Dear Editor,During the early spring of 2020,as the COVID-19(coronavirus disease 2019)pandemic spread across the globe like a viral tsunami,many countries urgently implemented unprecedented mitigation measures to slow ...Dear Editor,During the early spring of 2020,as the COVID-19(coronavirus disease 2019)pandemic spread across the globe like a viral tsunami,many countries urgently implemented unprecedented mitigation measures to slow it down,following the example of China,where the disease first emerged at the end of 2019.As a result,more than 3 billion unprepared people worldwide had to cope with living under stringent lockdown measures for weeks or months,depending on the country.Together with the deaths of hundreds of thousands of people from this disease,a frightening emotional shock has touched populations everywhere around the planet.Millions have lost their jobs,others have had their personal lives changed drastically;the elderly,for example,have sometimes been isolated from any visits.To our knowledge,no guidelines to prevent psychological trauma have been proposed,even for the most vulnerable individuals.Nonetheless,before this crisis began,several experts had warned about the potential impact of such measures on the populations’mental health.展开更多
<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical c...<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. <strong>Method:</strong> First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. <strong>Results: </strong>Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m<sup>2</sup>. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition.<strong> Conclusion: </strong>This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.展开更多
BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they ma...BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they may appear hyperdense on computed tomography(CT).Unfortunately,few reports have been published on this topic so far.In this case report,the hyperdense appearance on contrastenhanced CT of an enteric-coated mesalamine tablet was initially misinterpreted as a jejunal gastrointestinal stromal tumor(GIST).CASE SUMMARY An asymptomatic 81-year-old male patient,who had undergone laparoscopic right nephrectomy four years earlier for stage 1 renal carcinoma,was diagnosed with a jejunal GIST at the 4-year follow-up thoraco-abdominal CT scan.He was referred to our hub hospital for gastroenterological evaluation,and subsequently underwent 18-fluorodeoxyglucose positron emission tomography,abdominal magnetic resonance imaging,and video capsule endoscopy.None of these examinations detected any lesion of the small intestine.After reviewing all the CT images in a multidisciplinary setting,the panel estimated that the hyperdense jejunal image was consistent with a tablet rather than a GIST.The tablet was an 800 mg delayed-release enteric-coated oral mesalamine tablet(Asacol®),which had been prescribed for non-specific colitis,while not informing the hospital physicians.CONCLUSION Delayed-release oral mesalamine(Asacol®),like other enteric-coated medications,can appear as a hyperdense image on a CT scan,mimicking a small intestinal GIST.Therefore,adetailed knowledge of the patients’medications and a multidisciplinary review of the images areessential.展开更多
This paper summarizes the work held at the Cancéropôle Ile-de-France's annual SHS research seminar on the theme:Pluridisciplinarity and methods for SHS research in thefield of cancer.After clarifying the...This paper summarizes the work held at the Cancéropôle Ile-de-France's annual SHS research seminar on the theme:Pluridisciplinarity and methods for SHS research in thefield of cancer.After clarifying the concepts of pluri-,inter-,and transdisciplinarité,it aimed to describe how this type of research is carried out in practice,addressing successively:the role of stakeholders and their respective positions,the need for a shared language,the various temporalities involved and task sharing,the interview and analysis methods as well as the implication of patient-researchers.It highlighted the personal qualities required to practice this type of research,such as psychologicalflexibility and adaptability,a strong desire for collaborative work,acceptance of risk,and a humble stance.展开更多
