Radiological Disease Severity Research Articles

Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial.

<sec><title>INTRODUCTION</title>SHINE (Shorter Treatment for Minimal Tuberculosis in Children) was the first Phase 3 paediatric TB treatment-shortening trial. Robust chest X-ray (CXR) classification methods were integral to excluding severe disease for trial eligibility and to retrospectively adjudicating TB status at baseline. We describe and critically evaluate the CXR classification approaches and processes used in the SHINE trial.</sec><sec><title>METHODS</title>Children with non-severe TB were randomised to 4- vs 6-months anti-TB treatment. Radiologically non-severe TB was defined on CXR. CXRs were systematically interpreted by on-site clinicians prospectively for eligibility determination and retrospectively by experts to inform adjudication of baseline TB status and disease severity.</sec><sec><title>RESULTS</title>A screening CXR was successfully obtained from all 1,204 enrolled children; 1,134 CXRs from children with intra-thoracic TB were reviewed by expert readers. Compared with the expert panel, enrolling clinicians classified more CXRs as abnormal and 'typical TB' and all as radiologically non-severe. The expert panel retrospectively classified 71/1,134 (6%) CXRs as severe. Of these, 4 (5.6%) had unfavourable outcomes compared with 34 (3.0%) in the trial overall.</sec><sec><title>DISCUSSION</title>Using CXRs to classify radiological disease severity and inform eligibility decisions in real-time by local enrolling clinicians was feasible and safe in this large paediatric TB trial. Retrospective central expert CXR review was successful. Refinement of the CXR methods for the classification of both disease severity and TB status could support standardised implementation in routine care and research.</sec>.

Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis.

Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms' severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C>A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.

Ferritin/lymphocyte percentage ratio to predict the severity and mortality of COVID-19.

In this study, we aimed to investigate the relationship between ferritin/lymphocyte percentage ratio (FLPR) with clinical and radiological disease severity and mortality in COVID-19 patients. This retrospective study was conducted with patients who had polymerase chain reaction positive results for COVID-19. We calculated FLPRs from laboratory tests taken during emergency clinic admission. The relationship between chest computed tomography (CT) scores, disease severity, and 30-day mortality with FLPR was evaluated. Our study included 309 patients. 30-day mortality occurred in 12.3% (n=38) of the patients. A statistically significant association was found between FLPR and clinical disease severity (p <0.001). In the post hoc analysis, the difference was caused by the critical and severe groups and FLPR was significantly higher in these groups. A significant correlation was found between CT scores and FLPR (r=0.496, p<0.001). Logistic regression analysis revealed that hypertension, smoking, C-reactive protein (CRP), and FLPR levels were independent risk factors for mortality in COVID-19 patients. In the receiver operating characteristics curve analysis, determined the predictive value and the optimal cut-off value of FLPR. The areas under the curve of WBC, lymphocyte, neutrophil, ferritin, CRP, FLPR were found 0.707, 0.233, 0.735, 0.878, 0.831, 0.924 (p<0.001), respectively. This analysis showed that the FLPR can predict 30-day mortality better than the other biomarkers in the comparison. When the optimal cut-off value of FLPR is 42.4, the sensitivity is 84.2% and specificity is 86.7%. FLPR can be used as an independent biomarker of disease severity and mortality in COVID-19.

Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Prevalence of appendicolith in children with acute appendicitis and its correlation with disease severity.

