Suppression of Richtmyer-Meshkov Instability via Special Pairs of Shocks and Phase Transitions.

The classical Richtmyer-Meshkov instability (RMI) is a hydrodynamic instability characterizing the evolution of an interface following shock loading. In contrast to other hydrodynamic instabilities such as Rayleigh-Taylor, it is known for being unconditionally unstable: regardless of the direction of shock passage, any deviations from a flat interface will be amplified. In this article, we show that for negative Atwood numbers, there exist special sequences of shocks which result in a nearly perfectly suppressed instability growth. We demonstrate this principle computationally and experimentally with stepped fliers and phase transition materials. A fascinating immediate corollary is that in specific instances, a phase-transitioning material may self-suppress RMI.

The buzz within: the role of the gut microbiome in honeybee social behavior.

Gut symbionts influence the physiology and behavior of their host, but the extent to which these effects scale to social behaviors is an emerging area of research. The use of the western honeybee (Apis mellifera) as a model enables researchers to investigate the gut microbiome and behavior at several levels of social organization. Insight into gut microbial effects at the societal level is critical for our understanding of how involved microbial symbionts are in host biology. In this Commentary, we discuss recent findings in honeybee gut microbiome research and synthesize these with knowledge of the physiology and behavior of other model organisms to hypothesize how host-microbe interactions at the individual level could shape societal dynamics and evolution.

Early diagnosis of melanoma: a randomized trial assessing the impact of the transmission of photographs taken with a smartphone from the general practitioner to the dermatologist on the time to dermatological consultation.

BACKGROUND: Difficulty obtaining a dermatological consultation is an obstacle to the early diagnosis of melanoma. On the one hand, patients survival depends on the lesion thickness at the time of diagnosis. On the other hand, dermatologists treat many patients with benign lesions. Optimizing patient care pathways is a major concern. The aim of the present study was to assess whether the e-mail transmission of photographs of suspected melanoma lesions between general practitioners (GPs) and dermatologists reduces the time to dermatological consultation for patients whose suspicious skin lesions ultimately require resection. METHODS: We conducted a cluster-randomized controlled study in primary care involving 51 French GPs between April 2017 and August 2019. A total of 250 patients referred to a dermatologist for a suspected melanoma lesion were included GPs were randomized to either the smartphone arm or the usual care arm. In the smartphone arm, the GPs referred patients to the dermatologist by sending 2 photographs of the suspicious lesion using their smartphone. The dermatologist then had to set up an appointment at an appropriate time. In the usual care arm, GPs referred patients to a dermatologist according to their usual practice. The primary outcome was the time to dermatological consultation for patients whose lesion ultimately required resection. RESULTS: 57 GPs volunteered were randomized (27 to the smartphone arm, and 30 to the usual care arm). A total of 125 patients were included in each arm (mean age: 49.8 years; 53% women) and followed 8 months. Twenty-three dermatologists participated in the study. The time to dermatological consultation for patients whose suspicious skin lesion required resection was 56.5 days in the smartphone arm and 63.7 days in the usual care arm (mean adjusted time reduction: -18.5 days, 95% CI [-74.1;23.5], p = .53). CONCLUSIONS: The e-mail transmission of photographs from GPs to dermatologists did not improve the dermatological management of patients whose suspicious skin lesions ultimately required resection. Further research is needed to validate quality criteria that might be useful for tele-expertise in dermatology. TRIAL REGISTRATION: Registered on ClinicalTrials.gov under reference number NCT03137511 (May 2, 2017).

TRASS: a global approach to assess the severity of truncal acne.

