Incidence and trends of first basal cell carcinomas in France between 1980 and 2019: a regional population-based registry study.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent malignancy reported in populations with fair skin. In most countries, BCCs are only partially or not at all recorded, and incidence data are lacking. OBJECTIVES: This study assessed the current incidence rates and trends in the only two French départements where BCCs have been recorded for several decades. METHODS: This regional population-based study thus used data from two French cancer registries (Doubs and Haut-Rhin) where first-time BCC diagnoses were recorded. The European age-standardised incidence rates (EASR) were calculated per 100 000 person-years (p-y). The trends and the annual percentages of change were assessed using join-point analysis. RESULTS: In all, 48 989 patients were diagnosed with a first BCC in the study period. The median age at diagnosis was 69 years and the BCCs were mainly located on the head and neck (68.8%). In the Doubs area between 1980 and 2016, the EASR of BCC increased from 59.9 to 183.1 per 100 000 p-y. The annual increase for men was 5.73% before 1999 and 1.49% thereafter, and among women 4.56% before 2001 and 1.31% thereafter. In the Haut-Rhin area, the EASR increased from 139.2 in 1991 to 182.8 per 100 000 p-y in 2019. Among men, the EASR increased annually by 2.31% before 2000, and by 0.29% after 2000; among women, it increased by 0.95% over the entire period (1991-2019). In the most recent period and for these two départements, the age-specific incidence rates of BCC for men and women were close before the age of 60, except for the 40-49 age group, where the rates were significantly higher among women. For patients aged 60 years and over, men had much higher rates of BCC. CONCLUSIONS: BCC incidence has increased since 1980 and is still rising, particularly among men and the elderly. A slowing was observed since 2000, which could be explained by a shift in the management of BCCs and by the possible efficacy of prevention actions. This study provides insight into the BCC burden in France and highlights the need to maintain effective prevention strategies, since incidence is still increasing.

Personalized follow-up of circulating DNA in resected stage III/IV melanoma: PERCIMEL multicentric prospective study protocol.

BACKGROUND: With more than 15,000 new cases /year in France and 2,000 deaths, cutaneous melanoma represents approximately 4% of incidental cancers and 1.2% of cancer related deaths. In locally advanced (stage III) or resectable metastatic (stage IV) melanomas, medical adjuvant treatment is proposed and recent advances had shown the benefit of anti-PD1/PDL1 and anti-CTLA4 immunotherapy as well as anti-BRAF and anti-MEK targeted therapy in BRAF V600 mutated tumors. However, the recurence rate at one year is approximately 30% and justify extensive research of predictive biomarkers. If in metastatic disease, the follow-up of circulating tumor DNA (ctDNA) has been demonstrated, its interest in adjuvant setting remains to be precised, especially because of a lower detection rate. Further, the definition of a molecular response could prove useful to personalized treatment. METHODS: PERCIMEL is an open prospective multicentric study executed through collaboration of the Institut de Cancérologie de Lorraine (non-profit comprehensive cancer center) and 6 French university and community hospitals. A total of 165 patients with resected stage III and IV melanoma, eligible to adjuvant imunotherapy or anti-BRAF/MEK kinase inhibitors will be included. The primary endpoint is the presence of ctDNA, 2 to 3 weeks after surgery, defined as mutated ctDNA copy number calculated as the allelic fraction of a clonal mutation relative to total ctDNA. Secondary endpoints are recurrence-free survival, distant metastasis-free survival and specific survival. We will follow ctDNA along treatment, quantitatively through ctDNA mutated copy number variation, qualitatively through the presence of cfDNA and its clonal evolution. Relative and absolute variations of ctDNA during follow-up will be also analyzed. PERCIMEL study aims at provide scientific evidence that ctDNA quantitative and qualitative variations can be used to predict the recurrence of patients with melanoma treated with adjuvant immunotherapy or kinase inhibitors, thus defining the notion of molecular recurrence.

Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis.

BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.

Perinatal Administration of C-Phycocyanin Protects Against Atherosclerosis in apoE-Deficient Mice by Modulating Cholesterol and Trimethylamine-N-Oxide Metabolisms.

OBJECTIVE: Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life. Approach and Results: C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine N-oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as ß-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex. CONCLUSIONS: Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.

Chest CT for rapid triage of patients in multiple emergency departments during COVID-19 epidemic: experience report from a large French university hospital.

OBJECTIVES: To assess the diagnostic performances of chest CT for triage of patients in multiple emergency departments during COVID-19 epidemic, in comparison with reverse transcription polymerase chain reaction (RT-PCR) test. METHOD: From March 3 to April 4, 2020, 694 consecutive patients from three emergency departments of a large university hospital, for which a hospitalization was planned whatever the reasons, i.e., COVID- or non-COVID-related, underwent a chest CT and one or several RT-PCR tests. Chest CTs were rated as "Surely COVID+," "Possible COVID+," or "COVID-" by experienced radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the final RT-PCR test as standard of reference. The delays for CT reports and RT-PCR results were recorded and compared. RESULTS: Among the 694 patients, 287 were positive on the final RT-PCR exam. Concerning the 694 chest CT, 308 were rated as "Surely COVID+", 34 as "Possible COVID+," and 352 as "COVID-." When considering only the "Surely COVID+" CT as positive, accuracy, sensitivity, specificity, PPV, and NPV reached 88.9%, 90.2%, 88%, 84.1%, and 92.7%, respectively, with respect to final RT-PCR test. The mean delay for CT reports was three times shorter than for RT-PCR results (187 ± 148 min versus 573 ± 327 min, p < 0.0001). CONCLUSION: During COVID-19 epidemic phase, chest CT is a rapid and most probably an adequately reliable tool to refer patients requiring hospitalization to the COVID+ or COVID- hospital units, when response times for virological tests are too long. KEY POINTS: • In a large university hospital in Lyon, France, the accuracy, sensitivity, specificity, PPV, and NPV of chest CT for COVID-19 reached 88.9%, 90.2%, 88%, 84.1%, and 92.7%, respectively, using RT-PCR as standard of reference. • The mean delay for CT reports was three times shorter than for RT-PCR results (187 ± 148 min versus 573 ± 327 min, p < 0.0001). • Due to high accuracy of chest CT for COVID-19 and shorter time for CT reports than RT-PCR results, chest CT can be used to orient patients suspected to be positive towards the COVID+ unit to decrease congestion in the emergency departments.

Intestinal Proportion of Blautia sp. is Associated with Clinical Stage and Histoprognostic Grade in Patients with Early-Stage Breast Cancer.

Improving knowledge about breast cancer etiology is crucial in order to propose prevention strategies for this pathology. Gut microbiota is involved in numerous physiopathological situations including cancers. Although its potential involvement in breast cancer through the alteration of the enterohepatic circulation of estrogens and/or the metabolism of phytoestrogens has been discussed for some time, it remains to be demonstrated. The present study seeks to strengthen this hypothesis by identifying possible links between the fecal microbiota composition and clinical characteristics in breast cancer patients. Bacterial DNA was extracted from the feces of 31 patients with early-stage breast cancer and amplified by real-time polymerase chain reaction (qPCR), targeting 16S rRNA sequences specific to bacterial groups, and then analyzed in relation to clinical characteristics. The absolute numbers of total bacteria and of three bacterial groups (Firmicutes, Faecalibacterium prausnitzii, and Blautia) differed significantly according to the patient's body mass index. The percentage and the absolute numbers of certain bacterial groups, namely C. coccoides, F. prausnitzii, and Blautia, differed significantly according to the clinical stages and the histoprognostic grades. Our study highlighted that intestinal microbiota composition in these patients differs according to clinical characteristics and BMI. Further studies are required to clarify the link between breast cancer and intestinal microbiota.

How to Manipulate the Microbiota: Prebiotics.

During the last century, human nutrition has evolved from the definition of our nutritional needs and the identification of ways to meet them, to the identification of food components that can optimise our physiological and psychological functions. This development, which aims to ensure the welfare, health and reduced susceptibility to disease during life, gave birth to the concept of "functional foods". In this context, there is an increasing interest in the physiological effects induced by the dense and diverse microbiota which inhabits the human colon and whose development depends on the fermentation of undigested food residues. Thus, much research aims at identifying ways to guide these impacts in order to benefit the health of the host. It is in this context that the concept of "prebiotics" was developed in the 1990s. Since then, prebiotics have stimulated extensive work in order to clarify their definition, their nature and their physiological properties in accordance with the evolution of knowledge on the intestinal microbiota. However many questions remain open about their specificities, their mechanism(s) of action and therefore the relevance of their current categorisation.

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature.

In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis.

Spatial variation in age structure among colonies of a marine snake: the influence of ectothermy.

Several tetrapod lineages that have evolved to exploit marine environments (e.g. seals, seabirds, sea kraits) continue to rely upon land for reproduction and, thus, form dense colonies on suitable islands. In birds and mammals (endotherms), the offspring cannot survive without their parents. Terrestrial colonies contain all age classes. In reptiles (ectotherms), this constraint is relaxed, because offspring are independent from birth. Hence, each age class has the potential to select sites with characteristics that favour them. Our studies of sea snakes (sea kraits) in the lagoon of New Caledonia reveal marked spatial heterogeneity in age structure among colonies. Sea krait colonies exhibit the endothermic 'seal-seabird' pattern (mixed-age classes within populations) only where the lagoon is narrow. Where the lagoon is wide, most snake colonies are comprised primarily of a single age cohort. Nurseries are located near the coast, adult colonies offshore and mixed colonies in-between. We suggest that ectothermy allows individuals to utilize habitats that are best suited to their own ecological requirements, a flexibility not available to endothermic marine taxa with obligate parental care.

Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study.

Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

Dietary protein excess during neonatal life alters colonic microbiota and mucosal response to inflammatory mediators later in life in female pigs.

The interplay between the colonic microbiota and gut epithelial and immune cells during the neonatal period, which establishes the structure of the microbiota and programs mucosal immunity, is affected by the diet. We hypothesized that protein-enriched milk formula would disturb this interplay through greater flux of protein entering the colon, with consequences later in life. Piglets were fed from postnatal day (PND) 2 to 28 either a normal-protein formula (NP; 51 g protein/L) or high-protein formula (HP; 77 g protein/L) and weaned at PND28, when they received standard diets until PND160. HP feeding transiently increased the quantity of protein entering the colon (PND7) but did not change the microbiota composition at PND28, except for a higher production of branched-chain fatty acids (BCFAs) in an in vitro fermentation test (P < 0.05). HP piglets had greater colonic mucosa densities of cluster of differentiation (CD) 3(+) and CD172(+) cells and lower Il-1ß and Tnfα mRNA levels at PND28 (P < 0.05). Later in life (PND160), HP females, but not males, had a higher increase in colonic permeability after ex vivo oxidative stress and higher cytokine secretion in response to lipopolysaccharide in colonic explant cultures than NP females (P < 0.05). HP females also had lower colonic amounts of F. prausnitzii and BCFAs (P < 0.05). BCFAs displayed a dose-dependent protection against inflammation-induced alteration of barrier function in Caco-2 cells (P < 0.05). In conclusion, protein-enriched formula had little impact on colonic microbiota, but it modified colonic immune cell development and had a long-term effect on adult colonic mucosa sensitivity to inflammatory insults, probably through microbiotal and hormonal factors.

Shelter availability, stress level and digestive performance in the aspic viper.

The lack of shelter can perturb behaviors, increase stress level and thus alter physiological performance (e.g. digestive, immune or reproductive functions). Although intuitive, such potential impacts of lack of shelter remain poorly documented. We manipulated shelter availability and environmental and physiological variables (i.e. access to a heat source, predator attack, feeding status) in a viviparous snake, and assessed sun-basking behavior, digestive performance (i.e. digestive transit time, crude estimate of assimilation, regurgitation rate) and plasma corticosterone levels (a proxy of stress level). Shelter deprivation provoked a strong increase in sun-basking behavior and thus elevated body temperature, even in unfed individuals for which energy savings would have been otherwise beneficial. The lack of heat was detrimental to digestive performance; simulated predator attacks worsened the situation and entailed a further deterioration of digestion. The combination of the lack of shelter with cool ambient temperatures markedly elevated basal corticosterone level and was associated with low digestive performance. This hormonal effect was absent when only one negative factor was involved, suggesting a threshold response. Overall, our results revealed important non-linear cascading impacts of shelter availability on stress-hormone levels, behaviors and physiological performance. These results infer that shelter availability is important for laboratory studies, captive husbandry and possibly conservation plans.

Impact of cool versus warm temperatures on gestation in the aspic viper (Vipera aspis).

Previous experimental data suggested that digestion and growth rates are not impaired under cool constant temperature (23°C) in a viviparous snake (Vipera aspis). These results challenged the widespread notion that both elevated temperatures (e.g. 30°C) and temperature fluctuations are required for digestion and growth in temperate climate reptiles. Here, we investigated the impact of constant cool temperatures on another physiological performance that is crucial to population persistence: gestation. At the time when reproductive females were midway through vitellogenesis, we placed ten reproductive and two non-reproductive female aspic vipers at each of two contrasted constant temperature conditions: cool (23°C) versus warm (28°C). Sixty percent of the females placed at 28°C gave birth to healthy offspring, suggesting that constant warm body temperatures were compatible with normal offspring production. Conversely, none of the cool females gave birth to healthy offspring. A blister disease affected exclusively cool pregnant females. Apparently, the combination of cool temperatures plus gestation was too challenging for such females. Our results suggest that reproduction is more thermally sensitive than digestion or growth, indeed gestation faltered under moderately cool thermal constraints. This sensitivity could be a crucial factor determining the capacity of this species to colonize different habitats.

Preliminary results of transplantation with kidneys donated after cardiocirculatory determination of death: a French single-centre experience.

BACKGROUND: Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been re-introduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. METHODS: Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. RESULTS: From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 ± 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsy-proven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate ( Modification of Diet in Renal Disease formula) was 48 ± 16 mL/min/1.73 m(2) at 1 year and 48 ± 15 mL/min/1.73 m(2) at the last follow-up. CONCLUSIONS: DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.

Neonatal Programming of Microbiota Composition: A Plausible Idea That Is Not Supported by the Evidence.

Underpinning the theory "developmental origins of health and disease" (DOHaD), evidence is accumulating to suggest that the risks of adult disease are in part programmed by exposure to environmental factors during the highly plastic "first 1,000 days of life" period. An elucidation of the mechanisms involved in this programming is challenging as it would help developing new strategies to promote adult health. The intestinal microbiome is proposed as a long-lasting memory of the neonatal environment. This proposal is supported by indisputable findings such as the concomitance of microbiota assembly and the first 1,000-day period, the influence of perinatal conditions on microbiota composition, and the impact of microbiota composition on host physiology, and is based on the widely held but unconfirmed view that the microbiota is long-lastingly shaped early in life. In this review, we examine the plausibility of the gut microbiota being programmed by the neonatal environment and evaluate the evidence for its validity. We highlight that the capacity of the pioneer bacteria to control the implantation of subsequent bacteria is supported by both theoretical principles and statistical associations, but remains to be demonstrated experimentally. In addition, our critical review of the literature on the long-term repercussions of selected neonatal modulations of the gut microbiota indicates that sustained programming of the microbiota composition by neonatal events is unlikely. This does not exclude the microbiota having a role in DOHaD due to a possible interaction with tissue and organ development during the critical windows of neonatal life.

Faecal Microbiota Composition Varies between Patients with Breast Cancer and Healthy Women: A Comparative Case-Control Study.

The intestinal microbiota plays an essential role in many diseases, such as obesity, irritable bowel disease (IBD), and cancer. This study aimed to characterize the faecal microbiota from early-stage breast cancer (BC) patients and healthy controls. Faeces from newly diagnosed breast cancer patients, mainly for an invasive carcinoma of no specific type (HR+ and HER2-), before any therapeutic treatment and healthy controls were collected for metabarcoding analyses. We show that the Shannon index, used as an index of diversity, was statistically lower in the BC group compared to that of controls. This work highlights a reduction of microbial diversity, a relative enrichment in Firmicutes, as well as a depletion in Bacteroidetes in patients diagnosed with early BC compared to those of healthy women. A tendency towards a decreased relative abundance of Odoribacter sp., Butyricimonas sp., and Coprococcus sp. was observed. This preliminary study suggests that breast cancer patients may differ from healthy subjects in their intestinal bacterial composition.

Maternal Microbiota Transfer Programs Offspring Eating Behavior.

Understanding the link between mother's obesity and regulation of the child's appetite is a prerequisite for the design of successful preventive strategies. Beyond the possible contributions of genetic heritage, family culture, and hormonal and metabolic environment during pregnancy, we investigate in the present paper the causal role of the transmission of the maternal microbiotas in obesity as microbiotas differ between lean and obese mothers, maternal microbiotas are the main determinants of a baby's gut colonization, and the intestinal microbiota resulting from the early colonization could impact the feeding behavior of the offspring with short- and long-term consequences on body weight. We thus investigated the potential role of vertical transfers of maternal microbiotas in programming the eating behavior of the offspring. Selectively bred obese-prone (OP)/obese-resistant (OR) Sprague-Dawley dams were used since differences in the cecal microbiota have been evidenced from males of that strain. Microbiota collected from vagina (at the end of gestation), feces, and milk (at postnatal days 1, 5, 10, and 15) of OP/OR dams were orally inoculated to conventional Fischer F344 recipient pups from birth to 15 days of age to create three groups of pups: F-OP, F-OR, and F-Sham group (that received the vehicle). We first checked microbiotal differences between inoculas. We then assessed the impact of transfer (from birth to adulthood) onto the intestinal microbiota of recipients rats, their growth, and their eating behavior by measuring their caloric intake, their anticipatory food reward responses, their preference for sweet and fat tastes in solutions, and the sensations that extend after food ingestion. Finally, we searched for correlation between microbiota composition and food intake parameters. We found that maternal transfer of microbiota differing in composition led to alterations in pups' gut microbiota composition that did not last until adulthood but were associated with specific eating behavior characteristics that were predisposing F-OP rats to higher risk of over consuming at subsequent periods of their life. These findings support the view that neonatal gut microbiotal transfer can program eating behavior, even without a significant long-lasting impact on adulthood microbiota composition.

Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients.

BACKGROUND: Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate to tenofovir alafenamide. OBJECTIVE: Our study aimed to evaluate the effects on renal function and lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management. METHODS: Demographic, clinical and biological data was recorded from a retrospective clinical cohort study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir alafenamide. A descriptive analysis of the study population, with a comparison of biological parameters using the paired Student t test for paired data was performed. RESULTS: From January 2016 to January 2019, a total of 103 patients were included. There was no significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine, p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients received lipid-lowering therapy after switching. CONCLUSION: In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide, lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to monitor lipid parameters after this switch, despite the absence of an official recommendation.