Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Treatment with fostamatinib in patients with immune thrombocytopenia: Experience from the Andalusian region in Spain-The Fostasur Study.

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.

Glycosylation differences of an anti-VEGF monoclonal antibody (PRO-169) and its extensive comparison with Bevacizumab.

PRO-169 is an anti-VEGF monoclonal antibody developed by Laboratorios Sophia that shares its sequence with Bevacizumab (BVZ); though, PRO-169 is intended for intravitreal administration. In this study, analytical characterization showed that PRO-169 had glycosylation differences in comparison to BVZ reference product (RP); since it had more content of G1F, G2F, sialic acid and high mannose. Further investigation was performed to evaluate if differences between both products would affect the efficacy and safety profile of PRO-169. PRO-169 had no alteration in its in vitro biological activity; moreover, no cytotoxicity or immunogenicity concerns should be expected as demonstrated by different orthogonal methods at analytical, in vitro and in vivo assays. These results support moving to the clinical testing of PRO-169 since no major complications will be expected with its clinical use for the treatment of ophthalmic diseases.

Principales causas de riesgo obstétrico en el centro de salud "Roberto Astudillo" de la cuidad de Milagro enero-junio 2019 / Main causes of obstetric risk in the center of health "Roberto Astudillo" of the city of milagro

Un factor de riesgo obstétrico es una condición médica obstétrica o sociodemográfica que, en una mujer gestante puede ocasionar un aumento en la morbimortalidad que repercute como ya se ha mencionado a nivel materno -fetal con respecto al resto de la población. Objetivo: El objetivo primordial de evaluar el riesgo obstétrico, es poder realizar acciones preventivas que encaminen a evitar complicaciones que comprometan la vida materno fetal. Materiales y Métodos: Investigación cuantitativa documental, retrospectiva de corte transversal descriptivo. La investigación es cuantitativa, porque se obtiene datos los cuales son procesados, documental, porque toma la información de historia clínica que reposa en el área de estadística del centro de Salud Roberto Astudillo. Resultados: Dentro de los factores desencadenantes del alto riesgo obstétrico se encuentra el embarazo gemelar, y los embarazos mal controlados; entendiendo que el Síndrome de Hellp puede ser prevenible si hay un control exhaustivo desde el primer trimestre del embarazo, sobre todo cuando hay antecedentes de preeclampsia. Por otro lado, en los hábitos psicobiológicos se obtuvo una incidencia alta de consumo de café, de medicamentos, de consumo de alcohol y de pacientes con hábitos tabáquicos abandonados en el primer trimestre del embarazo (hábitos tóxicos). Aunque no hay una teoría que determine que el consumo de café influye directamente sobre la tensión arterial, se sabe, que las teofilinas estimulan los receptores B1 y B2 trayendo esto como consecuencia un leve incremento de la frecuencia cardíaca, y por ende un ligero incremento de la presión arterial. Conclusiones: Mantener una política de conducta expectante, generalmente incluye la atención intrahospitalaria con corticoides para la maduración pulmonar fetal, sulfato de magnesio (según sea necesario), antihipertensivos (según sea necesario) y monitoreo fetal y materno cuidadoso para identificar las indicaciones para el parto (por ejemplo, hipertensión no controlada, deterioro del estado de la madre y del feto, incluidos disfunción orgánica y sufrimiento fetal). Como parte de la conducta expectante, debe considerarse el traslado intraútero (antes del parto) a un centro de nivel terciario con capacidad para cuidados intensivos neonatales(AU)

An obstetric risk factor is a medical condition, obstetric or sociodemographic that, in a pregnant woman, can cause a increase in morbidity and mortality that has repercussions, as already mentioned, maternal-fetal level with respect to the rest of the population. Objective: The objective essential to assess the obstetric risk is to be able to carry out preventive actions that lead to avoid complications that compromise maternal and fetal life. Materials and Methods: Documentary quantitative research, retrospective of descriptive cross section. The research is quantitative, because it is obtained data which are processed, documentary because it takes the information from clinical history that rests in the statistics area of ​​the health center Robert Astudillo. Result: Within the triggering factors of the high obstetric risk is found in twin pregnancy, and miscarriages controlled; understanding that Hellp Syndrome can be preventable if there is comprehensive control from the first trimester of pregnancy, especially when there is a history of preeclampsia. On the other hand, in habits psychobiological results, a high incidence of coffee consumption, of drugs, alcohol consumption and patients with smoking habits abandoned in the first trimester of pregnancy (toxic habits). But not there is a theory that determines that coffee consumption directly influences on blood pressure, it is known that theophyllines stimulate B1 receptors and B2 bringing this as a consequence a slight increase in the frequency heart rate, and therefore a slight increase in blood pressure. Conclusions: Maintaining a watchful waiting policy generally includes inpatient care with corticosteroids for fetal lung maturation, magnesium sulfate (as needed), antihypertensives (as needed necessary) and careful fetal and maternal monitoring to identify indications for delivery (eg, uncontrolled hypertension, impaired of the condition of the mother and fetus, including organ dysfunction and distress fetal). As part of watchful waiting, transfer should be considered. intrauterine (before delivery) to a tertiary-level facility with the capacity to neonatal intensive care(AU)

