Allergic fungal rhinosinusitis and eosinophilic mucin chronic rhinosinusitis: Differential diagnostic criteria. A two-center comparative study following STROBE methodology.

OBJECTIVES: Allergic fungal rhinosinusitis (AFRS) and eosinophilic mucin chronic rhinosinusitis (EMRS) are two forms of chronic sinusitis distinguished by the presence (AFRS) or absence (EMRS) of fungal elements in sinus mucin. Detection of the fungal elements, however, is complex and it is difficult to say whether EMRS is in fact an entity distinct from AFRS. The aim of the present study, based on a retrospective series of AFRS and EMRS, was to identify the specific clinical and radiological elements distinguishing between the two. MATERIALS AND METHODS: A 2-center retrospective observational study following STROBE guidelines included patients managed for AFRS or EMRS between 2009 and 2022. Clinical, mycological, pathologic and radiological data were collected. Type of treatment and disease progression were also analyzed. Intergroup comparison used Student's test for mean values of quantitative variables, with calculation of P-values, and Pearson's Chi2 test or Fisher's exact test for categoric variables, with calculation of relative risk and 95% confidence intervals. RESULTS: The AFRS group comprised 41 patients and the EMRS group 34. Demographic data were comparable between groups. EMRS showed a higher rate of asthma (79.4 vs. 31.4%; P<0.001), more severe nasal symptomatology (rhinorrhea, P=0.01; nasal obstruction, P=0.001), and more frequent bilateral involvement (85.3 vs. 58.5%; P=0.021). AFRS showed more frequent complications (19 vs. 0%; P=0.006). Radiologically, mucin accumulation was greater in AFRS, filling the sinus in 84.2% of cases, versus 26.3% (P<0.001), with more frequent sinus wall erosion (19 vs. 5.8%; P=0.073). The recurrence rate was higher in EMRS: 38.2 vs.21.9% (P=0.087). CONCLUSION: The present retrospective study found a difference in clinical and radiological presentation between AFRS and EMRS, with EMRS more resembling the presentation of severe nasal polyposis.

Learning curve for robotic-assisted total mesorectal excision: a multicentre, prospective study.

AIM: Robotic-assisted surgery (RAS) is becoming increasingly important in colorectal surgery. Recognition of the short, safe learning curve (LC) could potentially improve implementation. We evaluated the extent and safety of the LC in robotic resection for rectal cancer. METHOD: Consecutive rectal cancer resections (January 2018 to February 2021) were prospectively included from three French centres, involving nine surgeons. LC analyses only included surgeons who had performed more than 25 robotic rectal cancer surgeries. The primary endpoint was operating time LC and the secondary endpoint conversion rate LC. Interphase comparisons included demographic and intraoperative data, operating time, conversion rate, pathological specimen features and postoperative morbidity. RESULTS: In 174 patients (69% men; mean age 62.6 years) the mean operating time was 334.5 ± 92.1 min. Operative procedures included low anterior resection (n = 143) and intersphincteric resection (n = 31). For operating time, there were two or three (centre-dependent) LC phases. After 12-21 cases (learning phase), there was a significant decrease in total operating time (all centres) and an increase in the number of harvested lymph nodes (two centres). For conversion rate, there were two or four LC phases. After 9-14 cases (learning phase), the conversion rate decreased significantly in two centres; in one centre, there was a nonsignificant decrease despite the treatment of significantly more obese patients and patients with previous abdominal surgery. There were no significant differences in interphase comparisons. CONCLUSION: The LC for RAS in rectal cancer was achieved after 12-21 cases for the operating time and 9-14 cases for the conversion rate. RAS for rectal cancer was safe during this time, with no interphase differences in postoperative complications and circumferential resection margin.

[Genitourinary complications after pelvic radiotherapy: Diagnosis and management]. / Complications génito-urinaires après radiothérapie pelvienne : diagnostic et prise en charge.

OBJECTIVE: The purpose of this review was to present the different genitourinary complications following pelvic radiotherapy as well as their assessment and treatments. METHODS: A review of literature was conducted using Medline/Pubmed database without period restriction. In order to write this article, we also use the 2016 AFSOS, SFRO and AFU recommendations. RESULTS: On the one hand, early side effects are common and mild. The symptomatic treatments available generally provide effective relief to patients. On the other hand, late adverse effects need long and complex care. Its side effects alter the quality of life and can be life-threatening. The effects of radiotherapy are irreversible. Except hyperbaric oxygen therapy and hyaluronic acid/chondroitin sulfate instillations, treatments remain symptomatic. Urethrovesical fibroscopy is essential in cases of gross hematuria, and urodynamic assessment (or videourodynamic) can be used in cases of severe vesicosphincter disorders. Pharmacological treatments are less effective than in non-radiation patients, and the morbidity of surgical treatments is higher in this population. CONCLUSION: Genitourinary complications after pelvic radiotherapy are frequent and mild in the early phase but rare and severe in the late phase. Their management is based on a vast diagnostic and therapeutic arsenal, but the treatments are only symptomatic, and the sequelae of radiotherapy remains, to date, irreversible.

[Treatments for SARS-CoV-2 infection: A retrospective study of drug-drug interactions and safety]. / Médicaments utilisés dans la prise en charge de l'infection à SARS-CoV-2 : étude rétrospective des principales associations à risque d'interactions médicamenteuses et des effets indésirables médicamenteux.

OBJECTIVES: The aim of the study is to provide an overview of Drug-drug Interactions (DDIs) and adverse effects caused by drugs used in SARS-CoV-2 infection during the first epidemic wave. METHODS: We retrospectively analyzed patients treated by drugs used in SARS-CoV-2 infection (Azithromycin, Hydroxychloroquine and/or Lopinavir/ritonavir) between 15th March 2020 to 17th April 2020. A review of adverse events and DDI-risky drug association on medical record was conducted for each patient. Each adverse events was analyzed by the Centre régional de pharmacovigilance (CRPV) to assess causality of drugs used in SARS-CoV-2 infection. RESULTS: A total of 312 precriptions were analyzed during the period, of which 110 prescriptions had 157 drug association at risk of DDIs; 26 adverse events were reported. Causality assessment by CRPV concluded that 10 (35,7 %) adverse effects were possibly related to SARS-CoV-2 drugs with only 2 (7,1 %) related to DDIs. CONCLUSIONS: Despite risk of adverse drug reactions and DDIs related to drugs used in SARS-CoV-2 infection, few iatrogenics diseases were found.

Early and late morbidity of local excision after chemoradiotherapy for rectal cancer.

BACKGROUND: Local excision (LE) after chemoradiotherapy is a new option in low rectal cancer, but morbidity has never been compared prospectively with total mesorectal excision (TME). Early and late morbidity were compared in patients treated either by LE or TME after neoadjuvant chemoradiotherapy for rectal cancer. METHOD: This was a post-hoc analysis from a randomized trial. Patients with clinical T2/T3 low rectal cancer with good response to the chemoradiotherapy and having either LE, LE with eventual completion TME, or TME were considered. Early (1 month) and late (2 years) morbidities were compared between the three groups. RESULTS: There were no deaths following surgery in any of the three groups. Early surgical morbidity (20 per cent LE versus 36 per cent TME versus 43 per cent completion TME, P = 0.025) and late surgical morbidity (4 per cent versus 33 per cent versus 57 per cent, P < 0.001) were significantly lower in the LE group than in the TME or the completion TME group. of LE, was associated with the lowest rate of early (10 versus 18 versus 21 per cent, P = 0.217) and late medical morbidities (0 versus 7 versus 7 per cent, P = 0.154), although this did not represent a significant difference between the groups. The severity of overall morbidity was significantly lower at 2 years after LE compared with TME or completion TME (4 versus 28 versus 43 per cent grade 3-5, P < 0.001). CONCLUSION: The rate of surgical complications after neoadjuvant chemoradiotherapy in the LE group was half that of TME group at 1 month and 10 times lower at 2 years. LE is a safe approach for organ preservation and should be considered as an alternative to watch-and-wait in complete clinical responders and to TME in subcomplete responders.

In vivo characterization of healthy human skin with a novel, non-invasive imaging technique: line-field confocal optical coherence tomography.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical technique recently developed for skin examination in vivo. It provides real-time, high-resolution vertical images with an isotropic resolution of ~1 µm and a penetration depth of ~500 µm. OBJECTIVES: Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC-OCT. METHODS: The skin of young healthy volunteers was imaged with a handheld LC-OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal-epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC-OCT images was performed. RESULTS: A total of 88 LC-OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites-related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter-observer agreement was excellent (SC thickness), good-to-excellent (epidermal thickness) and moderate-to-good (papillae). CONCLUSIONS: Line-field confocal-OCT provides non-invasive, real-time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology-like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC-OCT appears as a promising technique for the examination of physiological/pathological skin.

Pauli Shielding and Breakdown of Spin Statistics in Multielectron Multi-Open-Shell Dynamical Atomic Systems.

We report on C^{3+}(1s2ℓ2ℓ^{'} ^{2S+1}L)-resolved cross sections of electron capture in collisions of swift C^{4+}(1s2s ^{3}S) ions with helium and hydrogen. The study focuses on the formation of doubly excited triply open-shell C^{3+}(1s2s2p) ^{4}P and ^{2}P_{±} states with emphasis on the ratio R of their cross sections as a measure of spin statistics. Using zero-degree Auger projectile spectroscopy and a three-electron close-coupling semiclassical approach, we resolve a long-standing puzzle and controversy on the value of R and on the effect of cascades, to clarify the underlying physics. The present results invalidate the frozen core approximation generally used in the past when considering electron capture in multielectron multi-open-shell quantum systems. A distinctive screening effect due to the Pauli exclusion principle (Pauli shielding) is proposed to account for the value of R, consistent with our findings.

Pain Modulation Mechanisms in ASD Adults.

We tested endogenous pain modulation mechanisms in adults with autism spectrum disorders (ASD). Nineteen ASD adults without intellectual disabilities were included, matched with 19 healthy volunteers on the basis of sex and chronological age. An experimental pain model was used to measure excitatory and inhibitory pain mechanisms in a single session. Statistical analyses indicated that endogenous pain modulation mechanisms in ASD group did not differ significantly from those of healthy adults. The pain scores were very disparate in ASD group with a greater range of extreme scores than in control group. Unlike schizophrenic patients, there was no systematic dysfunction of endogenous excitatory pain modulation mechanisms, but the high variability requires to be wise to interpret the results and formulate conclusion.

Eliciting dose is associated with tolerance development in peanut and cow's milk allergic children.

BACKGROUND: Tolerance development rates differ between food allergies. Almost all previous studies have not used the gold standard method, the double-blind, placebo-controlled food challenge (DBPCFC), which may affect the reported prevalence rates. Little is known about the association of the eliciting dose (ED) obtained during the initial DBPCFC with later tolerance development. METHODS: This was a retrospective, tertiary care study of children who had a positive DBPCFC to either peanut, milk or egg, and at least one follow-up food challenge (open or DBPCFC) with the same food. The association between ED and negative (tolerant) follow-up food challenge outcome was analyzed by logistic regression, with adjustment for confounders. Suspected confounders were initial DBPCFC test characteristics, atopic comorbidities and serum specific IgE (sIgE) levels. RESULTS: In 47 peanut allergic children, tolerance developed in 27.7% (median follow-up duration of 43 months). In 80 milk (follow-up 23 months) and 55 egg (follow-up 37 months) allergic children, tolerance developed in 55.0% and 65.5%. The ED obtained during the initial DBPCFC was significantly associated with tolerance development in peanut and milk allergy, but not in egg allergy. CONCLUSION: Approximately 1 out of 4 children with DBPCFC confirmed peanut allergy developed tolerance, compared to more than half of the children with milk or egg allergy, respectively. Tolerance development in peanut and milk allergy is significantly associated with ED at initial DBPCFC.

[Alcohol dependence in primary care : a clinical approach by the GP]. / Prise en charge du mésusage de l'alcool avec dépendance par le médecin généraliste.

Clinical care to patients with alcohol dependence by GP's is described in this article. First, we have to destigmatize these patients and their illness. Diagnosis approach is specified. Therapeutic approach is first a motivational approach; subsequently it's like pedagogy : it's coping. Care is both physical and psychological. Empathy all along therapeutic relationship is a priority and how establishing a therapeutic alliance is described. A psychiatrist, a psychologist, a care network, self-help associations have also to be called on when needed. Physicians education creates new opportunities since 2016-2017 : in particular SSMG (Scientific Society of Primary Care) and three Belgian universities (UCL, ULB and ULiège) introduced a special study program called «?certificat interuniversitaire d'alcoologie?¼. Let's hope this new clinical rewarding approach for GP's contribute to reduce the treatment gap as far as clinical care of patients with alcohol dependence is concerned.

La prise en charge clinique du mésusage d'alcool avec dépendance par le médecin généraliste est décrite dans cet article. Il s'agit, d'abord, de déstigmatiser ces patients et leur pathologie. La démarche diagnostique est précisée. L'approche thérapeutique est, d'abord, motivationnelle; elle prendra, ensuite, des allures pédagogiques : il s'agit de coping. Les soins sont physiques et psychologiques. L'empathie, tout au long de la relation thérapeutique, est fondamentale et les techniques pour créer l'alliance thérapeutique sont décrites. Savoir référer au psychologue, faire appel au réseau, collaborer avec le psychiatre, conseiller l'entraide sont des initiatives nécessaires. La formation des médecins généralistes connaît de nouvelles opportunités : notamment, grâce à un certificat interuniversitaire d'alcoologie mis sur pied à la rentrée académique 2016-2017 à l'initiative de la Société Scientifique de Médecine Générale (SSMG) et de trois universités francophones (UCL, ULB et ULiège). On peut espérer que ces nouvelles pratiques cliniques, valorisantes pour le médecin généraliste, contribueront à réduire le «?treatment gap?¼ dans la prise en charge du mésusage d'alcool avec dépendance, un véritable défi de santé publique.

Double Electron Capture in H

We have investigated the double electron capture process in the H^{+}+H^{-} collision system for energies from 60 eV to 20 keV. Despite the apparent simplicity of this highly correlated system, all previous calculations fail to reproduce the experimental total cross sections. Moreover, the latter exhibit oscillations that have been previously attributed to quantum interferences between the gerade and ungerade ionic states of the transient molecule formed during the collision. For this process, we present the absolute cross sections obtained from a fully correlated two-active-electron semiclassical atomic-orbital close-coupling approach. Our results reproduce well the experimental data in both magnitude and shape. Furthermore, we demonstrate that the oscillations stem from coherence effects between double electron capture and other two-electron inelastic channels, namely the transfer-excitation processes. This alternative interpretation is supported by a Rosenthal-like model based on a molecular treatment of the collision. Our results shed new light on this old but challenging problem.

Design of a custom insertable probe platform for measurements of C-2W inner divertor plasma parameters.

A custom motor controlled probe system has been designed to make spatially resolved measurements of temperature, density, flow, and plasma potential in the C-2W inner divertors. Measurements in the inner divertors, which have a 1.7 m radius and are located on either end of the confinement vessel, are critical in order to gauge exactly how local settings affect the plasma conditions, confinement, and stability in the field-reversed configuration core. The inner Divertor Insertable Probe Platform (iDIPP) system consists of a custom motor controlled linear rack and pinion transporter that has a 1.9 m travel length in order to reach the center of the divertor. Mounted to the end of the transporter is a 1 m long segmented probe shaft made of individually floating stainless steel rings to prevent shorting out the electrode plates, which are biased up to 5 kV/m. A variety of interchangeable probe tips, including a triple Langmuir probe, a baffled probe, and a Gundestrup probe, can plug into the end of the probe shaft. Custom UHV coiled cabling comprised of 9 shielded conductors expands/retracts with the motion of the transporter in/out of the divertor. The physics motivating plasma parameter measurements in the inner divertors and the details of the design of the iDIPP system will be discussed.

[VIVOPTIM: Feedback of an e-Health experimental program of primary prevention of cardiovascular risk on 30 to 70 years old volunteers]. / VIVOPTIM : retour d'expérience d'un programme expérimental de e-santé et de prévention primaire du risque cardiovasculaire global chez des sujets volontaires âgés de 30 à 70 ans.

Today by the e-health and the telemedicine, many people are more and more interested by the improvement of disease knowledge on cardiovascular diseases and associated risk factors, personalized self management support follow-up and e-Health monitoring. MGEN is a not-for-profit complementary health insurance gave itself the ways to use the new digital tools in health. MGEN developed an original and personalized program VIVOPTIM for the primary prevention of the cardiovascular risks for their members. The VIVOPTIM Pilot program is based upon digital services and was experimented by November 2015 to December, 2017 with 8000 members of the MGEN, from 30 to 70 years old and resident in two French areas (Occitanie and Bourgogne Franche-Comté). The assessment of the experiment VIVOPTIM e -health program was positive for the personalized cardiovascular support and for their health. Therefore, the MGEN generalized the VIVOPTIM program of cardiovascular prevention, to the whole France on July 11th, 2018.

Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain.

The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. OBJECTIVE: We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3-5 mm depths without inserting fibers into the cortex. APPROACH: Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. MAIN RESULTS: The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200-500 mm3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. SIGNIFICANCE: The present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.

Association of STAT6 gene variants with food allergy diagnosed by double-blind placebo-controlled food challenges.

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analysed including 262 children (71.0%) with food allergy. Associations were tested by the Family based association test. The A alleles of both SNPs were associated with food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4 +  T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.

Retrospective observational cohort study regarding the effect of breastfeeding on challenge-proven food allergy.

BACKGROUND/OBJECTIVES: Human breast milk is generally regarded as the best nutrition for infants in their first months of life. Whether breastfeeding has a protective effect on food allergy is a point of debate and the subject of this study. SUBJECTS/METHODS: This retrospective study was conducted in 649 children who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part of routine care in a tertiary care clinic. Food allergy was defined as having at least one positive DBPCFC to any food. The association between both "any" breastfeeding (yes/no) and its duration in months with food allergy was studied by logistic regression analysis with correction for confounding variables. RESULTS: The prevalence of food allergy was 58.9% (n = 382). Of all subjects, 75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no significant association between food allergy and breastfeeding versus bottle-feeding after correction for the confounding effect of increased breastfeeding by atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85-1.79, p = 0.27). However, in breastfed children, every additional month of breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93-0.99, p = 0.02). No confounders were identified in this association. CONCLUSION: These results show for the first time that in children investigated for possible food allergy, every additional month of breastfeeding is associated with a lower risk of developing clinical food allergy as diagnosed by DBPCFC. However, overall, there was no association between the prevalence of food allergy and breastfeeding versus bottle-feeding in this tertiary care population.

How does dose impact on the severity of food-induced allergic reactions, and can this improve risk assessment for allergenic foods?: Report from an ILSI Europe Food Allergy Task Force Expert Group and Workshop.

Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single-dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.