Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.

INTRODUCTION: We report results from a phase I, three-part, dose-escalation study of peposertib, a DNA-dependent protein kinase inhibitor, in combination with avelumab, an immune checkpoint inhibitor, with or without radiotherapy in patients with advanced solid tumors. MATERIALS AND METHODS: Peposertib 100-400 mg twice daily (b.i.d.) or 100-250 mg once daily (q.d.) was administered in combination with avelumab 800 mg every 2 weeks in Part A or avelumab plus radiotherapy (3 Gy/fraction × 10 days) in Part B. Part FE assessed the effect of food on the pharmacokinetics of peposertib plus avelumab. The primary endpoint in Parts A and B was dose-limiting toxicity (DLT). Secondary endpoints were safety, best overall response per RECIST version 1.1, and pharmacokinetics. The recommended phase II dose (RP2D) and maximum tolerated dose (MTD) were determined in Parts A and B. RESULTS: In Part A, peposertib doses administered were 100 mg (n = 4), 200 mg (n = 11), 250 mg (n = 4), 300 mg (n = 6), and 400 mg (n = 4) b.i.d. Of DLT-evaluable patients, one each had DLT at the 250-mg and 300-mg dose levels and three had DLT at the 400-mg b.i.d. dose level. In Part B, peposertib doses administered were 100 mg (n = 3), 150 mg (n = 3), 200 mg (n = 4), and 250 mg (n = 9) q.d.; no DLT was reported in evaluable patients. Peposertib 200 mg b.i.d. plus avelumab and peposertib 250 mg q.d. plus avelumab and radiotherapy were declared as the RP2D/MTD. No objective responses were observed in Part A or B; one patient had a partial response in Part FE. Peposertib exposure was generally dose proportional. CONCLUSIONS: Peposertib doses up to 200 mg b.i.d. in combination with avelumab and up to 250 mg q.d. in combination with avelumab and radiotherapy were tolerable in patients with advanced solid tumors; however, antitumor activity was limited. GOV IDENTIFIER: NCT03724890.

S100A12 protein as a porcine health status biomarker when quantified in saliva samples.

The S100A12 protein was validated as a biomarker of health status in porcine saliva samples using a semi-quantitative approach based on Western blotting in four healthy and sixteen diseased animals, and in four animals with severe respiratory disease during three days of antibiotic therapy. Afterwards, a non-competitive sandwich immunoassay was then developed, validated, and used to quantify S100A12 in clinical porcine samples, using 14 healthy and 25 diseased pigs. Finally, the S100A12 concentrations in the saliva of ten pigs with respiratory disease were monitored during antibiotic therapy. Diseased animals showed higher concentrations of S100A12 than healthy animals, and the high concentrations of S100A12 in pigs with respiratory distress were reduced after antimicrobial therapy. The assay developed showed good precision and accuracy, as well as a low limit of detection of 3.19 ng/mL. It was possible to store saliva samples at -20 °C, or even at 4 °C, for two weeks before analysis without losing the validity of the results. The concentrations of S100A12 observed in serum and saliva samples showed a moderately positive association with a correlation coefficient of 0.48. The concentrations of the new validated biomarker S100A12 are highly associated with the novel salivary biomarker of inflammation, adenosine deaminase, and moderately to highly associated with the total oxidant status. The results reported in this study provide a new way of evaluating inflammatory diseases in pigs using saliva samples, which should be further explored for disease prevention and monitoring in the field.

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.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

BACKGROUND: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. MATERIALS AND METHODS: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. RESULTS: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. CONCLUSIONS: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

Influence of the circadian cycle, sex and production stage on the reference values of parameters related to stress and pathology in porcine saliva.

