Paraneoplastic Leukemoid reaction in soft tissue sarcoma: A case report and literature review.

INTRODUCTION: Paraneoplastic leukemoid reactions (PLRs) in the context of sarcomas represent a unique clinical entity that poses significant diagnostic challenges and adds valuable insights to the surgical literature. Characterized by an abnormal elevation of white blood cell count, these reactions are often associated with aggressive tumor biology and poor prognosis, emphasizing the need for heightened awareness among clinicians. CASE PRESENTATION: A 48-year-old male presented with a rapidly growing, ulcerated tumor on his thigh. Lab tests revealed an extreme leukocytosis with a white blood cell count of 92,860/mm3. Imaging and biopsy confirmed a high-grade spindle cell sarcoma. CLINICAL DISCUSSION: After excluding other causes of leukocytosis, a PLR secondary to sarcoma was diagnosed. Despite initial antibiotic treatment, leukocytosis persisted, prompting a decision for surgical intervention. The patient underwent successful tumor resection, resulting in a significant decrease in leukocyte count and subsequent stable recovery, supported by adjuvant radiotherapy. CONCLUSION: This case underscores the importance of recognizing PLRs in sarcoma patients as they can significantly impact clinical management and prognosis. It highlights the necessity of a multidisciplinary approach for accurate diagnosis and effective treatment. The case contributes to the surgical literature by detailing the diagnostic process and therapeutic interventions in managing such complex presentations, thereby providing key "take-away" lessons on the importance of considering PLRs in the differential diagnosis of leukocytosis in patients with malignancies.

The microbial composition of pancreatic ductal adenocarcinoma: A systematic review of 16S rRNA gene sequencing.

BACKGROUND: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. MATERIALS AND METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. RESULTS: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies. CONCLUSION: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

Use of Periodic Mesoporous Organosilica-Benzene Adsorbent for CO2 Capture to Reduce the Greenhouse Effect.

The CO2 adsorption of a phenylene-bridged ordered mesoporous organosilica (PMO-benzene) was analyzed. The maximum capture capacity was 638.2 mg·g-1 (0 °C and 34 atm). Approximately 0.43 g would be enough to reduce the amount of atmospheric CO2 in 1 m3 to pre-industrial levels. The CO2 adsorption data were analyzed using several isotherm models, including Langmuir, Freundlich, Sips, Toth, Dubinin-Radushkevich, and Temkin models. This study confirmed the capability of this material for use in reversible CO2 capture with a minimal loss of capacity (around 1%) after 10 capture cycles. Various techniques were employed to characterize this material. The findings from this study can help mitigate the greenhouse effect caused by CO2.

Health-Related Quality of Life and Injuries in Physical Education Students: A Multi-Group Model According to the Degree of Adherence to the Mediterranean Diet.

The Mediterranean diet is considered a healthy eating pattern. It has been shown to improve people's quality of life. When a person suffers injuries, their quality of life suffers. This research aims to accomplish the following: (a) to study the differences in the effect of the health-related quality of life on injuries according to the degree of adherence to the Mediterranean diet, (b) to analyse the existing differences in the variables that make up the health-related quality of life according to the degree of adherence to the Mediterranean diet, and (c) to analyse the degree of adherence to the Mediterranean diet according to whether the participants have suffered any injury. The study was descriptive, cross-sectional, and exploratory in a sample of 556 physical education students. The PREDIMED questionnaire, the SF-36 questionnaire, and a self-administered questionnaire were used. The results showed that high adherence to the Mediterranean diet was associated with higher quality of life and lower injury rates. It was also observed that high adherence to the Mediterranean diet improved the effect of the quality of life on injuries. In conclusion, the Mediterranean diet is beneficial for the quality of life of young university students.

Pathology results of endoscopic ultrasound-guided tissue acquisition in retroperitoneal masses: a multicenter study.

