Circumferential Inferior Vena Cavectomy Without Caval Replacement in the Management of Renal Cell Carcinoma with Tumor Thrombus.

PURPOSE OF REVIEW: Renal cell carcinoma presents a unique proclivity for vascular involvement giving rise to a peculiar form of locally advanced disease so-called tumor thrombus. To date, the only curative strategy for these cases remains surgery, which should aim to remove every vestige of macroscopic disease. Most of the preexisting literature advocates opening the vena cava to allow tumor thrombus removal and subsequent venous suture closure. However, inferior vena cava circumferential resection (cavectomy) without caval replacement is possible in the majority of cases since progressive occlusion facilitates the development of a collateral venous network aimed at maintaining cardiac preload. RECENT FINDINGS: Radical nephrectomy with tumor thrombectomy remains a surgical challenge not exempt of operative complications even in experienced hands. In opposition to what traditional cavotomy and thrombus withdrawal can offer, circumferential cavectomy without caval replacement would provide comparable or even better oncologic control, decrease the likelihood of operative bleeding, and prevent the development of perioperative pulmonary embolism. This review focuses on the rationale of circumferential IVC resection without caval replacement and the important technical aspects of this approach in cases of renal cell carcinoma with vascular involvement. We also include an initial report on the surgical outcomes of a contemporary series of patients managed under this approach at our center.

Comparative performance of vulvovaginal swab sampling versus endocervical sampling for the detection of Chlamydia, Gonorrhea, Mycoplasma genitalium, and Trichomoniasis: a cross-sectional study in Spain.

INTRODUCTION: The global increase in sexual transmitted infections (STI) makes it necessary to seek public health strategies that facilitate rapid and minimally invasive diagnosis. The objective was to evaluate the concordance between vaginal and endocervical samples for STI diagnosis. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out on vaginal and endocervical samples from women attended in our reference area with symptoms suggestive of vulvovaginitis or for STI screening during the study period. RESULTS: A total of 130 paired samples were analyzed; fifty-seven and 59 samples were positive for vaginal and endocervical specimens (Kappa index of 0.969 (Standard error = 0.022). The sensitivity of the vaginal samples was 96.5% (IC95%: 87.2-99.4), with a specificity of 100% (IC95%: 93.0-100). DISCUSSION: The introduction of STI screening in vaginal samples in our environment can facilitate rapid and effective diagnosis and allow early treatment of STI. Additionally, it facilitates sample collection and diagnosis in the community setting, essential for optimal screening.

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies.

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

[Medical-surgical complications and their impact on patients' return to work whilst follow-up major lower-limb amputations in Hospital del Trabajador in Santiago (HTS)]. / Complicaciones médico-quirúrgicas y su impacto en el retorno laboral durante el seguimiento de pacientes con amputación mayor de extremidades inferiores en el Hospital del Trabajador de Santiago (HTS).

INTRODUCTION: The presence of different complications whilst follow-up amputee patients reaches 10-80%. The main objective of this research is to assess the impact of these in the return-to-work of lower-limb traumatic amputation cases. MATERIALS AND METHODS: A retrospective cohort research was carried out. Clinic-demographic variables information was recollected in order to assess its linkage to different medical-surgical complications and functional outcomes. Survival curves were created to evaluate the return-to-work of patients with and without complications. RESULTS: A total of 46 patients, on average aged 45.7 years old (91.3% men, 71.7% without comorbidities), were included on this research. The most frequent level of amputation was transtibial (65.2%). Residual limb pain, phantom pain, dermatological-infectious complications and painful neuroma were registered in 80.4%, 58.7%, 50% y 30.4% of the cases respectively. Half of the patients had returned to their workplace after 2years of post-surgical follow-up. The return-to-work rates were significantly lower in patients suffering from residual limb pain (p=0.0083) and from painful neuroma (p=0.0051). CONCLUSION: Complications are frequent during traumatic-amputee patients' follow-up and, some of them, may impact on the return-to-work rate.

The MADS-box genes SOC1 and AGL24 antagonize XAL2 functions in Arabidopsis thaliana root development.

MADS-domain transcription factors play pivotal roles in numerous developmental processes in Arabidopsis thaliana. While their involvement in flowering transition and floral development has been extensively examined, their functions in root development remain relatively unexplored. Here, we explored the function and genetic interaction of three MADS-box genes (XAL2, SOC1 and AGL24) in primary root development. By analyzing loss-of-function and overexpression lines, we found that SOC1 and AGL24, both critical components in flowering transition, redundantly act as repressors of primary root growth as the loss of function of either SOC1 or AGL24 partially recovers the primary root growth, meristem cell number, cell production rate, and the length of fully elongated cells of the short-root mutant xal2-2. Furthermore, we observed that the simultaneous overexpression of AGL24 and SOC1 leads to short-root phenotypes, affecting meristem cell number and fully elongated cell size, whereas SOC1 overexpression is sufficient to affect columella stem cell differentiation. Additionally, qPCR analyses revealed that these genes exhibit distinct modes of transcriptional regulation in roots compared to what has been previously reported for aerial tissues. We identified 100 differentially expressed genes in xal2-2 roots by RNA-seq. Moreover, our findings revealed that the expression of certain genes involved in cell differentiation, as well as stress responses, which are either upregulated or downregulated in the xal2-2 mutant, reverted to WT levels in the absence of SOC1 or AGL24.

Spanish primary care in pediatric trauma (AITP) consensus: An AITP checklist. / Consenso AITP español: Una lista de verificación AITP.

INTRODUCTION: The course in Primary Care in Pediatric Trauma (ATIP in Spanish) has been taught in Spain since 1997, and there are currently 9 accredited training centers. Care of polytraumatized pediatric patients often takes place in an environment conducive to errors resulting from forgetfulness, which is why checklists - mnemonic tools widely used in industry and medicine - are particularly useful to avoid such errors. Although several checklists exist for pediatric trauma care, none have been developed within the setting of our course. MATERIALS AND METHODS: The criteria for being selected as an expert in Primary Care in Pediatric Trauma were agreed upon with the scientific polytrauma committee of the Spanish Pediatric Surgery Society. The items that make up the checklist were obtained from a review of the literature and consultation with selected experts, using the Delphi Technique. RESULTS: 10 experts representing the 9 groups or training centers in Primary Care in Pediatric Trauma were selected, and a 28-item checklist was drawn up in accordance with their design recommendations. CONCLUSIONS: With the consensus of all the groups, a checklist for the treatment of polytraumatized pediatric patients was drawn up using the Delphi Technique, an essential requirement for the dissemination of this checklist, which should be adapted and validated for use in each healthcare center.

INTRODUCCION: El curso de Asistencia Inicial al Trauma Pediátrico se imparte en España desde 1997, existiendo en la actualidad 9 centros formadores acreditados. La asistencia al paciente pediátrico politraumatizado se produce muchas veces en un ambiente proclive al error por olvido, por lo que las listas de verificación, como herramientas mnemotécnicas de amplia difusión en la industria y en medicina, serían especialmente útiles para evitarlos. Aunque existen varias listas de verificación para la asistencia al traumatismo pediátrico, ninguna se ha desarrollado en el entorno de nuestro curso. MATERIAL Y METODOS: Se acordaron los criterios para ser seleccionado como experto en Asistencia Inicial al Trauma Pediátrico con la comisión científica de politrauma de la Sociedad Española de Cirugía Pediátrica. Los ítems para formar la lista de verificación se obtuvieron a partir de una revisión bibliográfica y de la consulta a los expertos seleccionados, empleando un método Delphi. RESULTADOS: Se seleccionaron 10 expertos que representan los 9 grupos o centros formadores en Asistencia Inicial al Trauma Pediátrico y se elaboró una lista de verificación con 28 ítems, siguiendo sus recomendaciones de diseño. CONCLUSIONES: Se diseñó una lista de verificación para el manejo del paciente pediátrico politraumatizado, con el consenso de todos los grupos empleando un método Delphi, requisito fundamental para facilitar la difusión de esta lista. Sería preciso adaptar y validar dicha lista para su uso en cada centro asistencial.

NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.

Osteoporotic vertebral fractures: Natural history and impact. / Fracturas vertebrales osteoporóticas: historia natural e impacto.

Osteoporosis, and the consequences derived from it, such as fragility fractures, constitute a growing public health problem. Suffering from a fracture of this nature is the main risk factor for suffering a new fracture. It is documented that vertebral compression fractures lead to significant morbidity and mortality, in the short and long term, as well as other complications, such as sagittal imbalance and hyperkyphosis of the segment. However, we have not found documentation that analyzes the medium and long-term consequences of these injuries, assessing the type of treatment used, and the economic impact they represent. The purpose of this review is to analyze the main recent literature on the subject and make a breakdown of the consequences of these fractures in various spheres, such as economic, quality of life, sagittal balance and radiographic parameters, pain or mortality; as well as a brief analysis of epidemiology and natural history. CONCLUSION: Osteoporotic fractures constitute an emerging problem, both in the medical and economic fields. The consequences and sequelae on the patient are multiple and although surgical options offer good long-term results, it is necessary to properly select the patient, through multidisciplinary teams, to try to minimize potential complications.

