Eficacia y seguridad de la profilaxis con emicizumab en la hemofilia A: estudio de 13 pacientes / Efficacy and safety of prophylaxis with emicizumab in hemophilia A: A study of 13 patients

Introducción: Emicizumab es el primer tratamiento no sustitutivo para profilaxis en hemofilia A grave. Objetivos: Describir los resultados de nuestros pacientes en profilaxis con emicizumab, según la práctica clínica habitual. Material y métodos: Seguimiento de 13 pacientes desde el inicio de la profilaxis, registro de hemorragias, cirugías, reacciones adversas y necesidad o no de tratamiento factorial. Se midieron los niveles plasmáticos en las visitas de seguimiento; la técnica ha sido coagulativa en una etapa, modificada mediante dilución 1:20. Resultados: La mediana de niveles plasmáticos fue de 52,2mg [30,7-71,9]. La profilaxis resultó segura y eficaz; solamente se contabilizó una hemorragia espontánea a lo largo del tiempo y no precisó tratamiento. No hubo episodios tromboembólicos ni reacciones graves de hipersensibilidad, anafilaxia o anafilactoides. La incidencia de reacciones en el lugar de la inyección fue del 8%. El abordaje perioperatorio en las intervenciones menores se llevó a cabo sin tratamiento factorial coadyuvante, en 2 cirugías mayores se precisó una dosis de concentrado de FVIII plasmático en el paciente con hemofilia A sin inhibidor y FVII en el paciente con inhibidor, y fue suficiente para parar la hemorragia. Conclusión: Este estudio demostró que la farmacocinética de emicizumab y su vida media aseguran niveles óptimos con tratamiento profiláctico a las dosis establecidas en la ficha técnica.(AU)

Introduction: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. Aims: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. Material and methods: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. Results: Median plasma levels were 52.2mg [30.7–71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. Conclusion: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.(AU)

[Efficacy and safety of prophylaxis with emicizumab in hemophilia A: A study of 13 patients]. / Eficacia y seguridad de la profilaxis con emicizumab en la hemofilia A: estudio de 13 pacientes.

INTRODUCTION: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. AIMS: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. MATERIAL AND METHODS: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. RESULTS: Median plasma levels were 52.2mg [30.7-71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. CONCLUSION: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Epidemiology of non-oncological high-impact chronic pain in Ecuadorian adults in 2022.

Background: There are limited data on non-oncological high-impact chronic pain (HICP) in Ecuador; we report the epidemiological characteristics of HICP. Materials & methods: In this cross-sectional study, we included a random sample of adult individuals who had cell phones. Results & conclusion: The weighted prevalence of HICP was 9.0%: 12.3% for women and 5.6% for men (p = 0.001). HICP was more frequently localized in the lower back and affected the economically active population. Nonsteroidal anti-inflammatory drugs were more commonly used; however, 61% of patients indicated that the effectiveness of their management was low. Overall, HICP had a negative impact on daily life activities. The effectiveness of the current treatment was low and should include an integrated approach.

We report the frequency, characteristics and associated factors of non-cancer high-impact chronic pain (HICP) in Ecuador. HICP refers to pain that has been felt constantly in the last 3 months. Women were more often affected, and the pain was more commonly localized in the lower back. Most patients indicated that their pain treatment was poor. HICP was common and had a negative impact on daily life activities. The current treatment of HICP must consider the physical and mental aspects of the people who suffer from it; this requires a combination of treatments such as drugs, exercise, physical rehabilitation and mind­body interventions.

Rapid on-site cytologic evaluation during endoscopic ultrasound-guided biopsies of pancreatic solid lesions.

BACKGROUND: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is safe and effective for the diagnosis of pancreatic adenocarcinoma. Although rapid on-site evaluation (ROSE) can improve tissue collection and increase diagnostic yield, its utility has been recently questioned. OBJECTIVE: Determine the diagnostic efficacy of EUS-FNB with ROSE of pancreatic masses in a new echoendoscopy unit. METHOD: Cross-sectional and comparative study of patients who underwent EUS-FNB of pancreatic masses between January and July 2017. Patient demographics, ultrasonographic details and pathology reports were examined. RESULTS: A total of 23 procedures were analyzed. Median age was 59 years (range: 46-77). The group with ROSE had 13 patients (56.5%) and the group without ROSE 10 (43.5%). The final pathology report showed enough and adequate sample in 100% of the group with ROSE (13/13 vs. 5/10; p = 0.007). Diagnosis of malignancy was established in 84.6% of the biopsies (11/13 vs. 2/10; p = 0.003) in the group with ROSE. CONCLUSIONS: ROSE is useful to improve the diagnostic efficacy of EUS-FNB of pancreatic masses, especially in new EUS centers or in centers with a low diagnostic yield.

