The configuration of the screws in the osteosynthesis of fractures of the femoral neck does not influence the functional or mechanical outcomes. / La configuración de los tornillos en la osteosíntesis de las fracturas del cuello femoral no influye en los resultados funcionales ni mecánicos.

BACKGROUND AND OBJECTIVE: Synthesis with cannulated screws is one of the accepted methods in femoral neck fractures, although its optimal configuration is a subject in continuous debate. The main objective was to compare the results of the patient with a femoral neck fracture fixed with three screws in triangle and inverted triangle configuration in the frontal plane. MATERIALS AND METHODS: Retrospective and comparative study of 53 patients with femoral neck fracture, operated between 2015 and 2022 with fixation with three cannulated screws, 22 with a triangle configuration (triangle group) and 31 in an inverted triangle (inverted triangle group). Functionality was evaluated using the modified Merlé d'Aubigné scale, walking ability using the Koval scale, as well as postoperative complications. RESULTS: On the Merlé d'Aubigné scale, the mean score was 16.7 in the triangle group and 16.1 in the inverted triangle group (P=.259). On the Koval scale, a significant decrease was observed, going from 1.6 preoperative mean to 2.2 after surgery (P=.000), finding no differences between groups. There were six postoperative complications in the triangle group and three in the inverted triangle group (P=.140). CONCLUSION: The configuration of the screws in the femoral neck, both in the form of a triangle and an inverted triangle, did not influence the functional or mechanical outcomes of the patients with a femoral neck fracture fixed with three cannulated screws.

[Translated article] The configuration of the screws in the osteosynthesis of fractures of the femoral neck does not influence the functional or mechanical outcomes.

BACKGROUND AND OBJECTIVE: Synthesis with cannulated screws is one of the accepted methods in femoral neck fractures, although its optimal configuration is a subject in continuous debate. The main objective was to compare the results of the patient with a femoral neck fracture fixed with three screws in triangle and inverted triangle configuration in the frontal plane. MATERIALS AND METHODS: Retrospective and comparative study of 53 patients with femoral neck fracture, operated between 2015 and 2022 with fixation with three cannulated screws, 22 with a triangle configuration (triangle group) and 31 in an inverted triangle (inverted triangle group). Functionality was evaluated using the modified Merlé d'Aubigné scale, walking ability using the Koval scale, as well as postoperative complications. RESULTS: On the Merlé d'Aubigné scale, the mean score was 16.7 in the triangle group and 16.1 in the inverted triangle group (p=.259). On the Koval scale, a significant decrease was observed, going from 1.6 preoperative mean to 2.2 after surgery (p=.000), finding no differences between groups. There were six postoperative complications in the triangle group and three in the inverted triangle group (p=.140). CONCLUSION: The configuration of the screws in the femoral neck, both in the form of a triangle and an inverted triangle, did not influence the functional or mechanical outcomes of the patients with a femoral neck fracture fixed with three cannulated screws.

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.

[Anterior shoulder instability with Hill-Sachs on-track. Bankart or Bankart-remplissage?] / Inestabilidad anterior de hombro con lesión de Hill-Sachs on-track. ¿Bankart o Bankart-remplissage?

INTRODUCTION: in patients with anterior glenohumeral (GH) instability together with an off-track or engaging Hill-Sachs (HS) defect, Bankart-remplissage (B-R) surgery reduces the recurrence rate when compared to Bankart (B) surgery alone. There is controversy regarding whether the recurrence rate also decreases in patients with on-track or non-engaging Hill-Sachs defects. OBJECTIVE: to compare the recurrence rate and clinical evolution of patients with anterior glenohumeral instability with 'on-track' Hill-Sachs defect treated with either B or B-R surgery. MATERIAL AND METHODS: non-randomized, retrospective, single-center cohort study of patients with anterior glenohumeral instability and on-track Hill-Sachs defect, operated between January 2010 and December 2018. Patients operated with B versus B-R were compared. Recurrence, complications and re-operation were recorded. In addition, VAS, SSV, WOSI and qDASH scores were obtained and compared in both groups. RESULTS: of the 105 patients who met the inclusion criteria, 78 (74.3%) patients had a complete follow-up (52 B and 26 B-R, 4.3 years median follow-up). There was a higher recurrence rate in group B compared to B-R, with this difference not reaching statistical significance (17.3% vs 7.7%, p = 0.21). There were no significant differences in residual pain, feeling of instability, complications or VAS, qDASH, SSV or WOSI scores between both groups. In the subgroup analysis, patients who practiced contact sports and were operated with B showed higher recurrence rates (24.1% vs 0%, p = 0.08) and complications (41.4% vs 18.2%, p = 0.16) when compared to B + R, although these differences were not significant. CONCLUSION: there were no significant differences in recurrence rates and functional evolution between patients with anterior glenohumeral instability operated with B or B-R surgery. Comparative, prospective studies should be performed to establish definitive recommendations.

INTRODUCCIÓN: en pacientes con inestabilidad glenohumeral (GH) anterior con defecto de Hill-Sachs (HS) off-track o enganchante, Bankart-remplissage (B + R) reduce tasa de recurrencia en comparación a Bankart aislado (B). Hay controversia si tasa de recurrencia también disminuye en pacientes con defecto de HS on-track o no enganchantes. OBJETIVO: comparar la tasa de recurrencia y evolución clínica entre la cirugía de B versus B-R en pacientes operados por inestabilidad glenohumeral anterior con defecto de Hill-Sachs on-track. MATERIAL Y MÉTODOS: estudio de cohorte, no randomizado, retrospectivo y unicéntrico, en pacientes operados por inestabilidad glenohumeral anterior, entre Enero 2010 y Diciembre de 2018. Se incluyen sólo pacientes con defecto de Hill-Sachs on-track. Fueron comparados pacientes operados con cirugía de B versus B + R. Se consigna recurrencia, complicación, reoperación y sensación de inestabilidad. Además, se realizan y comparan puntajes de EVA, SSV, WOSI y qDASH. RESULTADOS: de los 105 pacientes que cumplieron criterios de inclusión, 78 (74.3%) realizaron seguimiento completo (52 B y 26 B + R, 4.3 años mediana de seguimiento). Hubo mayor tasa de recurrencia en grupo B en comparación a B + R, siendo esta diferencia no significativa (17.3% versus 7.7%, p = 0.21). No hubo diferencia significativa en dolor residual, sensación de inestabilidad residual, complicaciones o puntajes de escala EVA, qDASH, SSV ni WOSI. En análisis por subgrupo, pacientes con deportes de contacto, B tienen mayor tasa de recurrencia (24.1% versus 0%, p = 0.08) y complicaciones comparadas con B + R (41.4% versus 18.2%, p = 0.16), siendo estas diferencias no significativas. CONCLUSIÓN: no hubo diferencias significativas en tasa de recurrencia y evolución funcional entre cirugía de Bankart aislado o Bankart-remplissage para inestabilidad glenohumeral anterior asociada a defecto de Hill-Sachs on-track. Estudios comparativos, prospectivos deben realizarse para establecer recomendaciones definitivas.

[Neurocysticercosis, its clinical and tomographic correlation. Reply]. / Neurocisticercosis, correlación clínica y tomográfica. Réplica.

TITLE: Neurocisticercosis, correlación clínica y tomográfica. Réplica.

Inestabilidad anterior de hombro con lesión de Hill-Sachs on-track. ¿Bankart o Bankart-remplissage? / Anterior shoulder instability with Hill-Sachs on-track. Bankart or Bankart-remplissage?

Resumen: Introducción: en pacientes con inestabilidad glenohumeral (GH) anterior con defecto de Hill-Sachs (HS) off-track o enganchante, Bankart-remplissage (B + R) reduce tasa de recurrencia en comparación a Bankart aislado (B). Hay controversia si tasa de recurrencia también disminuye en pacientes con defecto de HS on-track o no enganchantes. Objetivo: comparar la tasa de recurrencia y evolución clínica entre la cirugía de B versus B-R en pacientes operados por inestabilidad glenohumeral anterior con defecto de Hill-Sachs on-track. Material y métodos: estudio de cohorte, no randomizado, retrospectivo y unicéntrico, en pacientes operados por inestabilidad glenohumeral anterior, entre Enero 2010 y Diciembre de 2018. Se incluyen sólo pacientes con defecto de Hill-Sachs on-track. Fueron comparados pacientes operados con cirugía de B versus B + R. Se consigna recurrencia, complicación, reoperación y sensación de inestabilidad. Además, se realizan y comparan puntajes de EVA, SSV, WOSI y qDASH. Resultados: de los 105 pacientes que cumplieron criterios de inclusión, 78 (74.3%) realizaron seguimiento completo (52 B y 26 B + R, 4.3 años mediana de seguimiento). Hubo mayor tasa de recurrencia en grupo B en comparación a B + R, siendo esta diferencia no significativa (17.3% versus 7.7%, p = 0.21). No hubo diferencia significativa en dolor residual, sensación de inestabilidad residual, complicaciones o puntajes de escala EVA, qDASH, SSV ni WOSI. En análisis por subgrupo, pacientes con deportes de contacto, B tienen mayor tasa de recurrencia (24.1% versus 0%, p = 0.08) y complicaciones comparadas con B + R (41.4% versus 18.2%, p = 0.16), siendo estas diferencias no significativas. Conclusión: no hubo diferencias significativas en tasa de recurrencia y evolución funcional entre cirugía de Bankart aislado o Bankart-remplissage para inestabilidad glenohumeral anterior asociada a defecto de Hill-Sachs on-track. Estudios comparativos, prospectivos deben realizarse para establecer recomendaciones definitivas.