Background Data on biosimilar use in pediatric inflammatory bowel diseases(IBD)are scarce compared to the status of studies in adults,resulting in limitations in its treatment.We compared effectiveness and safety of b...Background Data on biosimilar use in pediatric inflammatory bowel diseases(IBD)are scarce compared to the status of studies in adults,resulting in limitations in its treatment.We compared effectiveness and safety of biosimilars versus originators in this population.Methods We used data from the French National Health Data System to identify children(less than 18 years old at treatment initiation)initiating treatment with a biosimilar or the originator infliximab or adalimumab for Crohn’s disease(CD)or ulcerative colitis(UC),from first biosimilar launch(January 2015 and October 2018,respectively)to 31 December 2022.Patients’follow-up went until 30 June 2023.We compared the risks of treatment failure and overnight hospitalization in biosimilar versus originator new users using inverse harzard ratio(HR)of probability of treatment weighted Cox regressions(IPTW).Results We included 5870 patients(infliximab:n=3491;adalimumab:n=2379)in the study.Biosimilars represented,respectively,76.0%(n=2652)and 29.0%(n=691)of infliximab and adalimumab initiations.CD represented 70.9%(n=2476)and 69.0%(n=1642)of infliximab and adalimumab initiations.Biosimilar use was not associated with increased risks of treatment failure[IPTW HR(95%confidence interval,CI):infliximab 0.92(0.78–1.09)in CD,0.98(0.76–1.27)in UC;adalimumab 0.98(0.85–1.14)in CD,1.01(0.82–1.24)in UC].Occurrence of all-cause hospitalization was not different between exposure groups[IPTW HR(95%CI):infliximab 0.96(0.78–1.18);adalimumab 1.03(0.80–1.33)].No difference in occurrence of serious infections,mainly gastro-intestinal or dermatological,was found.Conclusion We provide reassuring results on the use,effectiveness and safety of biosimilars in a large unselected pediatric population suffering from IBD.展开更多
Organic anion-transporting polypeptides(OATP)transporter function,which mediates many drugs'liver uptake,was investigated as a molecular determinant of pharmacokinetic variability.Whole-body PET imaging using 11C-...Organic anion-transporting polypeptides(OATP)transporter function,which mediates many drugs'liver uptake,was investigated as a molecular determinant of pharmacokinetic variability.Whole-body PET imaging using 11C-glyburide,a metabolically stable OATP probe,was performed in 16 healthy humans.Ten subjects underwent another 11C-glyburide PET acquisition after OATP inhibition using rifampicin.Subjects were sorted according to age and sex:males<30y(24.0±3.2 y,n=7),males>50y(57.5±5.6 y,n=4),and females>50y(60.6±2.4 y,n=5).The blood-to-liver transfer rate(kuptake)was estimated to describe OATP function.Rifampicin decreased kuptake(−73±13%,P<0.001)and liver exposure(−50±10%,P<0.001)while increasing exposure in blood(+24±24%,P<0.01),myocardium,spleen,and brain(P<0.05).No evidence of extra-hepatic rifampicin-inhibitable transport of 11C-glyburide was found.Baseline liver exposure was 42.6±18.4%higher(P<0.05)in females>50y compared with males>50 y,consistent with higher kuptake values(P<0.05),with negligible impact on blood exposure(P<0.05).In males,neither liver exposure,blood exposure,nor kuptake were affected by aging(P<0.05).kuptake was positively and negatively correlated with liver(P<0.01,R^(2)=0.78)and blood(P<0.01,R2=0.40)exposures respectively.The impact of OATP function(kuptake)on liver exposure was 4-fold more pronounced than on blood exposure.OATP function may thus drive important sex-related differences in liver exposure,which were not discernible through conventional blood-based pharmacokinetics.展开更多
Dear Editor,Appendectomy is usually performed to treat acute appendicitis although it may also be conducted in the absence of appendicitis when patients suffer from chronic abdominal pain.Resection is also known to mi...Dear Editor,Appendectomy is usually performed to treat acute appendicitis although it may also be conducted in the absence of appendicitis when patients suffer from chronic abdominal pain.Resection is also known to mitigate the risk of ulcerative colitis[1],a risk factor for colorectal cancer.The impact of appendectomy on colorectal cancer risk,particularly in the long term,is unclear.The procedurewas initially hypothesized to increase colorectal cancer risk due to decreased immunocompetency.展开更多
Background:Populations of French Polynesia(FP),where France performed atmospheric tests between 1966 and 1974,experience a high incidence of differentiated thyroid cancer(DTC).However,up to now,no sufficiently large s...Background:Populations of French Polynesia(FP),where France performed atmospheric tests between 1966 and 1974,experience a high incidence of differentiated thyroid cancer(DTC).However,up to now,no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion.This research aimed to analyze the genetic factors of DTC risk among the native FP populations.Methods:We analyzed more than 300000 single nucleotide polymorphisms(SNPs)genotyped in 283 DTC cases and 418 matched controls born in FP,most being younger than 15 years old at the time of the first nuclear tests.We analyzed the genetic profile of our cohort to identify population subgroups.We then completed a genome-wide analysis study on the whole population.Results:We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations.We identified three regions associated with increased DTC risk at 6q24.3,10p12.2,and 17q21.32.The lead SNPs at these loci showed respective p-values of 1.66×10^(−7),2.39×10^(−7),and 7.19×10^(−7) and corresponding odds ratios of 2.02,1.89,and 2.37.Conclusion:Our study results suggest a role of the loci 6q24.3,10p12.2 and 17q21.32 in DTC risk.However,a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population.Moreover,the functional impact of these three new loci needs to be further explored and validated.展开更多
