Do professional painters comprise a high risk group for genotoxicity? A systematic review.

Professional painters represent an occupational population group that deserves attention for study in the field of occupational toxicology due to the wide range of complex chemical mixtures they are exposed to. It is imperative to underscore that the International Agency for Research on Cancer has classified commercial painting as a high-risk occupation for the development of cancer. Given this context, the primary objective of the present study was to conduct a systematic review aimed at addressing the following question: are car painters at occupational risk regarding potential genotoxicity? To address this question, a selection process was undertaken, with three reviewers carefully selecting, reading, and analyzing full manuscripts from 26 studies included in this review. The technical rigor of these studies underwent meticulous scrutiny, culminating in the classification of six studies as Strong, eight as Moderate, and 12 as Weak, predicated on the extent of confounders considered. Taken together, the findings suggest that chemical substances from paints may indeed pose a risk of genotoxicity for professionals in this field, as all studies indicated genotoxicity among professional painters through various tests.

Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cells.

BACKGROUND: Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3+ T cells towards a Treg cell lineage. The potency of T cells plays an important role in effective immunotherapy, underscoring the need for improving their metabolic fitness. In the present work, we evaluate the effect of MitoT on apoptotis of native T lymphocytes and engineered CAR-T cells. METHODS: We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3+ MitoTpos and MitoTneg sorted cells. Target cell apoptosis was induced with Staurosporine (STS), and cell viability was evaluated with Annexin V/7AAD and TUNEL assays. Changes in apoptotic regulators were assessed by flow cytometry, western blot, and qRT-PCR. The effect of MitoT on 19BBz CAR T-cell apoptosis in response to electroporation with a non-viral transposon-based vector was assessed with Annexin V/7AAD. RESULTS: Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3+ T cells after Mitoception. CD3+MitoTpos cells were resistant to STS-induced apoptosis compared to MitoTneg cells, showing a decreased percentage in apoptotic T cells as well as in TUNEL+ cells. Additionally, MitoT prevented the STS-induced collapse of the mitochondrial membrane potential (MMP) levels, decreased caspase-3 cleavage, increased BCL2 transcript levels and BCL-2-related BARD1 expression in FACS-sorted CD3+ T cells. Furthermore, UC-MSC-derived MitoT reduced both early and late apoptosis in CAR-T cells following electroporation, and exhibited an increasing trend in cytotoxic activity levels. CONCLUSIONS: Artificial MitoT prevents STS-induced apoptosis of human CD3+ T cells by interfering with the caspase pathway. Furthermore, we observed that MitoT confers protection to apoptosis induced by electroporation in MitoTpos CAR T-engineered cells, potentially improving their metabolic fitness and resistance to environmental stress. These results widen the physiological perspective of organelle-based therapies in immune conditions while offering potential avenues to enhance CAR-T treatment outcomes where their viability is compromised.

Efficient Mako Shark-Inspired Aerodynamic Design for Concept Car Bodies in Underground Road Tunnel Conditions.

The automotive industry continuously enhances vehicle design to meet the growing demand for more efficient vehicles. Computational design and numerical simulation are essential tools for developing concept cars with lower carbon emissions and reduced costs. Underground roads are proposed as an attractive alternative for reducing surface congestion, improving traffic flow, reducing travel times and minimizing noise pollution in urban areas, creating a quieter and more livable environment for residents. In this context, a concept car body design for underground tunnels was proposed, inspired by the mako shark shape due to its exceptional operational kinetic qualities. The proposed biomimetic-based method using computational fluid dynamics for engineering design includes an iterative process and car body optimization in terms of lift and drag performance. A mesh sensitivity and convergence analysis was performed in order to ensure the reliability of numerical results. The unique surface shape of the shark enabled remarkable aerodynamic performance for the concept car, achieving a drag coefficient value of 0.28. The addition of an aerodynamic diffuser improved downforce by reducing 58% of the lift coefficient to a final value of 0.02. Benchmark validation was carried out using reported results from sources available in the literature. The proposed biomimetic design process based on computational fluid modeling reduces the time and resources required to create new concept car models. This approach helps to achieve efficient automotive solutions with low aerodynamic drag for a low-carbon future.

The cardiotoxic effects of CAR-T cell therapy: An updated systematic review and meta-analysis.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in treating hematologic malignancies, yet its potential cardiotoxic effects require thorough investigation. OBJECTIVES: We aim to conduct a systematic review and meta-analysis to examine the cardiotoxic effects of CAR-T therapy in adults with hematologic malignancies. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting cardiovascular outcomes, such as arrhythmias, heart failure, and reduced left ventricle ejection fraction (LVEF). RESULTS: Our analysis of 20 studies involving 4789 patients revealed a 19.68% incidence rate of cardiovascular events, with arrhythmias (7.70%), heart failure (5.73%), and reduced LVEF (3.86%) being the most prevalent. Troponin elevation was observed in 23.61% of patients, while NT-Pro-BNP elevation was observed in 9.4. Subgroup analysis showed higher risks in patients with pre-existing conditions, such as atrial arrhythmia (OR 3.12; p < .001), hypertension (OR 1.85; p = .002), previous heart failure (OR 3.38; p = .003), and coronary artery disease (OR 2.80; p = .003). CONCLUSION: Vigilant cardiovascular monitoring is crucial for patients undergoing CAR-T therapy to enhance safety and treatment efficacy.Novelty Statements.

CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types.

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma.

Chimeric Antigen Receptor T-cell (CAR-T) therapies are transforming the treatment of B-cell lymphoproliferative disorders and multiple myeloma, yet global access challenges and barriers for their implementation persist. Global access disparities persist, particularly for persons living in low and middle-income countries and for underserved populations in high income countries. In this review we address patient-related factors including age, comorbidities, fitness, race and ethnicity, and geographic location for CAR-T access. Also, we review disease-related and health system barriers like disease biology, potential for short and long-term toxicity, insurance access, referrals, supply and manufacturing, regulation, costs and treatment center capacity. Lastly, alternatives for overcoming these barriers exemplified by research efforts worldwide are discussed, emphasizing the need for a multifaceted approach from all stakeholders to improve global accessibility and ensure equitable access and improved outcomes for patients worldwide.

IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.

In silico and in vivo analysis reveal impact of c-Myc tag in FMC63 scFv-CD19 protein interface and CAR-T cell efficacy.

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

Sicca syndrome/Sjögren's disease associated with cancer immunotherapy: a narrative review on clinical presentation, biomarkers, and management.

INTRODUCTION: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3-2.5%, possibly underreported. AREAS COVERED: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs. EXPERT OPINION: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40-60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation.

CAR T-cell therapy and the onco-nephrologist.

Cell therapy, specifically the revolutionary chimeric antigen receptor (CAR) T-cell therapy, has transformed the landscape of oncology, making substantial strides in practical treatment approaches. Today, established guidelines for diseases such as lymphomas, myelomas, and leukemias actively advocate the utilization of these once-unconventional therapies. The practical impact of these therapies is underscored by their unparalleled efficacy, reshaping the way we approach and implement treatments in the realm of oncology. However, CAR T-cell therapy, with its performance in anti-tumor aggression through cellular action and inflammatory response, also comes with various adverse events, one of which is kidney injury. Therefore, the management of these side effects is extremely important. The integration of knowledge between oncologists and specialized nephrologists has led to the emergence of a new sub-area of expertise for onco-nephrologists specializing in managing kidney complications from immune effector therapies.

CAR-T therapy for gastrointestinal cancers: current status, challenges, and future directions

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary immunotherapeutic strategy that has shown efficacy in hematological malignancies. However, its application in solid tumors, particularly gastrointestinal cancers, faces significant challenges. These include the selection of target antigens, the complexity of the tumor microenvironment, and safety and toxicity concerns. This review provides a current overview of CAR-T therapy in various gastrointestinal cancers, such as esophageal, gastric, colorectal, pancreatic, and liver cancers. It discusses the limitations and future directions of CAR-T therapy in this context. This review highlights innovative strategies, including novel target antigens, multispecific CAR-T cells, armored CAR-T cells, and the development of universal CAR-T cells. These insights aim to inform ongoing research and foster advancements in CAR-T therapy for gastrointestinal cancers.

CAR-T cell therapy: a game-changer in cancer treatment and beyond.

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.

