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Significance: Head and neck squamous cell carcinoma (HNSCC) has the sixth highest incidence worldwide, with > 650,000 cases annually. Surgery is the primary treatment option for HNSCC, during which surgeons balance two main goals: (1) complete cancer resection and (2) preservation of normal tissues to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissues, particularly nerves, and reduce life-altering comorbidities. Aim: Currently, no clinically validated technology exists to enhance intraoperative cancer and nerve recognition. Fluorescence-guided surgery (FGS) has successfully integrated into clinical medicine, providing surgeons with real-time visualization of important tissues and complex anatomy, where FGS imaging systems operate almost exclusively in the near-infrared (NIR, 650 to 900 nm). Notably, this spectral range permits the detection of two NIR imaging channels for spectrally distinct detection. Approach: Herein, we evaluated the utility of spectrally distinct NIR nerve- and tumor-specific fluorophores for two-color FGS to guide HNSCC surgery. Using a human HNSCC xenograft murine model, we demonstrated that facial nerves and tumors could be readily differentiated using these nerve- and tumor-specific NIR fluorophores. Results: The selected nerve-specific fluorophore showed no significant difference in nerve specificity and off-target tissue fluorescence in the presence of xenograft head and neck tumors. Co-administration of two NIR fluorophores demonstrated successful tissue-specific labeling of nerves and tumors in spectrally distinct NIR imaging channels. Conclusions: We demonstrate a comprehensive FGS tool for cancer resection and nerve sparing during HNSCC procedures for future clinical translation.
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Neoplasias de Cabeça e Pescoço , Imagem Óptica , Cirurgia Assistida por Computador , Cirurgia Assistida por Computador/métodos , Animais , Camundongos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imagem Óptica/métodos , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Camundongos NusRESUMO
Lung cancer continues to have one of the highest morbidity and mortality rates of any cancer. Although radiochemotherapy, in combination with immunotherapy, has significantly improved overall survival, new treatment options are urgently needed. However, preclinical radiotherapy testing is often performed in animal models, which has several drawbacks, including species-specific differences and ethical concerns. To replace animal models, this study used a micro-extrusion bioprinting approach to generate a three-dimensional (3D) human lung cancer model consisting of lung tumor cells embedded in human primary lung fibroblasts for radiotherapy research. The models were placed in a mouse phantom, i.e., a 3D-printed mouse model made of materials that mimic the X-ray radiation attenuation rates found in mice. In radiotherapy experiments, the model demonstrated a selective cytotoxic effect of X-rays on tumor cells, consistent with findings in 2D cells. Furthermore, the analysis of metabolic activity, cell death, apoptosis, and DNA damage-induced γH2AX foci formation revealed different results in the 3D model inside the phantom compared to those observed in irradiated models without phantom and 2D cells. The proposed setup of the bioprinted 3D lung model inside the mouse phantom provides a physiologically relevant model system to study radiation effects.
