Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass at 5 years (YOMEGA): a prospective, open-label, non-inferiority, randomised extension study.

BACKGROUND: The multicentre randomised trial YOMEGA (NCT02139813) comparing the one anastomosis gastric bypass (OAGB) with the Roux-en-Y gastric bypass (RYGB) confirmed the non-inferiority of OAGB on weight loss outcomes at 24 months. We aimed to report weight loss, metabolic, and safety outcomes at 5 years. METHODS: YOMEGA is a prospective, open-label, non-inferiority, randomised trial conducted at nine centres in France. Inclusion criteria were BMI of 40 kg/m2 or more, or 35 kg/m2 or more with comorbidities. Key exclusion criteria were severe gastro-oesophageal reflux disease or Barrett's oesophagus and previous bariatric surgery. Patients were randomly assigned (1 :1) to OAGB (one gastrojejunal anastomosis with a 200 cm biliopancreatic limb) or RYGB (with a 150 cm alimentary limb and a 50 cm biliary limb), stratified by centre, with blocks of variable size. The primary endpoint of this extension study was percentage excess BMI loss and was analysed in the per-protocol population, including patients with data who were operated on with the technique randomly assigned to them and excluding patients with major deviations from the protocol during the follow-up (change of surgical technique, death, or withdrawal of consent). Non-inferiority was concluded for the primary endpoint if the upper bound of the CI was less than the non-inferiority limit (7 percentage points). YOMEGA is registered with ClinicalTrials.gov, NCT02139813, and the 5-year follow-up of YOMEGA is registered with ClinicalTrials.gov, NCT05549271. FINDINGS: Between May 13, 2014, and March 2, 2016, 253 patients were randomly assigned to OAGB (n=129) or RYGB (n=124), and from these patients 114 in the OAGB group and 118 in the RYGB group were included in the per-protocol analysis. In the per-protocol population, at baseline, mean age was 43·0 years (SD 10·8), mean BMI was 44·0 kg/m2 (5·6), 54 (23%) patients were male and 178 (77%) were female; 55 (27%) of 207 patients had type 2 diabetes. After 5 years, mean percentage excess BMI loss was -75·6% (SD 28·1) in the OAGB group versus -71·4% (SD 29·8) in the RYGB group, confirming non-inferiority (mean difference -4·1% [90% CI -12·0 to 3·7], p=0·0099). Remission of type 2 diabetes was similar in both groups. Nutritional status did not differ; the most common adverse event was clinical gastro-oesophageal reflux disease, occurring in 27 (41%) of 66 patients in the OAGB group versus 14 (18%) of 76 patients in the RYGB group (p=0·0030). Among serious adverse events, ten (8%) of 127 patients converted from OAGB to RYGB. 171 (68%) of 253 patients were followed up. INTERPRETATION: OAGB was not inferior to RYGB regarding percentage excess BMI loss at 5 years with similar metabolic outcomes. The high rate of clinical gastro-oesophageal reflux disease after OAGB raises questions about its long-term consequences, which need to be further investigated. FUNDING: Medtronic.

Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.

BACKGROUND: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD). OBJECTIVES: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs. METHODS: We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 µg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success. RESULTS: Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6). DISCUSSION: Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted. TRIAL REGISTRATION: The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018.

Avelumab in patients with gestational trophoblastic tumors with resistance to polychemotherapy: Cohort B of the TROPHIMMUN phase 2 trial.

PURPOSE: There is a need for innovative treatments in women with gestational trophoblastic tumors (GTT) resistant to chemotherapy. The TROPHIMMUN trial assessed the efficacy of avelumab in patients with resistance to single-agent chemotherapy (cohort A), or to polychemotherapy (cohort B). Cohort B outcomes are reported here. METHODS: In the cohort B of this phase 2 multicenter trial (NCT03135769), women with GTT progressing after polychemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. The primary endpoint was the rate of hCG normalization enabling treatment discontinuation (2-stage Simon design). RESULTS: Between February 2017 and August 2020, 7 patients were enrolled. Median age was 37 years (range: 29-47); disease stage was I or III in 42.9% and 57.1%; FIGO score was 9-10 in 28.6%, 11 in 28.6%, and 16 in 14.3%, respectively. Median follow-up was 18.2 months. One patient (14.3%) experienced hCG normalization enabling treatment discontinuation. However, resistance to avelumab was observed in the remaining 6 patients (85.7%). The cohort B was stopped for futility. Grade 1-2 treatment-related adverse events occurred in 57.1%, most commonly fatigue (42.9%), nausea, diarrhea, infusion-related reaction, muscle pains, dry eyes (each 14.3%). The median resistance-free survival was 1.4 months (95% CI 0.7-5.3). CONCLUSIONS: Although avelumab is active in patients with single-agent chemotherapy-resistant GTT (cohort A), it was associated with limited efficacy in patients with resistance to polychemotherapy (cohort B). The prognosis of patients with polychemotherapy resistance remains poor, and innovative immunotherapy-based therapeutic combinations are needed.

Slowly absorbable mesh versus standard care in the management of contaminated midline incisional hernia (COMpACT-BIO): a multicentre randomised controlled phase III trial including a health economic evaluation.

INTRODUCTION: Incisional hernia (IH) is the most frequent mid-term and long-term complication after midline laparotomy. The current standard treatment includes repair using a mesh. In a contaminated field, the use of a non-absorbable mesh increases the risk of surgical site infection and the costs. Slowly absorbable meshes are safe in contaminated fields, but no data have been reported regarding their long-term recurrence rate. COMpACT-BIO is a multicentre prospective randomised controlled phase III trial designed to compare the 3-year recurrence rate in patients undergoing contaminated IH repair with either a slowly absorbable mesh or standard care. METHODS: In patients undergoing midline IH repair in a contaminated surgical field (grade III of the modified Ventral Hernia Working Group classification), the COMpACT-BIO study compares the use of a slowly absorbable mesh with that of conventional care according to standardised surgical procedures (primary closure, non-absorbable synthetic mesh or biologic mesh, at the discretion of the surgeon). Randomisation is done during surgery before closure the fascia with an allocation ratio of 1:1. The choice of the slowly absorbable mesh is left to the criteria of each centre. The primary endpoint is the proportion of patients with scan-confirmed IH recurrence within 3 years after repair. ETHICS/DISSEMINATION: This trial is conducted in compliance with international standards for research practice and reporting. Written informed consent will be obtained from patients prior to inclusion. All data were identified and anonymised prior to analysis. The protocol has been approved by an Institutional Review Board (2020-A0823-36/SI:20.07.03.66831), and will be conducted in compliance with the CONSORT (Consolidated Standards of Reporting Trials) statement. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. PROTOCOL VERSION: Version 2-13 October 2020. TRIAL REGISTRATION NUMBER: NCT04597840.

Multiprofessional intervention to improve adherence to medication in stroke patients: a study protocol for a randomised controlled trial (ADMED AVC study).

INTRODUCTION: Adherence to secondary preventive medications is often suboptimal in patients with stroke, exposing them to an increased risk of recurrent cerebral and/or cardiovascular events. Effective actions in the long term to improve adherence to medication are needed. The study will evaluate the efficacy of a collaborative multiprofessional patient-centred intervention conducted by a pharmacist on adherence to secondary preventive medication in stroke survivors. METHODS AND ANALYSIS: This is a multicentre cluster-randomised controlled trial. Two groups of 91 patients (intervention vs standard care) will be recruited. The clinical pharmacist intervention targeting secondary preventive medication will consist of three parts over 1 year: (1) an individual semi-structured interview at hospital discharge; (2) follow-up telephone interviews at 3, 6 and 9 months after discharge; and (3) a final individual semi-structured interview 1 year after discharge. Information on patient follow-up will be shared with the general practitioner and the community pharmacist by sending a report of each interview. The primary outcome is adherence to medication during the 12 months after hospital discharge, assessed using a composite endpoint: the medication possession ratio associated with a self-administered questionnaire. ETHICS AND DISSEMINATION: The local ethics committee, the national committee for use of personal data in medical research and the national data protection agency approved the study. The sponsor has no role in study design; collection, analysis and interpretation of data; or report writing. DISCUSSION: This pharmacist-led educational programme has the potential to significantly improve adherence to medication in stroke survivors which could lead to a decrease in recurrent cerebral and/or cardiovascular events. TRIAL REGISTRATION NUMBER: NCT02611440.

Effects of prismatic adaptation on balance and postural disorders in patients with chronic right stroke: protocol for a multicentre double-blind randomised sham-controlled trial.

INTRODUCTION: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion. METHODS AND ANALYSIS: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index). ETHICS AND DISSEMINATION: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke. TRIAL REGISTRATION NUMBER: NCT03154138.

Prostate hypofractionated radiotherapy (62Gy at 3.1Gy per fraction) with injection of hyaluronic acid: final results of the RPAH1 study.

OBJECTIVES: The present multicenter Phase II study evaluated the rate of late grade ≥2 gastrointestinal (GI) toxicities at 3 years, after hypofractionated radiotherapy (HFR) of prostate cancer with injection of hyaluronic acid (HA) between the prostate and the rectum. METHODS: Between 2010 and 2013, 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT. 20 fractions of 3.1 Gy were delivered, 5 days per week for a total dose of 62 Gy. A transperineal injection of 10cc of HA was performed between the rectum and the prostate. Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4). RESULTS: Median pretreatment prostate-specific antigen was 8 ng ml-1. Among the 36 included patients, 2 were not evaluated because they withdrew the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed.Late grade ≥2 GI toxicities occurred in 4 (12%) patients with 3 (9%) Grade 2 rectal bleedings and one diarrhoea. Therefore, the inefficacy hypothesis following Fleming one-stage design cannot be rejected. None of the patients experienced late Grade 3-4 toxicities. Among the 30 patients completing the 36 months' visit, none still had a grade ≥2 GI toxicity. Late grade ≥2 genitourinary (GU) toxicities occurred in 14 (41%) patients. The most frequent toxicities were dysuria and pollakiuria. Four patients still experienced a grade ≥2 GU toxicity at 36 months.The biochemical relapse rate (nadir +2 ng ml-1) was 6% (2 patients). Overall, HA was very well tolerated with no pain or discomfort. CONCLUSION: Despite the inefficacy of HA injection was not rejected, we observed the absence of Grade 3 or 4 rectal toxicity as well as a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up. Late urinary toxicities are the most frequent but the rate decreases largely at 3 years. ADVANCES IN KNOWLEDGE: With an injection of HA, hypofractionated irradiation in 4 weeks is well tolerated with no Grade 3 or 4 GI toxicity and a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up.

Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France.

The Rhône-Loire metropolitan areas' 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Quality of life in patients with uveitis: data from the ULISSE study (Uveitis: cLInical and medico-economic evaluation of a Standardised Strategy for the Etiological diagnosis).

AIMS: To assess vision-related (VR-QOL) and health-related quality of life (HR-QOL) in a large series of patients with de novo uveitis at baseline and 6-month follow-up. METHODS: Non-inferiority, prospective, multicentre, cluster randomised controlled trial registered under the Unique Identifier: NCT01162070. VR-QOL and HR-QOL were assessed by the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and the Medical Outcomes Study 36-item Short Form Survey (SF-36). RESULTS: At inclusion, 466 patients completed the VFQ-25. The mean composite score was 80.0 (±16.7). In multivariate analysis, higher age, female sex and insidious onset were significantly associated with lower QOL. At 6 months, 138 patients completed the VFQ-25, with a significantly higher mean composite score of 82.6 (±16.7). SF-36 mental component was 42.9 (±11.3) and physical component was 47.2 (±8.5) at inclusion (n=425). HR-QOL improvement at 6 months was not clinically significant. CONCLUSION: QOL seems relatively well preserved in this cohort; only VR-QOL improved significantly at 6 months, especially in patients with low initial visual acuity.

Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial.

PURPOSE: Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT. METHODS: In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design). RESULTS: Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%). CONCLUSION: In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.

O6-methylguanine-DNA methyltransferase (MGMT) status in neuroendocrine tumors: a randomized phase II study (MGMT-NET).

INTRODUCTION: Neuroendocrine tumors (NETs) are rare, but their incidence is rising. Alkylating agents (ALKY), temozolomide and streptozotocin, are the main chemotherapies used for advanced pancreatic NETs. According to retrospective data, O6-methylguanine-DNA methyltransferase (MGMT) status appears to be a predictive factor of the response to ALKY. AIMS: The main objective is to evaluate the value of tumor MGMT promoter (pMGMT) methylation in the prediction of the objective response (OR) at 3 months in patients treated with ALKY. Secondly, we will evaluate the value of MGMT immunohistochemistry and the efficacy of treatment with ALKY vs. oxaliplatin-based chemotherapy (Ox). MATERIALS AND METHODS: A national, prospective, open-label, randomized, controlled and multicenter trial was designed. Main inclusion criteria are: adult patients with well-differentiated advanced duodeno-pancreatic, lung, or unknown primitive NETs with a validated indication for chemotherapy. pMGMT methylation will be assessed by pyrosequencing, but an ancillary study will compare this technique with others ones including MGMT immunohistochemistry. RESULTS: A total of 104 patients will be randomly assigned (1:1 for unmethylated or 2:1 for methylated pMGMT NETs) to either the ALKY arm or to the Ox arm. CONCLUSION: Recruitment started on October 16, 2018 (NCT03217097) and will be open in 21 centers in France.

Toe dystonia in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation.

BACKGROUND: Off state toe dystonia (TD) is a symptom frequently encountered in Parkinson's disease (PD), but little is known about its evolution after subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVE: To analyze the prevalence and the evolution of TD in PD patients candidate to STN-DBS. METHODS: Individual data of consecutive 130 PD patients who underwent STN-DBS between 2010 and 2015 were collected. RESULTS: Data were successfully collected in 95 patients. TD affect 45.3% of the patients in our cohort. TD was present in 32.7% of patients before surgery and was alleviated by STN-DBS in 48% of the cases. Motor improvement provided by STN-DBS, levodopa-equivalent treatment diminution after surgery, disease duration or age at the time of surgery were not predictive of TD evolution. A younger age at PD diagnosis was significantly associated with TD resolution. CONCLUSION: STN-DBS is partially efficient for TD but its evolution seems independent of significant predictive factors.

Pregnancy Outcomes in French Hemodialysis Patients.

BACKGROUND: Pregnancy in hemodialysis (HD) women is a rare event and often associated with maternal and fetal complications. Scarcity of available data from large cohorts impedes fair medical counseling. METHODS: This is a descriptive, retrospective, multi-centric study. Pregnant women on HD during the period from 1985 to 2015 in France were included. The primary outcome was a living infant discharged from hospital, while secondary outcomes included gestational age and birth weight. RESULTS: We identified 100 pregnancies in 84 women on HD, from 41 centers. Chronic HD was initiated during pregnancy for 17.7% (14/79) of patients explaining a 19.8% prevalence of catheter (19/96) and a preserved residual diuresis for 50% of pregnancy (43/86). Seventy-six (89.4%) women performed daily dialysis during the third trimester (6 times per week). Our primary outcome was met for 78% of newborns with a mean gestational age of 33.2 ± 3.9 weeks and a mean birth weight of 1,719 ± 730 g. CONCLUSIONS: Our study is one of the largest series of -pregnancies in HD patients. Despite recent progresses, these pregnancies remain at high risk, reinforcing the need for an early nephrologist-obstetrician skilled team co-management.

Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis).

PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.

Randomized Controlled Trial Evaluating a Standardized Strategy for Uveitis Etiologic Diagnosis (ULISSE).

PURPOSE: To prospectively assess the efficiency of a standardized diagnostic approach, compared to an open strategy, for the etiologic diagnosis of uveitis. DESIGN: Noninferiority, prospective, multicenter, clustered randomized controlled trial. METHODS: Consecutive patients with uveitis, who visited 1 of the participating departments of ophthalmology, were included. In the standardized group, all patients had a minimal evaluation regardless of the type of uveitis (complete blood count, erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test, syphilis serology, and chest radiograph) followed by more complex investigations according to ophthalmologic findings. In the open group, the ophthalmologist could order any type of investigation. Main outcome was the percentage of etiologic diagnoses at 6 months. RESULTS: Nine hundred and three patients with uveitis were included from January 2010 to May 2013 and the per-protocol population comprised 676 patients (open 373; standardized 303). Mean age at diagnosis was 46 years. Anatomic distribution of uveitis was as follows: anterior (60.8% and 72.3%, P = .0017), intermediate (11.7% and 12.3%, P = .8028), posterior (17.8% and 8.2%, P = .0004), and panuveitis (15.3% and 15.2%, P = .9596). An etiologic diagnosis was established in 54.4% of cases in the open group and 49.5% in the standardized group (P = .2029). The difference between both strategies (standardized minus open) was -4.9% (95% CI [-12.5%; 2.6%]). There were more investigations in the open group than in the standardized group (5371 vs 3759, P < .0001). CONCLUSION: The standardized strategy appears to be an efficient diagnostic approach for the etiologic diagnosis of uveitis, although its noninferiority cannot be proved.

Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

PURPOSE: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. METHODS AND MATERIALS: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. RESULTS: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. CONCLUSIONS: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

Local recurrence after radical nephrectomy for kidney cancer: management and prediction of outcomes. a multi-institutional study.

BACKGROUND: Local recurrence (LR) after radical nephrectomy (RN) for kidney cancer is uncommon. Our objectives were to analyse characteristics and therapeutic options of LR after RN and to identify survival prognostic factors. MATERIALS AND METHODS: From a multi-institutional retrospective database, we identified 72 patients who experienced LR after RN. RESULTS: Mean time to LR was 26.5 ± 3.3 months. The location of the recurrence was renal fossa, regional lymph node, homolateral adrenal and both renal fossa and regional lymph node for 43 (59.7%), 27 (37.5%), 9 (12.5%) and 7 (9.7%) patients, respectively. Patients were treated by surgery, systemic therapies, combination of therapies and palliative treatment in 24 (33.3%), 18 (25%), 24 (33.3%) and 6 (8.4%) cases, respectively. Within a mean follow-up of 26.4 ± 3.3 months from the date of local recurrence, 12 (16.6%) patients were alive without disease, 30 (41.7%) patients were alive with disease, 30 patients (41.6%) died including 28 (38.8%) from the disease. In multivariate analysis, time to recurrence <1 year (P < 0.001; HR: 4.81) and surgical treatment (P = 0.027; HR: 0.33) were predictive factors. CONCLUSIONS: Local recurrence after radical nephrectomy is associated with poor prognosis. The time to recurrence and the completeness of the surgical treatment are major prognostic factors.