ANTECEDENTES: La biopsia con aguja fina guiada por ultrasonido endoscópico (BAF-USE) es segura y eficaz para el diagnóstico del adenocarcinoma pancreático. La revisión citológica rápida en sala (ROSE, rapid on-site evaluation) puede mejorar la calidad de la muestra y el rendimiento diagnóstico; en años recientes se ha cuestionado su utilidad. OBJETIVO: Determinar la eficacia diagnóstica de la ROSE durante las BAF-USE de lesiones pancreáticas sólidas en un nuevo centro de ecoendoscopia. MÉTODO: Estudio transversal y comparativo en el que se incluyeron todos los pacientes a quienes se realizó BAF-USE de lesiones pancreáticas sólidas entre enero y julio de 2017. Se evaluaron datos demográficos, ecográficos y de patología de las BAF-USE. RESULTADOS: Se analizaron 23 procedimientos. La mediana de edad fue de 59 años (rango: 46-77). En el grupo con ROSE hubo 13 pacientes (56.5%) y en el grupo sin ROSE hubo 10 (43.5%). En el grupo con ROSE, el reporte de patología mostró muestra adecuada en el 100% (13/13 vs. 5/10; p = 0.007), así como diagnóstico de malignidad en el 84.6% (11/13 vs. 2/10; p = 0.003). CONCLUSIONES: La ROSE es una herramienta útil para mejorar el diagnóstico de BAF-USE de lesiones pancreáticas sólidas, principalmente cuando hay bajo rendimiento diagnóstico y en nuevas unidades de ecoendoscopia.

Extensive genic and allelic heterogeneity underlying inherited retinal dystrophies in Mexican patients molecularly analyzed by next-generation sequencing.

BACKGROUND: Retinal dystrophies (RDs) are one of the most genetically heterogeneous monogenic disorders with ~270 associated loci identified by early 2019. The recent application of next-generation sequencing (NGS) has greatly improved the molecular diagnosis of RD patients. Genetic characterization of RD cohorts from different ethnic groups is justified, as it would improve the knowledge of molecular basis of the disease. Here, we present the results of genetic analysis in a large cohort of 143 unrelated Mexican subjects with a variety of RDs. METHODS: A targeted NGS approach covering 199 RD genes was employed for molecular screening of 143 unrelated patients. In addition to probands, 258 relatives were genotyped by Sanger sequencing for familial segregation of pathogenic variants. RESULTS: A solving rate of 66% (95/143) was achieved, with evidence of extensive loci (44 genes) and allelic (110 pathogenic variants) heterogeneity. Forty-eight percent of the identified pathogenic variants were novel while ABCA4, CRB1, USH2A, and RPE65 carried the greatest number of alterations. Novel deleterious variants in IDH3B and ARL6 were identified, supporting their involvement in RD. Familial segregation of causal variants allowed the recognition of 124 autosomal or X-linked carriers. CONCLUSION: Our results illustrate the utility of NGS for genetic diagnosis of RDs of different populations for a better knowledge of the mutational landscape associated with the disease.

Endoscopic management of massive rectal bleeding from a Dieulafoy's lesion: Case report.

BACKGROUND: Rectal Dieulafoy's lesions (DLs) are very rare; however, they can be life threatening when presented with massive hemorrhage. CASE SUMMARY: A 44-year-old female with medical history of chronic renal failure who was on renal replacement therapy presented with lower gastrointestinal hemorrhage. Physical examination revealed signs of hypovolemic shock and massive rectal bleeding. Complete blood count revealed abrupt decrease in hematocrit. After hemodynamic stabilization, an urgent colonoscopy was performed. A rectal DL was diagnosed, and it was successfully treated with two hemoclips. There were no signs of recurrent bleeding at thirty days of follow-up. CONCLUSION: Rectal DLs represent an unusual cause of lower gastrointestinal bleeding. Massive hemorrhage can increase the morbidity and mortality of these patients. Endoscopic management continues to be the reference standard in the diagnosis and therapy of these lesions. Thermal, mechanical (hemoclip or band ligation), or combination therapy (adrenaline injection combined with thermal or mechanical therapy) should be considered the first choice for treatment.

Prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 / Prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus

Resumen Introducción: La enfermedad cardiovascular es la causa principal de muerte en pacientes con diabetes mellitus. La prevalencia de cardiopatía isquémica asintomática es más alta en pacientes diabéticos que en no diabéticos y se asocia a peor pronóstico. Objetivo: Identificar la prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel de atención de Guatemala y analizar la posible asociación de dicha enfermedad con características epidemiológicas, clínicas y metabólicas. Métodos: Estudio de corte transversal en el que se estudió una muestra de 92 pacientes diabéticos seleccionados de forma aleatoria simple. Se realizó electrocardiograma, que cuando fue negativo para isquemia ameritó prueba de esfuerzo, o de lo contrario, ecocardiograma de estrés con dobutamina. Resultados: La edad media de los participantes fue de 57 años, 88% de los cuales eran mujeres; la duración media de la diabetes fue 7 años. Se encontró cardiopatía isquémica asintomática en el 22,8% de los casos. No se hallaron posibles asociaciones entre cardiopatía isquémica asintomática y edad, sexo, enfermedad arterial periférica, índice de masa corporal, índice tobillo-brazo, hipertensión arterial, dislipidemia, tabaquismo activo, sedentarismo, sobrepeso/obesidad, alcoholismo, glucosa en ayunas, hemoglobina glicosilada, colesterol total, colesterol HDL, colesterol LDL, ácido úrico, creatinina, tasa de filtrado glomerular y microalbuminuria. Conclusiones: La prevalencia de cardiopatía isquémica asintomática en la población estudiada con diabetes mellitus tipo 2 fue de 22,8%. No se encontraron posibles asociaciones de cardiopatía isquémica asintomática con las variables estudiadas.

Abstract Introduction: Cardiovascular disease is the main cause of death in patients with diabetes mellitus. The prevalence of asymptomatic ischaemic heart disease is higher in diabetic patients than in non-diabetic ones, and is associated with a worse prognosis. Objective: To determine the prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus in a third level of care hospital in Guatemala, as well as to analyse the possible relationship of this disease with epidemiological, clinical, and metabolic characteristics. Methods: A cross-sectional study was conducted on a sample of 92 randomly selected diabetic patients. An electrocardiogram was performed, which when it was negative for ischaemia, an exercise stress test or a dobutamine stress echocardiogram was performed. Results: The mean age of the participants was 57 years, 88% of whom were women. The mean duration of the diabetes was 7 years. Asymptomatic ischaemic heart disease was found in 22.8% of case. No significant associations were found between ischaemic heart disease and age, gender, peripheral arterial disease, body mass index, ankle-brachial index, arterial hypertension, dyslipidaemia, active smoking, sedentarism, overweight/obesity, alcoholism, fasting glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, creatinine, glomerular filtration rate, and urine microalbumin. Conclusions: The prevalence of asymptomatic ischaemic heart disease was 22.8% in the population studied with type 2 diabetes mellitus. No significant associations were found between ischaemic heart disease and the variables studied.

Thrombopoietin receptor agonist switch in adult primary immune thrombocytopenia patients: A retrospective collaborative survey involving 4 Spanish centres.

OBJECTIVE: To describe the reasons for and result of thrombopoietin receptor agonists (TPO-RA) switching in adult immune thrombocytopenia (ITP) patients of 4 Spanish centres. METHODS: We retrospectively analysed all patients who received sequential treatment with both TPO-RA between 2010 and 2015 recording clinical and biological parameters. RESULTS: Twenty-six patients were included; 17 received first romiplostim and 9 received first eltrombopag. Reasons for switching were inefficacy (n = 10), patient preference (n = 8), side effects (n = 5) and excessive platelet count fluctuation (n = 3). When the switch was due to inefficacy, 100% of patients who received romiplostim first and 66% who received eltrombopag first responded to the second drug. It is significant that none of the patients who received romiplostim first reached the maximum recommended dose before switching. When the change was due to patient preference or because of side effects, 100% of the patients responded to both TPO-RA. Three patients changed from romiplostim to eltrombopag due to platelet count fluctuation; one did not respond and the fluctuation persisted in the remaining 2 patients. We also found 4 sustained remissions after administering the second TPO-RA, 2 of these with inefficacy of the first drug. CONCLUSION: TPO-RA switching is a feasible strategy in different scenarios with high probability of success.