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Bioimpressão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Impressão Tridimensional , Animais , Camundongos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Bioimpressão/métodos , Linhagem Celular Tumoral , Imagens de Fantasmas , Modelos Animais de Doenças , Apoptose/efeitos da radiação , Dano ao DNA , Raios XRESUMO
Importance: Existing clinical trials favor neoadjuvant chemoradiation therapy (NCRT) followed by surgery alone for locally advanced esophageal cancer (EC) and perioperative chemotherapy as the preferred modality for esophageal adenocarcinoma (EAC). However, it is unclear whether these trial findings are reflected in the patterns of care and survival outcomes among patients in the clinical setting. Objective: To investigate survival outcomes in the clinical setting among patients with EC after various treatment modalities. Design, Setting, and Participants: This retrospective cohort study examined data from the National Cancer Database maintained by the American College of Surgeons and focused on patients with clinical stage II or III EC, excluding those with gastroesophageal junction cancer, who underwent trimodality therapy (NCRT followed by esophagectomy), definitive chemoradiation therapy (DCRT), radiotherapy (RT) alone, or perioperative chemotherapy from January 2006 to December 2020. Analyses were conducted from December 2023 to August 2024. Exposures: Perioperative chemotherapy, trimodality therapy, DCRT, and single-modality RT. Main Outcomes and Measures: A Cox proportional hazards regression model was used to compare overall survival (OS) between treatment groups in the entire cohort, among patients with squamous cell carcinoma or adenocarcinoma, and among those older than 65 years. Landmark survival analysis at 6 months was performed to reduce survivorship bias. Results: The study included 57â¯116 patients (median age, 64 [IQR, 57-72] years; 45â¯410 [79.5%] male); 21â¯619 patients (37.9%) received trimodality therapy, 32â¯493 (57.1%) received DCRT, 2692 (4.7%) received single-modality RT, and 312 (0.5%) received perioperative chemotherapy. In the overall study population, 37â¯698 patients (66.0%) had EAC, and of the 312 patients that received perioperative chemotherapy, 283 (90.7%) had EAC. In adjusted survival analysis, perioperative chemotherapy (adjusted hazard ratio [AHR], 0.33; 95% CI, 0.28-0.39; P <.001) and trimodality therapy (AHR, 0.45; 95% CI, 0.44-0.46; P < .001) were associated with improved OS compared with DCRT. In contrast, RT alone was associated with worse outcomes compared with DCRT (AHR, 1.37; 95% CI, 1.30-1.45; P < .001). The median OS for perioperative chemotherapy of 66.2 months (95% CI, 43.1-111.9 months; P < .001) was longer compared with that for DCRT alone (18.1 months; 95% CI, 17.8-18.4 months; P < .001). Trimodality therapy was associated with a median OS of 43.9 months (95% CI, 42.8-45.5 months; P < .001), which was shorter than that for perioperative chemotherapy but improved compared with DCRT and RT alone, which was associated with a median OS of 13.5 months (95% CI, 12.8-14.0 months; P < .001). In the subgroup of patients older than 65 years, those who received perioperative chemotherapy had longer median OS (56.7 months; 95% CI, 36.4-115.2 months; P < .001) compared with those receiving other treatment modalities (eg, trimodality therapy: 40.1 months; 95% CI, 38.1-42.0 months; P < .001). Patients who received RT alone had the worst median OS (13.6 months; 95% CI, 12.8-14.4 months; P < .001). Conclusions and Relevance: In this cohort study of patients with stage II to III EC, trimodality therapy was associated with improved OS compared with DCRT or RT alone for locally advanced EC and perioperative chemotherapy was associated with improved OS for adenocarcinoma.
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Adenocarcinoma , Neoplasias Esofágicas , Estadiamento de Neoplasias , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adenocarcinoma/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Esofagectomia , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Quimiorradioterapia/métodos , Quimiorradioterapia/estatística & dados numéricos , Modelos de Riscos Proporcionais , Terapia Combinada , Análise de SobrevidaRESUMO
BACKGROUND: The angiographic shape of an occlusion, like the clot meniscus sign and the claw sign, has been reported to potentially impact the recanalization rate and clinical outcome in patients undergoing mechanical thrombectomy for acute ischemic strokes. METHOD: Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, Embase and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl). RESULTS: We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR 1.95; 95% CI 0.76 to 5.01; P=0.167) and final recanalization (OR 1.36; 95% CI 0.81 to 2.27; P=0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive group than in the negative sign group (OR 1.91; 95% CI 1.25 to 2.92; P<0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared with using a stent retriever (OR 0.18; 95% CI 0.07 to 0.49; P<0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at 3 months (OR 0.22; 95% CI 0.02 to 2.33; P=0.210). CONCLUSION: The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence may need further confirmation.
