Transoperative Magnetic Resonance Imaging in Awake Glioma Surgery: Experience in a Latin American Tertiary-Level Center.

OBJECTIVE: Analyze the usefulness, efficacy, and safety of transoperative magnetic resonance imaging (tMRI) in glioma surgery in awake patients. METHODS: Retrospective, single-center, analytical study of a cohort of patients who underwent awake surgery for gliomas by the same surgeon in a third-level Argentine center, in the period between 2012 and 2022. Only patients with pathology-confirmed gliomas, with 6-month follow-up, who had preoperative and postoperative volumetric magnetic resonance imaging, were included in this sample. Subsequently, we analyzed which patients received surgery with the tMRI protocol and the results using multivariate regression analysis. RESULTS: A total of 71 patients were included. A tMRI study was performed on 22 (31%) of these patients. The use of tMRI increased the percentage of resection by 20% (P = 0.03), thereby increasing the possibility of gross total resection. However, using tMRI significantly extended surgical time by 84 minutes (P < 0.001). In 55% of the patients in whom tMRI was performed, the resection was continued after it. The use of tMRI did not increase the rate of infections or the development of surgically associated neurological deficits in the long term, despite the fact that 47% of the patients showed the development of a new deficit or worsening of a previous one during the intraoperative period. CONCLUSIONS: The use of tMRI in awake glioma surgery proved to be a safe tool that contributes to increasing the degree of tumor resection, compared to the use of neurophysiological mapping and neuronavigation, at the expense of increased surgical times and costs. We consider tMRI in awake glioma surgery should be used in properly selected cases.

[Endoscopic vs. microscopic techniques for the treatment of trigeminal neuralgia. Our experience at an Argentine care center]. / Descompresión microvascular endoscópica versus microscópica en neuralgia trigeminal en un Centro argentino.

INTRODUCTION: Trigeminal neuralgia is a highly invalidating pathology, whose natural course has been modified thanks to decompressive microvascular surgery. The intervention can be carried out either with a microscope or via an endoscopic technique. Our goal was to compare these two techniques for the treatment of this complex pathology. METHODS: Retrospective, analytical study of a cohort of patients treated by a single surgeon at our institution, in the period between 2015 and 2021. RESULTS: We identified 31 patients and divided them into two groups: 15 (49%) treated using the microscopic technique (group M), and 16 (51%) exclusively via an endoscopic one (group E). Differences were observed between the means of the size of the craniectomy in group M (3.7 cm) compared to group E (2.5 cm); The mean length of hospital stay for patients in group E was shorter (4.46 days compared to that of patients in group M, whose hospital stay averaged 2.43 days). There were no differences between the two groups regarding the length of the procedure. In both groups, the predominant compression was due to the superior cerebellar artery (SCA). Pain outcomes were equivalent, with every patient in both groups having an improved postoperative Barrow Neurological Institute Pain Intensity Score (BNI). DISCUSSION: Endoscopic microvascular decompression is an attractive option for the resolution of neurovascular conflict as it provides functional results similar to the microscope technique, without requiring an extensive craniectomy and associated to shorter in-hospital stay, which is beneficial for both the patient and the institution.

Introducción: La descompresión microvascular (DMV) en la neuralgia trigeminal es una técnica quirúrgica cuyo objetivo es revertir la compresión a la que se ve sometido un nervio por una estructura vascular. El objetivo de este estudio fue realizar una comparación directa entre la descompresión microvascular endoscópica (DMV-E) y la misma a través del uso del microscopio (DMV-M) en el tratamiento de la neuralgia del trigémino. Métodos: Se realizó un estudio de cohorte retrospectivo de pacientes operados de neuralgia de trigémino, por un mismo cirujano, entre 2015 y 2021 en nuestra institución, tanto por técnica microquirúrgica como endoscópica. Resultados: Se obtuvieron un total de 31 pacientes divididos en dos grupos: Grupo M correspondiente a 15 (49%) pacientes abordados con técnica microscópica y Grupo E, con 16 (51%) pacientes intervenidos con técnica endoscópica. Se identificaron diferencias en el tamaño de la craniectomía, más pequeña en el grupo E (2.50 cm vs 3.70 cm grupo M); y en el tiempo de internación, de 2.43 días en el grupo E vs. 4.46 días en el grupo M. El tiempo de cirugía fue similar para ambas técnicas quirúrgicas La principal compresión fue dada por la arteria cerebelosa superior (ACS) en ambos grupos. Todos los pacientes presentaron mejoría del Barrow Neurological Institute Pain Intensity Score (BNI) en el postoperatorio en ambos grupos. Discusión: La DMV-E constituye una alternativa quirúrgica interesante a la ya conocida DMV-M para el tratamiento de la neuralgia trigeminal, por requerir menores dimensiones en la incisión cutánea y tamaño de la craniectomía, acortando el tiempo de internación, lo cual no solo implica un beneficio para el paciente, sino que también representa menor costo de internación.