BACKGROUND: The concentration of biomarkers in saliva could be influenced by several factors not related to the specific condition under analyses, which should be considered for proper clinical interpretation. In the present study, the circadian rhythm of C-reactive protein (CRP), haptoglobin (Hp), Pig-MAP, S100A12, Cu, Zn, Adenosine deaminase (ADA), total protein (TP), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), cortisol and α-amylase in saliva of 20 female and 20 male pigs was investigated. Moreover, the influence of sex and production phase (post-weaning, fattening and finishing) on the concentrations of biomarkers in a total of 414 healthy pigs was studied and the reference intervals for all salivary biomarkers were calculated accordingly. RESULTS: All parameters except Pig-MAP, OSI and α-amylase varied significantly along the daytime, and most of them peak around early afternoon (13-15 h). The cosinor analysis described the temporal dynamics of circadian rhythms for all parameters. The range values showed differences between male and female pigs in 8 out of the 13 biomarkers, with higher concentrations in females in comparison to male pigs. The influence of the production phase on the salivary concentrations was observed for all the biomarkers. The highest concentrations were observed for Pig-MAP, S100A12 and α-amylase in post-weaning animals, for TP in growing pigs and for OSI in finishing animals. Most of the sex-influenced biomarkers showed the highest concentrations at growing stages with some exceptions such as ADA or Hp that showed the peak at finishing and post-weaning stages respectively. CONCLUSIONS: It is necessary to establish the optimal daytime for routine saliva sampling to avoid circadian variations and for that end, the time interval between 10:00 a.m. to 12:00 a.m. is highly recommended. The factors sex and production phase influence the concentration of biomarkers and should be considered for proper biomarker interpretation. The reference intervals presented here for each salivary biomarker will help to correctly interpret the results of these analytes and contribute to the use of saliva as a non-invasive sample for the diagnosis and monitoring of the health status of swine farms.

[Validity and reliability of DASH questionnaire in women who suffer from lymphedema as a side effect of a breast cancer treatment]. / Validez y fiabilidad del cuestionario DASH en mujeres con linfedema secundario a tratamiento de cáncer de mama.

INTRODUCTION: DASH questionnaire was designed to assess upper limb function in musculoskeletal pathologies. The aim of this manuscript is to study the reliability and validity of this questionnaire, to determine if is adequate to use in women with lymphedema due to breast cancer treatment. METHODS: Prospective study in 65 women with lymphedema due to breast cancer treatment was done, in which the reliability of DASH score with internal consistency (Cronbach's alpha) and test-retest reproducibility 15 days' interval (interclass correlation coefficient) and validity by correlation with SF-36v2 and FACT-B+4 (r or Kendall's τ b) scores was investigated. RESULTS: The internal consistency and the test-retest were Cronbach's alpha 0.969 and interclass correlation coefficient 0.861, respectively. There was correlation between the DASH score with the SF-36v2 score, mainly in the areas of physical function, body pain and physical role (r 0.800, 0.738, and 0.682, respectively; p<0.001), and lowest with the emotional and social wellbeing. The DASH score had correlation with FACT-B+4 (0.836; p<0.001) and the subscales the upper limb score (r=0.816; p<0.001), and there was no correlation with the social/familiar subscale (r=0.193; p=0.216). CONCLUSION: The DASH questionnaire is a reliable and valid tool to assess upper limb functionality in Spanish women with breast cancer related lymphedema.

Use of internal-external diversion stent in open pyeloplasty in patients under one year of age. / Uso de catéter de derivación interno-externo en la pieloplastia abierta en menores de un año.

INTRODUCTION: There are various alternatives available for renal pelvis drainage following pyeloplasty. One of them is the use of an internal-external diversion stent, which according to our protocol, is knotted 48 hours following surgery, prior to discharge, and removed 7 days later on an outpatient consultation basis, with no sedation or analgesia required. OBJECTIVE: To analyze the results of patients under one year of age who underwent open pyeloplasty associated with an outpatient internal-external diversion stent. MATERIALS AND METHODS: A retrospective, descriptive analysis of 28 patients (31 renal units) undergoing surgery from 2011 to 2021 was carried out. Diagnostic methods, indications, surgical approach, and postoperative progression were assessed. RESULTS: 28 patients (23 male) prenatally diagnosed with hydronephrosis confirmed by ultrasonography and/or renogram underwent pyeloplasty at a median age of 3 months (15 days-11 months). Pyeloplasty was conducted according to the Anderson-Hynes technique or dismembered pyeloplasty in 28 renal units, and according to the Culp-DeWeerd technique or spiral flap in 3. In all cases, an internal-external diversion stent was used according to our protocol. Mean hospital stay was 3.5 days (2-7 days), with a good postoperative progression. 2 patients had complications (urinary infection requiring intravenous antibiotics, and pyonephrosis requiring re-pyeloplasty). CONCLUSIONS: Using an internal-external diversion stent following pyeloplasty in patients under 1 year of age with ureteropelvic junction obstruction is a simple and safe option that allows for early discharge with outpatient management. It also avoids a second general anesthesia for drainage catheter removal purposes.