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Background: Evidence regarding the effect of long-term exposure to particulate matter (PM) 2.5 and comorbid cancer and cardiovascular disease (CVD) mortality is limited. Objectives: In this study, the author report the association between long-term exposure to PM 2.5 and CVD mortality, cancer mortality and comorbid cancer and CVD mortality in the U.S. population. Methods: The Centers for Disease Control and Prevention (CDC) WONDER (Wide-Ranging Online Data for Epidemiologic Research) multiple-cause-of-death database was used to obtain U.S. county-level mortality and population estimates from 2016 to 2020. Data on average daily density of PM 2.5 were abstracted from the 2018 CDC's National Environmental Public Health Tracking system. Counties were divided into quartiles with Q1 representing counties with least average daily density and Q4 representing counties with maximum average daily density of PM 2.5. Age-adjusted mortality rates were abstracted for each quartile, for the overall population and subgroups of population. Results: The age-adjusted mortality rates for CVD, cancer, and comorbid cancer and CVD mortality were 505.3 (range: 505.0-505.7), 210.7 (range: 210.5-210.9), and 62.0 (range: 61.8-62.1) per 100,000 person-years, respectively. CVD mortality had the highest percentage excess mortality in Q4 compared with Q1, followed by comorbid cancer and CVD. Cancer had the least percentage excess mortality. A disproportionate effect of PM 2.5 exposure was noted on vulnerable and minority groups, based on Social Vulnerability Index and race stratification, respectively. Conclusions: Higher levels of long-term PM 2.5 exposure reported increased CVD mortality, cancer mortality and comorbid cancer and CVD disease mortality, with a pronounced detrimental effect in vulnerable and minority population.
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Though significant research highlights higher rates of mental ill-health and substance use among trans, non-binary and gender diverse (henceforth 'trans') young people, little research has considered patterns, contextual characteristics, and correlates of co-occurring experiences of mental ill-health and substance use among trans young people. Using data from the Trans Pathways study, we used prevalence ratios and age- and gender-adjusted logistic regression models to examine prevalence and differences of co-occurring substance use (past six-month cigarette use, alcohol use, and other drug use) and contextual characteristics of substance use (past six-month solitary alcohol and/or drug use, substance use for coping) by mental ill-health (depression disorder, anxiety disorder, past 12-month self-harm thoughts and behaviours, suicidal thoughts, planning, and attempt/s). Age- and gender-adjusted models assessed associations between co-occurring depressive and anxiety disorders and recent cigarette, alcohol, and other drug use (six co-occurring items total) and 18 interpersonal stressors. Significantly increased odds of smoking or recent use of cannabis or sedatives was observed among trans young people reporting depressive disorder, anxiety disorder (aORs ranging 1.8-3.1). Trans young people who reported recent smoking or use of cannabis, inhalants, or sedatives, had 40% to 80% reduced odds of past 12-month self-harm thoughts, self-harm behaviours, suicidal thoughts, and suicide attempt/s (aORs ranging 0.2-0.6). On the other hand, solitary alcohol and/or other drug use and substance use for coping was significantly associated with increased odds of all mental ill-health outcomes. Issues with school, secure housing, and intimate partner abuse were the most robust correlates of co-occurring mental ill-health and substance use. Trans young people using substances, especially cigarettes, cannabis, and sedatives, often so do with co-occurring experiences of depression and anxiety though limited substance use in more 'social' contexts may confer benefits for preventing self-harm and suicide thoughts and behaviours. Continued research in partnership with trans young people is warranted to conceptualise more nuanced and precise conceptual parameters of trans-affirming substance use harm reduction approaches.
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BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive treatment for lower limb varicose veins. Studies indicate that RFA results in immediate occlusion of 90%-100% of treated long saphenous veins. Evidence suggests that post-operative scans rarely alter patient management or outcomes. OBJECTIVE: The aim of this study was to assess the potential necessity of routine postoperative scanning in the treatment of varicose veins. METHOD: Retrospective data were collected for the patients who had RFA under a single consultant from November 2015 to June 2018. Descriptive statistics were calculated to summarize patient demographics, procedural details, and outcome measures. RESULTS: A total of 124 patients underwent radiofrequency ablation (RFA). Most of the patients (n = 114, 92%) demonstrated complete ablation, indicating a high success rate for the procedure. CONCLUSION: This study suggested that routine postoperative scanning should be discontinued as this did not alter patient management in over 99% of cases. The resources currently used for postoperative scans could be redirected towards other critical areas.
