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1.
Nat Commun ; 15(1): 5826, 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38992028

RÉSUMÉ

Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.4 mg/kg (Part A), and 44 received a lower 5.6 mg/kg dose (Part B). The CelTIL score, measuring tumor cellularity and infiltrating lymphocytes from baseline to day 21, was used to assess drug activity. Part A demonstrated increased CelTIL score after one dose of HER3-DXd. Here we report CelTIL score and safety for Part B. In addition, the exploratory analyses of part A involve a comprehensive study of gene expression, somatic mutations, copy-number segments, and DNA-based subtypes, while Part B focuses on validating gene expression. RNA analyses show significant correlations between CelTIL responses, high proliferation genes (e.g., CCNE1, MKI67), and low expression of luminal genes (e.g., NAT1, SLC39A6). DNA findings indicate that CelTIL response is significantly associated with TP53 mutations, proliferation, non-luminal signatures, and a distinct DNA-based subtype (DNADX cluster-3). Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft  models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer.


Sujet(s)
Anticorps monoclonaux humanisés , Tumeurs du sein , Récepteur ErbB-2 , Récepteur ErbB-3 , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/génétique , Tumeurs du sein/métabolisme , Tumeurs du sein/anatomopathologie , Récepteur ErbB-3/métabolisme , Récepteur ErbB-3/génétique , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/génétique , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps neutralisants à large spectre/usage thérapeutique , Adulte d'âge moyen , Anticorps monoclonaux/usage thérapeutique , Adulte , Sujet âgé , Animaux , Protéine p53 suppresseur de tumeur/génétique , Protéine p53 suppresseur de tumeur/métabolisme , Mutation , Souris , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/pharmacologie , Résultat thérapeutique , Trastuzumab , Camptothécine/analogues et dérivés , Immunoconjugués
2.
Alzheimers Dement ; 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38837526

RÉSUMÉ

INTRODUCTION: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. RESULTS: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower socioeconomic status (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [-0.19, 0.59] and Native predominant p = 0.74 [-0.24, 0.33]). DISCUSSION: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities. HIGHLIGHTS: Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance.

3.
Article de Anglais | MEDLINE | ID: mdl-38828781

RÉSUMÉ

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

4.
Plants (Basel) ; 13(3)2024 Feb 02.
Article de Anglais | MEDLINE | ID: mdl-38337977

RÉSUMÉ

Aloina catillum is a variable moss typical of xerophytic environments in the Neotropics, characterized against other closely allied Aloina species with well-differentiated leaf border by its setae twisted to the left throughout. In order to clarify its variability and its relationships with the allied species with differentiated leaf border A. brevirostris, A. obliquifolia, and A. rigida, we performed an integrative study including sequence data from four markers (nuclear ITS, plastid atpB-rbcL, trnG, trnL-F), morphometry, and species assembling by automatic partitioning (ASAP) algorithm. Our data suggest that A. catillum consists of at least three species: A. calceolifolia (an earlier name for A. catillum), and two species described here as a new, A. bracteata sp. nov. and A. limbata sp. nov. This latter species includes the specimens previously identified as A. obliquifolia from South America. Additionally, some morphological and molecular variability was also detected in A. limbata, but was not consistent enough to be recognized taxonomically. The study supports the presence of A. brevirostris in the Neotropics and A. rigida is tentatively excluded from South America. Full descriptions of the A. catillum s.l. species and a diagnostic key to this complex in South America are provided.

5.
Int J Radiat Oncol Biol Phys ; 118(2): 362-367, 2024 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-37717786

RÉSUMÉ

PURPOSE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy. METHODS AND MATERIALS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2). RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%). CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.


Sujet(s)
Carcinome du canal pancréatique , Neutropénie , Tumeurs du pancréas , Protonthérapie , Humains , Adulte d'âge moyen , Sujet âgé , Protons , Protonthérapie/effets indésirables , Protonthérapie/méthodes , Protocoles de polychimiothérapie antinéoplasique , Neutropénie/étiologie , Carcinome du canal pancréatique/radiothérapie , Adjuvants immunologiques
6.
Neurosurgery ; 2023 Dec 05.
Article de Anglais | MEDLINE | ID: mdl-38051042

RÉSUMÉ

BACKGROUND AND OBJECTIVES: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization. METHODS: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances. RESULTS: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033). CONCLUSION: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability.

