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1.
Cells ; 13(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273054

RESUMO

The mechanisms underlying the sustained activation of the PI3K/AKT and Wnt/ß-catenin pathways mediated by HOTAIR in cervical cancer (CC) have not been extensively described. To address this knowledge gap in the literature, we explored the interactions between these pathways by driving HOTAIR expression levels in HeLa cells. Our findings reveal that HOTAIR is a key regulator in sustaining the activation of both signaling pathways. Specifically, altering HOTAIR expression-either by knockdown or overexpression-significantly influenced the transcriptional activity of the PI3K/AKT and Wnt/ß-catenin pathways. Additionally, we discovered that HIF1α directly induces HOTAIR transcription, which in turn leads to the epigenetic silencing of the PTEN promoter via DNMT1. This process leads to the sustained activation of both pathways, highlighting a novel regulatory axis involving HOTAIR and HIF1α in cervical cancer. Our results suggest a new model in which HOTAIR sustains reciprocal activation of the PI3K/AKT and Wnt/ß-catenin pathways through the HOTAIR/HIF1α axis, thereby contributing to the oncogenic phenotype of cervical cancer.


Assuntos
Metilação de DNA , Subunidade alfa do Fator 1 Induzível por Hipóxia , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Neoplasias do Colo do Útero , Via de Sinalização Wnt , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Via de Sinalização Wnt/genética , Células HeLa , Metilação de DNA/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Regulação Neoplásica da Expressão Gênica , beta Catenina/metabolismo , beta Catenina/genética , Regiões Promotoras Genéticas/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética
2.
Lancet Public Health ; 9(9): e644-e653, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39181156

RESUMO

BACKGROUND: Excessively high and low temperatures substantially affect human health. Climate change is expected to exacerbate heat-related morbidity and mortality, presenting unprecedented challenges to public health systems. Since localised assessments of temperature-related mortality risk are essential to formulate effective public health responses and adaptation strategies, we aimed to estimate the current and future temperature-related mortality risk under four climate change scenarios across all European regions. METHODS: We modelled current and future mortality due to non-optimal temperatures across 1368 European regions, considering age-specific characteristics and local socioeconomic vulnerabilities. Overseas territories were excluded from the analysis. We applied a three-stage method to estimate temperature-related risk continuously across age and spatial dimensions. Age and city-specific exposure-response functions were obtained for a comprehensive list of 854 European cities from the Urban Audit dataset of Eurostat. Regional aggregates were calculated using an aggregation and extrapolation method that incorporates the risk incidence in neighbouring cities. Mortality was projected for present conditions observed in 1991-2020 and for four different levels of global warming (1·5°C, 2°C, 3°C, and 4°C increase) by regions, and subregions using an ensemble of 11 climate models produced by the Coordinated Regional Climate Downscaling Experiment-CMIP5 over Europe, and population projection data from EUROPOP2019. FINDINGS: Our results highlight regional disparities in temperature-related mortality across Europe. Between 1991 and 2020, the number of cold-related deaths was 2·5 times higher in eastern Europe than western Europe, and heat-related deaths were 6 times higher in southern Europe than in northern Europe. During the same time period, there were a median of 363 809 cold-related deaths (empirical 95% CI 362 493-365 310) and 43 729 heat-related deaths (39 880-45 921), with a cold-to-heat-related death ratio of 8·3:1. Under current climate policies, aligned with 3°C increase in global warming, it is estimated that temperature-related deaths could increase by 54 974 additional deaths (24 112-80 676) by 2100, driven by rising heat-related deaths and an ageing population, resulting in a cold-to-heat-related death ratio of 2·6:1. Climate change is also expected to widen disparities in regional mortality, particularly impacting southern regions of Europe as a result of a marked increase in heat-related deaths. INTERPRETATION: This study shows that regional disparities in temperature-related mortality risk in Europe are substantial and will continue to increase due to the effects of climate change and an ageing population. The data presented can assist policy makers and health authorities in mitigating increasing health inequalities by prioritising the protection of more susceptible areas and older population groups. We identify the projected areas of heightened risk (southern Europe), where policy intervention aimed at building adaptation and enhancing resilience should be prioritised. FUNDING: European Commission.