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STUDY OBJECTIVE: To evaluate if extraction laparotomy (EL) for intact specimen removal adversely impacted the feasibility or safety of same-day discharge (SDD) in patients undergoing minimally invasive surgery (MIS) for confirmed or suspected gynecologic malignancies. DESIGN: Retrospective study SETTING: Single institution study PATIENTS: Patients undergoing minimally invasive surgery for gynecologic malignancy at a single institution, who underwent extraction laparotomy (N=67) and age matched controls (N=134) INTERVENTIONS: Comparing same day discharge rates, complications, readmission and outpatient follow up after between patients requiring extraction laparotomy to those that did not after minimally invasive gynecologic surgery. MEASUREMENTS AND MAIN RESULTS: A total of 1224 patients were identified. Sixty-seven patients underwent EL for specimen extraction. From the remainder, 134 patients were selected as age matched controls. SDD rate was 83% (EL) vs. 87% (no EL) (p=.39). There was no difference in median pain scores (1.8 vs. 1.9 p=.86), length of stay (LOS) (0 days for both) (p=.41), 30-day readmission rate (6% vs. 3%) (p=.45), ED visit (13% vs. 10%) (p=.76) or any patient contact (34% vs. 39%) (p=.53), between the groups. Specimen weight was higher for EL (524g vs 142g, p<.001), as was estimated blood loss (EBL) (104ml vs. 46ml, p<.001), and surgery time was increased by 22 minutes in the EL group (121 min vs. 99 min, p<.001). Patients who underwent EL did require more narcotics in PACU 20.5 vs 12.2 OME p=.033, however this did not translate to increased number of narcotics prescribed at discharge. On logistic regression a higher specimen weight trended to increase the likelihood of admission (OR 1.04 CI 1.01-1.08), however, surgery time, time in PACU, race, BMI, surgery type or need for EL did not predict SDD or need for admission. CONCLUSIONS: Minimally invasive surgery patients who require extraction laparotomy can still achieve SDD. Same-day discharge is safe and feasible without increased risk of readmission, pain score, or unscheduled patient contact post-operatively.
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This study aimed to analyze the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy for B-cell lymphoma using published literature data. Literature on CAR-T therapy for B-cell lymphoma was collected by searching common databases. The literature was screened, quality assessed, and data extracted according to the inclusion and exclusion criteria. We performed a quantitative meta-analysis of the efficacy and safety of combined literature data. If the data could not be combined, descriptive analysis was performed. The meta-analysis results indicated that compared with tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) had higher objective response rate (ORR) and complete response rate, with odds ratio (OR) of 0.63 for both sides (95% confidence interval [CI], 0.50-0.79) and statistically significant differences. Partial response rate was lower with axi-cel than with tisa-cel, with an OR of 1.02 for tisa-cel versus axi-cel (95% CI, 0.75-1.40) and no statistically significant difference. Compared with tisa-cel, axi-cel had longer progression-free survival and overall survival, with risk ratios of 0.70 (95% CI, 0.62-0.80) and 0.71 (95% CI, 0.61-0.84) for axi-cel and tisa-cel, respectively. Compared with tisa-cel, axi-cel had higher incidence rates of cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS), with ORs of 3.84 (95% CI, 2.10-7.03) and 4.4 (95% CI, 2.81-6.91), respectively. CAR T-cell therapy is an effective treatment option for relapsed/refractory B-cell lymphoma. Axi-cel has better ORR and survival advantages compared with tisa-cel; however, axi-cel has higher incidence rates of CRS and ICANS compared with tisa-cel.