Efectividad de la entrevista motivacional en la atención fisioterápica de los trastornos musculoesqueléticos de la espalda / Effectiveness of the motivational interview in the physiotherapy care of musculoskeletal disorders of the back: A quasi-experimental study

Objetivo: Evaluar la efectividad de la entrevista motivacional (EM) junto al tratamiento fisioterapéutico habitual en pacientes con trastornos musculoesqueléticos (TME) de la espalda en atención primaria (AP). Métodos: Estudio cuasiexperimental en pacientes que iniciaron su tratamiento en el año 2020 en una unidad de fisioterapia tras diagnóstico médico de TME en la espalda, con seguimiento prospectivo de 2grupos con actuación terapéutica: grupo experimental (GE) y grupo de control (GC). Se empleó la EM solo en el GE. A ambos grupos se les entrevistó telefónicamente a los 3y 6meses de finalizar el tratamiento fisioterápico, preguntando por el cumplimiento de pautas domiciliarias y por la percepción subjetiva del estado de salud (escala de Barthel). Se ajustaron modelos de regresión lineales (coeficiente de regresión, IC del 95%) y logísticos (OR, IC del 95%). Resultados: La población de estudio fue de 154 personas (76,6% mujeres). La salud percibida fue significativamente mejor (p<0,001) en el GE que en el GC, tanto a los 3meses de seguimiento (7,4 versus 5,0, respectivamente) como a los 6(7,1 versus 4,6, respectivamente). Hubo una fuerte asociación entre percepción de salud y cumplimiento (coeficiente de regresión 3,0 [IC del 95%=2,5-3,4]). La asociación entre la EM y el cumplimiento terapéutico se mantuvo tras ajustes multivariados (OR a 6meses=383,6 [IC del 95% = 31,0-4.742,4]). Conclusiones: la incorporación de la EM como complemento de los tratamientos de fisioterapia es una herramienta factible y efectiva para mejorar el cumplimiento de las pautas domiciliarias y la percepción subjetiva de salud. (AU)

Objective: To evaluate the effectiveness of motivational interviewing (MI) combined with the usual physiotherapy treatment in patients with back musculoskeletal disorders (MSD) in primary care (PC). Methods: Quasi-experimental study with 2groups with therapeutic action (control group and experimental group) and prospective follow-up, in a physiotherapy unit in PC, in patients who began their treatment in 2020, with a medical diagnosis of MSD in the back. MI was used only in the face-to-face visits of the experimental group. Both groups were interviewed by telephone about 3and 6months after finishing the physiotherapy treatment. For this purpose, the Barthel scale was used for the subjective perception of the state of health, and the scale of compliance with home guidelines. Linear (regression coefficient, 95% CI) and logistic (OR, 95% CI) regression models were fitted. Results: The study population was 154 people (76.6% women). Perceived health was significantly better (P<.001) in the experimental group than in the control group, both at 3(7.4 versus 5.0, respectively) and at 6months of follow-up (7.1 versus 4.6, respectively). There was a strong association between perceived health and compliance (regression coefficient 3.0 [95% CI=2.5–3.4]). The strong association between MI and treatment adherence was maintained after multivariate adjustments (6-month OR=383.6 [95% CI 31.0–4742.4]). Conclusions: MI is a feasible and effective complement to physiotherapy treatments to improve compliance with home recommendations and subjective perception of health. (AU)

Consenso AITP español: Una lista de verificación AITP / Spanish primary care in pediatric trauma (AITP) consensus: An AITP checklist

Introducción: El curso de Asistencia Inicial al Trauma Pediátricose imparte en España desde 1997, existiendo en la actualidad 9 centrosformadores acreditados. La asistencia al paciente pediátrico politraumatizado se produce muchas veces en un ambiente proclive al errorpor olvido, por lo que las listas de verificación, como herramientasmnemotécnicas de amplia difusión en la industria y en medicina, serían especialmente útiles para evitarlos. Aunque existen varias listas deverificación para la asistencia al traumatismo pediátrico, ninguna se hadesarrollado en el entorno de nuestro curso. Material y métodos: Se acordaron los criterios para ser seleccionado como experto en Asistencia Inicial al Trauma Pediátrico con lacomisión científica de politrauma de la Sociedad Española de CirugíaPediátrica. Los ítems para formar la lista de verificación se obtuvierona partir de una revisión bibliográfica y de la consulta a los expertosseleccionados, empleando un método Delphi. Resultados. Se seleccionaron 10 expertos que representan los 9grupos o centros formadores en Asistencia Inicial al Trauma Pediátri-co y se elaboró una lista de verificación con 28 ítems, siguiendo susrecomendaciones de diseño. Conclusiones: Se diseñó una lista de verificación para el manejodel paciente pediátrico politraumatizado, con el consenso de todos losgrupos empleando un método Delphi, requisito fundamental para facilitarla difusión de esta lista. Sería preciso adaptar y validar dicha lista parasu uso en cada centro asistencial.(AU)

