Epidemiology of marine turtle fibropapillomatosis and tumour-associated chelonid alphaherpesvirus 5 (ChHV5; Scutavirus chelonidalpha5) in North-Western Mexico: a scoping review implementing the one health approach.

Fibropapillomatosis (FP) - tumour-associated chelonid alphaherpesvirus 5 (ChHV5; Scutavirus chelonidalpha5) - is a disease that affect marine turtles around the world, and characterized by the formation of cutaneous tumours that can appear anywhere on the body. We carried out a thorough literature search (from 1990 to 2024) in the feeding sites of North-western Mexico, a region that hosts important habitats for feeding, development, and reproduction for five of the seven existing sea turtle species. We found 18 reports recording a total of 32 cases of FP and/or ChHV5/Scutavirus chelonidalpha5 in coastal and insular areas of North-western Mexico. Baja California Sur resulted with the highest number of cases (75%). While the first case of ChHV5/Scutavirus chelonidalpha5 infection was reported in 2004, the presence of FP tumours was reported in 2014 and became more frequent between 2019 and 2024. The affected species were black, Chelonia mydas (50%), olive ridley, Lepidochelys olivacea (46.8%) and loggerhead turtles, Caretta caretta (3.2%). Tumours occurred mainly in anterior flippers (46.1%) and neck (22.5%), and most had a nodular and verrucous appearance with a rough surface. In the study region, there is a potential sign of the emergence of the ChHV5/Scutavirus chelonidalpha5 infections and FP disease during the last 20 years, with a rapid increase during the last 10 years. As long as infections by ChHV5/Scutavirus chelonidalpha5 and the prevalence of the FP disease may be potentially influenced by anthropogenic activities, a One Health approach is needed to understand and improve sea turtles' health.

HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is one of the deadliest forms of cancer with limited therapy options. Overexpression of the heat shock protein 70 (HSP70) is a hallmark of cancer that is strongly associated with aggressive disease and worse clinical outcomes. However, the underlying mechanisms by which HSP70 allows tumor cells to thrive under conditions of continuous stress have not been fully described. Here, we report that PDAC has the highest expression of HSP70 relative to normal tissue across all cancers analyzed. Furthermore, HSP70 expression is associated with tumor grade and is further enhanced in metastatic PDAC. We show that genetic or therapeutic ablation of HSP70 alters mitochondrial subcellular localization, impairs mitochondrial dynamics, and promotes mitochondrial swelling to induce apoptosis. Mechanistically, we find that targeting HSP70 suppresses the PTEN-induced kinase 1 (PINK1) mediated phosphorylation of dynamin-related protein 1 (DRP1). Treatment with the HSP70 inhibitor AP-4-139B was efficacious as a single agent in primary and metastatic mouse models of PDAC. In addition, we demonstrate that HSP70 inhibition promotes the AMP-activated protein kinase (AMPK) mediated phosphorylation of Beclin-1, a key regulator of autophagic flux. Accordingly, we find that the autophagy inhibitor hydroxychloroquine (HCQ) enhances the ability of AP-4-139B to mediate anti-tumor activity in vivo. Collectively, our results suggest that HSP70 is a multi-functional driver of tumorigenesis that orchestrates mitochondrial dynamics and autophagy. Moreover, these findings support the rationale for concurrent inhibition of HSP70 and autophagy as a novel therapeutic approach for HSP70-driven PDAC.

Novel Spirocyclic Dimer, SpiD3, Targets Chronic Lymphocytic Leukemia Survival Pathways with Potent Preclinical Effects.

Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) have enhanced patient survival. However, resistance mechanisms wherein tumor cells bypass BTK inhibition through acquired BTK mutations, and/or activation of alternative survival mechanisms have rendered ibrutinib ineffective, imposing the need for novel therapeutics. We evaluated SpiD3, a novel spirocyclic dimer, in CLL cell lines, patient-derived CLL samples, ibrutinib-resistant CLL cells, and in the Eµ-TCL1 mouse model. Our integrated multi-omics and functional analyses revealed BCR signaling, NFκB signaling, and endoplasmic reticulum stress among the top pathways modulated by SpiD3. This was accompanied by marked upregulation of the UPR and inhibition of global protein synthesis in CLL cell lines and patient-derived CLL cells. In ibrutinib-resistant CLL cells, SpiD3 retained its antileukemic effects, mirrored in reduced activation of key proliferative pathways (e.g., PRAS, ERK, MYC). Translationally, we observed reduced tumor burden in SpiD3-treated Eµ-TCL1 mice. Our findings reveal that SpiD3 exploits critical vulnerabilities in CLL cells including NFκB signaling and the UPR, culminating in profound antitumor properties independent of TME stimuli. SIGNIFICANCE: SpiD3 demonstrates cytotoxicity in CLL partially through inhibition of NFκB signaling independent of tumor-supportive stimuli. By inducing the accumulation of unfolded proteins, SpiD3 activates the UPR and hinders protein synthesis in CLL cells. Overall, SpiD3 exploits critical CLL vulnerabilities (i.e., the NFκB pathway and UPR) highlighting its use in drug-resistant CLL.

High affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells.

Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T-cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28 activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3+ CAR Tregs uniquely acquiring CD40L surface expression and producing IFNγ. Interestingly, decreasing CAR antigen affinity reduced Teff cell gene expression and inflammatory cytokine production by CAR Tregs. Our findings showcase the impact of engineered receptor activation on Treg biology and support tailoring CAR constructs to Tregs for maximal therapeutic efficacy.

Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Planetary health education in the United States: four curricular models, one goal.

Global environmental crises demand scaled-up investment in education about planetary health. We identified college and university programs in the United States that focus on the human-animal-ecosystem nexus by systematically searching the 2023-2024 catalogs of more than 1000 schools. We identified four frequently-used curricular models: (1) One Health programs offered by universities with veterinary and agriculture schools that emphasize zoonotic diseases, antimicrobial resistance, food safety, and wildlife conservation; (2) climate change and health (climate medicine) programs for graduate and professional students at large universities with medical and public health schools; (3) global environmental public health programs focused on pollution and other exposures; and (4) sustainability and health programs emphasizing food security, environmental justice, and other health issues that can be improved with ethical design and engineering. Highlighting the shared goals of these distinct academic models may help make planetary health a more visible area of teaching, research, and practice.

Role of the clinical radiopharmacist in patient safety during myocardial perfusion imaging with vasodilator stress agents.

AIM: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. METHODS: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. RESULTS: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% - measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% - consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% - use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% - use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% - reassessment of patient's condition; acute exacerbation of COPD 0.8% - defer test until acute episode is over; severe asthma 0.4% - do not perform test; methylxanthine ingestion 0.3% - avoid consumption previously; other 6.1% - evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. CONCLUSIONS: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.

Immunogenicity in renal cell carcinoma: shifting focus to alternative sources of tumour-specific antigens.

Renal cell carcinoma (RCC) comprises a group of malignancies arising from the kidney with unique tumour-specific antigen (TSA) signatures that can trigger cytotoxic immunity. Two classes of TSAs are now considered potential drivers of immunogenicity in RCC: small-scale insertions and deletions (INDELs) that result in coding frameshift mutations, and activation of human endogenous retroviruses. The presence of neoantigen-specific T cells is a hallmark of solid tumours with a high mutagenic burden, which typically have abundant TSAs owing to non-synonymous single nucleotide variations within the genome. However, RCC exhibits high cytotoxic T cell reactivity despite only having an intermediate non-synonymous single nucleotide variation mutational burden. Instead, RCC tumours have a high pan-cancer proportion of INDEL frameshift mutations, and coding frameshift INDELs are associated with high immunogenicity. Moreover, cytotoxic T cells in RCC subtypes seem to recognize tumour-specific endogenous retrovirus epitopes, whose presence is associated with clinical responses to immune checkpoint blockade therapy. Here, we review the distinct molecular landscapes in RCC that promote immunogenic responses, discuss clinical opportunities for discovery of biomarkers that can inform therapeutic immune checkpoint blockade strategies, and identify gaps in knowledge for future investigations.

Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER+/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.

Estudio bibliométrico de las publicaciones en cirugía de columna en México / Publications on spine surgery in Mexico: a bibliometric study

