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1.
Front Public Health ; 12: 1392074, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39324158

RESUMEN

Background: Health equity is defined as the absence of unjust and avoidable disparities in access to healthcare, quality of care, or health outcomes. The World Health Organization (WHO) has developed a conceptual framework that outlines the main causes of health inequalities and how these contribute to health inequities within a population. Despite the WHO implementing health equity policies to ensure accessibility and quality of healthcare services, disparities persist in the management of patients suffering from low back pain (LBP). The objective of this study was to review the existing evidence on the impact of health inequities on the care trajectories and treatments provided to individuals with LBP. Methods: A narrative review was performed, which included a literature search without language and study design restrictions in MEDLINE Ovid database, from January 1, 2000, to May 15, 2023. Search terms included free-text words for the key concepts of "low back pain," "health inequities," "care pathways," and "sociodemographic factors." Results: Studies have revealed a statistically significant association between the prevalence of consultations for LBP and increasing age. Additionally, a significant association between healthcare utilization and gender was found, revealing that women were more likely to seek medical attention for LBP compared to men. Furthermore, notable disparities related to race and ethnicity were identified, more specifically in opioid prescriptions, spinal surgery recommendations, and access to complementary and alternative medical approaches for LBP. A cross-sectional analysis found that non-Hispanic White individuals with chronic LBP were more likely to be prescribed one or more pharmacological treatments. Lower socioeconomic status and level of education, as well as living in lower-income areas were also found to be associated with greater risks of receiving non-guideline concordant care, including opioid and MRI prescriptions, before undergoing any conservative treatments. Conclusion: Persistent inequalities related to sociodemographic determinants significantly influence access to care and care pathways of patients suffering from LBP, underscoring the need for additional measures to achieve equitable health outcomes. Efforts are needed to better understand the needs and expectations of patients suffering from LBP and how their individual characteristics may affect their utilization of healthcare services.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Disparidades en Atención de Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Masculino , Factores Socioeconómicos , Femenino , Factores Sociodemográficos , Determinantes Sociales de la Salud/estadística & datos numéricos , Inequidades en Salud
2.
Artículo en Inglés | MEDLINE | ID: mdl-39283714

RESUMEN

Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20). MHC-II immunostaining of myofibers was abnormal in 63/103 of patients (61%) but the patterns differed according to the IIM subgroup. They were diffuse in IBM (96%), negative in IMNM (83%), perifascicular in ASyS (70%), negative (61%) or perifascicular (32%) in DM, and either clustered (40%), perifascicular (30%), or diffuse heterogeneous (15%) in OM. Capillary MHC-II immunostaining also identified quantitative (capillary dropout, n = 47/88, 53%) and qualitative abnormalities, that is, architectural abnormalities, including dilated and leaky capillaries, (n = 79/98, 81%) in all IIM subgroups. Thus, MHC-II myofiber expression patterns allow distinguishing among IIM subgroups. We suggest the addition of MHC-II immunostaining to routine histological panels for IIM diagnosis.

3.
J Autism Dev Disord ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39127972

RESUMEN

A scoping review of the literature was undertaken using JBI guidelines to map the evidence of parent-led therapy (PLT) for young autistic children (≤ 6 years) raised in bilingual environments. Reviewers used Covidence to screen located sources. Sixteen papers met inclusion criteria. A strong acceleration of reports of PLT for young autistic children measured in bilingual environments was observed, with 93.8% of papers (n = 15) published since 2015. Reporting of participants' language environments (home language(s)/L1s and societal language(s)/L2s) was inconsistent. A large majority of these studies, 87.5% (n = 14) were conducted in North America or in collaboration with a North American institution. Diverse PLT programs and methodologies were identified. There is variation in demographic information collected and outcomes reported. Evidence gaps in the literature are identified and the value of undertaking systematic review on this topic is considered. This scoping review points to the necessity of further empirical research and practice that centres parents in early and specific support for autistic children raised in bilingual environments. Suggestions for improving reporting standards of language profiles are provided.

