Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.482
Filtrar
Más filtros











Intervalo de año de publicación
1.
Benef Microbes ; : 1-17, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39353590

RESUMEN

The world is witnessing an increasing incidence of chronic non-communicable diseases (NCDs), such as inflammatory bowel disease (IBD), a group of complex gastrointestinal disorders characterised by inflammation. It is believed that environmental factors, such as exposure to pollutants and endocrine-disrupting chemicals (i.e. bisphenol A [BPA]), are playing a role in IBD pathophysiology. New research suggests a potential treatment solution: next-generation probiotic (NGP) strains isolated from human gut microbiota that can biodegrade xenobiotics and thus possibly modulate IBD triggered by these xenobiotics. In this study, we hypothesised that specific BPA-tolerant bacteria would exhibit beneficial, anti-inflammatory properties that could counter the effects of BPA exposure and concomitantly reduce colitis severity. We observed that two such strains, Bacillus sp. AM1 and Paeniclostridium sp., exhibited potential anti-inflammatory properties in vitro and in vivo. First, these bacteria were able to decrease the secretion of interleukin (IL)-8 cytokines by HT-29 cells that had been exposed to the proinflammatory cytokine tumour necrosis factor (TNF)-α. Second, when treated with Bacillus sp. AM1 and Paeniclostridium sp. (this latter had a stronger reducing effect on inflammatory markers), mice with chemically induced colitis displayed lower levels of colon damage, monocyte chemotactic protein 1 (MCP-1), lipocalin-2 (LCN-2), and proinflammatory cytokines (IL-1ß and IL-6). Future research should clarify the underlying mechanisms at play and identify potential strategies for counteracting the systemic effects of IBD, including those exacerbated by BPA exposure. Our results suggest that one such strategy could be treatment with BPA-tolerant bacteria that possess anti-inflammatory properties.

2.
Fam Cancer ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39387980

RESUMEN

The discovery of "mismatch repair deficient (MMRd)-crypt foci" in non-neoplastic intestinal mucosa in Lynch syndrome (LS) has significantly enhanced our understanding of how tumors and tumor immunity form and evolve in LS. In this study, we report the frequent presence of "mismatch repair proficient (MMRp)-crypt foci" in both non-neoplastic and neoplastic intestinal mucosa in a patient with constitutional MMR deficiency (CMMRD), who carried a germline MSH6 pathogenic variant (c.3261dupC) in trans with an MSH6 likely pathogenic variant (c.3724_3726del) and whose tissues were otherwise deficient in MMR globally. The MMRp-crypts occurred at a rate of 1.1/100 crypts in non-neoplastic intestinal mucosa and were readily discernible in adenomas > 1 cm. Sequencing analysis revealed normalization of the MSH6c.3261dupC variant in MMRp-adenoma crypts, indicating reverse frameshifting of the exon 5 C8 microsatellite. Interestingly but not surprisingly, the MMRp-adenoma crypts remained microsatellite-instability-high (MSI-H), and shared oncogenic APC mutations with the background MMRd-adenoma. Contrasting with MSH6-CMMRD, no PMS2-CMMRD individuals (0/5) harbored MMRp-crypts. In conclusion, our study documents distinct MMRp-crypts in MSH6-CMMRD, a phenomenon in keeping with MSH6 being a frequent target of MSI-H due to its coding microsatellite and suggesting that MSH6-CMMRD can potentially serve as a unique model system to further our understanding of MSH6's role in MSI-H tumor formation and evolution. Our findings also bear diagnostic implications; when using MMR immunohistochemistry as an ancillary tool in detecting CMMRD, awareness of these MMRp crypts can help avoid diagnostic pitfalls.

3.
Ann Surg Oncol ; 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39395915

RESUMEN

INTRODUCTION: Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated. METHODS: We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival. RESULTS: Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19). CONCLUSIONS: The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.

