Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas.

INTRODUCTION: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement. MATERIALS AND METHODS: We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1. RESULTS: We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1). CONCLUSIONS: The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial. PATIENT SUMMARY: In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.

Aspects médico-légaux de la réparation des amputations traumatiques de membres en milieu professionnel reçues au Centre des Urgences de Yaoundé / Medico-legal aspects of the repair of traumatic limb amputations in the workplace received at the Yaoundé Emergency Center

Objectif : Décrire les aspects médico-légaux de la réparation des amputations traumatiques de membres en milieu professionnel. Méthodologie : Etude descriptive retrospective réalisée au centre des urgences de Yaoundé (CURY) de Janvier 2017 à Decembre 2022. Etait inclus, tout patient consentant ayant subi une amputation de membre consécutive à un accident de travail durant la période d'étude. Résultats : Au total, 96 patients amputes de membres ont ete colliges. Les victimes étaient majoritairement de sexe masculin soit 70.8%, la tranche d'âge la plus representee était celle de 30 à 35 ans. La categorie professionnelle la plus representee etait la categorie H (transport et entreposage) soit 34.5%. L'ecrasement a constitué le type lésionnel le plus pourvoyeur d'amputation soit 46,9 %, les membres inferieurs etaient le plus souvent atteint (66,6%). La duree moyenne d'arrêt de travail etait de 90,5 jours et l'incapacité permanent partielle (IPP) moyen etait de 47.9 %. Des patients amputes, 47.9 % avaient beneficies d'un changement de poste de travail. Conclusion: Les amputations traumatiques de membres en milieu professionnel sont relativement fréquentes. Toutes les catégories socioprofessionnelles peuvent être concernees. Elles sont source de prejudices importants.

Objective : To describe the medico-legal aspects of repairing traumatic limb amputations in the workplace. Methodology : Retrospective descriptive study conducted at the Yaounde emergency centre (YEC) from January 2017 to December 2022. All consenting patients who underwent a limb amputation following a work-related accident during the study period were included. Results : A total of 96 patients with limb amputations were enrolled. The victims were predominantly male (70.8%), and the most common age group was between 30 and 35 years. The most common occupational category was H (transport and storage), at 34.5%. Crushing was the most common type of injury causing amputations (46.9%), with the lower limbs most often affected (66.6%). The average length of time off work was 90.5 days, and the average permanent partial disability (PPD) was 47.9%. Of the amputated patients, 47.9% had benefited from a change of workstation. Conclusion : Traumatic limb amputations in the workplace are relatively common. All socioprofessional categories may be affected. They are a source of significant prejudice

A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer.

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules. METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules. RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries. CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

[Mite sensitization in children followed for respiratory allergy in a tropical African environment in Cotonou, Benin]. / Sensibilisation aux acariens chez les enfants suivis pour allergie respiratoire en milieu tropical africain à Cotonou, Bénin.

INTRODUCTION: In tropical Africa, allergies are not well documented. The objective of this work was to evaluate, by two methods, the sensitization to mites in children followed for respiratory allergy. METHODS: Skin prick-test and IgE assay by REAST test with 3 mites: Dermatophagoides pteronyssinus (D. pteronyssinus), Dermatophagoides farinae (D. farinae) and Blomia tropicalis (B. tropicalis) were carried out in children from 3 to 15 years followed up for asthma and/or allergic rhinitis. The positive results of the two tests were compared. RESULTS: Of the 130 (100%) children included, all eligible for the assay, 119 (91.5%) had the prick-test. The mean age and sex ratio (M/F) were 7±1 year, and 1.6. The association of rhinitis and asthma was the most frequent and found in 66 (55.6%). The sensitivity frequencies for the prick-test and assay were respectively 79% versus 36.1% for B. tropicalis, 71.4% versus 33.4% for D. pteronyssinus and 38.7% versus 37.8% for D. farinae. A moderate correlation between mean papule diameter and mean IgE concentration was observed. CONCLUSION: In African tropical environments, dust mite sensitization in children followed for respiratory allergy is frequent, with the order of frequency being: B. tropicalis, D. pteronyssinus, and D. farinae. The prick-test had better sensitivity than the assay for its evaluation.

Comparing different formulae to test for gastrointestinal nematode resistance to benzimidazoles in smallholder goat farms in Mexico.

The objective was to examine the coincidence in the prevalence of benzimidazole (Bz) resistance in smallholder goat herds, as determined by three average-based and two individually-based faecal egg count reduction (FECR) tests. Nineteen smallholder goat herds with more than 30 animals were selected from 84 herds in Yucatan. Animals shedding 150 eggs/g of faeces (EPG) on day zero were randomly divided into two groups. The control group did not receive treatment and the treated group received fenbendazole (10mg/kg body weight per os). Feed was withdrawn for 16 h before treatment. Ten days after treatment, both groups were sampled to determine their FEC. Faecal cultures and identification of infective larvae were performed for estimating the proportions of genera of gastrointestinal nematodes (GIN) present. Presence of resistant GIN was determined with three different average-based FECR (FECR(1), FECR(2) and FECR(3)) and two individually-based FECR (iFECR(1) and iFECR(2)). The prevalence of herds with Bz resistant nematodes (and 95% confidence interval (95% CI)) was calculated using each formula. Coincidence among formulae was estimated with Kappa values. The prevalence (+/- 95% CI) of Bz resistance calculated with FECR(1) (57.89 +/- 22.20) had a high coincidence with iFECR(1) and iFECR(2) (Kappa values of 0.86 and 0.79, respectively). The prevalence with FECR(2) (31.58 +/- 20.90) and FECR(3) (21.05 +/- 18.33) had a low coincidence with FECR(1) (Kappa < 0.50). Trichostrongylids found on Bz resistant farms were mainly Haemonchus spp., however, some Trichostrongylus spp. and Oesophagostomum spp. were found too. The high coincidence between the standard average-based FECR(1) and the individually based formulae is encouraging and may suggest that either formula could be applied to smallholder farmers. Further laboratory studies are needed to confirm the resistance status in the herds.

[Survey of foot and mouth disease in France]. / Le système de surveillance de la fièvre aphteuse en France.

The Foot and Mouth disease is considered a relatively mild disease in susceptible animals but it has a considerable economical impact in France and worldwide due to the huge economical losses that it generates. A system for the prevention of the disease was developed thirty years ago and has since been continuously improved. The current system for the prevention of FMD is based on training and information of all those involved in the surveillance of susceptible animals, over all the national territory, and on the control of imported animals and animal products. This system, developed in close collaboration with the European Commission and the other EU member states, allows control measures to be implemented almost instantaneously, if a case is suspected to avoid spreading of the disease.

Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors.

The synthesis, structure-activity relationships, and biological properties of a novel series of potent and selective phosphodiesterase type 4 (PDE4) inhibitors are described. These new aminodiazepinoindoles displayed in vitro PDE4 activity with submicromolar IC(50) values and PDE4 selectivity vs PDE1, -3, and -5. Specifically, one compound (CI-1044, 10e) provided efficient in vitro inhibition of TNFalpha release from hPBMC and hWB with IC(50) values of 0.34 and 0.84 microM, respectively. This compound was found to exhibit potent in vivo activity in antigen-induced eosinophil recruitment in Brown-Norway rats (ED(50) = 3.2 mg/kg po) and in production of TNFalpha in Wistar rats (ED(50) = 2.8 mg/kg po). No emetic side effects at therapeutic doses were observed in ferrets.

Levofloxacin: serum bactericidal activity against methicillin-resistant Staphylococcus aureus isolates.

The aim of this study was to assess the serum bactericidal activity (SBA) of levofloxacin compared with that of ofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) isolates. Serum from 10 healthy volunteers (seven females, three males) was collected after a single oral dose of either levofloxacin (500 mg) or ofloxacin (400 mg). Subjects were allocated randomly to treatment after at least a 1 week interval between antibiotic regimens. Three well-defined MRSA strains were tested, each susceptible to levofloxacin and ofloxacin, with different levels of resistance to methicillin (HBD 456, HBD 3 and HBD 2; class 1, 2 and 3 Tomasz heterogeneous resistance, respectively) together with a methicillin-susceptible (MSSA) reference strain (S. aureus ATCC 25,923). SBA was tested in vitro by a microtitration method 15 min before dosing and at 1, 4, 8 and 12 h after drug absorption. Levofloxacin was significantly more bactericidal than ofloxacin against all strains of S. aureus tested (SBA > or = 1:2). An SBA was recorded for only a short period with ofloxacin, and thereafter only bacteriostatic activity remained. This study, therefore, confirms the superior activity of levofloxacin over that of ofloxacin against MSSA and MRSA.

[Bleeding on probing. Significance--consequences]. / Le saignement au sondage. Signification--conséquences.

Bleeding on probing is one of the techniques for evaluation of the periodontal pocket tissues condition. Bleeding, leading sign of inflammation inside the connective tissue, is a critical factor for pocket depth measurements, and with other variable factors prevents making reproducible measurements. With the concept of periodontal disease with asynchronous bursts of activity and period of remission, has appeared the necessity to determine and even to predict the presence of destructive activity just as it occurs in a particular site in order to set up a selective therapy. Many authors investigated for a correlation between destructive activity and bleeding on probing. At the present time, the development of manual or electronic probes provides a useful diagnostic aid for the clinician in daily practice as well as the researcher in longitudinal studies.

[Radiographic evaluation in periodontology: development of technics]. / L'évaluation radiographique en parodontologie: évolution des techniques.

The recent development of digital imaging techniques for the analysis of dental radiographs provides an improved method for quantifying subtle changes in alveolar bone. The major application of this methodology appears to be in clinical trials.

Multiplication végétative in vitro de Gardenia jasminoïdes Ellis: In vitro Vegetative Multiplication of Gardenia jasminoïdes Ellis.

The vegetative propagation in vitro of Gardenia jasminoides Ellis, an ornamental shrub producing secondary metabolites useful in perfumery and pharmacy, has been investigated. In the presence of benzylaminopurine (0.3 to 1 mg l(-1)) and indoleacetic acid (1 mg l(-1)), axillary shoots arose from nodes of greenhause plants, but a decrease of morphogenic activity was noticed in subcultures. Mother plants have been developed in vitro from which shoots may be taken with the most effective system being a monthly subculture of nodal explants. As many as one million shoots per year could, theoretically, be produced from one shoot grown in vitro. Rooting occurred easily in three weeks in vitro in the presence of indoleacetic acid (1 mg l(-1)) and charcoal (2 g l(-1)) or in vivo by soaking the base of the shoot in the same auxin for two hours. After acclimatization, the rooted plants developed and flowered normally. The successive stages have been sufficiently well monitored to be used as an effective means of vegetative propagation.