scholarly journals Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS

2019 ◽  
Vol 6 (5) ◽  
pp. e591 ◽  
Author(s):  
Angelo Ghezzi ◽  
Giancarlo Comi ◽  
Luigi Maria Grimaldi ◽  
Lucia Moiola ◽  
Carlo Pozzilli ◽  
...  
Keyword(s):  
Safety Profile ◽  
Time Course ◽  
Pediatric Patients ◽  
Short Term ◽  
Elimination Phase ◽  
Relapsing Remitting ◽  
Distribution Phase

ObjectiveThis phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS).MethodsPediatric patients with RRMS who were prescribed natalizumab 300 mg IV every 4 weeks were enrolled. Blood samples were collected on days 1, 2, 8, 15, and 22 and at weeks 4, 8, 12, and 16 to estimate PK parameters; PD properties were evaluated by measuring α4-integrin saturation and lymphocyte counts over time. Natalizumab's safety profile was also evaluated.ResultsPK parameters were similar to those reported in adult patients; natalizumab concentrations peaked approximately 1 day after infusion in most of the participants (Cmax 142.9 μg/mL, AUClast 47389.4 hr*μg/mL), followed by a biphasic decline with a rapid distribution phase and a slow elimination phase, with a terminal half-life of 215.1 hours. In terms of PD, both time course and magnitude of α4-integrin saturation and increase in lymphocyte counts were similar to those observed in adults. During the 16-week study follow-up, 3 adverse events attributed to natalizumab were observed; no unexpected safety events occurred.ConclusionsPK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults.Classification of evidenceThis study provides Class I evidence that natalizumab PK/PD parameters and safety profile are similar in adults and pediatric patients in the short term. Longer studies, also including a larger number of younger subjects (aged 10–12 years), are required to further inform about long-term PK and PD parameters in pediatric patients with MS.

The predictive value of gadolinium enhancement for long term disability in relapsing-remitting multiple sclerosis-preliminary results

2001 ◽  
Vol 7 (1) ◽  
pp. 23-25 ◽  
Author(s):  
N A Losseff ◽  
D H Miller ◽  
D Kidd ◽  
A J Thompson
Keyword(s):  
Multiple Sclerosis ◽  
Median Number ◽  
Short Term ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Relapsing Remitting Multiple Sclerosis

As short-term MRI studies are increasingly being used to monitor disease activity in multiple sclerosis (MS) it is vital to establish if short-term MRI activity is predictive of long term clinical outcome. We followed up after 5 years a group of 10 benign (relapsing-remitting MS with a disease duration 410 years and EDSS 43) and 10 early relapsing-remitting patients who previously had monthly serial MRI scans for 6 months. In the early relapsing-remitting group median EDSS at entry to the initial serial study was three and in the benign group 2.5. At 5-year follow up, five of these 20 patients had developed a definite deterioration in EDSS. The median number of new enhancing lesions detected originally in the group that had deteriorated was 11 (7-17) compared to 0 (0-5) new enhancing lesions, for those who had not deteriorated (P50.05). There was a trend towards a higher baseline T2 lesion load in the group with a definite change in EDSS but this was not significant. This study suggests that short-term measurement of the number of gadolinium enhancing lesions may predict long term outcome in relapsing-remitting MS.

Predicting the severity of relapsing-remitting MS: The contribution of cross-sectional and short-term follow-up MRI data

2011 ◽  
Vol 17 (6) ◽  
pp. 695-701 ◽  
Author(s):  
C Enzinger ◽  
S Fuchs ◽  
A Pichler ◽  
M Wallner-Blazek ◽  
M Khalil ◽  
...  
Keyword(s):  
Clinical Course ◽  
Multiple Regression Model ◽  
Outcome Variable ◽  
Observational Period ◽  
Short Term ◽  
Cross Sectional ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri

Background and objective: Predicting the long-term clinical course of multiple sclerosis (MS) is difficult on clinical grounds. Recent studies have suggested magnetic resonance imaging (MRI) metrics to be helpful. We wanted to confirm this. Methods: Contactable individuals ( N = 84) from an initial 99 patients with relapsing–remitting MS (RRMS) who had undergone careful baseline and 2-year follow-up examinations including MRI were reassessed after a mean of 10.8 ± 2.7 years. We investigated using multivariate linear regression analyses if clinical and MRI data obtained at the prior time-points and the rates of change in morphologic variables over a mean observational period of 2.5 years could have served to predict a patient’s MS severity score (MSSS) 11 years later. Conversion to secondary progressive MS (SPMS) was a further outcome variable. Results: In univariate analyses, the ‘black hole ratio’ (BHR) at baseline ( p = 0.017, beta = 0.148) and at first follow-up ( p = 0.007, beta = −0.154) was the only MRI parameter showing a significant correlation with the MSSS. In a multiple regression model, the independent predictive value of imaging variables became statistically non-significant and the latest MSSS was predicted primarily by the baseline EDSS ( r2 = 0.28; p < 0.001). The BHR at baseline explained 9.4% of variance of conversion to SPMS ( p = 0.033). Over the observational period the MSSS remained stable in patients remaining RRMS, but increased in converters to SPMS from 4.0 to 6.4. Conclusions: We failed to confirm a clear independent contribution of cross-sectional and short-term follow-up MRI data for the prediction of the long-term clinical course of MS. The MSSS is not a stable indicator of disease severity but may increase in converters to SPMS.

Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study

2011 ◽  
Vol 17 (7) ◽  
pp. 867-875 ◽  
Author(s):  
E Le Page ◽  
E Leray ◽  
G Edan ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Safety Profile ◽  
Left Ventricular ◽  
Large Cohort ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients

Background: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS). Methods: Eight hundred and two patients from 12 MS centres (308 relapsing–remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6–12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after. Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.

scholarly journals Split laminotomy versus conventional laminotomy: postoperative outcomes in pediatric patients

2018 ◽  
Vol 21 (6) ◽  
pp. 615-625 ◽  
Author(s):  
Elsa V. Arocho-Quinones ◽  
Amie Kolimas ◽  
Peter S. LaViolette ◽  
Bruce A. Kaufman ◽  
Andrew B. Foy ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Postoperative Pain ◽  
Muscle Atrophy ◽  
Pediatric Patients ◽  
Spinal Instability ◽  
Opioid Use ◽  
Short Term ◽  
Daily Pain

OBJECTIVESplit laminotomy is a technique for accessing the spinal canal from the posterior midline that minimizes muscle dissection and bone removal. Benefits of this approach in minimizing postoperative pain and muscle atrophy in the adult population have been reported, but pediatric data are limited. Herein, the authors evaluate the benefits of the split laminotomy technique in pediatric patients.METHODSData obtained in patients who underwent posterior spine surgery at Children’s Hospital of Wisconsin for an intradural midline pathology between April 2008 and June 2015 were reviewed retrospectively. Each patient was assigned to one of two groups, the split-laminotomy or conventional-laminotomy group. The primary outcomes assessed were mean daily pain score, total opioid use over a period of 72 hours after surgery, and the degree of paraspinal muscle atrophy and fat infiltration found on short-term (1–4 months) and long-term (1–4 years) follow-up spine MRI studies.RESULTSA total of 117 patients underwent lumbar-level surgery (83 conventional laminotomy, 34 split laminotomy), and 8 patients underwent thoracic-level surgery (4 in each group). No significant difference in the mean daily pain scores between groups was found. The daily opioid use was significantly lower in the split-laminotomy group on postoperative day 0 (POD0) and POD1 but not on POD2 (p = 0.01, 0.01, and 0.10, respectively). The total opioid use over the 72-hour postoperative period was significantly lower in the split-laminotomy group (p = 0.0008). The fat/muscle ratio was significantly higher in both the short-term and long-term follow-up periods in the conventional-laminotomy group (p = 0.01 and 0.0002, respectively). The rate of change of paraspinal muscle fat infiltration was significantly lower in the split-laminotomy group than in the conventional-laminotomy group (p = 0.007). The incidence of complications was not significantly different between groups (p = 0.08).CONCLUSIONSThis study was of the largest series reported thus far of pediatric patients who underwent split laminotomy and the only controlled study that has involved children. The authors’ results reinforce the short-term benefit of split laminotomy in minimizing acute postoperative pain and long-term benefits of decreasing muscle atrophy and fatty degeneration, which are known to be associated with the development of chronic pain and spinal instability. Additional efforts for assessing long-term effects in the development of chronic pain, spinal instability, and spinal deformity are still necessary.

Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽  
2019 ◽  
Vol 48 (4) ◽  
pp. 321-329
Author(s):  
Mariya Kronlage ◽  
Erwin Blessing ◽  
Oliver J. Müller ◽  
Britta Heilmeier ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Limb Ischemia ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Short Term ◽  
Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

Long-term outcomes of lumbar microdiscectomy in the pediatric population: a large single-institution case series

2019 ◽  
Vol 24 (5) ◽  
pp. 549-557
Author(s):  
Malia McAvoy ◽  
Heather J. McCrea ◽  
Vamsidhar Chavakula ◽  
Hoon Choi ◽  
Wenya Linda Bi ◽  
...  
Keyword(s):  
Conservative Management ◽  
Functional Outcomes ◽  
Pediatric Patients ◽  
Clinical Presentation ◽  
Case Series ◽  
Csf Leak ◽  
Single Institution ◽  
The Mean

OBJECTIVEFew studies describe long-term functional outcomes of pediatric patients who have undergone lumbar microdiscectomy (LMD) because of the rarity of pediatric disc herniation and the short follow-up periods. The authors analyzed risk factors, clinical presentation, complications, and functional outcomes of a single-institution series of LMD patients over a 19-year period.METHODSA retrospective case series was conducted of pediatric LMD patients at a large pediatric academic hospital from 1998 to 2017. The authors examined premorbid risk factors, clinical presentation, physical examination findings, type and duration of conservative management, indications for surgical intervention, complications, and postoperative outcomes.RESULTSOver the 19-year study period, 199 patients underwent LMD at the authors’ institution. The mean age at presentation was 16.0 years (range 12–18 years), and 55.8% were female. Of these patients, 70.9% participated in competitive sports, and among those who did not play sports, 65.0% had a body mass index greater than 25 kg/m2. Prior to surgery, conservative management had failed in 98.0% of the patients. Only 3 patients (1.5%) presented with cauda equina syndrome requiring emergent microdiscectomy. Complications included 4 cases of postoperative CSF leak (2.0%), 1 case of a noted intraoperative CSF leak, and 3 cases of wound infection (1.5%). At the first postoperative follow-up appointment, minimal or no pain was reported by 93.3% of patients. The mean time to return to sports was 9.8 weeks. During a mean follow-up duration of 8.2 years, 72.9% of patients did not present again after routine postoperative appointments. The total risk of reoperation was a rate of 7.5% (3.5% of patients underwent reoperation for the same level; 4.5% underwent adjacent-level decompression, and one patient [0.5%] ultimately underwent a fusion).CONCLUSIONSMicrodiscectomy is a safe and effective treatment for long-term relief of pain and return to daily activities among pediatric patients with symptomatic lumbar disc disease in whom conservative management has failed.

Long-term stability of fusiform dilatation of the internal carotid artery following surgery adjacent to the circle of Willis: report of 2 cases

2020 ◽  
pp. 1-4
Author(s):  
Madeline B. Karsten ◽  
R. Michael Scott
Keyword(s):  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Arachnoid Cyst ◽  
Pediatric Patients ◽  
Internal Carotid ◽  
Imaging Finding ◽  
Neurological Status ◽  
Suprasellar Region

Fusiform dilatation of the internal carotid artery (FDCA) is a known postoperative imaging finding after craniopharyngioma resection. FDCA has also been reported following surgery for other lesions in the suprasellar region in pediatric patients and is thought to be due to trauma to the internal carotid artery (ICA) wall during tumor dissection. Here, the authors report 2 cases of pediatric patients with FDCA. Case 1 is a patient in whom FDCA was visualized on follow-up scans after total resection of a craniopharyngioma; this patient’s subsequent scans and neurological status remained stable throughout a 20-year follow-up period. In case 2, FDCA appeared after resection and fenestration of a giant arachnoid cyst in a 3-year-old child, with 6 years of stable subsequent follow-up, an imaging finding that to the authors’ knowledge has not previously been reported following surgery for arachnoid cyst fenestration. These cases demonstrate that surgery involving dissection adjacent to the carotid artery wall in pediatric patients may lead to the development of FDCA. On very long-term follow-up, this imaging finding rarely changes and virtually all patients remain asymptomatic. Neurointerventional treatment of FDCA in the absence of symptoms or significant late enlargement of the arterial ectasia does not appear to be indicated.

Exercise interventions in lateral elbow tendinopathy have better outcomes than passive interventions, but the effects are small: a systematic review and meta-analysis of 2123 subjects in 30 trials

2020 ◽  
pp. bjsports-2020-102525
Author(s):  
Stefanos Karanasios ◽  
Vasileios Korakakis ◽  
Rod Whiteley ◽  
Ioannis Vasilogeorgis ◽  
Sarah Woodbridge ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Short Term ◽  
Lateral Elbow ◽  
Long Term Follow Up ◽  
Wait And See ◽  
Lateral Elbow Tendinopathy

ObjectiveTo evaluate the effectiveness of exercise compared with other conservative interventions in the management of lateral elbow tendinopathy (LET) on pain and function.DesignSystematic review and meta-analysis.MethodsWe used the Cochrane risk-of-bias tool 2 for randomised controlled trials (RCTs) to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation methodology to grade the certainty of evidence. Self-perceived improvement, pain intensity, pain-free grip strength (PFGS) and elbow disability were used as primary outcome measures.Eligibility criteriaRCTs assessing the effectiveness of exercise alone or as an additive intervention compared with passive interventions, wait-and-see or injections in patients with LET.Results30 RCTs (2123 participants, 5 comparator interventions) were identified. Exercise outperformed (low certainty) corticosteroid injections in all outcomes at all time points except short-term pain reduction. Clinically significant differences were found in PFGS at short-term (mean difference (MD): 12.15, (95% CI) 1.69 to 22.6), mid-term (MD: 22.45, 95% CI 3.63 to 41.3) and long-term follow-up (MD: 18, 95% CI 11.17 to 24.84). Statistically significant differences (very low certainty) for exercise compared with wait-and-see were found only in self-perceived improvement at short-term, pain reduction and elbow disability at short-term and long-term follow-up. Substantial heterogeneity in descriptions of equipment, load, duration and frequency of exercise programmes were evident.ConclusionsLow and very low certainty evidence suggests exercise is effective compared with passive interventions with or without invasive treatment in LET, but the effect is small.PROSPERO registration numberCRD42018082703.

scholarly journals Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaorong Yan ◽  
Huiqing Wang ◽  
Cai Li ◽  
Yuanxiang Lin ◽  
Lin Lin ◽  
...  
Keyword(s):  
Surgical Technique ◽  
Spinal Deformity ◽  
Tumor Recurrence ◽  
Clinical Symptoms ◽  
Short Term ◽  
Before And After ◽  
Intradural Extramedullary ◽  
Controlled Surgery

Abstract Background To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. Methods In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. Results All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

scholarly journals Comparative short-term and long-term outcomes between internal and external intestinal plication in the management of small bowel obstruction

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Song Liu ◽  
Qiongyuan Hu ◽  
Lihua Shao ◽  
Xiaofeng Lu ◽  
Xiaofei Shen ◽  
...  
Keyword(s):  
Small Bowel ◽  
Small Bowel Obstruction ◽  
Bowel Obstruction ◽  
Short Term ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Gut Dysfunction ◽  
Gut Function

Abstract Background Small bowel obstruction (SBO) is common and usually requires surgical intervention. Intestinal plication is a traditional but critical strategy for SBO in certain scenarios. This study is to compare the short-term and long-term outcome between internal and external plications in the management of SBO. Methods All patients receiving intestinal plication in our hospital were retrospectively collected. Short-term outcome including postoperative complications, reoperation, postoperative ICU stay, starting day of liquid diet and postoperative hospitalization, as well as long-term outcome including recurrence of obstruction, readmission, reoperation and death were compared between groups. Gut function at annual follow-up visits was evaluated as well. Results Nine internal and 11 external candidates were recruited into each group. The major causes of plication were adhesive obstruction, abdominal cocoon, volvulus and intussusception. Lower incidence of postoperative complication (p = 0.043) and shorter postoperative hospitalization (p = 0.049) was observed in internal group. One patient receiving external plication died from anastomosis leakage. During the 5-year follow-up period, the readmission rate was low in both groups (22.2 % vs. 9.1 %), and none of patients required reoperation or deceased. None of patients exhibited gut dysfunction, and all patients restored normal gut function after 4 years. Patients in external group demonstrated accelerated recovery of gut function after surgery. Conclusions This study compares short-term and long-term outcome of patients receiving internal or external intestinal plication. We suggest a conservative attitude toward external plication strategy. Surgical indication for intestinal plication is critical and awaits future investigations.

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