Abstract: Introduction: in patients with anterior glenohumeral (GH) instability together with an off-track or engaging Hill-Sachs (HS) defect, Bankart-remplissage (B-R) surgery reduces the recurrence rate when compared to Bankart (B) surgery alone. There is controversy regarding whether the recurrence rate also decreases in patients with on-track or non-engaging Hill-Sachs defects. Objective: to compare the recurrence rate and clinical evolution of patients with anterior glenohumeral instability with 'on-track' Hill-Sachs defect treated with either B or B-R surgery. Material and methods: non-randomized, retrospective, single-center cohort study of patients with anterior glenohumeral instability and on-track Hill-Sachs defect, operated between January 2010 and December 2018. Patients operated with B versus B-R were compared. Recurrence, complications and re-operation were recorded. In addition, VAS, SSV, WOSI and qDASH scores were obtained and compared in both groups. Results: of the 105 patients who met the inclusion criteria, 78 (74.3%) patients had a complete follow-up (52 B and 26 B-R, 4.3 years median follow-up). There was a higher recurrence rate in group B compared to B-R, with this difference not reaching statistical significance (17.3% vs 7.7%, p = 0.21). There were no significant differences in residual pain, feeling of instability, complications or VAS, qDASH, SSV or WOSI scores between both groups. In the subgroup analysis, patients who practiced contact sports and were operated with B showed higher recurrence rates (24.1% vs 0%, p = 0.08) and complications (41.4% vs 18.2%, p = 0.16) when compared to B + R, although these differences were not significant. Conclusion: there were no significant differences in recurrence rates and functional evolution between patients with anterior glenohumeral instability operated with B or B-R surgery. Comparative, prospective studies should be performed to establish definitive recommendations.

Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Percutaneous cryoablation: a novel treatment option in non-visceral metastases of the abdominal cavity after prior surgery.

PURPOSE: To assess the primary safety and oncological outcome of percutaneous cryoablation in patients with non-visceral metastases of the abdominal cavity after prior surgery. METHODS: All patients with non-visceral metastases after prior abdominal surgery, treated with percutaneous cryoablation, and at least one year of follow-up were retrospectively identified. Technical success was achieved if the ice-ball had a minimum margin of 10 mm in three dimensions on the per-procedural CT images. Complications were recorded using the Society of Interventional Radiology (SIR) classification system. Time until disease progression was monitored with follow-up CT and/or MRI. Local control was defined as absence of recurrence at the site of ablation. RESULTS: Eleven patients underwent cryoablation for 14 non-visceral metastases (mean diameter 20 ± 9 mm). Primary tumor origin was renal cell (n = 4), colorectal (n = 3), granulosa cell (n = 2), endometrium (n = 1) and appendix (n = 1) carcinoma. Treated metastases were localized retroperitoneal (n = 8), intraperitoneal (n = 2), or in the abdominal wall (n = 4). Technical success was achieved in all procedures. After a median follow-up of 27 months (12-38 months), all patients were alive. Local control was observed in 10/14 non-visceral metastases, and the earliest local progression was detected after ten months. No major adverse events occurred. One patient suffered a minor asymptomatic adverse event. CONCLUSION: This proof-of-concept study suggests that cryoablation can be a minimal invasive treatment option in a selected group of patients with non-visceral metastases in the abdominal cavity after prior surgery.