INTRODUCTION: Only a small amount of published data regarding truncal acne is available, and no proper tool to assess its severity exists. AIM: The aim of the study was to provide dermatologists with an easy-to-use tool to assess truncal acne (TRASS, truncal acne severity scale) using a global approach. METHODS: A scoring tool that assesses the severity of acne (based on GEA and ECLA scales) on the trunk using a global approach was built, including three sub-scores: family history, clinical signs and quality of life (QoL). In order to test TRASS, the experts used photographs of 47 patients attending their clinics with truncal acne. The regression optimized (ROP) model was applied to assess the diagnosis performance of TRASS and to identify items contributing to the classification of the patients. Internal testing was made to demonstrate the robustness of the model. Correlation analyses between the different items were performed to evaluate the interaction between the different items and their impact on the severity grading of truncal acne. RESULTS: Patients with the most severe acne were identified by TRASS. The error level was 6.6% after internal validation and 10.4% when using the median value or the centile 75th (6.6% and 10.4%). Correlation was significant between systemic treatment and scars (P = 0.0025) and nodules (P = 0.01988) and between location and QoL (P = 0.0095). CONCLUSION: Truncal acne severity scale is the first global, patient-centred approach to evaluate truncal acne by scoring the importance of each factor independently from its clinical severity. TRASS may allow the practitioner to choose and validate the most suitable therapy together with the patient in order to treat his or her truncal acne successfully and to limit treatment failure.

Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+ CD163+ CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

Impact of maternal decision-making autonomy and self-reliance in accessing health care on childhood diarrhea and acute respiratory tract infections in Nepal.

OBJECTIVE: This study aimed to examine the impact of maternal decision-making autonomy and self-reliance in accessing health care on childhood diarrhea and acute respiratory tract infection (ARI) in Nepal. STUDY DESIGN: This was a cross-sectional study. METHODS: This study used data from the Nepal Demographic and Health Survey 2016. Mothers aged 15-49 years provided information about the health of 5308 children included in this analysis. Composite measures of maternal decision-making autonomy and self-reliance in accessing health care were used as exposure variables. Childhood diarrhea and ARI in the 2 weeks preceding the survey were primary outcome variables. Descriptive statistics and multivariable survey-weighted logistic regression methods were used in the analyses. RESULTS: Maternal decision-making autonomy was high for approximately one-fourth (24.7%) of the children's mothers, and 81.7% of children's mothers reported self-reliance in accessing health care as a big problem. Diarrhea among children in the prior 2 weeks was reported among 8% (95% confidence interval [CI]: 6.9-8.4), whereas ARI was reported among 22% (95% CI: 21.1-23.5). The children of women who viewed a lack of self-reliance as a big problem had a 88% (adjusted odds ratio [aOR] = 1.88, 95% CI: 1.26-2.82, P < 0.01) higher odds of diarrhea and 59% (aOR = 1.59, 95% CI: 1.29-1.95, P < 0.001) higher odds of ARI compared with children of women who did not view self-reliance as a big problem. CONCLUSIONS: The study found a significant effect of maternal self-reliance in accessing health care on childhood diarrhea and ARI, independent of other sociodemographic factors. Improvement in maternal self-reliance in accessing health care of women is essential, particularly their autonomy with regard to healthcare seeking behavior and financial empowerment.

Creation and Characterization of Matter-Wave Breathers.

We report the creation of quasi-1D excited matter-wave solitons, "breathers," by quenching the strength of the interactions in a Bose-Einstein condensate with attractive interactions. We characterize the resulting breathing dynamics and quantify the effects of the aspect ratio of the confining potential, the strength of the quench, and the proximity of the 1D-3D crossover for the two-soliton breather. Furthermore, we demonstrate the complex dynamics of a three-soliton breather created by a stronger interaction quench. Our experimental results, which compare well with numerical simulations, provide a pathway for utilizing matter-wave breathers to explore quantum effects in large many-body systems.

Same-day discharge of Gynecologic Oncology patients following ileostomy closure is feasible and safe.

OBJECTIVE: Gynecologic Oncology patients are traditionally admitted for 2-3 days following ileostomy closure. Our aim was to assess feasibility and safety of same-day discharge (SDD), by comparing 30-day clinical outcomes after SDD and standard admission. METHODS: Retrospective study of patients who underwent ileostomy closure at two academic tertiary centres in Toronto, Canada, between January 2010 and October 2017. RESULTS: In total 117 patients underwent ileostomy closure: 23 had SDD and 94 were admitted for a median of 3 days. There were no significant differences between groups in terms of age, body mass index, comorbidities, primary malignancy, tumor stage, indication for ileostomy, previous radiation therapy, chemotherapy, interval between ileostomy formation and closure, and intraoperative complications. Median operative time was shorter (47 versus 60 min, p = 0.0001) and there was a longer median interval between last chemotherapy cycle to ileostomy closure (145 versus 106 days, p = 0.01) in the SDD group. SDD was not associated with an increased risk of adverse events (13% versus 24.5%, p= 0.24), as assessed by a composite outcome which included small bowel obstruction, anastomotic leak, surgical site infection, clostridium difficile infection, sepsis, and thromboembolic events, when compared to standard admission. Moreover, SDD did not lead to more emergency room visits (17.4% versus 16%, p = 0.87) or readmissions within 30 days of surgery (17.4% versus 8.5%, p= 0.21). CONCLUSIONS: SDD is a safe alternative to routine hospitalization that has the potential to improve healthcare resource utilization, without increasing readmissions or emergency room visits. Careful patient selection is warranted.

Effect of an intensive lifestyle intervention on the prevalence of metabolic syndrome and its components among overweight and obese adults.

BACKGROUND: Despite the fact that up to a third of the global population has metabolic syndrome (MetS), it has been overlooked in clinical settings. This study assesses the impact of a physician-supervised nonsurgical weight management program on the prevalence of MetS and its key indicators. METHODS: Four-hundred seventy-nine overweight and obese participants aged 19 years or older were included in a prospective longitudinal study. Changes in MetS and its key indicators were assessed using the binomial exact, chi-square and Wilcoxon signed-rank tests in an intent-to-treat study population. Differences in age strata were assessed using a generalized linear model. RESULTS: Fifty-two percent of participants (n = 249) had MetS at baseline. Prevalence of MetS decreased steadily with significant changes from baseline observed at weeks 13 (31.8%, P < 0.0001), 26 (28.7%, P < 0.0012) and 39 (21.6%, P < 0.0002); changes from baseline were observed at week 52 as statistically significant (16.7%, P < 0.0012). Improvements in anthropometrics and levels of key indicators of MetS were observed throughout the study. CONCLUSION: These findings confirm that weight loss is inversely associated with prevalence of MetS and its key indicators among overweight and obese individuals. Future studies may benefit from a larger sample size and better retention (ClinicalTrials.gov ID: NCT03588117).

Predictive value of FDG-PET imaging for relapse in metastatic melanoma patients treated with immunotherapy.

BACKGROUND: Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified. OBJECTIVES: To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes. METHODS: Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2 months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR. RESULTS: Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7 months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P = 0.00231). CONCLUSIONS: Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process.

BACKGROUND: Acne has long been understood as a multifactorial chronic inflammatory disease of the pilosebaceous follicle, where Cutibacterium acnes (subdivided into six main phylotypes) is a crucial factor. In parallel, the loss of microbial diversity among the skin commensal communities has recently been shown as often accompanied by inflammatory skin disorders. OBJECTIVE: This study investigated the association of C. acnes phylotype diversity loss and the impact on Innate Immune System (IIS) activation. METHODS: The IIS response of skin after incubation with phylotypes IA1, II or III individually and with the combination of IA1 + II + III phylotypes, was studied in an in vitro skin explant system. The inflammatory response was monitored by immunohistochemistry and ELISA assays, targeting a selection of Innate Immune Markers (IIMs) (IL-6, IL-8, IL-10, IL-17, TGF-ß). RESULTS: IIMs were significantly upregulated in skin when being incubated with phylotype IA1 alone compared with the combination IA1 + II + III. In parallel, ELISA assays confirmed these results in supernatants for IL-17, IL-8 and IL-10. CONCLUSION: We identify the loss of C. acnes phylotype diversity as a trigger for IIS activation, leading to cutaneous inflammation. These innovative data underline the possibility to set up new approaches to treat acne. Indeed, maintaining the balance between the different phylotypes of C. acnes may be an interesting target for the development of drugs.

Increasing the Representation of Minority Students in the Biomedical Workforce: the ReTOOL Program.