Effect of Rectal Ozone (O3) in Severe COVID-19 Pneumonia: Preliminary Results.

The aim of this study is to evaluate the effectiveness of rectal ozone (O3) in COVID-19 patients with severe pneumonia admitted at Hospital Universitario Santa Cristina, Madrid. In a before-and-after study, four patients admitted with severe bilateral pneumonia due to COVID-19 were treated with rectal ozone and confirmed with (+) RT-PCR for SARS-CoV-2 and evaluated afterwards. The analyzed outcome variables were as follows: (a) clinical improvement (O2 saturation and O2 supply); (b) biochemical improvement (fibrinogen, D-dimer, urea, ferritin, LDH, IL-6, and CRP); (c) radiological improvement. The treatment protocol consisted of 5 sessions (1 session/day) of intra-rectal ozone, applied in a volume of 100 mL and a concentration of 35 µg/mL. The Protocol was previously approved by the Hospital's Health Care Ethics Committee (CEAS) (Report 15/4/2020) for compassionate use in the face of this exceptional pandemic situation, and prior informed consent was obtained from the patient/legal representative. The patients improved oxygen saturation, as observed by the lower number of desaturations and the lower supply of O2. Biomarkers of inflammation decreased (fibrinogen, D-dimer, urea, ferritin, LDH, IL-6, and CRP). Finally, the radiological signs of bilateral viral pneumonitis improved between 1 and 2 grades based on Taylor's radiological scale. Rectal ozone decreases O2 supply and improves O2 saturation, decreases inflammation biomarkers, and improves Taylor's radiological grade in patients with severe COVID-19 pneumonia. Rectal ozone is a safe, effective, cheap, and simple alternative capable of acting on the SARS-CoV-2 virus, and it is presented as an adjunctive therapeutic option to consider in the management of severe bilateral COVID-19 pneumonia.

Satisfacción de usuarios y calidad de atención en unidades primarias de Salud de Milagro / Satisfaction of the users and quality of attention In Primary Health Care Units-Milagro

Introducción: Uno de los problemas con mayor relevancia dentro del sistema de Salud Pública del Ecuador es la satisfacción de los usuarios ante los servicios recibidos, los que se relacionan con la efectividad, eficiencia y percepción del paciente a la atención brindadaal dolor que le aqueja, así como la sensación del bienestar físico y mental. Objetivo: Se planteó como objetivo identificar la satisfacción de los usuarios y la calidad de la atención que se brinda en las unidades operativas de atención primaria de Salud en la ciudad deMilagro.Metodología: La metodología utilizada se basó en un enfoque cuantitativo, de tipo no experimental, transversal-descriptivo; el instrumento de medición para la satisfacción de usuarios se alineó a los parámetros del modeloSERVQUAL. Resultados: El 77 % de los usuarios se encuentra satisfecho con el equipamiento e infraestructura respectiva en los centros de salud; de la misma forma, el 81 % señala estar satisfecho con la atención del personal que labora en dichas dependencias, mientras que el 80 % considera que la cantidad de las camillas cumple con sus expectativas. Conclusión: Con el estudio de estas dimensiones a través de la percepción del usuario se determinó que la calidad de la atención es media y en igual forma la variable satisfacción delusuario

Introduction: One of the problems with greater relevance within the Public Health System of Ecuador is the satisfaction of the users with the services received, which are related to the effectiveness, efficiency and patient perception to the attention given to the pain that afflicts, as well as the sensation of the physical and mental well-being. Objective the objective of the research it is based on identifies the user's satisfaction and quality of care that is provided in the Operational Units of Primary Health Care in the city of Milagro. Methods this study was based on a quantitative approach, non-experimental, cross-sectional-descriptive; the measuring instrument for the satisfaction of users was aligned to the parameters of the Servqual model. Results: The process data showed that 77 % of users are satisfied with the respective equipment and infrastructure in the health centers; in the same way, the 81 % reported being satisfied with the attention of the personnel working in these units, While 80 % believe that the quantity of the stretchers meet their expectations. Conclusion: With the study of these dimensions through the user's perception, it was determined that the quality of care is average and in the same way asthe user satisfactionvariable.