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Importance: Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. Objective: To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. Design, Setting, and Participants: Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. Exposures: Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. Results: The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). Conclusions and Relevance: In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.
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Transtorno Autístico , COVID-19 , Efeitos Tardios da Exposição Pré-Natal , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , Feminino , Gravidez , Masculino , Pré-Escolar , Lactente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtorno Autístico/epidemiologia , Transtorno Autístico/diagnóstico , Cidade de Nova Iorque/epidemiologia , Pandemias , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Programas de Rastreamento/métodos , Estudos Prospectivos , Adulto , Estudos Longitudinais , Estudos de CoortesRESUMO
BACKGROUND: Numerous conditions may lead to gastrointestinal bleeding (GIB). Compared with common causes, hemosuccus pancreaticus (HP) is a scarce and potentially life-threatening condition. CASE PRESENTATION: We report the case of a 45-year-old female patient who suffered from hematemesis and subsequent hemorrhagic shock. In repeat esophagogastroduodenoscopies, bleeding from the major duodenal papilla was detected. To stop the acute bleeding, an ERCP was performed, and a plastic stent was inserted into the pancreatic duct (PD). Subsequently, MR and CT scans demonstrated a pseudoaneurysm of the splenic artery (SA) with a fistula to the PD. An interventional therapy approach failed due to a highly twisted course of the SA. Thus, the patient underwent surgery with ligation of the SA. The stent from the PD was removed postoperatively, and the patient recovered well. A histological examination of the SA revealed fibromuscular dysplasia. A lifelong ASA therapy was prescribed, and the patient was discharged on the 14th postoperative day in good condition. CONCLUSION: The diagnosis and treatment of HP might be impeded due to its multiple causes, ambiguous symptoms, and challenging diagnostic verification. Being a potentially life-threatening condition, the knowledge of this rare entity and the provision of multidisciplinary and multimodal therapy are mandatory for the successful treatment of patients with obscure GIB and proven HP.
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Ductos Pancreáticos , Artéria Esplênica , Humanos , Feminino , Pessoa de Meia-Idade , Artéria Esplênica/diagnóstico por imagem , Ductos Pancreáticos/patologia , Ductos Pancreáticos/diagnóstico por imagem , Resultado do Tratamento , Terapia Combinada , Aneurisma Roto/terapia , Aneurisma Roto/cirurgia , Aneurisma Roto/diagnóstico por imagem , Stents , Fístula Pancreática/terapia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Fístula Pancreática/diagnóstico por imagem , Fístula Pancreática/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , LigaduraRESUMO
BACKGROUND: T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. RESULTS: The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. CONCLUSIONS: Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic.
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Imunoterapia , Verde de Indocianina , Anticorpos de Domínio Único , Linfócitos T , Animais , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Camundongos , Linfócitos T/imunologia , Verde de Indocianina/química , Imunoterapia/métodos , Linhagem Celular Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Feminino , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Lipossomos/química , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Complexo CD3/imunologiaRESUMO
INTRODUCTION: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). The review compiled genomic diversity data, incidence, and risk factor differences by geographical and racial cohorts. METHODS: The review methodology was created using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles from articles on PubMed and Embase through July 31, 2023, written and published in English, with diagnoses of primary or metastatic ccRCC via cytology or pathology, recorded the incidence of one or more of the 6 biomarkers, explored gene aberration via sequencing, were epidemiological in nature, and/or discussed basic science research, cohort studies, or retrospective studies. RESULTS: Aberrations in vHL, PBRM1, and SETD2 driving ccRCC are studied frequently, but the data are heterogeneous, whereas there is a paucity in the data regarding KDM5C, PBRM1, and mTOR mutations. CONCLUSION: Studying the genetic aberrations that frequently occur in different regions gives insight into what current research lacks. When more genomic landscape research arises, precision therapy, risk calculators, and artificial intelligence may help better prognosticate and individualize treatment for those at risk for ccRCC. Provided the scarcity of existing data, and the rising prevalence of ccRCC, more studies must be conducted at the clinical level.