Application of the QuEChERS method for the determination of organochlorine pesticide residues in Brazilian fruit pulps by GC-ECD.

The Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method was applied to the extraction of 14 organochlorine pesticides (OCPs) residues from commercial fruit pulps available in supermarkets in Fortaleza, Northeastern Brazil. The analyses were carried out by gas chromatography (GC), coupled to an electron-capture detector (ECD), and were confirmed by GC-tandem mass spectrometry (MS). The parameters of the analytical method, such as accuracy, precision, linear range, limits of detection and quantification, were determined for each pesticide. The results showed good linearity (R2 ≥ 0.9916) and the overall average recoveries were considered satisfactory obtaining values between 69 and 110%, RSD of 2-15 %, except for hexachlorobenzene (HCB) in açai, acerola and guava pulp samples. The OCPs were detected in guava (α-HCH; lindane) and soursop (α, ß-HCH isomers) samples. The QuEChERS method and GC-ECD were successfully used to analyze OCPs in commercially available Brazilian fruit pulps and can be applied in routine analytical laboratories.

Brazilian fruit pulps as functional foods and additives: evaluation of bioactive compounds.

Eight tropical fruit pulps from Brazil were simultaneously characterised in terms of their antioxidant and antimicrobial properties. Antioxidant activity was screened by DPPH radical scavenging activity (126-3987 mg TE/100g DW) and ferric reduction activity power (368-20819 mg AAE/100g DW), and complemented with total phenolic content (329-12466 mg GAE/100g DW) and total flavonoid content measurements (46-672 mg EE /100g DW), whereas antimicrobial activity was tested against the most frequently found food pathogens. Acerola and açaí presented the highest values for the antioxidant-related measurements. Direct correlations between these measurements could be observed for some of the fruits. Tamarind exhibited the broadest antimicrobial potential, having revealed growth inhibition of Pseudomonas aeruginosa. Escherichia coli, Listeria monocytogenes, Salmonella sp. and Staphylococcus aureus. Açaí and tamarind extracts presented an inverse relationship between antibacterial and antioxidant activities, and therefore, the antibacterial activity cannot be attributed (only) to phenolic compounds.

Segurança em equipamentos de monitoraçäo em sala cirúrgica e UTI - oxímetro, capnógrafo, monitor de EGC e monitor de pressäo / Safety in monitoring equipmentsin operating room and UTI - oximeter, capnograph, ECG monitor and pressure monitor

Na área de equipamentos eletromédicos é indispensável a utilização de procedimentos de uso, manipulação, instalação e segurança, principalmente na sala cirúrgica e na UTI onde estão os pacientes com maior potencial de risco. Além de debilitados, estão normalmente ligados simultaneamente a diversos equipamentos. Um estudo da forma NBR IEC 601-1, e um levantamento do histórico de manutenção dos equipamentos no Núcleo de Engenharia Clínica (NEC) do HU/UFSC, mostrou alguns problemas relativos à manipulação e algumas propostas foram elaboradas para a normatização desses procedimentos.

Abstract - The utilization. handling. installation, and security procedures are essential in electromedical equipment using. mainly in where the more criticai patients stay. They are very debilitated anel connected simultaneously to many equipments. A study of brazilian NBR IEC 601-1 standard and an equipment maintenance history investigation of Clinicai Engineering Group (NEC) of HU/UFSC showed problems relative to handling and procedure standardization were suggested

Incidencia de hipotensión luego de anestesia peridural para la operación cesárea

La técnica de anestesia epidural es la más utilizada para la operación césarea, conociendo sus ventajas y desventajas y conindicaciones Es sabido que la anestesia epidural puede provacar bloqueo simpático acompañado de hopotensión, que al parecer es más manifiesta y evidente cuando el bloque o se lo realiza con el paciente en posición sentada antes que acostada. Además conocemos que brinda buena analgesia, existiendo molestias en la tracción del peritoneo cuando no se ha llegado a bloquear hasta T34 (4) Las complicacines prbables son inyección subaracnoidea inadvertida, inyección intravascular, bloqueo raquídeo total, u cefáleas post punción dural (5) que debemos estar preparados para tratarlas...