4.
iScience ; 27(7): 110037, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39021809

RESUMEN

Although the roles of embryonic yolk sac-derived, resident microglia in neurodevelopment were extensively studied, the possible involvement of bone marrow-derived cells remains elusive. In this work, we used a fate-mapping strategy to selectively label bone marrow-derived cells and their progeny in the brain (FLT3+IBA1+). FLT3+IBA1+ cells were confirmed to be transiently present in the healthy brain during early postnatal development. FLT3+IBA1+ cells have a distinct morphology index at postnatal day(P)0, P7, and P14 compared with neighboring microglia. FLT3+IBA1+ cells also express the microglial markers P2RY12 and TMEM119 and interact with VGLUT1 synapses at P14. Scanning electron microscopy indeed showed that FLT3+ cells contact and engulf pre-synaptic elements. Our findings suggest FLT3+IBA1+ cells might assist microglia in their physiological functions in the developing brain including synaptic pruning which is performed using their purinergic sensors. Our findings stimulate further investigation on the involvement of peripheral macrophages during homeostatic and pathological development.

5.
Biol Aujourdhui ; 218(1-2): 33-39, 2024.
Artículo en Francés | MEDLINE | ID: mdl-39007775

RESUMEN

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.


Title: IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle. Abstract: L'interleukine (IL)-17A puis l'IL-17F ont été découvertes tour à tour pour leur rôle joué dans les maladies inflammatoires chroniques. Elles ont une homologie de séquence d'environ 50 % et partagent le même récepteur formé des chaînes IL-17RA et IL-17RC. Si elles ont des effets pro-inflammatoires assez similaires, il existe néanmoins quelques différences selon le type cellulaire considéré et selon la présence ou non de TNF, autre cytokine avec laquelle elles ont une synergie d'action. La troisième variable venant moduler leurs effets réside dans les interactions entre cellules immunes et cellules stromales, qui, là encore, varient selon le type de cellules stromales. La mise en évidence de leur rôle dans le psoriasis a notamment conduit au développement d'inhibiteurs de l'IL-17A, puis à la fois de l'IL-17A et de l'IL-17F et enfin d'un de leurs récepteurs. Ces inhibiteurs sont utilisés avec succès dans cette pathologie, et leur indication a été étendue progressivement au rhumatisme psoriasique et à certaines formes de spondylarthrite. Enfin, la récente compréhension de l'importance des cellules stromales dans la réaction inflammatoire chronique permet d'expliquer l'efficacité variable de ces biothérapies dans certaines pathologies.


Asunto(s)
Productos Biológicos , Interleucina-17 , Psoriasis , Investigación Biomédica Traslacional , Humanos , Interleucina-17/antagonistas & inhibidores , Interleucina-17/fisiología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Animales , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Inflamación/tratamiento farmacológico , Descubrimiento de Drogas/tendencias , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendencias , Receptores de Interleucina-17/fisiología , Receptores de Interleucina-17/antagonistas & inhibidores
6.
Bull Cancer ; 111(9): 893-903, 2024 Sep.
Artículo en Francés | MEDLINE | ID: mdl-38897911

RESUMEN

Endocrine therapy plays a crucial role in the treatment of women with hormone receptor-positive breast cancer. However, non-adherence remains a frequent issue known to negatively impact survival. Based on a comprehensive literature review, this article explores the terminologies employed to describe adherence and methods used for its assessment, the adherence data reported with adjuvant endocrine therapy with targeted therapies, the determinants of adherence or non-adherence, and finally, tested solutions to address it. The results show that a better understanding of the causes of non-adherence would help to better identify patients at risk, and to develop personalized intervention programs capable of improving adherence to adjuvant endocrine therapy. In light of the literature, interventions are likely to require a multimodal approach and integration into our future healthcare pathways.


Asunto(s)
Antineoplásicos Hormonales , Neoplasias de la Mama , Cumplimiento de la Medicación , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Antineoplásicos Hormonales/uso terapéutico , Quimioterapia Adyuvante , Terminología como Asunto , Tamoxifeno/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico
7.
JAMA Oncol ; 10(8): 1027-1035, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38900452

RESUMEN

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Irinotecán , Leucovorina , Oxaliplatino , Neoplasias Pancreáticas , Humanos , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Femenino , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Persona de Mediana Edad , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Terapia Neoadyuvante , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/mortalidad , Anciano de 80 o más Años , Supervivencia sin Progresión
8.
J Scleroderma Relat Disord ; 9(2): 134-142, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38910602