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BACKGROUND: Radiocapitellar arthritis can cause pain, loss of motion, and impaired elbow function. Current surgical treatment options are limited. We have developed an original and simple surgical technique to address this, called arthroscopic matched osteoplasty of the radial head (AMOR). In AMOR, the radial head is partially resected and recontoured to match the capitellum and decompress the degenerate radiocapitellar articulation while preserving the ulnohumeral articulation where the cartilage is usually well preserved. METHODS: Indications and the surgical technique of the AMOR procedure are described. A retrospective observational service evaluation study was conducted from electronic patient records. Collected clinical outcomes included range of motion, pain level, subjective functional score, and general satisfaction with the results of the procedure. The radiographic outcome was radiocapitellar joint space. RESULTS: Between 2017 and 2021, eight consecutive patients underwent AMOR as part of an arthroscopic osteocapsular arthroplasty procedure. Radiographically, the mean radiocapitellar joint space improved from an average of 1.7 mm to 4.6 mm. Clinically, the mean pain score decreased from 8/10 to 3/10. Six of the eight patients (75%) were satisfied with their results. In two cases, initial improvement following surgery lasted less than 1 year, and one of these patients underwent total elbow arthroplasty for painful ulnohumeral osteoarthritis. There were no complications of surgery recorded. CONCLUSIONS: AMOR is a safe treatment option for painful radiocapitellar osteoarthritis and can be incorporated as an "add-on" procedure by surgeons performing elbow osteocapsular arthroplasty in cases with a positive grip and grind test and radiographic evidence of radiocapitellar OA. Level of evidence: IV.
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Airborne radioactivity from fossil fuel production systems is poorly characterized, but a recent study showed elevated ambient levels with proximity to oil and gas production wells. Here, we report year-long, high temporal resolution monitoring results of airborne alpha radioactivity from both radon gas and radon progeny attached to particulates immediately northeast of an oil refinery in Commerce City, Colorado, USA, in an environmental justice community of concern. Gas and particle-associated radioactivity contributed nearly evenly to the total alpha radioactivity. Total radioactivity levels of 30-40 Bq m-3 were 2-3 times higher than background levels (~10-15 Bq m-3) when winds were light and southwesterly, suggesting the refinery as the geographic origin. Furthermore, elevated airborne radioactivity tracked most closely with the light hydrocarbon and natural gas tracer ethane. Thus, the data imply natural gas as the radon emission carrier. Our findings are unique and suggest a need for further investigations of radon emissions from oil and gas infrastructure such as natural gas processing plants, compressor stations, petrochemical plants, and oil refineries that process oil and natural gas from unconventional production.Implications: Regulatory agencies currently do not mandate or conduct monitoring of radioactivity releases and public exposure from petroleum industry air emissions. This study reports elevated radioactivity from radon gas and nonvolatile radon decay products attached to particulate matter, at about 2-3 times above background levels in proximity to Colorado's largest oil refinery. Observations were within an environmental justice community of concern that experiences well above-average exposure to many other harmful atmospheric pollutants, suggesting potential adverse health effects from this cumulative exposure. Our findings offer actionable insights for policymakers, industry stakeholders, and affected communities alike.
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Acute limb ischemia (ALI) is a vascular emergency that needs to be diagnosed and treated quickly to prevent permanent tissue damage and amputation. Catheter-directed thrombolysis is a possible treatment option for mild to moderate ALI, with improved results from endovascular procedures and thrombolytic drugs. However, patients receiving thrombolysis may experience higher rates of distal embolization, serious bleeding events, and stroke than those undergoing surgery. The review article emphasizes the need for postoperative and extended management of ALI patients, including monitoring for compartment syndrome, managing reperfusion damage, and reducing changeable cardiovascular risk factors such as lipid-lowering therapy, diabetes management, and smoking cessation. Complications that can arise from thrombolytic therapy are also discussed, including hemorrhagic complications, minor bleeding, and reperfusion damage, with recommendations to monitor patients closely during treatment and discontinue therapy immediately if any abnormalities are detected. Follow-up evaluations for patients, including Doppler ultrasound, ankle brachial index, pulse volume recordings, and laboratory tests, are recommended to ensure the best possible outcome for patients with ALI.