Tratamiento y complicaciones en la hemofilia A adquirida. Experiencia en un centro / Treatment and complications in acquired hemophilia A. Experience from a single center

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Validation of a Portable Coagulometer for Routine In-Hospital Use for Newborns.

OBJECTIVES: To verify the reliability and clinical benefits of the coagulation tests made by a point of care device in newborn admitted to a neonatal unit. DESIGN: We made a statistical comparison between results obtained by the point of care device versus conventional laboratory analysis. SETTING: Level 3 neonatal unit. PATIENTS: Thirty-one infants admitted to the neonatal unit at the San Cecilio University Hospital (Granada, Spain) were recruited to this study. INTERVENTIONS: All underwent a double analytical determination: a small drop of blood was taken for analysis with a portable coagulometer (qLabs Electrometer Plus) and the rest of the blood sample was analyzed with conventional hospital laboratory equipment. MEASUREMENTS AND MAIN RESULTS: According to the linearity test performed, the measuring methods presented a good linear regression fit. Lin's concordance coefficient showed a "good" agreement for activated partial prothrombin time and international normalized ratio (>0.61) and a moderate one for prothrombin time (0.41-0.6) for the sample of newborns. CONCLUSIONS: The portable coagulometer qLabs Electrometer Plus device has the potential to be an alternative to standard hospital coagulation autoanalyzers in a subset of patients where the amount of blood drawn can have significant risks. Our study is the first of its kind to analyze the use of this device with severely ill newborns.

Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction.

Friedreich ataxia (FRDA) is the most common hereditary ataxia that is caused mainly by an unstable GAA trinucleotide expansion in the first intron of the frataxin gene. Molecular tests for FRDA diagnosis and carrier detection include polymerase chain reaction (PCR) for the GAA expansion, triplet repeat primed PCR (TP-PCR), and/or Southern blotting. TP-PCR is a method developed to detect trinucleotide expansions successfully applied to FRDA diagnosis. In our laboratory, we have included a PCR for the GAA expansion using fluorescent primers polymerase chain reaction (F-PCR) to identify normal heterozygous and affected individuals unambiguously. The purpose of our study was to reanalyze 310 samples previously diagnosed in our laboratory and compare the results with those obtained by F-PCR and TP-PCR. Eight percent of the discrepancies between the carrier and the normal individuals were identified correctly by this protocol. No discrepancy was detected in the affected individuals. These techniques are effective, and compared with Southern blotting, they are less labor-intensive and suitable for automation. We suggest a new routine protocol for FRDA diagnosis that includes F-PCR and TP-PCR.

Screening for FXTAS in 95 Spanish patients negative for Huntington disease.

Fragile X syndrome is the most common form of hereditary mental retardation. The molecular basis of this syndrome is mainly a CGG expansion in the 5' untranslated region of the FMR1 gene. Expansions with more than 200 CGG repeats abolish gene expression causing the classical fragile X phenotype. Premutation carriers (55-200 CGG) have normal cognitive function with increased risk of developing premature ovarian failure and fragile X-associated tremor-ataxia syndrome (FXTAS). Some clinical features associated with FXTAS, such as tremor, gait ataxia, cognitive decline, and generalized brain atrophy, are also seen in other movement disorders. Ninety-five patients referred for HD, who tested negative for the expansion in the IT15 gene, were screened for FMR1 CGG-repeat expansion. One FMR1 premutation male carrier was detected, giving an FXTAS frequency of 1.6%. Our results highlight that FXTAS is still not well diagnosed; therefore, we recommend FMR1 premutation screenings in all patients with late-onset tremor, ataxia, and cognitive dysfunction.

