Teclistamab, cambiando el paradigma de pacientes con Mieloma Múltiple / Teclistamab, changing the paradigm of patients with Multiple Myeloma

Resumen El mieloma múltiple (MM) sigue siendo una patología incurable a pesar de las mejoras en las opciones de tratamiento que se desarrollaron en los últimos años. El antígeno de maduración de células B (BCMA) se expresa predominantemente en células de linaje B y representa un nuevo objetivo terapéutico prometedor para el MM recaído refractario (MMRR). Teclistamab (TECVAYLI) es el primer anticuerpo biespecífico de redirección de células T (CD3) contra BCMA (Figura 1) aprobado por la Administración de Drogas y Alimentos de Estados Unidos (FDA) en 2022 para pacientes con MMRR a 3 líneas de tratamiento previos, incluyendo Inhibi-dores de Proteosoma (IP), Inmunomoduladores (IMIDS), Anticuerpos Monoclonales (AcMo). La neurotoxicidad asociada a células efectoras inmunitarias (ICANS), el síndrome de liberación de citoquinas (CRS) e infecciones por hipogamaglobulinemia son los efectos adversos más comunes.

Abstract Multiple myeloma (MM) remains an incurable disease despite improvements in treatment options that have been developed recent years. B cell maturation antigen (BCMA) is predominantly expressed on B lineage cells and represents a promising new therapeutic target for relapsed re-fractory MM (RRMM). Teclistamab (TECVAYLI) is the first bispecific T cell (CD3) redirecting antibody against BCMA (Figure 1) approved by the US Food and Drug Administration (FDA) in 2022 for patients with RRMM on 3 prior lines of treatment, including Proteasome Inhibitors (PI), Immunomodulators (IMIDS), Monoclonal Antibodies (mAb). ICANS (immune effector cell-associated neurotoxicity), CRS (cytokine release syndrome), and hypogammaglobulinemia infections are the most common adverse effects.

Implant-supported fixed prosthesis restoration of fully edentulous patient using computer-guided implant surgery and immediate loading: A case report / 대한치과보철학회지

In a edentulous patient, various methods can be employed for prosthetic treatment using implants, such as implant-supported fixed prostheses, overdentures, hybrid prostheses, and implant assisted removable partial denture. In this case, in a patient with moderate to severe chronic periodontitis requiring full arch extractions, implants were strategically placed using computer-guided surgery. In the maxilla, due to inadequate bone quality and quantity leading to insufficient initial stability, delayed loading was implemented, and interim prosthesis was used during the osseointegration period. In the mandible, stable initial stability was achieved, allowing for immediate loading to reduce patient discomfort.Primary stability is considered the most crucial factor for obtaining immediate loading, so a thorough clinical and radiological evaluation of the remaining alveolar bone quantity and quality must be conducted before surgery.

Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends / Incidencia del cáncer infantil en América Latina y el Caribe: cobertura de los registros, patrones y tendencias a lo largo del tiempo / Incidência de câncer infantil na América Latina e no Caribe: cobertura, padrões e tendências temporais

ABSTRACT Objective. To provide a comprehensive overview of geographical patterns (2001-2010) and time trends (1993-2012) of cancer incidence in children aged 0-19 years in Latin America and the Caribbean (LAC) and interpret the findings in the context of global patterns. Methods. Geographical variations in 2001-2010 and incidence trends over 1993-2012 in the population of LAC younger than 20 years were described using the database of the third volume of the International Incidence of Childhood Cancer study containing comparable data. Age-specific incidence per million person-years (ASR) was calculated for population subgroups and age-standardized (WSR) using the world standard population. Results. Overall, 36 744 unique cases were included in this study. In 2001-2010 the overall WSR in age 0-14 years was 132.6. The most frequent were leukemia (WSR 48.7), central nervous system neoplasms (WSR 23.0), and lymphoma (WSR 16.6). The overall ASR in age group 15-19 years was 152.3 with lymphoma ranking first (ASR 30.2). Incidence was higher in males than in females, and higher in South America than in Central America and the Caribbean. Compared with global data LAC incidence was lower overall, except for leukemia and lymphoma at age 0-14 years and the other and unspecified tumors at any age. Overall incidence at age 0-19 years increased by 1.0% per year (95% CI [0.6, 1.3]) over 1993-2012. The included registries covered 16% of population aged 0-14 years and 10% of population aged 15-19 years. Conclusions. The observed patterns provide a baseline to assess the status and evolution of childhood cancer occurrence in the region. Extended and sustained support of cancer registration is required to improve representativeness and timeliness of data for childhood cancer control in LAC.

