Burden of status epilepticus: prognosis and cost driving factors, insight from a nationwide retrospective cohort study of the French health insurance database.

BACKGROUND: Status epilepticus (SE) imposes a significant burden in terms of in-hospital mortality and costs, but the relationship between SE causes, patient comorbidities, mortality, and cost remains insufficiently understood. We determined the in-hospital mortality and cost-driving factors of SE using a large and comprehensive database. METHODS: We conducted a retrospective cohort study involving patients experiencing their first hospitalization with an ICD-10 code diagnosis of SE, spanning from January 1, 2015, to December 31, 2019, using the French health insurance database which covers 99% of population. Patient characteristics, SE causes, Intensive Care Unit (ICU) admissions, mechanical ventilation, discharge status, and health insurance costs were extracted for each hospitalization. RESULTS: We identified 52,487 patients hospitalized for a first SE. In-hospital mortality occurred in 11,464 patients (21.8%), with associated factors including age (Odds Ratio [OR], 10.3, 95% Confidence Interval [CI] 7.87-13.8 for ages over 80 compared to 10-19), acute causes (OR, 15.3, 95% CI 13.9-16.8 for hypoxic cause), tumors (OR, 1.75, 95% CI 1.63-1.8), comorbidities (OR, 3.00, 95% CI 2.79-3.24 for 3 or more comorbidities compared to 0), and prolonged mechanical ventilation (OR, 2.61, 95% CI 2.42-2.82). The median reimbursed cost for each SE hospitalization was 6517€ (3364-13,354), with cost factors mirroring those of in-hospital mortality. CONCLUSION: Causes and co-morbidities are major determinants of mortality and hospital costs in status epilepticus, and factors associated with higher mortality are also often associated with higher costs. Further studies are needed to identify their long-term effects.

Short and Mid Term Outcomes of Cryopreserved Abdominal Aortic Allografts Used as a Substitute for Infected Prosthetic Grafts in 200 Patients.

OBJECTIVE: To investigate the use of cryopreserved arterial allografts (CAA) as a substitute for infected infrarenal aortic prostheses, and its outcomes. METHODS: A single centre retrospective study of consecutive patients receiving an abdominal aortic CAA after removal of an infected graft was conducted between January 1997 and December 2013. The primary outcome was the rate of allograft related revision surgery. Secondary outcomes were the 30 day mortality rate, survival, primary patency, limb salvage, and infection recurrence. Allograft ruptures secondary to infection and risk factors for allograft failure were also investigated. RESULTS: Two hundred patients (mean age 64.2 ± 9.4 years) were included. In 56 (28%) cases, infection was related to an enteric fistula. The mean follow up duration was 4.1 years. The 30 day mortality rate was 11%. Early revision surgery was needed in 59 patients (29.5%). Among them, 15 (7.5%) were allograft related and led to the death of three patients (1.5%), corresponding to a 7.5% 30 day allograft related revision surgery rate. During the first six months, 17 (8.5%) patients experienced 21 events with complete or partial rupture (pseudo-aneurysm) of the allograft responsible for five (2.5%) deaths, corresponding to a re-infection rate of 8.5%. The multivariable analysis showed that diabetes and pseudo-aneurysm of the native aorta on presentation were predictive factors for short term allograft rupture. After six months, 25 (12.5%) patients experienced long term allograft complications (rupture, n = 2, 1%; pseudo-aneurysm, n = 6, 3%; aneurysm, n = 2, 1%; thrombosis, n = 11, 5.5%; stenosis, n = 4, 2%;) requiring revision surgery resulting in one death. The five year rates of survival, allograft related revision surgery, limb salvage, primary patency, and infection recurrence were 56%, 30%, 89%, 80%, and 12%, respectively. CONCLUSION: CAAs provide acceptable results to treat aortic graft infection with few early graft related fatal complications. Long term allograft related complications are quite common but are associated with low mortality and amputation rates.

Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial.

BACKGROUND: Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome. METHODS: In this randomised, double-blind, controlled trial, we recruited patients aged 18-60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842. FINDINGS: Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period between groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR -23·9 to 38·1]; sham group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [-10·6 to 4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before stimulation and six each in the active and sham stimulation groups) occurred in 13 patients (three who withdrew before randomisation, four in the active group, and six in the sham group), with infections in DBS hardware in four patients (two who withdrew before randomisation, one in the sham stimulation group, and one in the active stimulation group). Other serious adverse events included one electrode misplacement (active stimulation group), one episode of depressive signs (active stimulation group), and three episodes of increased tic severity and anxiety (two in the sham stimulation group and one in the active stimulation group). INTERPRETATION: 3 months of aGPi DBS is insufficient to decrease tic severity for patients with Tourette's syndrome. Future research is needed to investigate the efficacy of aGPi DBS for patients over longer periods with optimal stimulation parameters and to identify potential predictors of the therapeutic response. FUNDING: French Ministry of Health.

Hypocalcemia after thyroidectomy in patients with a history of bariatric surgery.

BACKGROUND: Hypocalcemia is a common complication after total thyroidectomy. Previous bariatric surgery could be a higher factor risk for hypocalcemia due to alterations in calcium absorption and vitamin D deficiency. OBJECTIVES: To evaluate incidence and factors involved in the risk of hypocalcemia (transient and permanent) and the postoperative outcomes of these patients after total thyroidectomy. SETTING: University hospital in Paris, France. METHODS: All patients who had previously undergone obesity surgery (i.e., Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric band) who had a total thyroidectomy from 2006 to 2015 were included. No patient was lost to follow-up. Each patient was matched 1:1 with a patient who had no previous bariatric surgery for age, gender, body mass index, and year of surgery. RESULTS: Forty-eight patients were identified (43 female; mean age 48.9±9.2 yr). Nineteen patients (40%) had a postoperative hypocalcemia: transient in 14 patients (29.2%) and permanent in 5 patients (10.4%). No significant predictive clinical or biochemical factors were found for hypocalcemia risk, except for the type of bariatric procedure: Bypass surgery had a 2-fold increased risk of hypocalcemia compared to others procedures (60% versus 30%, P = .05). In the matched pair analysis, the risk of hypocalcemia was significantly higher in patients with previous bariatric surgery than in the matched cohort (40% versus 15%, P = .006). CONCLUSION: Patients with previous bariatric surgery have an increased risk for hypocalcemia after total thyroidectomy, especially after Roux-en-Y gastric bypass. Careful and prolonged follow-up of calcium, vitamin D, and parathyroid hormone levels should be suggested for these patients.

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Is Associated With Aggressive Histopathological Features and a Poor Outcome: Results of a Large Multicentric Study.

CONTEXT: Diffuse sclerosing variant (DSV) is a rare and aggressive subtype of papillary thyroid carcinoma (PTC). OBJECTIVE: The objective of the study was to investigate the clinicopathological features and prognosis of DSV patients and compare these findings with all other PTCs and high-risk PTCs. DESIGN AND SETTING: The data of patients who underwent surgery for DSV and PTC between 2003 and 2014 in seven surgical departments specialized in endocrine surgery were reviewed. PATIENTS: Fifty-six DSV patients were included (mean age 32.6 ± 12.5 y; 46 [82%] female) and were compared with 2945 non-DSV PTCs and 48 high-risk PTCs. RESULTS: Forty-six DSV patients (82%) were pT3, 43 (77%) had an extrathyroidal extension, and 54 (96%) had lymph node metastasis, including 48 patients with involvement in the lateral compartment (86%). During the follow-up period of 4.3 ±2.3 years, 19 patients (34%) had a recurrence, including 18 patients with an ipsilateral lateral compartment recurrence. The only prognostic factor for recurrence in the multivariate analysis was extranodal extension (odds ratio 3.4 [1.1; 10.8]). The 7-year recurrence-free survival (RFS) was 63%. The RFS was significantly worse in patients with DSV than in other PTC patients (hazard risk 8.5 [5.2; 13.9], P < .0001) and were similar to the RFS of high-risk PTCs (hazard risk 1.1 [0.6; 2.2], P = .5). CONCLUSION: DSV patients share the same recurrence rate as high-risk PTC patients. Despite aggressive surgical approaches, the recurrence rate within the first 5 years requires a careful ongoing surveillance, similar to the follow-up of high-risk PTC patients.

Unraveling the Role of Huntingtin in Breast Cancer Metastasis.

BACKGROUND: Huntingtin (HTT) is mutated in Huntington's disease but is ubiquitously expressed, and mutant HTT influences cancer progression. We investigated wild-type HTT function during breast cancer. METHODS: We analyzed HTT and ZO1 expression as well as the HTT phosphoserine 421-activated form (S421-P-HTT) in human breast cancer tissues by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. We performed in vitro migration and invasion assays as well as in vivo tail vein injections of the metastatic 4T1 cells in BALB/c mice (n = 11 per group). We analyzed tumor progression in knock-in mice with modified S421 crossed with the MMTV-PyVT mammary cancer model (at least n = 12 per group). Data were analyzed with unpaired t tests, analysis of variance, Pearson or Spearman correlation, and Mann Whitney or Kruskal-Wallis tests. All statistical tests were two-sided. RESULTS: Levels of HTT and of S421-P-HTT are abnormally low in poorly differentiated and metastatic human breast cancers. HTT expression is downregulated in invasive compared with in situ carcinoma (P < .001). In BALB/c mice, silencing of HTT promotes lung colonization by a metastatic mammary cancer cell line (P = .005) and S421-unphosphorylatable-HTT accelerates cancer progression. HTT interacts with ZO1 and regulates both its expression and its localization to tight junctions. In human breast tumors, the patterns of HTT and ZO1 expression are similar (Pearson correlation coefficient = 0.66, P < .001). CONCLUSIONS: HTT may inhibit breast tumor dissemination through maintenance of ZO1 at tight junctions. Downregulation of HTT transcript and protein levels is a prognostic factor for poor prognosis and metastasis development.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response.

BACKGROUND: Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. METHODS: We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. FINDINGS: Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas--anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate--27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. CONCLUSIONS: Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.

Working memory in Parkinson's disease patients: clinical features and response to levodopa / Memória de trabalho em pacientes com doença de Parkinson: características clínicas e resposta a levodopa

OBJECTIVE: To evaluate the clinical features of the working memory (WM) in Parkinson's disease (PD) patients and to test the effect of levodopa on WM. METHOD: The paradigm was based on the 'n-back' tasks, which enables to study the level of executive demand (three levels of difficulty) and the domain of the information being processed (spatial items, faces and letters). The effect of levodopa was studied by testing PD patients in "on" and "off" states. RESULTS: PD patients performed less well in WM tasks than controls. There was no interaction between groups and complexity. Levodopa therapy had a positive effect only on spatial WM tasks but no effect on complexity. CONCLUSION: Our results suggest that impairment observed may result from a maintenance deficit within WM regardless the level of processing and levodopa therapy presents a positive effect on spatial WM.

OBJETIVO: Avaliar as características clínicas da memória de trabalho (MT) em pacientes com doença de Parkinson (DP) e testar o efeito da levodopa na MT. MÉTODO: O paradigma baseou-se nas tarefas 'n-back', que permitem avaliar o nível de demanda executiva (três níveis de dificuldade) e o domínio da informação sendo processado (posições espaciais, faces e letras). O efeito da levodopa foi estudado pela testagem dos pacientes no estado "on" e "off". RESULTADOS: Pacientes com DP apresentam desempenho inferior ao dos controles em tarefas de MT. Não foi observada interação entre grupos e complexidade. A terapia com levodopa mostrou efeito positivo sobre a modalidade espacial, e nenhum efeito sobre a complexidade. CONCLUSÃO: Nossos resultados sugerem que o comprometimento observado pode resultar de défict de manutenção da MT, independente do nível de processamento. A terapia com levodopa apresenta efeito positivo sobre a MT espacial.

Prevalence and risk factors of mortality and morbidity after operation for adhesive postoperative small bowel obstruction.

BACKGROUND: Many factors are believed to influence the mortality and morbidity after operations for adhesive small bowel obstruction (SBO). METHODS: In a multicenter prospective cohort of 286 patients operated on for adhesive postoperative SBO, we studied the in-hospital and 30-day postdischarge mortality (early mortality) and morbidity as well as long-term mortality using univariate and multivariate analysis. RESULTS: In the present cohort, with a median follow-up of 41 months and 9% patients lost to follow-up at the end of the study, the prevalence of early postoperative mortality was 3%. All deceased patients were over 75 years old with an American Society of Anesthesiologists (ASA) class >/=III. The prevalence of long-term mortality was 7% with the following independent risk factors: age >75 years old (hazards ratio [HR] 6.6 [95% confidence interval [CI], 2.4-18.1]), medical complications (HR 7.4 [CI, 2.2-24.3]), and a mixed mechanism of obstruction (HR 4.5 [CI, 1.5-13.7]). Prevalence of medical and surgical morbidity was 8% and 6%, respectively. Independent risk factors for medical complications were ASA class >/=III (odds ratio [OR] 16.8 [CI, 2.1-133.1]) and bands (OR 14.1 [CI, 1.8-111.5]) and for the surgical complications the number of obstructive structures >/=10 (OR 8.3 [CI, 1.6-19.7]), a nonresected intestinal wall injury (OR 5.3 [CI, 1.5-18.3]), and intestinal necrosis (OR 5.6 [CI, 1.6-19.7]). Otherwise, 3 patients with "apparent" reversible ischemia developed a postoperative intestinal necrosis followed by 2 reoperations and 1 death. CONCLUSION: The early postoperative mortality is strongly linked with the age and the ASA class and the long-term mortality with postoperative complications. More frequent bowel resections might be suggested for patients featuring a number of obstructive structures >/=10 and an intestinal wall injury, especially when associated with a reversible intestinal ischemia.

Reliability of the Burke-Fahn-Marsden scale in a multicenter trial for dystonia.

BACKGROUND: The multicenter SPIDY trial (pallidal stimulation for generalized, idiopathic dystonia) recently reported a marked improvement in dystonia which was assessed by the Burke-Fahn-Marsden (BFM) scale. However, the reliability of this tool has rarely been evaluated and its use in a multicenter study has never been assessed prospectively. PURPOSE: To evaluate the concordance between three unblinded clinical raters and one single-blinded rater for 10 prospective series of ratings on the BFM scale in 22 dystonic patients of the SPIDY study. METHODS: Ten assessments on the BFM scale were performed under various stimulation conditions at different time points (before surgery and 1, 3, 6, and 12 months afterwards). Patients were first evaluated by three unblinded clinical raters (one per center). All assessments were videotaped and sent to a blinded rater. Intra- and inter-rater reliability was assessed using intraclass correlation coefficients. RESULTS: The intra-rater reliability at inclusion was better for the blinded rater than for the clinical raters. The inter-rater reliability (comparing the blinded rater with each clinical rater) was "very good" at inclusion, "fair" at month 1 and was "good" at month 3, month 6, and month 12. CONCLUSION: Blinding (rather than video) is probably the key factor in better intra-rater reliability and can produce more accurate rating than clinical rating. Consequently, a blind procedure should be performed systematically in multicenter studies. As inter-rater reliability is good in trained unblinded raters, the BFM scale may also be used in the follow up of dystonic patients in movement disorders centers, in clinical practice.

Adhesive postoperative small bowel obstruction: incidence and risk factors of recurrence after surgical treatment: a multicenter prospective study.

OBJECTIVE: The aim of the present study was to determine the cumulative incidence and the risk factors of recurrence in patients operated on for an adhesive postoperative small bowel obstruction (SBO). SUMMARY BACKGROUND DATA: Postoperative intraperitoneal adhesions, or bands, resulting from any type of abdominal surgery, are the main cause of adhesive postoperative small bowel obstructions, which represent a life-long issue. Recurrences after operated adhesive postoperative SBO are a threatening potentiality for patients and a difficult problem facing any surgeon. Today the cumulative incidence and the risk factors of recurrence have been retrospectively reported but have never been prospectively evaluated in a multicenter study. METHODS: From January 1997 to January 2002, we enrolled 286 patients operated on for an adhesive postoperative SBO in a prospective multicenter trial. A systematic follow-up was carried out and ended in April 2003. Studied factors for recurrent adhesive postoperative SBO were as follows: age, gender, ASA status, number and sites of previous operations, previous operation for adhesive postoperative SBO, elapsed time from the latest operation, surgical approach, number and type of obstructive structures, site and mechanism of obstruction, final operations, and postoperative surgical and medical complications. They were analyzed using Kaplan-Meier method. A Cox regression model was used to determine the independent risk factor of recurrence. RESULTS: The median follow-up was 41 months (range, 1-75 months). The cumulative incidence of overall recurrence was 15.9%, and for surgically managed recurrence 5.8%. In multivariate analysis, the risk factors for the overall recurrences were age <40 years (hazard ratio [HR], 2.97; confidence interval [CI], 1.48-5.94), adhesion or matted adhesion (HR, 3.79; CI, 1.84-7.78) and, for the surgically managed: adhesions or matted adhesions (HR, 3.64; CI, 1.12-11.84), and postoperative surgical complications (HR, 5.63; CI, 1.73-18.28). CONCLUSION: Operated adhesive postoperative SBO is a clinical entity with a high recurrence rate and specific risk factors of recurrences. Thus, the patients operated on for adhesive postoperative SBO may be candidates for the preventive use of anti-adhesion agents, particularly when a risk factor of recurrence is present.