Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of ...cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls’ microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.
Risk prediction of acute mountain sickness, high altitude (HA) pulmonary or cerebral edema is currently based on clinical assessment. Our objective was to develop a risk prediction score of Severe ...High Altitude Illness (SHAI) combining clinical and physiological factors. Study population was 1017 sea-level subjects who performed a hypoxia exercise test before a stay at HA. The outcome was the occurrence of SHAI during HA exposure. Two scores were built, according to the presence (PRE, n = 537) or absence (ABS, n = 480) of previous experience at HA, using multivariate logistic regression. Calibration was evaluated by Hosmer-Lemeshow chisquare test and discrimination by Area Under ROC Curve (AUC) and Net Reclassification Index (NRI).
The score was a linear combination of history of SHAI, ventilatory and cardiac response to hypoxia at exercise, speed of ascent, desaturation during hypoxic exercise, history of migraine, geographical location, female sex, age under 46 and regular physical activity. In the PRE/ABS groups, the score ranged from 0 to 12/10, a cut-off of 5/5.5 gave a sensitivity of 87%/87% and a specificity of 82%/73%. Adding physiological variables via the hypoxic exercise test improved the discrimination ability of the models: AUC increased by 7% to 0.91 (95%CI: 0.87-0.93) and 17% to 0.89 (95%CI: 0.85-0.91), NRI was 30% and 54% in the PRE and ABS groups respectively. A score computed with ten clinical, environmental and physiological factors accurately predicted the risk of SHAI in a large cohort of sea-level residents visiting HA regions.
•Isolated loss of smell without nasal obstruction is an early red-flag of COVID-19.•These patients should adopt all the preventive measures and a lockdown.•Olfactory/gustative dysfunction had high ...predictive value to identify COVID-19.•Olfactory/gustative dysfunction had high specificity to identify COVID-19.•Self-reported loss of smell, among other symptoms, could help to screen COVID-19.
To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period.
Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19.
i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)).
Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts.
The benefit of belatacept on antibody‐mediated rejection (ABMR) incidence after kidney transplant with preformed donor‐specific antibodies (DSAs) has never been assessed. Between 2014 and 2016, we ...conducted a multicenter prospective clinical trial with 49 patients to determine kidney allograft outcome in recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000) treated with belatacept (BELACOR trial). Immunosuppressive strategy included antithymocyte globulin, belatacept, mycophenolate mofetil, and steroids. An ancillary control group was designed retrospectively, including patients fulfilling the same inclusion criteria treated with calcineurin inhibitors. In BELACOR group, no patient exhibited acute ABMR, patient and allograft survival at 1 year was 100% and 95.4%, respectively, and the estimated glomerular filtration rate was 53.2 mL/min/1.73 m2. However, the 12‐month incidence of acute T cell–mediated rejection was 25.4% (14.5% to 42.4%). Comparison with the control group showed significantly higher T cell–mediated rejection incidence only in the BELACOR group (P = .003). Considering the DSAs, the outcome was similar in the 2 groups except a significantly higher number of patients displayed a complete disappearance of class II DSAs in the BELACOR group (P = .001). Belatacept was not associated with an acute ABMR increased risk and may be considered as immunosuppressive strategy in transplant recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000). Prospective randomized trials are needed to confirm these results.
The BELACOR prospective clinical trial finds no increased risk of antibody‐mediated rejection when kidney transplant recipients with mild immunological risks are treated with belatacept.
ObjectivesHealthcare professionals are expected to firmly ground their practice in sound evidence. That implies that they know and use evidence-based medicine (EBM). In this study, our aim was to ...know how often health professionals actually made use of EBM in their daily practice.DesignA questionnaire survey of healthcare professionals.ParticipantsHealthcare professionals who attended six university postgraduate courses. 226 answered the questionnaire (144 physicians, 64 nurses and 24 pharmacists; response rate 63.3%).Setting56.5% of respondents worked in hospitals (mostly non-teaching), 25.0% in nursing homes and 10.2% in primary care. All participants were French-speaking and lived in France or Switzerland.MeasuresDeclared degree of knowledge and use of EBM, use of EBM-related information sources.ResultsOverall, 14.2% of respondents declared to use EBM regularly in their daily practice and 15.6% declared to use EBM only occasionally. The remaining respondents declared they: knew about EBM but did not use it (33.1%), had just heard about EBM (31.9%) or did not know what EBM is (4.0%). Concerning the use of EBM-related information sources, 83.4% declared to use at least monthly (or more often) clinical guidelines, 47.1% PubMed, 21.3% the Cochrane Library and 6.4% other medical databases.Fewer pharmacists (12%) declared to use EBM in their practice than nurses (22%) or doctors (36%). No difference appeared when analysed by gender, work setting or years after graduation. The most frequent obstacles perceived for the practice of EBM were: lack of general knowledge about EBM, lack of skills for critical appraisal and lack of time.ConclusionsOnly a minority of health professionals—with differences between physicians, nurses and pharmacists—declare to regularly use EBM in their professional practice. A larger proportion appears to be interested in EBM but seems to be deterred by their lack of knowledge, skills and personal time.
Summary
In women with pre‐existing immune thrombocytopenic purpura (ITP), the effect of pregnancy on the course of the disease is poorly known. We performed a dual‐centre retrospective cohort study ...of 118 pregnancies in 82 women with primary ITP. In early pregnancy, the platelet count was <100 × 109/l in 35·6% of pregnancies. During pregnancy the median platelet count nadir was 66 × 109/l (25th–75th percentile: 42–117), with platelet count <30 × 109/l for 26 pregnancies (22%). In 49% of pregnancies, a significant decrease of the platelet count required treatment at least transiently in preparation for delivery. At the time of delivery, the median platelet count was 110 × 109/l (77–155). Compared to before pregnancy, at 3 months post‐partum, only 11% of pregnancies 95% confidence interval (95% CI): 6·8–20·2 showed disease worsening. Previous splenectomy was the only factor significantly associated with ITP worsening after pregnancy (53·9% vs. 10·3%, P < 0·001). For 8·3% of the pregnancies (95% CI: 3·8–15·1), neonatal thrombocytopenia required treatment, especially in case of previous maternal splenectomy (adjusted odds ratio 16·7, 95% CI: 2·61–106). The overall risk of exacerbation of ITP and severe thrombocytopenia during pregnancy is acceptable.
Objective. The primary objective was to describe the occupations people engaged in more frequently during lockdown than before the coronavirus disease 2019 pandemic as a function of generation. The ...secondary objectives were to (i) describe the levels of importance, performance, and satisfaction for these occupations and (ii) identify factors affecting the levels of importance, performance, and satisfaction. Method. We conducted an online, cross-sectional survey of young adults (YAs, aged 18-39), middle-aged adults (MAs, aged 40-59), and older adults (OAs, aged 60 or over). Results. 2534 participants (YAs: 47%, MAs: 33%, and OAs: 20%) cited 4500 occupations. The occupations in which people most engaged were leisure occupations (67%), followed by productive occupations (31%) and then self-care (2%) occupations. YAs gave a median (interquartile range) importance score of 8 (6; 9) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. MAs gave a median importance score of 8 (6; 10) to leisure, 8 (7; 10) to productivity, and 8 (7; 10) to self-care. OAs gave a median importance score of 8 (7; 10) to leisure, 8 (7; 9) to productivity, and 9 (8; 10) to self-care. In a pre-/postlockdown comparison, the changes in performance scores among YAs were +5 (3; 6) for leisure, +4 (2; 5) for productivity, and +4 (3; 6) for self-care. Among MAs, these changes were, respectively, +4 (3; 6), +3 (2; 5), and +4.5 (3; 6). Among OAs, these changes were, respectively, +3 (1; 5) for leisure, +3 (2; 5) for productivity, and +2 (0; 4) for self-care. The changes in satisfaction scores among YAs were +3 (0; 5) for leisure, +3 (0; 5) for productivity, and +3 (1; 6) for self-care. Among MAs, these changes were, respectively, +3 (0; 5), +2 (0; 4), and +5 (0; 6). Among OAs, these changes were, respectively, +2 (0; 4), +2 (0; 4), and +2 (0; 4). Conclusions. Lockdown led to stronger engagements in quiet leisure and alternative forms of socialization. Occupational therapists may have a role in helping community-dwelling people to balance and structure their new daily routine.
Prostate cancer (PCa) and obesity are two ever-increasing public health issues that can independently impair the quality of life (QOL) of affected patients. Our objective was to evaluate the impact ...of overweight and obesity on the QOL of patients with PCa receiving an anticancer treatment.
We performed a systematic review of the literature using PubMed, Embase, Cochrane Library and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search equation targeted studies that included PCa patients who had a body mass index (BMI) greater than 25 kg/m
, who were receiving anticancer therapy, and whose QOL was analyzed according to validated or non-validated scores.
Of 759 identified articles, we selected 20 studies published between 2000 and 2019 of 12,529 patients treated for PCa, including 5549 overweight or obese patients. QOL assessment was performed using nine validated scales and two non-validated questionnaires. Of seven studies on radiotherapy, six found obesity to have a negative impact on patients' QOL (especially urinary, sexual, and bowel-related QOL). Thirteen studies assessed the QOL of patients who underwent radical prostatectomy, with a BMI > 25 kg/m
having no observed impact. In obese patients under 65 years of age and without comorbidities, nerve-sparing surgery appeared to limit the deterioration of QOL. Four studies on brachytherapy found discordant results. One study showed greater QOL impairment in obese patients receiving first-generation hormone therapy than in those with normal or decreased BMI. No study evaluated the QOL of overweight or obese patients receiving other types of systemic treatment.
Based on the published data, the level of evidence for an association between QOL and overweight or obesity in patients treated for PCa is not high. Prospective cohort studies including this type of patient population are warranted to answer this topical public health issue.
To analyze reticular pseudodrusen progression using spectral domain-optical coherence tomography (SD-OCT).
Thirty-three consecutive patients (48 eyes) underwent SD-OCT using the eye-tracked follow-up ...protocol 24 ± 2 months after baseline examination. Each pair of B-scans (only one per eye was evaluated among those showing pseudodrusen progression) was compared with respect to pseudodrusen appearance and retinal layer structure. Stage 1 pseudodrusen was defined as granular material between the RPE and the inner segment/outer segment (IS/OS), stage 2 as mounds of material sufficient to alter the contour of the IS/OS, stage 3 as thicker material adopting a conical appearance and breaking through the IS/OS, and stage 4 as fading of the material because of reabsorption and migration within the inner retinal layers.
A total of 78 pseudodrusen (detected on the 48 analyzed B-scans, and counting for a mean of 2.3 pseudodrusen per scan) showed progression over a mean of 23.9 ± 1.2 months. All 58 pseudodrusen (100%) graded as stage 1 at baseline examination progressed to stage 2. Thirteen of 16 pseudodrusen (81.3%) graded as stage 2 at baseline examination progressed to stage 3, and three (18.7%) progressed to stage 4. All four pseudodrusen (100%) graded as stage 3 at baseline examination progressed to stage 4. Among pseudodrusen that were stage 3 or 4 at follow-up (n = 20), 100% had IS/OS disruption whereas 12.1% (n = 7) had IS/OS disruption at stage 1 or 2 (n = 58) (OR, 1.736; 95% CI, 1.02-2.43).
The frequency of stage changes over time suggest that reticular pseudodrusen are dynamic pathologic structures.
We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations.
PUBMED database was searched in October 2021 for articles ...published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines.
Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80-85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case.
The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75-80 age group. IRB: An institutional review board composed of members of the 2 learned societies (SOFOG and FFCD) defined the issues of interest, followed the evolution of the work and reviewed and validated the report.
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