INTRODUCCION: Existen diversas alternativas para el drenaje de la pelvis renal tras una pieloplastia. Una de ellas es la utilización de un catéter de derivación interno-externo que, según nuestro protocolo, se anuda a las 48 horas posoperatorias previas al alta y se retira a los siete días de forma ambulatoria en consulta, sin necesidad de sedoanalgesia. OBJETIVO: Analizar los resultados de los pacientes menores de un año intervenidos mediante pieloplastia abierta, asociando un catéter de derivación interno-externo de manejo ambulatorio. MATERIAL Y METODOS: Análisis descriptivo retrospectivo de 28 pacientes (31 unidades renales) intervenidos entre los años 2011 y 2021. Se evaluaron métodos diagnósticos, indicaciones, abordaje quirúrgico y evolución posoperatoria. RESULTADOS: Veintiocho pacientes (23 varones) con diagnóstico prenatal de hidronefrosis confirmado con ecografía y/o renograma, fueron intervenidos mediante pieloplastia a una mediana de edad de tres meses (15 días-11 meses). Se realizó pieloplastia según técnica de Anderson-Hynes o pieloplastia desmembrada en 28 unidades renales y según técnica de Culp-DeWeerd o colgajo en espiral en 3. En todos los casos se utilizó un catéter de derivación interno-externo según protocolo. El tiempo medio de ingreso fue 3,5 días (2-7 días) con buena evolución posoperatoria. Dos pacientes presentaron complicaciones (infección urinaria que requirió antibioterapia intravenosa y pionefrosis que requirió repieloplastia). CONCLUSIONES: Asociar un catéter de derivación interno-externo a la pieloplastia en pacientes menores de un año con estenosis de la unión pieloureteral es una opción sencilla y segura que permite un alta precoz con manejo ambulatorio y evita una segunda anestesia general para la retirada del catéter de drenaje.

[Involuntary movements of the stump after transtibial amputation: Jumping stump syndrome]. / Movimientos involuntarios del muñón tras una amputación transtibial: síndrome del muñón saltarín.

45-year-old woman with history of hallux valgus surgery and torpid evolution, which led to transtibial amputation. Six months after surgery, she began to experience involuntary movements of the stump such as myoclonus, that were triggered by touch or hip extension, associating worsening of the previous stump and phantom limb pain. During the following year, concurring with change of prosthesis, symptoms progressively worsened, which limited walking. The therapeutic approach to pain and myoclonus was initially pharmacological, without response. Given the clinical and ultrasound suspicion of neuroma in the external popliteal sciatic nerve, it was infiltrated with corticosteroid and anesthetic, and the gastrocnemius with botulinum toxin type A, without success. Finally, the myoclonus disappeared, and the pain decreased after surgical remodeling of the stump and resection of the neuroma. This clinical picture is known as jumping stump syndrome and is a rare complication that must be considered after amputation.

[Glomus tumor of subungual presentation in the thumb and use of ultrasound in its diagnosis. Case report and literature review]. / Tumor glómico de presentación subungueal en pulgar y uso de ecografía en su diagnóstico. Reporte de caso y revisión de bibliografía.

INTRODUCTION: the glomus tumor is a benign neoplasm originated in the smooth muscle cells of the vascular glomus. Approximately 80% of lesions are located on the upper extremity and, of these, the majority are in the subungual area. The diagnosis must include imaging tests, among which ultrasound stands out, being a good alternative due to its low cost and accessibility. OBJECTIVE: we present a case of late diagnosis of surgically managed glomus tumor, as well as a review of the existing literature for diagnosis, treatment, and prognosis of this uncommon pathology. CLINICAL CASE: the case of a 52-year-old female patient who reported chronic, burning pain, radiating to the distal phalanx of the thumb with no history of trauma, of 2 years of evolution and which limited her daily life activities, is presented. The exploration with interphalangeal Doppler ultrasound is complemented, being an excellent alternative due to its easy accessibility. A glomus tumor was diagnosed in the interphalangeal thumb. An "H" approach was performed on the interphalangeal fold with subungual dissection with resection of the tumor piece and follow-up by an outpatient clinic where a surgical wound with adequate healing was found. Physical examination with capacity for the mobilization of the distal interphalangeal joint (IFJ) and visual analogue scale (VAS) 1 point. The updated pathological evaluation of the existence of a glomus tumor. CONCLUSIONS: ultrasound is an excellent aid in the diagnosis, as well as in the surgical planning for the treatment of the glomus tumor; for being accessible, low cost and highly effective. The anatomopathological study is the gold standard.

INTRODUCCIÓN: el tumor glómico es una neoplasia benigna originada en las células musculares lisas del glomus vascular. Aproximadamente 80% de las lesiones se localiza en la extremidad superior y, de éstas, la mayoría se sitúa en la zona subungueal. El diagnóstico debe incluir exámenes de imágenes, entre los que destaca la ecografía, siendo una buena alternativa por su bajo costo y accesibilidad. OBJETIVO: presentamos un caso de diagnóstico tardío de tumor glómico manejado quirúrgicamente, así como revisión de la literatura existente para diagnóstico, tratamiento y pronóstico de esta patología poco común. CASO CLÍNICO: paciente femenino de 52 años que refería un dolor crónico, ardoroso, irradiado hacia falange distal del pulgar sin antecedente traumático, de dos años de evolución y que limitaba actividades de su vida diaria. Se complementa exploración con ultrasonido Doppler interfalángico siendo una excelente alternativa por su fácil accesibilidad. Se diagnostica tumor glómico en interfalángica pulgar. Se realiza abordaje en "H" sobre pliegue interfalángico con disección subungueal con resección de pieza tumoral y seguimiento por consulta externa donde se encuentra herida quirúrgica con adecuada cicatrización. Exploración física con capacidad para la movilización de movilización de la articulación interfalángica distal (IFD) y escala visual análoga (EVA) de 1 punto. La evaluación anatomopatológica informó la existencia de tumor glómico. CONCLUSIONES: la ecografía es una excelente ayuda en el diagnóstico, así como en la planificación operatoria para el tratamiento del tumor glómico, por ser accesible, de bajo costo y de alta efectividad. El estudio anatomopatológico es el estándar de oro que da la certeza diagnóstica.

[Reconstruction of painful neuroma of superficial branch of radial nerve after first dorsal compartment release: presentation of two cases]. / Reconstrucción de neuroma de nervio radial superficial con injerto autólogo de nervio sural: presentación de dos casos.

INTRODUCTION: nerve lesions are potentially catastrophic injuries. They can cause motor loss, severe pain and neuroma formation. The superficial branch of the radial nerve is at risk during first dorsal compartment release, its injury can cause neuroma formation. Autologous nerve reconstruction is the gold standard for treatment of small nerve gaps. CASES PRESENTATION: we present two cases of adult women (F/47 y F/51) with a prior history of first dorsal compartment release in another institution. Both patients developed debilitating neuropathic pain, as well as allodynia in the surgical site. They were diagnosed with superficial radial nerve neuroma. Oral medication and physical therapy was attempted without success. Surgical exploration and autologous nerve reconstruction was performed. Both patients had excellent relief of pain from visual analogue scale (VAS 9-10 to VAS 1-2). Postoperatively, both patients recovered partial sensitivity to pain in the zones distal to the repair. CONCLUSIONS: neuromas are feared complications that occur with unrecognized nerve lesions during surgery, they are difficult to treat and require multidisciplinary management. These two cases demonstrate that autologous nerve reconstruction is an excellent option for recovering function in small gaps of nerve tissue.

INTRODUCCIÓN: las lesiones iatrogénicas de nervio son complicaciones devastadoras de cualquier procedimiento quirúrgico. Ocasionan pérdida motora, dolor y formación de neuromas. En el abordaje para la liberación del primer compartimiento extensor de la muñeca, la rama superficial del nervio radial debe identificarse y protegerse previo a la liberación tendinosa. La lesión de este nervio sensitivo puede ocasionar dolor postoperatorio clínicamente significativo. La reconstrucción nerviosa con nervio autólogo ha demostrado en diversos escenarios buenos resultados para mejorar el dolor y recuperar la conducción nerviosa. PRESENTACIÓN DE LOS CASOS: se presentan dos casos de mujeres adultas (F/47 y F/51) con antecedente de liberación de primer compartimiento dorsal de muñeca en otro centro hospitalario. Desarrollaron posteriormente dolor incapacitante y alodinia en sitio quirúrgico, así como limitación funcional. Fueron evaluadas y diagnosticadas como neuroma de rama superficial del nervio radial. No hubo mejoría con terapia física, por lo que se realizó reconstrucción nerviosa con injerto autólogo de nervio sural. Ambas pacientes tuvieron alivio del dolor de EVA 9-10 hasta EVA 1-2. A los cuatro meses de seguimiento, las dos mujeres recuperaron parcialmente la sensibilidad distal al sitio del neuroma, sin recurrencia del dolor presentado. CONCLUSIONES: los neuromas son complicaciones devastadoras que ocurren con lesiones inadvertidas de nervios motores y sensitivos. La reconstrucción con nervio autólogo es una excelente opción para reconstrucción de pequeños tramos de nervio periférico.

Common surgical training program: standardization of learning quality. / Programa de formación quirúrgica común: uniformidad en la calidad del aprendizaje.

INTRODUCTION: The various surgical specialties in our center have used the simulation and experimental surgery resources available for their training tasks in minimally invasive surgery (MIS) in an individualized manner. With this learning model, a great dispersion of effort and expense was observed, so it was decided to create a unified program based on the following: shared learning, synergy among specialties, moderation of the economic cost, and rational use of the facilities. OBJECTIVE: To describe and assess our consensually designed training program in order to consolidate a shared learning strategy that will enable our residents to acquire and perfect surgical skills in MIS. MATERIALS AND METHODS: The program consists of various increasingly complex phases implemented on a continuous basis throughout the period of specialized training in the virtual laboratory and experimental operating room. The assessment methods were based on quantifiable criteria: percentage of efficiency and completion time of the "McGill Inanimate System for Training and Evaluation of Laparoscopic Skills" (MISTELS) exercises at the beginning and end of the program. An economic study was also conducted. RESULTS: 20 residents have completed the program. Mean times show a significant reduction in each of the exercises. The efficiency percentages at the end of the program were higher than at the beginning (p < 0.001). The cost of the program represented a saving of 67.89%. CONCLUSION: The new MIS training program improved the quality of learning in a safe environment, establishing common criteria among the different specialties and an improved use of resources.

INTRODUCCION: Las diferentes especialidades quirúrgicas de nuestro centro han usado los recursos de simulación y cirugía experimental para sus tareas de formación en cirugía mínimamente invasiva (CMI) de manera individualizada. Con este modelo de aprendizaje se detectó una gran dispersión de esfuerzos y gasto, por lo que se decidió crear un programa unificado basado en: aprendizaje compartido, sinergia entre especialidades, moderación del coste económico y uso racional de las instalaciones. OBJETIVO: Describir y evaluar nuestro programa de entrenamiento diseñado por consenso de cara a la consolidación de una estrategia de aprendizaje compartido que permita a nuestros residentes adquirir y perfeccionar habilidades quirúrgicas en CMI. MATERIAL Y METODOS: El programa consta de diferentes fases con complejidad creciente desarrolladas durante todo el periodo de formación especializada de forma continuada en laboratorio virtual y quirófano experimental. Los criterios de evaluación se basaron en criterios cuantificables: porcentaje de eficiencia y tiempo de realización de los ejercicios de McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) al inicio y final del programa. Se realizó también el estudio económico. RESULTADOS: Han completado el programa 20 residentes. Los tiempos medios demuestran una reducción significativa en cada uno de los ejercicios. Los porcentajes de eficiencia al final fueron mayores que al inicio del programa (p < 0,001). El coste del programa supuso un ahorro del 67,89%. CONCLUSION: El nuevo programa de entrenamiento en CMI mejoró la calidad de aprendizaje en un entorno seguro, estableciendo criterios comunes entre las diferentes especialidades y un mayor aprovechamiento de los recursos.

The Connection Between Stress and Immune Status in Pigs: A First Salivary Analytical Panel for Disease Differentiation.

This paper analyzes the association between stress and immune response activations in different diseases, based on the salivary analytics. Moreover, a first attempt to discriminate between diseases was performed by principal component analysis. The salivary analytics consisted of the measurement of psychosocial stress (cortisol and salivary alpha-amylase) indicators, innate (acute phase proteins: C-reactive protein and haptoglobin), and adaptive immune (adenosine deaminase, Cu and Zn) markers and oxidative stress parameters (antioxidant capacity and oxidative status). A total of 107 commercial growing pigs in the field were divided into six groups according to the signs of disease after proper veterinary clinical examination, especially, healthy pigs, pigs with rectal prolapse, tail-biting lesions, diarrhea, lameness, or dyspnea. Associations between stress and immune markers were observed with different intensities. High associations (r = 0.61) were observed between oxidative stress markers and adaptive immune markers. On the other hand, moderate associations (r = 0.31-0.48) between psychosocial stress markers with both innate and adaptive immune markers were observed. All pathological conditions showed statistically significant differences in at least 4 out of the 11 salivary markers studied, with no individual marker dysregulated in all the diseases. Moreover, each disease condition showed differences in the degree of activation of the analyzed systems which could be used to create different salivary profiles. A total of two dimensions were selected through the principal component analysis to explain the 48.3% of the variance of our data. Lameness and rectal prolapse were the two pathological conditions most distant from the healthy condition followed by dyspnea. Tail-biting lesions and diarrhea were also far from the other diseases but near to healthy animals. There is still room for improvements, but these preliminary results displayed a great potential for disease detection and characterization using salivary biomarkers profiling in the near future.

Recuperación laboral clínica y funcional a 3 meses del alta en pacientes hospitalizados por neumonía por SARS-CoV-2: relación con la terapia recibida / Clinical and functional recovery and return to work 3 months after discharge in patients hospitalized for SARS-CoV-2 pneumonia: relationship with the therapy received

Resumen Introducción: La presentación clínica de neumonía por COVID-19 ha sido bien documentada; sin embargo, sus repercusiones a largo plazo son aún motivo de investigación. Objetivo: Evaluar la recuperación laboral, clínica y funcional respiratoria, a 3 meses del egreso de pacientes hospitalizados por neumonía por SARS-CoV-2, en relación con la terapia ventilatoria recibida. Pacientes y Métodos: Se analizó una cohorte prospectiva de 116 pacientes con neumonía por COVID-19 del Hospital Naval Almirante Nef de Viña del Mar, con seguimiento clínico y funcional respiratorio 3 meses después de su alta. Resultados: Mediana del seguimiento: 100 días. Constitución de la cohorte: 75 hombres, mediana de edad 60 años, 50% obesos, 34,5% fumadores y 13,8% con comorbilidad respiratoria. 16% recibió rehabilitación. Se reportó disnea en 48,3% y fatigabilidad en 33,6%. Solo 54,8% retornó al trabajo. El 65,2% que utilizó oxigenoterapia (O2) volvió a trabajar comparado con 44% que utilizó cánula nasal de alto flujo (CNAF) y 33,3% con ventilación mecánica invasiva (VMI). Mayoritariamente el grupo de O2 volvió a la vida normal en comparación con CNAF y VMI (71,4 versus 17,5% y 11,1% respectivamente). La función pulmonar fue normal en 39 pacientes (33,6%). La serie que volvió a vida normal tuvo mayor porcentaje de DLCO y test de caminata de 6 minutos normales. En comparación con la serie O2, la serie CNAF tuvo mayor frecuencia de alteración de DLCO (OR = 5) seguido por la serie VMI (OR = 3,6). Conclusión: A 3 meses de seguimiento, se evidenció ausentismo laboral, persistencia de síntomas y alteración funcional respiratoria (DLCO), especialmente en quienes recibieron soporte ventilatorio adicional a oxigenoterapia.

Introduction: The clinical presentation of COVID-19 pneumonia has been well documented; however, its long-term repercussions are still a matter of investigation. Objective: to evaluate the occupational, clinical and functional respiratory recovery, 3 months after the discharge of patients hospitalized for SARS-CoV-2 pneumonia, in relation to the ventilatory therapy received. Patients and Methods: A prospective cohort of 116 patients with COVID-19 pneumonia from Hospital Naval Almirante Nef (Viña del Mar, Chile) was analyzed, with clinical and functional respiratory follow-up at 3 months after being discharged. Results: Median follow-up: 100 days. Composition of the cohort: 75 men, median age 60 years-old, 50% obese, 34.5% smokers and 13.8% with respiratory comorbidity. 16% received rehabilitation. Dyspnea was reported in 48.3% and fatigue in 33.6%. Only 54.8% returned to work. 65.2% who used oxygen therapy (O2) returned to work compared to 44% who used high-flow nasal cannula (HFNC) and 33.3% with invasive mechanical ventilation (IMV). Mostly the O2 group returned to normal life compared to HFNC and VMI (71.4 versus 17.5% and 11.1% respectively). Lung function was normal in 39 patients (33.6%). The series that returned to normal life had higher percentage of normal DLCO and six-minute walk test. Compared to the O2 series, the CNAF series had a higher frequency of DLCO alteration (OR = 5) followed by the VMI series (OR = 3.6). Conclusion: At 3 months of follow-up, absenteeism from work, persistence of symptoms and respiratory functional alteration (DLCO) were evident, especially in those who received ventilatory support in addition to oxygen therapy.

Indications and results of sentinel lymph node biopsy in breast cancer: Changes observed in 2018 compared to 2012.

BACKGROUND AND OBJECTIVE: Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for Sentinel Lymph Node Biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our Center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. MATERIALS AND METHODS: We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. RESULTS: 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the two groups: in 2018 there were fewer lobular invasive cancers (14 vs 28) (P < .05), a smaller mean pathological size (P < .001), a higher proportion of HER2 and triple negative tumors (28 vs 49) (P < .01) and, finally, an increase in use of neoadjuvant treatments (42.0% vs 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs 42.4% in 2012) (P < .0001) as well as in the proportion of ALND performed (12.6% in 2018 vs 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs74.3%) (ns) CONCLUSION: Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla.

A descriptive study of transthyretin amyloidosis in a tertiary hospital without a referral unit.

BACKGROUND AND OBJECTIVE: Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. MATERIAL AND METHODS: Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. RESULTS: A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. CONCLUSIONS: ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Venous thromboembolism incidence in cancer patients with germline BRCA mutations.

BACKGROUND: Germline BRCA (gBRCA) mutations predispose to an increased risk of breast and ovarian cancer among other neoplasms. Recently, several genomic alterations such as ALK and ROS-1 rearrangements have been described as molecular drivers of venous thromboembolism (VTE). The association of gBRCA mutations and VTE is unknown. MATERIALS AND METHODS: We performed an observational, retrospective, single-center study to determine the VTE incidence in consecutive patients with gBRCA mutations and cancer diagnosis attended in the multidisciplinary heredofamiliar cancer unit (HFCU) of Hospital General Universitario Gregorio Marañón, Spain, from 2010 to 2019. RESULTS: One-hundred and forty-one patients were included in the analysis. The overall VTE incidence was 12.8%. The highest incidence was reported in ovarian cancer patients (20.0%), followed by patients with both ovarian and breast cancers (16.6%) and the lowest was found in breast cancer (4.9%). No difference in the type of gBRCA mutation (1 or 2) in terms of VTE rate was observed. Sixty one percent of the patients were receiving anti-cancer therapy at the time of VTE diagnosis and the majority of the events (83.3%) were diagnosed in ambulatory setting. Khorana score was of limited value to detect high-risk patients. CONCLUSIONS: The VTE incidence observed in our study is consistent with prior data described in general population of breast and ovarian cancer. The risk of VTE in these patients seems to be driven by the type of cancer. We have not observed any significant interaction of gBRCA mutation status and cancer-associated thrombosis.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

A multi-herd study shows that saliva is more than a reflection of serum biomarkers in pigs.