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RESUMO Objetivo. Apresentar uma visão abrangente dos padrões geográficos (2001 a 2010) e das tendências temporais (1993 a 2012) da incidência de câncer em crianças e jovens de 0 a 19 anos na América Latina e no Caribe (ALC) e interpretar os resultados no contexto de padrões mundiais. Métodos. Foram descritas variações geográficas de 2001 a 2010 e tendências de incidência de 1993 a 2012 na população com menos de 20 anos da ALC usando informações comparáveis da base de dados do terceiro volume do estudo International Incidence of Childhood Cancer. Foram calculadas taxas de incidência específica por idade por milhão de pessoas-ano (ASR, na sigla em inglês) para subgrupos populacionais e taxas padronizadas por idade usando a população padrão mundial (WSR, na sigla em inglês). Resultados. No total, foram incluídos 36 744 casos únicos. No período de 2001 a 2010, a WSR para todos os tumores combinados na faixa etária de 0 a 14 anos foi de 132,6. Os diagnósticos mais frequentes foram leucemia (WSR de 48,7), neoplasias do sistema nervoso central (WSR de 23,0) e linfoma (WSR de 16,6). A ASR para todos os tumores combinados na faixa etária de 15 a 19 anos foi de 152,3, e a maior taxa foi a de linfoma (ASR de 30,2). A incidência foi maior no sexo masculino do que no sexo feminino e maior na América do Sul do que na América Central e no Caribe. De modo geral, em comparação com as estimativas mundiais, a incidência na ALC foi menor, exceto para leucemia e linfoma entre 0 e 14 anos e para outros tumores e tumores não especificados em qualquer idade. A taxa de incidência na faixa etária de 0 a 19 anos aumentou em 1,0% ao ano (IC de 95% [0,6, 1,3]) entre 1993 e 2012. Os registros incluídos cobriam 16% da população de 0 a 14 anos e 10% da população de 15 a 19 anos. Conclusões. Os padrões observados servem de referência para avaliar o status e a evolução da ocorrência de câncer infantil na região. É necessário garantir um apoio ampliado e consistente aos registros de câncer para aprimorar a representatividade e a disponibilidade das informações em tempo adequado para o controle do câncer infantil na ALC.

Comparing the effects of serum GPER-1 and oxidant/antioxidant levels on retinopathy in patients with diabetes and healthy individuals: a pilot study / Comparando o impacto do soro GPER-1 e dos níveis de oxidante/antioxidante na retinopatia em pacientes diabéticos e em indivíduos saudáveis: um estudo piloto

ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.

RESUMO Objetivo: Esta pesquisa buscou determinar o im­pacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacio­nados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mos­trou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.

A novel spot mutation leading to sialidosis type 1-myoclonus syndrome and optical coherence tomography findings / Uma nova mutação pontual levando à sialidose tipo 1 - síndrome mioclônica e seus achados na tomografia de coerência óptica

ABSTRACT This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.

RESUMO Neste artigo, objetivamos apresentar os achados da tomografia de coerência óptica em uma nova mutação detectada no gene NEU1 em um caso de síndrome macular vermelho-cereja bilateral associada à sialidose tipo 1. Um paciente de 19 anos com um achado de mancha macular vermelho-cereja foi submetido a análises metabólicas e genéticas, apoiadas por imagens de tomografia de coerência óptica de domínio espectral (SD-OCT). Ao exame de fundo de olho, foi observada uma mancha macular vermelho-cereja bilateral. Nas imagens de SD-OCT, observou-se hiper-refletividade nas camadas internas da retina e na camada fotorreceptora na região foveal. Foi realizada uma análise genética e uma nova mutação foi detectada no gene NEU1, resultando em sialidose tipo 1. Nos casos em que é detectada uma mancha vermelho-cereja na mácula, o diagnóstico diferencial de sialidose deve ser feito e mutações do gene NEU1 devem ser rastreadas. A SD-OCT por si só não é suficiente para o diagnóstico diferencial, porque achados de aparência semelhante podem se manifestar em casos de doenças metabólicas da infância.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Sarcopenia and risk of malnutrition as risk factors for complications from COVID-19 / Sarcopenia e risco de desnutrição como fatores de risco para complicações da COVID-19

Purpose: This study aimed to associate nutritional and sarcopenia risk with clinical outcomes in elderly patients with COVID-19. Methods: This is a longitudinal retrospective cohort study. Hospitalized elderly individuals diagnosed with COVID-19 were included in the study. Nutritional risk was assessed using the Malnutrition Universal Screening Tool (MUST), and Sarcopenia risk was assessed using the SARC-F. Associations were assessed through multivariable logistic models. Results: In total, 127 patients (mean age: 71.25 ±8.06 years) were followed up until the clinical outcome. Sarcopenia risk was diagnosed in 63.8% of the sample, whereas nutritional risk was observed in 72%. Hospitalization in the intensive care unit (ICU) was required in 48.8% of the sample, 38.6% required mechanical ventilation, and 32.3% died. Elderly individuals with sarcopenia risk were more likely to be hospitalized in ICUs (OR: 5.62; 95%CI: 2.2-14.3), require mechanical ventilation (OR: 4.0; 95% CI: 1.5-10.2), and die (OR: 5.06; 95% CI: 1.7-14.2). The risk of malnutrition assessed through MUST was an important risk factor for death (OR = 30.15; 95% CI: 3.6-245.8; p<0.01). Conclusion: Sarcopenia risk was a risk factor for death, hospitalization in ICU, and mechanical ventilation, while nutritional risk was a risk factor for death (AU).

