scholarly journals Fluid Biomarkers for Monitoring Structural Changes in Polyneuropathies: Their Use in Clinical Practice and Trials

2021 ◽  
Author(s):  
Luuk Wieske ◽  
Duncan Smyth ◽  
Michael P. Lunn ◽  
Filip Eftimov ◽  
Charlotte E. Teunissen
Keyword(s):  
Disease Activity ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Clinical Care ◽  
Nerve Damage ◽  
Clinical Tool ◽  
Neurofilament Light ◽  
Vasculitic Neuropathy ◽  
Response Biomarker ◽  
Response Biomarkers

AbstractReliable and responsive tools for monitoring disease activity and treatment outcomes in patients with neuropathies are lacking. With the emergence of ultrasensitive blood bioassays, proteins released with nerve damage are potentially useful response biomarkers for many neurological disorders, including polyneuropathies. In this review, we provide an overview of the existing literature focusing on potential applications in polyneuropathy clinical care and trials. Whilst several promising candidates have been identified, no studies have investigated if any of these proteins can serve as response biomarkers of longitudinal disease activity, except for neurofilament light (NfL). For NfL, limited evidence exists supporting a role as a response biomarker in Guillain-Barré syndrome, vasculitic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Most evidence exists for NfL as a response biomarker in hereditary transthyretin-related amyloidosis (hATTR). At the present time, the role of NfL is therefore limited to a supporting clinical tool or exploratory endpoint in trials. Future developments will need to focus on the discovery of additional biomarkers for anatomically specific and other forms of nerve damage using high-throughput technologies and highly sensitive analytical platforms in adequality powered studies of appropriate design. For NfL, a better understanding of cut-off values, the relation to clinical symptoms and long-term disability as well as dynamics in serum on and off treatment is needed to further expand and proceed towards implementation.

scholarly journals CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

2020 ◽  
Vol 7 (6) ◽  
pp. e880 ◽  
Author(s):  
Saúl Reyes ◽  
Ide Smets ◽  
David Holden ◽  
Karina Carrillo-Loza ◽  
Tatiana Christmas ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Oral Disease ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Treatment Escalation

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

scholarly journals Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongze Wu ◽  
James F. Griffith ◽  
Steven H. M. Lam ◽  
Priscilla C. H. Wong ◽  
Lin Shi ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Structural Changes ◽  
Bone Erosion ◽  
Clinical Care ◽  
Tnf Inhibitor ◽  
Bone Erosions ◽  
Damage Accrual ◽  
Significant Difference ◽  
Smallest Detectable Change

Abstract Background Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. Methods HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). Results A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3, P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. Conclusion Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.

scholarly journals Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110019
Author(s):  
Sinah Engel ◽  
Maria Protopapa ◽  
Falk Steffen ◽  
Vakis Papanastasiou ◽  
Christoforos Nicolaou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Single Molecule ◽  
Light Chain ◽  
Clinical Symptoms ◽  
Threshold Value ◽  
Sample Collection ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Mean

Background: Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine. Methods: The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array. Results: The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort ( n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0–128) versus 80.2 pg/ml (IQR 46.4–97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up. Conclusion: Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.

Quality of Life in Patients With Behçet Disease and Its Relation With Clinical Symptoms and Disease Activity

2021 ◽  
Vol 17 (1) ◽  
pp. 1-6
Author(s):  
Alireza Khabbazi ◽  
Vahideh Ebrahimzadeh Attari ◽  
Mohammad Asghari Jafarabadi ◽  
Aida Malek Mahdavi
Keyword(s):  
Quality Of Life ◽  
Disease Activity ◽  
Clinical Symptoms ◽  
Behçet Disease ◽  
Behcet Disease

scholarly journals Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Paulo Roberto Arruda Zantut ◽  
Mariana Matera Veras ◽  
Sarah Gomes Menezes Benevenutto ◽  
Angélica Mendonça Vaz Safatle ◽  
Ricardo Augusto Pecora ◽  
...  
Keyword(s):  
Young Adult ◽  
Light Microscopy ◽  
Prenatal Exposure ◽  
Structural Changes ◽  
Volume Fraction ◽  
Clinical Care ◽  
Retinal Layer ◽  
Exposed Population ◽  
The Central Nervous System ◽  
The Impact