RESUMEN

Objective: The study aimed to assess the construct validity of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire in Algerian patients with systemic sclerosis. Methods: Consecutive Algerian patients who fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis were included. In addition to disease characteristics, global disability and hand disability were assessed using the Arabic Health Assessment Questionnaire and the Arab Hand Function Index, respectively. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis. The scale reliability was assessed using the Cronbach's alpha. Results: We evaluated 100 systemic sclerosis patients (83 females) of mean ± standard deviation age 46.7 ± 12.3 years, including 59 limited cutaneous systemic sclerosis and 41 diffuse cutaneous systemic sclerosis. Raynaud's phenomenon was detected in 99 patients and digital ulcers in 25. Gastrointestinal tract involvement and interstitial lung disease were detected in 86/100 (86%) and 46/72 (63.9%) patients, respectively. Anti-topoisomerase I and anti-centromere antibodies were detected in 33/76 (43.4%) and 23/76 (30.3%) patients, respectively. The Arab Hand Function Index had a good construct validity with a total score explaining 61% of the variance of the Arabic Health Assessment Questionnaire which also had a good construct validity. Factor analysis of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire items extracted two factors explaining 64% of the variance for the Arab Hand Function Index and one factor explaining 55% of the variance for the Arabic Health Assessment Questionnaire. The Arab Hand Function Index and the Arabic Health Assessment Questionnaire were reliable questionnaires with a Cronbach's alpha >0.8. Conclusion: In Algerian patients with systemic sclerosis, Arab Hand Function Index and Arabic Health Assessment Questionnaire have a good construct validity and reliability.

9.
Trends Immunol ; 45(6): 406-418, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38796404

RESUMEN

Sarcoidosis is a chronic immune disease of unknown origin for which we still lack an immunological framework unifying causal agents, host factors, and natural history of disease. Here, we discuss the initial triggers of disease, and how myeloid cells drive granuloma formation and contribute to immunopathogenesis. We highlight recent advances in our understanding of innate immune memory and propose the hypothesis that maladaptive innate immune training connects previous environmental exposure to granuloma maintenance and expansion. Lastly, we consider how this hypothesis may open novel therapeutic avenues, while corticosteroids remain the front-line treatment.


Asunto(s)
Inmunidad Innata , Memoria Inmunológica , Sarcoidosis , Humanos , Sarcoidosis/inmunología , Inmunidad Innata/inmunología , Animales , Granuloma/inmunología , Células Mieloides/inmunología , Inmunidad Entrenada
10.
PLoS One ; 19(5): e0304556, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38820299

RESUMEN

BACKGROUND: Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level. OBJECTIVE: To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized breast cancer (BC) during the COVID-19 pandemic. METHODS: We used data from the PAPESCO-19 multicenter cohort study, which included patients from 4 French comprehensive cancer centers. We measured the delay to first treatment as the number of days between diagnosis and the first treatment regardless of whether this was neoadjuvant chemotherapy or surgery. COVID-19 pandemic exposure was estimated with a composite index that considered both the severity of the pandemic and the level of lockdown restrictions. We ran generalized linear models with a log link function and a gamma distribution to model the association between delay and the pandemic. RESULTS: Of the 187 patients included in the analysis, the median delay to first treatment was 42 (IQR:32-54) days for patients diagnosed before and after the start of the 1st lockdown (N = 99 and 88, respectively). After adjusting for age and centers of inclusion, a higher composite pandemic index (> = 50 V.S. <50) had only a small, non-significant effect on times to treatment. Longer delays were associated with factors other than the COVID-19 pandemic. CONCLUSION: We found evidence of no direct impact of the pandemic on the actual delay to treatment among patients with localized BC.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Tiempo de Tratamiento , Humanos , COVID-19/epidemiología , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/epidemiología , Persona de Mediana Edad , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , Francia/epidemiología , Adulto , Pandemias , SARS-CoV-2/aislamiento & purificación , Estudios de Cohortes
11.
J Proteome Res ; 23(6): 2219-2229, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38682820

RESUMEN

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by exocrine gland dysfunction, mainly from the lacrimal and salivary glands. The disease causes severe aqueous dry eye syndrome (DED) and is associated with high rates of complications, including corneal ulceration, scaring, and perforation. Systemic complications may occur as well as a higher risk of developing lymphoma. Diagnosis of SS-DED is often delayed and difficult to establish. With the aim of discovering biomarkers to help discriminate SS-DED patients, a combination of untargeted and targeted LC-MS/MS analyses were performed on tear samples collected on Schirmer strips and subjected to tryptic digestion. Following the analysis of three cohorts and the development of two targeted LC-sMRM methods for the verification of putative biomarkers found in the first cohort of samples, 64 proteins could be linked to Sjögren's syndrome, in the hopes of helping to confirm diagnoses as well as potentially stratifying the severity of disease in these patients. Proteins that were increased in SS-DED showed activation of the immune system and alterations in homeostasis. Several proteases and protease inhibitors were found to be significantly changing in SS-DED, as well as a consistent decrease in specific proteins known to be secreted by the lacrimal gland.