4.
J Am Soc Nephrol ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352759

RESUMEN

BACKGROUND: Understanding the genetic basis of human diseases has become integral to drug development and precision medicine. Recent advancements have enabled the identification of molecular pathways driving diseases, leading to targeted treatment strategies. The increasing investment in rare diseases by the biotech industry underscores the importance of genetic evidence in drug discovery and approval processes. Here we studied a monogenic Mendelian kidney disease, TRPC6-associated podocytopathy (TRPC6-AP), to present its natural history, genetic spectrum, and clinicopathological associations in a large cohort of patients with causal variants in TRPC6, in order to help define the specific features of disease and further facilitate drug development and clinical trials design. METHODS: the study involved 64 individuals from 39 families with TRPC6 causal missense variants. Clinical data, including age of onset, laboratory results, response to treatment, kidney biopsy findings, and genetic information, were collected from multiple centers nationally and internationally. Exome or targeted sequencing was performed and variant classification was based on strict criteria. Structural and functional analyses of TRPC6 variants were conducted to understand their impact on protein function. In depth re-analysis of light and electron microscopy specimens for 9 available kidney biopsies was conducted to identify pathological features and correlates of TRPC6-AP. RESULTS: Large-scale sequencing data did not support causality for TRPC6 protein-truncating variants. We identified 21 unique TRPC6 missense variants, clustering in three distinct regions of the protein, and with different effects on TRPC6 3D protein structure. Kidney biopsy analysis revealed FSGS patterns of injury in most cases, along with distinctive podocyte features including diffuse foot process effacement and swollen cell bodies. The majority of patients presented in adolescence or early adulthood but with ample variation (average 22, SD ± 14 years), with frequent progression to kidney failure but with variability in time between presentation and ESKD. CONCLUSIONS: This study provides insights into the genetic spectrum, clinicopathological associations, and natural history of TRPC6-AP.

5.
Eur Respir J ; 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39362671

RESUMEN

BACKGROUND: Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking. METHODS: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease (COPD) Study was a multi-center longitudinal COPD case-control study of participants 50-79 years with ≥10 pack-years smoking without clinical cardiovascular disease. Segmental airway wall area (WA) and percent emphysema were measured on computed tomography. Right and left ventricle (RV, LV) parameters were assessed on magnetic resonance imaging (MRI) in exams six years apart. Longitudinal and period cross-sectional associations were evaluated with mixed models adjusted for demographics, body size, and smoking. RESULTS: The 187 participants with repeated MRI were 67±7 years old; 42% had COPD; 22% currently smoked; and the race/ethnicity distribution was 54% white, 30% Black, 14% Hispanic, and 3% Asian. Greater WA at enrollment was associated with longitudinal increase in RV mass (3.5 g per 10mm2 WA, 95% CI: 1.1, 5.9). Greater percent emphysema was associated with stably lower LV end diastolic volume (-7.8 mL per 5% emphysema, 95% CI: -10.3, -3.0) and CO (-0.2 L·min-1 per 5% emphysema, 95% CI: -0.4, -0.1). CONCLUSION: Cardiac associations varied by lung structure over six years in this multi-ethnic study. Greater WA at enrollment was associated with longitudinal increases in RV mass; whereas greater percent emphysema was associated with stable decrements in LV filling and CO.