Appendicitis typically develops secondary to obstruction of appendiceal lumen and one of the causes of obstruction is appendicolith. Appendicolith has become a relevant issue due to heightened interest in the treatment of uncomplicated appendicitis with antibiotics. This study aimed to determine the prevalence of appendicolith in pediatric patients with appendicitis and to investigate the association between the presence of appendicoliths and radiological disease severity. Patients under the age of 18 diagnosed with appendicitis between March 2021 and April 2022 and had available preoperative computed tomography (CT) images were identified retrospectively. The presence of an appendicolith and if present, its longest diameter in the axial plane, its visibility on direct radiographs, appendiceal diameter, degree of inflammation, and the presence of perforation were evaluated. Radiological severity of inflammation was rated on a 3-point scale. CT scans were available in 77 (32.1%) of 240 patients with histopathologically confirmed diagnosis of acute appendicitis. 39% (n=30) of the patients were girls and the median age was 13 years. The prevalence of appendicoliths detected on CT scans was 32.5% (n=25) and the median size of appendicoliths was 6 mm. In only 1 patient, appendicolith was detected by direct radiography. The median appendiceal diameter was significantly greater in the group with appendicoliths (10 mm vs. 8 mm; p=0.001). A moderate correlation was found between appendicolith size and appendiceal diameter (r=0.407, p=0.043). Perforation was present in 10.4% (n=8) of the patients with appendicitis and 25% (n=2) of them had appendicoliths. The presence of appendicoliths was not significantly associated with the occurrence of perforation (p=0.485). Periappendiceal inflammation scores were 1.52±0.74 in the group with appendicoliths and 1.42±0.63 in the group without appendicoliths (p=0.591). The prevalence of CT-detected appendicoliths was 32.5% in pediatric patients with appendicitis. Patients with appendicoliths showed higher inflammation scores and greater appendiceal diameter than those without appendicoliths. These factors may be associated with poor outcomes in patients with appendicoliths treated with antibiotics. Therefore, knowledge of the prevalence of appendicoliths and questioning their presence may guide clinicians when deciding on the suitability of nonoperative treatment in a patient diagnosed with uncomplicated acute appendicitis.

Correlation of Magnetic Resonance Imaging findings with Clinical Grading in Lumbar Disc Degeneration: A Cross-sectional Study

Introduction: Low Back Pain (LBP) is the most common musculoskeletal symptom encountered on a daily basis in clinical practice and has a significant impact on healthcare resources. Magnetic Resonance Imaging (MRI) is the most sensitive tool for diagnosing spinal degenerative disease and has proven to be a standard imaging modality for its evaluation. Assessment of the correlation between clinical and radiological severity of lumbar disc degeneration will help in better management of the LBP patients. Aim: To determine the correlation between the clinical and radiological severity of lumbar disc degeneration in non surgical LBP patients. Materials and Methods: This observational, cross-sectional study was conducted at the Department of Radiology and Imaging, Sagar Hospitals, Bengaluru, Karnataka, India, from December 2019 to June 2021. A total of 90 patients with LBP who were referred for MRI evaluation were included. Modified Oswestry questionnaire was given to the patients and the clinical severity of the LBP was quantified. Patients with disc degeneration were evaluated on MRI based on six parameters viz., T2-signal intensity, Disc Extension Beyond Interface (DEBIT), annular fissure, modic changes, endplate integrity and osteophytes. Fisher's exact test was used for qualitative data to look into the association between clinical and MRI grades of severity. Correlation was assessed for continuous variables using Pearson correlation analysis. Results: The study included a total of 90 patients with LBP, with a mean age of 57±13.75 years with equal sex preponderance (45 (50%) male and 45 (50%) female). Clinically, 51 (56.7%) of the study population revealed moderate disability. On quantifying the MRI total score of disc degeneration, 65 (72.3%) of the patients were found to show mild degeneration. In terms of involvement of all the evaluated six MRI parameters, the L4-L5 disc was most commonly affected, followed by the L5-S1 disc. Disc desiccation 353 (78.45%) and osteophytes 336 (74.67%) were the most consistently observed variations. Disc bulges 251 (55.78%) were the next most frequently observed parameter in disc degeneration. Conclusion: The correlation between the clinical and radiological severity of disc degenerative disease was found to be weakly positive and statistically insignificant. Disc desiccation, osteophytes and disc bulges were the most commonly observed parameters that contributed to lumbar degenerative disease.