Objetivo: Este estudo teve como objetivo associar o risco nutricional e de sarcopenia com desfechos clínicos em pacientes idosos com COVID-19. Métodos: Trata-se de um estudo de coorte retrospectivo longitudinal. Idosos hospitalizados com diagnóstico de COVID-19 foram incluídos no estudo. O risco nutricional foi avaliado usando o Malnutrition Universal Screening Tool (MUST) e o risco de sarcopenia foi avaliado usando o SARC-F. As associações foram avaliadas por modelos logísticos multivariados. Resultados: No total, 127 pacientes (média de idade: 71,25 ±8,06 anos) foram acompanhados até o desfecho clínico. Risco de sarcopenia foi diagnosticado em 63,8% da amostra, enquanto risco nutricional foi observado em 72% deles. Além disso, 48,8% da amostra necessitou de internação em unidade de terapia intensiva (UTI), 38,6% necessitaram ventilação mecânica e 32,3% foram a óbito. Idosos com risco de sarcopenia tiveram maior chance de internação em UTI (OR: 5,62; IC 95%: 2,2-14,3), necessidade de ventilação mecânica (OR: 4,0; IC 95%: 1,5-10,2) e óbito (OR: 5,06; IC 95%: 1,7-14,2). O risco de desnutrição avaliado pelo MUST foi um importante fator de risco para óbito (OR = 30,15; IC 95%: 3,6-245,8; p<0,01). Conclusão: O risco de sarcopenia foi fator de risco para óbito, internação em UTI e ventilação mecânica, enquanto o risco nutricional foi fator de risco para óbito (AU).

Osteosarcoma parostal de fémur y cirugía de salvamento con prótesis intercalar. Experiencia en una unidad de tercer nivel y técnica quirúrgica / Parosteal osteosarcoma of the femur and salvage surgery with intercalary prosthesis. Experience in a third level unit and surgical technique

Resumen: Introducción: el osteosarcoma parostal es un tumor óseo maligno extramedular en el cual las células tumorales producen osteoide. Representa menos de 5% de los osteosarcomas. Se presenta predominantemente en la mujer, entre la segunda y cuarta década de la vida. Su localización más frecuente es la región distal del fémur y proximal de la tibia. Clínicamente, se manifiesta con aumento de volumen y dolor en muslo o rodilla. Debido a su baja incidencia y características clínicas, se presenta un caso clínico de osteosarcoma parostal femoral con descripción de la técnica quirúrgica realizada. Caso clínico: femenino de 14 años edad con cuadro clínico caracterizado por aumento de volumen y dolor en muslo derecho de seis meses de evolución. Se realizaron radiografías de fémur derecho, encontrando lesión ósea con características compatibles de malignidad, por lo que es enviada a unidad de tercer nivel para iniciar protocolo oncológico; se realizan dos biopsias percutáneas con aguja de Jamshidi, ambas con reporte histológico negativo para células malignas. En tomografía pulmonar de alta resolución se observó presencia de metástasis y la gammagrafía ósea con Tc99 reportó actividad osteoblástica en fémur derecho. Se decide tratamiento con resección en bloque y colocación de prótesis intercalar más quimioterapia adyuvante. Conclusión: la prótesis intercalar resulta una opción terapéutica adecuada en la cirugía de salvamento de extremidad para pacientes con diagnóstico de osteosarcoma parostal femoral.

Abstract: Introduction: parosteal osteosarcoma is an extramedullary malignant bone tumor in which cells produce osteoid, represents less than 5% of all osteosarcomas, it occurs predominantly in women between the second and fourth decade of life. It is often located in the distal region of the femur and proximal tibia. Clinically it presents with increased volume and thigh or knee pain. Due to its low incidence and clinical features, a clinical case of femoral parosteal osteosarcoma is presented, with description of the surgical technique performed. Case report: a 14-year-old female presented with a 6-month history of increased volume and right thigh pain. Radiological studies revealed a bone lesion with malignant characteristics, for which she was sent to third-level hospital where oncology study protocol was set up; consisting in two percutaneous biopsies of the lesion with Jamshidi needle, which were histopathology reported as negative for malignant cells. The pulmonary high-resolution computed tomography showed metastasis and a Tc-99m MDP bone scintigraphy showed increased osteoblastic activity in the right femoral shaft. Given the results, is confirmed the need of en-bloc resection and intercalary prosthesis implantation with adjuvant chemotherapy. Conclusion: the intercalary prosthesis is a suitable therapeutic option in limb-salvage surgery for patients with femoral parosteal osteosarcoma.