Assuntos
Mudança Climática , Humanos , Europa (Continente)/epidemiologia , Idoso , Pessoa de Meia-Idade , Adulto , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Mortalidade/tendências , Lactente , Temperatura Alta/efeitos adversos , Idoso de 80 Anos ou mais , Modelos Teóricos , Recém-Nascido , Previsões
3.
Discov Oncol ; 15(1): 378, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196408

RESUMO

BACKGROUND: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. METHODS: Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. RESULTS: Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA's. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. CONCLUSIONS: This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

4.
Eur Radiol Exp ; 8(1): 95, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186171

RESUMO

BACKGROUND: We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration. METHODS: We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1-2), moderate (grade 3-4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality. RESULTS: In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3-4) and good image quality (median 4; interquartile range 4-4). CONCLUSION: DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs. RELEVANCE STATEMENT: Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated. KEY POINTS: A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI.


Assuntos
Colágeno , Degeneração do Disco Intervertebral , Imageamento por Ressonância Magnética , Vértebras Torácicas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Degeneração do Disco Intervertebral/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
Cells ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891028

RESUMO

Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Inflamação , MicroRNAs , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Adulto , Inflamação/genética , Inflamação/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Células HeLa , Janus Quinase 1/metabolismo , Janus Quinase 1/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Pessoa de Meia-Idade
6.
Res Sq ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38853915

RESUMO

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

7.
Br J Clin Pharmacol ; 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38817150

RESUMO

AIMS: To investigate perioperative opioid requirements in patients on methadone or buprenorphine as medication for opioid-use disorder (MOUD) who attended a transitional pain clinic (Personalized Pain Program, PPP). METHODS: This retrospective cohort study assessed adults on MOUD with surgery and attendance at the Johns Hopkins PPP between 2017 and 2022. Daily non-MOUD opioid use over 6 time-points was evaluated with regression models controlling for days since surgery. The time to complete non-MOUD opioid taper was analysed by accelerated failure time and Kaplan-Meier models. RESULTS: Fifty patients (28 on methadone, 22 on buprenorphine) were included with a median age of 44.3 years, 54% male, 62% Caucasian and 54% unemployed. MOUD inpatient administration occurred in 92.8% of patients on preoperative methadone but only in 36.3% of patients on preoperative buprenorphine. Non-MOUD opioid use decreased over time postoperatively (ß = -0.54, P < .001) with a median decrease of 90 mg morphine equivalents (MME) between the first and last PPP visit, resulting in 46% tapered off by PPP completion. Older age and duration in PPP were associated with lower MME, while mental health conditions, longer hospital stays and higher discharge opioid prescriptions were associated with higher MME. The average time to non-MOUD opioid taper was 1.79× longer in patients on buprenorphine (P = .026), 2.75× in males (P = .023), 4.66× with mental health conditions (P < .001), 2.37× with chronic pain (P = .031) and 3.51× if on preoperative non-MOUD opioids; however, higher initial MOUD level decreased time to taper (P = .001). CONCLUSIONS: Postoperative opioid tapering utilizing a transitional pain service is possible in patients on MOUD.

8.
PLoS One ; 19(5): e0298154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809901

RESUMO

BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.


Assuntos
Países em Desenvolvimento , Neoplasias Ovarianas , Qualidade de Vida , Humanos , Feminino , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/diagnóstico , Inquéritos e Questionários , Ásia/epidemiologia , África/epidemiologia , América do Sul/epidemiologia , Taxa de Sobrevida , Adulto , Pessoa de Meia-Idade
9.
PLoS One ; 19(5): e0303250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38718003

RESUMO

The spatial patterns of taxonomic diversity of annelid polychaete species from the continental shelf in the Southern Gulf of Mexico were examined in this study. We used taxonomic distinctness and its spatial variations to explore the diversity patterns and how they change between Southern Gulf of Mexico regions. In addition, using taxonomic distinctness as a dissimilarity measure and Ward's Clustering, we characterized three distinct faunal assemblages. We also investigated patterns of richness, taxonomic distinctness, and distance decay of similarity between sampling stations as a ß-diversity measure. Finally, we examined the spatial relationships between polychaete assemblages and environmental variables to test the relative importance of spatial and environmental components in annelid polychaete community structure from the Southern Gulf of Mexico. We used a combination of eigenvector-based multivariate analyses (dbMEMs) and distance-based redundancy analysis (dbRDA) to quantify the relative importance of these explanatory variables on the spatial variations of taxonomic distinctness. The significance level of spatial and environmental components to the distribution of polychaete species showed that the combined effect of spatial processes and sediment characteristics explained a higher percentage of the variance than those parameters could alone.


Assuntos
Biodiversidade , Poliquetos , Animais , Golfo do México , Poliquetos/classificação , Ecossistema , Sedimentos Geológicos
10.
PLoS One ; 19(4): e0300536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635573

RESUMO

Nurses' household preparedness is critical if they are to avoid role conflict and report for duty during an emergency. To date, the alignment between nurses' perceived and actual household preparedness remains under examined. Investigating one of these variables in isolation fails to consider that perceived and actual household preparedness must be high and aligned. If misaligned, vulnerabilities could surface during emergencies, like concerns about family safety, potentially impacting a nurse's commitment to duty during a crisis, or nurses may lack the actual preparedness to continue working long hours during an emergency. An online questionnaire was distributed to registered nurses in Ireland. The questionnaire was informed by a review of the literature and captured nurses' perceived and actual household preparedness, attitudes towards and exposure to a range of emergencies, and pertinent demographic characteristics. The results showed a relationship between how nurses view their household preparedness and their actual preparedness. Regression analyses indicate that while there is an overlap, the factors associated with how prepared nurses think they are and how prepared they are can differ. This means that strategies to boost actual preparedness may differ from those needed to boost perceived preparedness. This finding underscores the importance of psychosocial preparedness. Feeling prepared is crucial as it can influence how one responds in an emergency. Considering both the perceived and actual aspects of household preparedness can lead to a more effective response during emergencies.


Assuntos
Planejamento em Desastres , Enfermeiras e Enfermeiros , Humanos , Atitude do Pessoal de Saúde , Emergências , Inquéritos e Questionários , Irlanda
11.
Phys Chem Chem Phys ; 26(18): 13667-13674, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38563329

RESUMO

We characterize the effect of rubidium ions on water-ice nanoislands in terms of area, fractal dimension, and apparent height by low-temperature scanning tunneling microscopy. Water nanoislands on the pristine Cu(111) surface are compared to those at similar coverage on a Rb+ pre-covered Cu(111) surface to reveal the structure-giving effect of Rb+. The presence of Rb+ induces changes in the island shape, and hence, the water network, without affecting the nanoisland volume. The broad area distribution shifts to larger values while the height decreases from three bilayers to one or two bilayers. The nanoislands on the Rb+ pre-covered surface are also more compact, reflected in a shift in the fractal dimension distribution. We relate the changes to a weakening of the hydrogen-bond network by Rb+.

12.
Diagnostics (Basel) ; 14(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38472968

RESUMO

BACKGROUND: Despite a considerable amount of literature on dual-energy CT (DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. METHODS: Consecutive venous DECT scans of the head and neck were reviewed, and unremarkable exams were included (n = 617). A total of 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male (n = 403) vs. female (n = 214); young (n = 207) vs. middle-aged (n = 206) vs. old (n = 204); and normal weight (n = 314) vs. overweight (n = 196) vs. obese (n = 107)). RESULTS: Overall mean iodine uptake values ranged between 0.5 and 9.4 mg/mL. Women showed higher iodine concentrations in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p ≤ 0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for the tongue and palatine tonsils were lower compared to younger subjects (p ≤ 0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with a higher BMI (p ≤ 0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with a higher BMI (p ≤ 0.04). CONCLUSION: physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in the clinical routine of head and neck DECT.

13.
Int J Gynecol Cancer ; 34(7): 1020-1026, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453180

RESUMO

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.


Assuntos
Neoplasias do Endométrio , Testes Genéticos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , México/epidemiologia , Brasil/epidemiologia , Pessoa de Meia-Idade , Estados Unidos , Testes Genéticos/estatística & dados numéricos , Testes Genéticos/métodos , Adulto , Idoso
14.
Evol Med Public Health ; 12(1): 50-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380130

RESUMO

In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and foetus, that evolved to reduce risks of obstructed labour. First, the foetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain foetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote foetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessively for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk.

15.
Int J Surg Pathol ; : 10668969231225773, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389391

RESUMO

INTRODUCTION: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. METHODS: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. RESULTS: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). CONCLUSION: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

16.
Eur Radiol ; 34(8): 5370-5378, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38221584

RESUMO

BACKGROUND: Although core needle biopsy is an important tool in minimally invasive tissue sampling and diagnostics for head and neck masses, comprehensive data about safety and outcomes is lacking. PURPOSE: To retrospectively evaluate the diagnostic performance and safety of computed tomography (CT)-guided percutaneous core needle biopsy of head and neck masses. MATERIAL AND METHODS: This retrospective single-center study included patients from 04/2007 to 12/2021, and a total of 156 core needle biopsies were evaluated. The initial histopathological results were compared with the long-term final diagnosis to evaluate the diagnostic yield of CT-guided core needle biopsies. The patients' age, sex, and history of malignancy, as well as procedural complications and radiation exposure were collected. RESULTS: A total of 156 biopsies of 150 patients (mean age 56 years ± 17; 89 men) were evaluated. 57.3% (86/150) of patients had a history of malignancy. 55.1% (86/156) of the lesions were accessed by an infrahyoid needle approach. 92.9% (145/156) of biopsies yielded conclusive results. There were no false positives and 4 false negatives, resulting in a total false negative rate of 2.7% (4/145) and a total diagnostic yield of 90.4% (141/156). There were nine puncture-related complications (9/156-5.7%). None of the complications required further reintervention. The average dose length product was 311.3 mGy × cm. CONCLUSION: CT-guided core needle biopsies of head and neck masses showed excellent results with high diagnostic yield and clinical safety. CLINICAL RELEVANCE STATEMENT: General anesthesia for open biopsy carries a higher risk for elderly patients, and fine needle aspiration has a poor reputation in terms of its diagnostic yield. This study focuses on safety and diagnostic yield of CT-guided core needle biopsies. KEY POINTS: • CT-guided core needle biopsy in head and neck tumors was a reliable and safe procedure. • The most common cause for an inconclusive biopsy result was a shortage of tissue collected during the biopsy. • During our study period of nearly 15 years, the radiation exposure of head and neck biopsies decreased.


Assuntos
Neoplasias de Cabeça e Pescoço , Biópsia Guiada por Imagem , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/efeitos adversos , Radiografia Intervencionista/métodos , Idoso , Adulto , Idoso de 80 Anos ou mais
17.
Vasc Endovascular Surg ; 58(5): 567-570, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38240584

RESUMO

Coil migration during endovascular embolization is a complication that can result in thromboembolic occlusion leading to potentially large infarcts if not removed. Microsnares are commonly used to remove migrated coils. Current techniques, however, struggle in cases where the microsnare is unable to loop over and secure a free end of the coil. We present a case in which a microsnare combined with a microwire successfully removed a migrated coil in a patient with a bleeding hepatic pseudoaneurysm post-embolization. This technique proved beneficial when traditional methods were insufficient, especially in small vessels or coil packs that cannot be snared. The synergy of the microsnare and microwire technique presents a promising solution for challenging migrated coil retrievals.


Assuntos
Falso Aneurisma , Remoção de Dispositivo , Embolização Terapêutica , Migração de Corpo Estranho , Humanos , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/terapia , Migração de Corpo Estranho/cirurgia , Embolização Terapêutica/instrumentação , Resultado do Tratamento , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Falso Aneurisma/etiologia , Artéria Hepática/diagnóstico por imagem , Masculino , Hemorragia/etiologia , Hemorragia/terapia , Idoso , Desenho de Equipamento , Feminino
20.
Curr Environ Health Rep ; 10(4): 478-489, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38052753

RESUMO

PURPOSE OF REVIEW: This review addresses the pressing issue of air pollution's threat to human health, focusing on its connection to non-small cell lung cancer (NSCLC) development. The aim is to explore the role of extracellular vesicles (EVs) as potential pathogenic mechanisms in lung cancer, including NSCLC, induced by air pollutants. RECENT FINDINGS: Recent research highlights EVs as vital mediators of intercellular communication and key contributors to cancer progression. Notably, this review emphasizes the cargo of EVs released by both cancerous and non-cancerous lung cells, shedding light on their potential role in promoting various aspects of tumor development. The review underscores the importance of comprehending the intricate interplay between air pollution, biological damage mechanisms, and EV-mediated communication during NSCLC development. Major takeaways emphasize the significance of this understanding in addressing air pollution-related lung cancer. Future research avenues are also highlighted, aiming to enhance the applicability of EVs for diagnosis and targeted therapies, ultimately mitigating the inevitable impact of air pollution on NSCLC development and treatment.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos
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