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INTRODUCTION: There is a dire paucity of research into the burden, correlates and motives of substance use among trans young people in Australia. METHOD: Using data from a national survey of Australian trans young people (N = 859, Mage = 19.4), we estimated prevalence of past 6-month substance use (tobacco, alcohol, cannabis, other drugs) and lifetime substance use disorder diagnoses. Covariate-adjusted multivariate logistic regression models tested associations between substance use types with 18 interpersonal factors. Open-ended responses regarding substance use motives (n = 489) were qualitatively analysed using thematic analysis with an interpretative phenomenological approach. RESULTS: Prevalence of lifetime substance use disorder diagnosis was 13.5% (95% confidence interval [CI] 11.1, 16.1). Alcohol use was most reported (72.4%; 95% CI 68.9, 75.6) followed by tobacco (31.1%; 95% CI 27.7, 34.6) and cannabis (30.6%; 95% CI 27.2, 34.2). Trans women reported highest rates of alcohol and cannabis use; use of other drugs was highest among trans men. Highest risk of substance use was observed among trans youth who experienced discrimination, intimate partner abuse, peer rejection and lack of family support (adjusted odds ratios ranging 1.5 to 3.0). Four multi-levelled themes of substance use motives were identified: circumstantial use, somatic use, feeling better about oneself and one's life, and harm reduction. DISCUSSION AND CONCLUSIONS: While substance use among trans young is largely circumstantial, hedonistic and altruistic, facilitating self-exploration, friendship and community connectedness, substance use among trans young people is highly prevalent and may be used to cope with sleep difficulties, depression/anxiety and cisnormativity, including delays and waitlists for accessing gender-affirming care.
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Eating disorders (EDs) are severe mental illnesses with a multifactorial etiology and a chronic course. Among the biological factors related to pathogenesis and maintenance of EDs, inflammation acquired growing scientific interest. This study aimed to assess the inflammatory profile of EDs, focusing on anorexia nervosa, bulimia nervosa, and including for the first time binge eating disorder. A comprehensive research of existing literature identified 51 eligible studies for meta-analysis, comparing levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), osteoprotegerin (OPG), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), interleukin-1ß (IL-1ß), and interleukin-10 (IL-10) between patients with EDs and healthy controls (HCs). The systematic review explored other inflammatory biomarkers of interest, which did not meet the meta-analysis criteria. Results revealed significantly elevated levels of TNF-α, OPG, sRANKL, and IL-1ß in patients with EDs compared to HCs. Additionally, the results highlighted the heterogeneity of inflammatory state among patients with EDs, emphasizing the need for further research into the association between inflammatory biomarkers and psychopathological correlates. This approach should transcend categorical diagnoses, enabling more precise subcategorizations of patients. Overall, this study contributed to the understanding of the inflammatory pathways involved in EDs, emphasizing potential implications for diagnosis, staging, and targeted interventions.
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Biomarcadores , Inflamação , Humanos , Biomarcadores/sangue , Inflamação/sangue , Inflamação/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Osteoprotegerina/sangue , Proteína C-Reativa/metabolismo , Interleucina-1beta/sangue , Interleucina-6/sangue , Anorexia Nervosa/sangue , Anorexia Nervosa/diagnósticoRESUMO
Background: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM) and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over two years from HT initiation. Results: After propensity score matching, 2,155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (HR 0.689, 95% CI 0.582-0.816; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations and all-cause mortality. Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.