Descompresión microvascular endoscópica versus microscópica en neuralgia trigeminal en un centro Argentino / Endoscopic vs. microscopic techniques for the treatment of trigeminal neuralgia. Our experience at an Argentine care center

Resumen Introducción: La descompresión microvascular (DMV) en la neuralgia trigeminal es una técnica quirúrgica cuyo objetivo es revertir la compresión a la que se ve someti do un nervio por una estructura vascular. El objetivo de este estudio fue realizar una comparación directa entre la descompresión microvascular endoscópica (DMV-E) y la misma a través del uso del microscopio (DMV-M) en el tratamiento de la neuralgia del trigémino. Métodos: Se realizó un estudio de cohorte retrospec tivo de pacientes operados de neuralgia de trigémino, por un mismo cirujano, entre 2015 y 2021 en nuestra institución, tanto por técnica microquirúrgica como endoscópica. Resultados: Se obtuvieron un total de 31 pacientes divididos en dos grupos: Grupo M correspondiente a 15 (49%) pacientes abordados con técnica microscópica y Grupo E, con 16 (51%) pacientes intervenidos con técnica endoscópica. Se identificaron diferencias en el tamaño de la cra niectomía, más pequeña en el grupo E (2.50 cm vs 3.70 cm grupo M); y en el tiempo de internación, de 2.43 días en el grupo E vs. 4.46 días en el grupo M. El tiempo de cirugía fue similar para ambas técnicas quirúrgicas La principal compresión fue dada por la arteria ce rebelosa superior (ACS) en ambos grupos. Todos los pacientes presentaron mejoría del Barrow Neurological Institute Pain Intensity Score (BNI) en el postoperatorio en ambos grupos. Discusión: La DMV-E constituye una alternativa qui rúrgica interesante a la ya conocida DMV-M para el tratamiento de la neuralgia trigeminal, por requerir menores dimensiones en la incisión cutánea y tamaño de la craniectomía, acortando el tiempo de internación, lo cual no solo implica un beneficio para el paciente, sino que también representa menor costo de internación.

Abstract Introduction: Trigeminal neuralgia is a highly invali dating pathology, whose natural course has been modi fied thanks to decompressive microvascular surgery. The intervention can be carried out either with a microscope or via an endoscopic technique. Our goal was to compare these two techniques for the treatment of this complex pathology. Methods: Retrospective, analytical study of a cohort of patients treated by a single surgeon at our institution, in the period between 2015 and 2021. Results: We identified 31 patients and divided them into two groups: 15 (49%) treated using the microscopic technique (group M), and 16 (51%) exclusively via an endoscopic one (group E). Differences were observed between the means of the size of the craniectomy in group M (3.7 cm) compared to group E (2.5 cm); The mean length of hospital stay for patients in group E was shorter (4.46 days compared to that of patients in group M, whose hospital stay averaged 2.43 days). There were no differences between the two groups regarding the length of the procedure. In both groups, the predomi nant compression was due to the superior cerebellar artery (SCA). Pain outcomes were equivalent, with every patient in both groups having an improved postoperative Barrow Neurological Institute Pain Intensity Score (BNI). Discussion: Endoscopic microvascular decompression is an attractive option for the resolution of neurovas cular conflict as it provides functional results similar to the microscope technique, without requiring an exten sive craniectomy and associated to shorter in-hospital stay, which is beneficial for both the patient and the institution.

Modulation of the functional interfaces between retroviral intasomes and the human nucleosome.

Infection by retroviruses as HIV-1 requires the stable integration of their genome into the host cells. This process needs the formation of integrase (IN)-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes within cell chromatin. To provide new tools to analyze this association and select drugs, we applied the AlphaLISA technology to the complex formed between the prototype foamy virus (PFV) intasome and nucleosome reconstituted on 601 Widom sequence. This system allowed us to monitor the association between both partners and select small molecules that could modulate the intasome/nucleosome association. Using this approach, drugs acting either on the DNA topology within the nucleosome or on the IN/histone tail interactions have been selected. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, in silico molecular simulations and cellular approaches. These drugs were shown to inhibit both PFV and HIV-1 integration in vitro. Treatment of HIV-1-infected PBMCs with the selected molecules induces a decrease in viral infectivity and blocks the integration process. Thus, in addition to providing new information about intasome-nucleosome interaction determinants, our work also paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring. IMPORTANCE In this work, we report the first monitoring of retroviral intasome/nucleosome interaction by AlphaLISA. This is the first description of the AlphaLISA application for large nucleoprotein complexes (>200 kDa) proving that this technology is suitable for molecular characterization and bimolecular inhibitor screening assays using such large complexes. Using this system, we have identified new drugs disrupting or preventing the intasome/nucleosome complex and inhibiting HIV-1 integration both in vitro and in infected cells. This first monitoring of the retroviral/intasome complex should allow the development of multiple applications including the analyses of the influence of cellular partners, the study of additional retroviral intasomes, and the determination of specific interfaces. Our work also provides the technical bases for the screening of larger libraries of drugs targeting specifically these functional nucleoprotein complexes, or additional nucleosome-partner complexes, as well as for their characterization.