7.
Mitochondrion ; 73: 95-107, 2023 11.
Article de Anglais | MEDLINE | ID: mdl-37944836

RÉSUMÉ

Mitochondrial function at synapses can be assessed in isolated nerve terminals. Synaptosomes are structures obtained in vitro by detaching the nerve endings from neuronal bodies under controlled homogenization conditions. Several protocols have been described for the preparation of intact synaptosomal fractions. Herein a fast and economical method to obtain synaptosomes with optimal intrasynaptic mitochondria functionality was described. Synaptosomal fractions were obtained from mouse brain cortex by differential centrifugation followed by centrifugation in a Ficoll gradient. The characteristics of the subcellular particles obtained were analyzed by flow cytometry employing specific tools. Integrity and specificity of the obtained organelles were evaluated by calcein and SNAP-25 probes. The proportion of positive events of the synaptosomal preparation was 75 ± 2 % and 48 ± 7% for calcein and Synaptosomal-Associated Protein of 25 kDa (SNAP-25), respectively. Mitochondrial integrity was evaluated by flow cytometric analysis of cardiolipin content, which indicated that 73 ± 1% of the total events were 10 N-nonylacridine orange (NAO)-positive. Oxygen consumption, ATP production and mitochondrial membrane potential determinations showed that mitochondria inside synaptosomes remained functional after the isolation procedure. Mitochondrial and synaptosomal enrichment were determined by measuring synaptosomes/ homogenate ratio of specific markers. Functionality of synaptosomes was verified by nitric oxide detection after glutamate addition. As compared with other methods, the present protocol can be performed briefly, does not imply high economic costs, and provides an useful tool for the isolation of a synaptosomal preparation with high mitochondrial respiratory capacity and an adequate integrity and function of intraterminal mitochondria.


Sujet(s)
Mitochondries , Synaptosomes , Souris , Animaux , Synaptosomes/composition chimique , Synaptosomes/métabolisme , Synaptosomes/ultrastructure , Mitochondries/métabolisme , Métabolisme énergétique , Encéphale/métabolisme , Cortex cérébral
8.
Transplant Direct ; 9(11): e1529, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37899780

RÉSUMÉ

Background: Idiopathic ileal ulceration after intestinal transplantation (ITx) has been discussed infrequently and has an uncertain natural history and relation to graft rejection. Herein, we review our experience with this pathology. Methods: We retrospectively reviewed 225 ITx in 217 patients with minimum 1 y graft survival. Routine graft endoscopy was conducted up to twice weekly within the first 90 d after ITx, gradually decreasing to once yearly. Risks for ulceration over time were evaluated using Cox regression. Results: Of 93 (41%) patients with ulcers, 50 were found within 90 d after ITx mostly via ileoscopy; delayed healing after biopsy appeared causal in the majority. Of the remaining 43 patients with ulcers found >90 d after ITx, 36 were after ileostomy closure. Multivariable modeling demonstrated within 90-d ulcer associations with increasing patient age (hazard ratio [HR], 1.027; P < 0.001) and loop ileostomy (versus Santulli ileostomy; HR, 0.271; P < 0.001). For ulcers appearing after ileostomy closure, their sole association was with absence of graft colon (HR, 7.232; P < 0.001). For ulcers requiring extended anti-microbial and anti-inflammatory therapy, associations included de novo donor-specific antibodies (HR, 3.222; P < 0.007) and nucleotide oligomerization domain mutations (HR, 2.772; P < 0.016). Whole-cohort post-ITx ulceration was not associated with either graft rejection (P = 0.161) or graft failure (P = 0.410). Conclusions: Idiopathic ulceration after ITx is relatively common but has little independent influence on outcome; risks include ileostomy construction, colon-free ITx, immunologic mutation, and donor sensitization.

9.
Alzheimers Dement ; 19(12): 5730-5741, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37427840

RÉSUMÉ

BACKGROUND: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. METHODS: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs. RESULTS: NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden. DISCUSSION: Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.


Sujet(s)
Démence , Maladies neurodégénératives , Syndromes parkinsoniens , Humains , Sujet âgé , Démence/diagnostic , Maladies neurodégénératives/épidémiologie , Prévalence , Amérique latine/épidémiologie , Aidants/psychologie , Tests neuropsychologiques
10.
Int J Cardiol ; 382: 52-59, 2023 07 01.
Article de Anglais | MEDLINE | ID: mdl-37080467

RÉSUMÉ

INTRODUCTION: Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A. METHODS: 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed. RESULTS: Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3). CONCLUSIONS: Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.