6.
Eur Heart J Digit Health ; 5(5): 509-523, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39318699

RESUMEN

Mobile health (mHealth) solutions have the potential to improve self-management and clinical care. For successful integration into routine clinical practice, healthcare professionals (HCPs) need accepted criteria helping the mHealth solutions' selection, while patients require transparency to trust their use. Information about their evidence, safety and security may be hard to obtain and consensus is lacking on the level of required evidence. The new Medical Device Regulation is more stringent than its predecessor, yet its scope does not span all intended uses and several difficulties remain. The European Society of Cardiology Regulatory Affairs Committee set up a Task Force to explore existing assessment frameworks and clinical and cost-effectiveness evidence. This knowledge was used to propose criteria with which HCPs could evaluate mHealth solutions spanning diagnostic support, therapeutics, remote follow-up and education, specifically for cardiac rhythm management, heart failure and preventive cardiology. While curated national libraries of health apps may be helpful, their requirements and rigour in initial and follow-up assessments may vary significantly. The recently developed CEN-ISO/TS 82304-2 health app quality assessment framework has the potential to address this issue and to become a widely used and efficient tool to help drive decision-making internationally. The Task Force would like to stress the importance of co-development of solutions with relevant stakeholders, and maintenance of health information in apps to ensure these remain evidence-based and consistent with best practice. Several general and domain-specific criteria are advised to assist HCPs in their assessment of clinical evidence to provide informed advice to patients about mHealth utilization.

7.
J Clin Invest ; 134(18)2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39286977

RESUMEN

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3ß-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.


Asunto(s)
Complejos Multienzimáticos , Progesterona Reductasa , Neoplasias de la Próstata , Esteroide Isomerasas , Masculino , Humanos , Progesterona Reductasa/genética , Progesterona Reductasa/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Esteroide Isomerasas/genética , Anciano , Complejos Multienzimáticos/genética , Persona de Mediana Edad , Antagonistas de Andrógenos/uso terapéutico , Benzamidas , Metástasis de la Neoplasia , Nitrilos , Feniltiohidantoína/uso terapéutico , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Tasa de Supervivencia , Glándulas Suprarrenales/patología , Glándulas Suprarrenales/metabolismo
8.
JAMA Netw Open ; 7(9): e2433863, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39287944

RESUMEN

Importance: Observed treatment effects on overall survival (OS) differed substantially in the first 2 randomized clinical trials of lutetium Lu 177 vipivotide tetraxetan (Lu-177) prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer. Objective: To investigate factors associated with the observed difference in treatment effects on OS, including differences in the risk of crossover from randomized treatment after disease progression. Design, Setting, and Participants: This comparative effectiveness study used individual participant data from 2 randomized clinical trials, TheraP (A Randomised Phase 2 Trial of 177Lu-PSMA617 Theranostic Versus Cabazitaxel in Progressive Metastatic Castration Resistant Prostate Cancer [ANZUP Protocol 1603]) (n = 200), recruited from February 2018 to September 2019 in Australia, and published data from VISION (An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer) (n = 831), recruited from June 2018 to October 2019 in North America and Europe. Individual participant data for OS were reconstructed from VISION using the published survival curves. Data were analyzed February 6, 2018, to December 31, 2021, for TheraP and June 4, 2018, to January 27, 2021, for VISION. Interventions: TheraP randomized participants to receive treatment with Lu-177 PSMA or cabazitaxel. VISION randomized participants to receive treatment with or without Lu-177 PSMA in addition to physicians' choice of protocol-permitted treatments (PPT; approved hormonal treatments [such as abiraterone and enzalutamide], bisphosphonates, radiotherapy, denosumab, or glucocorticoids), excluding cabazitaxel. Main Outcomes and Measures: Patient characteristics, treatment protocols, and OS outcomes of the 2 trials were compared. Estimates of the effect on OS from TheraP were adjusted for crossover from randomly assigned treatment using a rank-preserving structural failure time model (RPSFTM) and inverse probability of censoring weights (IPCW) methods. Results: The 200 participants in TheraP and 831 participants in VISION were similar in age (median [range], 72 [49-86] vs 71 [40-94] years). Improved OS was observed in the comparator treatment group (cabazitaxel) in TheraP compared with VISION (PPT) (hazard ratio [HR], 0.53 [95% CI, 0.39-0.71]). The Lu-177 PSMA treatment groups in TheraP and VISION had similar OS (HR, 0.92 [95% CI, 0.70-1.19]). In TheraP, 20 of 101 participants in the cabazitaxel group crossed over to Lu-177 PSMA, while 32 of 99 participants in the Lu-177 PSMA arm crossed over to cabazitaxel. No statistically significant differences in OS between the Lu-177 PSMA and cabazitaxel groups of TheraP were observed after controlling for crossover to cabazitaxel: RPSFTM HR, 0.97 (95% CI, 0.60-1.58); IPCW HR, 0.92 (95% CI, 0.65-1.32); RPSFTM HR, 0.97 (95% CI, 0.60-1.58) and IPCW HR, 0.82 (95% CI, 0.54-1.24) for crossover to Lu-177 PSMA; RPSFTM HR, 0.96 (95% CI, 0.53-1.74) and IPCW HR, 0.82 (95% CI, 0.53-1.27) for crossover to either Lu-177 PSMA or cabazitaxel. Conclusions and Relevance: Findings of this secondary analysis of the TheraP and VISION randomized clinical trials suggest that the choice of comparator treatments (ie, cabazitaxel vs PPT) may explain the difference in the observed effect of Lu-177 PSMA on OS between the 2 trials. Causal inference methods such as RPSFTM and IPCW may help rule out crossover as a plausible explanation.