Postoperative Third Nerve Palsy after Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenoma: Elucidating its Mechanism.

Third nerve palsy is a rare complication of transsphenoidal surgery and has been merely mentioned in different studies, but there is not any rigorous analysis focusing on this particular complication. The purpose of this study is to analyze this complication after transsphenoidal surgery for a pituitary adenoma to better understand its pathophysiology and outcome. The authors retrospectively analyzed 3 cases of third nerve palsy selected from the 377 patients operated via a transsphenoidal route between 2012 and 2021 at FLENI, a private tertiary neurology and neurosurgical medical center located in Buenos Aires, Argentina. The three patients who presented this complication were operated on via an endoscopic approach. It was observed that an extension into the cavernous sinus (Knosp grade 4) and to the oculomotor cistern was present in the three patients. The deficit was apparent immediately after surgery in two patients. For these two patients, the supposed mechanism of ophthalmoplegia was an intraoperative nerve lesion. The other patient became symptomatic in the 48 h following the surgery. The mechanism implied in this case was intracavernous hemorrhagic suffusion. The latter patient completely recovered the third nerve deficit in the 3 months that followed, while the other two recovered after 6 months postoperative. Oculomotor nerve palsy after transsphenoidal surgery is a very rare complication and appears to be transient in most cases. The invasion of both the cavernous sinus and the oculomotor cistern seems to be a major factor in its physiopathology and should be preoperatively analyzed on magnetic resonance imaging (MRI); recognizing such extension should play an important role in the surgeon's operative considerations.

Encuesta sobre usos y prácticas de Doppler transcraneal en pacientes neurocríticos en unidades de cuidados intensivos pediátricos de Argentina / Survey on the use and practice of transcranial Doppler ultrasound in neurocritical patients in pediatric intensive care Units in Argentina

Introducción. El uso del Doppler transcraneal (DTC) en pacientes neurocríticos se reporta cada vez más en las terapias intensivas pediátricas. El objetivo de esta encuesta es conocer los usos y prácticas del DTC en la atención neurocrítica y el proceso de formación del personal que realiza el estudio. Materiales y métodos. Encuesta a profesionales de 23 unidades de terapia intensiva pediátrica de Argentina. Resultados. Porcentaje de respuesta del 86 %. Se utilizó en sospecha de muerte encefálica (n = 20), trauma de cráneo (n = 16) y accidente cerebrovascular (n = 16). El intensivista pediátrico es quien realiza los estudios (n = 13/20). Los encuestados utilizan el Doppler para decidir conductas y tratamientos, comenzar el proceso de evaluación de muerte encefálica, solicitar tomografía de cerebro y manejar la presión de perfusión cerebral con vasopresores. Conclusión. Todos los encuestados utilizan los hallazgos del DTC para guiar tratamientos o conductas. La mitad de los encuestados está poco conforme con la capacitación recibida.

Introduction. The use of transcranial Doppler (TCD) ultrasoundin neurocritical patients is reported to be increasingly common in pediatric intensive care units. The objective of this survey was to know about the use and practice of TCD ultrasound in neurocritical care and the training process of staff members performing it. Materials and methods. Survey administered to providers from 23 pediatric intensive care units of Argentina. Results. The percentage of response was 86%. TCD ultrasound was used for suspected brain death (n = 20), head injury (n = 16), and stroke (n = 16). Pediatric intensivists perform the test (n = 13/20). Surveyed participants use TCD ultrasound to decide on treatment and management, start brain death assessment, request brain computed tomography, and manage cerebral perfusion pressure with vasopressors. Conclusion. All surveyed participants use TCD ultrasound findings to guide management or treatments. Half of surveyed participants are little satisfied with their training.

Establishing minimal clinically important difference for the UCLA and ASES scores after rotator cuff repair.