Sujet(s)
Tumeurs du sein , Cardiomyopathies , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/complications , Cardiotoxicité/diagnostic , Cardiotoxicité/épidémiologie , Cardiotoxicité/étiologie , Anthracyclines/effets indésirables , Études prospectives , Incidence , Antibiotiques antinéoplasiques/effets indésirables , Peptide natriurétique cérébral , Marqueurs biologiques
11.
JNCI Cancer Spectr ; 7(2)2023 03 01.
Article de Anglais | MEDLINE | ID: mdl-36806942

RÉSUMÉ

CDK4/6 inhibitors benefit a minority of patients who receive them in the breast cancer adjuvant setting. p27Kip1 is a protein that inhibits CDK/Cyclin complexes. We hypothesized that single-nucleotide polymorphisms that impaired p27Kip1 function could render patients refractory to endocrine therapy but responsive to CDK4/6 inhibitors, narrowing the patient subpopulation that requires CDK4/6 inhibitors. We found that the p27Kip1 V109G single-nucleotide polymorphism is homozygous in approximately 15% of hormone-positive breast cancer patients. Polymorphic patients experience rapid failure in response to endocrine monotherapy compared with wild-type or heterozygous patients in the first-line metastatic setting (progression-free survival: 92 vs 485 days, P < .001); when CDK4/6 inhibitors are added, the differences disappear (progression-free survival: 658 vs 761 days, P = .92). As opposed to wild-type p27Kip1, p27Kip1 V109G is unable to suppress the kinase activity of CDK4 in the presence of endocrine inhibitors; however, palbociclib blocks CDK4 kinase activity regardless of the p27Kip1 status. p27Kip1 genotyping could constitute a tool for treatment selection.


Sujet(s)
Tumeurs du sein , Femelle , Humains , Marqueurs biologiques , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/génétique , Kinase-4 cycline-dépendante/génétique , Kinase-4 cycline-dépendante/métabolisme , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/usage thérapeutique
12.
Neurosurgery ; 92(3): 472-480, 2023 03 01.
Article de Anglais | MEDLINE | ID: mdl-36790211

RÉSUMÉ

BACKGROUND: Most patients with severe traumatic brain injury (sTBI) in low- or-middle-income countries and surprisingly many in high-income countries are managed without intracranial pressure (ICP) monitoring. The impact of the first published protocol (Imaging and Clinical Examination [ICE] protocol) is untested against nonprotocol management. OBJECTIVE: To determine whether patients treated in intensive care units (ICUs) using the ICE protocol have lower mortality and better neurobehavioral functioning than those treated in ICUs using no protocol. METHODS: This study involved nineteen mostly public South American hospitals. This is a prospective cohort study, enrolling patients older than 13 years with sTBI presenting within 24 h of injury (January 2014-July 2015) with 6-mo postinjury follow-up. Five hospitals treated all sTBI cases using the ICE protocol; 14 used no protocol. Primary outcome was prespecified composite of mortality, orientation, functional outcome, and neuropsychological measures. RESULTS: A total of 414 patients (89% male, mean age 34.8 years) enrolled; 81% had 6 months of follow-up. All participants included in composite outcome analysis: average percentile (SD) = 46.8 (24.0) nonprotocol, 56.9 (24.5) protocol. Generalized estimating equation (GEE) used to account for center effects (confounder-adjusted difference [95% CI] = 12.2 [4.6, 19.8], P = .002). Kaplan-Meier 6-month mortality (95% CI) = 36% (30%, 43%) nonprotocol, 25% (19%, 31%) protocol (GEE and confounder-adjusted hazard ratio [95% CI] = .69 [.43, 1.10], P = .118). Six-month Extended Glasgow Outcome Scale for 332 participants: average Extended Glasgow Outcome Scale score (SD) = 3.6 (2.6) nonprotocol, 4.7 (2.8) protocol (GEE and confounder-adjusted and lost to follow-up-adjusted difference [95% CI] = 1.36 [.55, 2.17], P = .001). CONCLUSION: ICUs managing patients with sTBI using the ICE protocol had better functional outcome than those not using a protocol. ICUs treating patients with sTBI without ICP monitoring should consider protocolization. The ICE protocol, tested here and previously, is 1 option.


