente con hipertransaminasemia crónica

La hepatitis autoinmune es una patología poco frecuente en pediatría cuya incidencia ha aumentado en los últimos años. Aunque su espectro clínico es muy variado, debe sospecharse ante el aumento de transaminasas séricas tras haber descartado otras etiologías. A continuación, se presenta el caso de una paciente de 9 años con hipertransaminasemia crónica que fue diagnosticada de hepatitis autoinmune y enfermedad celiaca. (provisto por Infomedic International)

Autoimmune hepatitis is a rare pathology in pediatrics whose incidence has increased in recent years. Although its clinical spectrum is very varied, it should be suspected due to the increase in serum transaminases after having ruled out other etiologies. The case of a 9-year-old patient with chronic hypertransaminasemia who was diagnosed with autoimmune hepatitis and celiac disease is presented below. (provided by Infomedic International)

Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy.

Sulphated proteoglycans are essential in skeletal and brain development. Recently, pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis have been identified in a range of chondrodysplasia associated with intellectual disability. Nevertheless, several patients remain with unidentified molecular basis. This study aimed to contribute to the deciphering of new molecular bases in patients with chondrodysplasia and neurodevelopmental disease. Exome sequencing was performed to identify pathogenic variants in patients presenting with chondrodysplasia and intellectual disability. The pathogenic effects of the potentially causative variants were analysed by functional studies. We identified homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2 in two patients with pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy. By functional analyses, we showed that the variants affect SLC35B2 mRNA expression and protein subcellular localization leading to a functional impairment of the protein. Consistent with those results, we detected proteoglycan sulphation impairment in SLC35B2 patient fibroblasts and serum. Our data support that SLC35B2 functional impairment causes a novel syndromic chondrodysplasia with hypomyelinating leukodystrophy, most likely through a proteoglycan sulphation defect. This is the first time that SLC35B2 variants are associated with bone and brain development in human.

Thromboprophylaxis Management in Surgical Patients: The Efficacy of a Protocol in the Electronic Prescription Program.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE) continues to be a problem in surgical patients, but thromboprophylactic measures are not always implemented. This study aimed to evaluate thromboprophylaxis practice in surgical patients at our institution by assessing appropriateness during admission and discharge; 60-day clinical outcomes are analyzed, and finally further interventions are discussed for continued improvement. METHODS: A cross-sectional, observational study was conducted in patients undergoing orthopedic and abdominal surgical procedures. Initially, the institution protocol was updated and embedded in the Computerized Physician Order Entry system. We then assessed prospective adequacy of thromboprophylaxis as per established in the protocol. The primary endpoint was thromboprophylaxis initiation and, secondarily, the quality of related prescriptions during hospitalization and at discharge. RESULTS: A total of 114 patients were included in the study. According to VTE risk, thromboprophylaxis was initiated in 85.1% of the patients as needed during hospitalization and 94.8% at discharge. The following inadequacies versus the protocol were found: no duration information in the discharge summary (32.5%), incorrect postsurgical administration time of pharmacological prophylaxis (15.8%), omission of mechanical prophylaxis (13.7%), misdosing (9.6%), and omission of pharmacological prophylaxis (2.6%). No VTE events occurred 60 days postdischarge. CONCLUSION: The electronic protocol was an effective tool, as evidenced by the fact that thromboprophylaxis was initiated in the majority of surgical patients in our institution during hospitalization and at discharge. Still, some aspects leave room for improvement (duration, dosing, and timing), and further measures such as implementation of Electronic Medication Administration Records and new functionalities in the Clinical Decision Support systems are proposed.

Effectiveness and Safety of Ombitasvir-Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin for HCV Genotype 1 Infection for 12 Weeks Under Routine Clinical Practice.

BACKGROUND: No previous studies exist examining the effectiveness and safety in real clinical practice of the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV). OBJECTIVE: To evaluate the effectiveness and safety in real clinical practice of the combination of OBV/PTV/r+DSV with or without ribavirin for 12 weeks in treatment-naïve and previously treated adult patients with chronic hepatitis C virus (HCV) genotype 1 infection. METHODS: This was an observational study of a prospective cohort of treatment-naïve and pretreated adult patients who received 12 weeks of OBV/PTV/r (25/150/100 mg once daily) and DSV (250 mg twice daily) with or without ribavirin. The primary effectiveness outcome was sustained virological response 12 weeks after the end of treatment (SVR12). Safety outcomes were presented by the incidence of adverse events. RESULTS: A total of 116 of 121 patients achieved a SVR12 (95.9%, 95% CI = 90.6-98.6). The SVR12 rate was 93.8% (95% CI = 86.0-97.9) in cirrhotic patients and 100% (95% CI = 91.4-100.0) in noncirrhotic patients. Adverse events occurred in 91.7% of patients, of which 81.8% were grade 1/2, and none led to premature discontinuation. Grade 3 adverse events were reported in 9.9% of patients. The most frequent adverse event was anemia (52.1%), although only 1.6% had a hemoglobin level below 8 g/dL. The incidence of any adverse event was higher in the group of patients who received ribavirin (96.5% vs 80.0%, P = 0.002). CONCLUSIONS: The combination of OBV/PTV/r+DSV with or without ribavirin for 12-week settings achieved a high rate of SVR12, with an acceptable safety profile in routine clinical care.

Chronic lymphocytic leukemia: a paradigm of innate immune cross-tolerance.

Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors.

Epidemiología de las úlceras por presión en un hospitalde agudos / Epidemiology of pressure ulcers in an acute care hospital

Fundamento: Uno de los objetivos prioritarios del grupo de mejora (GM) de las úlceras por presión (UPP) de nuestro hospital ha sido monitorizar la incidencia y la prevalencia de las UPP, así como la proporción de pacientes de riesgo para poder establecer los indicadores más adecuados para medir la calidad de los cuidados enfermeros e introducir medidas correctoras para mejorarlos. Material y métodos: El GM ha creado unos registros mensuales con un corte semanal de incidencia y prevalencia (CSIP) de UPP, así como de proporción de pacientes de riesgo. Se ha usado la escala de Norton para determinar el riesgo de desarrollar UPP. Se presentan los datos de este estudio descriptivo prospectivo pertenecientes al año 2000 en un hospital de agudos de 650 camas. La población estudiada han sido los pacientes ingresados en ese período en unidades de riesgo. Resultados: Se ha obtenido una media de 44,7 CSIP (desviación típica [DT], 5,77). La prevalencia media de UPP en el hospital ha sido del 3,8 por ciento (DT, 0.60) y la tasa de incidencia del 1,31 por ciento. El porcentaje medio de pacientes de riesgo ha sido del 24,28 por ciento (DT 1,76). Conclusiones: La prevalencia media en el hospital es similar a la encontrada en la bibliografía. La incidencia es un indicador más exacto para conocer la calidad de los cuidados de enfermería. En cambio, la prevalencia y el porcentaje de pacientes de riesgo es más bien un indicador de cargas de trabajo de enfermería. Con el método de corte semanal se consigue una adecuada monitorización de la incidencia y la prevalencia de las UPP en nuestro medio hospitalario (AU)