Evaluación de la hemostasia y heparinización de pacientes neonatos menores a 5 kg de peso sometidos a cirugía cardiovascular con pruebas viscoelásticas y pruebas de coagulación convencionales / Evaluation of hemostasis and heparinization of neonatal patients weighing less than 5 kg undergoing cardiovascular surgery with viscoelastic and conventional laboratory tests

Resumen Introducción. El manejo correcto de la heparinización, la monitorización de la hemostasia y los signos de coagulopatía constituyen desafíos importantes durante la cirugía cardiovascular (CCV) en neonatos. Objetivos. Evaluar el monitoreo de la hemostasia y heparinización de pacientes neonatos con peso <5 Kg sometidos a CCV con pruebas viscoelásticas (PV) y pruebas convencionales (PC). Metodología. Estudio retrospectivo de un único centro en donde se incluyeron neonatos consecutivos sometidos a CCV (octubre 2020 a septiembre 2021). Etapas de la cirugía: basal (B), circulación extracorpórea (CEC) y post protamina (PostProt). PV: tromboelastómetro ROTEM® delta (Werfen). PC: TP % actividad (TP%), APTT, fibrinógeno, tiempo de trombina (TT), recuento de plaquetas (PLT), antitrombina (AT) y actividad antifactor Xa (AntiXa) analizados inmediatamente post heparinización (PostHep), en CEC y PostProt. Medición de PC en coagulómetro ACL TOP con reactivos de Werfen. PLT: HemoCell DXH800 (Beckman Coulter). ACT: realizado mediante el uso del equipo ACT Plus (Medtronic) en quirófano para guiar la heparinización. Estadística: programa SPSS 23. Resultados expresados en mediana y rango intercuartilo (RIC). Resultados. Pacientes: 32 (24 varones). Edad: 19 (6-25) días; peso: 3380 (3082-3785) gramos. Los CT (tiempo de coagulación) y CFT (tiempo de formación del coágulo) de EXTEM, INTEM, FIBTEM y HEPTEM se prolongaron significativamente y A5, A10, MCF (firmezas) fueron menores en CEC comparados con B y PostProt (p<0,001). Los TP% fueron menores y APTT mayores en PostProt comparados con B. CEC presentó los menores PLT. AT en B: 0,56 (RIC 0.46-0.68) UI/mL, ningún paciente recibió suplementos de AT. La mediana de AntiXa fue 6,8 (5,4-7,9) y 5,3 (4,16,9) en PostHep y CEC, respectivamente. PostProt antiXa 0.1 (0.03-0.33), 9/32 >0.2U/mL. AntiXa correlacionó significativamente con EXTEM CT y ACT en CEC, hallándose AntiXa >6 U/ mL 10/32 pacientes, pero sólo con TT en PostProt. Sin embargo, PostProt ACT correlacionó con TP%, APTT, INTEM y HEPTEM CT y la relación HEPTEMCT/INTEMCT. La mediana (RIC) de sangrado postquirúrgico a las 12 h fue de 50 (28-91) mL correlacionando significativamente sólo con antiXa y TT en PostProt, y adicionalmente con la heparina total infundida. Conclusiones. El control de la antiXa permitiría una mejor heparinización durante la cirugía y estimación de la heparina residual en PostProt, que correlacionó con un mayor sangrado, no detectada por PC (excepto por prolongaciones moderadas de TT), CT de PV o ACT. Esta estrategia podría ser de utilidad para evitar excesos en la cantidad de heparina infundida que se asociarían a mayores sangrados.

