Background: The use of antibiotics (ATB) and proton-pump inhibitors (PPI) alters the composition and diversity of the gut microbiota, which can influence the immune system, consequently interfering with response to anti-PD1 immune checkpoint inhibitors (ICI). We assessed the impact of ATB and/or PPI use on the efficacy and safety of ICI. Methods: Two hundred twelve patients treated with anti-PD1 ICI for non-small cell lung carcinoma, melanoma, upper airway & digestive tract carcinoma or renal cell carcinoma were retrospectively included. Patients having received ATB within 60 days before ICI initiation were included in the ATB+ group. Patients having received PPI within 30 days before ICI initiation were included in the PPI+ group. Four groups were thus considered: ATB-/PPI-, ATB+/PPI-, ATB-/PPI+, ATB+/PPI+. Response rate was assessed by RECIST v1.1. Overall survival (OS), progression-free survival (PFS) and adverse events, recorded using Common Terminology Criteria for Adverse Events Version 5, were compared using inverse probability of treatment weighting to account for selection bias. Results: PFS at 6 months was 56.7 %, 95%CI (49.6%; 63.2%) and 47.2 %, 95%CI (39.8%;54.1%) at 12 months. OS was 81.6%, 95%CI (75.6%; 86.2%) at 6 months, and 69.4%, 95%CI (61.9%;75.7%) at 12 months. Compared to ATB-/PPI- group, PFS was lower for the ATB+/PPI- group [Hazard ratio (HR) 1.90, 95%CI (1.41;2.57)] and the ATB-/PPI+ group [HR 1.51, 95%CI (1.11;2.05)], and lowest in the ATB+/PPI+ group [HR 3.65, 95%CI (2.75;4.84)]. For OS, the use of ATB alone or PPI alone or in combination was a risk factor for death, with each increasing HR values by a similar magnitude, and the combination of ATB and PPI did not increase risk further. AEs were observed in 78 cases (36.8%) with no significant impact of ATB or PPI use. Conclusions: This study reveals that ATB and/or PPI use can alter response to anti-PD1 ICI, and the prognosis of cancer patients. The microbiota mechanisms involved in the response to ICI should be investigated to optimize patient management.

Introduction: The primary objective of this study was to determine the efficiency of hydrogen peroxide (H₂O₂) techniques in disinfection of ICU rooms contaminated with multidrug-resistant organisms (MDRO) after patient discharge. Secondary objectives included comparison of the efficiency of a vaporizator (HPV, Bioquell®) and an aerosolizer using H₂O₂, and peracetic acid (aHPP, Anios®) in MDRO environmental disinfection, and assessment of toxicity of these techniques. Methods: This prospective cross-over study was conducted in five medical and surgical ICUs located in one University hospital, during a 12-week period. Routine terminal cleaning was followed by H₂O₂ disinfection. A total of 24 environmental bacteriological samplings were collected per room, from eight frequently touched surfaces, at three time-points: after patient discharge (T0), after terminal cleaning (T1) and after H₂O₂ disinfection (T2). Results: In total 182 rooms were studied, including 89 (49%) disinfected with aHPP and 93 (51%) with HPV. At T0, 15/182 (8%) rooms were contaminated with at least 1 MDRO (extended spectrum β–lactamase-producing Gram-negative bacilli 50%, imipenem resistant Acinetobacter baumannii 29%, methicillin-resistant Staphylococcus aureus 17%, and Pseudomonas aeruginosa resistant to ceftazidime or imipenem 4%). Routine terminal cleaning reduced environmental bacterial load (P <0.001) without efficiency on MDRO (15/182 (8%) rooms at T0 versus 11/182 (6%) at T1; P = 0.371). H₂O₂ technologies were efficient for environmental MDRO decontamination (6% of rooms contaminated with MDRO at T1 versus 0.5% at T2, P = 0.004). Patient characteristics were similar in aHPP and HPV groups. No significant difference was found between aHPP and HPV regarding the rate of rooms contaminated with MDRO at T2 (P = 0.313). 42% of room occupants were MDRO carriers. The highest rate of rooms contaminated with MDRO was found in rooms where patients stayed for a longer period of time, and where a patient with MDRO was hospitalized. The residual concentration of H₂O₂ appears to be higher using aHPP, compared with HPV. Conclusions: H₂O₂ treatment is efficient in reducing MDRO contaminated rooms in the ICU. No significant difference was found between aHPP and HPV regarding their disinfection efficiency.