Background:While malaria morbidity and mortality have declined since 2000,viral central nervous system infections appear to be an important,underestimated cause of coma in malaria-endemic Eastern Africa.We aimed to de...Background:While malaria morbidity and mortality have declined since 2000,viral central nervous system infections appear to be an important,underestimated cause of coma in malaria-endemic Eastern Africa.We aimed to describe the etiology of non-traumatic comas in young children in Benin,as well as their management and early outcomes,and to identify factors associated with death.Methods:From March to November 2018,we enrolled all HIV-negative children aged between 2 and 6 years,with a Blantyre Coma Score≤2,in this prospective observational study.Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol,including blood cultures,malaria diagnostics,and cerebrospinal fluid analysis using multiplex PCR.To determine factors associated with death,univariate and multivariate analyses were performed.Results:From 3244 admissions,84 children were included:malaria was diagnosed in 78,eight of whom had a viral or bacterial co-infection.Six children had a non-malarial infection or no identified cause.The mortality rate was 29.8%(25/84),with 20 children dying in the first 24 h.Co-infected children appeared to have a poorer prognosis.Of the 76 children who consulted a healthcare professional before admission,only 5 were prescribed adequate antimalarial oral therapy.Predictors of early death were jaundice or increased bilirubin[odd ratio(OR)=8.6;95% confidential interval(CI):2.03-36.1]and lactate>5 mmol/L(OR=5.1;95%CI:1.49-17.30).Antibiotic use before admission(OR=0.1;95%CI:0.02-0.85)and vaccination against yellow fever(OR=0.2,95%CI:0.05-0.79)protected against mortality.Conclusions:Infections were found in all children who died,and cerebral malaria was by far the most common cause of non-traumatic coma.Missed opportunities to receive early effective antimalarial treatment were common.Other central nervous system infections must be considered in their management.Some factors that proved to be protective against early death were unexpected.展开更多
Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigeneti...Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.展开更多
Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechani...Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].展开更多
Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regardin...Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.展开更多
基金funded by the French and National Agency for Research(ANR,grant ANR-20-COVI-0035-01)the Fondation de France and the National Research Institute for Sustainable Development(IRD).
文摘Dear Editor,During the early spring of 2020,as the COVID-19(coronavirus disease 2019)pandemic spread across the globe like a viral tsunami,many countries urgently implemented unprecedented mitigation measures to slow it down,following the example of China,where the disease first emerged at the end of 2019.As a result,more than 3 billion unprepared people worldwide had to cope with living under stringent lockdown measures for weeks or months,depending on the country.Together with the deaths of hundreds of thousands of people from this disease,a frightening emotional shock has touched populations everywhere around the planet.Millions have lost their jobs,others have had their personal lives changed drastically;the elderly,for example,have sometimes been isolated from any visits.To our knowledge,no guidelines to prevent psychological trauma have been proposed,even for the most vulnerable individuals.Nonetheless,before this crisis began,several experts had warned about the potential impact of such measures on the populations’mental health.
文摘<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. <strong>Method:</strong> First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. <strong>Results: </strong>Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m<sup>2</sup>. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition.<strong> Conclusion: </strong>This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.