Asunto(s)
Lutecio , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Lutecio/uso terapéutico , Anciano , Persona de Mediana Edad , Radioisótopos/uso terapéutico , Taxoides/uso terapéutico
9.
Nat Commun ; 15(1): 8251, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304655

RESUMEN

Determining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. rs2113389 is associated with higher CYP1B1 expression and methylation levels. Mouse model studies provide additional functional evidence for a relationship between CYP1B1 and tau deposition but not amyloid beta. These results provide insight into the genetic basis of cerebral tau deposition and support novel pathways for therapeutic development in AD.


Asunto(s)
Enfermedad de Alzheimer , Citocromo P-450 CYP1B1 , Endofenotipos , Estudio de Asociación del Genoma Completo , Tomografía de Emisión de Positrones , Proteínas tau , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Ratones , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Modelos Animales de Enfermedad , Polimorfismo de Nucleótido Simple , Tomografía de Emisión de Positrones/métodos , Proteínas tau/metabolismo , Proteínas tau/genética
10.
Basic Clin Androl ; 34(1): 14, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223491

RESUMEN

BACKGROUND: Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use. METHODS: Clinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) < 10 nmol/L, and was classified as primary by a serum concentration of luteinising hormone (LH) > 8 IU/L, otherwise as secondary. RESULTS: Two hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort. CONCLUSIONS: Low total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up.


RéSUMé: CONTEXTE: L'hypogonadisme primaire est une complication reconnue chez les survivants d'un cancer du testicule. Cependant, l'hypogonadisme secondaire peut résulter d'autres causes qui suppriment l'axe hypothalamo-hypophysaire, notamment l'obésité, les glucocorticoïdes à forte dose, la défaillance chronique des organes cibles et le diabète. Le but de cette étude était d'explorer un faible taux de testostérone totale sérique chez les survivants australiens d'un cancer du testicule, et d'examiner les associations avec l'indice de masse corporelle, l'âge et l'utilisation antérieure d'une chimiothérapie. Les données cliniques, y compris la taille, le poids, le diagnostic, le traitement et les évaluations hormonales au cours du suivi, ont été extraites de l'étude Chemocog de l'Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group (2007­2012), accompagnées de données, provenant de deux centres australiens à fort volume de prise en charge de cancers du testicule, incluses dans le registre du cancer du testicule iTestis (2012­2019). Un taux faible de testostérone a été défini par une concentration sérique de testostérone (T) < 10 nmol/L, et a été classé comme primaire pour une concentration sérique d'hormone lutéinisante (LH) > 8 UI/L, sinon comme secondaire. RéSULTATS: Deux cent quatre-vingt-cinq personnes atteintes d'un cancer des testicules de stade 1 ou avancé ont été incluses. Parmi ceux-ci, 105 (37%) ont été traités par orchidectomie et chimiothérapie. Quarante-neuf (17%) répondaient aux critères d'un taux faible de testostérone au cours du suivi: 21 (43%) avaient un taux faible de testostérone primaire et 27 (55%) un faible taux secondaire. Les survivants d'un cancer du testicule avec un indice de masse corporelle plus élevé étaient plus susceptibles de présenter un taux faible de testostérone, à la fois primaire (p = 0,032) et secondaire (p = 0,028). Nos données n'ont pas montré de preuve d'une association entre un âge avancé ou l'utilisation de la chimiothérapie, et un taux faible de testostérone, dans notre cohorte. CONCLUSIONS: Un faible taux de testostérone sérique totale était fréquent chez les survivants d'un cancer du testicule, et associé à un indice de masse corporelle plus élevé avant l'orchidectomie; ceci suggère qu'un indice de masse corporelle élevé peut contribuer à un faible taux de testostérone dans cette population, et que le poids corporel, l'alimentation et l'exercice devraient être pris en compte dans le suivi du cancer du testicule.

