scholarly journals No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML

Neurology ◽  
2017 ◽  
Vol 88 (12) ◽  
pp. 1144-1152 ◽  
Author(s):  
Doriana Landi ◽  
Nicola De Rossi ◽  
Sara Zagaglia ◽  
Cristina Scarpazza ◽  
Luca Prosperini ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Clinical Outcomes ◽  
Jc Virus ◽  
Clinical Status ◽  
Class Iii ◽  
Beneficial Effects ◽  
Poor Outcome ◽  
Important Benefit ◽  
Statistical Precision

Objective:To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)–associated progressive multifocal leukoencephalopathy (PML).Methods:The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution. The effects on survival and clinical outcome of PLEX, sex, age, country, pre-PML Expanded Disability Status Scale score, NTZ infusion number, prior immunosuppressant exposure, PML symptoms, PML lesion location at diagnosis, CSF JC virus status and copies, additional PML treatments and steroids, and PML immune reconstitution inflammatory syndrome (IRIS) development were investigated with both univariate and multivariate analyses.Results:A total of 219 NTZ-PML cases were analyzed, and 184 (84%) underwent PLEX, which did not reduce the mortality risk or the likelihood of poor vs favorable outcomes. Country was predictive of mortality and poor outcome, while PML-IRIS development was predictive of poor outcome.Conclusions:PLEX did not improve the survival or clinical outcomes of Italian or international patients with MS and NTZ-PML, suggesting that this treatment should be performed cautiously in the future.Classification of evidence:This study provides Class III evidence that for patients with NTZ-PML, PLEX does not improve survival. The study lacks the statistical precision to exclude an important benefit or harm of PLEX.

scholarly journals JC Virus Regulatory Region Tandem Repeats in Plasma and Central Nervous System Isolates Correlate with Poor Clinical Outcome in Patients with Progressive Multifocal Leukoencephalopathy

2001 ◽  
Vol 75 (12) ◽  
pp. 5672-5676 ◽  
Author(s):  
Luz-Andrea Pfister ◽  
Norman L. Letvin ◽  
Igor J. Koralnik
Keyword(s):  
Clinical Outcome ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Tandem Repeats ◽  
Jc Virus ◽  
Regulatory Region ◽  
Tata Box ◽  
Type I ◽  
Type Ii ◽  
Poor Clinical Outcome ◽  
Immunodeficiency Virus

ABSTRACT JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), has a hypervariable regulatory region (JCV RR). A conserved archetype form is found in the urines of healthy and immunocompromised individuals, whereas forms with tandem repeats and deletions are found in the brains of PML patients. Type I JCV RR, seen in MAD-1, the first sequenced strain of JCV, contains two 98-bp tandem repeats each containing a TATA box. Type II JCV RR has additional 23-bp and 66-bp inserts or fragments thereof and only one TATA box. We cloned and sequenced JCV RR from different anatomic compartments of PML patients and controls and correlated our findings with the patients' clinical outcome. Twenty-three different sequences were defined in 198 clones obtained from 16 patients. All 104 clones with tandem repeats were type II JCV RR. Patients with poor clinical outcome had high proportions of JCV RR clones with both tandem repeats in plasma (54%) and brain or cerebrospinal fluid (85%). In those who became survivors of PML, archetype sequences predominated in these anatomic compartments (75 and 100%, respectively). In patients with advanced human immunodeficiency virus infection without PML, only 8% of JCV RR clones obtained in the plasma contained tandem repeats. These data suggest that the presence of tandem repeats in plasma and CNS JCV RR clones is associated with poor clinical outcome in patients with PML.

Effect of Manipulation under Anesthesia of the First Knee in Staged Bilateral Total Knee Arthroplasty on Clinical Outcome and Satisfaction

2020 ◽  
Author(s):  
Jung-Won Lim ◽  
Yong-Beom Park ◽  
Dong-Hoon Lee ◽  
Han-Jun Lee
Keyword(s):  
Total Knee Arthroplasty ◽  
Patient Satisfaction ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Knee Arthroplasty ◽  
Knee Flexion ◽  
Functional Score ◽  
Manipulation Under Anesthesia ◽  
Total Knee

AbstractThis study aimed to evaluate whether manipulation under anesthesia (MUA) affect clinical outcome including range of motion (ROM) and patient satisfaction after total knee arthroplasty (TKA). It is hypothesized that MUA improves clinical outcomes and patient satisfaction after primary TKA. This retrospective study analyzed 97 patients who underwent staged bilateral primary TKA. MUA of knee flexion more than 120 degrees was performed a week after index surgery just before operation of the opposite site. The first knees with MUA were classified as the MUA group and the second knees without MUA as the control group. ROM, Knee Society Knee Score, Knee Society Functional Score, Western Ontario and McMaster Universities (WOMAC) score, and patient satisfaction were assessed. Postoperative flexion was significantly greater in the MUA group during 6 months follow-up (6 weeks: 111.6 vs. 99.8 degrees, p < 0.001; 3 months: 115.9 vs. 110.2 degrees, p = 0.001; 6 months: 120.2 vs. 117.0 degrees, p = 0.019). Clinical outcomes also showed similar results with knee flexion during 2 years follow-up. Patient satisfaction was significantly high in the MUA group during 12 months (3 months: 80.2 vs. 71.5, p < 0.001; 6 months: 85.8 vs. 79.8, p < 0.001; 12 months: 86.1 vs. 83.9, p < 0.001; 24 months: 86.6 vs. 85.5, p = 0.013). MUA yielded improvement of clinical outcomes including ROM, and patient satisfaction, especially in the early period after TKA. MUA in the first knee could be taken into account to obtain early recovery and to improve patient satisfaction in staged bilateral TKA.

Alanine Aminotransferase Predicts Outcomes in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage

2019 ◽  
Vol 16 (1) ◽  
pp. 89-95
Author(s):  
Jianfeng Zheng ◽  
Rui Xu ◽  
Zongduo Guo ◽  
Xiaochuan Sun
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Laboratory Data ◽  
Cardiac Complications ◽  
World Population ◽  
Systemic Complications ◽  
Poor Outcome ◽  
Poor Outcomes

Objective: With the aging of the world population, the number of elderly patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is gradually growing. We aim to investigate the potential association between plasma ALT level and clinical complications of elderly aSAH patients, and explore its predictive value for clinical outcomes of elderly aSAH patients. Methods: Between January 2013 and March 2018, 152 elderly aSAH patients were analyzed in this study. Clinical information, imaging findings and laboratory data were reviewed. According to the Glasgow Outcome Scale (GOS), clinical outcomes at 3 months were classified into favorable outcomes (GOS 4-5) and poor outcomes (GOS 1-3). Logistic regression analysis was used to assess the indicators associated with poor outcomes, and receiver curves (ROC) and corresponding area under the curve (AUC) were used to detect the accuracy of the indicator. Results: A total of 48 (31.6 %) elderly patients with aSAH had poor outcome at 3 months. In addition to ICH, IVH, Hunt-Hess 4 or 5 Grade and Modified Fisher 3 or 4 Grade, plasma ALT level was also strongly associated with poor outcome of elderly aSAH patients. After adjusting for other covariates, plasma ALT level remained independently associated with pulmonary infection (OR 1.05; 95% CI 1.00–1.09; P = 0.018), cardiac complications (OR 1.05; 95% CI 1.01–1.08; P = 0.014) and urinary infection (OR 1.04; 95% CI 1.00–1.08; P = 0.032). Besides, plasma ALT level had a predictive ability in the occurrence of systemic complications (AUC 0.676; 95% CI: 0.586– 0.766; P<0.001) and poor outcome (AUC 0.689; 95% CI: 0.605–0.773; P<0.001) in elderly aSAH patients. Conclusion: Plasma ALT level of elderly patients with aSAH was significantly associated with systemic complications, and had additional clinical value in predicting outcomes. Given that plasma ALT levels on admission could help to identify high-risk elderly patients with aSAH, these findings are of clinical relevance.

Clinicopathological and Imaging Features Predictive of Clinical Outcome in Metaplastic Breast Cancer

2020 ◽  
Vol 16 (6) ◽  
pp. 729-738
Author(s):  
Ga Young Yoon ◽  
Joo Hee Cha ◽  
Hak Hee Kim ◽  
Hee Jung Shin ◽  
Eun Young Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Tumor Size ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Imaging Features ◽  
Peritumoral Edema ◽  
Imaging Findings ◽  
Metaplastic Breast Cancer

Background: Metaplastic breast cancer (MC) is a rare disease, thus it is difficult to study its clinical outcomes. Objective: To investigate whether any clinicopathological or imaging features were associated with clinical outcome in MC. Methods: We retrospectively evaluated the clinicopathological and imaging findings, and the clinical outcomes of seventy-two pathologically confirmed MCs. We then compared these parameters between triple-negative (TNMC) and non-TNMCs (NTNMC). Results: Oval or round shape, and not-circumscribed margin were the most common findings on mammography, ultrasound (US), and magnetic resonance imaging (MRI). It was mostly a mass without calcification on mammography, and revealed complex or hypoechoic echotexture, and posterior acoustic enhancement on US, and rim enhancement, wash-out kinetics, peritumoral edema, and intratumoral necrosis on MRI. Of all 72, 64 were TNMCs, and eight were NTNMCs. Clinicopathological and imaging findings were similar between the two groups, except that MRI showed peritumoral edema more frequently in TNMCs than NTNMCs (p=0.045). There were 21 recurrences and 13 deaths. Multivariable analysis showed that larger tumor size and co-existing DCIS were significantly predictive of Disease free survival (DFS), and larger tumor size and neoadjuvant chemotherapy were significantly predictive of overall survival (OS). Conclusion: MC showed characteristic imaging findings, and some variables associated with survival outcome may help to predict prognosis.

scholarly journals Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mendy M Welsink-Karssies ◽  
Sacha Ferdinandusse ◽  
Gert J Geurtsen ◽  
Carla E M Hollak ◽  
Hidde H Huidekoper ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Newborn Screening ◽  
Clinical Outcomes ◽  
Movement Disorders ◽  
Brain Mri ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Classical Galactosemia ◽  
Intellectual Outcome

Abstract Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was &lt;85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome &lt; 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P &lt; 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients.

scholarly journals Impact of Tocilizumab on Clinical Outcomes in COVID-19-Associated Cytokine Release Syndrome: A Single-Center Experience

2021 ◽  
pp. 089719002110282
Author(s):  
Karan Raja ◽  
Nicole Daniel ◽  
Susan Morrison ◽  
Ruben Patel ◽  
Jessica Gerges ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Status ◽  
Rank Test ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Single Center ◽  
Post Dose ◽  
Single Center Experience ◽  
Signed Rank Test ◽  
The Impact

Background: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. Methods: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. Results: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. Conclusion: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

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