[Correlation between clinical and tomographic variables in patients with neurocysticercosis. A study in a cohort of patients in Sierra Norte, Ecuador, between 2019 and 2020]. / Correlación entre variables clínicas y tomográficas en pacientes con neurocisticercosis. Estudio en una cohorte de pacientes de la Sierra Norte ecuatoriana entre 2019 y 2020.

INTRODUCTION: Neurocysticercosis (NCC) is the most frequent parasitic disease in the central nervous system of humans. OBJECTIVE: to establish the correlation between clinical and tomographic variables in patients with neurocysticercosis in the neurology consultation of Hospital San Vicente de Paul and Hospital IESS Ibarra, during the year 2020. PATIENTS AND METHODS: descriptive, correlational and cross-sectional research. POPULATION AND SAMPLE: 93 patients. The information was collected in the neurology consultation. Clinical and imaging criteria were used for diagnosis. Odds Ratio (OR; 95% CI) was calculated. For multivariate analysis, binary logistic regression models were used. Statistical significance was considered when the value of p <0.05. SYMPTOMS: headache (77.4%), epilepsy (41.9%). Tomographic findings: size < 1 cm (67.7%), single lesion (54.8%), supratentorial (93.5%). There were several clinical / tomographic correlations in the bivariate analysis, the presence of epilepsy was associated with lesions of size >1 cm (OR: 9.65; 95% CI: 3.48-26.7), the vesicular + ventricular colloidal stage + nodular (OR: 3.90; 95% CI: 1.64-9.28) and parenchymal topography (OR: 5.03; 95% CI: 2.03-12.4) (p < 0.05). In the multivariate analysis, epilepsy was not associated with tomographic aspects such as the size, stage and topography of the cysticerci (p < 0.05). Headache and reduced muscle strength were associated with parenchymal topography and stage of lesions respectively (p < 0.05). CONCLUSIONS: Despite having a wide clinical spectrum, the presence of epilepsy, headache, and reduced muscle strength seem to be the most representative manifestations, so their inclusion in the development of prognostic scores should be evaluated, which allow evaluating the approach diagnostic and evolutionary in subsequent research.

TITLE: Correlación entre variables clínicas y tomográficas en pacientes con neurocisticercosis. Estudio en una cohorte de pacientes de la Sierra Norte ecuatoriana entre 2019 y 2020.Introducción. La neurocisticercosis es la enfermedad parasitaria más frecuente en el sistema nervioso central de los humanos. Objetivo. Establecer la correlación entre variables clínicas y tomográficas en pacientes con neurocisticercosis en la consulta de neurología del Hospital San Vicente de Paúl y el Hospital Instituto Ecuatoriano de Seguridad Social de Ibarra durante 2020. Pacientes y métodos. Investigación descriptiva, correlacional y transversal. Población y muestra: 93 pacientes. La información se recolectó en la consulta de neurología. Para el diagnóstico se utilizaron criterios clínicos e imagenológicos. Se calculó la odds ratio (OR) ­intervalo de confianza al 95% (IC 95%)­. Para el análisis multivariado, se utilizaron modelos de regresión logística binaria. Se consideró significación estadística cuando p menor de 0,05. Resultados. Síntomas: cefalea (77,4%) y crisis epilépticas (41,9%). Hallazgos tomográficos: tamaño menor de 1 cm (67,7%), lesión única (54,8%) y lesión supratentorial (93,5%). Hubo varias correlaciones clinicotomográficas en el análisis bivariado: la presencia de crisis epilépticas se asoció con lesiones de tamaño > 1 cm (OR: 9,65; IC 95%: 3,48-26,7), el estadio vesicular + ventricular coloidal + nodular (OR: 3,9; IC 95%: 1,64-9,28) y la topografía parenquimatosa (OR: 5,03; IC 95%: 2,03-12,4) (p menor de 0,05). La cefalea y la reducción de la fuerza muscular se asociaron con topografía parenquimatosa y estadio de las lesiones, respectivamente (p menor de 0,05). Conclusiones. A pesar de cursar con un amplio espectro clínico, la presencia de crisis epilépticas, cefalea y reducción de la fuerza muscular parece ser la manifestación más representativa, por lo que debería evaluarse su inclusión en el desarrollo de puntuaciones pronósticas que permitan evaluar el enfoque diagnóstico y evolutivo por estudio de imagen en investigaciones posteriores.

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1.

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.

