Oral gliadin-protected superoxide dismutase in addition to phototherapy for treating non-segmental vitiligo: A 24-week prospective randomized placebo-controlled study.

BACKGROUND: Despite a solid rationale, the usefulness of antioxidants in treating vitiligo has not been clearly demonstrated. Combining superoxide dismutase (SOD) with a wheat gliadin biopolymer protects it during the passage through the gastrointestinal tract. OBJECTIVE: To evaluate the efficacy of gliadin-protected SOD (GP-SOD), associated with narrowband ultraviolet B(NB-UVB), for treating vitiligo. METHODS: We conducted a 24-week monocentric interventional prospective randomized placebo-controlled trial in the tertiary center for vitiligo care in the department of Dermatology of Nice University hospital, Nice, France. Subjects with non-segmental vitiligo affecting more than 5% of the total body surface were included. The subjects received gliadin-protected SOD (GP-SOD; 1 g/day for 12 weeks followed by 0.5 g/day for 12 weeks) or placebo in combination with twice-weekly sessions of NB-UVB. The primary endpoint was the total repigmentation rate at 24 weeks, compared with baseline, as assessed by investigator-assessed Vitiligo Extent Score (VES) on standardized pictures. RESULTS: A total of 50 patients were included. After 24 weeks, a greater improvement in VES was observed in the GP-SOD group (19.85%; SE 4.63, P < 0.0001) compared with the placebo group (8.83%; SE 4.72, P = 0.0676). Tolerance was good in both groups. No related side-effect was reported. CONCLUSIONS: The use of GP-SOD appears to be a useful add-on to phototherapy in the treatment of vitiligo patients.

Evaluation of bladder stimulation as a non-invasive technique for urine collection to diagnose urinary tract infection in infants under 6 months: a randomized multicenter study ("EE-Sti.Ve.N").

BACKGROUND: Febrile urinary tract infection (UTI) is common in infants and needs to be diagnosed quickly. However, the symptoms are non-specific, and diagnosis can only be confirmed after high quality urinalysis. The American Academy of Pediatrics recommends suprapubic aspiration (1-9% contamination) and urinary catheterization (8-14% contamination) for urine collection but both these procedures are invasive. Recent studies have shown a new non-invasive method of collecting urine, bladder stimulation, to be quick and safe. However, few data about bacterial contamination rates have been published for this technique. We hypothesize that the contamination rate of urine collection by bladder stimulation to diagnose febrile UTI in infants under 6 months is equivalent to that of urinary catheterization. METHODS/DESIGN: This trial aims to assess equivalence in terms of bacterial contamination of urinary samples collected by urinary catheterization and bladder stimulation to diagnose UTI. Seven hundred seventy infants under 6 months presenting with unexplained fever in one of four Pediatric Emergency Departments in France will be enrolled. Each child will be randomized into a bladder stimulation or urinary catheterization group. The primary endpoints will be the validity of the urine sample assessed by the presence of contamination on bacterial culture. CONCLUSION: A high recruitment rate is achievable due to the high prevalence of suspected UTIs in infants. The medical risk is the same as that for routine clinical care as we analyze patients with isolated fever. If our hypothesis holds true and the rate of urine contamination collected by bladder stimulation is acceptable, the infants included in the study will have benefited from a non-invasive and reliable means of collecting urine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03801213. Registered on 11 January 2019.

Efficacy and safety data for checkpoint inhibitors in advanced melanoma under real-life conditions: A monocentric study conducted in Nice from 2010 to 2016.

BACKGROUND: Immunotherapies using anti-CTLA4 and anti-PD1 antibodies have revolutionised the management of patients with advanced melanoma. The aim of our study was to analyse the efficacy and safety of immunotherapies in patients with advanced melanoma under real-life conditions. METHODS: We conducted a monocentric, retrospective, observational study that included all patients treated with immunotherapies (ipilimumab, i.e. ipi; nivolumab, i.e. niv and pembrolizumab, i.e. pbr) for advanced melanoma with exclusion of primary mucosal or ocular melanoma. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 110 patients were included. Median PFS was better in the anti-PD1 group than in the anti-CTLA4 group (3.9 months vs. 2.9 months, P=0.025). The frequency of adverse events of any grade was 53.4% with ipi, 66.7% with niv and 75% with pbr. DISCUSSION: Our study shows slightly inferior efficacy data vs. clinical trials of ipi and niv because patients were presenting more severe illness at inclusion. Nevertheless, the study argues in favour of the superiority of anti-PD1 antibodies vs. anti-CTLA4 antibodies in terms of PFS and best overall response. Moreover, our study exhibits safety data comparable to those from clinical trials except for a lower frequency with ipi. CONCLUSION: Our efficacy and safety data obtained under real-life conditions are reassuring since they are consistent with data already published.

Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV-positive persons: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

OBJECTIVES: Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort. METHODS: The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models. RESULTS: Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04-1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04-1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count. CONCLUSIONS: We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

Antiretroviral Regimens and CD4/CD8 Ratio Normalization in HIV-Infected Patients during the Initial Year of Treatment: A Cohort Study.

BACKGROUND: As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. METHODS: We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. RESULTS: 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54-23.2)]. CONCLUSIONS: Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents".

Oxytocin and bone status in men: analysis of the MINOS cohort.

UNLABELLED: Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies. INTRODUCTION: We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men. METHODS: In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk. RESULTS: In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) (r = 0.17, p < 0.001), total or bioavalaible 17ß-estradiol (r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone (r = 0.17, p < 0.001), and leptin (r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04. CONCLUSION: In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies.

[Impact of pulmonary rehabilitation after lung resection for cancer on patients' level of anxiety and depression]. / Impact de la réhabilitation respiratoire sur l'anxiété et la dépression après chirurgie thoracique pour cancer.

INTRODUCTION: Pulmonary rehabilitation (PR) for patients undergoing lung resection for cancer remains controversial. We studied the effects of PR, its impact on quality of life and the level of anxiety and depression. METHODS: In 2011 and 2012, PR was offered to all patients referred to our institution after lung resection for cancer. Patients were evaluated between admission and discharge by a 6 minutes walking test (6MWD), a Visual Analogue Pain Intensity Scale, a quality of life questionnaire (EORTC QLQ C30) and by the Hospital Anxiety and Depression Scale (HAD). The same questionnaires were mailed 6 months after completing PR. RESULTS: Between early 2011 and late 2012, 133 patients were admitted to our institution following lung resection for cancer. Of these, 59 (44%) patients completed PR and returned their questionnaires 6 months after discharge. During PR of these 59 patients, the mean quality of life score increased from 56.3 to 65.9 (P<0.05), the median anxiety score decreased from 5.5 to 4 (P<0.05) and that of depression from 3 to 2 (P<0.05). At 6 months post-discharge, the mean quality of life score remained stable at 66.3 (P=0.8), the median anxiety score reverted to 6 (P<0.05) and the median depression score reverted to 4.5 (P<0.05). CONCLUSION: This observational study during PR, showed that quality of life and the levels of anxiety and depression were improved at the end of the course. After returning home, the average quality of life score remained stable but the level of anxiety and depression increased.

[Elastography shows promise in testicular cancer detection]. / Apport de l'élastographie en temps réel pour la caractérisation des masses testiculaires.

PURPOSE: Elastography is a novel imaging technology that shows promise in the identification of anatomic structures. The widespread use of ultrasound for screening testicular tumors in patients with cancer risk factors highlights unclassified testicular micronodules. We investigated the ability of elastography to accurately diagnose testicular nodules. MATERIAL: Patients with clinical testicular nodules were assigned to undergo elastography in a prospective study. The imaging was carried out by a single radiologist using a static elastography unit with a 9-14MHz frequency linear transducer, to identify hardness score, loss of architecture of testicular parenchyma, and surrounding effect. When orchidectomy was required, the corresponding specimens were subjected to hematoxylin and eosin staining for histologic correlation. RESULTS: We imaged 34 testicular lesions: 26/34 (76%) malignant tumors and 8/34 (24%) non-tumor lesion including 4 hematomas, 3 orchitis and 1 ischemia. Se, Sp, PPV and NPV of hardness in elastography in differentiating between malignant and benign tissue was found to be 96.2%, 37.5%, 83%, and 75%, respectively. Further, for recognizing cancer, the loss of architecture of the testicular parenchyma detecting in elastography was 92.3%, 75%, 92.3%, and 75%, respectively, and the surrounding effect was 84.6%, 87.5%, 95.6% and 63.6%, respectively. CONCLUSION: Elastography may be a promising tool at diagnosing testicular tumor when the loss of architecture and the surrounding effect were present. Further studies are needed to evaluate whether the utility of elastography is worth pursuing to identify of unclassified testicular micronodules. LEVEL OF EVIDENCE: 3.

Dermoscopic features of congenital acral melanocytic naevi in children: a prospective comparative and follow-up study.

BACKGROUND: Acral naevi are a peculiar subtype of naevus with specific dermoscopic patterns. Little is known about congenital melanocytic naevi affecting acral volar skin in children. OBJECTIVES: To determine the dermoscopic features of acquired and congenital acral melanocytic naevi in children and to assess their key differences in this age group. METHODS: This was a prospective observational controlled study conducted in two outpatient dermatology university hospitals in Nice, France. We recruited 24 children with 24 congenital acral melanocytic naevi (CAMNs) and 26 children with 33 acquired acral melanocytic naevi (AAMNs), and determined the clinical and dermoscopic features of both. Images were evaluated and compared by two dermatologists. Fourteen patients with CAMN were followed up. RESULTS: CAMNs were larger, and more asymmetrical and comma shaped than AAMNs. The parallel furrow pattern was predominant in CAMN (75%) and AAMN (79%). Globules were more frequent in CAMN (88%) than in AAMN (61%) (P = 0·026), often with a 'pearl necklace' distribution along skin markings. Central blue-grey pigmentation was present in 50% of CAMNs vs. 9% of AAMNs (P = 0·001). A new dermoscopic feature of central enlarged pink ridges was observed in 54% of CAMNs vs. 6% of AAMNs (P < 0·001). The follow-up of CAMNs did not reveal the appearance of dermoscopic features of melanoma. CONCLUSIONS: CAMNs in children have specific features compared with AAMNs. Our results suggest that small CAMNs need not be excised, but should be followed up.

Treatment of port wine stains with pulsed dye laser and topical timolol: a multicenter randomized controlled trial.

BACKGROUND: Neoangiogenesis occurs within days following laser treatment of port wine stains (PWS), and plays a central role in treatment failures. Topical use of timolol can significantly reduce the production of vascular endothelial growth factor in vitro, and in animal models. OBJECTIVES: The aim of this study was to assess the efficacy of topical timolol in combination with pulsed dye laser (PDL) treatment, compared with PDL alone, for treating PWS. METHODS: This was a prospective multicenter controlled trial performed in children with PWS of the face who had not previously received laser treatment. After randomization, one group was treated with PDL alone, and the other with PDL followed by twice daily applications of timolol gel. Three laser sessions were performed at 1-month intervals with fixed parameters. The evaluation was performed on standardized pictures by two independent physicians blinded to the treatment received. The primary endpoint was marked or complete improvement of the PWS [Investigator Global Assessment (IGA) 3 or 4] 1 month after the third session. RESULTS: Twenty-two children were included. Two patients were lost to follow-up. There was no difference in the success rate between the two groups (IGA 3 or 4 observed in one of 10 patients and two of 12 patients, for PDL alone, and for PDL associated with topical timolol, respectively; P = 1·0). No side-effect related to the application of topical timolol was observed. CONCLUSIONS: The addition of timolol gel for preventing neoangiogenesis failed to significantly improve the efficacy of PDL treatment of PWS.

Impact of systemic treatment of psoriasis on inflammatory parameters and markers of comorbidities and cardiovascular risk: results of a prospective longitudinal observational study.

BACKGROUND: Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood. OBJECTIVES: To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments. METHODS: Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters. RESULTS: Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients. CONCLUSIONS: We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.

[Pulmonary rehabilitation after lung resection for tumor - a feasibility study]. / Intérêt de la réhabilitation respiratoire après résection pulmonaire pour tumeur.

INTRODUCTION: To investigate the safety, feasibility and effectiveness of an inpatient pulmonary rehabilitation program (i-PR) after lung resection (LR) for cancer. METHODS: Between January 2007 and December 2009, we conducted a prospective observational study on patients admitted in our institution. An i-PR was offered to all patients. They completed respiratory function tests and a quality of life (QoL) questionnaire at the start and after completing the i-PR. RESULTS: During the study, 154 out of 175 patients who underwent LR and who were admitted in our center followed an i-PR. The remaining 21 patients were excluded because of emergency re-hospitalisation (10 patients), anticipated departure (six patients) or refusal to participate (five patients). Most functional parameters in the 154 treated patients improved between the beginning and the end of their stay: FVC (69.9% versus 79.6%; P<0.0001); FEV(1) (61.2% versus 69.9%; P<0.0001); timed walk-6MWT (356 m versus 444 m; P<0.0001) and constant work cycle ergometry test (281 s versus 683 s; P<0.0001). Also, the EORTC QLQ-C30 and the EORTC QLQ-LC13 improved during the stay, especially global health status (50.5 versus 64.5; P<0.0001). CONCLUSION: Postoperative PR is safe and could positively impact on functional status and QoL among this population.

Fully covered self-expanding metal stents for benign colonic strictures.

BACKGROUND AND STUDY AIMS: Uncovered self-expanding metal stents offer effective relief for colonic obstruction. The aim of this study was to determine the effectiveness of fully covered self-expanding metal stents (FCSEMSs) in the treatment of benign colonic strictures. PATIENTS AND METHODS: All patients presenting with a symptomatic benign colonic stricture (occlusion or subocclusion) during a 6-year study period were treated with FCSEMSs. The stents were placed and removed 4 - 6 weeks later at one of 10 endoscopy centers. The efficacy of the stent (clinical and radiological signs of colonic decompression within 48 hours), technical success, stent retrieval, safety, and recurrence of symptoms were evaluated during follow-up. Univariate and multivariate analyses were performed to identify variables associated with clinical success, stent migration, and symptom recurrence. RESULTS: The study included 43 patients (24 men, 19 women; mean age 67.6 ± 10.4) with occlusive (n = 18) or subocclusive symptoms (n = 25) due to anastomotic (n = 40), post-ischemic (n = 2), or post-radiation (n = 1) strictures. Insertion was successful in all patients. Clinical success was obtained in 35 patients (81 %). Migration was observed in 27 patients (63 %). The median duration of stenting was 21 days (95 %CI 17.8 - 35.4 days). Multivariate analysis showed that stents more than 20 mm wide migrated significantly less often. Recurrence of obstructive symptoms was observed in 23 patients (53 %), irrespective of migration. No predictive factors for recurrence or clinical efficacy were found. CONCLUSIONS: FCSEMSs for treatment of symptomatic benign colonic strictures are safe and effective, despite a high rate of spontaneous migration.

Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke.

Concerns have arisen about possible effects of protease inhibitors (PIs) on cardiac conductivity. We found no significant association between current or recent PI exposure and sudden death or nonhemorrhagic stroke (adjusted rate ratio, 1.22; 95% confidence interval, .95-1.57), whereas cumulative exposure to PIs was associated with an increased risk (adjusted rate ratio, 1.06 per year of exposure; 95% confidence interval, 1.01-1.11).

Effect of a preceding laser dermabrasion on the outcome of combined therapy with narrowband ultraviolet B and potent topical steroids for treating nonsegmental vitiligo in resistant localizations.

BACKGROUND: The treatment of vitiligo remains unsatisfactory. OBJECTIVES: To assess in patients with vitiligo the effect of a laser dermabrasion in addition to the association of topical steroids and ultraviolet (UV) B in difficult-to-treat areas. METHODS: This was a single-centre prospective randomized trial including patients with nonsegmental vitiligo who had at least two symmetrical lesions located on bony prominences and/or extremities. An erbium laser-assisted dermabrasion was first performed on one side (randomly assigned). After 48 h, hydrocortisone 17-butyrate cream applied daily for three periods of 3weeks followed by a 1-week steroid-free interval and narrowband UVB treatment was performed on both sides twice weekly for 12weeks. The evaluation was performed on standardized pictures by two physicians blinded to the type of treatment received. The criterion of success was a repigmentation of at least 50%, 1month after the end of the treatment. RESULTS: Eighteen patients were included (24 paired lesions treated). Two patients dropped out for personal reasons. Almost 50% of lesions achieved at least 50% repigmentation in the dermabrasion side while only 4·2% did so with topical steroids and UVB alone (P<10(-4) ). Side-effects were delayed healing, pain and two hypertrophic scars. The tolerance and patient satisfaction were 4·2 and 4/10 for the laser-treated side and 8·4 and 3/10 in the UVB+ steroids alone group, respectively. CONCLUSIONS: Laser dermabrasion significantly improves the repigmentation rate in vitiligo lesions. Despite a high rate of repigmentation in such difficult-to-treat areas the high rate of side-effects and the poor tolerance strongly limit its use in current practice.

[Management of delivery after previous caesarean section in France]. / État des lieux en France de la prise en charge des utérus cicatriciels.

UNLABELLED: Since many years, caesarean section rate has increased in France. The purpose of the study was to compare the different French obstetrical attitudes after a prior caesarean section. METHODS: This retrospective study was performed between March 2008 and February 2010. We collected the answers of a majority of maternity centres contacted with an anonymous questionnaire sent by postal, electronic, fax mails. RESULTS: Of the 194 maternity centres which have responded, there were 37 university hospitals and 312 obstetricians: 75.6% of them worked in public sector and 19.2% in private one. The use of a protocol is registered for 29.6% of questioned obstetricians (only 14% in private sector, P=0.002). Pelvimetry is consistently proposed by 44.4% of them. A trial of labour in case of breech presentation is proposed by 20% of questioned obstetricians, with twin pregnancies by 23.7%, with two prior low-transverse caesarean delivery by 12%, most in university hospitals, level III, with more than 1500 births per year. Induction of labour is allowed by 73.9% of questioned obstetricians, by ocytocics as a majority. Induction by Prostine(®) is underwent by 14.5% of them (24.6% in academic centres, P=0.01), by Propess(®) by 19.2% of them (30% in university hospitals, P=0.008). CONCLUSION: These findings showed that the management of delivery after caesarean section is associated with statistically significant differences in France. These informations are relevant for counselling French obstetrical practices.