Asunto(s)
Biomarcadores , Síndrome de Sjögren , Espectrometría de Masas en Tándem , Lágrimas , Síndrome de Sjögren/metabolismo , Humanos , Lágrimas/metabolismo , Lágrimas/química , Biomarcadores/metabolismo , Biomarcadores/análisis , Cromatografía Liquida , Femenino , Persona de Mediana Edad , Proteómica/métodos , Masculino , Síndromes de Ojo Seco/metabolismo , Adulto , Anciano , Aparato Lagrimal/metabolismo , Aparato Lagrimal/patología , Proteínas del Ojo
12.
Virchows Arch ; 484(4): 597-608, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570364

RESUMEN

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20-30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28-8 assay. A 2-h training module on the 28-8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.


Asunto(s)
Inteligencia Artificial , Antígeno B7-H1 , Biomarcadores de Tumor , Variaciones Dependientes del Observador , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Reproducibilidad de los Resultados , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias Urológicas/patología , Neoplasias Urológicas/metabolismo , Inmunohistoquímica/métodos , Patólogos , Urotelio/patología , Urotelio/metabolismo
13.
Autoimmun Rev ; 23(4): 103529, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38492906

RESUMEN

The current therapeutic strategy used in immune-mediated inflammatory diseases (IMIDs) primarily targets immune cells or associated-pathways. However, recent evidence suggests that the microenvironment modulates immune cell development and responses. During inflammation, structural cells acquire a pathogenetic phenotype and the interactions with immune cells are often greatly modified. Understanding the importance of these tissue-specific interactions may allow to explain why some biologics are effective in some IMIDs but not in others. The differential effects of interleukin (IL)-17 A, IL-17F and IL-23 in joint versus skin inflammation depends on structural cell heterogeneity. In addition, the sometimes opposite effects of immune/structural cell interactions on the production of these cytokines illustrate the importance of these cells in chronic inflammation, using the examples of rheumatoid arthritis, psoriasis and spondyloarthritis. This review describes these concepts, shows their interests through clinical observations, and finally discusses strategies to optimize therapeutic strategies.


Asunto(s)
Interleucina-17 , Interleucina-23 , Humanos , Interleucina-17/inmunología , Interleucina-17/metabolismo , Interleucina-23/inmunología , Interleucina-23/metabolismo , Inflamación/inmunología , Animales , Piel/inmunología , Piel/patología , Enfermedad Crónica , Artritis Reumatoide/inmunología , Psoriasis/inmunología
14.
NPJ Precis Oncol ; 8(1): 37, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38366021

RESUMEN

Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.

15.
Gastroenterology ; 167(1): 79-89, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38302007

RESUMEN

The accumulating data regarding a non-biopsy diagnosis of celiac disease has led to its adoption in certain scenarios, although debate on whether and when to use non-biopsy criteria in clinical practice is ongoing. Despite the growing popularity and evidence basis for a biopsy-free approach to diagnosis in the context of highly elevated serologies, there will continue to be a role for a biopsy in some groups. This review summarizes the current evidence supporting a non-biopsy approach and arguments supporting continued reliance on biopsy, and focuses on opportunities to improve both approaches.


Asunto(s)
Enfermedad Celíaca , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Humanos , Biopsia , Valor Predictivo de las Pruebas
17.
Arch Pathol Lab Med ; 148(3): 359-370, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37327187

RESUMEN

CONTEXT.­: Cholangiocarcinoma (CCA) is a heterogeneous cancer of the bile duct, and its diagnosis is often challenging. OBJECTIVE.­: To provide insights into state-of-the-art approaches for the diagnosis of CCA. DATA SOURCES.­: Literature review via PubMed search and authors' experiences. CONCLUSIONS.­: CCA can be categorized as intrahepatic or extrahepatic. Intrahepatic CCA is further classified into small-duct-type and large-duct-type, whereas extrahepatic CCA is classified into distal and perihilar according to site of origin within the extrahepatic biliary tree. Tumor growth patterns include mass forming, periductal infiltrating, and intraductal tumors. The clinical diagnosis of CCA is challenging and usually occurs at an advanced tumor stage. Pathologic diagnosis is made difficult by tumor inaccessibility and challenges in distinguishing CCA from metastatic adenocarcinoma to the liver. Immunohistochemical stains can assist in differentiating CCA from other malignancies, such as hepatocellular carcinoma, but no distinctive CCA-specific immunohistochemical profile has been identified. Recent advances in next-generation sequencing-based high-throughput assays have identified distinct genomic profiles of CCA subtypes, including genomic alterations that are susceptible to targeted therapies or immune checkpoint inhibitors. Detailed histopathologic and molecular evaluations of CCA by pathologists are critical for correct diagnosis, subclassification, therapeutic decision-making, and prognostication. The first step toward achieving these goals is to acquire a detailed understanding of the histologic and genetic subtypes of this heterogeneous tumor group. Here, we review state-of-the-art approaches that should be applied to establish a diagnosis of CCA, including clinical presentation, histopathology, staging, and the practical use of genetic testing methodologies.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Medicina de Precisión , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Conductos Biliares Intrahepáticos/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología
18.
J Oncol Pharm Pract ; 30(2): 278-285, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37254519