Resumen: Introducción: el análisis bi-bliométrico es una forma útil de evaluar el pasado, el pre-sente y el futuro de las publicaciones relacionadas con un área determinada de forma cualitativa y cuantitativa. Objetivo: determinar las características de la productividad nacional en investigación escrita por autores mexicanos en el campo de cirugía de columna a través del tiempo. Material y métodos: se realizó una búsqueda exhaustiva en línea en Octubre de 2021 utilizando la base de datos Scopus desarrollada por Elsevier. La información de las publicaciones recolectadas fue la siguiente: año, título, acceso, idioma, revista, tipo de artículo, tema, objetivo, citas, autores e instituciones de afiliación. Resultados: se identificó un total de 404 publicaciones entre 1973 y 2021. El número de publicaciones entre la década 1991-2000 y 2011-2021 incrementó 68.28 veces. La mayoría de las publicaciones se realizaron en instituciones de la región centro-sur de México (66.16%), seguida de la región occidente (15.03%) y noreste (8.27%). El índice H más alto encontrado fue de revistas de origen estadounidense (102). La mayor parte de las publicaciones se realizó en la revista Coluna/Columna (15.53%), seguida de Cirugía y Cirujanos (10.52%) y de Acta Ortopédica Mexicana (8.52%). La institución con la más alta productividad fue el Instituto Nacional de Rehabilitación «Luis Guillermo Ibarra Ibarra¼ (17.57%), seguida del Centro Médico Nacional de Occidente del IMSS (6.67%) y del Centro Médico ABC (5.44%). Conclusiones: el número de artículos publicados en el campo de cirugía de columna ha incrementado rápidamente en los últimos 15 años. Las publicaciones escritas en inglés son las más citadas. La distribución geográfica de la investigación en este campo en México está centralizada, realizándose la mayor parte de las publicaciones en la región centro-sur del país (66.16%).

Abstract: Introduction: bibliometric analysis is a useful way of assessing the past, present and future publications related to a given area in a qualitative and quantitative way. Objective: to determine characteristics of national authors productivity in the field of spine surgery research across the time. Material and methods: an online research was performed using the Elsevier´s database Scopus in October, 2021. All studies were assessed for the following parameters: year, title, access, language, journal, type of article, focus of research, objective of research, cites, authors and institutions. Results: a total of 404 publications were identified between 1973 and 2021. Between 1991-2000 decade to 2011-2021 decade the number of published articles tended to increase by 68.28 times. The largest number of articles was from South-Central Region (66.16%), followed by Western (15.03%) and Northwest (8.27%). The highest h-index was found for USA journals (102). The highest number of articles was published in Coluna/Columna (15.53%), followed by Cirugía y Cirujanos (10.52%) and Acta Ortopédica Mexicana (8.52%). Instituto Nacional de Rehabilitación published the largest number of articles (17.57%), followed by Centro Médico Nacional de Occidente del IMSS (6.67%) and Centro Médico ABC (5.44%). Conclusions: the number of articles published in the field of spine surgery in Mexico has increased rapidly in the past 15 years. In terms of quality, publications written in English are the most cited. The geographical distribution of research in Mexico is centralized, the largest number of publications was from South-Central Region of Mexico.

Biomecánica de la interfaz hueso-tornillo en instrumentación transpedicular de columna / Biomechanics of the bone-screw interface in transpedicular spinal instrumentation

Resumen: El aflojamiento de los implantes, la falla catastrófica de la interfaz hueso-tornillo, la migración de material y la pérdida de estabilidad de los componentes del ensamble de la fijación constituyen una seria complicación en la cirugía de columna de adultos. La contribución de la biomecánica se basa en la medición experimental y la simulación de las fijaciones transpediculares de columna. La trayectoria de inserción cortical mostró un incremento en la resistencia de la interfase tornillo-hueso respecto a la inserción pedicular tanto para fuerzas de tracción axiales al tornillo como en distribución de esfuerzos en la vértebra. Los tornillos de doble rosca tuvieron una resistencia similar a los pediculares estándar. Los tornillos de rosca parcial de cuatro filetes mostraron mejor resistencia a la fatiga en cuanto a mayor carga de rotura y número de ciclos para la falla. Los tornillos aumentados, ya sea con cemento o hidroxiapatita mejoraron también la resistencia a la fatiga en vértebras osteoporóticas. Las simulaciones de segmentos rígidos confirmaron la presencia de esfuerzos superiores en los discos intervertebrales que provocan el daño de los segmentos adyacentes. La parte posterior de las vértebras puede estar sometida a mayores esfuerzos, fundamentalmente en la superficie de la interfaz hueso-tornillo, por lo que son más susceptibles a la falla en esta región.

Abstract: Implant loosening, catastrophic failure of the bone-screw interface, material migration, and loss of stability of the fixation component assembly constitute a serious complication in adult spinal surgery. The contribution of biomechanics is based on experimental measurement and simulation of transpedicular spinal fixations. The cortical insertion trajectory showed an increase in the resistance of the screw-bone interface with respect to the pedicle insertion trajectory, both for axial traction forces to the screw and for stress distribution in the vertebra. The double-threaded screws and standard pedicle screws had similar strength. Partially threaded screws with four-thread showed better resistance to fatigue in terms of a higher failure load and number of cycles to fail. Cement or hydroxyapatite augmented screws with also showed a better fatigue resistance in osteoporotic vertebrae. Rigid segment simulations confirmed the presence of higher stresses on the intervertebral discs causing damage to adjacent segments. The posterior body of the vertebra may be subjected to high stresses, in the bone-screw interface, being this bone region more susceptible to failure.

Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7 ±â€¯11.4 years. Tumor size: 34.1 ±â€¯14.6 mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7 ±â€¯111.2 cm3. Of the 5 s local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.

Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study. / Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018.

INTRODUCTION: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. MATERIAL AND METHODS: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. RESULTS: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. CONCLUSIONS: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgroup.

[Publications on spine surgery in Mexico: a bibliometric study]. / Estudio bibliométrico de las publicaciones en cirugía de columna en México.

INTRODUCTION: bibliometric analysis is a useful way of assessing the past, present and future publications related to a given area in a qualitative and quantitative way. OBJECTIVE: to determine characteristics of national authors productivity in the field of spine surgery research across the time. MATERIAL AND METHODS: an online research was performed using the Elsevier´s database Scopus in October, 2021. All studies were assessed for the following parameters: year, title, access, language, journal, type of article, focus of research, objective of research, cites, authors and institutions. RESULTS: a total of 404 publications were identified between 1973 and 2021. Between 1991-2000 decade to 2011-2021 decade the number of published articles tended to increase by 68.28 times. The largest number of articles was from South-Central Region (66.16%), followed by Western (15.03%) and Northwest (8.27%). The highest h-index was found for USA journals (102). The highest number of articles was published in Coluna/Columna (15.53%), followed by Cirugía y Cirujanos (10.52%) and Acta Ortopédica Mexicana (8.52%). Instituto Nacional de Rehabilitación published the largest number of articles (17.57%), followed by Centro Médico Nacional de Occidente del IMSS (6.67%) and Centro Médico ABC (5.44%). CONCLUSIONS: the number of articles published in the field of spine surgery in Mexico has increased rapidly in the past 15 years. In terms of quality, publications written in English are the most cited. The geographical distribution of research in Mexico is centralized, the largest number of publications was from South-Central Region of Mexico.

INTRODUCCIÓN: el análisis bi­bliométrico es una forma útil de evaluar el pasado, el pre­sente y el futuro de las publicaciones relacionadas con un área determinada de forma cualitativa y cuantitativa. OBJETIVO: determinar las características de la productividad nacional en investigación escrita por autores mexicanos en el campo de cirugía de columna a través del tiempo. MATERIAL Y MÉTODOS: se realizó una búsqueda exhaustiva en línea en Octubre de 2021 utilizando la base de datos Scopus desarrollada por Elsevier. La información de las publicaciones recolectadas fue la siguiente: año, título, acceso, idioma, revista, tipo de artículo, tema, objetivo, citas, autores e instituciones de afiliación. RESULTADOS: se identificó un total de 404 publicaciones entre 1973 y 2021. El número de publicaciones entre la década 1991-2000 y 2011-2021 incrementó 68.28 veces. La mayoría de las publicaciones se realizaron en instituciones de la región centro-sur de México (66.16%), seguida de la región occidente (15.03%) y noreste (8.27%). El índice H más alto encontrado fue de revistas de origen estadounidense (102). La mayor parte de las publicaciones se realizó en la revista Coluna/Columna (15.53%), seguida de Cirugía y Cirujanos (10.52%) y de Acta Ortopédica Mexicana (8.52%). La institución con la más alta productividad fue el Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra" (17.57%), seguida del Centro Médico Nacional de Occidente del IMSS (6.67%) y del Centro Médico ABC (5.44%). CONCLUSIONES: el número de artículos publicados en el campo de cirugía de columna ha incrementado rápidamente en los últimos 15 años. Las publicaciones escritas en inglés son las más citadas. La distribución geográfica de la investigación en este campo en México está centralizada, realizándose la mayor parte de las publicaciones en la región centro-sur del país (66.16%).

[Biomechanics of the bone-screw interface in transpedicular spinal instrumentation]. / Biomecánica de la interfaz hueso-tornillo en instrumentación transpedicular de columna.

Implant loosening, catastrophic failure of the bone-screw interface, material migration, and loss of stability of the fixation component assembly constitute a serious complication in adult spinal surgery. The contribution of biomechanics is based on experimental measurement and simulation of transpedicular spinal fixations. The cortical insertion trajectory showed an increase in the resistance of the screw-bone interface with respect to the pedicle insertion trajectory, both for axial traction forces to the screw and for stress distribution in the vertebra. The double-threaded screws and standard pedicle screws had similar strength. Partially threaded screws with four-thread showed better resistance to fatigue in terms of a higher failure load and number of cycles to fail. Cement or hydroxyapatite augmented screws with also showed a better fatigue resistance in osteoporotic vertebrae. Rigid segment simulations confirmed the presence of higher stresses on the intervertebral discs causing damage to adjacent segments. The posterior body of the vertebra may be subjected to high stresses, in the bone-screw interface, being this bone region more susceptible to failure.

El aflojamiento de los implantes, la falla catastrófica de la interfaz hueso-tornillo, la migración de material y la pérdida de estabilidad de los componentes del ensamble de la fijación constituyen una seria complicación en la cirugía de columna de adultos. La contribución de la biomecánica se basa en la medición experimental y la simulación de las fijaciones transpediculares de columna. La trayectoria de inserción cortical mostró un incremento en la resistencia de la interfase tornillo-hueso respecto a la inserción pedicular tanto para fuerzas de tracción axiales al tornillo como en distribución de esfuerzos en la vértebra. Los tornillos de doble rosca tuvieron una resistencia similar a los pediculares estándar. Los tornillos de rosca parcial de cuatro filetes mostraron mejor resistencia a la fatiga en cuanto a mayor carga de rotura y número de ciclos para la falla. Los tornillos aumentados, ya sea con cemento o hidroxiapatita mejoraron también la resistencia a la fatiga en vértebras osteoporóticas. Las simulaciones de segmentos rígidos confirmaron la presencia de esfuerzos superiores en los discos intervertebrales que provocan el daño de los segmentos adyacentes. La parte posterior de las vértebras puede estar sometida a mayores esfuerzos, fundamentalmente en la superficie de la interfaz hueso-tornillo, por lo que son más susceptibles a la falla en esta región.

The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma.

INTRODUCTION: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT: Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS: MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.

Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy. / Cirugía radioguiada con semillas de yodo-125 en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante.

OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.

Lumbar degenerative spondylolisthesis II: treatment and controversies / Espondilolistesis degenerativa lumbar II: tratamiento y controversias

Abstract: There are various approaches and surgical techniques with the objective of nerve root decompression, restrict mobility, and fusion of the listhesis. Among the techniques, posterior interbody fusion combines direct and indirect root decompression with the fusion between vertebral bodies, placing an autologous bone graft between transverse apophysis and vertebral bodies. Transforaminal lumbar and posterior interbody fusion, on the same way, look to decompress and fuse but with a different approach to the spine. The anterior approach for interbody fusion provides a better fusion rate. Lateral lumbar interbody fusion is considered less invasive, with an anterolateral transpsoas approach. The lumbar fusion technique in degenerative spondylolisthesis must be individualized. Non-fusion decompression is considered a less invasive procedure. Various studies suggest that decompression has better results when fusion is added. Surgery had several potential benefits and greater improvement in those patients who fail conservative management. An optimal technique is not conclusively identified.

Resumen: El tratamiento de la espondilolistesis degenerativa lumbar es específico para cada etapa de la enfermedad y el manejo quirúrgico no debe de ser la primera elección en la mayoría de los casos. El manejo conservador está basado en el uso de antiinflamatorios no esteroideos, control de peso y rehabilitación. En caso de falla después de cuatro a seis semanas, el siguiente paso es la infiltración facetaria. En caso de dolor persistente, alteraciones neurológicas o claudicación neurogénica el siguiente paso es la cirugía. Existen varios abordajes y técnicas quirúrgicas con el objetivo de descomprimir las raíces nerviosas, restringir la movilidad y fusionar la listesis. Entre las técnicas quirúrgicas, la fusión posterior combina la descompresión directa e indirecta con artrodesis entre los cuerpos vertebrales, colocando injerto entre las apófisis transversas y los cuerpos vertebrales. La artrodesis intersomática transforaminal y posterior buscan de la misma manera la descompresión y fusión, pero con un abordaje distinto. El abordaje anterior para artrodesis intersomática provee la mejor tasa de fusión. La artrodesis intersomática lateral se considera un procedimiento menos invasivo, con un abordaje anterolateral transpsoas. La técnica de artrodesis lumbar en la espondilolistesis debe ser individualizada. La descompresión sin artrodesis se considera un procedimiento menos invasivo; varios estudios sugieren que la descompresión tiene mejores resultados cuando se agrega una artrodesis. La cirugía tiene múltiples beneficios posibles en pacientes en quienes el tratamiento conservador ha fallado. No se ha identificado una técnica óptima de tratamiento.