This study evaluates if biomarkers of porcine health status in saliva samples is a mere reflection of serum to detect disease in pigs under field conditions. Four farms from the same commercial company were included to obtain samples from animals with different pathological conditions. A total of 10 healthy animals and 10-15 animals from each farm with clinical symptoms of the disease were sampled for paired saliva and blood during a veterinary clinical visit. The biomarker panel included acute-phase proteins (APPs), C-reactive protein (CRP), haptoglobin (Hp), an inflammatory marker, adenosine deaminase (ADA), the total antioxidant capacity (TAC), the levels of essential trace elements, copper (Cu) and zinc (Zn), and the measurement of the total protein content (TP). After detailed statistical analysis, the results showed that saliva could replace serum for APP measurements since a good agreement has been observed between the concentrations of APPs in both body fluids. For any other biomarker, no agreement between the concentrations quantified in serum and saliva samples was observed visually. However, salivary ADA and TP concentrations were statistically significantly higher in the diseased, whereas the statistical tests with serum concentrations were inconclusive. Furthermore, greater differentiation between healthy and diseased animals could be observed when the distribution of biomarkers was analysed in saliva than in other serum samples. The diagnostic power to discriminate between healthy and diseased pigs is similar in saliva and in serum samples. Preliminary regression models may offer an optimal combination of biomarkers for disease detection in saliva (Hp, CRP, and TAC) and serum (Hp, CRP, and Cu), which demands less labour, sample, and financial cost for saliva determinations. The contradictory results observed for TAC, Cu, and Zn levels between body fluids indicate a need for further studies. To sum up, saliva-based biomarkers instead of serum-based biomarkers could contribute to more efficient detection of diseased animals.

[Cognitive reserve as a modulating factor in the impact of surgery on visual memory and naming in temporal lobe epilepsy patients]. / La reserva cognitiva como factor modulador del impacto de la cirugía sobre la memoria visual y la denominación en pacientes con epilepsia del lóbulo temporal.

INTRODUCTION: Temporal lobe epilepsy (TLE) surgery is an effective procedure that produces cognitive changes. Factors modulating such changes have been proposed, but the influence of cognitive reserve remains unclear. OBJECTIVE: To examine the effect of intellectual quotient (IQ) on postsurgical changes in verbal fluency, naming, and verbal and visual memory in a sample of patients with TLE. PATIENTS AND METHODS: 64 adult patients with drug-resistant TLE (mean age ± SD: 39.16 ± 11.67) underwent a neuropsychological evaluation before and one year after surgery. RESULTS: Patients with high IQ showed better immediate visual memory before surgery than those with medium IQ, as well as an absence of postsurgical changes. Patients with high manipulative IQ had better naming before surgery than those with medium manipulative IQ, as well as a significant postsurgical worsening. Both before and after surgery, patients with high IQ showed better phonemic and semantic verbal fluency and short- and long-term verbal memory than those with medium IQ. CONCLUSIONS: IQ is a relevant factor in the evolution of immediate visual memory and naming after surgery in patients with TLE. Surgery does not impact on the advantage of high IQ patients in verbal fluency and verbal memory, suggesting that cognitive reserve has a positive effect on cognitive function, even after TLE surgery.

TITLE: La reserva cognitiva como factor modulador del impacto de la cirugía sobre la memoria visual y la denominación en pacientes con epilepsia del lóbulo temporal.Introducción. La cirugía de la epilepsia del lóbulo temporal (ELT) es un procedimiento eficaz que produce cambios cognitivos. Se han propuesto factores moduladores de dichos cambios, pero permanece sin esclarecer la influencia de la reserva cognitiva. Objetivo. Examinar el efecto del cociente intelectual (CI) sobre los cambios posquirúrgicos en medidas de fluencia verbal, denominación y memoria verbal y visual en una muestra de pacientes con ELT. Pacientes y métodos. Sesenta y cuatro pacientes adultos con ELT farmacorresistente (edad media ± desviación típica: 39,16 ± 11,67) fueron sometidos a una evaluación neuropsicológica antes y un año después de la cirugía. Resultados. Los pacientes con un CI alto presentaron un mejor funcionamiento de la memoria visual inmediata antes de la cirugía que los que tenían un CI medio, así como ausencia de cambios posquirúrgicos. Los pacientes con un CI manipulativo alto presentaron mejor denominación antes de la cirugía que los que tenían un CI manipulativo medio, así como un empeoramiento posquirúrgico significativo. Tanto antes como después de la cirugía, los pacientes con un CI alto presentaron mejor fluencia verbal fonémica y semántica y memoria verbal a corto y largo plazo que los que tenían un CI medio. Conclusiones. El CI es un factor relevante en la evolución de la memoria visual inmediata y de la denominación tras la cirugía en pacientes con ELT. La cirugía no repercute en la ventaja que tienen los pacientes con un CI alto en fluencia verbal y memoria verbal, lo que sugiere que la reserva cognitiva tiene un efecto positivo sobre la función cognitiva, incluso tras la cirugía de la ELT.