Sujet(s)
Lésions traumatiques de l'encéphale , Lésions encéphaliques , Humains , Mâle , Adulte , Femelle , Pression intracrânienne , Études prospectives , Lésions traumatiques de l'encéphale/imagerie diagnostique , Lésions traumatiques de l'encéphale/thérapie , Monitorage physiologique/méthodes
13.
Alzheimers Dement ; 19(2): 602-610, 2023 02.
Article de Anglais | MEDLINE | ID: mdl-35661582

RÉSUMÉ

INTRODUCTION: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. METHODS: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample. RESULTS: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%-25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups. DISCUSSION: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples.


Sujet(s)
Maladie d'Alzheimer , Apolipoprotéine E4 , Mâle , Humains , Femelle , Sujet âgé , Apolipoprotéine E4/génétique , Apolipoprotéines E/génétique , Maladie d'Alzheimer/épidémiologie , Maladie d'Alzheimer/génétique , Génotype , Hispanique ou Latino/génétique , Caraïbe , Allèles
14.
Eur J Clin Nutr ; 77(4): 454-459, 2023 04.
Article de Anglais | MEDLINE | ID: mdl-36550218

RÉSUMÉ

BACKGROUND/OBJECTIVES: Malnutrition is a prevalent problem in patients with cancer and is associated with poor prognosis. The European Society for Clinical Nutrition and Metabolism (ESPEN) recommends the provision of nutritional support and evaluation. This study aims to describe the nutritional management of patients with cancer, including assessment of adherence, from the perspective of both patients and healthcare professionals (HCPs). SUBJECTS/METHODS: A cross-sectional descriptive observational study was carried out through two surveys addressed to patients and HCPs. RESULTS: A total of 230 cancer patients and 461 HCPs completed the questionnaire. The survey found 55.0% of patients experienced eating problems during treatment and 64.0% reported sequelae affecting nourishment. However, 60.1% of patients and 42.6% of HCPs indicated that nutritional status is not generally assessed. While 86.6% of HCPs stated that nutritional information is provided to patients, only 33.5% of patients reported having received it. Regarding nutritional adherence, 87.4% of HCPs stated that it is assessed whereas only 49.2% of patients receiving nutritional supplements confirmed this. General discomfort or gastrointestinal problems were the main issues hampering correct adherence perceived by both patients (41.8%) and HCPs (95.4%). CONCLUSIONS: Our study demonstrate that different perceptions exist between patients and HCPs about nutritional management in cancer and suggests that in Spain nutritional approach is suboptimal in terms of screening/assessment of malnutrition, nutritional information provided to the patient, nutritional intervention and assessment of adherence to nutritional support. Therefore, measure should be taken to foster the adoption of ESPEN recommendations in clinical practice and to promote nutritional education of HCPs.


Sujet(s)
Malnutrition , Tumeurs , Humains , Études transversales , Espagne , Personnel de santé , Tumeurs/complications , Tumeurs/thérapie , Malnutrition/étiologie , Malnutrition/thérapie
15.
Biomedicines ; 10(9)2022 Aug 25.
Article de Anglais | MEDLINE | ID: mdl-36140180

RÉSUMÉ

We analyzed the fecal microbiome by deep sequencing of the 16S ribosomal genes and the metabolomic profiles of 43 intestinal transplant recipients to identify biomarkers of graft function. Stool samples were collected from 23 patients with stable graft function five years or longer after transplant, 15 stable recipients one-year post-transplant and four recipients with refractory rejection and graft loss within one-year post-transplant. Lactobacillus and Streptococcus species were predominant in patients with stable graft function both in the short and long term, with a microbiome profile consistent with the general population. Conversely, Enterococcus species were predominant in patients with refractory rejection as compared to the general population, indicating profound dysbiosis in the context of graft dysfunction. Metabolomic analysis demonstrated significant differences between the three groups, with several metabolites in rejecting recipients clustering as a distinct set. Our study suggests that the bacterial microbiome profile of stable intestinal transplants is similar to the general population, supporting further application of this non-invasive approach to identify biomarkers of intestinal graft function.