Intra-Arterial Therapies for Liver Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Performing a systematic review and meta-analysis to assess the evidence of intra-arterial therapies in liver metastatic breast cancer (LMBC) patients. METHODS: A systemic literature search was performed in PubMed, EMBASE, SCOPUS for studies regarding intra-arterial therapies in LMBC patients. Full text studies of LMBC patients (n ≥ 10) published between January 2010 and December 2020 were included when at least one outcome among response rate, adverse events or survival was available. Response rates were pooled using generalized linear mixed models. A weighted estimate of the population median overall survival (OS) was obtained under the assumption of exponentially distributed survival times. RESULTS: A total of 26 studies (1266 patients) were included. Eleven articles reported on transarterial radioembolization (TARE), ten on transarterial chemoembolization (TACE) and four on chemo-infusion. One retrospective study compared TARE and TACE. Pooled response rates were 49% for TARE (95%CI 32-67%), 34% for TACE (95%CI 22-50%) and 19% for chemo-infusion (95%CI 14-25%). Pooled median survival was 9.2 months (range 6.1-35.4 months) for TARE, 17.8 months (range 4.6-47.0) for TACE and 7.9 months (range 7.0-14.2) for chemo-infusion. No comparison for OS was possible due to missing survival rates at specific time points (1 and 2 year OS) and the large heterogeneity. CONCLUSION: Although results have to be interpreted with caution due to the large heterogeneity, the superior response rate of TARE and TACE compared to chemo-infusion suggests first choice of TARE or TACE in chemorefractory LMBC patients. Chemo-infusion could be considered in LMBC patients not suitable for TARE or TACE. LEVEL OF EVIDENCE: 3a.

BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis.

INTRODUCTION: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. PATIENTS AND METHODS: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells. Functionally relevant cutoffs were based on the sensitivity of lymphoma cell lines to venetoclax. This assay was highly reproducible across laboratories. The prognostic impact of BCL2 expression was assessed in DLBCL patients from the phase 3 MAIN (n = 230) and GOYA (n = 366) trials, and a population-based registry (n = 310). RESULTS: Approximately 50% of tumors were BCL2 positive, with a higher frequency in high International Prognostic Index (IPI) and activated B-cell-like DLBCL subgroups. BCL2 expression was associated with poorer progression-free survival in the MAIN study (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.81-3.40; multivariate Cox regression adjusted for IPI and cell of origin). This trend was confirmed in the GOYA and registry cohorts in adjusted multivariate analyses (GOYA: HR, 1.72; 95% CI, 1.05-2.82; registry: HR, 1.89; 95% CI, 1.29-2.78). Patients with BCL2 immunohistochemistry-positive and IPI-high disease had the poorest prognosis: 3-year progression-free survival rates were 51% (GOYA) and 37% (registry). CONCLUSION: Findings support use of our BCL2 immunohistochemistry scoring system and assay to select patients with BCL2-positive tumors for future studies.

Diversidad genética de ovinos criollos colombianos

RESUMEN Objetivo. Caracterizar genéticamente los ovinos criollos colombianos y sus relaciones con razas de origen europeo. Materiales y métodos. 261 muestras de sangre de las siguientes poblaciones, fueron colectadas: Criollos de Lana (CL), Mora Colombiana (MC), Criollo de Pelo (CP), mestizos (Mes), Hampshire (Hamp), Corriedale (Corr), Katahdin (Kath), Pelibuey (Pel), En 40 fincas de ocho departamentos (Córdoba, Magdalena, Cesar, Atlántico, Valle del Cauca, Nariño, Boyacá y Tolima) y 30 muestras de Merino Español (ME), Merino Precoz (MP), Merinofleischschaf (MF), Segureño (Seg) y Uda (UD) de Nigeria. Un total de 15 marcadores microsatélites fueron incluidos en este estudio. Resultados. En ovinos criollos, el número promedio de alelos encontrado fue 6.20±1.48 (CL), 7.27±1.39 (CP) y 3.60±1.55 (MC); hallándose también alta diversidad genética en ellos (heterocigosidades superiores al 75%), valores negativos en el FIS revelaron alto grado de introgresión; además el FST reveló estructura genética tanto en los grupos criollos (FST=0.02**), como en los departamentos muestreados (FST=0.039**). Según la distancia genética, los ovinos criollos colombianos presentan diferencias con los ovinos foráneos. Conclusiones. Los resultados obtenidos recomiendan proteger la ovinocultura criolla puesto que se encuentra amenazada por los constantes cruzamientos con razas foráneas, lo que conllevaría a pérdida de la identidad genética y de los rasgos de adaptación propios de los animales criollos.

ABSTRACT Ojective. genetical characterization the creole Colombian sheep and their relationships with breeds of European origins. Materials and methods. Blood samples of 261 sheeps from the following populations were collected: Criollos de Lana (CL), Mora Colombiana (MC), Criollo de Pelo (CP), criollos mestizos (Mes), Hampshire (Hamp), Corriedale (Corr), Katahdin (Kath), Pelibuey (Pel), in 40 farms of 8 departments (Córdoba, Magdalena, Cesar, Atlántico, Valle del Cauca, Nariño, Boyacá, Tolima) and 30 samples of Merino Spanish, Merino Precoz (MP), Merinofleischschaf (MF), Segureño (Seg) and Uda (UD) de Nigeria. A total of 15 microsatellites markers were included inthis study. Results. In creole sheep, the average number of alleles was found 6.20±1.48 (CL), 7.27±1.39 (CP) y 3.60±1.55 (MC); high genetic diversity found (high heterozygosities 75%), negative values in the FIS revealed high degree of introgression; furthermore the FST revealed genetic structure in both: Creole sheep (FST=0.02**) and departments (FST=0.039**).According to genetic distance, the creole Colombian sheep differs with outsider sheep. Conclusions. The results recommend protecting the Creole sheep production because it has been threatened by constant cross with foreign breeds, which would lead to the loss of genetic identity and adapting traits of creole sheep themselves.

Does Rapid Drug Desensitization to Chemotherapy Affect Survival Outcomes?

BACKGROUND AND OBJECTIVE: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. Objective: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. METHODS: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). RESULTS: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). CONCLUSIONS: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.

Percutaneous Needle Electrolysis Reverses Neurographic Signs of Nerve Entrapment by Induced Fibrosis in Mice.

Nerve entrapments such as carpal tunnel syndrome are the most common mononeuropathies. The lesional mechanism includes a scarring reaction that causes a vascular compromise. The most effective treatment is surgery, which consists of removing the scarred area, thus reverting the vascular impairment. In the present study, a more conservative therapeutic approach has been undertaken to release the nerve by means of galvanic current (GC) applied with a needle: percutaneous needle electrolysis (PNE). For this purpose, a mouse model of sciatic nerve entrapment has been created using albumin coagulated by glutaraldehyde (albumin 35% and glutaraldehyde 2% volume applied, 10 µl). After two weeks, a fibrous reaction was obtained which entrapped the nerve to the extent of causing atrophy of the leg musculature (14.7%, P < 0.05 compared to the control leg). Ultrasound imaging confirmed that the model's image was compatible with that of nerve entrapment in patients. To quantify the degree of entrapment, nerve conduction recordings were made. The amplitude (peak-to-peak) of the compound muscle action potential (CMAPs) decreased by 32.2% (P < 0.05), and the proximal latency increases by 17.7% (P < 0.05, in both cases). In order to release the sciatic nerve, PNE was applied (1.5 mA for 3 seconds and 3 repetitions; 1.5/3/3) by means of a solid needle in the immediacy of perineural fibrosis before and 5 minutes after the application of GC, and the proximal latency shows a decrease of 16% (P < 0.05). The recovery of CMAPs amplitude was about 48.7% (P < 0.05). Three weeks later, the CMAPs amplitude was almost completely recovered (94.64%). Therefore, with the application of GC by means of a solid needle, the sciatic nerve was definitively released from its fibrous entrapment.

Eye lens radiation exposure in paediatric interventional treatment of retinoblastoma.

Retinoblastoma represents 3% of cancers in children under fifteen years of age. The standard paediatric treatment for saving the affected eye is supraselective intra-arterial chemotherapy performed in interventional rooms. In order to address the radiation toxicity due to the angiography, the aim of this study was to determine the typical dose value corresponding to the procedure, estimate the paediatric patients' eye lens dose and study the relationship between dose indicators and dose to the lens. An automatic dose management software was installed in two interventional rooms to obtain the distribution of the dose indicators kerma-area product and reference-point air kerma, getting a typical value 16 Gy·cm2 and 130 mGy, respectively (n = 35). The eye lens dose estimates were obtained with photoluminescent dosimeters placed on the patient's eyelids. In the left eye, the entrance surface air kerma was 44.23 ± 2.66 mGy, and 12.72 ± 0.89 mGy in the right eye (n = 10). There was a positive correlation between dose to the lens per procedure and dose indicators, with R2 > 0.65 for both eyes. Based on this information, the threshold for the onset of radiation-induce cataracts (500 mGy) will be exceeded if the treatment is performed for more than 8 sessions.

