INSIGHTS ON AROMATASE IMMUNOHISTOCHEMISTRY: VARIATIONS BETWEEN INTRINSIC MOLECULAR SUBTYPES OF BREAST CANCERS.

CONTEXT: Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. MATERIAL AND METHODS: Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. RESULTS: Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=-0.359, p=0.007) was observed. CONCLUSION: Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.

Air pollution and humidity as triggering factors for stroke. Results of a 12-year analysis in the West Paris area.

BACKGROUND AND PURPOSE: Previous studies have suggested an association between stroke and meteorological factors, air pollution and acute respiratory infections as triggering factors. Often, these factors have been evaluated separately. We evaluated the association between all these environmental triggering factors and calls for suspected stroke in a suburb in west Paris from 2004 to 2015. METHODS: We used data from the emergency medical dispatching center of all calls for suspected stroke (SAMU 78), climatic parameters (MétéoFrance), pollution (AIRPARIF), and data from influenza epidemic surveillance networks (GROG and Sentinelles). The association between short-term exposure (1-day lag) to environmental triggering factors and stroke occurrence was analyzed using negative-binomial log linear regression model for counting time series. RESULTS: Between 2004 and 2015, a total of 11,037 calls for suspected stroke were recorded. In bivariate analysis, there were associations between calls for suspected stroke and temperature (mean, maximum and minimum), humidity and influenza epidemic. In multivariable analysis, only two variables were associated with calls for suspected stroke: humidity [3.93% excess relative risk (ERR) of stroke per 10% increase in humidity; 95% confidence interval (CI), 1.42 to 6.51; P<0.002] and pollution on the "Air Parif Atmo" scale (2.86% ERR of stroke per 1 unit increase; 95% CI, 1.01 to 4.75; P=0.002). CONCLUSIONS: This study suggests that short-term exposure to air pollution and a high level of humidity are associated with a significant excess relative risk of calls for suspected stroke.

Risk of hepatitis B virus reactivation in hepatitis B virus + hepatitis C virus-co-infected patients with compensated liver cirrhosis treated with ombitasvir, paritaprevir/r + dasabuvir + ribavirin.

Hepatitis B virus may reactivate in patients with chronic hepatitis C treated with direct-acting antivirals. The aim of this study was to investigate the risk of hepatitis B virus (HBV) reactivation in HBV + hepatitis C virus (HCV)-co-infected patients with compensated liver cirrhosis treated with paritaprevir/ombitasvir/ritonavir, dasabuvir with ribavirin. We reviewed prospectively gathered data from a national cohort of 2070 hepatitis C virus patients with compensated liver cirrhosis who received reimbursed paritaprevir/ombitasvir/r, dasabuvir with ribavirin for 12 weeks from the Romanian National Health Agency during 2015-2016. Twenty-five patients in this cohort were HBs antigen positive (1.2%); 15 untreated with nucleotide analogues agreed to enter the study. These patients were followed up: ALT monthly, serology for HBV and DNA viral load at baseline, EOT and SVR at 12 weeks. Hepatitis B virus (HBV)-co-infected patients were all genotype 1b and 52% females, with a median age of 60 years (51 ÷ 74); 76% were pretreated with peginterferon + ribavirin; 72% were with severe necroinflammatory activity on FibroMax assessment; 40% presented comorbidities; and all were HBe antigen negative. Hepatitis C virus (HCV) SVR response rate was 100%. Hepatitis B virus (HBV)-DNA viral load was undetectable in 7/15 (47%) before therapy, and for the other 8 patients, it varied between below 20 and 867 IU/mL. Five patients (33%) presented virological reactivation (>2 log increase in HBV-DNA levels) during therapy. One patient presented with hepatitis associated with HBV reactivation, and two started anti-HBV therapy with entecavir. Hepatitis B virus (HBV) virological reactivation was present in 33% in our patients. Generally, HBV-DNA elevations were mild (<20 000 IU/mL); however, we report one case of hepatitis associated with HBV reactivation.

Assessing the burden of Clostridium difficile infections for hospitals.

BACKGROUND: Nosocomial infections place a heavy burden on the healthcare system. However, quantifying the burden raises many questions, ranging from the way to accurately estimate the extra length of stay at hospital to defining and costing the preventive methods among the different care providers. AIM: To estimate the cost of nosocomial infection by C. difficile to inform the hospital managers. METHODS: Multi-state modelling based on Markov processes and bootstrapping was used to derive individual estimates of the prolongation of stay at hospital associated with Clostridium difficile infection (CDI). Indicators of cost for hospitals were then computed, including an estimation of the productivity losses derived from diagnosis-related group (DRG)-based payment systems. Patients were aged ≥55 years, admitted in two hospital facilities in Lille, with and without an episode of CDI from January 1st, 2013 to September 15th, 2014. FINDINGS: A total of 52 episodes were screened during the study period. The estimated mean cost of CDI was approximately €23,909 (SD: 17,458) for an extended length of hospital stay (N = 27). In the case of a reduced length of hospital stay (N = 25), the mean cost was approximately €-14,697 (SD: 16,936), which represents net savings for the hospitals. The main cost/savings driver was the productivity losses/gains resulting from the nosocomial infection. A sensitivity analysis showed that the main factor explaining the amount of costs or savings due to nosocomial infections was the length of the hospital stay. CONCLUSION: The notion of productivity gains in the case of deaths as a factor revealing the incompleteness of the payment systems is discussed, followed by the methodological issues associated with the statistical method used to control for temporality bias.

CHANGES IN BONE MINERAL PARAMETERS AFTER SLEEVE GASTRECTOMY: RELATIONSHIP WITH GHRELIN AND PLASMA ADIPOKINE LEVELS.

CONTEXT: Metabolic surgery is currently the most efficient treatment for obesity, but concern is raised about the possible long-term nutritional side effects. Bone metabolism is often adversely affected after surgery, but literature data are contradictory. OBJECTIVE: The aim of this study was to evaluate the evolution of bone mass parameters in the first year after laparoscopic sleeve gastrectomy in relation to anthropometric and body composition parameters and specific hormones of obesity. DESIGN: We conducted a prospective study on 75 patients with obesity that underwent metabolic surgery over a course of 18 months at our center, with a follow-up period of 12 months. SUBJECTS AND METHODS: All patients underwent a complex preoperative assessment and were required to return for medical follow-up at 6 and 12 months after surgery. Each visit included anthropometric parameters, DEXA and determination of specific hormonal parameters. RESULTS: We noticed a significant improvement in anthropometric and body composition parameters after surgery. The value of adiponectin presented a significant increase after surgery and leptin showed a significant decrease at 6 and 12 months postoperative; ghrelin level decreased postoperative compared to preoperative, but without statistical significance. We observed no reduction in BMD after surgery, but a significant improvement in BMC at 12 months after surgery compared to preoperative. Ghrelin negatively correlated to BMD preoperative. CONCLUSIONS: Despite the significant alterations in anthropometric, body composition and hormonal parameters, we found no negative effect on BMD and BMC in our study population.

THE VOLUME OF SOLITARY PARATHYROID ADENOMA IS RELATED TO PREOPERATIVE PTH AND 25OH-D3, BUT NOT TO CALCIUM LEVELS.

PURPOSE: To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). PATIENTS AND METHODS: Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. RESULTS: We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). CONCLUSIONS: The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

Exchangeable copper: a reflection of the neurological severity in Wilson's disease.

BACKGROUND AND PURPOSE: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. METHODS: Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. RESULTS: Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 µmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score. CONCLUSIONS: Exchangeable copper determination is useful when diagnosing WD as a value >2.08 µmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.

Impact of Modified TICI 3 versus Modified TICI 2b Reperfusion Score to Predict Good Outcome following Endovascular Therapy.

BACKGROUND AND PURPOSE: The TICI score is widely used to evaluate cerebral perfusion before and after the endovascular treatment of stroke. Recent studies showing the effectiveness and safety of mechanical thrombectomy combine modified TICI 2b and modified TICI 3 to assess the technical success of endovascular treatment. The purpose of this study was to determine how much clinical outcomes differ between patients achieving modified TICI 2b and modified TICI 3 reperfusion. MATERIALS AND METHODS: We analyzed 222 consecutive patients with acute large intracranial artery occlusion of the anterior circulation having achieved modified TICI 2b or modified TICI 3 reperfusion after thrombectomy. The primary end point was the rate of favorable outcome defined as the achievement of a modified Rankin Scale score of 0-2 at 3 months. RESULTS: Patients with modified TICI 3 more often had favorable collateral circulation and atherosclerosis etiology, with a shorter time from onset to reperfusion than patients with modified TICI 2b (all P < .05). The number of total passes to achieve reperfusion was higher in the modified TICI 2b group (median, 2; interquartile range, 1-3, 1-9) versus (median, 1; interquartile range, 1-2, 1-8) in the modified TICI 3 group (P = .0002). Favorable outcome was reached more often for patients with modified TICI 3 than for those with modified TICI 2b (71.7% versus 50.5%, P = .001), with a similar difference when considering excellent outcome. In addition, patients with modified TICI 3 had a lower intracerebral hemorrhage rate (23.0% versus 45.0%, P < .001). CONCLUSIONS: Patients with modified TICI 3 reperfusion have better functional outcomes than those with modified TICI 2b. Given the improving reperfusion rates obtained with thrombectomy devices, future thrombectomy trials should consider modified TICI 2b and modified TICI 3 status separately.

A Direct Aspiration, First Pass Technique (ADAPT) versus Stent Retrievers for Acute Stroke Therapy: An Observational Comparative Study.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers is now the standard therapy for selected patients with ischemic stroke. The technique of A Direct Aspiration, First Pass Technique for the Endovascular Treatment of Stroke (ADAPT) appears promising with a high rate of recanalization. We compared ADAPT versus stent retrievers (the Solitaire device) for efficacy and safety as a front-line endovascular procedure. MATERIALS AND METHODS: We analyzed 243 consecutive patients with large intracranial artery occlusions of the anterior circulation, treated within 6 hours with mechanical thrombectomy by either ADAPT or the Solitaire stent. Th primary outcome was complete recanalization (modified TICI ≥ 2b); secondary outcomes included complication rates and procedural and clinical outcomes. RESULTS: From November 2012 to June 2014, 119 patients were treated with stent retriever (Solitaire FR) and 124 by using the ADAPT with Penumbra reperfusion catheters. The median baseline NIHSS score was the same for both groups (Solitaire, 17 [interquartile range, 11-21] versus ADAPT, 17 [interquartile range, 12-21]). Time from groin puncture to recanalization (Solitaire, 50 minutes [range, 25-80 minutes] versus ADAPT, 45 minutes [range, 27-70 minutes], P = .42) did not differ significantly. However, compared with the Solitaire group, patients treated with ADAPT achieved higher final recanalization rates (82.3% versus 68.9%; adjusted relative risk, 1.18; 95% CI, 1.02-1.37; P = .022), though differences in clinical outcomes between the cohorts were not significant. Use of an adjunctive device was more frequent in the ADAPT group (45.2% versus 13.5%, P < .0001). The rate of embolization in new territories or symptomatic hemorrhage did not differ significantly between the 2 groups. CONCLUSIONS: Front-line ADAPT achieved higher recanalization rates than the Solitaire device. Further randomized controlled trials are warranted to define the best strategy for mechanical thrombectomy.

Impact of thrombolysis in acute ischaemic stroke without occlusion: an observational comparative study.

BACKGROUND AND PURPOSE: The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use. METHODS: A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1. RESULTS: A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results. CONCLUSIONS: Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended.

Adalimumab and Infliximab in Crohn's disease - real life data from a national retrospective cohort study.

AIM: to compare the efficacy and safety of Adalimumab(ADA) and Infliximab(IFX), in a large Romanian population and to identify predictors of response. Methods We performed a national retrospective cohort study including 265 patients (136 ADA, 129 IFX) between 2008-2014. Binary logistic regression was performed with the statistical program Minitab. RESULTS: Patients were half women, with a median age of 36, a median disease duration of 2.5 years, 80% received Azathioprine. Mean therapy duration was 20 months in ADA group and 36 months in IFX group. Complete response to Adalimumab respectively Infliximab was recorded in 77%vs.65%, secondary loss of response in 18%vs.28%, statistically comparable. We failed to identify predictors of response. In 79.2%of patients with secondary loss of response to ADA, the dose was escalated, 12.5% were switched to Infliximab. In 70%of patients that lost response to IFX, the dose was increased, 30% were switched to Adalimumab. CONCLUSIONS: Adalimumab and Infliximab have similar efficacy, with a complete response rate of~70%. In case of secondary loss of response to IFX, the best solution is to switch to ADA, with 83% response rate, while in case of secondary loss of response to ADA, increasing the dose leads to 84 % response rate.

DEVELOPMENT OF SYNTHETIC GROWTH CHARTS FOR ROMANIAN POPULATION.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study.The aim of the present paper is to present the new synthetic growth references for Romanian children. MATERIAL AND METHODS: We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. RESULTS: We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. CONCLUSION: We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

A RARE CASE OF SEVERE TYPE 4 POLYGLANDULAR AUTOIMMUNE SYNDROME IN A YOUNG ADULT.

OBJECTIVE: The association of type 1 diabetes mellitus with autoimmune thyroiditis or with celiac disease is frequently mentioned in literature, but the concomitant presence of these three autoimmune diseases, especially in adults, represents a rarity. CASE REPORT: We present the case of a young man with severe generalized oedema admitted to the emergency department and diagnosed with severe hypothyroidism (TSH=100 µUI/mL, fT4 = 0.835 pmol/L) in the context of a long-lasting autoimmune thyroiditis (anti-TPO antibodies 64 UI/mL, anti-TG antibodies 17 UI/mL, the thyroid ultrasonography). At the same time, he was diagnosed with type 1 diabetes mellitus. He was also submitted to further tests which confirmed the diagnosis of celiac disease (endoscopy with intestinal mucosa biopsy, confirmed by immunological tests). The association of these three diseases slows down the process of reaching a final diagnosis and delays the adoption of a therapeutic strategy. CONCLUSION: This case underlines the difficulty of differential diagnosis of severe oedema syndrome with polyserositis in a patient with polyglandular autoimmune syndrome. Whenever there is a suspicion of the association of these autoimmune diseases, the evolution of the patient is unpredictable and most medical results are highly dependent upon the decision of applying a concomitant treatment.

Progress in digestive endoscopy: Flexible Spectral Imaging Colour Enhancement (FICE)-technical review.

Background. A substantial advance in digestive endoscopy that has been made during the last decade is represented by digital chromoendoscopy, which was developed as a quicker and sometimes better alternative to the gold standard of dye spraying. Fujifilm developed a virtual coloration technique called Flexible spectral Imaging Color Enhancement (FICE). FICE provides a better detection of lesions of "minimal" esophagitis, of dysplasia in Barrett's esophagus and of squamous cell esophageal cancer. The use of FICE resulted in an improvement in the visualization of the early gastric cancer, being less invasive, and time consuming than the classic dye methods. Current evidence does not support FICE for screening purposes in colon cancer but it definitely improves characterization of colonic lesions. Its use in inflammatory bowel disease is still controversial and in video capsule endoscopy is considered a substantial progress. Conclusions. The use of FICE endoscopy in routine clinical practice can increase the diagnostic yield and can provide a better characterization of lesions. Future studies to validate its use, the good choice of channels, and the "perfect indications" and to provide common definitions and classifications are necessary.

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report]. / Invaginatie intestinala prin tumora gastrointestinala stromala ileala--prezentare de caz.

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

Isolated splenic metastasis of endometrial adenocarcinoma--a case report.

The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

[Radical neck dissection in advanced thyroid cancer]. / Disectia radicala a gâtului in cancerul tiroidian avansat.

We try to ascertain whether total thyroidectomy with radical neck dissection offers a survival and recurrency advantage for thyroid cancer. Between January 2000 and September 2009 in the 3rd Surgical Unit of the "Sf. Spiridon" Hospital of Iasi 189 operations were performed for malign thyroid disorders, 164 (86,77%) of which were performed for the papillary or foliculary cancer. The diagnosis was confirmed by hystopathological examination. The patients had a medium age of 51,48 (extremes 19 - 81 years). Women had a greater proportion, as expected (sex ratio F:M = 2,85:1). 59 total thyroidectomy with radical or modified radical neck dissection were performed. There were immediate (6 bleedings which needed reoperation for haemostasis, 7 unilateral recurrent laryngeal nerve injury) and late complications (8 cases of recurrency in the first 2 years). Total thyroidectomy with radical neck dissection became the ellective method for advanced thyroid cancer (the best results were for papillary cancer, female and age over 55).

Functional data analysis for gait curves study in Parkinson's disease.

In Parkinson's disease, precise analysis of gait disorders remains essential for the diagnostic or the evaluation of treatments. During a gait analysis session, a series of successive dynamic gait trials are recorded and data involves a set of continuous curves for each patient. An important aspect of such data is the infinite dimension of the space data belong. Therefore, classical multivariate statistical analysis are inadequate. Recent methods known as functional data analysis allow to deal with this kind of data. In this paper, we present a functional data analysis approach for solving two problems encountered in clinical practice: (1) for a given patient, assessing the reliability of the gait curves corresponding to the different trials (2) performing intra individual curves comparisons for assessing the effect of a therapy. In a first step, each discretized curve was interpolated using cubic B-splines bases in order to ensure the continuous character of data. A cluster analysis was performed on the smoothed curves to assess the reliability and to identify a subset of representative curves for a given patient. Intra individual curves comparisons were carried out in the following way: (1) functional principal component analysis was performed to describe the temporal structure of data and to derive a finite number of reliable principal components. (2) These principal components were used in a linear discriminant analysis to point out the differences between the curves. This procedure was applied to compare the gait curves of 12 parkinsonian patients under 4 therapeutic conditions. This study allowed us to develop objective criteria for measuring the improvements in a subject's gait and comparing the effect of different treatments. The methods presented in this paper could be used in other medical domains when data consist in continuous curves.