16.
Rev. colomb. cardiol ; 29(2): 248-254, ene.-abr. 2022. graf
Article de Espagnol | LILACS-Express | LILACS | ID: biblio-1376887

RÉSUMÉ

Resumen La disección espontánea de la arteria coronaria es una causa no aterosclerótica de infarto de miocardio, la cual es más común en mujeres jóvenes con pocos o ningún factor de riesgo cardiovascular. Es infrecuente, no se asocia a iatrogenia ni trauma, y se presenta por acumulación espontánea de sangre entre las capas de la pared arterial coronaria, por ruptura de la íntima; de ahí que genera una falsa luz que produce compresión externa del verdadero lumen arterial, con lo cual altera el flujo sanguíneo coronario y ocluye la arteria comprometida. Se expone el caso de una mujer de 31 años, sin factores de riesgo cardiovascular, quien ingresó a un servicio de urgencias con dolor torácico típico, de 2 horas de evolución. En el electrocardiograma se apreció elevación del segmento ST en las derivaciones de la cara anteroseptal e inferior, y troponina T de alta sensibilidad positiva, por lo que se realizó terapia trombolítica con tenecteplasa, sin obtener criterios de reperfusión. Se hizo angiografía coronaria, la cual mostró obstrucción total de la arteria coronaria descendente anterior en el tercio medio. El ultrasonido intravascular documentó flap de disección y hematoma en este segmento, los cuales confirmaron la disección coronaria espontánea. Se realizó angioplastia con implante de stent coronario y se restableció la circulación, observando mejoría de los síntomas.


Abstract Spontaneous coronary artery dissection is a non-atherosclerotic cause of myocardial infarction, more frequent in young women with few or no cardiovascular risk factors, it is infrequent, and it is not associated with iatrogenesis or trauma. It occurs due to spontaneous accumulation of blood between the layers of the coronary artery wall, due to rupture of the intima, generating a false lumen that produces external compression of the true arterial lumen, altering coronary blood flow, occluding the compromised artery. It is presented the case of a 31-year-old woman with no cardiovascular risk factors, who was admitted to an emergency department, with typical chest pain of 2 hours of evolution, showing ST-segment elevation in leads of anteroseptal and inferior face on the electrocardiogram and troponin T with high sensitivity positive. Therefore, thrombolytic therapy was performed with tenecteplase, without obtaining reperfusion criteria. Coronary angiography was performed that demonstrates total obstruction of the anterior descending coronary artery in the middle third. Intravascular ultrasound documents the dissection flap and hematoma in this segment that confirm spontaneous coronary dissection, performing angioplasty with implantation of a coronary stent, restoring circulation with improvement of symptoms.

17.
Plants (Basel) ; 11(5)2022 Feb 25.
Article de Anglais | MEDLINE | ID: mdl-35270096

RÉSUMÉ

In the course of a worldwide revision of the genus Syntrichia, we identified problems in the circumscription of some species of the genus as well as among some allied genera grouped in the tribe Syntricheae. This is the case for the two propagulose Syntrichia amphidiacea and S. gemmascens, closely related to Streptopogon. We analyzed phylogenetic relationships between these species, based on nuclear (ITS) and two plastid (trnL-F and trnG) markers and morphological features. Species delimitation using molecular data was consistent with our preliminary morphological inference. Phylogenetic analyses were performed using maximum likelihood and Bayesian inference methods. Our results placed Syntrichia amphidiacea in the Streptopogon clade. Syntrichia gemmascens is also included in Streptopogon in spite of the discrepancy of the ITS and plastid relationships, which could be evidence of an exchange of genetic material between species in various lineages in the Pottioideae. Streptopogon is maintained as a separate genus on the basis of morphology characters, and we consider the differentiation of laminal papillae and the presence of a stem central strand as new characters in the genus. We accept Sagenotortula as distinct genus sister to Syntrichia. We consider the lack of costal dorsal epidermis and the differentiation of a crescent-shaped costal dorsal stereid band as distinctive generic characters in Syntrichia. Additionally, we include Syntrichia percarnosa as a new synonym for S. breviseta. Three names are lectotypified.

18.
J Med Internet Res ; 24(3): e29063, 2022 03 10.
Article de Anglais | MEDLINE | ID: mdl-35266870

RÉSUMÉ

BACKGROUND: Tumor boards constitute the main consensus and clinical decision-making body of multidisciplinary teams (MDTs) in cancer care. With the increasing clinical complexity of treatment options (eg, targeted therapies, multimodal treatments) and the progressive incorporation of new areas of intervention (eg, survivorship care), tumor boards are now required to play a central role in all cancer processes. However, although frameworks are in place to evaluate MDT quality, only few web-based tools are available for this purpose; indeed, no web-based MDT evaluation tools have been developed for or adapted to the Spanish National Health System. OBJECTIVE: The first aim of this study was to develop a web-based self-assessment model (Autoevaluación de Equipos Multidisciplinares de Atención al Cáncer [AEMAC]) for evaluating multidisciplinary cancer teams in Spain and the second aim was to validate this tool by testing its metric properties, acceptability, and usability. METHODS: We designed and validated the AEMAC program in 3 stages. In the first stage (research), we reviewed the available scientific evidence and performed a qualitative case study of good practice in multidisciplinary care within the Spanish National Health System (n=4 centers and 28 health care professionals). The results were used to define the thematic areas and quality criteria for the self-evaluation model, which were then discussed and validated by a group of experts. The second stage (development) involved the technological development of a web app that would be accessible from any mobile device. In the third stage (piloting and validation), we conducted 4 pilot tests (n=15 tumor boards, 243 professionals) and used the results to analyze the acceptability and usefulness of the tool. RESULTS: We designed a self-assessment model based on 5 thematic areas encompassing a total of 25 quality components, which users rated on a 3-option development scale. The evaluation process, which was managed entirely from the web app, consisted of individual self-assessment, group prioritization, and creation of an improvement plan. Cronbach alpha (.86), McDonald's omega (0.88), and various fit indices (comparative fit index between 0.95 and 1 and goodness-of-fit index between 0.97 and 0.99 for all 5 aspects) confirmed internal consistency. The mean rating for overall satisfaction with the tool and for consistency between the content of the tool and the reality of tumor boards was 7.6 out of 10. CONCLUSIONS: The results obtained during the period of research and piloting of the AEMAC program showed that it has an appropriate structure and metric properties and could therefore be implemented in a real context and generalized to other hospitals. As a virtual tool, it helps to measure the key aspects of MDT quality, such as effectiveness of collaboration and communication, leadership, and the organizational environment.


Sujet(s)
Tumeurs , Auto-évaluation (psychologie) , Humains , Internet , Tumeurs/thérapie , Projets pilotes , Espagne
19.
Lancet Reg Health Am ; 7: None, 2022 Mar.
Article de Anglais | MEDLINE | ID: mdl-35300390

RÉSUMÉ

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohort of elderly individuals from Latin America (LatAm). Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and lived in six LatAm countries were analyzed to estimate parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson's Disease Society Brain Bank's clinical criteria. Findings: In this cohort, the prevalence of parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69vs. 80 years or older, p < 0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I 2 = 56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I 2 = 0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I 2 = 58.6%). Interpretation: The reported prevalence of PD in LatAm is similar to reports from high-income countries (HIC). A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations currently undergoing rapid demographic aging and epidemiological transition. Funding: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

20.
Virchows Arch ; 480(4): 759-769, 2022 Apr.
Article de Anglais | MEDLINE | ID: mdl-35089403

RÉSUMÉ

Stomach cancer (SC) incidence and mortality are relevant public health issues worldwide. In Colombia, screening for preneoplastic lesions (PNL) and the presence of H. pylori is not routinely performed. Therefore, the aim of this study was to evaluate OLGA-OLGIM staging and the interobserver agreement in gastritis and preneoplastic lesions in patients with gastroduodenal symptoms from Colombia. A cross-sectional study was conducted in 272 patients with gastroduodenal symptoms. Gastric biopsies were taken following the Updated Sydney System with the OLGA-OLGIM classification, and the results were evaluated by two pathologists. Chronic gastritis and PNL were reported in 76% and 24% of the patients, respectively. Furthermore, 25% of the patients with PNL displayed gastric atrophy (GA) and 75% intestinal metaplasia (IM). Agreement in the histopathological reading for IM was good, whereas for OLGA was variable, and for the H. pylori quantity was poor. OLGA-OLGIM stages 0-II were the most frequent (96%), while stage III (4%) and SC (4%) were the least frequent. Age and coffee consumption were associated with a higher prevalence of PNL. This work determined that 4% of the population is at high risk of developing SC and would benefit from follow-up studies. Reinforcement of training programs to improve the agreement in histopathology readings is required.


Sujet(s)
Gastrite atrophique , Gastrite , Infections à Helicobacter , Helicobacter pylori , États précancéreux , Tumeurs de l'estomac , Études transversales , Gastrite/diagnostic , Gastrite atrophique/complications , Gastrite atrophique/diagnostic , Gastrite atrophique/anatomopathologie , Infections à Helicobacter/complications , Infections à Helicobacter/diagnostic , Humains , Métaplasie , Biais de l'observateur , États précancéreux/diagnostic , États précancéreux/anatomopathologie , Facteurs de risque , Tumeurs de l'estomac/diagnostic , Tumeurs de l'estomac/anatomopathologie
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