Abstract Background Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.

scholarly journals Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study]

2019 ◽  
Vol 14 (5) ◽  
pp. 595-607 ◽  
Author(s):  
Julius Z H von Martels ◽  
Arno R Bourgonje ◽  
Marjolein A Y Klaassen ◽  
Hassan A A Alkhalifah ◽  
Mehdi Sadaghian Sadabad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Clinical Symptoms ◽  
Fish Analysis ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
Faecal Microbiome ◽  
Chronic Intestinal Inflammation

Abstract Background and Aims Crohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. Methods In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. Results In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. Conclusions Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

scholarly journals Production of SARS-CoV-2 Antibodies and Emergence of the Clinical Symptoms of COVID-19

2021 ◽  
Author(s):  
Ahmad Hormati ◽  
Hossein Poustchi ◽  
Mohammad Reza Ghadir ◽  
Saeede Jafari ◽  
Narges Jafari ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Care ◽  
Public Health Problem ◽  
Cross Sectional Study ◽  
Clinical Findings ◽  
Time Duration ◽  
Cross Sectional ◽  
Igm Antibodies ◽  
Gi Symptoms ◽  
Antibody Levels

Coronavirus disease 2019 (COVID-19) is a worldwide public health problem that has attracted much attention due to its clinical findings. Measurement of IgG and IgM antibodies is of great importance for researchers and it will help to develop a new diagnostic and therapeutic method in clinical care. In this cross-sectional study, we aim to measure the IgG and IgM antibody levels in 401 suspected COVID-19 volunteers. We also measure the time duration for the appearance of IgG and IgM antibodies from the onset of symptoms to sampling time. Of 401 participants enrolled in the study, 255 (63.59%) were healthy, 79 (19.70%) were a carrier, 59 (14.71%) were cured and 8 (1.99%) were borderline. Of 142 subjects diagnosed with COVID-19, 41 (28.87%) presented with gastrointestinal (GI) symptoms, 83 (58.45%) had no GI symptoms, and 18 (12.68%) were asymptomatic. According to our findings, the measurement of IgG and IgM antibodies will provide the tool for the diagnosis of COVID-19 and significantly boost research into novel diagnostic and therapeutic approaches.

scholarly journals Extensively drug-resistant Alcaligenes faecalis infection

2020 ◽  
Author(s):  
Chienhsiu Huang
Keyword(s):  
Bacterial Infections ◽  
Opportunistic Infections ◽  
Clinical Symptoms ◽  
Clinical Care ◽  
Alcaligenes Faecalis ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Intravenous Antibiotics ◽  
Sensitivity Rate ◽  
Antibiotics Sensitivity

Abstract Background: Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients’ clinical care. Methods: We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes. Results: Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to A. faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%. Conclusions: The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.

Medical Therapy for Crohn Disease

2015 ◽  
Author(s):  
Jessica R Allegretti ◽  
Joshua R. Korzenik
Keyword(s):  
Disease Activity ◽  
Crohn Disease ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Severe Disease ◽  
Treatment Options ◽  
Injection Site Reaction ◽  
Perianal Fistula ◽  
Perianal Disease ◽  
Aminosalicylic Acid

Crohn disease (CD) is an inflammatory condition that can affect any portion of the gastrointestinal tract from the mouth to the perianal area. The resulting transmural inflammation can lead to a spectrum of clinical presentations depending on disease location and severity. The treatment of CD depends on the severity of the disease, phenotype, presence of perianal disease, and response to previous therapies. This review examines the goals of therapy for CD, clinical symptoms and disease activity, treatment of disease based on mild to moderate to severe stages, treatment of refractory disease, perianal disease, postoperative CD, and noninflammatory treatment options. Figures show adalimumab injection-site reaction and perianal fistula with seton placement. Tables list the Crohn Disease Activity Index (CDAI), the Harvey Bradshaw Index, 5-aminosalicylic acid formulations, standard dosing of CD medications for moderate to severe disease, and rates of clinical response and remission in patients receiving anti–tumor necrosis factor agents versus placebo, by trial. This review contains 2 highly rendered figures, 5 tables, and 85 references. 

Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria

2019 ◽  
Vol 20 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Frederick Wolfe ◽  
Stephen H. Butler ◽  
MaryAnn Fitzcharles ◽  
Winfried Häuser ◽  
Robert L. Katz ◽  
...  
Keyword(s):  
Functional Disability ◽  
Clinical Symptoms ◽  
Clinical Care ◽  
Chronic Widespread Pain ◽  
The Body ◽  
Clinical Severity ◽  
Widespread Pain ◽  
Effective Measure ◽  
American College Of Rheumatology ◽  
Pain Site

AbstractBackground and aimsPersons with chronic widespread pain (CWP) have poor medical outcomes and increased mortality. But there are no universally accepted criteria for CWP or of methods to assess it. The most common criteria come from the 1990 American College of Rheumatology (ACR) fibromyalgia (FM) criteria, but that method (WP1990) can identify CWP with as few as three pain sites, and in subjects with wide differences in illness severity. Recently, to correct WP1990 deficiencies, the 2016 fibromyalgia criteria provided a modified CWP definition (WP2016) by dividing the body into five regions of three pain sites each and requiring a minimum of four regions of pain. Although solving the geographic problem of pain distribution, the problem of just how many pain sites (pain diffuseness) are required remained a problem, as WP2016 required as few as four painful sites. To better characterize CWP, we compared four CWP definitions with respect to symmetry, extent of pain sites and association with clinical severity variables.MethodsWe characterized pain in 40,960 subjects, including pain at 19 individual sites and five pain regions, and calculated the widespread pain index (WPI) and polysymptomatic distress scales (PDS) from epidemiology, primary care and rheumatology databases. We developed and evaluated a new definition for CWP, (WP2019), defined as pain in four or five regions and a pain site score of at least seven of 15 sites. We also tested a definition based on the number of painful sites (WPI ≥ 7).ResultsIn rheumatology patients, WP1990 and WPI ≥ 7 classified patients with <4 regions as WSP. CWP was noted in 51.3% by WP1990, 41.7% by WP2016, 37.6% of WPI ≥ 7 and 33.9% by WP2019. 2016 FM criteria was satisfied in WP1990 (51.1%), WP2016 (63.3%), WPI ≥ 7 (69.0%) and WP2019 (76.6%). WP2019 positive patients had more severe clinical symptoms compared with WP1990, WP2016 and WPI ≥ 7, and similar to but less than FM 2016 positive patients. In stepwise fashion, scores for functional disability, visual analog scale fatigue and pain, WPI, polysymptomatic distress score and Patient Health Questionnaire 15 (PHQ-15) worsened from WP1990 through WP2016, WPI ≥ 7 and WP2019.ConclusionsWP2019 combines the high WPI scores of WPI ≥ 7 and the symmetry of WP2016, and is associated with the most abnormal clinical scores. The WP1990 does not appear to be an effective measure. We suggest that CWP can be better defined by combining 4-region pain and a total pain site score ≥7 (WP2019). This definition provides a simple, unambiguous measure that is suitable for clinical and research use as a standalone diagnosis that is integrated with fibromyalgia definitions.ImplicationsDefinitions of CWP in research and clinic care are arbitrary and have varied, and different definitions of CWP identify different sets of patients, making a universal interpretation of CWP uncertain. In addition, CWP is a mandatory component of some fibromyalgia criteria. Our study provides quantitative data on the differences between CWP definitions and their criteria, allowing better understanding of research results and a guide to the use of CWP in clinical care.

Sign in / Sign up

Export Citation Format

Share Document