BACKGROUND/HYPOTHESIS: Minimal clinically important difference (MCID) is a vital tool in the analysis of clinical results. It allows the determination of clinical relevance of statistical data. Our hypothesis was that specific differences between preoperative and postoperative scores would be able to accurately predict patient perception of improvement and satisfaction as reflected by anchor and distribution-based questions. METHODS: Retrospective cohort with patients that underwent rotator cuff repair. We evaluated the University of California at Los Angeles Shoulder Rating Scale (UCLA) and the American Shoulder and Elbow Surgeons Assessment Form (ASES) before and 12-months after surgery. Anchor-based, distribution-based and minimum detectable change (MDC) approaches were utilized. RESULTS: We evaluated 289 shoulders. The MCID for the UCLA scale was 4.5 points using the anchor method, 2.5 by the distribution method and 3.6 by MDC. Patients with a baseline score>20 presented a lower MCID (1.5, 1.1 and 1.7, respectively). For the ASES score, the MCID was 6.1 by the anchor method, 10.5 based on the distribution method and 26.3 by MDC. In the group of patients above the 60 point cutoff, the obtained values were 2.4, 4.9 and 13.6, respectively. CONCLUSION: The mean MCID value for the UCLA shoulder score is 3.5 points, ranging from 2.5 points (distribution method) to 4.5 points (anchor method). The mean MCID value for the ASES score was 15.2 points, ranging from 6.1 (anchor method) to 26.3 (MDC). Patients groups presenting with higher preoperative scores showed lower MCID values. This fact needs to be considered in postoperative comparisons between treatment groups. LEVEL OF EVIDENCE: Basic Science Study, Validation of Outcomes Instruments/Classification Systems.

Fibrosis assessment in patients with nonalcoholic fatty liver disease: Adherence to proposed algorithms and barriers to complying with them.

INTRODUCTION AND AIMS: Fibrosis staging in patients with nonalcoholic fatty liver disease (NAFLD) is carried out through the application of stepwise algorithms but there is little real-world data on their use. Our aim was to calculate the number of patients with NAFLD and indeterminate or high risk for fibrosis, assessed through noninvasive scores, that consequently underwent further staging evaluation. MATERIALS AND METHODS: A cross-sectional multicenter cohort study was conducted on patients with NAFLD evaluated by hepatologists within the time frame of June 1 and July 31, 2018. The FIB-4 and NAFLD fibrosis scores were calculated in all the patients, and if at least one of the scores suggested indeterminate or high risk for fibrosis, we believed the patient should have undergone additional fibrosis staging assessment. RESULTS: The study included 238 patients. The median time interval from NAFLD diagnosis and inclusion in the analysis was 12.2 months (IQR 3.0-36.5). A total of 128 (54%) patients had at least one noninvasive score that suggested indeterminate or high risk for fibrosis but studies to confirm the fibrosis grade (elastography, biopsy, etc.) were performed on only 72 (56%). The main barriers encountered by the physicians for applying the staging algorithms were related to health insurance coverage and imaging study costs. CONCLUSIONS: A high percentage of patients with NAFLD were at indeterminate or high risk for fibrosis, according to noninvasive scores, but additional studies were carried out on only half of them, showing low adherence to current recommendations.

Pinto Bean Amino Acid Digestibility and Score in a Mexican Dish with Corn Tortilla and Guacamole, Evaluated in Adults Using a Dual-Tracer Isotopic Method.

BACKGROUND: Ultra-processed foodstuffs have been replacing traditional beans with tortillas in the Mexican diet in the last decades. Therefore, scientific support is needed to promote a return to good-quality traditional dishes. OBJECTIVES: This study aims to evaluate the amino acid digestibility and score of pinto beans (Phaseolus vulgaris) consumed with corn tortillas and guacamole in adults using the dual-tracer method. METHODS: The pinto beans were intrinsically labeled using 250 mL of 2H2O (99.8%) per 19 L pot with 3 plants. A paste of cooked beans on toasted corn tortillas and guacamole topping were administered to 3 male and 3 female adults (21-25 years old; BMI, 19-23.5 kg/m2). The protocol was plateau feeding given along with U-[13C]-spirulina protein to evaluate indispensable amino acid (IAA) digestibility using the dual-tracer method. Blood samples were taken in the plateau state. The digestibility of each IAA of the bean protein was calculated by the ratio of its enrichment in the beans to the spirulina in the meal and its appearance in plasma collected in the plateau state, as a percentage corrected by spirulina digestibility. Additionally, the digestible IAA score (DIAAS) was calculated. RESULTS: The 2H enrichment of IAA in the pinto beans was 471 parts per million excess. The isotopic enrichment of 2H and 13C in IAA at 5-8 hours presented plateau states with mean CVs of 12.2% and 13.3%, respectively. The mean digestibility of IAA from pinto beans was 77% ± 1.6%, with the lowest value for threonine. The DIAAS calculated with respect to the pattern requirement for children older than 3 years, adolescents, and adults was 83%, with methionine and cysteine being the limiting amino acids. CONCLUSIONS: A Mexican dish of pinto beans, tortillas, and guacamole is a good source of protein as evaluated in adults and could be promoted as a nutritious snack. The assay is registered with the Ethical Committee of the Centro de Investigación en Alimentación y Desarrollo, A.C. as CE/015/2019.

Fibrosis assessment in patients with nonalcoholic fatty liver disease: Adherence to proposed algorithms and barriers to complying with them. / Evaluación de fibrosis en pacientes con enfermedad por hígado graso no alcohólico: adherencia a los algoritmos propuestos y barreras para cumplir con ellos.