In bronchiectasis, poor physical capacity correlates with poor quality of life

ABSTRACT Purpose Patients with bronchiectasis (BE) who suffer frequent exacerbations are likely to experience negative effects on quality of life (QoL) and require more healthcare utilization. We aimed to discover, in a cohort of Finnish BE patients, those risk factors that influence QoL. Methods Non-cystic fibrosis BE patients of a Helsinki University Hospital cohort were examined with high-resolution computed tomography (HRCT) of the chest. They completed a disease-specific quality of life-bronchiectasis (QoL-B) questionnaire in Finnish translation. We considered scores in the lowest quarter (25%) of that QoL-B scale to indicate poor QoL. The bronchiectasis severity index (BSI), FACED score, and modified Medical Research Council (mMRC) dyspnoea scale were used. Results Overall, of 95 adult BE patients, mean age was 69 (SD ± 13) and 79% were women. From the cohort, 82% presented with chronic sputum production and exacerbations, at a median rate of 1.7 (SD ± 1.6). The number of exacerbations (OR 1.7), frequent exacerbations (≥3 per year) (OR 4.9), high BSI score (OR 1.3), and extensive disease (≥3 lobes) (OR 3.7) were all predictive of poor QoL. Frequent exacerbations were associated with bronchial bacterial colonisation, low forced expiratory volume in 1 s (FEV1), and radiological disease severity. Based on the BSI, 34.1% of our cohort had severe disease, with 11.6% classified as severe according to their FACED score. The mMRC dyspnoea score (r = −0.57) and BSI (r = −0.60) correlated, in the QoL-B questionnaire, negatively with physical domain. Conclusion The strongest determinants of poor QoL in the cohort of Finnish BE patients were frequent exacerbations, radiological disease severity, and high BSI score. Neither comorbidities nor BE aetiology appeared to affect QoL. Reduced physical capacity correlated with dyspnoea and severe disease. Study registration University of Helsinki, Faculty of Medicine, 148/16.08.2017.

Tomographic score (RAD-Covid Score) to assess the clinical severity of the novel coronavirus infection

ObjectivesThe severity of pulmonary Covid-19 infection can be assessed by the pattern and extent of parenchymal involvement observed in computed tomography (CT), and it is important to standardize the analysis through objective, practical, and reproducible systems. We propose a method for stratifying the radiological severity of pulmonary disease, the Radiological Severity Score (RAD-Covid Score), in Covid-19 patients by quantifying infiltrate in chest CT, including assessment of its accuracy in predicting disease severity. MethodsThis retrospective, single-center study analyzed patients with a confirmed diagnosis of Covid-19 infection by real-time reverse-transcriptase polymerase chain reaction, who underwent chest CT at hospital admission between March 6 and April 6, 2020. CT scans were classified as positive, negative, or equivocal, and a radiological severity score (RAD-Covid Score) was assigned. Clinical severity was also assessed upon hospital admission. Results658 patients were included. Agreement beyond chance (kappa statistic) for the RAD-Covid Score was almost perfect among observers (0.833), with an overall agreement of 89.5%. The RAD-Covid Score was positively correlated with clinical severity and death, i.e., the higher the RAD-Covid Score, the greater the clinical severity and mortality. This association proved independent of age and comorbidities. Accuracy of this score was 66.9%. ConclusionsThe RAD-Covid Score showed good accuracy in predicting clinical severity at hospital admission and mortality in patients with confirmed Covid-19 infection and was an independent predictor of severity.

Serum levels of inflammatory mediators as prognostic biomarker in silica exposed workers

Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed: interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.

Monitoring response to conventional treatment in children with XLH: Value of ALP and Rickets Severity Score (RSS) in a real world setting.

X-linked hypophosphataemia (XLH) is conventionally managed with oral phosphate and active vitamin D analogues. To evaluate long term treatment response by assessing biochemical disease activity [serum alkaline phosphatase (ALP)], radiological rickets severity score (RSS), growth and morbidity in patients with XLH on conventional therapy and assess the correlation between serum ALP and RSS. XLH patients from 3 UK tertiary centres with ≥3 radiographs one year apart were included. Data was collected retrospectively. The RSS was assessed from routine hand and knee radiographs and ALP z scores were calculated using age-specific reference data. Thirty-eight (male=12) patients met the inclusion criteria. The mean±SD knee, wrist and total RSS at baseline (median age 1.2years) were 2.0±1.2, 1.9±1.2 and 3.6±1.3 respectively; and at the most recent clinic visit (median age 9.0years, range 3.3-18.9) were 1.6±1.0, 1.0±1.0 and 2.5±1.5 respectively. The mean±SD serum ALP z scores at baseline and the most recent visit were 4.2±2.3 and 4.0±3.3. Median height SDS at baseline and most recent visit were -1.2 and -2.1 (p=0.05). Dental abscess, craniosynostosis, limb deformity requiring orthopaedic intervention and nephrocalcinosis were present in 31.5%, 7.9%, 31.6% and 42.1% of the cohort respectively. There was no statistically significant (p>0.05) correlation between ALP z scores and knee (r=0.07) or total (r=0.12) RSS. Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. The lack of association between serum ALP and rickets severity on radiographs limits the value of ALP as the sole indicator of rickets activity in patients receiving conventional therapy.