With the growing burden of cancer in minority populations and limited progress in eliminating cancer disparities, it has become important to develop a diverse oncology workforce in basic, clinical, and behavioral research who will address cancer disparities and increase the participation of minority populations in clinical trials. To address the lack of well-trained underrepresented minority cancer scientists in Florida, the University of Florida collaborated with Florida A&M University in 2012 to establish the Florida Prostate Cancer Research Training Opportunities for Outstanding Leaders (ReTOOL) Program. Since 2012, the ReTOOL program has expanded to (1) cover all areas of cancer disparities; (2) offer training opportunities to minority students from all historically Black colleges and universities (HBCUs) in Florida; and (3) successfully secure both intramural and extramural federal funding to continuously provide research training opportunities for minority students in Florida. Focusing primarily on training Black students, the ReTOOL model includes culturally sensitive recruitment, mentorship, didactic curriculum, networking, and hands on experience in cancer research. This paper discusses the lessons learned from administering the ReTOOL program for 5 years, which includes having the right inputs (such as majority-minority institutions partnership, funding, faculty advisors, committed mentors, culturally competent staff, and standardized program requirements) and processes (such as pipeline approach, structured applications system, didactic curriculum, research experience, and continuous mentoring) for an effective research training program. The program impact is an increase in the pool of underrepresented minority candidates with scientific and academic career progression paths focused on reducing cancer health disparities.

Single-use versus reusable medical devices in spinal fusion surgery: a hospital micro-costing analysis.

PURPOSE: Healthcare facilities could minimize the cost of surgical instrument and implant processing by using single-use devices. The main objective was to prospectively compare the total cost of a single-use and reusable device used in short lumbar spine fusion. METHODS: A 1-year, single-centre, prospective study was performed on patients requiring a one- or two-level lumbar arthrodesis. Patients were randomized in two groups treated with either reusable or single-use device. A cost minimization analysis was performed using a micro-costing approach from a hospital perspective. Every step of the preparation process was timed and costed based on hourly wages of hospital employees, cleaning supplies and hospital waste costs. RESULTS: Forty cases were evaluated. No significant difference in operation time was noted (reusable 176.1 ± 68.4 min; single use 190.4 ± 71.7 min; p = 0.569). Mean processing time for single-use devices was lower than for reusable devices (33 min vs. 176 min) representing a cost of 14€ versus 58€ (p < 0.05). Pre-/post-sterilization and spinal set recomposing steps were the most time-consuming in reusable device group. A total cost saving of 181€ per intervention resulted from the use and processing of the single-use device considering an additional sterilization cost of 137€ with the reusable device. The weight of the reusable device was 42 kg for three containers and 1.2 kg for the single-use device. CONCLUSIONS: Owing to the absence of re-sterilization, single-use devices in one- and two-level lumbar fusion allow significant money and time savings. They may also avoid delaying surgery in case of reusable device unavailability.

Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores.

Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.

Cebranopadol: novel dual opioid/NOP receptor agonist analgesic.

WHAT IS KNOWN AND OBJECTIVE: Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol. METHODS: Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized. RESULTS: The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed. WHAT IS NEW AND CONCLUSION: Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.

Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States.

Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.

The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.

Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas. OBJECTIVES: In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms. MATERIALS AND METHODS: We used a national transversal observational study by questionnaire. Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre). Sun exposure level by geographic area was assessed using climate data provided by the French national meteorological service (Météo France). RESULTS: Eighty-nine patients were included. We notably observed that 40% of patients declared an improvement in their tolerance of sun exposure after repeated sun exposures. In the more sunny areas, the intensity of the pain was lower (r = -0·26) and the duration of the sun exposure responsible for flares was longer (r = 0·39) than in the areas that were less sunny (P < 0·05). CONCLUSIONS: This study proposes a benefit of natural progressive sun exposure for patients with EPP.

Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab.

UNLABELLED: Ipilimumab is a monoclonal antibody blocking the inhibitory molecule CTLA4 expressed by activated T lympocytes, used for the treatment of metastatic melanoma. Recent studies have shown its potential efficacy on brain metastases. OBJECTIVES: To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.