13 C NMR as an analytical tool for the detection of carbonic acid and pKa determination.

NMR spectroscopy has become a standard technique in studies both on carbon capture and storage. 13 C NMR allows the detection of two peaks for carbonated aqueous samples: one for CO2(aq) and another one for the species H2 CO3 , HCO3 - , and CO3 2- -herein collectively named Hx CO3 x-2 . The chemical shift of this second peak depends on the molar fraction of the three species in equilibrium and has been used to assess the equilibrium between HCO3 - and CO3 2- . The detection of H2 CO3 at low pH solutions is hindered, because of the concurrent liberation of CO2 when the medium is acidified. Herein, a valved NMR tube facilitates the detection of the Hx CO3 x-2 peak across a wide pH range, even at pH 1.8 where the dominant species is H2 CO3 . The method employed the formation of frozen layers of NaH13 CO3 and acid solutions within the tube, which are mixed as the tube reaches room temperature. At this point, the tube is already securely sealed, preventing any loss of CO2 to the atmosphere. A spectrophotometry approach allowed the measurement of the actual pH inside the pressurized NMR tube. The chemical shift for H2 CO3 was determined as 160.33 ± 0.03 ppm, which is in good agreement with value obtained by DFT calculations combined with Car-Parrinello molecular dynamics. The H2 CO3 pKa value determined by the present method was 3.41 ± 0.03, for 15% D2 O aqueous medium and 0.8 mol/L ionic strength. The proposed method can be extended to studies about analogs such as alkyl carbonic and carbamic acids.

Cuidado de Enfermagem à Pessoa com Paraplegia à Luz de Betty Neuman / Nursing Care for the Person with Paraplegia in the Light of Betty Neuman / Cuidados de enfermería a la persona con paraplejia a la luz de Betty Neuman

Objetivo: Relatar e compreender o cuidado de enfermagem à pessoa com paraplegia secundária a acidente automobilístico. Método:Estudo qualitativo descritivo, tipo relato de caso, realizado em hospital público de Feira de Santana/BA. Procedeu-se à entrevista, com uma participante em situação de paraplegia. Utilizou-se a elaboração da SAE e suas etapas considerando os aspectos da Teoria de Betty Neuman. Resultados:O relato da paciente e informações obtidas em prontuário demonstraram desinformações e condutas soltas que dificultam o cuidado, alimentavam sentimento de angústia e tristeza à paciente. Conclusão:proporcionou o entendimento acerca do indivíduo vítima de politrauma e suas necessidades, entendendo o adoecer com transcurso multifatorial onde segundo a teoria de Betty Neuman o ambiente e o indivíduo dialogam entre si surtindo efeito positivo e negativo sob o equilíbrio do corpo humano

Objective: To report and understand nursing care for individuals with paraplegia secondary to car accidents. Method:Descriptive qualitative study, in the form of a case report, conducted at a public hospital in Feira de Santana/BA. An interview was conducted with a participant in a paraplegic situation. The Nursing Process (NP) was developed, and its stages were considered, taking into account aspects of Betty Neuman's Theory. Results:The patient's account and information obtained from medical records revealed misinformation and disjointed behaviors that hindered care, fostering feelings of anguish and sadness in the patient. Conclusion:This study provided an understanding of individuals suffering from polytrauma and their needs, understanding illness as a multifactorial process where, according to Betty Neuman's theory, the environment and the individual interact, having both positive and negative effects on the balance of the human body.

Objetivo: Informar y comprender el cuidado de enfermería para personas con paraplejia secundaria a accidentes automovilísticos. Método:Estudio cualitativo descriptivo, tipo informe de caso, llevado a cabo en un hospital público en Feira de Santana/BA. Se realizó una entrevista con una participante en situación de paraplejia. Se utilizó el desarrollo del Proceso de Enfermería (PE) y sus etapas considerando los aspectos de la Teoría de Betty Neuman. Resultados:El relato de la paciente y la información obtenida de los registros médicos revelaron desinformación y conductas desarticuladas que dificultaron el cuidado, fomentando sentimientos de angustia y tristeza en la paciente. Conclusión:Este estudio proporcionó una comprensión de las necesidades de individuos que sufren politraumatismos, entendiendo la enfermedad como un proceso multifactorial donde, según la teoría de Betty Neuman, el entorno y el individuo interactúan, teniendo efectos tanto positivos como negativos en el equilibrio del cuerpo humano.

CAR-T Cell Therapy: From the Shop to Cancer Therapy.

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect in vivo.

Introduction: Natural killer 92 (NK-92) cells are an attractive therapeutic approach as alternative chimeric antigen receptor (CAR) carriers, different from T cells, once they can be used in the allogeneic setting. The modest in vivo outcomes observed with NK-92 cells continue to present hurdles in successfully translating NK-92 cell therapies into clinical applications. Adoptive transfer of CAR-NK-92 cells holds out the promise of therapeutic benefit at a lower rate of adverse events due to the absence of GvHD and cytokine release syndrome. However, it has not achieved breakthrough clinical results yet, and further improvement of CAR-NK-92 cells is necessary. Methods: In this study, we conducted a comparative analysis between CD19-targeted CAR (CAR.19) co-expressing IL-15 (CAR.19-IL15) with IL-15/IL-15Rα (CAR.19-IL15/IL15Rα) to promote NK cell proliferation, activation, and cytotoxic activity against B-cell leukemia. CAR constructs were cloned into lentiviral vector and transduced into NK-92 cell line. Potency of CAR-NK cells were assessed against CD19-expressing cell lines NALM-6 or Raji in vitro and in vivo in a murine model. Tumor burden was measured by bioluminescence. Results: We demonstrated that a fourth- generation CD19-targeted CAR (CAR.19) co-expressing IL-15 linked to its receptor IL-15/IL-15Rα (CAR.19-IL-15/IL-15Rα) significantly enhanced NK-92 cell proliferation, proinflammatory cytokine secretion, and cytotoxic activity against B-cell cancer cell lines in vitro and in a xenograft mouse model. Conclusion: Together with the results of the systematic analysis of the transcriptome of activated NK-92 CAR variants, this supports the notion that IL-15/IL-15Rα comprising fourth-generation CARs may overcome the limitations of NK-92 cell-based targeted tumor therapies in vivo by providing the necessary growth and activation signals.

Delivery of Plasmid DNA by Ionizable Lipid Nanoparticles to Induce CAR Expression in T Cells.

Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR. Methods: Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19+) cells. Results: LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19+ target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19+ target cells in vitro. Conclusion: Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.

[When to resume driving after primary total hip arthroplasty?] / ¿Cuándo se reanuda la conducción después del reemplazo total de cadera primario?

INTRODUCTION: the current literature relates the return to driving with multiple variables. For various reasons, the current data on the time to return to driving after a total hip arthroplasty (THA) are diverse and even contradictory. We have proposed the objective of determining the time required to drive a manual gear vehicle again in a group of patients who underwent primary THA through a posterolateral approach with focus on manual gear cars. MATERIAL AND METHODS: we have studied the functional results of 112 patients who underwent primary THA between January 2019 and January 2020 in a high level in Cadiz, Andalusia, Spain. RESULTS: the median return to driving was three weeks (IQR 2-4). We have identified that 89.3% of the patients were able to drive again before the sixth week after surgery and in 92% of the cases they did so feeling even safer than before the THA. CONCLUSION: we consider that after the sixth week of an THA it is safe to resume driving a vehicle.

INTRODUCCIÓN: la literatura actual relaciona el regreso a la conducción vehicular con múltiples variables. Sin embargo, los datos actuales sobre el tiempo de regreso a la conducción luego de una artroplastía total de cadera (ATC) son diversos e incluso contradictorios. Por lo tanto, nos hemos planteado el objetivo de determinar el tiempo requerido para volver a conducir en un grupo de pacientes sometidos a una ATC primaria mediante un abordaje posterolateral, centrándonos específicamente en vehículos de marcha manual. MATERIAL Y MÉTODOS: hemos estudiado los resultados clínico-funcionales de 112 pacientes sometidos a una ATC primaria entre Enero de 2019 y Enero de 2020 en un hospital de alta complejidad en Cádiz, Andalucía, España. RESULTADOS: la mediana del tiempo de regreso a la conducción fue de tres semanas (RIC 2-4). Hemos identificado que 89.3% de los pacientes pudo volver a conducir antes de la sexta semana posterior a la cirugía. Además, en 92% de los casos, los pacientes se sintieron aún más seguros al conducir después de la ATC que antes de la intervención. CONCLUSIÓN: consideramos que a la sexta semana de una ATC es seguro reanudar la conducción de un vehículo.

Autologous, allogeneic hematopoietic cell transplantation and CAR-T/NK therapy: what is their real importance in PTCL?

Peripheral T cell lymphoma (PTCL) is a rare and aggressive type of non-Hodgkin's lymphoma that affects mature T cells. This type of cancer is characterized by the abnormal growth of T cells, which can accumulate in the lymph nodes, spleen, bone marrow, and other organs, leading to a variety of symptoms. PTCLs are often difficult to diagnose and treat, and they have a poorer prognosis than other types of lymphoma. However, recent advancements in treatment options, such as targeted therapies have shown promise in improving outcomes for patients with PTCL. Here, we discuss the use of autologous and allogeneic hematopoietic cell transplantation (HCT) as a treatment strategy for patients with PTCL, as well as the recent treatment approaches based on advanced cellular therapy. The current evidence for the use of HCT in PTCL is mainly derived from registry data, retrospective studies, and expert opinion, as randomized trials are limited due to the low incidence and histological heterogeneity of PTCL subtypes.

Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.