INTRODUCTION AND AIMS: Fibrosis staging in patients with nonalcoholic fatty liver disease (NAFLD) is carried out through the application of stepwise algorithms but there is little real-world data on their use. Our aim was to calculate the number of patients with NAFLD and indeterminate or high risk for fibrosis, assessed through noninvasive scores, that consequently underwent further staging evaluation. MATERIALS AND METHODS: A cross-sectional multicenter cohort study was conducted on patients with NAFLD evaluated by hepatologists within the time frame of June 1 and July 31, 2018. The FIB-4 and NAFLD fibrosis scores were calculated in all the patients, and if at least one of the scores suggested indeterminate or high risk for fibrosis, we believed the patient should have undergone additional fibrosis staging assessment. RESULTS: The study included 238 patients. The median time interval from NAFLD diagnosis and inclusion in the analysis was 12.2months (IQR 3.0-36.5). A total of 128 (54%) patients had at least one noninvasive score that suggested indeterminate or high risk for fibrosis but studies to confirm the fibrosis grade (elastography, biopsy, etc.) were performed on only 72 (56%). The main barriers encountered by the physicians for applying the staging algorithms were related to health insurance coverage and imaging study costs. CONCLUSIONS: A high percentage of patients with NAFLD were at indeterminate or high risk for fibrosis, according to noninvasive scores, but additional studies were carried out on only half of them, showing low adherence to current recommendations.

An individualized food-based nutrition intervention reduces visceral and total body fat while preserving skeletal muscle mass in breast cancer patients under antineoplastic treatment.

BACKGROUND & AIMS: Breast cancer patients (BCP) during treatment often experience an increase in body weight and fat mass, and a decrease in muscle mass known as sarcopenic obesity, affecting their prognosis and quality of life. We aimed to evaluate the effect of a 6-month individualized food-based nutrition intervention program in nonmetastatic BCP body composition during treatment. METHODS: This is a pre-post study in recently diagnosed women with invasive ductal/lobular breast carcinoma (clinical stage I-III). The individualized nutrition intervention was based on the dynamic macronutrient meal equivalent menu method (MEM). Dietary plans were developed according to WCRF/AICR guidelines, BCP total energy expenditure, 1.2-1.5 g/kgBW/d of protein intake, 5-9 servings/day of fruits and vegetables, and a caloric restriction (500-1000 kcal/d) when applicable (BMI ≥ 25 kg/m2). Follow-up was every 2-weeks and a different diet menu was provided in each session during 6 months. Baseline and final measurements included the assessment of anthropometry, body composition, and physical activity. RESULTS: Twenty-two participants completed the study and at diagnosis 68% were overweighed or obese. After the 6-month nutrition intervention program, BCP lost 3.1 kg (p < 0.01) of body weight, 2.7 kg (p < 0.01) of fat-mass, 400 g (p < 0.01) of abdominal fat, 118 g (p < 0.05) of visceral fat, 1.2 kg/m2 of body mass index and 1.1 kg/m2 of fat mass index (p < 0.01). During the period, no changes were observed in bone mineral density (p = 0.3), fat-free mass (p = 0.1) and appendicular skeletal muscle mass (p = 0.2). Menopausal status in BCP did not modify the effect of the nutrition intervention. CONCLUSIONS: The individualized food-based nutrition intervention program empowered BCP to make informed healthy food choices within their personal preferences, socioeconomic and cultural background. With this type of intervention, nonmetastatic BCP reduced body weight, fat-mass, fat mass index, visceral and abdominal fat, while preserving skeletal muscle mass, during antineoplastic treatment. ClinicalTrials.govNCT03625635.

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

OBJECTIVE: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective. BACKGROUND: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature. STUDY DESIGN: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival. RESULTS: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT. CONCLUSION: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.

Microcirugía de las fístulas durales arteriovenosas espinales, más un repaso de la anatomía vascular vertebromedular / Microsurgery of spinal dural arteriovenous fistulas, plus a review of the vertebromedullary vascular anatomy

Introducción: la fístula dural arteriovenosa espinal (FDAVE) es una enfermedad vascular rara, de etiología desconocida y frecuentemente subdiagnosticada. El tratamiento puede ser microquirúrgico o endovascular. Material y Método: Análisis retrospectivo de una serie de 8 pacientes consecutivos con FDAVE tratados por microcirugía entre 2010 y 2020. Fueron evaluados parámetros como edad, sexo, cuadro clínico pre y postoperatorio medido con las escalas de Aminoff-Logue y Rankin modificada. Los estudios diagnósticos con RMN (Resonancia Magnética Nuclear), ARM (Angio Resonancia Magnética) y ADM (Angiografía Digital Medular) se utilizaron para determinar nivel lesional y resultados quirúrgicos. Resultados: Fueron operados 8 pacientes (7 masculinos y 1 femenino) con un promedio de edad de 58 años. El tiempo de evolución del cuadro clínico al diagnóstico fue menor a 12 meses salvo un caso de 32 meses. Las FDAVE fueron localizadas en: 6 a nivel dorsal entre D6 y D12, una en L2 y la última en S1 (5 derechas y 3 izquierdas). La arteria de Adamkiewicz se identificó en: 4 casos en L1, 2 en D12, 1 en D10 y un caso en D7 (6 izquierdas y 2 derechas). De los 8 pacientes operados, 3 fueron embolizados previamente. La evolución postoperatoria del cuadro neurológico fue: 2 de 8 permanecieron estables y 6 de 8 mejoraron uno o más puntos en la escala de Rankin modificada; no hubo complicaciones en el postoperatorio. Todos los pacientes mejoraron las imágenes en RMN diferida y la ADM luego de los 6 meses fue negativa. El seguimiento promedio fue de 48 meses con un rango de 11 a 116 meses, ningún paciente presentó recidiva de la FDAVE. Conclusiones: El tratamiento quirúrgico de las FDAVE es un método muy eficaz, de baja morbilidad y menor tasa de recurrencia comparado con el tratamiento endovascular.

Introduction: Spinal dural arteriovenous fistula (SDAVF) is a rare vascular disease, of unknown etiology and frequently underdiagnosed. Treatment can be microsurgical or endovascular. Material and Method: Retrospective analysis of a series of 8 SDAVF patients treated by microsurgery between 2010 and 2020. Parameters including age, sex, pre and postoperative clinical condition were analyzed according to modified Aminoff-Logue and modified Rankin scales. Diagnostic studies such as MRI (Magnetic Resonance Imaging), MRA (Magnetic Resonance Angiogram) and spinal DSA (Digital Subtraction Angiography), were evaluated for lesion level, as were surgical results. Results: Eight patients (7 male and 1 female), average age of 58 years were operated. The interval from symptom onset to diagnosis was less than 12 months in all cases except one (32 months). SDAVF locations were thoracic in 6 cases between T6 and T12, at L2 in one and at S1 in one case (5 on the right and 3 on the left). The Adamkiewicz artery was identified in: 4 cases at L1, 2 at D12, 1 at D10 and in one case at D7 (6 left-sided and 2 right-sided). Three of the 8 patients operated had undergone prior embolization. Postoperative neurological outcomes showed: 2 patients remained stable and 6 had improved one or more points on the modified Rankin scale; no postoperative complications were observed. Follow-up MRI images improved in all cases and spinal DSA was negative at six months. Average follow-up was 48 months (range 11 to 116 months), no patient presented recurrence. Conclusions: Microsurgical treatment of SDAVF proved to be efficient, with low morbidity and lower recurrence rates compared to endovascular results.

Surgical Treatment of Post-traumatic Elbow Stiffness by Wide Posterior Approach.

Objective To demonstrate the clinical outcomes and complication rates of the surgical release with a single posterior approach in the treatment of post-traumatic elbow stiffness. Methods A prospective study with patients submitted to surgery between May 2013 and June 2018 in a single center. The access to the elbow was made through the posterior approach. The patients were followed up by an occupational therapy team, and were submitted to a standardized rehabilitation protocol, with static progressive orthoses and dynamic orthoses. The primary outcome was the range of flexion-extension of the elbow after 6 months. Results A total of 26 patients completed the minimum follow-up of 6-months. The mean range of flexion-extension of the elbow at the end of 6 months was of 98.3 ± 22.0°, with an amplitude gain of 40.0 ± 14.0° in relation to the pre-operative period ( p < 0.001). The average flexion-extension gain at the end of 6 months was of 51.7% ± 17.1% ( p < 0.001). The mean pronosupination at the end of 6 months was of 129.0 ± 42.7° ( p < 0.001). Half of the cases had moderate and severe stiffness in the pre-operative period, compared with 7.7% at 6 months post-operatively ( p < 0.001). The mean score for the Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) instruments was 74.4 ± 16.8 points and 31.7 ± 21.9 points respectively ( p < 0.001 for both). The visual analogue scale (VAS) score presented no statistically significant difference compared to the pre-operative period ( p = 0.096). Complications were observed in 6 (23%) patients, and no new surgical procedures were necessary. Conclusions The surgical release of the elbow associated with a rehabilitation protocol is a safe technique, with satisfactory results and low rate of complications.