Background: Malignant etiologies are found in 70-80% of symptomatic retroperitoneal masses. Histology is required for diagnosis and treatment. Information about endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-GTA) is scant for retroperitoneal masses. This study aimed to assess the pathology results of EUS-GTA for diagnosing retroperitoneal masses. Methods: This retrospective, multicenter study involved patients from 5 care centers. All patients with retroperitoneal masses who underwent EUS evaluation were enrolled. We recorded demographic and clinical characteristics, location and size of the mass, type of needle (FNA/FNB), and complications related to the procedure. Results: A total of 43 patients were included. The median age was 50.5 (range: 23-83) years, and 22 (51.2%) were female. The initial symptom was abdominal pain in 23 (52.3%) cases and weight loss in 11 (25%). Initial imaging was by computed tomography in 33 (75%) patients. Diagnosis with EUS-GTA was reached in 67.5% (29/43) cases. The most frequent histological diagnosis was carcinoma, in 25.5% (11/43). A malignant etiology was found in 31 (72%): 20 were primary tumors from the retroperitoneum, and 11 were metastases. In patients with metastasis, surgery was avoided and medical treatment was indicated. No adverse events were reported. Conclusion: EUS and EUS-GTA can frequently provide accurate tissue diagnosis and significantly impact the subsequent management.

Bile Microbiome Signatures Associated with Pancreatic Ductal Adenocarcinoma Compared to Benign Disease: A UK Pilot Study.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.

Ontogeny of digestive enzymes in larvae of the Clown Anemonefish, Amphiprion ocellaris (Perciformes: Pomacentridae)

Introduction: The Clown anemonefish (Amphiprion ocellaris) is the most popular fish species in the marine aquarium trade; however, there is a lack of information on their digestive physiology during larval ontogeny, valuable information needed for diet design and management protocols. Objective: To characterize the early digestive enzymes of A. ocellaris larvae. Methods: We used three pools (10 larvae each) and extracted 10 samples per tank, from just before hatching to the 38th day. We analyzed the specific activity of acid and alkaline proteases, trypsin, chymotrypsin, leucine aminopeptidase and lipase; and did acid and alkaline protease zymograms. Results: We detected all measured enzymes at hatching. Acid proteases increased in activity until the 38th day. Alkaline proteases, trypsin, chymotrypsin, and leucine aminopeptidase had the same pattern, and maximum activity on the 8th day, decreasing at the 38th day. Lipase activity peaked on the 8th and 30th day. The acid zymogram had a single band, appearing on the 8th day. A total of eight alkaline proteases were revealed (154.2, 128.1, 104.0, 59.8, 53.5, 41.9, 36.5 and 25.1 KDa), with seven bands on the 1st day and all bands from the 3rd to 8th day, decreasing at two bands (41.9 and 25.1 KDa) in the 38th day. Conclusion: A. ocellaris has a functional stomach on the 8th day, and, on the 38th day, a digestive omnivore pattern with a tendency to carnivory.

Introducción: El pez payaso (Amphiprion ocellaris) es la especie de pez más popular en el comercio de acuarios marinos; sin embargo, falta información sobre su fisiología digestiva durante la ontogenia larval, información valiosa necesaria para protocolos de diseño y manejo dietético. Objetivo: Caracterizar las enzimas digestivas tempranas de larvas de A. ocellaris. Métodos: Usamos tres homogenados (con 10 larvas cada uno) y extrajimos 10 muestras por tanque, justo antes de la eclosión hasta el día 38. Analizamos la actividad específica de proteasas ácidas y alcalinas, tripsina, quimotripsina, leucina aminopeptidasa y lipasa; e hicimos zimogramas de proteasas ácidas y alcalinas. Resultados: Detectamos todas las enzimas medidas en la eclosión. La actividad de proteasas ácidas incrementó hasta el día 38. Proteasas alcalinas, tripsina, quimotripsina, y leucina aminopeptidasa tuvieron el mismo patrón, con actividad máxima en el octavo día, decreciendo en el día 38. Hubo picos en la actividad lipasa a los ocho y 30 días. El zimograma ácido tuvo una banda única, apareciendo al octavo día. Se hallaron ocho proteasas alcalinas (154.2, 128.1, 104.0, 59.8, 53.5, 41.9, 36.5 y 25.1 KDa), con siete bandas al primer día, y todas las bandas entre el tercer y octavo día, bajando a dos bandas (41.9 y 25.1 KDa) al día 38. Conclusión: A. ocellaris tiene un estómago funcional al octavo día, y, al día 38, un patrón digestivo omnívoro con tendencias carnívoras.

Resistin Induces Migration and Invasion in PC3 Prostate Cancer Cells: Role of Extracellular Vesicles.

Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue expression of resistin increases the aggressiveness of prostate tumor cells. Extracellular vesicles (EVs) are secreted constitutively and induced by cytokines, growth factors, and calcium and are found in multiple biological fluids such as saliva, serum, semen, and urine. In particular, EVs have been shown to promote tumor progression through the induction of proliferation, growth, angiogenesis, resistance to chemotherapy, and metastasis. However, the role of resistin in the migration, invasion, and secretion of EVs in invasive prostate tumor cells remains to be studied. In the present study, we demonstrate that resistin induces increased migration and invasion in PC3 cells. In addition, these phenomena are accompanied by increased p-FAK levels and increased secretion of MMP-2 and MMP-9 in resistin-treated PC3 cells. Interestingly, EVs isolated from supernatants of PC3 cells treated with resistin induce an increase in migration and invasion accompanied by high MMP-2 and MMP-9 secretion in an autocrine stimulation model. In summary, our data for the first time demonstrate that resistin induces migration and invasion, partly through the secretion of EVs with pro-invasive characteristics in PC3 cells.

Changes in the quality of life of adults with an ostomy during the first year after surgery as part of the Best Practice Spotlight Organisation® Programme.

The aim was to analyse changes in the perceived quality of life of patients with an ostomy during the first year after surgery at two or three follow-ups. This is a prospective study of a cohort of 55 patients who were ostomised between June 2021 and September 2022 and cared for under the recommendations set out in the Registered Nurses' Association of Ontario® best practice guideline Supporting Adults Who Anticipate or Live with an Ostomy as part of the Best Practice Spotlight Organisation® (BPSO®) programme. The Stoma Quality of Life tool was used. A univariate analysis was performed to identify variables associated with a non-improvement in quality of life. Variables showing p < 0.1 were included in a multivariate model. Patients with an ostomy exhibited a moderate-to-good perception of quality of life in both the personal and social dimensions, with no worsening over the first year. Being female (OR = 10.32) and being younger (OR = 0.89) were associated with a higher risk of no improvement in quality of life. The most frequent complications were urinary leakage (p = 0.027) and dermatitis (p = 0.052) at first follow-up; and parastomal hernia (p = 0.009) and prolapse (p = 0.05) at third follow-up. However, they did not lead to a worsening of quality of life, suggesting that these patients were adequately supported under the BPSO® programme.

Are there differences between Mediterranean diet and the consumption of harmful substances on quality of life?-an explanatory model in secondary education regarding gender.

Background: Adolescence is a key life stage in human development. It is during this stage of development that healthy and physical behaviors are acquired that will last into adulthood. Gender differences in the acquisition of these behaviors have been observed. This research aims to (a) study the levels of Mediterranean diet adherence, quality of life and alcohol and tobacco consumption as regarding the gender of the participants and (b) study the effects of the variable adherence to the Mediterranean diet, alcohol consumption and tobacco consumption on quality of life as a function of the gender of the participants. Methods: A non-experimental, cross-sectional, exploratory study was carried out in a sample of 1,057 Spanish adolescents (Average Age = 14.19; Standard Deviation = 2.87). Results: The comparative analysis shows that the male teenagers shows a higher Mediterranean diet adherence compared to the male adolescents (p ≤ 0.05) and a higher consumption of alcoholic beverages (p ≤ 0.05). On the contrary, adolescent girls show a higher consumption of alcoholic beverages than male participants (p ≤ 0.05). The exploratory analysis indicates that for boys, alcohol consumption has a beneficial effect on the quality of life of adolescents (ß = 0.904; p ≤ 0.001). Conclusion: In this case, participants show differences in the levels of Mediterranean diet adherence, consumption of harmful substances and quality of life according to gender. Likewise, there are different effects between the variables according to gender. Therefore, gender is a key factor to consider during adolescence.

Does compartmental resection really impact retroperitoneal soft tissue sarcomas? A retrospective analysis from a Single Referral Center.