Introduction: The course in Primary Care in Pediatric Trauma(ATIP in Spanish) has been taught in Spain since 1997, and there arecurrently 9 accredited training centers. Care of polytraumatized pedi-atric patients often takes place in an environment conducive to errorsresulting from forgetfulness, which is why checklists –mnemonic toolswidely used in industry and medicine– are particularly useful to avoidsuch errors. Although several checklists exist for pediatric trauma care,none have been developed within the setting of our course. Materials and methods: The criteria for being selected as an expertin Primary Care in Pediatric Trauma were agreed upon with the scientific polytrauma committee of the Spanish Pediatric Surgery Society.The items that make up the checklist were obtained from a review ofthe literature and consultation with selected experts, using the DelphiTechnique. Results: 10 experts representing the 9 groups or training centers inPrimary Care in Pediatric Trauma were selected, and a 28-item checklistwas drawn up in accordance with their design recommendations.Conclusions: With the consensus of all the groups, a checklist forthe treatment of polytraumatized pediatric patients was drawn up usingthe Delphi Technique, an essential requirement for the disseminationof this checklist, which should be adapted and validated for use in eachhealthcare center.(AU)

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding.

The obesity epidemic is principally driven by the consumption of more calories than the body requires. It is therefore essential that the mechanisms underpinning feeding behavior are defined. Neurons within the brainstem dorsal vagal complex (DVC) receive direct information from the digestive system and project to second-order regions in the brain to regulate food intake. Although γ-aminobutyric acid is expressed in the DVC (GABADVC), its function in this region has not been defined. In order to discover the unique gene expression signature of GABADVC cells, we used single-nucleus RNA sequencing (Nuc-seq), and this revealed 19 separate clusters. We next probed the function of GABADVC cells and discovered that the selective activation of GABADVC neurons significantly controls food intake and body weight. Optogenetic interrogation of GABADVC circuitry identified GABADVC → hypothalamic arcuate nucleus (ARC) projections as appetite suppressive without creating aversion. Electrophysiological analysis revealed that GABADVC → ARC stimulation inhibits hunger-promoting neuropeptide Y (NPY) neurons via GABA release. Adopting an intersectional genetics strategy, we clarify that the GABADVC → ARC circuit curbs food intake. These data identify GABADVC as a new modulator of feeding behavior and body weight and a controller of orexigenic NPY neuron activity, thereby providing insight into the neural underpinnings of obesity.

Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.

[Translated article] Frequency of use of discography findings for the diagnosis of low back pain of discogenic origin. Systematic review of the literature.

INTRODUCTION: There are different techniques and interpretations of discography findings to determine it positive for the diagnosis of discogenic pain. This study aims to evaluate the frequency of use of discography findings for the diagnosis of low back pain of discogenic origin. MATERIAL AND METHODS: A systematic review of the literature of the last 17 years was performed in MEDLINE and BIREME. A total of 625 articles were identified, 555 were excluded for duplicates, title and abstract. We obtained 70 full texts of which 36 were included in the analysis after excluding 34 for not meeting the inclusion criteria. RESULTS: Among the criteria in discography to determine it as positive, 8 studies used only the pain response to the procedure, 28 studies used more than one criterion during discography to consider it as positive, the evaluation of at least one adjacent intervertebral disc with a negative result was necessary in 26 studies to consider a discography as positive. Five studies formally expressed the use of the technique described by SIS/IASP to determine a discography as positive. CONCLUSIONS: Pain in response to contrast medium injection, assessed with the visual analogue pain scale ≥6, was the most used criterion in the studies included in this review. Although there are already criteria to determine a discography as positive, the use of different techniques and interpretations of discography findings to determine a positive discography for low back pain of discogenic origin persists.

Development of functional consortia for the pretreatment of compostable lignocellulosic waste: A simple and effective solution to a large-scale problem.

Microorganisms drive the degradation of organic matter thanks to their enzymatic versatility. However, the structure of lignocellulose poses a great challenge for the microbiota inhabiting a compost pile. Our purpose was to increase the biodegradability of vegetable waste in the early stages of the composting process by applying a microbial consortium with lignocelllulolytic capacity. For this, a previous screening was performed among the culturable microbiota from different composting processes to find inoculants with ligninocellulolytic activity. Selected strains were applied as a pure culture and as a microbial consortium. The starting material was composed of tomato plant and pruning remains mixed in a ratio (50:50 v/v), whose humidity was adjusted to around 65%. To determine the ability of both treatments to activate the biodegradation of the mixtures, moisture, organic matter, ash, C/N ratio, 4-day cumulative respirometric index (AT4) and degradation rates of cellulose, hemicellulose and lignin were evaluated. Subsequently, a real composting process was developed in which the performance of the microbial consortium was compared with the composting process without inoculum (control). According to our tests, three microbial strains (Bacillus safensis, Bacillus licheniformis and Fusarium oxysporum) were selected. The results showed that the application of the bacteria strains at low doses (104 CFU g-1 on the complete residual material of the pile) resulted in higher rates of lignocelullose degradation after 10 days of treatment compared to that observed after application of the fungus in pure culture or untreated controls. The implementation of the strategy described in this work resulted in obtaining compost with better agronomic quality than the uninoculated controls. Therefore, the application of this consortium could be considered as an interesting tool for bioactivation of lignocellulosic waste prior to the composting process.

Genetic diversity of P1/pathogenic Leptospira species hosted by bats worldwide.

INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.

Economic analysis of the robotic approach to inguinal hernia versus laparoscopic: is it sustainable for the healthcare system?

INTRODUCTION: There has been a rapid proliferation of the robotic approach to inguinal hernia, mainly in the United States, as it has shown similar outcomes to the laparoscopic approach but with a significant increase in associated costs. Our objective is to conduct a cost analysis in our setting (Spanish National Health System). MATERIALS AND METHODS: A retrospective single-center comparative study on inguinal hernia repair using a robotic approach versus laparoscopic approach. RESULTS: A total of 98 patients who underwent either robotic or laparoscopic TAPP inguinal hernia repair between October 2021 and July 2023 were analyzed. Out of these 98 patients, 20 (20.4%) were treated with the robotic approach, while 78 (79.6%) underwent the laparoscopic approach. When comparing both approaches, no significant differences were found in terms of complications, recurrences, or readmissions. However, the robotic group exhibited a longer surgical time (86 ± 33.07 min vs. 40 ± 14.46 min, p < 0.001), an extended hospital stays (1.6 ± 0.503 days vs. 1.13 ± 0.727 days, p < 0.007), as well as higher procedural costs (2318.63 ± 205.15 € vs. 356.81 ± 110.14 €, p < 0.001) and total hospitalization costs (3272.48 ± 408.49 € vs. 1048.61 ± 460.06 €, p < 0.001). These results were consistent when performing subgroup analysis for unilateral and bilateral hernias. CONCLUSIONS: The benefits observed in terms of recurrence rates and post-surgical complications do not justify the additional costs incurred by the robotic approach to inguinal hernia within the national public healthcare system. Nevertheless, it represents a simpler way to initiate the robotic learning curve, justifying its use in a training context.

Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in urothelial cancer.

Immune checkpoint inhibitors (ICI) improve overall survival in patients with metastatic urothelial cancer (mUC), but therapeutic success at the individual patient level varies significantly. Here we identify predictive markers of response, based on whole-genome DNA (n = 70) and RNA-sequencing (n = 41) of fresh metastatic biopsy samples, collected prior to treatment with pembrolizumab. We find that PD-L1 combined positivity score does not, whereas tumor mutational burden and APOBEC mutagenesis modestly predict response. In contrast, T cell-to-stroma enrichment (TSE) score, computed from gene expression signature data to capture the relative abundance of T cells and stromal cells, predicts response to immunotherapy with high accuracy. Patients with a positive and negative TSE score show progression free survival rates at 6 months of 67 and 0%, respectively. The abundance of T cells and stromal cells, as reflected by the TSE score is confirmed by immunofluorescence in tumor tissue, and its good performance in two independent ICI-treated cohorts of patients with mUC (IMvigor210) and muscle-invasive UC (ABACUS) validate the predictive power of the TSE score. In conclusion, the TSE score represents a clinically applicable metric that potentially supports the prospective selection of patients with mUC for ICI treatment.