文摘BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they may appear hyperdense on computed tomography(CT).Unfortunately,few reports have been published on this topic so far.In this case report,the hyperdense appearance on contrastenhanced CT of an enteric-coated mesalamine tablet was initially misinterpreted as a jejunal gastrointestinal stromal tumor(GIST).CASE SUMMARY An asymptomatic 81-year-old male patient,who had undergone laparoscopic right nephrectomy four years earlier for stage 1 renal carcinoma,was diagnosed with a jejunal GIST at the 4-year follow-up thoraco-abdominal CT scan.He was referred to our hub hospital for gastroenterological evaluation,and subsequently underwent 18-fluorodeoxyglucose positron emission tomography,abdominal magnetic resonance imaging,and video capsule endoscopy.None of these examinations detected any lesion of the small intestine.After reviewing all the CT images in a multidisciplinary setting,the panel estimated that the hyperdense jejunal image was consistent with a tablet rather than a GIST.The tablet was an 800 mg delayed-release enteric-coated oral mesalamine tablet(Asacol®),which had been prescribed for non-specific colitis,while not informing the hospital physicians.CONCLUSION Delayed-release oral mesalamine(Asacol®),like other enteric-coated medications,can appear as a hyperdense image on a CT scan,mimicking a small intestinal GIST.Therefore,adetailed knowledge of the patients’medications and a multidisciplinary review of the images areessential.
文摘This paper summarizes the work held at the Cancéropôle Ile-de-France's annual SHS research seminar on the theme:Pluridisciplinarity and methods for SHS research in thefield of cancer.After clarifying the concepts of pluri-,inter-,and transdisciplinarité,it aimed to describe how this type of research is carried out in practice,addressing successively:the role of stakeholders and their respective positions,the need for a shared language,the various temporalities involved and task sharing,the interview and analysis methods as well as the implication of patient-researchers.It highlighted the personal qualities required to practice this type of research,such as psychologicalflexibility and adaptability,a strong desire for collaborative work,acceptance of risk,and a humble stance.
文摘Background Data on biosimilar use in pediatric inflammatory bowel diseases(IBD)are scarce compared to the status of studies in adults,resulting in limitations in its treatment.We compared effectiveness and safety of biosimilars versus originators in this population.Methods We used data from the French National Health Data System to identify children(less than 18 years old at treatment initiation)initiating treatment with a biosimilar or the originator infliximab or adalimumab for Crohn’s disease(CD)or ulcerative colitis(UC),from first biosimilar launch(January 2015 and October 2018,respectively)to 31 December 2022.Patients’follow-up went until 30 June 2023.We compared the risks of treatment failure and overnight hospitalization in biosimilar versus originator new users using inverse harzard ratio(HR)of probability of treatment weighted Cox regressions(IPTW).Results We included 5870 patients(infliximab:n=3491;adalimumab:n=2379)in the study.Biosimilars represented,respectively,76.0%(n=2652)and 29.0%(n=691)of infliximab and adalimumab initiations.CD represented 70.9%(n=2476)and 69.0%(n=1642)of infliximab and adalimumab initiations.Biosimilar use was not associated with increased risks of treatment failure[IPTW HR(95%confidence interval,CI):infliximab 0.92(0.78–1.09)in CD,0.98(0.76–1.27)in UC;adalimumab 0.98(0.85–1.14)in CD,1.01(0.82–1.24)in UC].Occurrence of all-cause hospitalization was not different between exposure groups[IPTW HR(95%CI):infliximab 0.96(0.78–1.18);adalimumab 1.03(0.80–1.33)].No difference in occurrence of serious infections,mainly gastro-intestinal or dermatological,was found.Conclusion We provide reassuring results on the use,effectiveness and safety of biosimilars in a large unselected pediatric population suffering from IBD.
基金funded by grant ANR-16-CE17-0011(France)and performed on a platform member of the France Life Imaging network(grant ANR-11-INBS-0006,France).
文摘Organic anion-transporting polypeptides(OATP)transporter function,which mediates many drugs'liver uptake,was investigated as a molecular determinant of pharmacokinetic variability.Whole-body PET imaging using 11C-glyburide,a metabolically stable OATP probe,was performed in 16 healthy humans.Ten subjects underwent another 11C-glyburide PET acquisition after OATP inhibition using rifampicin.Subjects were sorted according to age and sex:males<30y(24.0±3.2 y,n=7),males>50y(57.5±5.6 y,n=4),and females>50y(60.6±2.4 y,n=5).The blood-to-liver transfer rate(kuptake)was estimated to describe OATP function.Rifampicin decreased kuptake(−73±13%,P<0.001)and liver exposure(−50±10%,P<0.001)while increasing exposure in blood(+24±24%,P<0.01),myocardium,spleen,and brain(P<0.05).No evidence of extra-hepatic rifampicin-inhibitable transport of 11C-glyburide was found.Baseline liver exposure was 42.6±18.4%higher(P<0.05)in females>50y compared with males>50 y,consistent with higher kuptake values(P<0.05),with negligible impact on blood exposure(P<0.05).In males,neither liver exposure,blood exposure,nor kuptake were affected by aging(P<0.05).kuptake was positively and negatively correlated with liver(P<0.01,R^(2)=0.78)and blood(P<0.01,R2=0.40)exposures respectively.The impact of OATP function(kuptake)on liver exposure was 4-fold more pronounced than on blood exposure.OATP function may thus drive important sex-related differences in liver exposure,which were not discernible through conventional blood-based pharmacokinetics.