Abstract Introduction. Correct management of heparinization, hemostasis and signs of coagulopathy are challenging in neonates undergoing cardiovascular surgery (CVS). Aim . To evaluate hemostasis and heparinization monitoring of neonatal patients weighing <5 kg undergoing CVS with viscoelastic (VT) and conventional laboratory (CL) tests. Methodology. Single center retrospective study that included consecutive neonates undergoing CVS (October-2020 to September-2021) were included. Surgery stages: basal (B), extracorporeal circulation (ECC) and post protamine (PostProt). VT: ROTEM® delta thromboelastometry (Instrumentation Laboratory, IL). CL: PT % activity (PT%), APTT, fibrinogen, thrombin time (TT), platelet count (PLT), antithrombin (AT) and antifactor Xa activity (AntiXa) analyzed immediately post heparinization (PostHep), in ECC and PostProt. CL measurement in ACL TOP coagulometer with Werfen reagents. PLT: HemoCell DXH800 (Beckman Coulter). ACT: performed by using ACT Plus (Medtronic) in the operating room to guide heparinization. Results were expressed as median (interquartile range, IQR). Statistics: SPSS 23 software. Results. Patients: 32 (24 men). Age: 19(6-25) days; weight: 3380 (3082-3785) grams. CT (clotting time) and CFT (clot formation time) of EXTEM, INTEM, FIBTEM and HEPTEM were significantly prolonged and A5, A10, MCF (firmness) were lower in ECC compared to B and PostProt (p<0.001). PT% were lower and APTT higher in PostProt compared to B. ECC presented the lowest PLT. AT in B: 0.56 (IQR: 0.46-0.68) IU/mL, no patient received AT supplements. Median AntiXa was 6.8 (5.4-7.9) and 5.3 (4.1-6.9) in PostHep and ECC, respectively. PostProt antiXa 0.1(0.03-0.33), 9/32 >0.2U/mL. AntiXa correlated significantly with EXTEM CT and ACT in ECC, with AntiXa >6 U/mL being found in 10/32 patients, but only with TT in PostProt. However, PostProt ACT correlated with PT%, APTT, INTEM and HEPTEM CT and the HEPTEMCT/ INTEMCT ratio. The median of postoperative bleeding at 12 hours was 50 (28-91) mL, significantly correlating only with antiXa, and TT in PostProt, and additionally with the total heparin infused. Conclusions. The control of antiXa would allow a better heparinization during surgery and estimation of residual heparin in PostProt, which correlated with increased bleeding, not detected by PC (except for moderate prolongations of TT), CT of PV or ACT. This strategy could be useful to avoid excesses in the amount of heparin infused that would be associated with increased bleeding.

Cerebellar ataxia after a single day of metronidazole use: Case report

Cerebellar ataxic syndromes, although uncommon, have been reported previously in patients taking metronidazole. However, almost all cases describe instances where patients were taking prolonged or high doses of the drug. We report a 65-year-old man who consumed 400 mg of metronidazole 3 times over 1 day and presented with slurring of speech, imbalance while walking and diplopia. The symptoms developed the day after consumption of metronidazole. Examination showed slurring of speech, gaze-evoked nystagmus, and dysmetria in all limbs. MRI brain revealed symmetric hyperintense lesions in the dentate nucleus and pons on T2-weighted imaging and FLAIR, which have a well-established association with metronidazole-induced central nervous system (CNS) toxicity. On discontinuation of the drug, symptoms improved, and complete recovery was noted at follow-up 2 weeks later. This case indicates that CNS side effects of metronidazole may not necessarily occur only at high doses or after prolonged courses of metronidazole, but may occur as an idiosyncratic reaction to the drug. Reasons for variable susceptibility require further investigation.

Complications-of-chronic-cholesteatomatous-otitis-media-at-the-university-hospital-center-of-andohatapenaka-antananarivo-madagascar

Chronic cholesteatomatous otitis media is the particularly aggressive form of chronic otitis media. This ear infection can lead to functional impairment of the ear and exposes you to serious complications that can be life-threatening. The purpose of this work was to list the complications of cholesteatomatous otitis in our hospital center. Patients And Method: This is a descriptive retrospective study of cases of complicated cholesteatomatous otitis. The study was carried out within the university hospital center Andohatapenaka from January 2015 to December 2019 (5 years). Complications of chronic not cholesteatomatous otitis media have been ruled out. The frequency ofResults: cholesteatomatous otitis media is 2.57%. It mainly affects patients between 10 and 20 years old with a male predominance. Extra-cranial complications are more frequent (78.94%) compared to intracranial complications. The circumstances of discovery are dominated by otorrhea (31.57%) and retro-auricular swelling (21.05%). The clinical signs are variable and depend on the complications. The otological history badly or not treated (60.52%) remains a predictive factor of these complications. Computed tomography has a very important place in the diagnostic component. Cholesteatomatous otitis media is always at risk of serious complications in the absence ofConclusion : well-adapted treatments. Complications can be functional which blames the hearing or vital following the endocranial extension.