Purpose: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)–associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. Experimental Design: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. Results: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. Conclusions: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158

To report grade ≥2 overall late rectal and urinary toxicities in patients (pts) with prostate cancer treated by intensity-modulated radiotherapy (IMRT) at 3 dose-levels. Identify predictors of radiation toxicity and report biochemical progression free survival (bPFS). A total of 277 pts were treated with 70Gy (10.8%), 74Gy (63.9%) and 80 Gy (25.3%) using IMRT without pelvic irradiation were analyzed. Short or long-course androgen deprivation therapy (ADT) was allowed in 46.1% of pts. The toxicity was described using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scale. Cox regression models addressed demographics, disease and dosimetry characteristics as potential predictors of late grade ≥2 toxicity after adjusting for other modifying factors. The median follow-up was 77 months (range 15; 150). There was no grade ≥4 toxicity. The 5-year cumulative rate of grade ≥2 late rectal and urinary toxicities was 6.3% (95% CI = 3.8%; 10.3%) and 25.3% (95% CI = 19.8%; 31.8%) respectively. In multivariate analysis, only the dose (80Gy vs 74 and 70Gy) was found to increase the risk of rectal toxicity (HR = 2.96 [1.07; 8.20]). For pts receiving 74 Gy, International Prostate Symptom Score (IPSS) at baseline ≥8 (HR = 2.40 [1.08; 5.35]) and dose ≥73Gy delivered in more than 2% of bladder (D2%) were found to be predictors of bladder toxicity (HR = 3.29 [1.36; 7.98]). The 5–year biochemical relapse free survival was 81.0% [74.5%; 86.0%] in the entire population, 97.5% [83.5%; 99.6%] in the low risk group, 84.9% [76.7%; 90.3%] in the intermediate risk group and 66.4% [51.8%; 77.4%] in the high-risk group. D’Amico low (HR = 0.09 [0.01; 0.69]) and intermediate risk groups (HR = 0.50 [0.28; 0.88]) as well as PSA nadir ≥0.2 ng/ml (HR = 1.79 [1.01; 3.21]) were predictive of biochemical relapse. The rate of late rectal toxicity increased with higher doses, while Dmax ≥74Gy, D2% ≥ 73Gy for bladder wall and baseline IPSS ≥8 increased late urinary toxicity.

To assess the time course of the central venous–arterial carbon dioxide tension difference (∆PCO₂)—as an index of the carbon dioxide production (VCO₂)/cardiac index (CI) ratio—in stable septic shock patients receiving incremental doses of dobutamine. Twenty-two hemodynamically stable septic shock patients with no signs of global tissue hypoxia, as testified by normal blood lactate levels, were prospectively included. A dobutamine infusion was administered at a dose of up to 15 μg/kg/min in increments of 5 μg/kg/min every 30 min. Complete hemodynamic and gas measurements were obtained at baseline, and at each dose of dobutamine. Dobutamine induced a significant dose-dependent increase of CI from 0 to 15 μg/kg/min (P < 0.001). Oxygen consumption (VO₂) and VCO₂ were progressively increased by dobutamine. These increases were more marked between 10 and 15 μg/kg/min (8.3 and 8.6 %, respectively) than between the lower doses. ∆PCO₂ and oxygen extraction (EO₂) significantly decreased between 0 (8.0 ± 2.0 mmHg and 43.8 ± 13.4 %, respectively) and 10 μg/kg/min of dobutamine (4.2 ± 1.6 mmHg and 28.9 ± 7.9 %, respectively), but remained unchanged from 10 to 15 μg/kg/min (5.4 ± 2.4 mmHg and 29.5 ± 8.2 %, respectively). The central venous oxygen saturation significantly (ScvO₂) increased from 0 to 10 μg/kg/min and remained unchanged from 10 to 15 μg/kg/min. Time courses of ∆PCO₂, ScvO₂, and EO₂ were linked therefore to the biphasic changes of VO₂ and VCO₂. ∆PCO₂ is a good indicator of the change of VCO₂ induced by dobutamine. Measurement of ∆PCO₂, along with ScvO₂ and EO₂, may be presented as a useful tool to assess the adequacy of oxygen supply versus metabolic and oxygen demand.

Little information is currently available concerning young medical students desire to pursue a career in oncology, or their career expectations. This project is a cross-sectional epidemiological study. A voluntary and anonymous questionnaire was distributed to all young oncologists studying in France between the 2nd of October 2013 and the 23rd of February 2014. The overall response rate was 75.6%. A total of 505 young oncologists completed the questionnaire. The main determining factors in the decision to practice oncology were the cross-sectional nature of the field (70.8%), the depth and variety of human relations (56.3%) and the multi-disciplinary field of work (50.2%). Most residents would like to complete a rotation outside of their assigned region (59.2%) or abroad (70.2%) in order to acquire additional expertise (67.7%). In addition, most interns would like to undertake a fellowship involving care, teaching and research in order to hone their skills (85.7%) and forge a career in public hospitals (46.4%). Career prospects mainly involve salaried positions in public hospitals. Many young oncologists are concerned about their professional future, due to the shortage of openings (40.8%), the workload (52.8%) and the lack of work-life balance (33.4%). This investigation provides a comprehensive profile of the reasons young oncologists chose to pursue a career in oncology, and their career prospects.