11.
Cancers (Basel) ; 16(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39123369

RESUMEN

(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.

13.
J Cancer Res Clin Oncol ; 150(8): 407, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212783

RESUMEN

INTRODUCTION: Training of interdisciplinary clinical reasoning and decision-making skills, essential in daily clinical practice in oncological specialties, are still underrepresented in medical education. Therefore, at LMU University Hospital Munich, we implemented a didactically modified tumor board simulation with experts from five different disciplines (medical oncology, pathology, radiation oncology, radiology, and surgery) presenting patient cases into a one-week course on the basic principles of oncology. In this survey, we examined the self-assessed impact of our course on the interdisciplinary decision-making skills of medical students. METHODS: Between November-December 2023 and January-February 2024, we surveyed two cohorts of medical students in the third year of medical school in our one-week course before and after participating in the tumor board simulation. The objective was to evaluate the self-assessed knowledge in interdisciplinary clinical decision-making, in integrating ethical considerations into clinical reasoning, and in comprehension of various professional viewpoints in interdisciplinary decision-making. Knowledge was assessed using a five-step Likert scale from 1 (no knowledge) to 5 (complete knowledge). RESULTS: The survey was answered by 76 students before and 55 after the simulation, equaling 60-70% of all 100 course participants. Mean knowledge level regarding principles of interdisciplinary clinical decision-making improved significantly in all of the following exemplary aspects: purpose and procedure of tumor boards in clinical practice (from 2.4 ± 1.1 to 4.0 ± 1.0, Spearman's ρ = 0.6, p < 0.001), principles of dealing with ethical challenges in oncology (from 2.4 ± 1.1 to 3.4 ± 1.0, ρ = 0.4, p < 0.001), and principles of shared decision-making in oncology (2.7 ± 1.1 to 3.7 ± 1.0, ρ = 0.4, p < 0.001). Students reported that their skills in clinical decision-making and ability to discuss oncological patient cases from different professional viewpoints improved due to the teaching course. CONCLUSION: By employing our interdisciplinary one-week course and a didactically modified tumor board simulation featuring experts from various oncological disciplines, medical students' comprehension of interdisciplinary clinical decision-making in oncology improved significantly.


Asunto(s)
Toma de Decisiones Clínicas , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Competencia Clínica , Masculino , Femenino , Neoplasias , Oncología Médica/educación , Encuestas y Cuestionarios , Grupo de Atención al Paciente , Adulto , Toma de Decisiones , Educación de Pregrado en Medicina/métodos
14.
Eur J Cancer ; 210: 114291, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39180940

