Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU) - methotrexate (MTX) combination. We report here our clinical experience regarding this combination.</p> <p>Patients and Methods</p> <p>Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity.</p> <p>Results</p> <p>50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5). Median number of cycles was 3 (1-20). There were 11 objective responses (23% [95%CI 12-37]) among 48 evaluable patients. Median progression-free survival and overall survival (OS) were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis.</p> <p>Conclusions</p> <p>This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.</p

Convalescent plasma therapy for B-cell depleted patients with protracted COVID-19 disease

International audienceAnti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2-antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative IgG-IgM SARS-CoV-2 serology and a positive RNAemia measured by digital PCR who were treated with four units of COVID-19 convalescent plasma. Within 48 hours following transfusion, all patients except one experienced an amelioration of their clinical symptoms. The inflammatory syndrome abated within a week. Only one patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in 9 out of 9 evaluated patients. Analysis of virus-specific T-cell responses using T-cell enzyme linked immunoSpot (ELISPOT) assay was analyzed before convalescent plasma transfusion in 3 patients. All showed a conserved SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. In COVID-19 patients unable to mount a specific humoral response to SARS-CoV-2, convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms

Population pharmacokinetics of daptomycin in patients with bone and joint infection: minimal effect of rifampicin co-administration and confirmation of a sex difference

International audienceBackground Daptomycin is increasingly used in the treatment of bone and joint infection (BJI), but its pharmacokinetics (PK) and dosage requirements have not been thoroughly investigated in this indication. Daptomycin may be co-administered with rifampicin, which raises questions about a potential drug interaction. Objectives To investigate the population PK and dosage requirements of daptomycin in patients with BJI, and examine the influence of rifampicin co-administration. Methods A population approach was used to analyse PK data from patients who received daptomycin in our regional reference for BJI. We examined the influence of available covariates, including rifampicin co-administration on daptomycin PK. Simulations performed with the final model investigated the influence of dosages and covariates on PTA for both efficacy and safety. Results A total of 1303 daptomycin concentrations from 183 patients were analysed. A two-compartment model best described the data. Significant intra-individual variability was observed. Daptomycin clearance was influenced by renal function and sex, with females having a 26% lower typical clearance than males. Central volume of distribution (V1) was influenced by body weight, age, sex and rifampicin co-administration. Typical V1 was 11% lower in patients who were co-administered rifampicin. In PK/PD simulations, sex influenced the probability of AUC24/MIC target attainment, while rifampicin had a marginal effect. Conclusions A daptomycin dosage of 8 mg/kg/24 h in women and 10 mg/kg/24 h in men should optimize efficacy but may lead to excessive trough concentrations in many patients, especially in women. Therapeutic drug monitoring appears necessary for precision dosing of daptomycin

Coxiella burnetti prosthetic joint infection in an immunocompromised woman: iterative surgeries, prolonged ofloxacin-rifampin treatment and complex reconstruction were needed for the cure

International audienceAbstract Background Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii , a strictly intracellular pathogen that can cause acute and chronic infection. Chronic Q fever can occur in immunocompetent as well as in immuno-compromised hosts, as a persistent localized infection. The main localizations are endocardial, vascular and, less frequently, osteoarticular. The most frequent osteoarticular form is spondyliscitis. Recommended treatment is combined doxycycline and hydroxychloroquine for 18 months, with cotrimoxazole as another option. Coxiella burnetti infection has been implicated in rare cases of prosthetic joint infection (PJI), and the medical and surgical management and outcome in such cases have been little reported. Case presentation We report an unusual case of chronic Q fever involving a hip arthroplasty in an immunocompromised woman treated with tumor necrosis factor (TNF)-α blockers for rheumatoid arthritis. Numerous surgical procedures (explantation, “second look”, femoral resection and revision by megaprosthesis), modification of the immunosuppressant therapy and switch from doxycycline-hydroxychloroquine to prolonged ofloxacin-rifampin combination therapy were needed to achieve reconstruction and treat the PJI, with a follow-up of 7 years. Conclusions Coxiella burnetti PJI is a complex infection that requires dedicated management in an experienced reference center. Combined use of ofloxacin-rifampin can be effective

Type I IFN immunoprofiling in COVID-19 patients

International audienceNo abstract availabl

Necrotizing external otitis: analysis of relapse risk factors in 66 patients managed during a 12 year period

International audienceAbstract Background Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. Objectives To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. Methods We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan–Meier curve. Results Sixty-six patients were included. Median age was 75 (IQR 69–81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12–40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1–15); P = 0.03]. Conclusions NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome

Evaluation of intraosteoblastic activity of dalbavancin against Staphylococcus aureus in an ex vivo model of bone cell infection

International audienceAbstract Objectives Long-acting lipoglycopeptides are promising therapeutic options in Staphylococcus aureus bone and joint infections (BJIs). This study evaluated the ability of dalbavancin to eradicate the intraosteoblastic reservoir of S. aureus, associated with BJI chronicity. Methods Osteoblastic cells were infected with a standardized inoculum of the S. aureus reference strain HG001 and incubated for 24 h with dalbavancin, vancomycin or rifampicin using the MIC, 10×MIC, 100×MIC and/or the intraosseous concentrations reached using standard therapeutic doses (i.e. vancomycin, 10 mg/L; rifampicin, 2 mg/L; and dalbavancin, 6 mg/L). The remaining intracellular bacteria were quantified by plating cell lysates. Results MICs of dalbavancin, vancomycin and rifampicin were 0.125, 1 and 0.004 mg/L, respectively. Dalbavancin significantly reduced the intracellular inoculum of S. aureus starting at a concentration equal to the MIC, with a significant dose effect, ranging from a reduction of 31.4% (95% CI = 17.6%–45.2%) at MIC to 51.6% (95% CI = 39.8%–63.4%) at 100×MIC compared with untreated cells. Of note, dalbavancin was the only molecule to significantly reduce the intraosteoblastic inoculum at low concentration (MIC). At intraosseous concentrations, dalbavancin reduced the intracellular inoculum by 49.6% (95% CI = 45.1%–54.1%) compared with untreated cells (P &lt; 0.001), with no significant difference compared with vancomycin (38.1%; 95% CI = 19.2%–57.0%; P = 0.646), and was less efficient than rifampicin (69.0%; 95% CI = 63.2-74.8; P &lt; 0.001). Conclusions Dalbavancin was able to decrease the intraosteoblastic S. aureus inoculum by 50% at intraosseous concentrations reached during standard human therapeutic dosing, with no difference compared with vancomycin, and remained less efficient than rifampicin. However, it was the only molecule significantly active at low concentration

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer