Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database.

BACKGROUND: Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib. MATERIALS AND METHODS: This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment. RESULTS: Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months). CONCLUSION: Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms.

Is There an Optimal Definition for a Positive Circumferential Resection Margin in Locally Advanced Esophageal Cancer?

BACKGROUND: Two definitions of a positive circumferential resection margin (CRM) in esophageal cancer coexist: one by the College of American Pathologists (CAP) (CRM = 0 mm) and another by the Royal College of Pathologists (RCP) (CRM ≤ 1 mm). This study aimed to evaluate the prognostic value of both definitions in esophageal cancer and to identify a new cutoff value for the CRM to predict survival. METHODS: Patients who underwent curative esophageal resection for locally advanced (≥ pT3) adenocarcinoma or squamous cell carcinoma were selected from 2007 to 2016. The CRM was reassessed using an ocular micrometer. Overall survival (OS) and disease-free survival were estimated with uni- and multivariate analyses. RESULTS: The study enrolled 283 patients: 48 with a positive CRM according to the CAP definition and 171 with a positive CRM according to the RCP definition. In the multivariate analysis, a positive CRM according to both definitions was significantly associated with a poor OS (CAP: hazard ratio [HR], 2.26, p < 0.001; RCP: HR, 1.42, p = 0.035). A CRM of 0 mm was predictive of a worse OS and DFS than a CRM of 1 mm or less (p < 0.0001), whereas no significant difference was found between a CRM greater than 1 mm and a CRM of 1 mm or less, indicating that the CAP definition was more accurate for predicting prognosis and recurrence. New cutoff CRM values of 100 µm in squamous cell carcinoma and 200 µm in adenocarcinoma were optimal for predicting OS. CONCLUSION: The CAP definition was more accurate for predicting prognosis and recurrence. The study identified a new cutoff value of CRM according to histologic type.

Longitudinal study of AMH variations in 122 Adolescents and Young Adults (AYA) and non-AYA lymphoma patients to evaluate the chemo-induced ovarian toxicity to further personalise fertility preservation counselling.

STUDY QUESTION: What is the influence of age and chemotherapy regimen on the longitudinal blood anti-Müllerian hormone (AMH) variations in a large series of adolescents and young adult (AYA) (15-24 years old) and non-AYA (25-35 years old) lymphoma patients? SUMMARY ANSWER: In case of alkylating regimen treatment, there was a deep and sustained follicular depletion in AYA as well as non-AYA patients; however in both groups, the ovarian toxicity was extremely low in cases of non-alkylating treatments. WHAT IS KNOWN ALREADY: AMH is now well-recognised to be a real-time indicator of ovarian follicular depletion and recovery in women treated by chemotherapy. Its longitudinal variations may discriminate between highly and minimally toxic protocols regarding ovarian function. It has been shown, in different cancer types, that age, type of chemotherapy regimen and pre-treatment AMH levels are the main predictors of ovarian recovery. Large studies on longitudinal AMH variations under chemotherapy in lymphoma patients are few but can provide the opportunity to assess the degree of follicle loss at a young age. STUDY DESIGN, SIZE, DURATION: This prospective cohort study was conducted in the Fertility Observatory of the Lille University Hospital. Data were collected between 2007 and 2016. Non-Hodgkin or Hodgkin lymphoma patients (n = 122) between 15 and 35 years old were prospectively recruited before commencing chemotherapy. Patients were treated either by a non-alkylating protocol (ABVD group; n = 67) or by an alkylating regimen (alkylating group; n = 55). PARTICIPANTS/MATERIALS, SETTING, METHODS: Serial AMH measurements were performed at baseline (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 9, 12, 18 and 24 months from the end of chemotherapy. The whole study population was divided into two groups according to age: AYA (15-24; n = 65) and non-AYA (25-35; n = 57). All patients received a once monthly GnRH agonist injection during the whole treatment period. A linear mixed model was used to account for the repeated measures of single patients. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, non-AYA patients had higher BMI and lower AMH levels than AYA patients. All AYA and non-AYA patients having received ABVD protocols had regular cycles at 12 months of follow-up. In case of alkylating regimens, amenorrhoea was more frequent in non-AYA patients than in AYA patients at 12 months (37% vs 4%, P = 0.011) and at 24 months (24% vs 4%, P = 0.045). We distinguished a similar depletion phase from AMH0 to AMH2 between ABVD and alkylating groups but significantly different recovery phases from AMH2 to AMH + 24 months. AMH recovery was fast and complete in case of ABVD protocols whatever the age: AMH reached pre-treatment values as soon as the 6th month of follow-up in the AYA group (mean (95% CI) in log AMH M0 vs M6: 3.07 (2.86 to 3.27) vs 3.05 (2.78 to 3.31), P = 1.00) and in the non-AYA group (mean (95% CI) in log AMH M0 vs M6: 2.73 (2.40 to 3.05) vs 2.47 (2.21 to 2.74), P = 1.00). In contrast, no patients from the alkylating group returned to pre-treatment AMH values whatever the age of patients (AYA or non-AYA). Moreover, none of the AMH values post-chemotherapy in the non-AYA group were significantly different from AMH2. Conversely in the AYA group, AMH levels from 6 months (mean (95% CI) in log AMH: 1.79 (1.47 to 2.11), P < 0.001) to 24 months (mean (95% CI) in log AMH: 2.16 (1.80 to 2.52), P ≤ 0.001) were significantly higher than AMH2 (mean (95% CI) in log AMH: 1.13 (0.89 to 1.38)). Considering the whole study population (AYA and non-AYA), pre-treatment AMH levels influenced the pattern of the AMH variation both in alkylating and ABVD protocols (interaction P-value = 0.005 and 0.043, respectively). Likewise, age was significantly associated with the pattern of the recovery phase but only in the alkylating group (interaction P-value =0.001). BMI had no influence on the AMH recovery phase whatever the protocol (interaction P-value = 0.98 in alkylating group, 0.72 in ABVD group). LIMITATIONS, REASONS FOR CAUTION: There was a large disparity in subtypes of protocols in the alkylating group. The average duration of chemotherapy for patients treated with alkylating protocols was longer than that for patients treated with ABVD. WIDER IMPLICATIONS OF THE FINDINGS: These results make it possible to develop strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients. In addition, it was confirmed that young age does not protect against ovarian damage caused by alkylating agents. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (n° DOS/SDES/AR/FIR/2019/282). There are no competing interests. TRIAL REGISTRATION NUMBER: DC-2008-642 and CNIL DEC2015-112.

[Use of the SBAR tool: Assessment of the value of a short training course on the quality of communication between caregivers in the short and long term]. / Utilisation de l'outil SAED : évaluation de l'intérêt d'une formation courte sur la qualité de la communication entre soignants à court et à long terme.

OBJECTIVES: Communication breakdown is one of the main causes of adverse events in clinical routine. The main objective of this study was to assess whether a short training course on medical communication based on the situation-background-assessment-recommendation (SBAR) tool improved the quality of communication in clinical practice. METHODS: Interventional study, conducted at the Jeanne de Flandre maternity unit (Lille University Hospital, France) between January 2017 and December 2019. The training sessions lasted 1 hour and consisted of a theoretical part, based on the SBAR tool, and of a practical part (video-stimulated recall and role-play case scenarios). The main outcome measure was the evaluation of the quality of the telephone calls made by a caregiver to the on-call doctor, using a questionnaire completed before (Q1) and remotely from training (Q2). RESULTS: One hundred and twenty health professionals were trained (n=120). Following the trainings, there was an improvement in communication in the short term, whether in terms of relevance (64.9 vs. 52.6, P<0.001) or conciseness of the message (36.9 vs. 32.2, P<0.001), but also in terms of long-term in a real clinical situation (Q2: 3.9 vs. Q1: 3.0, P<0.001). Finally, 81% of participants were satisfied with the training. CONCLUSIONS: Short training sessions on communication based on the SBAR tool appeared to improve participants' knowledge and skills in the short-term, but also in the longer term in a real clinical situation.

Real-life evaluation of the treatment of actinic keratoses by textile photodynamic therapy (FLUXMEDICARE® device).

INTRODUCTION: Actinic keratoses (AK) are a common precancerous skin condition in dermatology practice. Photodynamic therapy (PDT) with ALA or MAL is an effective but painful treatment of fields of cancerization particularly when conventional illumination sources and irradiation rates are used. Two prior studies showed that illumination with textile PDT was not inferior to conventional PDT. FLUXMEDICARE® (FLX-PDT) is the first medical device marketed with textile based lighting . We performeda real-life study to evaluate efficacy and tolerance of this device. METHODS: We carried out a single-center retrospective study. We collected data from patients treated with FLX-PDT with MAL for AKs localized on scalp and temples between November 2018 and November 2019. The primary endpoint was complete clearance rate (CR) at 3 months-follow up. RESULTS: Data of 39 patients were reviewed in the study, with a total of 417 AKs. The CR rate was 72.6 % (95 %CI 67.9-77.0) at 3 months-follow up and 67.5 % (95 %CI 61.2-73.3) at 6 months-follow up. The median pain felt during the session was 0 and there wasn't erythema after the session for 64.1 %. CONCLUSION: Our real-life study confirms efficacy and safety of textile PDT by FLUXMEDICARE device in the treatment of scalp and temples AKs, with excellent tolerance and minimal pain reported.

A blended cognitive behavioral intervention for patients with adjustment disorder with anxiety: A randomized controlled trial.

Adjustment disorder with anxiety (ADA) is a common psychiatric pathology worldwide, but it is often undertreated. Cognitive behavioral therapy (CBT) is the first-line treatment, but very few studies have been carried out for the treatment of ADA. Internet-delivered CBT (iCBT) appears to be an effective treatment option, with the potential to reach a larger proportion of individuals suffering from ADA. Guidance is a beneficial feature of iCBT, provided in most studies by email or telephone (traditional guided iCBT). Blended CBT, which combines an online intervention and therapeutic guidance provided in person (face-to-face), could be a way to benefit from both the advantages of face-to-face CBT regarding human interactional quality and the advantages of internet-based CBT in terms of improved access to treatment. In this randomized controlled trial, the effectiveness of two forms of administration of Seren@ctif, a 5-week CBT program for patients with ADA according the DSM-5, was examined: one delivered through face-to-face sessions (face-to-face CBT) and the other delivered online and guided with face-to-face contact with a nurse (blended CBT); these formats were compared with a wait-list control group (WLC). A total of 120 patients were included and randomized to one of these three conditions. Measures were administered before treatment, after treatment and 6 months after inclusion in the study. Both treatment conditions displayed significant decreases in anxiety, depression, worry and perceived stress at posttreatment when compared to the WLC group. The decrease in symptoms was mostly maintained 6 months after inclusion for the two experimental groups. Blended CBT showed significantly greater reductions in anxiety and depression than did face-to-face CBT on some secondary outcome measures. We conclude that both face-to-face CBT and blended CBT are effective treatments for patients with ADA, and we suggest that blended CBT may be slightly more effective than classical face-to-face CBT. Trial Registration: Clinicaltrials.gov NCT02621775;https://clinicaltrials.gov/ct2/show/NCT02621775(Archived by WebCite at http://www.webcitation.org/6tQrkPs1u).

The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

MRI for characterization of benign hepatocellular tumors on hepatobiliary phase: the added value of in-phase imaging and lesion-to-liver visual signal intensity ratio.

OBJECTIVES: To evaluate the lesion-to-liver visual signal intensity ratio (SIR) before and at the hepatobiliary phase MRI (HBP-MRI) after gadobenate dimeglumine (Gd-BOPTA) injection, using several T1-weighted images (T1-WI), for the characterization of benign hepatocellular lesions. METHODS: Patients with histologically proven focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), who underwent Gd-BOPTA-enhanced HBP-MRI from 2009 to 2017, were retrospectively identified. The lesion-to-liver SIR was visually assessed by two radiologists on HBP (post-HBP analysis) and compared with that of unenhanced sequences (pre/post-HBP analysis) on T1-WI in-phase (T1-IP), out-of-phase (T1-OP), and fat suppression (T1-FS). Lesions were classified as hyper-, iso-, or hypointense on post-HBP, and as decreasing, stable, or increasing SIR on pre/post-HBP analyses. The performance of the different T1-WI sequences for the diagnostic of FNH was evaluated on post-HBP analysis. RESULTS: Twenty-nine FNHs and 33 HCAs were analyzed. On post-HBP analysis, FNHs appeared hyper-/isointense in 89.7% of all T1-WI. HCAs appeared hypointense in 93.9%, 63.6%, and 69.7% of T1-IP, T1-OP, and T1-FS, respectively. FNHs exhibited an increasing SIR in 55.2-58.6%, a stable SIR in 44.8-58.6%, and a decreasing SIR in 0%, whereas HCAs exhibited a decreasing SIR in 66.7-93.9%, a stable SIR in 6.1-33.3%, and an increasing SIR in 0% (p < 0.0001). The specificity of T1-IP was significantly higher than that of T1-OP (p = 0.015) and T1-FS (p = 0.042). CONCLUSION: T1-IP is the most reliable sequence due to misleading tumor/liver signal ratio in the case of fatty liver when using T1-FS or T1-OP. The pre/post-HBP lesion-to-liver SIR is accurate to classify benign hepatocellular lesions and contributes to avoid biopsy. KEY POINTS: •The T1-weighted images in-phase should be systematically included in the HBP-MRI protocol, as it is the most reliable sequence especially in the case of fatty liver. •The comparison between lesion-to-liver signal intensity ratios on unenhanced and at the hepatobiliary phase sequences is useful to classify benign hepatocellular lesions in three categories without misclassification: FNH (increasing signal intensity ratio), HCA (decreasing signal intensity ration), and indeterminate lesions (stable signal intensity ratio).

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.

A-kinase anchor protein 4 precursor (pro-AKAP4) in human spermatozoa.

BACKGROUND: A-kinase anchor protein 4 (AKAP4) and its precursor pro-AKAP4 are two major proteins in spermatozoa of rodents and mammals. Although researchers have characterized the AKAP4 expression in various species, the protein's expression in humans has not been described in detail. OBJECTIVES: The objective of this study was to characterize human pro-AKAP4 more precisely (notably the definition of its localization and expression levels in human spermatozoa and testes). MATERIALS AND METHODS: pro-AKAP4 protein expression levels were assessed by Western blotting. The pro-AKAP4's localization in spermatozoa and testes was determined using immunofluorescence staining and immunogold electron microscopy. Furthermore, pro-AKAP4 protein expression levels were assessed in a series of 77 human semen samples, and associations with semen parameters were evaluated. RESULTS: Western blotting revealed a 100-kDa band in human sperm protein extracts. The pro-AKAP4 was immunolocalized in the fibrous sheath of the flagellum of ejaculated spermatozoa and in elongated spermatids in human testes. A Western blot analysis of 77 normozoospermic semen samples evidenced striking differences in pro-AKAP4 levels from one to another sample (median [interquartile range] integrated optical density = 305 [49-1038]). No correlations were found for pro-AKAP4 levels on one hand and semen volume, sperm concentration, sperm count, sperm motility, or sperm morphology on the other (p > 0.05 for all). However, pro-AKAP4 levels were positively correlated with motility after density gradient centrifugation of the semen (r = 0.224, p = 0.049). DISCUSSION: AKAP4 protein might be activated as an alternative pathway to rescue sperm motility. In human spermatozoa, pro-AKAP4 might therefore be a 'reservoir' of mature AKAP4. CONCLUSION: This study generated new knowledge about pro-AKAP4 in human semen, which may be of interest in the management of male infertility.

First-line treatment using high-flow nasal cannula for children with severe bronchiolitis: Applicability and risk factors for failure.

BACKGROUND: Viral bronchiolitis is the leading cause of hospitalization in children during the first 12 months of life. There is evidence to support the use of noninvasive ventilation in bronchiolitis. A recent respiratory management of bronchiolitis is the use of high-flow nasal cannula (HFNC) therapy. The primary objective of this study was to evaluate the use of HFNC as the first-line treatment for children with severe bronchiolitis and the secondary objective was to identify factors for HFNC therapy failure. METHODS: Observational prospective study in a pediatric intensive care unit (PICU), during two consecutive seasons (2013-2014 without recommendation and 2014-2015 with a study design suggesting HFNC as first-line treatment). The percentages of children treated with HFNC, nasal continuous or biphasic positive airway pressure (nCPAP/BiPAP) and invasive ventilation were compared. Associations between parameters recorded and HFCN therapy failure were established. RESULTS: The percentage of patients treated with HFNC at admission was higher during the second season (90%, n=55/61) than the first season (34%, n=14/41) (p<0.0001). In bivariate analysis, heart rate, pH, and pCO2 were significantly associated with the occurrence of HFNC therapy failure in time-varying Cox regression models using all available values (i.e., admission and repeated measures during the first 5 days of hospitalization). Only pCO2 remained independently associated as a factor of HFNC failure in the multivariate Cox model with a hazard ratio per 5mmHg of 1.37 (95%CI: 1.01-1.87; P=0.046). CONCLUSION: In our PICU, HFNC therapy for children with bronchiolitis can potentially decrease the use of nCPAP. In this study, the factor of failure was higher pCO2. Studies to evaluate PCO2 level to discriminate HFNC versus CPAP indication could be useful.

Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT.

There is no consensus on the type of nutritional support to introduce in children undergoing allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning (MAC). This retrospective, multicenter, observational study compared the early administration of enteral nutrition (EN group, n = 97) versus parenteral nutrition (PN group, n = 97) in such patients with matching for important covariates. The primary endpoint was the study of day 100 overall mortality. The early outcome at day 100 was better in EN group regarding mortality rate (1% vs. 13%; p = 0.0127), non relapse mortality (1% vs. 7%; p = 0.066), acute GVHD grades II-IV (37% vs. 54%; p = 0.0127), III-IV (18% vs. 34%; p = 0.0333) and its gut localization (16% vs. 32%; p = 0.0136). Platelet engraftment was better in EN group than in PN group for the threshold of 20 G/L (97% vs. 80% p < 0.0001) and 50 G/L (92% vs. 78%, p < 0.0001). The length of stay was shorter in EN group (28 vs. 52 days, p < 0.0001). There were no differences between the two groups regarding the polynuclear neutrophil engraftment, infection rate or mucositis occurrence. These results suggest that, in children undergoing MAC allo-SCT, PN should be reserved to the only cases when up-front EN is insufficient or impossible to perform.

Impact of Wilms' tumor 1 expression on outcome of patients undergoing allogeneic stem cell transplantation for AML.

The monitoring of the minimal residual disease by Wilms' tumor 1 expression (MRDWT1) is a standardized test, which can be used in over 80% of patients with AML. To investigate the prognostic value of MRDWT1 in patients undergoing allogeneic stem cell transplantation (allo-SCT) for AML, MRDWT1 was monitored 3 months after transplantation in 139 patients. MRDWT1 positivity did not lead to any therapeutic intervention. Median follow-up was 39.3 (6.4-99.8) months. Patients with positive MRDWT1 at 3 months experienced more often post-transplant relapse (27/30, 90%) than those with negative MRDWT1 (16/109, 14.7%) (P<0.0001). Similarly, a shorter 3-year event-free survival (EFS) was observed in MRDWT1-positive patients (10% vs 72.3% in MRDWT1-negative patients, P<0.0001). The correlation between relapse and MRDWT1 was stronger in blood than in bone marrow samples. Multivariate analysis confirmed the detrimental role of 3-month positive MRDWT1 for relapse (hazard ratio (HR): 15.42; 95% confidence interval (CI): 7.53-31.59; P<0.0001) and EFS (HR: 10.71; 95% CI: 5.41-21.21; P<0.0001). Interestingly, 3-month chimerism was less predictive of relapse than positive MRDWT1. In conclusion, our results demonstrate the usefulness of peripheral blood MRDWT1 monitoring in identifying very high-risk patients, who could benefit from an early preemptive treatment, and those who do not need such an intervention.

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients.

INTRODUCTION: Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. OBJECTIVE: The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. METHODS: Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. RESULTS: The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). CONCLUSION: The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR.

Management of severe fetal anemia by Doppler measurement of middle cerebral artery: are there other benefits than reducing invasive procedures?

OBJECTIVE: Doppler measurement of peak velocity of systolic blood flow in the middle cerebral artery (PVS-MCA) can safely replace invasive testing in the diagnosis of fetal anemia in Rh-alloimmunized pregnancies and PSV-MCA is now the reference technique. However, no study has evaluated its impact in antenatal care and in survival rate. Our objective was to evaluate the impact of the measurement of PVS-MCA in antenatal management and neonatal outcome in maternal red cell alloimmunization requiring in utero transfusion (IUT). STUDY DESIGN: Retrospective study between January 1999 and January 2013. We excluded all cases of hydrops without follow-up before first IUT. From 1999 to 2006, an IUT was indicated on the optical index at 450 nm (Period 1) and was then replaced by the use of PVS-MCA (Period 2). RESULTS: 77 patients were included, 39 in Period 1 (104 IUT) and 38 in Period 2 (89 IUT). 5 cases of hydrops fetalis (12.8%) were diagnosed during the follow up in Period 1 and none during Period 2. The average number of IUT, the delays between 2 IUT and between last IUET and birth were comparable. The total rate of complication per IUT during the first period was 9.6% vs 1.1% during the second one (p=0.01). The overall survival rate in our population was 34/39 (86.8%) during Period 1 vs 38/38 (100%) during Period 2. CONCLUSION: PSV-ACM allowed an improved monitoring with fewer occurrences of hydrops. Conversely, it did not modify antenatal management and timing of delivery.