Surgical Treatment of Post-traumatic Elbow Stiffness by Wide Posterior Approach / Tratamento cirúrgico da rigidez pós-traumática do cotovelo por via posterior ampla

Abstract Objective To demonstrate the clinical outcomes and complication rates of the surgical release with a single posterior approach in the treatment of post-traumatic elbow stiffness. Methods A prospective study with patients submitted to surgery between May 2013 and June 2018 in a single center. The access to the elbow was made through the posterior approach. The patients were followed up by an occupational therapy team, and were submitted to a standardized rehabilitation protocol, with static progressive orthoses and dynamic orthoses. The primary outcome was the range of flexion-extension of the elbow after 6 months. Results A total of 26 patients completed the minimum follow-up of 6-months. The mean range of flexion-extension of the elbow at the end of 6 months was of 98.3 ± 22.0°, with an amplitude gain of 40.0 ± 14.0° in relation to the pre-operative period (p< 0.001). The average flexion-extension gain at the end of 6 months was of 51.7% ± 17.1% (p< 0.001). The mean pronosupination at the end of 6 months was of 129.0 ± 42.7° (p< 0.001). Half of the cases had moderate and severe stiffness in the pre-operative period, compared with 7.7% at 6 months post-operatively (p< 0.001). The mean score for the Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) instruments was 74.4 ± 16.8 points and 31.7 ± 21.9 points respectively (p< 0.001 for both). The visual analogue scale (VAS) score presented no statistically significant difference compared to the pre-operative period (p= 0.096). Complications were observed in 6 (23%) patients, and no new surgical procedures were necessary. Conclusions The surgical release of the elbow associated with a rehabilitation protocol is a safe technique, with satisfactory results and low rate of complications.

Resumo Objetivo Demonstrar os resultados clínicos e a taxa de complicações da liberação cirúrgica por via única posterior no tratamento da rigidez pós-traumática de cotovelo. Métodos Estudo prospectivo, com pacientes submetidos a cirurgia entre maio de 2013 e junho de 2018 em um único centro. Foi realizado acesso ao cotovelo por via posterior. O seguimento dos pacientes foi feito por uma equipe de terapia ocupacional, e eles foram submetidos a um protocolo de reabilitação padronizado, com órteses estáticas progressivas e dinâmicas. O desfecho primário foi a amplitude de flexoextensão do cotovelo após 6 meses. Resultados Um total de 26 pacientes completaram o seguimento mínimo de 6 meses. A média de flexoextensão do cotovelo, ao final de 6 meses, foi de 98,3° ± 22,0°, com um ganho de amplitude de 40,0° ± 14,0° em relação ao pré-operatório (p< 0,001). A média de ganho relativo de flexoextensão, ao final de 6 meses, foi de 51,7% ± 17,1% (p< 0,001). A média de pronossupinação, ao final de 6 meses, foi de 129,0° ± 42,7° (p< 0,001). Metade dos casos apresentava rigidez moderada e grave no pré-operatório, contra 7,7% aos 6 meses de pós-operatório (p< 0,001). A pontuação nos instrumentos Mayo Elbow Performance Score (MEPS) e Disabilities of the Arm, Shoulder and Hand (DASH) apresentou melhora estatisticamente significativa em relação ao pré-operatório, atingindo 74,4 ± 16,8 pontos e 31,7 ± 21,9 pontos, respectivamente. A escala visual analógica (EVA) não apresentou diferença estatisticamente significativa em relação ao pré-operatório (p= 0,096). Complicações foram observadas em 6 (23%) pacientes, não sendo necessária nova abordagem cirúrgica em nenhum paciente. Conclusões A liberação cirúrgica do cotovelo associada a protocolo de reabilitação é técnica segura, com resultados satisfatórios e baixa taxa de complicações.

Canonical ErbB-2 isoform and ErbB-2 variant c located in the nucleus drive triple negative breast cancer growth.

Triple negative breast cancer (TNBC) refers to tumors that do not express clinically significant levels of estrogen and progesterone receptors, and lack membrane overexpression or gene amplification of ErbB-2/HER2, a receptor tyrosine kinase. Transcriptome and proteome heterogeneity of TNBC poses a major challenge to precision medicine. Clinical biomarkers and targeted therapies for this disease remain elusive, so chemotherapy has been the standard of care for early and metastatic TNBC. Our present findings placed ErbB-2 in an unanticipated scenario: the nucleus of TNBC (NErbB-2). Our study on ErbB-2 alternative splicing events, using a PCR-sequencing approach combined with an RNA interference strategy, revealed that TNBC cells express either the canonical (wild-type) ErbB-2, encoded by transcript variant 1, or the non-canonical ErbB-2 isoform c, encoded by alternative variant 3 (RefSeq), or both. These ErbB-2 isoforms function in the nucleus as transcription factors. Evicting both from the nucleus or silencing isoform c only, blocks TN cell and tumor growth. This reveals not only NErbB-2 canonical and alternative isoforms role as targets of therapy in TNBC, but also isoform c dominant oncogenic potential. Furthermore, we validated our findings in the clinic and observed that NErbB-2 correlates with poor prognosis in primary TN tumors, disclosing NErbB-2 as a novel biomarker for TNBC. Our discoveries challenge the present scenario of drug development for personalized BC medicine that focuses on wild-type RefSeq proteins, which conserve the canonical domains and are located in their classical cellular compartments.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Randomized trial for the treatment of post-traumatic elbow stiffness: surgical release vs. rehabilitation.

