Final Clinical Diagnosis Research Articles

Clinical metagenomic sequencing for diagnosis of pulmonary tuberculosis

The aim of this study is to investigate the clinical usefulness of metagenomic Next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples to discriminate pulmonary tuberculosis (PTB) from Non-TB community-acquired pneumonia (CAP) in PTB suspects. We investigate the performance of mNGS on BALF samples from 110 PTB suspects, in comparison with conventional microbiological testing (solid media culture, acid-fast bacilli staining (AFS), Xpert) of BALF or sputum samples and final clinical diagnosis. We finally clinically diagnosed 48 cases of pulmonary tuberculosis patients and 62 cases of non-tuberculosis patients. Comparing to the final clinical diagnosis, mNGS produced a sensitivity of 47.92%, which was similar to that of Xpert (45.83%) and culture (46.81%), but much higher than that of AFS (29.17%) for TB diagnosis in BALF samples. Apart from detecting Mycobacterium tuberculosis, mNGS also identified mixed infections in PTB patients, including 3 fungal cases and 1 bacteria case. Meanwhile, mNGS efficiently identified 14 of 22 (63.63%) cases of non-tuberculous mycobacteria (NTM), 7 cases of fungi, 1 case of viral infection, and other common bacterial pathogens in Non-PTB group. Finally, mNGS identified 67.23% infection cases within 3 days, while the conventional methods identified 49.58% infection cases for over 90 days. Our data show that mNGS of BALF represents a potentially effective tool for the rapid diagnosis of PTB suspects.

Machine learning-based CT fractional flow reserve assessment in acute chest pain: first experience.

Computed tomography (CT)-derived fractional flow reserve (FFRCT) enables the non-invasive functional assessment of coronary artery stenosis. We evaluated the feasibility and potential clinical role of FFRCT in patients presenting to the emergency department with acute chest pain who underwent chest-pain CT (CPCT). For this retrospective IRB-approved study, we included 56 patients (median age: 62 years, 14 females) with acute chest pain who underwent CPCT and who had at least a mild (≥25% diameter) coronary artery stenosis. CPCT was evaluated for the presence of acute plaque rupture and vulnerable plaque features. FFRCT measurements were performed using a machine learning-based software. We assessed the agreement between the results from FFRCT and patient outcome (including results from invasive catheter angiography and from any non-invasive cardiac imaging test, final clinical diagnosis and revascularization) for a follow-up of 3 months. FFRCT was technically feasible in 38/56 patients (68%). Eleven of the 38 patients (29%) showed acute plaque rupture in CPCT; all of them underwent immediate coronary revascularization. Of the remaining 27 patients (71%), 16 patients showed vulnerable plaque features (59%), of whom 11 (69%) were diagnosed with acute coronary syndrome (ACS) and 10 (63%) underwent coronary revascularization. In patients with vulnerable plaque features in CPCT, FFRCT had an agreement with outcome in 12/16 patients (75%). In patients without vulnerable plaque features (n=11), one patient showed myocardial ischemia (9%). In these patients, FFRCT and patient outcome showed an agreement in 10/11 patients (91%). Our preliminary data show that FFRCT is feasible in patients with acute chest pain who undergo CPCT provided that image quality is sufficient. FFRCT has the potential to improve patient triage by reducing further downstream testing but appears of limited value in patients with CT signs of acute plaque rupture.

Granulomatous inflammation in lymph nodes of the head and neck-a retrospective analysis of causes in a population with very low incidence of tuberculosis.

The purpose of this study was to investigate the risk of the patient having: (1) TB, (2) sarcoidosis, (3) atypical mycobacteria, or (4) malignant disease, if FNAC or histology from a cervical lymph node shows granulomatous inflammation (GI). And to elucidate clinical characteristics associated with these causes of GI, patients with a pathological diagnosis of GI in head and neck lymph nodes were identified though a search of the Danish national pathology database. Charts were reviewed to identify the final clinical diagnosis and specific clinical characteristics. For the most common clinical diagnoses, association to clinical characteristics was analyzed using logistic regression (Odense University Hospital January 2006 to December 2015). We included 121 patients. Clinical diagnoses fell into the following categories: sarcoidosis (26%), tuberculosis (TB) (22%), cat scratch disease (6%), atypical mycobacteriosis (7%), malignancy (2%), and other (4%). In 33% of cases, the diagnosis was unknown. In the pediatric group, atypical mycobacteriosis was the most frequent clinical diagnosis (50%). TB and sarcoidosis were dependent variables in regression analysis. Characteristics significantly related to TB were histology showing necrotizing GI, gland localization in level 3-6, and origin other than Danish and TB being the tentative diagnosis. Characteristics significantly related to sarcoidosis were histology showing non-necrotizing GI, gland localization in level 3-6, the patient being of Danish origin, and unknown duration of symptoms. TB and sarcoidosis were the most common clinical diagnoses, and they were associated with specific clinical characteristics. In a third of cases, a specific clinical diagnosis was never given.