BACKGROUND: The treatment of choice for retroperitoneal soft tissue sarcomas (RPS) is surgical resection; the outcomes with more radical surgeries, notably compartmental resection, remains a subject of debate. Arguments against it, include the complexity of the technique and high morbidity. MATERIALS AND METHODS: A retrospective analysis of cases treated in a single center from January 2010 to December 2019 is presented. Two time periods were evaluated: 2010-2015 and 2016-2019, corresponding to before and after the implementation of routine compartmentectomy. We evaluated the short- and long-term outcomes of compartmental resection compared to limited surgeries through a multivariate analysis of prognostic factors. RESULTS: A total of 176 cases were included, of which 102 met the inclusion criteria. The sex distribution was similar. The average age was 52.9 years, and the average tumor size was 24.5 cm. The most frequent histology was liposarcoma (65.7%), followed by leiomyosarcoma (12.7%), and malignant peripheral nerve sheath tumor (8.8%). The median follow-up period was 40 months. We found a lower local recurrence in the group treated in the recent period (compartmentectomy) 42.3% vs 20% p = 0.007. The median overall survival (OS) was 38.7 months, and there was no difference in distant recurrence between the two time periods. Postoperative morbidity was higher in the recent period (25% vs 10% p 0.041), with no difference in 30-day mortality. CONCLUSIONS: The implementation of extensive surgery, specifically compartmentectomy, for retroperitoneal sarcomas has been linked to reduced local recurrence. We recommend considering this surgical approach for RPS in alignment with current expert consensus guidelines, as highlighted by the updated TARPSWG consensus.

Sesamoidectomía peroneal por necrosis séptica

Introducción: Los sesamoideos del hallux son huesos constantes de pequeño tamaño y lentiformes. Se localizan en la región plantar de la cabeza del primer metatarsiano dentro de la cápsula de la primera articulación metatarsofalángica. El diagnóstico diferencial de metatarsalgia sobre el primer radio del pie, sin antecedente traumático, incluye patologías referidas a los sesamoideos y otras. Entre las primeras se encuentran principalmente la sesamoiditis, las fracturas de estrés y la necrosis avascular de los sesamoideos. Objetivo: Presentar un caso de sesamoiditis y su evolución después del tratamiento quirúrgico. Presentación del caso: Mujer de 25 años con un cuadro de fractura por estrés del sesamoideo peroneal. Tras infiltración seriada con corticoesteroides, desencadenó una necrosis séptica del sesamoideo. Se determinó realizar una sesamoidectomía por abordaje plantar. Conclusiones: La sesamoidectomía resulta una opción quirúrgica en procesos degenerativos de los sesamoideos, cuando los tratamientos conservadores son insuficientes. El abordaje plantar se considera adecuado para la extirpación del sesamoideo peroneal. Esta técnica requiere un adecuado seguimiento posoperatorio para optimizar la cicatrización plantar.

Introduction: The hallux sesamoid are constant bones of small size and lentiform. They are located in the plantar region of the first metatarsal head within the capsule of the first metatarsophalangeal joint. The differential diagnosis of metatarsalgia over the first radius of the foot, without traumatic history, includes pathologies related to the sesamoids and others. Among the former are mainly sesamoiditis, stress fractures and avascular necrosis of the sesamoids. Objective: To report a case of sesamoiditis and its evolution after surgical treatment. Case report: This the case of a 25-year-old woman with a stress fracture of the fibular sesamoid. After serial infiltration with corticosteroids, it triggered a septic sesamoid necrosis, it was decided to perform a sesamoidectomy by plantar approach. Conclusions: Sesamoidectomy is a surgical option in degenerative processes of the sesamoids, when conservative treatments are insufficient. The plantar approach is considered adequate for removal of the fibular sesamoid. This technique requires adequate postoperative follow-up to optimize plantar healing.

A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials.

BACKGROUND: Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing. METHODS: We implemented VIGex using the nCounter platform (Nanostring) on a large clinical cohort encompassing 909 tumor samples across 45 tumor types. VIGex was developed as a continuous variable, with cutoffs selected to detect three main categories (hot, intermediate-cold and cold) based on the different inflammatory status of the tumor microenvironment. FINDINGS: Hot tumors had the highest VIGex scores and exhibited an increased abundance of tumor-infiltrating lymphocytes as compared with the intermediate-cold and cold. VIGex scores varied depending on tumor origin and anatomic site of metastases, with liver metastases showing an immunosuppressive tumor microenvironment. The predictive power of VIGex-Hot was observed in a cohort of 98 refractory solid tumor from patients treated in early-phase immunotherapy trials and its clinical performance was confirmed through an extensive metanalysis across 13 clinically annotated gene expression datasets from 877 patients treated with immunotherapy agents. Last, we generated a pan-cancer biomarker platform that integrates VIGex categories with the expression levels of immunotherapy targets under development in early-phase clinical trials. CONCLUSIONS: Our results support the clinical utility of VIGex as a tool to aid clinicians for patient selection and personalized immunotherapy interventions. FUNDING: BBVA Foundation; 202-2021 Division of Medical Oncology and Hematology Fellowship award; Princess Margaret Cancer Center.

Do peri-operative parathyroid hormone (PTH) analogues improve bone density and decrease mechanical complications in spinal deformity correction?-a minimum 2-year radiological study measuring Hounsfield units.

OBJECTIVE: To delineate whether use of a PTH analogue in the 1-year peri-operative period improves lumbar bone density. METHODS: A prospectively collected data registry of 254 patients who underwent CMIS correction of ASD (Cobb angle > 20 or SVA > 50 mm or (PI-LL) > 10) from Jan 2011 to Jan 2020 was analysed. Patients who were placed on PTH analogues for one year in conjunction with surgery were included in the study. Ultimately, 41 patients who had pre- and two-year post-operative CT scans for review were included in this study. Hounsfield units were measured off of the L1-L3 levels for all patients before and after surgery on pre-op and post-op CT scans. RESULT: The mean age of patients in this study was 70 (52-84, SD 7). Mean follow-up was 66 (24-132, SD 33) months. Twenty-three patients met criteria for severe deformity (Cobb angle > 50 degrees or SVA > 95 mm or PI/LL mismatch > 20 or PT > 30). Based off 2-year post-op CT scan, there were significant improvements in L1 Hounsfield units when comparing pre-op values (96; SD 55) to post-op values (185 SD 102); p. < 0.05. There was no screw loosening or screw pull out. There were 2 patients with PJF (4.8%). Both these patients had not completed their PTH treatment: one only took PTH for 3 months (PJF at 2-year post-op) and the other one took it only for 1 month (PJF at 1-year post-op). No increase in bone density was noted (based off of Hounsfield units) in five patients (12%) despite completion of their PTH therapy. Only one patient experienced nausea from PTH therapy. There were no other PTH related adverse events. CONCLUSION: The incidence of PTH analogues failing to increase bone density in our series was low at 12%. This study shows that PTH analogues may be a powerful adjunct for increasing bone density and may help to mitigate the risk of mechanical complications in patients undergoing deformity correction with minimally invasive techniques. Future comparative studies are warranted to confirm these latter findings and to potentially protocolize the ideal peri-operative bone health optimization strategy.

A shared origin from a common ancestor: A case report of two histologically different tumors.

The origin of tumors has been under discussion over the years. Different theories have been suggested to explain this phenomenon. Among them, the Cancer-Stem Cells model, is one of the most outstanding. In this study, we reported a case of a 72-year-old man who presented two histologically different tumors with a 7-years gap, a Penile Squamous Cell Carcinoma and a Pleomorphic Undifferentiated Sarcoma, that share some molecular features. Phonotypical differences were showed and confirmed at histological and IHC levels. Molecular analysis showed an HPV infection in the carcinoma. Additionally, sequencing results revealed common (CDKN2A and TERT) and exclusive (FBXW7 and TP53) genetic alterations in both tumors (Table 1). The possible germline origin of common mutations was discarded after negative germline testing. Here we describe, for the first time a clinical case of a possible origin of two histologically different tumors from a common ancestor based on molecular data. Even if different hypothesis appear as possible, the Cancer Stem Cell-based model appears as the most suitable.

A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells.

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify protein expression, and the zymography technique was used to observe the secretion of metalloproteinases. Molecular docking showed interactions in regions of interest of the FAK and Src proteins. Moreover, the biological activity assays demonstrated an inhibitory effect on cell migration and invasion, an important suppression of metalloproteinase secretion, and a decrease in the expression of p-FAK and p-Src proteins in treated PC3 cells. Triazaspirane-type molecules have important inhibitory effects on the mechanisms associated with metastasis in PC3 tumor cells.

Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor.

The World Health Organization's tumor classification guidelines are frequently updated and renewed as knowledge of cancer biology advances. For instance, in 2021, a novel lung tumor subtype named SMARCA4-deficient, undifferentiated tumor (SMARCA4-dUT, code 8044/3) was included. To date, there is no defined cell model for SMARCA4-dUT that could be used to help thoracic clinicians and researchers in the study of this newly defined tumor type. As this tumor type was recently described, it is feasible that some cell models formerly classified as lung adenocarcinoma (LUAD) could now be better classified as SMARCA4-dUT. Thus, in this work, we aimed to identify a bona fide cell model for the experimental study of SMARCA4-dUT. We compared the differential expression profiles of 36 LUAD-annotated cell lines and 38 cell lines defined as rhabdoid in repositories. These comparative results were integrated with the mutation and expression profiles of the SWI/SNF complex members, and they were surveyed for the presence of the SMARCA4-dUT markers SOX2, SALL4, and CD34, measured by RT-qPCR and western blotting. Finally, the cell line with the paradigmatic SMARCA4-dUT markers was engrafted into immunocompromised mice to assess the histological morphology of the formed tumors and compare them with those formed by a bona fide LUAD cancer cell line. NCI-H522, formerly classified as LUAD, displayed expression profiles nearer to rhabdoid tumors than LUAD tumors. Furthermore, NCI-H522 has most of the paradigmatic features of SMARCA4-dUT: hemizygous inactivating mutation of SMARCA4, severe SMARCA2 downregulation, and high-level expression of stem cell markers SOX2 and SALL4. In addition, the engrafted tumors of NCI-H522 did not display a typical differentiated glandular structure as other bona fide LUAD cell lines (A549) do but had rather a largely undifferentiated morphology, characteristic of SMARCA4-dUT. Thus, we propose the NCI-H522 as the first bona fide cell line model of SMARCA4-dUT. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Efecto del Ejercicio en el Medio Acuático sobre la Aptitud Física en Personas con Discapacidad Intelectual: Una Revisión Sistemática / Effect of Exercise in Aquatic Environments on Physical Fitness in People with Intellectual Disabilities: A Systematic Review / Efeito do exercício aquático sobre a aptidão física em pessoas com deficiência intelectual: uma revisão sistemática

Resumen: Los programas de ejercicio en el medio acuático proporcionan un ambiente motivante y divertido, en el cual las personas con discapacidad intelectual pueden realizar actividades deportivas o recreativas de manera accesible, lo que incide positivamente en la condición física. Propósito: El objetivo de la revisión sistemática fue conocer los efectos del ejercicio acuático sobre la aptitud física en personas con discapacidad intelectual. Metodología: Para lograr el propósito del estudio, se llevó a cabo una búsqueda de literatura en las bases de datos Sport Discus, Science Direct, Scopus y PubMed, cuyas publicaciones comprenden del 2009 al 2018; como criterios de inclusión debían especificar el tipo de ejercicio, los componentes de la carga de entrenamiento, el tipo de discapacidad que presentaban los sujetos del estudio y que la duración de la intervención fue mayor a 4 semanas. Resultados: Solamente 5 trabajos cumplieron los criterios de selección. Aquellos en los que aplicaron intervenciones de natación y ejercicio combinado indicaron que se mejoraron elementos de la aptitud física importantes para la salud, así como el desenvolvimiento de actividades de la vida diaria. Se pudo concluir que se requieren investigaciones con mayor rigor metodológico, para clarificar el efecto del ejercicio en el medio acuático sobre los componentes de la aptitud física en personas con discapacidad intelectual.

Abstract: Exercise programs in aquatic environments guarantee a motivating and fun environment in which people with intellectual disabilities can carry out sports or recreational activities in an accessible way, which has a positive effect on their physical condition. Purpose: the objective of the systematic review was to know the effects of aquatic exercise on physical fitness in people with intellectual disabilities. Methodology: To achieve the purpose of the study, a literature search was conducted in the Sport Discus, Science Direct, Scopus, and PubMed databases, whose publications cover from 2009 to 2018. As selection criteria, these publications had to specify the type of exercise, the components of a load of training, the type of disability presented by the study subjects, and the duration of the intervention that should be greater than four weeks. Results: Only five studies met the selection criteria. the studies in which they applied swimming interruption and combined exercise showed that components of physical fitness important for health were improved, as well as the development of activities of daily living. It was concluded that studies with greater methodological rigor are required to clarify the effect of exercise in aquatic environments on the components of physical fitness in people with intellectual disabilities.

Resumo: Os programas de exercícios aquáticos proporcionam um ambiente motivador e divertido no qual pessoas com deficiências intelectuais podem praticar esportes ou atividades recreativas de maneira acessível, o que tem um impacto positivo sobre a condição física. Objetivo: O objetivo da revisão sistemática era descobrir os efeitos do exercício aquático sobre a aptidão física das pessoas com deficiência intelectual. Metodologia: Para atingir o objetivo do estudo, foi feita uma pesquisa bibliográfica nas bases de dados Sport Discus, Science Direct, Scopus e PubMed, cujas publicações foram de 2009 a 2018. Como critérios de seleção, essas publicações tinham que especificar o tipo de exercício, os componentes de uma carga de treinamento, o tipo de deficiência apresentada pelos sujeitos do estudo e a duração da intervenção que devia ser superior a quatro semanas. Resultados: Apenas cinco estudos cumpriram os critérios de seleção. Os estudos nos quais foram aplicados intervenções de natação e exercícios combinados indicaram que os componentes de aptidão física importantes para a saúde, assim como no desempenho das atividades da vida diária, foram melhorados. Concluiu-se que são necessários estudos com maior rigor metodológico para esclarecer o efeito do exercício aquático sobre os componentes da aptidão física das pessoas com deficiência intelectual.

Rituximab en el tratamiento de esclerosis múltiple. Experiencia de un hospital de tercer nivel en México / Rituximab in the treatment of multiple sclerosis. Experience of a tertiary care hospital in Mexico

Resumen Antecedentes: La esclerosis múltiple es una enfermedad crónica, autoinmune y degenerativa. Las terapias blanco contra los linfocitos B han probado ser efectivas en su tratamiento; sin embargo, existen pocos estudios que evalúen su eficacia en población mexicana. Objetivo: Evaluar el impacto clínico del rituximab en pacientes con esclerosis múltiple remitente recurrente (EMRR) de reciente diagnóstico. Material y métodos: Estudio de vida real, descriptivo, en el que se evalúa rituximab como tratamiento de EMRR durante un periodo de 24 meses. Se analizaron variables clínicas pre y postratamiento; se realizó la comparación entre pacientes naïve y no naïve. Resultados: Se incluyeron 28 pacientes con EMRR. La edad media al diagnóstico fue de 30.7 años y 22 pacientes fueron naïve (78.5 %). Después de 24 meses, se observó una reducción media de 1.8 puntos en EDSS y en el número de lesiones activas por resonancia magnética. Aunque se logró establecer una diferencia significativa en ambas variables con p < 0.05, el modelo de regresión logística no mostró una relación entre las variables para alcanzar un NEDA-3. No se observaron eventos adversos graves. Conclusiones: El tratamiento con rituximab resultó en mejoría significativa clínica y radiológica en pacientes mexicanos con EMRR naïve y no-naïve.

Abstract Background: Multiple sclerosis is a chronic, autoimmune, degenerative disease. Therapies targeting B-cells have been shown to be effective in its treatment; however, there are few studies evaluating their efficacy in the Mexican population. Objective: To evaluate the clinical impact of rituximab in patients with newly-diagnosed relapsing-remitting multiple sclerosis (RRMS). Material and methods: Real life, descriptive study, in which rituximab was evaluated as treatment for RRMS over a 24-month period. Pre- and post-treatment clinical variables were analyzed; a comparison was made between treatment-naïve and non-treatment-naïve patients. Results: Twenty-eight patients with RRMS were included. Mean age at diagnosis was 30.7 years, and 22 patients were treatment-naïve (78.5 %). After 24 months, there was a mean reduction of 1.8 points in the EDSS scale and a decrease in the number of active lesions on magnetic resonance imaging; a significant difference in both variables could be established (p < 0.05). However, the logistic regression model did not show a relationship between the variables for achieving NEDA-3 criteria. No serious adverse events were observed. Conclusions: Treatment with rituximab resulted in significant clinical and radiological improvement in treatment-naïve and non-treatment-naïve Mexican patients with RRMS.

A Bayesian adaptive design for dual-agent phase I-II oncology trials integrating efficacy data across stages.

Combination of several anticancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main objective is to characterize both the toxicity and efficacy profiles. We propose a two-stage Bayesian adaptive design that accommodates a change of patient population in-between. In stage I, we estimate a maximum tolerated dose combination using the escalation with overdose control (EWOC) principle. This is followed by a stage II, conducted in a new yet relevant patient population, to find the most efficacious dose combination. We implement a robust Bayesian hierarchical random-effects model to allow sharing of information on the efficacy across stages, assuming that the related parameters are either exchangeable or nonexchangeable. Under the assumption of exchangeability, a random-effects distribution is specified for the main effects parameters to capture uncertainty about the between-stage differences. The inclusion of nonexchangeability assumption further enables that the stage-specific efficacy parameters have their own priors. The proposed methodology is assessed with an extensive simulation study. Our results suggest a general improvement of the operating characteristics for the efficacy assessment, under a conservative assumption about the exchangeability of the parameters a priori.