679 Anxiety and Depression Impacts on The Correlation Between Symptom and Radiological Severity in Patients with Chronic Rhinosinusitis

Abstract Introduction Previous studies have reported little correlation between sino-nasal outcome test (SNOT-22) in chronic rhinosinusitis (CRS) and objective radiological scoring. We investigated whether anxiety and depression, which are highly prevalent in patients with CRS may cause symptom amplification and account for the lack of correlation in previous studies. Method 100 patients with CRS were evaluated using the General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), SNOT-22 and Lund Mackay Score (LMS). Results Overall correlation analysis did not show a significant relationship between SNOT-22 and LMS. Subgroup analysis of patients without anxiety or depression showed a significant correlation between SNOT-22 and LMS. We also observed a significant difference in both median SNOT-22 and LMS between patients who suffered with both anxiety and depression and patients without either. Conclusions When CRS patients who do not have anxiety and depression are analysed in isolation, or when these conditions are controlled in a multivariable regression, there is a significant correlation between radiological findings and symptom score. This correlation is absent in patients with anxiety and depression. Anxiety and depression should be considered in patients in whom there is a mismatch in symptom and radiological disease severity as it is associated with symptom amplification.

Co-morbid anxiety and depression impacts on the correlation between symptom and radiological severity in patients with chronic rhinosinusitis.

Previous studies have reported that there is little correlation between sino-nasal outcome test (SNOT-22) score in chronic rhinosinusitis (CRS) and objective radiological scoring, although conclusions vary. We aimed to investigate whether comorbid anxiety and depression, which are highly prevalent in patients with CRS may cause symptom amplification and account for the lack of correlation in previous studies. 100 patients with CRS were evaluated using the General Anxiety Disorder-7 (GAD-7), Patient Health Question- naire-9 (PHQ-9) and SNOT-22 questionnaires as well as the Lund Mackay Score (LMS). Overall correlation analysis did not show a significant relationship between SNOT-22 and LMS scores. Subgroup analysis of patients who do not suffer with anxiety and depression showed a significant correlation between SNOT-22 and LMS scores. The nasal domain of the SNOT-22 showed strongest correlation to LMS in this patient group. We also observed a significant difference in both median SNOT-22 and LMS between patients who suffered both anxiety and depression and patients without either co- morbidity. When CRS patients who do not have anxiety and depression are analysed in isolation, or when these conditions are controlled in a multivariable regression, there is a significant correlation between radiological findings and symptom score. This correlation is absent in patients with co-morbid anxiety and depression. Anxiety and depression should be considered in patients in whom there is a mismatch in symptom and radiological disease severity as it is associated with symptom amplification.

Role of interleukin-35 in rheumatoid arthritis pathogenesis and its relation to disease activity and joint damage

AimThis study aimed to discuss the role of interleukin-35 (IL-35) in the pathogenesis of rheumatoid arthritis (RA) and its relation to disease activity and radiological severity.Patients and methodsThirty patients diagnosed with RA were selected from the outpatient clinic and inpatient unit of Physical Medicine, Rheumatology and Rehabilitation Department, Tanta University Hospitals fulfilling the American College of Rheumatology/ European League Against Rheumatism 2010 criteria for the diagnosis of RA, and 20 apparently healthy individuals who were matched in age and sex participated as controls. Patients with other autoimmune diseases, malignancy, or any current infections were excluded. Disease activity score in 28 joints was assessed for all patients. Rheumatoid factor, anticyclic citrullinated peptide, complete blood count, erythrocyte sedimentation rate and C-reactive protein and serum level of IL-35 measured by enzyme-linked immunosorbent assay were evaluated. The degree of joint destruction was assessed by Larsen score.ResultsOf the RA patients, 73.3%showed low serum levels of IL-35 with significant difference compared with controls, and its levels showed negative association with disease activity. IL-35 serum levels were significantly correlated with hemoglobin level, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor and not correlated with anticyclic citrullinated peptide antibodies. Also IL-35 serum levels significantly correlated with radiological disease severity were assessed by Larsen score.ConclusionIL-35 had an immunoregulatory role in RA pathogenesis as its serum level is significantly low in RA patients and correlated with different parameters of disease activity and radiological severity.

Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis

Background: Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically. Objectives: We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS. Methods: A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability. Results: SIR-qMT measures differed between lesional and non-lesional tissue (p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs (p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores (p ⩽ 0.002). Conclusion: SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.