Factores asociados al consumo de sustancias psicoactivas de un grupo de pacientes con diagnóstico de esquizofrenia de una institución de salud mental de Medellín, Antioquia / Factors associated with the consumption of psychoactive substances in a group of patients diagnosed with schizophrenia from a mental health institution in Medellín, Antioquia / Fatores associados ao consumo de substâncias psicoativas em um grupo de pacientes com diagnóstico de esquizofrenia de uma instituição de saúde mental de Medellín, Colômbia

Objetivo: establecer la relación entre factores sociodemográficos y clínicos con el con­sumo de sustancias psicoactivas (SPA) en un grupo de pacientes con diagnóstico de esquizofrenia, atendidos en una institución de salud mental de la ciudad de Medellín, Colombia. Metodología: estudio observacional, retrospectivo de intención analítica, de un grupo de 268 pacientes atendidos en una institución de salud mental de Medellín, en los últi­mos seis meses del año 2021. Se identificaron factores sociodemográficos, de consumo de SPA y clínicos como tipo de medicamentos, reingresos hospitalarios y adherencia al tratamiento farmacológico. Se consideraron valores de Odds Ratio con intervalo de confianza (IC95%) y se identificaron factores asociados al consumo por medio de un modelo de regresión logística. Resultados: se identificó que el 34.7% de la muestra reporta consumo de SPA; variables clínicas asociadas, tipo de medicamentos, número de ingresos hospitalarios y adherencia al tratamiento. Se encontraron diferencias significativas en la edad entre el grupo de consumidores y no consumidores, con una mediana de edad menor para el grupo de consumidores. Se determinó que ser hombre, tener una mediana de edad de 27 años y estar desempleado representa un riesgo mayor para el consumo de SPA. Finalmente se establece que la edad, el sexo, la ocupación y la adherencia al tratamiento, podrían predecir el consumo en un 34%. Conclusiones: los pacientes jóvenes, en su mayoría hombres, con diagnóstico de es­quizofrenia, tienen mayor riesgo de consumo de SPA, lo que implica mayor riesgo de recaídas y menor adherencia al tratamiento farmacológico.

Objective: to establish the relationship between sociodemographic and clinical factors with the consumption of psychoactive substances (PAS) in a group of patients diagnosed with schizophrenia, treated at a mental health institution in the city of Medellín, Colombia. Methodology: observational, retrospective study with analytical intent, of a group of 268 patients treated at a mental health institution in Medellín, in the last six months of 2021. Sociodemographic, SPA consumption, and clinical factors such as the type of medication, hospital readmissions and adherence to drug treatment were identified. Odds Ratio values with confidence interval (95% CI) were considered and factors associated with consumption were identified by means of a logistic regression model. Results: it was shown that 34.7% of the sample reports PAS consumption, associated clinical variables, type of medication, number of hospital admissions, and adherence to treatment. Significant differences in age were found between the group of users and non-users, with a lower median age for the group of users. It was determined that being a man, having a median age of 27 years and being unemployed represent a greater risk for the consumption of PAS. Finally, it is established that age, sex, occupation, and adherence to treatment could predict consumption by 34%. Conclusions: young patients, mostly men, with a diagnosis of schizophrenia, have a higher risk of PAS consumption, which implies a higher risk of relapse and lower adherence to drug treatment.

Objetivo: estabelecer a relação entre fatores sociodemográficos e clínicos com o consumo de substâncias psicoativas (SPA) em um grupo de pacientes diagnosticados com esquizofrenia, atendidos em uma instituição de saúde mental na cidade de Medellín, Colômbia. Metodologia:estudo observacional, retrospectivo com intenção analítica, de um grupo de 268 pacientes atendidos em uma instituição de saúde mental em Medellín, nos últimos seis meses de 2021. Foram identificados fatores sociodemográficos, consumo de SPA e clínicos quanto ao tipo de medicamento, readmissões hospitalares e adesão ao tratamento medicamentoso. Valores de Odds Ratio com intervalo de confiança (IC95%) foram considerados e fatores associados ao consumo foram identificados por meio de um modelo de regressão logística. Resultados: identificou-se que 34,7% da amostra relata consumo de SPA; variáveis clínicas associadas, tipo de medicamento, número de internações e adesão ao tratamento. Foram encontradas diferenças significativas de idade entre o grupo de usuários e não usuários, com menor mediana de idade para o grupo de usuários. Foi determinado que ser homem, ter idade mediana de 27 anos e estar desempregado representa maior risco para o consumo de SPA. Por fim, estabelece-se que idade, sexo, ocupação e adesão ao tratamento poderiam predizer o consumo em 34%. Conclusões: pacientes jovens, em sua maioria homens, com diagnóstico de esquizofrenia, apresentam maior risco de consumo de SPA, o que implica maior risco de recaída e menor adesão ao tratamento medicamentoso

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Abstract Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic

Abstract Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00-7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08-3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12-4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93-0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95-0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16-0.77; p = 0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

Cáncer colorrectal ­ diagnóstico y tratamiento: revisión bibliográfica / Colorectal cancer ­ diagnosis and treatment: literature review

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Although improvements in detection and treatment have been implemented; CRC incidence, prevalence, and mortality remain high, even in developed countries. The risk of developing this cancer is related to poor eating habits, smoking, inflammatory bowel disease, polyps, genetic factors, and aging. There are several methods for detecting colorectal cancer, including the guaiac test, stool immunochemical test, stool DNA test, sigmoidoscopy, colonoscopy, and barium enema. The stage at which the cancer is detected determines the patient's prognosis, survival, and treatment. Treatments include endoscopic and surgical local excision, preoperative radiation therapy and systemic downstage therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative, targeted chemotherapy and immunotherapy.