RESUMEN

INTRODUCTION: During administration of chemotherapies, disconnection presents risks for nurses. Thus, it is recommended to flush the infusion line with solvent to reduce this risk and ensure that the entire dose is administered. Objectives of this study were to evaluate flushing practices and to investigate the efficiency of flushing, according to the type of hospitalization, in hospitalization (HU) or day-care unit (DCU), for three drugs. METHODS: Twenty secondary infusion lines were collected in five HU and 20 in two DCU. Flushing volumes were estimated by weighing solvent bags. The amount of residual drug was measured for secondary lines by mass spectrometry coupled with high-performance liquid chromatography. RESULTS: Chemotherapies were administered by 26 nurses. All of infusion lines contained chemotherapy after flushing. Flushing volumes, residual concentrations and flushing efficiencies were significantly different between these two types of units. In contrast, flushing volumes administrated did not differ between chemotherapy drugs. CONCLUSIONS: Local recommendations are fully implemented in HU and partially in DCU. The use of small volumes in DCU is related to the patient length of stay, it may, also, be due to omitting the average tubing volume. All infusion lines still contained chemotherapy, including those with a flush volume much higher than recommended, showing that the risk of exposure persists. To achieve a rinse volume greater than 50 mL, it is necessary to use at least 100 mL. It is also important to insist on personal protective equipment and to consider closed safety system for administration.


Asunto(s)
Infusiones Intravenosas , Humanos , Solventes
19.
Can J Ophthalmol ; 59(2): 79-82, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36610703

RESUMEN

OBJECTIVE: Pterygium and ocular surface squamous neoplasia (OSSN) have been recognized as likely related conditions and share similar risk factors such as ultraviolet radiation and chronic inflammation. The purpose of this study is to review the incidence of OSSN in pathology specimens sent as pterygium at a single tertiary centre between 2010 and 2022. METHODS: This is a retrospective chart review of patients operated on for pterygium between 2010 and 2022 at the University of Montreal Health Centre. Data collected include baseline demographics, results of pathology specimen, and clinical information for cases diagnosed as OSSN on pathology. RESULTS: A total of 1559 patients were operated on for a clinical diagnosis of pterygium between 2010 and 2022, of which 854 patients (55%) were male. A total of 1142 specimens had available pathology reports, and most of the specimens were consistent with pterygium on pathology (1105 of 1142; 97%). There was an unexpected finding of 3 cases of OSSN (3 of 1142; 0.3%). Other diagnosis besides pterygium were seen in 3% of specimens (34 of 1142), including nevus (n = 12), spheroidal degeneration (n = 3), pyogenic granuloma (n = 3), and lymphangiectasia (n = 2). The 3 cases of OSSN included an 81-year-old male of French-Canadian background, a 52-year-old male of South Asian background, and a 59-year-old female of French-Canadian background. The pathology was diagnosed as conjunctival intraepithelial neoplasia (CIN) grade 3, CIN grade 2, and CIN grade 2, respectively. CONCLUSION: The finding of OSSN in pterygium is rare in our population but can be clinically difficult to distinguish. It is important to send all pterygium specimens for pathology.


Asunto(s)
Carcinoma de Células Escamosas , Conjuntiva/anomalías , Neoplasias de la Conjuntiva , Neoplasias del Ojo , Pterigion , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anciano de 80 o más Años , Pterigion/diagnóstico , Pterigion/epidemiología , Estudios Retrospectivos , Incidencia , Rayos Ultravioleta , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Canadá , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias de la Conjuntiva/epidemiología , Neoplasias de la Conjuntiva/patología , Neoplasias del Ojo/cirugía
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