Paediatric and adult bronchiectasis: Monitoring, cross-infection, role of multidisciplinary teams and self-management plans.

Bronchiectasis is a chronic lung disease associated with structurally abnormal bronchi, clinically manifested by a persistent wet/productive cough, airway infections and recurrent exacerbations. Early identification and treatment of acute exacerbations is an integral part of monitoring and annual review, in both adults and children, to minimize further damage due to infection and inflammation. Common modalities used to monitor disease progression include clinical signs and symptoms, frequency of exacerbations and/or number of hospital admissions, lung function (forced expiratory volume in 1 s (FEV1 )% predicted), imaging (radiological severity of disease) and sputum microbiology (chronic infection with Pseudomonas aeruginosa). There is good evidence that these monitoring tools can be used to accurately assess severity of disease and predict prognosis in terms of mortality and future hospitalization. Other tools that are currently used in research settings such as health-related quality of life (QoL) questionnaires, magnetic resonance imaging and lung clearance index can be burdensome and require additional expertise or resource, which limits their use in clinical practice. Studies have demonstrated that cross-infection, especially with P. aeruginosa between patients with bronchiectasis is possible but infrequent. This should not limit participation of patients in group activities such as pulmonary rehabilitation, and simple infection control measures should be carried out to limit the risk of cross-transmission. A multidisciplinary approach to care which includes respiratory physicians, chest physiotherapists, nurse specialists and other allied health professionals are vital in providing holistic care. Patient education and personalized self-management plans are also important despite limited evidence it improves QoL or frequency of exacerbations.

Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. To establish if there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.

Pretreatment chest x-ray severity and its relation to bacterial burden in smear positive pulmonary tuberculosis

BackgroundChest radiographs are used for diagnosis and severity assessment in tuberculosis (TB). The extent of disease as determined by smear grade and cavitation as a binary measure can predict 2-month smear results, but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis.MethodsPre-treatment chest x-rays from 1837 participants with smear-positive pulmonary TB enrolled into the REMoxTB trial (Gillespie et al., N Engl J Med 371:1577–87, 2014) were retrospectively reviewed. Two clinicians blinded to clinical details using the Ralph scoring system performed separate readings. An independent reader reviewed discrepant results for quality assessment and cavity presence. Cavitation presence was plotted against time to positivity (TTP) of sputum liquid cultures (MGIT 960). The Wilcoxon rank sum test was performed to calculate the difference in average TTP for these groups. The average lung field affected was compared to log 10 TTP by linear regression. Baseline markers of disease severity and patient characteristics were added in univariable regression analysis against radiological severity and a multivariable regression model was created to explore their relationship.ResultsFor 1354 participants, the median TTP was 117 h (4.88 days), being 26 h longer (95% CI 16–30, p < 0.001) in patients without cavitation compared to those with cavitation. The median percentage of lung-field affected was 18.1% (IQR 11.3–28.8%). For every 10-fold increase in TTP, the area of lung field affected decreased by 11.4%. Multivariable models showed that serum albumin decreased significantly as the percentage of lung field area increased in both those with and without cavitation. In addition, BMI and logged TTP had a small but significant effect in those with cavitation and the number of severe TB symptoms in the non-cavitation group also had a small effect, whilst other factors found to be significant on univariable analysis lost this effect in the model.ConclusionsThe radiological severity of disease on chest x-ray prior to treatment in smear positive pulmonary TB patients is weakly associated with the bacterial burden. When compared against other variables at diagnosis, this effect is lost in those without cavitation. Radiological severity does reflect the overall disease severity in smear positive pulmonary TB, but we suggest that clinicians should be cautious in over-interpreting the significance of radiological disease extent at diagnosis.

A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal fluid: analytical validation and clinical evaluation

BackgroundCerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable marker of neuro-axonal damage in different neurological disorders that is related to disease severity. To date, all recent studies performed in human CSF have used the same enzyme-linked immunosorbent assay (ELISA). To confirm the large body of evidence for NfL, we developed a new ELISA method and here we present the performance characteristics of this new ELISA for CSF NfL in different neurological disorders.MethodsWe produced two monoclonal antibodies (NfL21 and NfL23) directed against the NfL core domain, and developed a novel sandwich ELISA method that we evaluated in patients with: 1) inflammatory demyelinating diseases (IDD; n = 97), including multiple sclerosis (MS; n = 59), clinically isolated syndrome (CIS; n = 32), and radiologically isolated syndrome (RIS; n = 6); 2) Alzheimer’s disease (AD; n = 72), including mild cognitive impairment due to AD (MCI-AD, n = 36) and probable AD dementia (AD-dem; n = 36); 3) Parkinson’s disease (PD; n = 30); and 4) other neurological noninflammatory and non-neurodegenerative diseases (OND; n = 30).ResultsOur new NfL ELISA showed a good analytical performance (inter-plate coefficient of variation (CV) < 13%), with no cross-reactivity with neurofilament medium and heavy (NfM and NfH). With respect to the other available ELISAs, CSF NfL showed the same range of values with a strong correlation (r = 0.9984, p < 0.001) between the two methods. CSF NfL levels were significantly higher in MCI-AD/AD-dem and IDD patients as compared with both PD and OND patients. The highest discriminative power was obtained between IDD and OND patients (area under the curve (AUC) 0.87, 95% confidence interval (CI) 0.80–0.95). Within the IDD group, CSF NfL positively correlated with several clinical and radiological disease severity parameters.ConclusionsThese results show a good analytical performance of the new ELISA for quantification of NfL concentrations in the CSF. CSF NfL is confirmed to be a reliable marker in AD and MS, and a disease-severity marker in MS patients.

Post-transplant adaptive function in childhood cerebral adrenoleukodystrophy.

ObjectiveHematopoietic stem cell transplantation (HSCT) is the only treatment known to slow or halt inflammatory demyelination among boys with the cerebral form of X‐linked adrenoleukodystrophy (cALD), a devastating childhood condition affecting the central nervous system. HSCT can lead to a range of adverse outcomes including fatality. Previous studies have examined the potential predictors of post‐HSCT survival and neurologic functioning. However, little is known about patients' daily‐life adaptive functional outcomes (i.e., ability to communicate, maintain social relationships, and independently execute tasks of daily living). The purpose of this retrospective cohort study was to identify which patient characteristics and treatment‐related variables predict long‐term adaptive function among the survivors of HSCT for cALD.MethodsWe obtained caregiver ratings of adaptive functioning of 65 transplant survivors at an average of 4.6 years (range: 1.0–24.1 years) post‐HSCT. Using linear regression with penalized maximum likelihood estimation, we modeled the relative contribution of pre‐transplant neurocognitive test performance, MRI severity, transplant regimen, and length of time since transplant on patient adaptive functioning outcomes.ResultsHigher radiographic disease severity and poorer performance on baseline neurocognitive tests requiring fine motor skills and visual perception were associated with inferior adaptive functioning after HSCT. Use of radiation during the transplant preparative regimen also predicted poorer adaptive outcomes.InterpretationIn addition to radiological disease severity, baseline neurocognitive test performance is associated with post‐transplant adaptive functional outcomes. Neurocognitive measures may play an important role in prognostic counseling and post‐transplant treatment planning for patients considering HSCT for cALD.

Is It the Age at Disease Onset or the Disease Radiological Severity That Affects Cervical Spine Involvement in Patients With Rheumatoid Arthritis?

Background:Cervical spine involvement in patients with rheumatoid arthritis (RA) can cause pain and disability, with a variety of neurologic signs and symptoms.Objectives:To investigate the relationship between structural cervical spine involvement in patients with RA with the age at disease onset and the degree of radiologic severity of RA measured by Larsen scoring.Patients and methods:This cross-sectional study included 50 adult patients with RA. Patients who complained or not complained from symptoms of cervical spine involvement in RA were included; we did X-ray of the cervical spine, hands, and feet; Larsen scoring method; disease activity score (DAS28); and Neck Disability Index.Results:The results revealed that patients with cervical involvement tend to be younger at their disease onset than those with no cervical involvement, as detected by cervical X-ray. The relation was significant P < .05 regarding all cervical involvements except for basilar invagination. Disease radiological severity (measured by Larsen score) significantly increases the risk for subaxial subluxation, P = .040. All other cervical complications of RA tend to have nonsignificant relation with disease severity. Using univariate binary regression analysis for risk factors for cervical involvement showed that the only probable risk factor for cervical involvement (detected by X-ray) in patients with RA is age at disease onset.Conclusions:The early age at disease onset tends to affect cervical spine involvement in patients with RA more than the disease radiological severity.