Long-term outcomes of primary constrained condylar knee arthroplasty.

BACKGROUND: Although constrained condylar knee (CCK) inserts are widely used for total knee arthroplasty (TKA), their long-term outcomes remain unclear. We sought to evaluate patients with at least 10 years' follow-up after CCK TKA to identify potential adverse events (osteolysis, loosening, constraint-mechanism failure), assess functional outcomes with special emphasis on range of motion, and determine prosthesis survival. HYPOTHESIS: Increasing constraint by implantation of a CCK insert does not increase the long-term frequencies of osteolysis or mechanical loosening. MATERIAL AND METHODS: We studied 43 knees after Legacy(®) CCK TKA. The indication was severe deformity (n=20), pre-operative laxity (n=6), or failure to achieve intra-operative balancing (n=17). There were 41 patients with a mean age of 66 years (21-88). A history of one or more surgical procedures was noted for 27 (63%) knees. Outcome measures were the Hospital for Special Surgery (HSS) knee score, Knee Society Score (KSS), and change in the hip-knee-ankle (HKA) angle. Prosthesis survival was assessed using revision surgery for any reason or for reasons other than infection as the censoring criterion. RESULTS: Complications other than venous thrombosis occurred in 16% of patients, including 3 who required revision surgery (septic loosening, n=2; and major instability in a patient with ipsilateral hip arthrodesis). No cases of osteolysis or aseptic loosening were recorded. Mean follow-up was 12.7 years (range, 10-14). At last follow-up, the HSS score had improved from 53 (26-83) pre-operatively to 80 (55-93), the KSS knee component from 42 (16-77) to 90 (77-99), and the KSS function component from 31 (0-80) to 61 (10-90) (P<0.001). Mean range of flexion increased from 109° (50°-140°) to 112° (90°-130°) (P=0.12). The HKA angle changed from 182°±15.5° (150°-210°) to 179.5°±2.5° (174°-184°) (P=0.5). The 11-year prosthesis survival rate was 88.5% (95% confidence interval, 0.69-0.94) overall and 97.7% (0.76-0.99) after excluding the cases of infection. DISCUSSION: Long-term functional gains after CCK TKA were similar to those reported after standard posterior-stabilised TKA, with no cases of constraint-mechanism failure or osteolysis. The complication rate was higher, with decreased survival compared to standard TKA, but the knee deformities and/or instability were particularly severe and two-thirds of knees had a history of one or more surgical procedures.

[Indoor tanning: motivations and beliefs among users and non-users in the population of Lille (Northern France)]. / Cabines de bronzage : étude des motivations et croyances des utilisateurs et non-utilisateurs dans la population lilloise.

BACKGROUND: Uncontrolled use of tanning beds is a major public health problem. The role of UV in skin carcinogenesis has in fact been clearly demonstrated. AIMS: The main purpose of the study was to assess the motivations and beliefs of the population concerning the use of indoor tanning. The secondary objectives were to compare the knowledge of users and non-users and to screen for addiction criteria among users. PATIENTS AND METHODS: This was a transversal descriptive study conducted between April and June 2013 in Lille town center. The motivations of the participants were determined using a multiple-choice questionnaire. A Likert scale was used to assess beliefs and an m-CAGE questionnaire was used to screen for addiction. RESULTS: Of the 200 respondents, 30% (n=60) had used tanning beds in a non-medical setting. The median age of first use was 23 years (15-59). 11.7% of respondents had started before the authorised age of 18 years. "To prepare the skin for exposure to the sun" was the main reason given (68.3%) for use of tanning beds. The population was aware that use of such apparatus favours onset of skin cancer and ageing of the skin. Users were more convinced than non-users that UV cabins "prepare the skin for exposure to the sun" (75% vs. 49.6%, P=0.0009) and that they "favour skin cancer" (56.9% against 36.2%, P=0.0444). Addictive behaviour was detected in 3.3% (2/60) of users. CONCLUSION: Users are aware of the carcinogenic risk of UV cabins but expose themselves to such risk, as they believe it prepares their skin for sun exposure.