基金The French E3N cohort is maintained with the support of the Mutuelle Générale de l’Education Nationale(MGEN),Gustave Roussy and the French League against Cancer(LNCC).E3N-E4N is also supported by the French National Research Agency(ANR)under the Investment for the future Program(PIA)(ANR-10-COHO-0006)by the French Ministry of Higher Education,Research and Innovation(subsidy#2102918823).
文摘Dear Editor,Appendectomy is usually performed to treat acute appendicitis although it may also be conducted in the absence of appendicitis when patients suffer from chronic abdominal pain.Resection is also known to mitigate the risk of ulcerative colitis[1],a risk factor for colorectal cancer.The impact of appendectomy on colorectal cancer risk,particularly in the long term,is unclear.The procedurewas initially hypothesized to increase colorectal cancer risk due to decreased immunocompetency.
基金supported by Institut National du Cancer(Grant No.9533)Fondation ARC(Grant No.PGA120150202302).
文摘Background:Populations of French Polynesia(FP),where France performed atmospheric tests between 1966 and 1974,experience a high incidence of differentiated thyroid cancer(DTC).However,up to now,no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion.This research aimed to analyze the genetic factors of DTC risk among the native FP populations.Methods:We analyzed more than 300000 single nucleotide polymorphisms(SNPs)genotyped in 283 DTC cases and 418 matched controls born in FP,most being younger than 15 years old at the time of the first nuclear tests.We analyzed the genetic profile of our cohort to identify population subgroups.We then completed a genome-wide analysis study on the whole population.Results:We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations.We identified three regions associated with increased DTC risk at 6q24.3,10p12.2,and 17q21.32.The lead SNPs at these loci showed respective p-values of 1.66×10^(−7),2.39×10^(−7),and 7.19×10^(−7) and corresponding odds ratios of 2.02,1.89,and 2.37.Conclusion:Our study results suggest a role of the loci 6q24.3,10p12.2 and 17q21.32 in DTC risk.However,a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population.Moreover,the functional impact of these three new loci needs to be further explored and validated.
基金funded by the French National Research Agency(ANR-17-CE17-0001).
文摘Background:While malaria morbidity and mortality have declined since 2000,viral central nervous system infections appear to be an important,underestimated cause of coma in malaria-endemic Eastern Africa.We aimed to describe the etiology of non-traumatic comas in young children in Benin,as well as their management and early outcomes,and to identify factors associated with death.Methods:From March to November 2018,we enrolled all HIV-negative children aged between 2 and 6 years,with a Blantyre Coma Score≤2,in this prospective observational study.Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol,including blood cultures,malaria diagnostics,and cerebrospinal fluid analysis using multiplex PCR.To determine factors associated with death,univariate and multivariate analyses were performed.Results:From 3244 admissions,84 children were included:malaria was diagnosed in 78,eight of whom had a viral or bacterial co-infection.Six children had a non-malarial infection or no identified cause.The mortality rate was 29.8%(25/84),with 20 children dying in the first 24 h.Co-infected children appeared to have a poorer prognosis.Of the 76 children who consulted a healthcare professional before admission,only 5 were prescribed adequate antimalarial oral therapy.Predictors of early death were jaundice or increased bilirubin[odd ratio(OR)=8.6;95% confidential interval(CI):2.03-36.1]and lactate>5 mmol/L(OR=5.1;95%CI:1.49-17.30).Antibiotic use before admission(OR=0.1;95%CI:0.02-0.85)and vaccination against yellow fever(OR=0.2,95%CI:0.05-0.79)protected against mortality.Conclusions:Infections were found in all children who died,and cerebral malaria was by far the most common cause of non-traumatic coma.Missed opportunities to receive early effective antimalarial treatment were common.Other central nervous system infections must be considered in their management.Some factors that proved to be protective against early death were unexpected.
