Publications by authors named "Julien Berthiller"

60 Publications

Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.

Acta Neurochir (Wien) 2021 Mar 2. Epub 2021 Mar 2.

Service de Neurologie C, Centre Expert Parkinson, Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Hospices Civils de Lyon, 69003, Lyon, France.

Background: Several surgical methods are used for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). This study aimed to compare clinical outcomes and electrode placement accuracy after robot-assisted (RAS) versus frame-based stereotactic (FSS) STN DBS in Parkinson's disease.

Methods: In this single-center open-label study, we prospectively collected data from 48 consecutive PD patients who underwent RAS (Neuromate®; n = 20) or FSS (n = 28) STN DBS with the same MRI-based STN targeting between October 2016 and December 2018 in the university neurological hospital of Lyon, France. Clinical variables were assessed before and 1 year after surgery. The number of electrode contacts within the STN was determined by merging post-operative CT and pre-operative MRI using Brainlab® GUIDE™XT software.

Results: One year after surgery, the improvement of motor manifestations (p = 0.18), motor complications (p = 0.80), and quality of life (p= 0.30) and the reduction of dopaminergic treatment (p = 0.94) and the rate of complications (p = 0.99) were similar in the two groups. Surgery duration was longer in the RAS group (p = 0.0001). There was no difference in the number of electrode contacts within the STN.

Conclusion: This study demonstrates that RAS and FSS STN DBS for PD provide similar clinical outcomes and accuracy of electrode placement.
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http://dx.doi.org/10.1007/s00701-021-04790-7DOI Listing
March 2021

Patients with acute heart failure treated with the CARRESS-HF diuretic protocol in association with canrenoate potassium: Tolerance of high doses of canrenoate potassium.

Arch Cardiovasc Dis 2020 Nov 15;113(11):679-689. Epub 2020 Sep 15.

Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France.

Background: Oral mineralocorticoid receptor antagonists have failed to prove their efficacy for decongestion and potassium homeostasis in acute heart failure. Intravenous mineralocorticoid receptor antagonists have yet to be studied.

Aim: The aim of this study was to confirm the safety of high-dose potassium canrenoate in association with classic diuretics in acute heart failure.

Methods: This retrospective single-centre study included consecutive patients who were hospitalized with acute heart failure between 2013 and 2018. One hundred patients with overload treated with the standardized diuretic protocol from the CARRESS-HF trial were included. There were no exclusion criteria relating to creatinine or kalaemia at the time of admission. Two groups were constituted on the basis of potassium canrenoate posology: a low-dose group (<300mg/day) and a high-dose group (≥300mg/day); the groups were similar in terms of baseline characteristics.

Results: Mean daily potassium canrenoate doses were 198mg/day (range 100-280mg/day) in the low-dose group and 360mg/day (range 300-600mg/day) in the high-dose group. There was no significant difference between the high-dose and low-dose groups in terms of mortality, dialysis, renal function, hyperkalaemia, haemorrhage, sepsis or confusion.

Conclusions: Potassium canrenoate at high doses can be used safely in association with standard diuretics in acute heart failure, even in patients with altered renal function. A prospective study is required to evaluate the efficacy of high-dose potassium canrenoate in preventing hypokalaemia and improving decongestion.
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http://dx.doi.org/10.1016/j.acvd.2020.05.017DOI Listing
November 2020

Hemodynamic Response to Treatment and Outcomes in Pulmonary Hypertension Associated With Interstitial Lung Disease Versus Pulmonary Arterial Hypertension in Systemic Sclerosis: Data From a Study Identifying Prognostic Factors in Pulmonary Hypertension Associated With Interstitial Lung Disease.

Arthritis Rheumatol 2021 02 29;73(2):295-304. Epub 2020 Dec 29.

Hospices Civils de Lyon, Centre de Référence National des Maladies Pulmonaires Rares, Centre de Compétence de l'Hypertension Pulmonaire, Hôpital Louis Pradel, UMR 754, Université Claude Bernard Lyon 1, OrphaLung, RespiFil, and ERN-LUNG, Lyon, France.

Objective: Patients with systemic sclerosis and both pulmonary hypertension and interstitial lung disease (SSc-PH-ILD) generally carry a worse prognosis than patients with SSc and pulmonary arterial hypertension (SSc-PAH) without ILD. There is no evidence of the efficacy of PAH therapies in SSc-PH-ILD. We undertook this study to compare survival of and response to treatment in patients with SSc-PH-ILD and those with SSc-PAH.

Methods: We analyzed 128 patients (66 with SSc-PH-ILD and 62 with SSc-PAH) from 15 centers, in whom PH was diagnosed by right-sided heart catheterization; they were prospectively included in the PH registry. All patients received PAH-specific therapy. Computed tomography of the chest was used to confirm or exclude ILD.

Results: At baseline, patients with SSc-PH-ILD had less severe hemodynamic impairment than those with SSc-PAH (pulmonary vascular resistance 5.7 Wood units versus 8.7 Wood units; P = 0.0005) and lower diffusing capacity for carbon monoxide (median 25% [interquartile range (IQR) 18%, 35%] versus 40% [IQR 31%, 51%]; P = 0.0005). Additionally, patients with SSc-PH-ILD had increased mortality (8.1% at 1 year, 21.2% at 2 years, and 41.5% at 3 years) compared to those with SSc-PAH (4.1%, 8.7%, and 21.4%, respectively; P = 0.04). Upon treatment with PAH-targeted therapy, no improvement in the 6-minute walk distance was observed in either group. Improvement in the World Health Organization functional class was observed less frequently in patients with SSc-ILD-PH compared to those with SSc-PAH (13.6% versus 33.3%; P = 0.02). Hemodynamics improved similarly in both groups.

Conclusion: ILD confers a worse prognosis to SSc-PH. Response to PAH-specific therapy is clinically poor in SSc-PH-ILD but was not found to be hemodynamically different from the response observed in SSc-PAH.
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http://dx.doi.org/10.1002/art.41512DOI Listing
February 2021

Association of characteristics of tampon use with menstrual toxic shock syndrome in France.

EClinicalMedicine 2020 Apr 10;21:100308. Epub 2020 Mar 10.

Centre National de Référence de Staphylocoques - Institut des Agents Infectieux, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.

Background: Menstrual tampons are widely used in western countries. Indirect evidence suggests that tampon misuse could be associated with an increased risk of menstrual toxic shock syndrome (MTSS). The aim of this study was to determine what characteristics of tampon use are associated with increased risk of menstrual toxic shock syndrome (MTSS).

Methods: A nationwide, case-control study in France, was conducted with women that use tampons with MTSS diagnoses according to the CDC diagnostic criteria ( = 55, from January 2011, to December 2017) and a control group of women with no MTSS history ( = 126, from February to December 2017). Information regarding tampon use during a 6-month period was collected. Associations between tampon use and MTSS were assessed using logistic regression models stratified by residential area.

Findings: Compared to controls, women diagnosed with MTSS more frequently reported maximum tampon wear of >6 h (62% vs. 41%;  = 0.02), overnight tampon use (77% vs. 54%;  0.006), and neither read nor followed tampon instructions in case of reading (65% vs. 42%;  0.006). In univariate analysis, MTSS risk was two-fold higher with tampon use for >6 consecutive hours (odds ratio, 2.3 [95% CI, 1.2-4.5]), and three-fold higher with tampon use during sleep for >8 h (odds ratio, 3.2 [95% CI, 1.4-7.7]). In multivariate logistic regression analysis, only maximum tampon use for >6 h (odds ratio, 2.03 [95% CI, 1.04-3.98]), and neither read nor followed the tampon instructions in case of reading (odds ratio, 2.25 [95% CI, 1.15-4.39]) were independently associated with MTSS.

Interpretation: Our study suggests that the risk of MTSS was associated with using tampons for more than 6 h, overnight tampon use during sleep, and neither read nor followed tampon insertion instructions in case of reading.

Funding: LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon within the programme "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).
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http://dx.doi.org/10.1016/j.eclinm.2020.100308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201028PMC
April 2020

Symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments.

Eur J Emerg Med 2020 Oct;27(5):338-343

Service d'Accueil des Urgences, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon.

Objective: The aim of our study was to assess anxiety and depression in patients' relatives after a decision of withholding and withdrawing life-sustaining treatments.

Methods: We conducted a prospective observational multicenter study in three university hospitals' emergency departments. The Hospital Anxiety and Depression Scale (HADS) was assessed on the relatives of patients admitted in emergency departments 3 days and 21 days after the decision of withholding or withdrawing life-sustaining treatments.

Results: Among the 109 patients with a decision of withholding or withdrawing life-sustaining treatments, 88 relatives were included and 74 (67, 8%) completed the 21-day follow up. Among those, 14 (18.9%) and 13 (17.6%) displayed symptoms of anxiety and depression at 3 days, respectively. After 21 days, symptoms anxiety and depression were still present in the same way for nine (12.2%) of the relatives. The median total HADS score was 13.5 [interquartile range (IQR): 8-16] at 3 days and 10 [IQR: 5-17] at 21 days. The symptoms of depression at 21 days were more frequent for the relatives of patients who died at 21 days (P = 0.03).

Conclusion: We found symptoms of anxiety and depression in relatives after decisions of withholding and withdrawing life-sustaining treatments in emergency departments, which persist at 21 days. Further studies are needed to support these results and to search the relatives at risk to develop these symptoms.
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http://dx.doi.org/10.1097/MEJ.0000000000000669DOI Listing
October 2020

Poor Involvement of General Practitioners in Decisions of Withholding or Withdrawing Life-Sustaining Treatment in Emergency Departments.

J Gen Intern Med 2020 01 4;35(1):177-181. Epub 2019 Nov 4.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Accueil des urgences, 5 place d'Arsonval, F-69003, Lyon, France.

Background: Decisions of withholding or withdrawing life-sustaining treatment are frequent in emergency departments (ED) and patients are often unable to communicate their wishes concerning end of life desires.

Objective: To evaluate the participation of general practitioners (GPs) during the decision-making process of withholding or withdrawing life-sustaining treatments in ED.

Design: Prospective observational multicenter study.

Patients: We included patients for whom a decision of withdrawing or withholding life-sustaining treatments was made in ED. For each patient, we enrolled one general practitioner.

Main Measures: GPs were interviewed about their perception of end of life patient's management and the communication with ED and families.

Key Results: There were 109 potential patient participants. We obtained answers from 54 (49.5%) of the patient's associated GPs. Only 4 (7.4%) GPs were involved during the decision-making process of withholding or withdrawing life-sustaining treatments. Among GPs, 29 (53.7%) were contacted by family after the decision, most often to talk about their difficult experience with the decision. A majority (94%) believed their involvements in these decisions were important and 68% wished to "always" participate in end of life decisions despite the fact that they usually don't participate in these decisions. Finally, 66% of GPs believed that management of end of life in the emergency department was a failure and should be anticipated.

Conclusions: GPs would like to be more involved and barriers to GP involvement need to be overcome. We do not have any outcome data to suggest that routine involvement of GPs in all end of life patients improves their outcomes. Moreover, it requires major system and process-based changes to involve all primary care physicians in ED decision-making.

Nih Trial Registry Number: NCT02844972.
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http://dx.doi.org/10.1007/s11606-019-05464-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957665PMC
January 2020

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

Cancer Epidemiol 2019 12 3;63:101615. Epub 2019 Oct 3.

Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States. Electronic address:

Background: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk.

Methods: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models.

Results: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed.

Conclusions: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.
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http://dx.doi.org/10.1016/j.canep.2019.101615DOI Listing
December 2019

Difficulty of the decision-making process in emergency departments for end-of-life patients.

J Eval Clin Pract 2019 Dec 9;25(6):1193-1199. Epub 2019 Jul 9.

Hospices Civiles de Lyon, Hôpital Edouard Herriot, Service d'Accueil des urgences, 5 place d'Arsonval, Lyon, F-69003, France.

Background: In emergency departments, for some patients, death is preceded by a decision of withholding or withdrawing life-sustaining treatments. This concerns mainly patients over 80, with many comorbidities. The decision-making process of these decisions in emergency departments has not been extensively studied, especially for noncommunicating patients.

Aim: The purpose of this study is to describe the decision-making process of withholding and withdrawing life-sustaining treatments in emergency departments for noncommunicating patients and the outcome of said patients.

Design: We conducted a prospective multicenter study in three emergency departments of university hospitals from September 2015 to January 2017.

Results: We included 109 patients in the study. Fifty-eight (53.2%) patients were coming from nursing homes and 52 (47.7%) patients had dementia. Decisions of withholding life-sustaining treatment concerned 93 patients (85.3%) and were more frequent when a surrogate decision maker was present 61 (65.6%) versus seven (43.8%) patients. The most relevant factors that lead to these decisions were previous functional limitation (71.6%) and age (69.7%). Decision was taken by two physicians for 80 patients (73.4%). The nursing staff and general practitioner were, respectively, involved in 31 (28.4%) and two (1.8%) patients. A majority of the patients had no advance directives (89.9%), and the relatives were implicated in the decision-making process for 96 patients (88.1%). Death in emergency departments occurred for 47 patients (43.1%), and after 21 days, 84 patients (77.1 %) died.

Conclusion: There is little anticipation in end-of-life decisions. Discussion with patients concerning their end-of-life wishes and the writing of advance directives, especially for patients with chronic diseases, must be encouraged early.
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http://dx.doi.org/10.1111/jep.13229DOI Listing
December 2019

Ziconotide for spinal cord injury-related pain.

Eur J Pain 2019 10 29;23(9):1688-1700. Epub 2019 Aug 29.

Neurosurgical Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Lyon 1 University, Lyon, France.

Background: Central neuropathic pain related to spinal cord injury is notoriously difficult to treat. So far most pharmacological and surgical options have shown but poor results. Recently ziconotide has been approved for use both neuropathic and non-neuropathic pain. In this cohort study, we assessed responder rate and long-term efficacy of intrathecal ziconotide in patients with pain related to spinal cord injury.

Methods: Patients presenting chronic neuropathic related to spinal cord lesions that was refractory to medical pain management were considered for inclusion. Those accepting were tested by lumbar puncture injection of ziconotide or continuous intrathecal infusion and if a significant decrease in pain scores (>40%) was noted they were implanted with a continuous infusion pump. They were then followed up for at least 1 year with constant assessment of the evolution of pain and side effects.

Results: Out of the 20 patients tested 14 had a decrease in pain scores of more than 40% but only 11 (55%) were implanted with permanent pumps due to side effects and patient choice. These were followed up on average for 3.59 years (±1.94) and in eight patients an above threshold decrease in pain scores was maintained. Overall in patients that responded to the test baseline VAS was 7.91 and 4.31 at last follow-up with an average dose of 7.2 μg of ziconotide per day. Six patients (30%) did not respond to any test and in three patients side effects precluded pump implantation. No significant long-term effects of the molecule were noted.

Conclusion: This study shows response to intrathecal ziconotide test in 40% of the patients of a very specific population in whom other therapeutic options are not available. This data justifies the development further studies such as a long-term randomized controlled trial.

Significance: Intrathecal Ziconotide is a posible alternative for the treatment of pain in patients with spinal cord injury and below level neuropathic pain.
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http://dx.doi.org/10.1002/ejp.1445DOI Listing
October 2019

Clostridium difficile: A Frequent Infection in Children After Intestinal Transplantation.

Transplantation 2020 01;104(1):197-200

Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Université Paris Descartes - Sorbonne Paris Cité, Paris, France.

Background: Organ transplantation (Tx) is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection.

Methods: We included retrospectively all children after ITx in our unit, with at least 1 year of graft survival. All samples positive for Clostridium difficile (CD) and its toxin were considered.

Results: Among the 57 ITx recipients (60 Txs), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, and 1 after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, and 1 hypothermia. Nine were hospitalized for an average of 6.5 days (2-20) and 4 with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6, and both in 3. Three children presented mild-to-severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for 1 patient with ongoing infection.

Conclusions: CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event.
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http://dx.doi.org/10.1097/TP.0000000000002795DOI Listing
January 2020

Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes.

J Neuroophthalmol 2020 06;40(2):198-206

Hospices Civils de Lyon (EN, LA, FP-V, A-LV, AV, CT), Neuro-Ophthalmology and Neuro-Cognition Unit, Hôpital Neurologique Pierre Wertheimer, Bron, France; Lyon I University (EN, SV, JB, AV, CT), Lyon, France; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Bron, France; INSERM U1028 CNRS UMR5292 Lyon Neuroscience Center, Team ImpAct (AV, CT) and Observatoire Français de la Sclérose en Plaques (SV), Bron, France; Hospices Civils de Lyon (JB), Pôle Information Médicale Evaluation Recherche Unit, Equipe d'Accueil 4129, Bron, France; and Hospices Civils de Lyon (BC), Pharmacie Department, Hôpital Neurologique Pierre Wertheimer, Bron, France.

Background: The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and oculopalatal tremor (OPT), both of which result in poor visual quality of life. The objective of our study was to evaluate the effects of memantine and gabapentin treatments on visual function. We also sought to correlate visual outcomes with ocular motor measures and to describe the side effects of our treatments.

Methods: This study was single-center cross-over trial. A total of 16 patients with chronic pendular nystagmus, 10 with MS and 6 with OPT were enrolled. Visual acuity (in logarithm of the minimum angle of resolution [LogMAR]), oscillopsia amplitude and direction, eye movement recordings, and visual function questionnaires (25-Item National Eye Institute Visual Functioning Questionnaire [NEI-VFQ-25]) were performed before and during the treatments (gabapentin: 300 mg 4 times a day and memantine: 10 mg 4 times a day).

Results: A total of 29 eyes with nystagmus were evaluated. Median near monocular visual acuity improved in both treatment arms, by 0.18 LogMAR on memantine and 0.12 LogMAR on gabapentin. Distance oscillopsia improved on memantine and on gabapentin. Median near oscillopsia did not significantly change on memantine or gabapentin. Significant improvement in ocular motor parameters was observed on both treatments. Because of side effects, 18.8% of patients discontinued memantine treatment-one of them for a serious adverse event. Only 6.7% of patients discontinued gabapentin. Baseline near oscillopsia was greater among those with higher nystagmus amplitude and velocity.

Conclusions: This study demonstrated that both memantine and gabapentin reduce APN, improving functional visual outcomes. Gabapentin showed a better tolerability, suggesting that this agent should be used as a first-line agent for APN. Data from our investigation emphasize the importance of visual functional outcome evaluations in clinical trials for APN.
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http://dx.doi.org/10.1097/WNO.0000000000000807DOI Listing
June 2020

Hangman's fracture: Management strategy and healing rate in a prospective multi-centre observational study of 34 patients.

Orthop Traumatol Surg Res 2019 06 17;105(4):703-707. Epub 2019 Apr 17.

Société Française de Chirurgie Rachidienne, 56, rue Boisonnade, 75014 Paris, France.

Background: Hangman's fractures account for 15% to 20% of all cervical spine fractures. The grading system developed by Effendi and modified by Levine and Edwards is generally used as the basis for management decisions. Nonetheless, the optimal management remains controversial. The objective of this study was to describe the treatments used in France in patients with hangman's fractures. The complications and healing rates were analysed according to the fracture type and treatment used.

Hypothesis: Among patients with hangman's fracture, those with disc damage must be treated surgically.

Material And Methods: A prospective, multi-centre, observational study was conducted under the aegis of the French Society for Spine Surgery (SociétéFrançaisedeChirurgieRachidienne, SFCR). Patients were included if they had computed tomography (CT) evidence of hangman's fracture. Follow-up data were collected prospectively. Fracture healing was assessed on CT scans obtained 3 and 12 months after the injury. The type of treatment and complications were recorded routinely.

Results: We included 34 patients. The fracture type according to Effendi modified by Levine and Edwards was I in 68% of patients, II in 29% of patients, and III in a single patient (3%). The treatment was non-operative in 21 (62%) patients and surgical in 11 (32%). All 28 patients re-evaluated after 1 year had evidence of fracture healing. The remaining 6 patients were lost to follow-up.

Conclusion: Hangman's fracture is associated with low rates of mortality and neurological complications. Non-operative treatment is appropriate in Type I hangman's fracture, with a 100% healing rate in our study. Types II and III are characterised by damage to the ligaments and discs requiring either anterior C2-C3 fusion or posterior C1-C3 screw fixation.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.otsr.2019.03.009DOI Listing
June 2019

TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma.

Eur J Cancer 2019 02 12;108:41-49. Epub 2019 Jan 12.

Hospices Civils de Lyon, Fédération D'Endocrinologie, Bron Cedex, F-69677, France; Université Lyon 1, HESPER EA 7425, Lyon, F-69008, France.

Background: TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer.

Patients: Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes.

Results: The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients.

Conclusion: Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.
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http://dx.doi.org/10.1016/j.ejca.2018.12.003DOI Listing
February 2019

Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort.

Liver Int 2019 06 1;39(6):1136-1146. Epub 2019 Feb 1.

Hépatologie, Gastroentérologie et Nutrition pédiatriques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France.

Background & Aims: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort.

Methods: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model.

Results: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow-up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty-eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0-11.6): diagnosis of alpha-1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIM Z in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007).

Conclusion: Alpha-1 antitrypsin-deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non-homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.
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http://dx.doi.org/10.1111/liv.14035DOI Listing
June 2019

Mortality, complication, and fusion rates of patients with odontoid fracture: the impact of age and comorbidities in 204 cases.

Arch Orthop Trauma Surg 2019 Jan 13;139(1):43-51. Epub 2018 Oct 13.

Service de neurochirurgie C et chirurgie du rachis, Hôpital P Wertheimer, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 59 boulevard Pinel, 69003, Lyon, France.

Purpose: The French Society of Spine Surgery (SFCR) conducted a prospective epidemiologic multicenter study. The purpose was to investigate mortality, complication, and fusion rates in patients with odontoid fracture, depending on age, comorbidities, fracture type, and treatment.

Methods: Out of 204 patients, 60 were ≤ 70 years and 144 were > 70 years. Demographic data, comorbidities, treatment types and complications (general medical, infectious, neurologic, and mechanical), and death were registered within the first year. Fractures were classified according to Anderson-D'Alonzo and Roy-Camille on the initial CT. A 1-year follow-up CT was available in 144 patients to evaluate fracture consolidation.

Results: Type II and oblique-posterior fractures were the most frequent patterns. The treatment was conservative in 52.5% and surgical in 47.5%. The mortality rate in patients ≤ 70 was 3.3% and 16.7% in patients > 70 years (p = 0.0002). Fracture pattern and treatment type did not influence mortality. General medical complications were significantly more frequent > 70 years (p = 0.021) and after surgical treatment (p = 0.028). Neurologic complications occurred in 0.5%, postoperative infections in 2.0%, and implant-related mechanical complications in 10.3% (associated with pseudarthrosis). Fracture fusion was observed in 93.5% of patients ≤ 70 years and in 62.5% >70 years (p < 0.0001). Pseudarthrosis was present in 31.5% of oblique-posterior fractures and in 24.3% after conservative treatment.

Conclusions: Age and comorbidities influenced mortality and medical complication rates most regardless of fracture type and treatment choice. Pseudarthrosis represented the main complication, which increased with age. Pseudarthrosis was most frequent in type II and oblique-posterior fractures after conservative treatment.
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http://dx.doi.org/10.1007/s00402-018-3050-6DOI Listing
January 2019

C1 fracture: Analysis of consolidation and complications rates in a prospective multicenter series.

Orthop Traumatol Surg Res 2018 11 9;104(7):1049-1054. Epub 2018 Oct 9.

Service de neurochirurgie C et chirurgie du Rachis, université Claude-Bernard Lyon 1, hôpital P. Wertheimer, 59, boulevard Pinel, 69003 Lyon, France.

Introduction: Three types of C1 fracture have been described, according to location: type 1 (anterior or posterior arc), type 2 (Jefferson: anterior and posterior arc), and type 3 (lateral mass). Stability depends on transverse ligament integrity. The main aim of the present study was to analyze complications and consolidation rates according to fracture type, age and treatment.

Material And Methods: The French Society of Spinal Surgery (SFCR) performed a multicenter prospective study on C1-C2 trauma. All patients with recent fracture diagnosed on CT were included. Consolidation on CT was studied at 3 months and 1 year. Medical, neurologic, infectious and mechanical complications were inventoried using the KEOPS data-base.

Results: Sixty-three of the 417 patients (15.1%) had C1 fracture: type 1 (33.3%), type 2 (38.1%), or type 3 (28.6%). The transverse ligament was intact in 53.9% of cases. Treatment was non-operative in 63.5% of cases, surgical in 27.0%, and surgical after failure of non-operative treatment in 9.5%. There were 8 medical complications, more frequently in patients aged >70 years, following surgery (p<0.0001). The consolidation rate was 84.2% with non-operative treatment, 100% for primary surgery, and 33.3% for secondary surgery (p=0.002). There were 10 cases of non-union, in 4.8% of type 1, 13.6% of type 2 and 33.3% of type 3 fractures (p=0.001).

Conclusion: Medical complications showed association with age and with type of treatment. Non-operative treatment was suited to types 1, 2 and 3 with minimal displacement and intact transverse ligament. C1-C2 fusion was suited to displaced unstable type 2 fracture. Displaced type 3 fracture incurred risk of non-union. Early surgery may be recommended.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.otsr.2018.06.014DOI Listing
November 2018

Biomechanical Characterization of Intracranial Aneurysm Wall: A Multiscale Study.

World Neurosurg 2018 Nov 9;119:e882-e889. Epub 2018 Aug 9.

Department of Interventional Neuroradiology, Hospices Civils de Lyon, Lyon, France.

Objective: Aneurysm wall biomechanics are not yet an integral part of aneurysm rupture risk evaluation. We aimed to develop a new technique describing the biomechanical properties of aneurysm wall and correlating them to rupture status.

Methods: Aneurysm wall samples collected during surgery were submitted before and after freezing to tensile tests or as fresh samples to indentation tests. The lateral stiffness or the Young's modulus of the different samples was determined as a function of the mechanical test used. The impact of freezing on biomechanical properties was evaluated. The correlation of clinical and radiologic data with the biomechanical profile of the aneurysm samples was investigated. Two-photon microscopy was used to study collagen fiber organization.

Results: Sixteen aneurysm samples (11 unruptured and 5 ruptured) were included. Freezing decreased tissue stiffness. No significant difference was found between ruptured and unruptured aneurysm wall samples regarding demographic characteristics, ethnicity, smoking status, arterial hypertension, site, size and shape of the aneurysm, PHASES score, mechanical profile, or overall Young's modulus. Indentation tests found that the rupture occurred in a restricted area of increased elastic capacity and unruptured areas had increased stiffness. Two-photon microscopy found disruption of the collagen fiber network in rupture zones.

Conclusions: The indentation test of fresh aneurysm wall samples described the heterogeneity of biomechanical properties of the tissue and found increased elastic capacity in the rupture zone and increased stiffness in the remainder of the aneurysm. This study could be a basis for further research aimed at building a biomechanical-based model of aneurysm rupture risk.
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http://dx.doi.org/10.1016/j.wneu.2018.07.290DOI Listing
November 2018

SEEG-guided radiofrequency coagulation (SEEG-guided RF-TC) versus anterior temporal lobectomy (ATL) in temporal lobe epilepsy.

J Neurol 2018 Sep 26;265(9):1998-2004. Epub 2018 Jun 26.

Department of Neurosurgery, Hospices Civils de Lyon, Neurology and Neurosurgery Hospital Pierre Wertheimer, 59, Bd Pinel, 69677, Bron, France.

Background: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a super-selective procedure. Hippocampus has a limited volume and is widely accessible to SEEG so that SEEG-guided RF-TC could be an alternative to the anterior temporal lobectomy (ATL) in case of temporal lobe epilepsy (TLE) syndrome.

Objective: To compare seizure-free rate at 1-year follow-up between patients undergoing SEEG-guided RF-TC and patients undergoing ATL in TLE over a 15-year period.

Methods: All patients had a drug-resistant epilepsy and underwent SEEG after non-conclusive phase I investigations suspecting a TLE. Two groups were selected according to the procedure which the patients underwent (ATL or SEEG-guided RF-TC); TLE had to be confirmed by SEEG in the two groups. The primary outcome was seizure freedom at 1 year. The secondary outcome was response (at least 50% reduction of seizure frequency) at 1 year. In case of persistent seizures after SEEG-guided RF-TC, ATL was performed.

Results: A total of 21 patients underwent SEEG-guided RF-TC and 49 ATL. At 12 months, none of the patients of the SEEG-guide RF-TC group was seizure free, while 37 (75.5%) in the ATL group were so (p < 0.001). Ten patients (47.6%) were responders after 12 months of follow-up after SEEG-guided RF-TC; all patients in the ATL group who were seizure free were responders.

Conclusion: SEEG-guided RF-TC is not as effective as ATL in TLE. As no memory impairment following SEEG-guided RF-TC was found, patients with dominant mesial involvement for whom hippocampectomy is not an option could benefit from the technique.
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http://dx.doi.org/10.1007/s00415-018-8958-9DOI Listing
September 2018

Returning to work after multimodal treatment in glioblastoma patients.

Neurosurg Focus 2018 06;44(6):E17

1Neurosurgical Department, Oncological and Vascular Service, Pierre Wertheimer University Hospital, Lyon.

OBJECTIVE Although multimodal treatment for glioblastoma (GBM) has resulted in longer survival, uncertainties exist regarding health-related quality of life and functional performance. Employment represents a useful functional end point and an indicator of social reintegration. The authors evaluated the rate of patients resuming their employment and the factors related to work capacity. METHODS The authors performed a retrospective study of working-age patients treated with surgery and radiochemotherapy between 2012 and 2015. Data were collected before and after surgery and at 6, 12, 18, and 24 months. Employment was categorized according to the French Socio-Professional Groups and analyzed regarding demographic and clinical data, performance status, socio-professional category, radiological features, type, and quality of resection. RESULTS A total of 125 patients, mean age 48.2 years, were identified. The mean follow-up was 20.7 months with a median survival of 22.9 months. Overall, 21 patients (18.3%) went back to work, most on a part-time basis (61.9%). Of the patients who were alive at 6, 12, 18, and 24 months after diagnosis, 8.7%, 13.8%, 15.3%, and 28.2%, respectively, were working. Patients going back to work were younger (p = 0.03), had fewer comorbidities (p = 0.02), and had a different distribution of socio-professional groups, with more patients belonging to higher occupation categories (p = 0.02). Treatment-related symptoms (36.2%) represented one of the main factors that prevented the resumption of work. Employment was strongly associated with performance status (p = 0.002) as well as gross-total removal (p = 0.04). No statistically significant difference was found regarding radiological or molecular features and the occurrence of complications after surgery. CONCLUSIONS GBM diagnosis and treatment has a significant socio-professional impact with only a minority of patients resuming work, mostly on a part-time basis.
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http://dx.doi.org/10.3171/2018.3.FOCUS1819DOI Listing
June 2018

Predictive factors of outcome in poorly differentiated thyroid carcinomas.

Eur J Cancer 2018 03 3;92:40-47. Epub 2018 Feb 3.

Endocrinology Department-INSERM, UMR 1052, University Lyon I, Lyon, France.

Background: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis.

Methods: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome).

Results: All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10-0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions -124 (C228T) and -146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations.

Conclusion: PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness.
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http://dx.doi.org/10.1016/j.ejca.2017.12.027DOI Listing
March 2018

Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BMC Nephrol 2018 01 8;19(1). Epub 2018 Jan 8.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Université Claude Bernard Lyon 1, service d'Anesthésie Réanimation, Lyon, France.

Background: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes.

Methods: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre.

Results: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis.

Conclusions: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.
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http://dx.doi.org/10.1186/s12882-017-0805-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759186PMC
January 2018

Faltering growth in the critically ill child: prevalence, risk factors, and impaired outcome.

Eur J Pediatr 2018 Mar 14;177(3):345-353. Epub 2017 Dec 14.

Paediatric Intensive Care Unit, Hôpital Universitaire Femme Mère Enfant, Hospices Civils de Lyon, 59 bd Pinel, 69677, Lyon-Bron, France.

Low body mass index (BMI) z score is commonly used to define undernutrition, but faltering growth allows for a complementary dynamic assessment of nutritional status. We studied the prevalence of undernutrition and faltering growth at admission in the pediatric intensive care (PICU) setting and their impacts on outcome. All (685) consecutive children (aged 0 to 18 years old) admitted in a single-center PICU over a 1-year period were prospectively enrolled. Nutritional status assessment was based on anthropometric measurements performed at admission and collected from medical files. Undernutrition was considered when z score BMI for age was < - 2SD. Faltering growth was considered when the weight for age curve presented a deceleration of > - 1 z score in the previous 3 months. Undernutrition was diagnosed in 13% of children enrolled, and faltering growth in 13.7% mostly in children with a normal BMI. Faltering growth was significantly associated with a history of underlying chronic disease, and independently with extended length of PICU stay in a multivariate analysis.

Conclusion: Assessment of nutritional status in critically ill children should include both undernutrition and faltering growth. This study highlights that faltering growth is independently associated with suboptimal outcome in PICU. What is Known: • Malnutrition, defined according to BMI-for-age z score, is correlated with poor outcome in the critically ill child. • In this setting, nutritional assessment should consist not only of a static assessment based on BMI-for-age z score but also of a dynamic assessment to identify recent faltering growth. What is New: • Critically ill children frequently present with faltering growth at admission. • Faltering growth is a newly identified independent associated factor of suboptimal outcome in this setting (extended length of stay).
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http://dx.doi.org/10.1007/s00431-017-3062-1DOI Listing
March 2018

Research protocol on early palliative care in patients with acute leukaemia after one relapse.

BMJ Support Palliat Care 2017 Dec 31;7(4):480-484. Epub 2017 Jul 31.

Clinical Research, Université Claude Bernard Lyon 1, HESPER unit EA 7425, Lyon, France.

Objectives: According to the American Society of Clinical Oncology palliative care referrals are made within the last 3 weeks of patients' lives and most frequently when oncological treatments have ceased especially for patients with haematological malignancies. Recent publications indicate that patients with acute leukaemia are prone to symptoms, an indication for which a close collaboration between the patient's haematologist and a palliative care team might result in improved symptom management. The object of this pilot study is to evaluate the feasibility of a clinical research trial to assess the effect of early palliative care in patients with acute leukaemia after one relapse.

Methods: This project is a multicentre, non-blinded, randomised, controlled trial. Patients in group 1 will receive standard haematological care associated with palliative care (intervention group). Patients in group 2 will receive standard haematological care with palliative care only if requested by the haematologist (control group). In order to measure an accurate sample size, patients who participate will complete a standardised questionnaire to assess their quality of life, as well as their psychological and physical symptoms, before being randomised to one of two groups in a 1:1 ratio without stratified randomisation.

Results: The aim of this study is to analyse causes of dropout, non-adherence and missing data in order to refine the protocol for the subsequent clinical research trial.

Conclusion: The ultimate objective of this project is to develop collaboration between haematologists and palliative care teams in order to improve patients' quality of life.
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http://dx.doi.org/10.1136/bmjspcare-2016-001173DOI Listing
December 2017

Worldwide view of nephropathic cystinosis: results from a survey from 30 countries.

BMC Nephrol 2017 Jul 3;18(1):210. Epub 2017 Jul 3.

Centre de référence des maladies rénales rares Néphrogones, hôpital Femme-Mère-Enfant, Hospices Civils de Lyon & Université Claude-Bernard Lyon 1, Lyon, France.

Background: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN].

Methods: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries.

Results: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis.

Conclusions: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.
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http://dx.doi.org/10.1186/s12882-017-0633-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496396PMC
July 2017

Trigeminal neuralgia due to venous neurovascular conflicts: outcome after microvascular decompression in a series of 55 consecutive patients.

Acta Neurochir (Wien) 2017 02 5;159(2):237-249. Epub 2016 Nov 5.

Neurosurgical Department, Hospital Pierre Wertheimer, University Lyon 1, Lyon, France.

Background: Implication of veins as neurovascular conflict (NVC) in the genesis of trigeminal neuralgia (TN) remains a matter of debate. Few reports dealing with venous NVC have been published. The objective of this study is to describe the outcome in a historical cohort of consecutive patients with classical TN due to venous compression.

Methods: All patients with TN treated by microvascular decompression (MVD) from 2005 to 2013 were included if a marked venous compression was found at the surgery either alone or accompanied by an artery. Patients were evaluated for clinical presentation, operative findings and the long-term outcome. Outcome was considered favourable if patients were classed as BNI I or II (i.e. not requiring any medication). Kaplan-Meier analysis was used to determine probability of a favourable outcome at 10 years of follow-up.

Results: Out of the overall series of 313 patients having been treated by MVD and considered for the study, in 55 (17.5 %) a vein was the main compressive vessel; in 26 (8.3 %) it was the only compressive vessel. Probability of relief with no need for medication at 10 years was 70.6 %. The patients with focal arachnoiditis had a poor long-term outcome, i.e. BNI III-V, in 85.7 % compared with 20.8 % without arachnoiditis (p = 0.0037 Fisher's exact test). No differences in outcome were found between patients presenting with purely venous compression and patients with mixed compression. Outcome was similarly good for patients with atypical neuralgia when compared to patients with typical clinical presentation.

Conclusions: Venous NVC as a cause of TN is far from rare. MVD with complete liberation of the entire root in cases with clear-cut venous compression on imaging studies gives a good probability of long-term pain relief, thus encouraging to propose surgery for such patients.
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http://dx.doi.org/10.1007/s00701-016-2994-yDOI Listing
February 2017

Pediatric combined liver-kidney transplantation: a single-center experience of 18 cases.

Pediatr Nephrol 2016 09 8;31(9):1517-29. Epub 2016 Apr 8.

Centre de Référence des Maladies Rénales Rares Néphrogones, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.

Background: Experience in combined liver-kidney transplantation (CLKT) in children is limited.

Methods: We conducted a retrospective study of all pediatric CLKTs performed at our medical institution between 1992 and 2013.

Results: We identified 18 pediatric patients (9 girls) who had undergone CLKT at our institution during the study period. The median age [range] and body weight [range] of this patient group was 3.6 [1.0-18.6] years and 13 [10-40] kg, respectively; 11 patients weighed <15 kg at the time of CLKT. Indications for CLKT were primary hyperoxaluria (PH1; n = 14), association of hepatic fibrosis and end-stage renal disease (n = 3) and methylmalonic acidemia (n = 1). In the early postoperative period, eight patients required dialysis. Median stay in the pediatric intensive care unit was 10 [6-29] days. One patient died from cardiovascular disease 10 years after CLKT. There were no liver graft losses despite six acute liver rejection episodes, whereas four kidney grafts were lost. At last follow-up (6 [0.5-21] years) for patients with a functioning renal graft, the glomerular filtration rate was 71 [26-146] mL/min/1.73 m(2). In PH1 patients, urine oxalate normalized in six patients within 3 years after CLKT, but three patients still presented with elevated oxaluria at 1, 2 and 3 years after CLKT.

Conclusions: Pediatric CLKT provides encouraging results in the long term, even in the youngest patients.
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http://dx.doi.org/10.1007/s00467-016-3324-6DOI Listing
September 2016

Impact of Pregnancy on Weight Loss and Quality of Life Following Gastric Banding.

Obes Surg 2016 08;26(8):1843-50

University Claude Bernard Lyon 1, Lyon, France.

Background-objectives: Despite pregnancy being a common event following laparoscopic adjustable gastric banding (LAGB), there is little comprehensive data regarding its effect on postoperative outcome. The aim of this study was to assess the impact of pregnancy on the postoperative changes in quality of life (QOL) and total weight loss 3 years after LAGB.

Setting: Multi-institutional, France.

Methods: This is a study of the subgroup of 561 women of childbearing age included in a 3-year prospective multicenter trial assessing the results of patients undergoing LAGB surgery. Data from the 61 women who got pregnant and delivered during the follow-up period were compared with the 270 who did not.

Results: Pregnant women achieved lower final weight loss compared to the non-pregnant group [final body mass index (BMI) 35.4 vs. 31.1 kg/m(2), p < 0.0001; excess weight loss (%EBL) 43.6 vs. 64.7 %, p < 0.0001]. Longitudinal assessment demonstrated pregnancy as a significant and independent factor of poor weight loss (p < 0.0001). The timing of conception after LAGB (between the first 18 months or after) had no significant impact on weight loss changes. There was no significant difference in short form-36 health survey (SF-36) QOL scores between both groups.

Conclusions: Pregnancy following gastric banding affects negatively postoperative final weight loss, even if occurring 18 months postoperatively, but has no effect on QOL improvement.
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http://dx.doi.org/10.1007/s11695-015-2011-1DOI Listing
August 2016

Burnout among physicians in palliative care: Impact of clinical settings.

Palliat Support Care 2016 08 14;14(4):402-10. Epub 2015 Oct 14.

Department of Palliative Care,Centre Hospitalier de Lyon-Sud,Hospices Civils de Lyon,Pierre-Bénite,France.

Objective: Burnout syndrome is a work-related professional distress. Palliative care physicians often have to deal with complex end-of-life situations and are at risk of presenting with burnout syndrome, which has been little studied in this population. Our study aims to identify the impact of clinical settings (in a palliative care unit (PCU) or on a palliative care mobile team (PCMT)) on palliative care physicians.

Method: We undertook a cross-sectional study using a questionnaire that included the Maslach Burnout Inventory (MBI), and we gathered sociodemographic and professional data. The questionnaire was sent to all 590 physicians working in palliative care in France between July of 2012 and February of 2013.

Results: The response rate was 61, 8% after three reminders. Some 27 (9%) participants showed high emotional exhaustion, 12 (4%) suffered from a high degree of depersonalization, and 71 (18%) had feelings of low personal accomplishment. Physicians working on a PCMT tended (p = 0.051) to be more likely to suffer from emotional exhaustion than their colleagues. Physicians working on a PCMT worked on smaller teams (fewer physicians, p < 0.001; fewer nonphysicians, p < 0.001). They spent less time doing research (p = 0.019), had fewer resources (p = 0.004), and their expertise seemed to be underrecognized by their colleagues (p = 0.023).

Significance Of Results: The prevalence of burnout in palliative care physicians was low and in fact lower than that reported in other populations (e.g., oncologists). Working on a palliative care mobile team can be a more risky situation, associated with a lack of medical and paramedical staff.
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http://dx.doi.org/10.1017/S1478951515000991DOI Listing
August 2016

Palliative care referral and associated outcomes among patients with cancer in the last 2 weeks of life.

BMJ Support Palliat Care 2019 Mar 23;9(1):e16. Epub 2015 Sep 23.

Département de Soins Palliatifs, Centre Hospitalier de Lyon-Sud, Hospices Civils de Lyon, Lyon, France.

Background: Palliative care (PC) improves the quality of life of patients with advanced cancer. Our aim was to describe PC referral among patients with advanced cancer, and associated outcomes in an academic medical centre.

Methods: We reviewed the medical records of 536 inpatients with cancer who had died in 2010. Our retrospective study compared patients who accessed PC services with those who did not. Statistical analysis was conducted using non-parametric tests due to non-normal distribution. We also conducted a multivariate analysis using a logistic regression model including age, gender, type of cancer and metastatic status.

Results: Out of 536 patients, 239 (45%) had PC referral. The most common cancer types were respiratory (22%) and gastrointestinal (19%). Patients with breast cancer (OR 23.76; CI 6.12 to 92.18) and gynaecological cancer (OR 7.64; CI 2.61 to 22.35) had greater PC access than patients with respiratory or haematological cancer. Patients referred to PC had significantly less chemotherapy in the last 2 weeks of life than non-referred patients, with 22 patients (9%) vs 59 (19%; p<0.001). PC-referred patients had significantly fewer admissions to intensive care units in the last month of life than non-referred patients, with 14 (6%) vs 58 (20%; p<0.001).

Conclusions: There was a large variation in access to PC according to the type of cancer. There is a need to improve collaboration between the PC service and the respiratory, cancer and haematology specialists. Further research will be required to determine the modality and the impact of this collaboration.
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http://dx.doi.org/10.1136/bmjspcare-2014-000791DOI Listing
March 2019