FXTAS in spanish patients with ataxia: support for female FMR1 premutation screening.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly described disorder characterized by progressive action tremor and ataxia that occurs in premutation carriers of the FMR1 gene. The incidence of FMR1 premutated carriers in the general population is relatively high, and therefore FXTAS might explain a considerable number of sporadic, late-onset ataxias. To better establish the prevalence of FXTAS among undiagnosed Spanish patients with ataxia, we have performed a FMR1 premutation screening. Our results evidenced three individuals carrying premutated alleles, giving an estimated FXTAS prevalence of 1.95% among patients with late-onset ataxia (1.15% for males and 3% for females). Molecular characterization of premutation carriers evidences lower fragile X mental retardation 1 protein levels and increased FMR1 mRNA levels. Clinical and neuroimaging findings support FXTAS diagnosis in these patients. Because of the high prevalence of FMR1 premutation in the general population, the description and characterization of the FXTAS syndrome is of great interest as it may represent one of the more common monogenic causes of ataxia, tremor, and dementia. The results obtained in this study demonstrate that FXTAS should be incorporated to spinocerebellar ataxia genetic screening protocols. Early diagnosis of these patients benefits not only them but also the rest of the family that should be advised for the fragile X syndrome.

Marketed oral triptans in the acute treatment of migraine: a systematic review on efficacy and tolerability.

BACKGROUND: In the current literature, there is neither a reported systematic review comparing the efficacy of triptans at 30 minutes and 1 hour after the migraine treatment, nor data related to efficacy of new marketed triptans. OBJECTIVE: The main objective of this analysis was to compare the efficacy and tolerability of currently marketed oral, non-reencapsulated triptan formulations vs placebo in the treatment of moderate-to-severe migraine attacks. METHODS: A systematic review of double-blind, randomized clinical trials reporting data after a single migraine attack was conducted. Efficacy results are shown using relative risk ratios with 95% confidence intervals. A sensitivity analysis was also conducted. RESULTS: After reviewing 221 publications, 38 studies were included. All marketed triptans provided significant relief and/or absence of pain at 2 hours, and relief at 1 hour when compared with placebo. After 30 minutes, fast-dissolving sumatriptan 50 and 100 mg, sumatriptan 50 mg, and rizatriptan 10 mg showed significant relief when compared to placebo, whereas the fast-dissolving formulation of sumatriptan 100 mg was the only oral triptan that was superior to placebo in meeting the pain-free endpoint. On the other hand, fast-dissolving sumatriptan 50 and 100 mg and eletriptan 40 mg showed a lower rate of recurrence than placebo, whereas rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo. Adverse events associated with treatment with tablet formulations of sumatriptan and zolmitriptan were significantly more frequent than those of the placebo group. The inclusion of trials with reencapsulated triptans in the analysis introduced minor specific changes in these results. CONCLUSION: This analysis updates the comparative data available for the 7 currently marketed oral triptans and clearly demonstrates their efficacy when compared to placebo, even with stricter endpoints, such as efficacy at 30 minutes. No triptan exhibited better tolerability than placebo. Results are diverse, depending on the triptan, which probably is a reflection of heterogeneous pharmacokinetics.

Role of the CDKN2A locus in patients with multiple primary melanomas.

PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.

Melatonin modulates the effects of gastric injury in rats: role of prostaglandins and nitric oxide.

Experimental evidence has been presented connecting melatonin with the prevention or treatment of gastrointestinal disorders either by the scavenging properties of active oxygen or by receptor-mediated stimulation of gene expression of neutralizing enzymes. Prostaglandins and nitric oxide are important neuroimmunomodulators in digestive physiology and different studies have indicated that the protective properties of melatonin may be explained by prostaglandin and/or nitric oxide mechanisms. The aim of the present study was to examine the effect of intraperitoneal administration of melatonin on in vivo changes in PGE(2), generated in gastric mucosal lesions by ischemia-reperfusion. Cyclic GMP nucleotide was also studied as an index of the principal enzymatic activity involved in the metabolism of nitric oxide, the nitric oxide synthase. The different immunological tests showed that the intraperitoneal administration of melatonin prevents the postischemic decrease in prostaglandins. The concentration of this eicosanoid in the rat mucosa treated with 20 mg.kg(-1) of melatonin was significantly higher (p < 0.05) than that in the control rats. The amount of cyclic GMP in the stomach decreased because of ischemia-reperfusion. In treated animals however, a marked increase occurred in concentrations of GMP, but the difference was not statistically significant. The results suggest that the mechanism of protection afforded by melatonin against lesions induced by gastric ischemia-reperfusion may be due to stimulation of the synthesis of eicosanoid protectors during the ischemic process.

Mechanisms involved in protection afforded by L-arginine in ibuprofen-induced gastric damage: role of nitric oxide and prostaglandins.

L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response.