文摘Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.
基金funded by the French National Cancer Institute(INCA_N◦2018-123)and supported by Canccrole Ile-de-France(N◦2018-1-PL SHS-06-CIRC-1)supported by the International Agency for Research on Cancer(IARC)and also by the Department of Epidemiology and Biostatistics,School of Public Health,Imperial College London,which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre(BRC)+9 种基金supported by:Danish Cancer Society(Denmark)Ligue Contre le Cancer,Institut Gustave Roussy,Mutuelle Générale de l’Education Nationale,Institut National de la Santéet de la Recherche Médicale(INSERM)(France)German Cancer Aid,German Cancer Research Center(DKFZ),German Institute of Human Nutrition Potsdam-Rehbruecke(DIfE),Federal Ministry of Education and Research(BMBF)(Germany)Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy,Compagnia di SanPaolo and National Research Council(Italy)Dutch Ministry of Public Health,Welfare and Sports(VWS),Netherlands Cancer Registry(NKR),LK Research Funds,Dutch Prevention Funds,Dutch ZON(Zorg Onderzoek Nederland),World Cancer Research Fund(WCRF),Statistics Netherlands(The Netherlands)Health Research Fund(FIS)-Instituto de Salud Carlos III(ISCIII),Regional Governments ofAndalucía,Asturias,Basque Country,Murcia and Navarra,and the Catalan Institute of Oncology-ICO(Spain)Swedish Cancer Society,Swedish Research Council and County Councils of Skane and Vasterbotten(Sweden)Cancer Research UK(14136 to EPIC-NorfolkC8221/A29017 to EPIC-Oxford),Medical Research Council(1000143 to EPIC-NorfolkMR/M012190/1 to EPIC-Oxford)(United Kingdom).
文摘Owing to shared risk factors between cardiometabolic diseases(CMDs)and cancer,coupled with population aging,the lifetime risk of an individual developing cancer after a CMD is increasing.Furthermore,biological mechanisms such as insulin resistance or inflammation may not only predispose individuals withCMDto an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage[1,2].
基金supported by a Wellcome Trust PhD studentship in Molecular,Genetic and Lifecourse Epidemiology(224982/Z/22/Z).
文摘Recent epidemiological studies have suggested a positive association between ultra-processed food consumption and breast cancer risk,although some studies also reported no association.Furthermore,the evidence regarding the associations between intake of food with lower degrees of processing and breast cancer risk is limited.Thus,we investigated the associations between dietary intake by degree of food processing and breast cancer risk,overall and by breast cancer subtypes in the European Prospective Investigation into Cancer and Nutrition(EPIC)study.Dietary intake of EPIC participants was assessed via questionnaires at baseline.More than 11,000 food ingredients were classified into four groups of food processing levels using the NOVA classification system:unprocessed/minimally processed(NOVA 1),culinary ingredients(NOVA 2),processed(NOVA 3)and ultra-processed(NOVA 4).Cox proportional hazards models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)of breast cancer per standard deviation increase in daily consumption(grams)of foods from each NOVA group.The current analysis included 14,933 breast cancer cases,diagnosed among the 318,686 EPIC female participants,(median follow-up of 14.9 years).No associations were found between breast cancer risk and the level of dietary intake from NOVA 1[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)],NOVA 2[HR_(per 1 SD)=1.01(95%CI 0.98-1.03)]and NOVA 4[HR_(per 1 SD)=1.01(95%CI 0.99-1.03)]foods.However,a positive association was found between NOVA 3 and breast cancer risk[HR_(per 1 SD)=1.05(95%CI 1.03-1.07)]which became non-significant after adjustment for alcohol intake[HR_(per 1 SD)=1.01(95%CI 0.98-1.05)]or when beer and wine were excluded from this group[HR_(per 1 SD)=0.99(95%CI 0.97-1.01)].The associations did not differ by breast cancer subtype,menopausal status or body mass index.Findings from this large-scale prospective study suggest that the positive association between processed food intake and breast cancer risk was likely driven by alcoholic beverage consumption.
