Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Joint FAO/IAEA Coordinated Research Project on "Mosquito Handling, Transport, Release and Male Trapping Methods" in Support of SIT Application to Control Mosquitoes.

Mosquito-borne diseases are among the most important public health problems worldwide [...].

Mathematical modelling of the mosquito Aedes polynesiensis in a heterogeneous environment.

BACKGROUND: The mosquito Aedes polynesiensis inhabits Pacific islands and territories and transmits arboviruses and parasites. In the context of rapid environmental change, understanding the effects of environmental heterogeneity on mosquitoes is crucial. METHODS: First, empirical field data and remote sensing data were combined to model spatial heterogeneity in the environmental suitability for Ae. polynesiensis. Second, a model of mosquito population dynamics was applied to predict mosquito distributions over a heterogeneous landscape assuming different dispersal behaviours. Motu Tautau, French Polynesia, was used as a case study of the utility of this methodological approach. Ae. polynesiensis use land crab Cardisoma carnifex burrows for oviposition in French Polynesia; environmental suitability was therefore quantified using C. carnifex burrow density. RESULTS: Micro-regions with large Ae. polynesiensis populations facilitated by high C. carnifex burrow density were accurately captured by our methodology. Preferential dispersal towards oviposition sites promoted larger population sizes than non-preferential dispersal but did not offer greater resilience to environmental change. Reduced environmental suitability for Ae. polynesiensis resulted in spatially non-linear effects upon the mosquito distribution. CONCLUSIONS: Environmental change has complex spatial effects upon mosquito populations. Mosquito control strategies must carefully balance spatial effects with net effects.

[Central control malfunction in Wolfram syndrome: Report of one case of difficult weaning]. / Dysfonction de la commande centrale dans le syndrome de Wolfram : à propos d'un cas de sevrage ventilatoire difficile.

INTRODUCTION: Wolfram syndrome is a rare autosomal recessive genetic disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. A neurodegenerative syndrome is usually associated, including cerebellar ataxia. A few cases of central apnea have been reported in the literature. Here, we report a case of Wolfram syndrome with respiratory symptoms that led to the discovery of central apneas as well as complicated and delayed weaning in an intensive care unit (ICU). OBSERVATION: The patient is a 39-year-old woman diagnosed with Wolfram syndrome who was admitted to an ICU for septic shock. She experienced difficult weaning before central apneas were observed while spontaneous ventilation was being attempted. After two extubation failures, cerebral MRI was performed and revealed parenchymatous atrophy of the posterior brain fossa involving the cerebral trunk, cerebellar peduncles, as well as both cerebellum hemispheres and the cerebellar vermis. Even after the patient was tracheotomized, central apneas persisted when the patient breathed spontaneously with her tracheotomy, necessitating nocturnal ventilation. CONCLUSION: While central apneas Wolfram syndrome remain rare, they should be systematically investigated due to their association with severe morbimortality.

Treating strangeness: Medicine and human dignity at the time of COVID-19.

The concomitance of a migratory wave and the hospital crisis once again raises the question of the care that the French healthcare system is able to provide to migrants. On the occasion of SFFEM's 19th annual day, we present a synthesis of the research work that has been communicated at that time. Firstly, we will discuss how doctors have been able to overcome strangeness to revive the notion of hospitality according to Levinas; secondly, we will discuss how the hospital is departing from its mission of institutional hospitality because of administrative injunctions; thirdly, we will discuss how ethnomedicine gives us keys to open up to other cultural norms; fourthly, we will see the inadequacy that exists between rights of access to medical care and their effectiveness; finally, the conclusion of Xavier Emmanuelli, founder of the social ambulance service, will remind us how much the values of the French Republic call us to the notion of care and openness to otherness.

The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study.

BACKGROUND AND OBJECTIVE: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy. MATERIALS AND METHODS: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract. RESULTS AND LIMITATIONS: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)]. CONCLUSION: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM.

Specific human antibody responses to Aedes aegypti and Aedes polynesiensis saliva: A new epidemiological tool to assess human exposure to disease vectors in the Pacific.

BACKGROUND: Aedes mosquitoes severely affect the health and wellbeing of human populations by transmitting infectious diseases. In French Polynesia, Aedes aegypti is the main vector of dengue, chikungunya and Zika, and Aedes polynesiensis the primary vector of Bancroftian filariasis and a secondary vector of arboviruses. Tools for assessing the risk of disease transmission or for measuring the efficacy of vector control programmes are scarce. A promising approach to quantify the human-vector contact relies on the detection and the quantification of antibodies directed against mosquito salivary proteins. METHODOLOGY/PRINCIPAL FINDINGS: An ELISA test was developed to detect and quantify the presence of immunoglobulin G (IgG) directed against proteins from salivary gland extracts (SGE) of Ae. aegypti and Ae. polynesiensis in human populations exposed to either species, through a cross-sectional study. In Tahiti and Moorea islands where Ae. aegypti and Ae. polynesiensis are present, the test revealed that 98% and 68% of individuals have developed IgG directed against Ae. aegypti and Ae. polynesiensis SGE, respectively. By comparison, ELISA tests conducted on a cohort of people from metropolitan France, not exposed to these Aedes mosquitoes, indicated that 97% of individuals had no IgG directed against SGE of either mosquito species. The analysis of additional cohorts representing different entomological Aedes contexts showed no ELISA IgG cross-reactivity between Ae. aegypti and Ae. polynesiensis SGE. CONCLUSIONS/SIGNIFICANCE: The IgG response to salivary gland extracts seems to be a valid and specific biomarker of human exposure to the bites of Ae. aegypti and Ae. polynesiensis. This new immuno-epidemiological tool will enhance our understanding of people exposure to mosquito bites, facilitate the identification of areas where disease transmission risk is high and permit to evaluate the efficacy of novel vector control strategies in Pacific islands and other tropical settings.

Exploring Mosquito Fauna of Majuro Atoll (Republic of Marshall Islands) in the Context of Zika Outbreak.

First autochthonous Zika clinical case was reported in the Republic of Marshall Islands (RMI) on Majuro Atoll in February 2016. An entomological survey of mosquito larvae and adult populations was carried out in four areas of Majuro, the most populated atoll of RMI encompassing different habitats (forest, rural, or urban) including some with confirmed clinical Zika cases to evaluate which mosquito species could be involved in the Zika transmission. A total of 2,367 immature and adult mosquito specimens were collected and identified to the species level. In total, five mosquito species were detected, Aedes aegypti (Linnaeus), Aedes albopictus (Skuse), Aedes marshallensis (Stone and Bohart), Culex quinquefasciatus (Say), and Culex annulirostris (Skuse) (Diptera: Culicidae), a first record for RMI. The most abundant species was Ae. aegypti presumed to be the main vector of Zika virus followed by Ae. albopictus. Improved management of breeding containers through better public awareness and community engagement, mosquito surveillance and innovative mosquito control strategies using the sterile insect technique (SIT) and/or the incompatible insect technique (IIT) could help prevent outbreaks of arboviruses in the RMI.

[The myth of virgin cleansing: Latest news on an archaic magico-religious practice]. / Le mythe du nettoyage par les vierges : actualité d'un archaïsme magico-religieux.

BACKGROUND: In the medical anthropology section of the Nanterre Hospital (France) for migrants and refugees, three cases were recorded of "virgin cleansing" in sub-Saharan African countries. PATIENTS AND METHODS: These consisted of sexual assaults (2 instances of rape and 1 of sexual interference) on sexually immature females (young girls) by patients with sexually transmitted infections (mainly HIV, syphilis) hoping they might thereby be cured. DISCUSSION: These particularly atrocious hetero-aggressive sexual practices based on magical arguments are unfortunately universal and are not limited to a specific culture. At the medical anthropology level, the belief in cleansing by virgins is based on the notion that the patient is dirty and impure. In the same way that emetics and/or laxatives are prescribed in the case of intestinal disorders (to "eliminate" the disease), some subjects use diuretics for urinary abnormalities or, literally, "clean vaginas (or anuses)" to purge their own miasma. The rising tide of population migrations (some of whom carry chronic infections), refugee camps, prolonged incarcerations, etc., makes observations of such phenomena increasingly frequent. Belief in cleansing by virgins (and the fatal consequences thereof) will be difficult to eradicate. The education of populations and health professionals should promote absolute respect for the body of children, and, more generally, of others, particularly since at this time of increasingly marked migratory flows, this problem sadly risks becoming widespread.

Peak inspiratory flow as predictor for tracheotomy.

OBJECTIVES: Quantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy. MATERIALS AND METHODS: A single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction. MAIN OUTCOME MEASURES: The decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values. RESULTS: PIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min). CONCLUSIONS: PIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.

["Palimpsest scar" lesions in a context of torture (Darfur, Sudan)]. / Cicatrices « palimpsestes ¼ en contexte de torture (Darfour, Soudan).

BACKGROUND: As a result of the current exponentially growing refugee population from the Middle-East and East Africa (Sudan, Darfur, Eritrea), clinicians (including forensic pathologists) are seeing atypical skin lesions, mainly of a traumatic nature, but in some cases associated with long-standing lesions related to ethnic practices. PATIENTS AND METHODS: A case of torture sequelae is presented herein in a patient originally from Darfur (Sudan): cutaneous incisions were made on old scars several times using a knife. DISCUSSION: The clinical presentation of scarification lesions and that of atypically healed wounds (presumably an effect of inflammation induced by the introduction of irritating foreign bodies such as sand, salt, etc.) are completely different: in all cases they indicate a relative timeframe of the facts, which the clinician should not overlook in reconstructing the patient's course and the injuries to which he has been subjected (hence the proposed designation of "palimpsest scar", in the sense that a palimpsest is a manuscript on a parchment that previously contained writing but has been scratched clean to be overwritten). Thus, a "palimpsest scar" constitutes a fresh scar on top of and hiding another (ritual) scar in a context of ethnic cleansing. The diagnostic and clinical significance comes from the importance of differentiating between ethnic-type lesions and those induced by physical violence and abuse in a context of war.