El cáncer colorrectal (CCR) es el tercer cáncer más prevalente a nivel mundial. A pesar de que se han implementado mejoras en la detección y el tratamiento; la incidencia, la prevalencia y la mortalidad del CCR siguen siendo altas, incluso en países desarrollados. El riesgo de desarrollar este cáncer está relacionado con malos hábitos alimentarios, tabaquismo, enfermedad inflamatoria intestinal, pólipos, factores genéticos y envejecimiento. Existen varios métodos para detectar el cáncer colorrectal, como la prueba de guayaco, la prueba inmunoquímica de heces, la prueba de ADN en heces, la sigmoidoscopia, la colonoscopia y el enema de bario. El estadio en el que se detecta el cáncer determina el pronóstico, la supervivencia y el tratamiento del paciente. Los tratamientos incluyen escisión local endoscópica y quirúrgica, radioterapia preoperatoria y terapia sistémica de reducción del estadio, cirugía extensa para enfermedad locorregional y metastásica, terapias ablativas locales para metástasis y quimioterapia paliativa, terapia dirigida e inmunoterapia.

Evaluation of knowledge, awareness, and practice of antimicrobial stewardship among prescribers of a teaching hospital in South India

Background: The injudicious and indiscriminate use of antimicrobials has led to the development of antimicrobial resistance (AMR), particularly in the low- and middle-income countries. Antimicrobial Stewardship (AMS) is the coordinated intervention to enhance the appropriate use of antimicrobials. Antimicrobial stewardship program (ASP) is a multidisciplinary program with interventions and strategies to encourage AMS to prevent emergence of AMR. Aims and Objectives: This study aimed at evaluating the knowledge, awareness, and practice (KAP) of AMS among prescribers of a teaching hospital in South India. Materials and Methods: A cross-sectional questionnaire based study conducted after obtaining Institutional Ethics Committee approval was conducted among prescribers of a teaching hospital from September 2022 to October 2022. Responses to the questionnaires issued to the prescribers through Google Forms were analyzed by descriptive statistics using Microsoft excel. Results: A total of 230 prescribers submitted the filled in questionnaires. The definition of AMS was known to 62%. The constitution and functioning of ASP was known to 59%. However, only a few (38%) prescribers agreed that antimicrobials are avoided in viral infections. More than 60% had good awareness of AMS. However, only 25% were aware of an ASP program is their hospital. Fifty percent agreed to the practice of reviewing antimicrobial use after 48–72 h and only 38% to the practice of obtaining cultures before prescribing antimicrobials. Conclusions: The prescribers had moderate knowledge and awareness and poor practice of AMS. To address these gaps, educational interventions and capacity building approaches are required.

Variability of PDYN and OPRK1 genes in four argentinian populations and its genetic association with clinical variables related to acute postsurgical pain / Variabilidad de los genes PDYN y OPRK1 en cuatro poblaciones argentinas y su asociación con variables clínicas relacionadas al dolor agudo post-quirúrgico

ABSTRACT Several population studies showed an association between variation in pain sensitivity and genetic polymorphisms located in Prodynorphin (PDYN) and Kappa Opioid Receptor (OPRK1) human genes. We analysed polymorphisms of these two genes to characterise their variation in Argentinian populations, as well as to evaluate their association with acute pain sensitivity. We studied 11 genetic markers in individuals from four locations in Argentina (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, and Misión Nueva Pompeya), calculated the population parameters, and evaluated the possible association among pain sensitivity, clinical, and genetic variables through a Generalised Estimating Equation model. High linkage disequilibrium was observed in the four populations for both genes, and significant differences were found among frequencies of Argentinian populations and those from other continents reported in the 1000 Genomes Project. Four PDYN gene polymorphisms from 3´ untranslated region and exon 4 showed association with acute pain sensitivity. One genotype of each of these polymorphisms was associated with a higher pain sensitivity, probably related with the activation of the N-methyl-D-aspartate (NMDA) receptors. We found a strong association with acute pain for the following clinical variables: 1) time after surgery, 2) intravenous klosidol supplied every 8 h, and 3) type of incision. Our results highlight the importance of a regional study of genetic variants which influence pain sensitivity and analgesic response.

RESUMEN La asociación entre la sensibilidad al dolor y los polimorfismos que presentan los genes humanos de prodinorfina (PDYN) y receptor opioide kappa (OPRK1) se ha evidenciado en distintos estudios poblacionales. Con el objetivo de caracterizar la variación de estos genes y evaluar su asociación con dolor agudo en la población argentina, analizamos 11 polimorfismos en individuos provenientes de cuatro localidades argentinas (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, y Misión Nueva Pompeya). Calculamos los parámetros poblacionales y evaluamos la posible asociación entre sensibilidad al dolor, variables clínicas y variables genéticas a través de un modelo de ecuación generalizada de estimación. Se observó alto desequilibrio de ligamiento para ambos genes en las cuatro poblaciones analizadas, y se encontraron diferencias significativas entre las frecuencias de poblaciones argentinas y las reportadas en el Proyecto 1000 Genomes para poblaciones de otros continentes. Cuatro polimorfismos de la región 3´UTR y el exón 4 de PDYN mostraron asociación con la sensibilidad al dolor agudo. En cada uno de estos polimorfismos, un genotipo resultó asociado con alta sensibilidad al dolor, probablemente en relación con la activación de receptores N-metil-D-aspartato (NMDA). Encontramos una fuerte asociación con dolor agudo para las siguientes variables clínicas: 1) tiempo post-cirugía, 2) administración intravenosa de klosidol cada 8 h, y 3) tipo de incisión. Nuestros resultados resaltan la importancia de realizar estudios regionales de variables genéticas que influyen en la sensibilidad al dolor y la respuesta analgésica.

Detección clonal de cepas parentales de streptococcus agalactiae Lehmann y Neumann por amplificación aleatoria de ADN polimórfico / Clonal detection of streptococcus agalactiae Lehmann and Neumann parental strains by random amplification of polymorphic DNA

RESUMEN Streptococcus agalactiae (SGB) produce infecciones invasivas en neonatos siendo la transmisión materna la más frecuente. Estudios epidemiológicos utilizan técnicas moleculares que evalúan la diversidad genética, entre ellas la de amplificación aleatoria de ADN polimórfico (RAPD) que resulta ser accesible, sensible y utiliza cebadores arbitrarios para amplificar segmentos polimórficos de ADN mediante PCR. El objetivo fue determinar la relación clonal entre aislamientos de SGB recuperados de madres y sus respectivos recién nacidos. Se estudiaron por RAPD cuatro parejas de aislamientos de SGB obtenidos de hisopados vagino-rectales de madres y de hemocultivos de sus neonatos. Se utilizaron los cebadores OPS11, OPB17 y OPB18 para seleccionar uno con capacidad de discriminar entre cepas no relacionadas genéticamente. Se utilizó la fórmula de Hunter-Gaston que establece el índice de discriminación (D), cuando D>0,90 se considera que los aislamientos pertenecen a clones diferentes. Los perfiles de amplificación para los ocho aislamientos, empleando independientemente cada cebador, permitieron calcular un D=1 para OPS11, y D=0,84 para OPB17 y OPB18. Por lo tanto, OPS11 fue seleccionado para el estudio de la relación clonal de los aislamientos, encontrándose perfiles de amplificación similares por RAPD para cada par de cepas madre-recién nacido. Se observaron diferentes perfiles de amplificación entre los pares de cepas madre-recién nacido, lo que revela la discriminación entre cepas no relacionadas, resultados confirmados por electroforesis en campo pulsante (PFGE). Estos resultados indican transmisión vertical para cada caso estudiado y robustez del cebador OPS11. Se encontraron condiciones apropiadas del ensayo de RAPD, lo que es útil para estudios epidemiológicos.

ABSTRACT Streptococcus agalactiae (GBS) causes invasive infections in newborns, being the most frequent the maternal transmission. Epidemiological studies use molecular techniques that assess genetic diversity, including random amplification of polymorphic DNA (RAPD) that is found to be accessible, sensitive and uses arbitrary primers to amplify polymorphic segments of DNA by PCR. The objective was to determine the clonal relationship between GBS strains recovered from mothers and their respective newborns. Four pairs of GBS isolates obtained from vaginal-rectal swabs of mothers and blood cultures of their newborns were studied with RAPD. Primers OPS11, OPB17 and OPB18 were used to select one with the ability to discriminate between non-genetically related strains. The Hunter-Gaston formula that establishes the discrimination index (D) was used; when D>0.90, it is considered that the isolates belong to different clones. The amplification profiles for the eight isolates, using each primer independently, allowed to calculate a D=1 for OPS11, and D=0.84 for OPB17 and OPB18. Therefore, OPS11 was selected for the study of the clonal relationship of the isolates, and similar amplification profiles were found by RAPD for each mother-newborn pair of GBS isolates. Different amplification profiles were observed between pairs of mother-newborn strains, which reveals the discrimination between unrelated strains, confirmed by pulsating field electrophoresis (PFGE). These results indicated vertical transmission for each studied case and robustness of the OPS11 primer. Appropriate conditions of the RAPD trial were found, which is useful for epidemiological studies.