Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS) : study protocol for a randomized controlled trial

Background: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS. Methods/Design: The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography. Discussion: The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Effect of an apple brandy from normandy and of ethanol on epithelial cell proliferation in the esophagus of rats

The effects on cell population kinetics in the distal esophagus of an apple brandy from Normandy (Calvados), of ethanol diluted at a similar concentration, and of saline were investigated in rats. Animals were killed at 0. 6, 12, 18 and 24 h after a single intraesophageal instillation, and at 3 weeks after chronic administration of these solutions. In vivo labeling with [3H]-thymidine and autoradiography were carried out to determine the proliferative parameters. Vincristine sulfate was used to increase metaphase figures during the chronic experiment. Instillation of saline did not modify the parameters under study. Single instillations of both apple brandy and 56° ethanol were followed by a significant increase in labeling (p < 0.01) and mitotic indices (p < 0.01). Chronic administration of both apple brandy and 56° ethanol increased the labeling index (p < 0.01) as well as the metaphase index (p < 0.01). The proliferative responses after the apple brandy and after 56° ethanol were similar in amplitude. These data suggest that ethanol alone may explain the mitogenic effect of Calvados in the esophagus. © 1987 S. Karger AG, Basel.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Long-term evolution of the mineral metabolism after renal transplantation : a prospective, single-center cohort study

Background. Abnormalities in bone and mineral metabolism are common after renal transplantation (RT) but information on their long-term time course is scarce. Objectives. (1) Evaluate the time course of biochemical parameters of bone and mineral metabolism over 60 months after RT; (2) identify predictors for persistent hyperparathyroidism (HPT). Design. Prospective, longitudinal, single-center cohort study. Methods. We determined serum levels (mean values +/- standard deviations) of intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (APh), calcitriol, and creatinine (Cr) preoperatively as well as 6, 12, 24, 36, 48, and 60 months after cadaveric RT in 49 patients. We in addition recorded demographic, clinical, and therapeutic data. Results. Pretransplantation iPTH stabilized from 194.2 +/- 273.5 to 71.5 +/- 50.7 ng/L at 6 months. Serum Ca (9.5 +/- 1.1 mg/dL) and APh (81.9 +/- 42.1 U/L) did not change. Baseline serum P (5.7 +/- 1.8 mg/dL) and serum Mg (2.4 +/- 0.4 mg/dL) decreased to normal ranges from month 6 onward. Low baseline calcitriol (22.4 +/- 21.8 pmol/L) normalized slowly by 12 months (95.4 +/- 46.7 pmol/L). Stable graft function (53.2 +/- 15.8 mL/min) was achieved from 6 months onward. By 60 months, 26.5% of patients had a serum Ca above 9.8 mg/dL and serum P below 2.7 mg/dL; 22.4%, an Mg below 1.7 mg/dL and 8.2%, a serum iPTH more than 2.5-fold the upper limit of normal. Upon multiple regression analyses the iPTH at 60 months was influenced by a dialysis duration >= 2 years (beta = 0.259, P = .003), body mass index > 25 kg/m(2) (beta = 0.257, P = .006), baseline iPTH (beta = 0.182, P = .036), serum Cr (beta = 0.268, P = .002) and Mg (beta = -0.242, P = .006). Conclusions. Hypercalcemia, hypophosphatemia, hypomagnesemia, and elevated iPTH persist in a subset of post-RT patients. Pretransplantation iPTH and obesity, dialysis duration, and posttransplant serum creatininemia and hypomagnesemia independently contribute to persistent HPT

Laparoscopic versus open resection of gastrointestinal stromal tumors of the stomach

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Surgical treatment is the only chance of cure for patients with a primary localized GIST. A laparoscopic approach has been considered reasonable for these tumors of gastric origin. The current study compares the outcome of laparoscopic versus open resection of gastric GISTs and compares our series with the few published studies comparing the open versus the laparoscopic approach. From a prospectively collected database, we found 53 primary gastric GIST resections that were performed in our department. Laparoscopic (LAP) resections were performed in 37 patients and traditional (OPEN) resections in 16 patients. Clinical and pathologic characteristics and surgical outcomes were analyzed according to surgical procedure. Patients who underwent LAP or OPEN resection of gastric GISTs did not differ with respect to age at operation, gender, clinical presentation, and tumor size. Operative time was significantly lower for LAP than for OPEN resection, with a mean duration of 45 and 132.5 min, respectively (p < 0.001). LAP resection yielded a significantly shorter length of stay (median 7 vs. 14 days; p = 0.007) and lower 30-day morbidity rate (2.7 % vs. 18.9 %; p = 0.077). The operative mortality was 12.5 % after OPEN resection and there was no operative mortality after LAP (p = 0.087). The recurrence rate was significantly lower after LAP surgery (0 % vs. 37.5 %; p < 0.001). All patients in the LAP group are alive without recurrence, and 25 % (4/16) of the OPEN group are alive with recurrence but in complete remission under imatinib mesylate treatment. Two patients of the open group died due to progression of GIST (p = 0.087). Compared to open resection, laparoscopic resection of gastric stromal tumors is associated with a shorter operation time, a shorter hospital stay, and a lower recurrence rate

Loosening of a noncemented porous-coated anatomic femoral component in Gaucher's disease. A case report and review of literature.

There are few reports of experiences with hip arthroplasty in patients with Gaucher's disease. Review of the literature shows a high rate of loosening after any type of arthroplasty. The clinical, roentgenographic and histopathological findings of a porous-coated hip arthroplasty in Gaucher's disease necessitating revision after 5 years are reported. Because we found typical lipid-laden Gaucher cells at the bone prosthesis interface we support the hypothesis that loosening in Gaucher's disease is due to continued Gaucher cell proliferation and erosion of bone. Loosening seems to be related to the disease and not to a specific type of prosthetic component.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Massive resection and prosthetic replacement for the treatment of metastases of the trochanteric and subtrochanteric femoral region bipolar arthroplasty versus total hip arthroplasty.

Twenty-eight metastases of the proximal femur were treated by resection and by prosthetic replacement using a large femoral component with diaphyseal support (megaprosthesis). When metastatic involvement of the acetabulum was not evident a mobile self-centering cup was used (bipolar hip arthroplasty: 17 cases). When metastatic destruction of the acetabulum was evident acetabular reconstruction was performed (total hip arthroplasty: 11 cases). Postoperative pain relief according to Habermann was excellent in 81.5% and good in 14.8% of the patients. The functional results according to Merle d'Aubigné were rated as excellent in 19%, very good in 22%, and good in 22% of the hips. The rate of postoperative dislocation was significantly lower (p < 0.05) in the bipolar arthroplasty group when compared to the total hip arthroplasty group. Our experience indicates that, when bone disease of the acetabulum is not evident, a bipolar arthroplasty rather than a total hip arthroplasty should be recommended. In the current series pain relief as well as postoperative walking ability were comparable in both groups but the dislocation rate was significantly lower with bipolar arthroplasty.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Self-reported health promotion and disability progression in multiple sclerosis

<p>Background: Health behavior may be associated with disability progression in multiple sclerosis (MS).</p><p>Objectives: To investigate health-promoting behavior as measured by the Health-Promoting Lifestyle Profile II, which includes the subscales of health responsibility, physical activity, nutrition, spiritual growth, interpersonal relationships and stress management.</p><p>Methods: We conducted a cross-sectional survey among individuals with MS, registered by the Flemish MS society, Belgium. Scores for the total scale and subscales were categorized into quintiles. A time-to-event analysis and Cox proportional hazard regression were performed with time to Expanded Disability Status Score (EDSS) of 6 (requires a cane) as an outcome measure. Hazard ratios for the time from onset and the time from birth were adjusted for gender, age at onset and immunomodulatory treatment. The first category was the reference group (first quintile).</p><p>Results: Data on 1372 respondents with definite MS were collected. Subjects with relapsing onset MS and higher scores for overall health-promoting behavior, and the subscales of physical activity, nutrition and spiritual growth, had a reduced risk of reaching EDSS 6 compared to the reference group. No associations were found for the subscales of health responsibility, stress management and interpersonal relations. In progressive onset MS, no significant associations were obtained.</p><p>Conclusion: Our study shows an association of self-reported health promoting behavior with disability progression in subjects with relapsing onset MS. (C) 2012 Elsevier B.V. All rights reserved.</p>

Waist circumference is an independent risk factor for the development of parastomal hernia after permanent colostomy

PURPOSE: This study was performed to evaluate the risk factors of parastomal hernia after abdominoperineal rectal amputation. METHODS: This was a retrospective study of consecutive patients who underwent abdominoperineal rectal amputation for rectal cancer between January 1999 and August 2006. The effects of age, sex, surgical approach, chemotherapy, waist circumference, and body mass index on the development of a parastomal hernia were analyzed. RESULTS: Forty-one patients underwent 19 open and 22 laparoscopic abdominoperineal rectal amputations. A parastomal hernia developed in 19 patients (46 percent) after a median follow-up period of 31 (range, 5-80) months. We observed ten hernias in the open group and nine in the laparoscopic group (P=0.453). There were no significant differences in the type of surgical approach, age, sex, or adjuvant therapy in patients who developed a parastomal hernia compared with those who did not. Waist circumference proved to be an independent risk factor (P=0.011). When the waist circumference exceeds the calculated threshold of 100 cm, there is a 75 percent probability to develop a parastomal hernia. CONCLUSIONS: Abdominal obesity increases the risk of developing a parastomal hernia, therefore, it might be advisable to place a prophylactic mesh during colostomy formation when the patient's waist exceeds 100 cm