14 research outputs found
Anomalies de la tolƩrance au glucose chez les patients atteints de fibrose kystique Nouveaux facteurs de risque
Introduction : La fibrose kystique (FK) est une maladie geĢneĢtique qui atteint plusieurs organes dont le pancreĢas, le foie et les poumons. Elle sāexprime par une accumulation de mucus visqueux qui va entraiĢner une alteĢration des fonctions de ces organes. Les progreĢs scientifiques ont permis dāameĢliorer la condition de vie et dāaugmenter consideĢrablement lāespeĢrance de vie des patients atteints de FK. LāameĢlioration de lāespeĢrance de vie des patients FK est associeĢe aĢ lāapparition dāanomalies de la toleĢrance au glucose preĢceĢdant lāapparition du diabeĢte associeĢ aĢ la FK (DAFK). Le DAFK preĢsente des similitudes avec le diabeĢte de type 1 [DT1] (faible poids, faible seĢcreĢtion dāinsuline) et le diabeĢte de type 2 [DT2] (intoleĢrance au glucose, anomalies de la sensibiliteĢ aĢ lāinsuline), mais il est speĢcifique pour ses causes et ses conseĢquences. Le DAFK est associeĢ aĢ un risque accru de perte de poids, de reĢduction de la fonction pulmonaire et de mortaliteĢ preĢcoce et touche 50 % des patients adultes. La principale cause de ce diabeĢte est deĢcrite par une seĢcreĢtion d'insuline reĢduite et retardeĢe. Les facteurs de risque, menant au deĢveloppement du DAFK et les conseĢquences de son apparition ne sont pas encore bien comprises. La dieĢte (riche en lipides et en eĢnergie) recommandeĢe en FK visant aĢ maintenir un poids adeĢquat pourrait eĢtre responsable de lāaccumulation de graisse ectopique, de reĢsistance aĢ lāinsuline, de steĢatose heĢpatique et dāanomalies du bilan lipidique rapporteĢs en FK. Pour les patients sans FK, ces anomalies sont associeĢes au deĢveloppement du DT2.
Objectif : Le but de ce travail de theĢse visait aĢ lāidentification de nouveaux facteurs de risque dāanomalies de la toleĢrance au glucose dans une population dāadultes atteints de FK.
MeĢthode : Pour cela nous avons i) observeĢ lāeĢvolution de la seĢcreĢtion dāinsuline chez les patients FK aĢgeĢs ; ii) identifieĢ lāassociation entre les enzymes heĢpatiques et la preĢvalence du DAFK ; iii) identifieĢ la preĢvalence de dyslipideĢmie chez les patients FK adultes et lāassociation avec le risque de deĢveloppement du DAFK.
ReĢsultats : Nos reĢsultats ont montreĢ que les patients FK adultes preĢsentent une seĢcreĢtion dāinsuline alteĢreĢe, mais quāelle ne se deĢgrade pas davantage sur une deĢcennie. Par contre, sur la meĢme peĢriode, les patients deviennent plus reĢsistants aĢ lāinsuline. Nous avons mis en eĢvidence lāexistence dāune relation entre le niveau dāenzymes alanine aminotransfeĢrase (ALT) eĢleveĢ et la preĢvalence de DAFK. Enfin, nous avons montreĢ lāexistence dāune forte preĢvalence de dyslipideĢmie en FK, mais ces anomalies ne sont pas associeĢes aĢ la survenue du DAFK.
Conclusion : Ces travaux ont permis de mieux comprendre lāassociation entre diffeĢrents facteurs de risque en lien avec les anomalies de la toleĢrance au glucose chez des patients adultes FK. Nous avons identifieĢ un meĢcanisme et un possible biomarqueur du DAFK, les enzymes heĢpatiques ALT, chez les patients FK adultes. Ces donneĢes peuvent fournir un rationnel pertinent pour la poursuite dāautres eĢtudes cliniques dans le but dāameĢliorer la qualiteĢ de vie des patients atteints de FK.Introduction: Cystic fibrosis (CF) is a genetic disorder that affects several organs including the
pancreas, liver, and lungs. It is expressed by an accumulation of viscous mucus which will cause
an impairment of the functions of these organs. Scientific advances have improved the condition
of life and significantly increased the life expectancy of patients with CF. This improved life
expectancy of CF patients is associated with the onset of glucose tolerance abnormalities before
the onset of CF-associated diabetes (CFRD).
CFRD has similarities with type 1 diabetes [T1D] (low body weight, low insulin secretion) and
type 2 diabetes [T2D] (glucose intolerance, abnormal insulin sensitivity), but it is specific for its
causes and consequences. CFRD is associated with an increased risk of weight loss, reduced lung
function and early mortality and affects 50% of adult patients. The main cause of this diabetes is
described as a reduced and delayed insulin secretion. The risk factors leading to the development
of CFRD and the consequences of its appearance are not well understood. The diet (rich in lipids
and energy) recommended in CF, that aims at maintaining an adequate body weight, could be
responsible for the accumulation of ectopic fat, insulin resistance, fatty liver and abnormalities of
the lipid balance reported in FK. For patients without CF these anomalies are associated with the
development of T2D.
Objective: The aim of this thesis work was to identify new risk factors for abnormal glucose
tolerance in a population of adults with CF.
Method: For this we have i) observed the evolution of insulin secretion in elderly CF patients; ii)
identified the association between liver enzymes and the prevalence of CFRD; iii) studied the
prevalence of dyslipidemia in adult CF patients and the association with the risk of developing
CFRD.
Results: Our results have shown that adult CF patients have impaired insulin secretion, but it has
not degraded further over a decade. However, over the same period, patients become more
resistant to insulin. We have highlighted a relationship between the high alanine aminotransferase
(ALT) enzyme level and the prevalence of CFRD. Finally, we have shown the existence of a high
prevalence of dyslipidemia in CF but these anomalies are not associated with the occurrence of
CFRD.
Conclusion: This work has made possible to better understand the association between different
risk factors linked to glucose tolerance abnormalities in adult CF patients. We have identified a
mechanism and a possible biomarker, ALT hepatic enzyme, of CFRD in adult CF patients. These
data may provide a relevant rationale for the pursuit of other clinical studies in order to improve
the quality of life of patients with CF
Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study
Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU.
Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models.
Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts.
Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted
Impact of 1h oral glucose tolerance test on the clinical status of adult cystic fibrosis patients over a 4-year period.
ObjectiveTo report the clinical profile associated with G60 and I60 over a 4-year prospective observational period in 2 large cohorts of adult patients with CF.Methods319 patients were included (210 Canadian and 119 French) and classified according to their inclusion G60 (ā„ or ResultsHigh G60 was not associated to a lower FEV1 at inclusion and the follow-up decline was not higher in the high G60 group (Coefficient [95% CI]: -3.4 [-7.4;0.6], p = 0.0995.). There was no significant association between BMI and G60. Patients with high I60 tended to have a higher mean BMI (+0.5 kg/m2 [0.0 to 1.1], p = 0.05) but no interaction over time was observed.ConclusionsHigh G60 is not associated with a lower lung function at inclusion nor its decline over a 4-year follow-up. High I60 is slightly associated to a higher weight at inclusion, but not with BMI evolution over time in adult patients
Hepatic enzyme ALT as a marker of glucose abnormality in men with cystic fibrosis.
AimCystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). In non-CF patients, liver disease, specifically steatosis and non-alcoholic fatty liver disease (NAFLD), is strongly associated with type 2 diabetes. We compared glycemic status and metabolic profiles in CF patients according to a biomarker of hepatic injury, alanine aminotransferase (ALT).MethodsWe conducted a cross-sectional study among 273 adult CF patients recruited from the Montreal CF Cohort. A 2-hour oral glucose tolerance test (OGTT) was performed to collect glucose and insulin measures every 30 minutes. Fasting ALT levels and anthropometric measures were also obtained. Patients were categorized into 2 groups based on ALT cut-off of 25 U/L.ResultsPatients in the high ALT group were mostly men (83%), had higher mean weight and BMI (pConclusionsAdult CF men with higher ALT show an increased frequency of dysglycemia and de novo CFRD, lower insulin sensitivity and higher eight. Our data suggests that ALT levels could be an interesting tool to guide targeted diabetes screening, particularly among CF men. Prospective studies are needed to confirm these observations
EpCAMhigh and EpCAMlow circulating tumor cells in metastatic prostate and breast cancer patients
The presence of high expressing epithelial cell adhesion molecule (EpCAMhigh) circulating tumor cells (CTC) enumerated by CellSearchĀ® in blood of cancer patients is strongly associated with poor prognosis. This raises the question about the presence and relation with clinical outcome of low EpCAM expressing CTC (EpCAMlow CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAMhigh and EpCAMlow CTC using CellSearch, followed by microfiltration of the EpCAMhigh CTC depleted blood. Blood samples of 108 castration-resistant prostate cancer patients and 22 metastatic breast cancer patients were processed at six participating sites, using protocols and tools developed in the CTC-Trap program. Of the prostate cancer patients, 53% had ā„5 EpCAMhigh CTC and 28% had ā„5 EpCAMlow CTC. For breast cancer patients, 32% had ā„5 EpCAMhigh CTC and 36% had ā„5 EpCAMlow CTC. 70% of prostate cancer patients and 64% of breast cancer patients had in total ā„5 EpCAMhigh and/or EpCAMlow CTC, increasing the number of patients in whom CTC are detected. Castration-resistant prostate cancer patients with ā„5 EpCAMhigh CTC had shorter overall survival versus those with <5 EpCAMhigh CTC (p = 0.000). However, presence of EpCAMlow CTC had no relation with overall survival. This emphasizes the importance to demonstrate the relation with clinical outcome when presence of CTC identified with different technologies are reported, as different CTC subpopulations can have different relations with clinical outcome
Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study
Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection.
Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974.
Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22Ā·1 months (IQR 8Ā·4-57Ā·8) from cancer diagnosis and 44 days (28-329) from COVID-19 diagnosis. 234 (15Ā·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49Ā·6%]) and residual fatigue (96 [41Ā·0%]). Sequelae were more common in men (vs women; p=0Ā·041), patients aged 65 years or older (vs other age groups; p=0Ā·048), patients with two or more comorbidities (vs one or none; p=0Ā·0006), and patients with a history of smoking (vs no smoking history; p=0Ā·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0Ā·0001), complicated COVID-19 (p<0Ā·0001), and COVID-19 therapy (p=0Ā·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113-148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1Ā·80 [95% CI 1Ā·18-2Ā·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15Ā·0%) permanently discontinued therapy, and 178 (38Ā·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3Ā·53 [95% CI 1Ā·45-8Ā·59]), but dose or regimen adjustments were not (0Ā·84 [0Ā·35-2Ā·02]).
Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients
Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study
Background: Despite high contagiousness and rapid spread, severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across
affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected
country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the
national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients
with cancer versus those in continental EU.
Methods: We performed a retrospective analysis of the OnCovid study database, a European
registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from
27th February to 10th September 2020. We analysed case fatality rates and risk of death at
30 days and 6 months stratified by region of origin (UK versus EU). We compared patient
characteristics at baseline including oncological and COVID-19especific therapy across UK
D.J. Pinato et al. / European Journal of Cancer 150 (2021) 190e202 191
and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes
in multivariable Cox regression models.
Findings: Compared with EU (n Z 924), UK patients (n Z 468) were characterised by higher
case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard
ratio [HR], 1.64 [95% confidence interval {CI}, 1.36e1.99]) and 6 months after COVID-19
diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33e1.88]). UK patients
were more often men, were of older age and have more comorbidities than EU counterparts
(p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001).
Despite equal proportions of complicated COVID-19, rates of intensive care admission and
use of mechanical ventilation, UK patients with cancer were less likely to receive anti
eCOVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists
(p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed
the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent
of the patient\u2019s age, gender, tumour stage and status; number of comorbidities; COVID-
19 severity and receipt of anticancer and antieCOVID-19 therapy. Rates of permanent cessation
of anticancer therapy after COVID-19 were similar in the UK and EU cohorts.
Interpretation: UK patients with cancer have been more severely impacted by the unfolding of
the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer
therapy. The increased frailty of UK patients with cancer highlights high-risk groups
that should be prioritised for antieSARS-CoV-2 vaccination. Continued evaluation of
long-term outcomes is warranted
Time-Dependent COVID-19 Mortality in Patients with Cancer:An Updated Analysis of the OnCovid Registry
IMPORTANCE: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all Pā<ā.001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; Pā=ā.03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; Pā=ā.001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; Pā<ā.001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; Pā<ā.001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; Pā<ā.001) and antiāCOVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; Pā<ā.001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; Pā<ā.001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, antiāCOVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time