Imaging of rectal cancer.

International guidelines dictate that magnetic resonance imaging (MRI) should be part of the primary standard work up of patients with rectal cancer because MRI can accurately identify the main risk factors for local recurrence and stratify patients into a differentiated treatment. The role of endoscopic ultrasound (EUS) is restricted to staging of superficial tumors because EUS is able to differentiate between T1 and T2 rectal cancer. Recent guidelines recommend the addition of diffusion-weighted (DWI) MRI to clinical and endoscopic assessment of response to preoperative radiochemotherapy (RCT). MRI is able to identify significant tumor regression which may alter the surgical approach.

[Imaging of rectal cancer. German version]. / Bildgebung des Rektumkarzinoms.

International guidelines dictate that magnetic resonance imaging (MRI) should be part of the primary standard work up of patients with rectal cancer because MRI can accurately identify the main risk factors for local recurrence and stratify patients into a differentiated treatment. The role of endoscopic ultrasound (EUS) is restricted to staging of superficial tumors because EUS is able to differentiate between T1 and T2 rectal cancer. Recent guidelines recommend the addition of diffusion-weighted (DWI) MRI to clinical and endoscopic assessment of response to preoperative radiochemotherapy (RCT). MRI is able to identify significant tumor regression which may alter the surgical approach.

Analysis of Genetic Variation in CD40 and CD40L: Relationship with mRNA Relative Expression and Soluble Proteins in Acute Coronary Syndrome.

Acute coronary syndrome (ACS) can be triggered by the presence of inflammatory factors which promote the activation of immune cells by costimulatory molecules such as CD40 and its ligand CD40L. Environmental and genetic factors are involved in the etiology of the ACS. The aim of this study was to explore the gene and protein expression associated with CD40 and CD40L genetic variants in ACS patients from the western Mexican population. A total of 620 individuals from western Mexico were recruited: 320 ACS patients and 300 individuals without a history of ischemic cardiopathy were evaluated. The genotype was determined using TaqMan SNP genotyping assays. CD40 and CD40L expressions at the mRNA level were quantified using TaqMan Gene Expression Assays. Soluble protein isoforms were measured by enzyme-linked immunosorbent assay. We did not find evidence of association between CD40 (rs1883832, rs4810485, and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS, although rs1883832 and rs4810485 were significantly associated with high sCD40 plasma levels. Plasma levels of sCD40L can be affected by gender and the clinical spectrum of acute coronary syndrome. Our results do not suggest a functional role of CD40 and CD40L genetic variants in ACS. However, they could reflect the inflammatory process and platelet activation in ACS patients, even when they are under pharmacological therapy. Due to the important roles of the CD40-CD40L system in the pathogenesis of ACS, longitudinal studies are required to determine if soluble levels of CD40 and CD40L could be clinically useful markers of a recurrent cardiovascular event after an ACS.

Therapeutic drug monitoring of tumour necrosis factor inhibitors in the management of chronic inflammatory diseases.

Tumour necrosis factor inhibitor therapy has drastically changed the management of chronic inflammatory diseases. Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of antidrug antibodies that increase its clearance. Therapeutic drug monitoring of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms. Proactive therapeutic drug monitoring represents a new strategy with many potential clinical benefits, including the prevention of immunogenicity, a reduction in the need for rescue therapy and greater durability of tumour necrosis factor inhibitor treatment. The review is based on a systematic search of the literature for controlled trials, systematic reviews, experimental studies, guideline papers and cohort studies addressing the best practice in tumour necrosis factor inhibitor therapeutic drug monitoring. Although there is ample evidence supporting the use of therapeutic drug monitoring in clinical practice to achieve better outcomes, some challenges have been detected. Many studies are focused on finding solutions for the lack of standardization of analytical methods to measure tumour necrosis factor inhibitor and antidrug antibodies concentrations. Other challenges are development of effective cost-saving proactive algorithms to identify optimal drug concentrations and the research on the role of antidrug antibodies, especially in the management and prevention of loss of response. Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease. Although prospective controlled trials yield little conclusive evidence of its benefits, there is growing acceptance of its value in clinical practice.