BACKGROUND: There are no previous randomized trials comparing surgical to conservative treatment for post-traumatic elbow stiffness. The aim of our study was to compare elbow range of motion (ROM) and clinical outcomes among patients undergoing surgical treatment or a standardized rehabilitation for post-traumatic elbow stiffness. METHODS: Randomized clinical trial of patients with post-traumatic elbow stiffness for more than 6 months who failed conventional physical therapy for 4 months. Patients were randomized into 2 treatment groups. The conservative group underwent the rehabilitation protocol associated with the use of orthoses (static progressive for extension and dynamic for flexion) and continuous passive motion. The surgical group underwent surgical release by a posterior approach without triceps detachment, followed by a rehabilitation protocol similar to the conservative group. The primary outcome of the study was flexion-extension ROM at 6 months of follow-up. Secondary outcomes included the visual analog scale for pain, the Mayo Elbow Performance Score, the Disabilities of the Arm, Shoulder, and Hand score, absolute and relative increase in flexion-extension ROM, and complication rates. RESULTS: Thirty patients were analyzed in the study, 15 in each group. The mean elbow flexion-extension ROM at the end of 6 months of follow-up was 108° in the surgical group and 88° in the conservative group (P = .002). The mean absolute and the relative increase of elbow flexion-extension at 6 months were, respectively, 17° and 27% in the conservative group and 41° and 59% in the surgical group (P < .001). CONCLUSION: Surgical elbow release associated with the rehabilitation protocol resulted in a greater flexion-extension ROM, as well as a greater absolute and relative increase compared with rehabilitation alone at 6 months of follow-up. The groups did not differ regarding clinical scores and complication rates.

Nuclear PDCD4 Expression Defines a Subset of Luminal B-Like Breast Cancers with Good Prognosis.

The hormone receptor-positive (estrogen and/or progesterone receptor (PR)-positive) and HER2-negative breast cancer (BC) subtype is a biologically heterogeneous entity that includes luminal A-like (LumA-like) and luminal B-like (LumB-like) subtypes. Decreased PR levels is a distinctive biological feature of LumB-like tumors. These tumors also show reduced sensitivity to endocrine therapies and poorer prognosis than LumA-like tumors. Identification of biomarkers to accurately predict disease relapse in these subtypes is crucial in order to select effective therapies. We identified the tumor suppressor PDCD4 (programmed cell death 4), located in the nucleus (NPDCD4), as an independent prognostic factor of good clinical outcome in LumA-like and LumB-like subtypes. NPDCD4-positive LumB-like tumors presented overall and disease-free survival rates comparable to those of NPDCD4-positive LumA-like tumors, indicating that NPDCD4 improves the outcome of LumB-like patients. In contrast, NPDCD4 loss increased the risk of disease recurrence and death in LumB-like compared with LumA-like tumors. This, along with our results showing that LumB-like tumors present lower NPDCD4 positivity than LumA-like tumors, suggests that NPDCD4 loss contributes to endocrine therapy resistance in LumB-like BCs. We also revealed that PR induces PDCD4 transcription in LumB-like BC, providing a mechanistic explanation to the low PDCD4 levels in LumB-like BCs lacking PR. Finally, PDCD4 silencing enhanced BC cell survival in a patient-derived explant model of LumB-like disease. Our discoveries highlight NPDCD4 as a novel biomarker in LumA- and LumB-like subtypes, which could be included in the panel of immunohistochemical markers used in the clinic to accurately predict the prognosis of LumB-like tumors.

Blockade of Stat3 oncogene addiction induces cellular senescence and reveals a cell-nonautonomous activity suitable for cancer immunotherapy.

Stat3 is constitutively activated in several tumor types and plays an essential role in maintaining their malignant phenotype and immunosupression. To take advantage of the promising antitumor activity of Stat3 targeting, it is vital to understand the mechanism by which Stat3 regulates both cell autonomous and non-autonomous processes. Here, we demonstrated that turning off Stat3 constitutive activation in different cancer cell types induces senescence, thus revealing their Stat3 addiction. Taking advantage of the senescence-associated secretory phenotype (SASP) induced by Stat3 silencing (SASP-siStat3), we designed an immunotherapy. The administration of SASP-siStat3 immunotherapy induced a strong inhibition of triple-negative breast cancer and melanoma growth associated with activation of CD4 + T and NK cells. Combining this immunotherapy with anti-PD-1 antibody resulted in survival improvement in mice bearing melanoma. The characterization of the SASP components revealed that type I IFN-related mediators, triggered by the activation of the cyclic GMP-AMP synthase DNA sensing pathway, are important for its immunosurveillance activity. Overall, our findings provided evidence that administration of SASP-siStat3 or low dose of Stat3-blocking agents would benefit patients with Stat3-addicted tumors to unleash an antitumor immune response and to improve the effectiveness of immune checkpoint inhibitors.