RESUMEN

BACKGROUND: Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate. METHODS: We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS). Patients with stage II/III rectal cancer were randomized to CRT (50.4-54 Gy) with either induction (INCT-CRT) or consolidation CT (CRT-CNCT) with fluorouracil, leucovorin, oxaliplatin (CAO/ARO/AIO-12 and OPRA) or capecitabine and oxaliplatin (OPRA) followed by mandatory total mesorectal excision (TME) (CAO/ARO/AIO-12) or selective watch-and-wait surveillance (OPRA). 311 and 324 patients were recruited from June 15, 2015 to January 31, 2018; and from April 12, 2014 to March 30, 2020 in the two trials, respectively. Pretreatment clinical and tumor characteristics included were age, sex, ECOG, cT-category, cN-category, clinical UICC stage, location from anal verge, and tumor grade. FINDINGS: In total, 628 eligible patients were included in the pooled analysis (CAO/ARO/AIO-12, n = 304; OPRA, n = 324). Of those, 313 were randomly assigned to the INCT-CRT group, and 315 to the CRT-CNCT group. Median follow-up was 43 months (IQR, 35-49) months in the CAO/ARO/AIO-12 trial and 61,2 months (IQR, 42-68,4) in the OPRA trial. Pooled analysis of baseline clinical and tumor characteristics did not identify any subgroups of patients that would benefit by the one TNT sequence over the other with regard to DFS. INTERPRETATION: To our knowledge, this is the first pooled analysis of two randomized trials after direct head-to-head comparison of both TNT sequences. Both trials reported higher rates of complete response with CRT-CNCT, and this should be considered the preferred TNT sequence if organ preservation is a priority.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Quimioterapia de Consolidación , Quimioterapia de Inducción , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Femenino , Masculino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Anciano , Quimioradioterapia/métodos , Quimioterapia de Consolidación/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción/métodos , Adulto , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico
15.
JCO Clin Cancer Inform ; 8: e2300233, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39121392

RESUMEN

PURPOSE: Outcome for patients with nonmetastatic, microsatellite instability (MSI) colon cancer is favorable: however, high-risk cohorts exist. This study was aimed at developing and validating a nomogram model to predict freedom from recurrence (FFR) for patients with resected MSI colon cancer. PATIENTS AND METHODS: Data from patients who underwent curative resection of stage I, II, or III MSI colon cancer in 2014-2021 (model training cohort, 384 patients, 33 events; median follow-up, 38.8 months) were retrospectively collected from institutional databases. Variables associated with recurrence in multivariable analysis were selected for inclusion in the clinical calculator. The calculator's predictive accuracy was measured with the concordance index and validated using data from patients who underwent treatment for MSI colon cancer in 2007-2013 (validation cohort, 164 patients, eight events; median follow-up, 84.8 months). RESULTS: T category and number of positive lymph nodes were significantly associated with recurrence in multivariable analysis and were selected for inclusion in the clinical calculator. The calculator's concordance index for FFR in the model training cohort was 0.812 (95% CI, 0.742 to 0.873), compared with 0.759 (95% CI, 0.683 to 0.840) for the staging schema of the eighth edition of the American Joint Committee on Cancer Staging Manual. The concordance index for the validation cohort was 0.744 (95% CI, 0.666 to 0.822), confirming robust predictive accuracy. CONCLUSION: Although in general patients with nonmetastatic MSI colon cancer had favorable outcome, patients with advanced T category and multiple metastatic lymph nodes had higher risk of recurrence. The clinical calculator identified patients with MSI colon cancer at high risk for recurrence, and this could inform surveillance strategies. In addition, the model could be used in trial design to identify patients suitable for novel adjuvant therapy.


Asunto(s)
Neoplasias del Colon , Inestabilidad de Microsatélites , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Humanos , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Neoplasias del Colon/diagnóstico , Femenino , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Persona de Mediana Edad , Anciano , Nomogramas , Estudios Retrospectivos , Pronóstico , Adulto
16.
J Clin Oncol ; : JCO2301836, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39151115

RESUMEN

PURPOSE: The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components. PATIENTS AND METHODS: Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A). RESULTS: We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD. CONCLUSION: THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.

17.
J Natl Cancer Inst ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118255

RESUMEN

Chemotherapy treatment-related side-effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity (RDI). The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium, to address this knowledge gap. This paper describes the mechanisms hypothesized to underpin intervention effects on clinically-relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the paper includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that cancer patients could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve RDI for a curative outcome.

18.
Diagnostics (Basel) ; 14(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39202192

RESUMEN

In colorectal carcinoma (CRC), tumor deposits (TDs) are described as macroscopic/microscopic nests/nodules in the lymph drainage area discontinuous with the primary mass, without identifiable lymph node (LN) tissue, and not confined to vascular or perineural spaces. A TD is categorized as pN1C only when no bona fide LN metastasis exists. However, there has been an ongoing debate on whether TDs should be counted as LNs. The fact that the origin of TDs is not fully understood adds further uncertainty. This pilot study aims to evaluate whether whole-block imaging by micro-computed tomography (micro-CT WBI) that enables three-dimensional reconstruction of whole-mount (WM) blocks can serve as a tool to assess the origin and path of CRC TDs. We evaluated whole-slide imaging (WSI) and micro-CT WBI of 20 WM blocks from a rectal cancer resection that contained TDs. Each TD was tracked through the contiguous blocks to define their origin and path. Of eleven TDs identified on WSI, six were detected on WBI. Strikingly, six of six TDs trackable through the blocks on WBI revealed an origin from the main tumor. This pilot study provided evidence that micro-CT WBI can serve as an effective tool to evaluate the origin and path of CRC TDs.

19.
Front Plant Sci ; 15: 1346046, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086916

RESUMEN

Micronutrient deficiencies (MNDs) particularly zinc (Zn) and iron (Fe) remain widespread in sub-Saharan Africa (SSA) due to low dietary intake. Wheat is an important source of energy globally, although cultivated wheat is inherently low in grain micronutrient concentrations. Malawian wheat/Am. muticum and Malawian wheat/T. urartu BC1F3 introgression lines, developed by crossing three Malawian wheat varieties (Kenya nyati, Nduna and Kadzibonga) with DH-348 (wheat/Am. muticum) and DH-254 (wheat/T. urartu), were phenotyped for grain Zn and Fe, and associated agronomic traits in Zn-deficient soils, in Malawi. 98% (47) of the BC1F3 introgression lines showed higher Zn above the checks Paragon, Chinese Spring, Kadzibonga, Kenya Nyati and Nduna. 23% (11) of the introgression lines showed a combination of high yields and an increase in grain Zn by 16-30 mg kg -1 above Nduna and Kadzibonga, and 11-25 mg kg -1 above Kenya nyati, Paragon and Chinese Spring. Among the 23%, 64% (7) also showed 8-12 mg kg -1 improvement in grain Fe compared to Nduna and Kenya nyati. Grain Zn concentrations showed a significant positive correlation with grain Fe, whilst grain Zn and Fe negatively and significantly correlated with TKW and grain yield. This work will contribute to the efforts of increasing mineral nutrient density in wheat, specifically targeting countries in the SSA.

20.
ASAIO J ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39116303

RESUMEN

We present the case of a 62-year-old man with severe coronary artery disease who presented to the hospital in refractory ventricular fibrillation cardiac arrest. He showed signs of life despite prolonged resuscitation. We thus decided to initiate extracorporeal cardiopulmonary resuscitation (ECPR). The patient had a known total occlusion of his infrarenal aorta that had been surgically bypassed with a bifemoral-axillary graft. We successfully initiated ECPR via the surgical graft, establishing blood flow to the central circulation through the axillary artery in a peripheral configuration while ensuring blood flow to the left leg via the femoral-femoral graft. The patient was extubated neurologically intact the following day and subsequently underwent coronary artery bypass graft surgery while on extracorporeal membrane oxygenation (ECMO) support. He was subsequently weaned off inotropic support and decannulated from ECMO. He was discharged home neurologically intact and independent in his activities of daily living. This case demonstrates that cannulation for ECPR via a surgical vascular graft is possible and that a total occlusion of the infrarenal aorta in the presence of a surgical bypass is not an absolute contraindication to ECMO.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA