scholarly journals Using biomarkers to predict clinical outcomes in multiple sclerosis

2019 ◽  
Vol 19 (4) ◽  
pp. 342-349 ◽  
Author(s):  
Daniel Castle ◽  
Ray Wynford-Thomas ◽  
Sam Loveless ◽  
Emily Bentley ◽  
Owain W Howell ◽  
...  

Long-term outcomes in multiple sclerosis (MS) are highly varied and treatment with disease-modifying therapies carries significant risks. Finding tissue biomarkers that can predict clinical outcomes would be valuable in individualising treatment decisions for people with MS. Several candidate biomarkers—reflecting inflammation, neurodegeneration and glial pathophysiology—show promise for predicting outcomes. However, many candidates still require validation in cohorts with long-term follow-up and evaluation for their independent contribution in predicting outcome when models are adjusted for known demographic, clinical and radiological predictors. Given the complexity of MS pathophysiology, heterogeneous panels comprising a combination of biomarkers that encompass the various aspects of neurodegenerative, glial and immune pathology seen in MS, may enhance future predictions of outcome.

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.


2022 ◽  
Vol 58 (1) ◽  
pp. 7-16
Author(s):  
Claudio Motta ◽  
Philip Witte ◽  
Andrew Craig

ABSTRACT The objective of this study was to document the short- and medium-to-long-term outcomes and complication rates of Y-T humeral condylar fractures fixed using titanium polyaxial locking plate (T-PLP). A retrospective review was performed of the medical records and radiographs of dogs with a Y-T humeral condylar fracture treated with T-PLP at a single veterinary referral center (2012–2018). Seventeen cases met the inclusion criteria. Medium- to long-term follow-up (.6 mo) information was derived using the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. Recorded complications were catastrophic (1/17) and minor (2/17). Gait at 10–12 wk following surgery was subjectively assessed as good or excellent for 13 cases. Radiographic bone union was achieved in 7/12 cases at 4–6 wk. LOAD scores obtained a mean of 15 mo (range 6–29 mo) following surgery and indicated no or mild impairment in 15/16 and moderate functional impairment in 1. The application of T-PLP for the treatment of Y-T humeral condylar fractures resulted in adequate stabilization allowing successful fracture healing and medium- to long-term outcomes comparable to previous reports. According to results of LOAD testing, the medium- to long-term follow-up suggests that clients were aware of mild to moderate functional impairment in all cases.


2018 ◽  
Vol 24 (6) ◽  
pp. 666-673 ◽  
Author(s):  
Sung Hyun Baik ◽  
Hyo Sung Kwak ◽  
Gyung Ho Chung ◽  
Seung Bae Hwang

Background Insertion of a balloon-expandable stent (BES) in patients with symptomatic intracranial atherosclerosis is a treatment option for reperfusion therapy. In this study, we retrospectively reviewed clinical outcomes during long-term follow-up after insertion of balloon-expandable stents in patients with symptomatic middle cerebral artery (MCA) stenosis. Methods Institutional review board approval was obtained for retrospective review of patient data. Thirty-four patients (15 men, 19 women; median age, 67.5 years) with symptomatic MCA stenosis underwent balloon-expandable stent insertion between June 2008 and December 2010. Patient records were reviewed for angiographic findings and clinical outcomes during long-term follow-up. Results Of these patients, 22 presented with acute ischemic stroke with underlying MCA atherosclerosis and had good clinical outcomes (modified Rankin Scale score (mRS): 0–2) after reperfusion therapy. Indications for stenting for the remaining 12 patients were recurrent transient ischemic attacks (TIAs) refractory to medical therapy and MCA stenosis greater than 70%. During the poststenting follow-up period, which ranged from 61 to 108 months (median, 67.5 months), a TIA occurred in five patients. Of these five patients, one experienced a complete reocclusion of the MCA stent, and three had symptomatic restenosis. The remaining 29 patients did not experience any further ischemic events or restenosis during the follow-up period. Conclusions In our study, treatment with balloon-expandable stents in patients with symptomatic MCA stenosis resulted in low recurrence rates for both ischemic events and restenosis during long-term follow-up.


2021 ◽  
Vol 8 ◽  
Author(s):  
Congcong Luo ◽  
Ruidong Qi ◽  
Yongliang Zhong ◽  
Suwei Chen ◽  
Hao Liu ◽  
...  

Background: This study aimed to evaluate the early and long-term outcomes of a single center using a frozen elephant trunk (FET) procedure for chronic type B or non-A non-B aortic dissection.Methods: From February 2009 to December 2019, 79 patients diagnosed with chronic type B or non-A non-B aortic dissection who underwent the FET procedure were included in the present study. We analyzed operation mortality and early and long-term outcomes, including complications, survival and interventions.Results: The operation mortality rate was 5.1% (4/79). Spinal cord injury occurred in 3.8% (3/79), stroke in 2.5% (2/79), and acute renal failure in 5.1% (4/79). The median follow-up time was 53 months. The overall survival rates were 96.2, 92.3, 88.0, 79.8, and 76.2% at 1/2, 1, 3, 5 and 7 years, respectively. Moreover, 79.3% of patients did not require distal aortic reintervention at 7 years. The overall survival in the subacute group was superior to that in the chronic group (P = 0.047).Conclusion: The FET technique is a safe and feasible approach for treating chronic type B and non-A non-B aortic dissection in patients who have contraindications for primary endovascular aortic repair. The technique combines the advantages of both open surgical repair and endovascular intervention, providing comparable early and long-term follow-up outcomes and freedom from reintervention.


2018 ◽  
Vol 129 (6) ◽  
pp. 1492-1498 ◽  
Author(s):  
Masaomi Koyanagi ◽  
Akira Ishii ◽  
Hirotoshi Imamura ◽  
Tetsu Satow ◽  
Kazumichi Yoshida ◽  
...  

OBJECTIVELong-term follow-up results of the treatment of unruptured intracranial aneurysms (UIAs) by means of coil embolization remain unclear. The aim of this study was to analyze the frequency of rupture, retreatment, stroke, and death in patients with coiled UIAs who were followed for up to 20 years at multiple stroke centers.METHODSThe authors retrospectively analyzed data from cases in which patients underwent coil embolization between 1995 and 2004 at 4 stroke centers. In collecting the late (≥ 1 year) follow-up data, postal questionnaires were used to assess whether patients had experienced rupture or retreatment of a coiled aneurysm or any stroke or had died.RESULTSOverall, 184 patients with 188 UIAs were included. The median follow-up period was 12 years (interquartile range 11–13 years, maximum 20 years). A total of 152 UIAs (81%) were followed for more than 10 years. The incidence of rupture was 2 in 2122 aneurysm-years (annual rupture rate 0.09%). Nine of the 188 patients with coiled UIAs (4.8%) underwent additional treatment. In 5 of these 9 cases, the first retreatment was performed more than 5 years after the initial treatment. Large aneurysms were significantly more likely to require retreatment. Nine strokes occurred over the 2122 aneurysm-years. Seventeen patients died in this cohort.CONCLUSIONSThis study demonstrates a low risk of rupture of coiled UIAs with long-term follow-up periods of up to 20 years. This suggests that coiling of UIAs could prevent rupture for a long period of time. However, large aneurysms might need to be followed for a longer time.


2020 ◽  
Vol 7 (1) ◽  
pp. e000487
Author(s):  
Tess McClure ◽  
Wanyuan Cui ◽  
Khashayar Asadi ◽  
Thomas John ◽  
Adam Testro

Nivolumab is an immune checkpoint inhibitor used to treat multiple solid-organ malignancies. While many of its immune-related adverse events are well established, nivolumab-induced sclerosing cholangitis remains poorly characterised, with no defined diagnostic criteria. Moreover, data regarding long-term outcomes are particularly lacking. We present a biopsy-proven case of nivolumab-induced sclerosing cholangitis, which uniquely captures 18 months of follow-up post-treatment. Our case highlights key features of intrahepatic subtype sclerosing cholangitis and suggests durable response to corticosteroid therapy.


2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0017
Author(s):  
Julien T Aoyama ◽  
Joshua T Bram ◽  
John Todd R. Lawrence ◽  
Theodore J Ganley

Background: Studies on pediatric anterior cruciate ligament reconstructions (ACLRs) often focus on graft choice, as rates of these injuries have risen in recent years. Large multicenter studies have found younger age and smaller graft size to be risk factors for graft failure and contralateral tears, but despite large sample sizes these studies have not looked specifically at graft strand number. Therefore the purpose of this study was to use a large sample size to ask whether ACLR graft strand number affects long-term outcomes. Hypothesis/Purpose: Examine long-term effects of ACLR graft strand number using a large cohort. Methods: This was a retrospective comparison study of all patients presenting between 1/1/2008 and 12/31/16 for a first-time ACLR at a single pediatric hospital. After querying medical records for all ACLRs using CPT codes, graft strand number, graft diameter, and other variables were abstracted. Long-term outcomes on graft rupture, contralateral ACL tear, and subsequent meniscus injury were collected via phone calls and REDCap emails. Patient groups were compared for differences in graft strand number and diameter using bivariate analyses, and differences in long-term outcomes were analyzed using multivariate regression. Results: 436 patients met the inclusion criteria also completed the long-term follow-up on outcomes. Long-term follow-up ranged from 18 months post surgery to 10 years post surgery. Patients with larger graft diameter were significantly less likely to suffer a complication (graft rupture, contralateral ACL tear, or subsequent meniscus injury) in multivariate regression (p=0.03), while strand number, sex, weight, and age showed no significant difference. Transphyseal reconstructions had larger graft diameters (8.8mm) than partial hybrid (8.6mm) and all-epiphyseal reconstructions (8.3mm) (p<0.001), but had no differences in graft strand number. Males had larger graft diameters (8.9mm) than females (8.6mm) (p=0.03), but also had no differences in graft strand number. Obese patients had larger graft diameters (9.1mm) than overweight (8.9mm) and normal weight patients (8.6mm) (p=0.002). Obese patients also had more graft strands (6.9) than overweight (6.2) or normal weight patients (6.1), but this difference was not significant (p=0.051). Conclusion: This data supports the existing literature that pediatric ACLR patients with larger graft diameters are less likely to suffer long-term complications. Using both a large patient cohort and long-term follow-up, this data also showed that graft strand number was not significantly correlated with outcomes. This suggests that strand number is not important when constructing ACLR grafts, as long as sufficient graft diameter can be achieved.


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