Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma.

BACKGROUND: Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. METHODS: This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). RESULTS: Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3-3.9; p = 0.003) and 2.5 (95%CI:1.3-4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). DISCUSSION: This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.

[Factors associated to loss of follow-up in patients underwent antiretroviral therapy in an ambulatory HIV treatment center at Conakry]. / Facteurs associés aux perdus de vue des patients sous traitement antirétroviral dans un centre de traitement ambulatoire du VIH à Conakry, Guinée.

BACKGROUND: Late or inadequate therapeutic management increases the risk of mortality associated with HIV/AIDS. The aim of this study was to analyze the proportion and factors associated with loss of follow-up in HIV patients who receiving antiretroviral therapy at Conakry. METHODS: A retrospective cohort study was conducted in HIV patients aged over 15 years and who receiving antiretroviral therapy. Between August 1, 2008 and July 31, 2015, all patients managed by the ambulatory treatment center of the Guinean Women Association against AIDS and sexually and transmissible infection were included. Loss of follow-up was defined as no follow-up visit within 3 months. Kaplan-Meier curves and multivariate Cox regression models were used to analyze factors associated with loss of follow-up. Analyses were performed by using Stata 13 software. RESULTS: 614 patients aged 36.3±11.2 years, mainly females (68.4%) and living in Conakry (80.5%) were included. Among them, 104 were loss to follow-up, corresponding to a proportion rate of 16.9% (95% CI: 14.2-19.7%) or 5.79/100 person-years. The results of multivariate analyses showed that factors independently associated with loss of follow-up were malnutrition (AHR=7.05; 95% CI: 2.05-24.27; P=0.002) and CD4 cells account at the initiation of AHR (2.35; 95% CI: 1.61-6.39; P=0.016) in patients with 201-350 CD4/µL and 5.83 (95% CI: 2.85-11.90; P<0.001) in patients with less than 150CD4/µL. CONCLUSION: Despite efforts of health care workers and free antiretroviral therapy, many patients were loss to follow-up. Multivariate analysis showed that malnutrition and low CD4 account were independently associated with loss to follow-up.

Susceptibilities of clinical Clostridium difficile isolates to antimicrobials: a systematic review and meta-analysis of studies since 1970.

OBJECTIVES: Although exposure to antibiotics can cause Clostridium difficile infection, certain antibiotics are used to treat C. difficile. Measurements of antimicrobial C. difficile activity could help to identify antibiotic risk and emergent resistance. Here, we describe publication patterns relating to C. difficile susceptibilities and estimate minimum inhibitory concentrations (MIC) for antibiotic classes in the published literature between January 1970 and June 2014. METHODS: We queried PUBMED and EMBASE for studies reporting antibiotic C. difficile MIC in English or French. We used mixed-effects models to obtain pooled estimates of antibiotic class median MIC (MIC50), 90th percentile of MIC (MIC90), and MIC90:MIC50 ratio. RESULTS: Our search identified 182 articles that met our inclusion criteria, of which 27 were retained for meta-analysis. Aminoglycosides (MIC50 120 mg/L, 95% CI 62-250), 3rd (MIC50 75 mg/L, 95% CI 39-130) and 2nd generation cephalosporins (MIC50 64 mg/L, 95% CI 27-140) had the least C. difficile activity. Rifamycins (MIC50 0.034 mg/L, 95% CI 0.012-0.099) and tetracyclines (MIC50 0.29 mg/L, 95% CI 0.054-1.7) had the highest level of activity. The activity of 3rd generation cephalosporins was more than three times lower than that of 1st generation agents (MIC50 19 mg/L, 95% CI 7.0-54). Time-trends in MIC50 were increasing for carbapenems (70% increase per 10 years) while decreasing for tetracyclines (51% decrease per 10 years). CONCLUSIONS: We found a 3500-fold variation in antibiotic C. difficile MIC50, with aminoglycosides as the least active agents and rifamycins as the most active. Further research is needed to determine how in vitro measures can help assess patient C. difficile risk and guide antimicrobial stewardship.

Hospital management of Clostridium difficile infection: a review of the literature.

BACKGROUND: The emergence of the epidemic Clostridium difficile 027 strain has renewed interest in infection control practices. AIM: To review the effectiveness of different practices to reduce hospital C. difficile infection (CDI) in non-outbreak settings. METHODS: Data sources were identified by a MEDLINE search in English and French. The ORION statement was used to extract key data from articles describing interventions to manage CDI. FINDINGS: Twenty-one studies, published between 1982 and December 2013, were reviewed. Most studies were before-after interventions, and a few studies were planned, formal, prospective investigations. The effects of the following single or combined interventions were described: antibiotic management; environmental disinfection and/or cleaning; hand hygiene; bathing; surveillance; cohorting; and isolation of infected patients in private rooms. CONCLUSION: With many methodological weaknesses and some inadequate research reporting, the observed reduction in CDI may not be entirely attributable to interventions. Although infection control programmes involving education and handwashing/gloving protocols were found to have contributed to a reduction in the incidence of CDI, these measures were usually a component of multi-faceted interventions that did not provide for evaluation of the relative impact of each factor. Appropriate environmental disinfection and antibiotic stewardship would appear to offer the most effective benefits.

Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia--results of a prospective observational study.

Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton-Valentine leucocidin (PVL). NP was initially described for methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of methicillin resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to methicillin resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of methicillin resistance. By Cox regression analysis, methicillin resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that methicillin resistance is not associated with the severity of staphylococcal necrotizing pneumonia.

Hemodialysis patient management by telemedicine: design and implementation.

The authors describe the design and implementation of a personal computer based telemedicine system for managing patients by telemedicine. With three identical systems connected by high speed T1 lines, the physician (or allied healthcare giver) can interact, by videoconferencing, and by using multimedia files, with patients at two remote hemodialysis sites. The physician is able to visualize specifically the patient's fistula/graft, and auscultate fistula, heart and lung sounds, and incorporate still pictures or audio sounds in the patient's multimedia database folder, which also contains an electronic and paperless medical record. In addition there is the capability of downloading into this database all the machine parameters during dialysis.