A multicenter study evaluation of the ClearLLab 10C panels.

Multiparameter flow cytometry plays an important role in the diagnosis, staging, and monitoring of patients with a suspected hematological malignancy. The ClearLLab 10C Panels consist of four reagent panels (B‐Lineage Tube, T‐Lineage Tube, and 2 Myeloid Lineage Tubes), each consisting of 10 color/10 antibody conjugates utilizing Beckman Coulters proprietary dry format optimized for investigating patients with suspected leukemia or lymphoma. A multicenter study was conducted to evaluate the performance of the ClearLLab 10C Panels for qualitative assessment of normal versus abnormal phenotype in peripheral blood, bone marrow, and lymph node samples with suspected hematological malignancies. ClearLLab 10C was compared to laboratory developed tests (LDTs) and final clinical diagnosis. Four clinical sites were used to enroll patient's spent specimens (n = 453); three laboratories in North America and one in Europe. Of the 453 specimens, 198 had no malignancy and 255 contained an abnormal population. The diagnostic accuracy of the ClearLLab 10C Panels was achieved with sensitivity of 96% and specificity of 95% with respect to patient final clinical diagnosis. The agreement of phenotyping between ClearLLab10C Panels and LDTs was 98%. Any differences noted between ClearLLab 10C and LDT were due to either the presence of populations below the level of detection, the lack of clinical information provided to the evaluators, or marker(s) not present in these panels. Overall, the ClearLLab 10C demonstrated excellent agreement to LDTs and diagnosis. These four reagent panels can be adopted by individual laboratories to assess the presence or absence of malignancy.

Emergency neck MRI: feasibility and diagnostic accuracy in cases of neck infection.

BackgroundComputed tomography (CT) has traditionally been the first-line imaging method in neck emergencies such as deep neck infections. Due to superior soft-tissue contrast, magnetic resonance imaging (MRI) may be an alternative to CT, also in emergency situations.PurposeTo characterize the use of routine MRI in neck emergencies, with an emphasis on clinical feasibility and diagnostic accuracy in cases of neck infection.Material and MethodsWe conducted a retrospective cohort study of all primary neck MRI scans performed using a 3-T MRI device during a five-year follow-up period in a tertiary emergency radiology department. Imaging data were compared with final clinical diagnosis and surgical findings as reference standards.ResultsThe search identified 461 primary neck MRI scans, of which 334 (72%) were performed on the basis of clinical suspicion of infection. Radiological evidence of infection was observed in 95% of these scans, and at least one abscess was detected in 229 cases (72% of confirmed infection). MRI had an overall technical success rate of 95% and had high positive predictive value for both infection (0.98) and detection of abscess (0.95).ConclusionWe found that emergency neck MRI can be successfully performed on most patients, and that MRI detects neck infection with a high accuracy. These results suggest that MRI may be an alternative to CT as the first or only imaging modality in neck emergencies.

Pigments test strips: A rapid companion test to exclude sub-arachnoid haemorrhage

ObjectivesSubarachnoid haemorrhage (SAH) is characterised by 25% of mortality or induces long-term care. It needs immediate diagnosis with computed tomography (CT) scan. For the inconclusive CT scans, the detection of haem pigments can be performed in the cerebrospinal fluid (CSF). The reference method is spectrophotometry but it requires a large volume of CSF, and specific equipment. Sometimes, urine test strips are used as an alternative method for haem pigments detection. However, this method needs validation in SAH context. The aim of the study was to compare the performance of Multistix® urine test strips for haem pigments detection to the reference spectrophotometry and the final clinical SAH diagnosis. MethodsWe collected 136 CSFs sampled for suspected SAH. We detected haem pigments with urine test strips and spectrophotometry and compared performances for 100 samples. ResultsUrine tests strips displayed a high sensitivity (0.97) as compared to the reference spectrophotometry for haem pigments detection. Interestingly, absence of haem pigments fully correlated with absence of SAH. ConclusionsNegative Multistix® urine test strips could help to exclude SAH diagnosis in combination with clinical data when a spectrophotometer is not available, or as a bedside diagnosis test.

COVID-19 S: A new proposal for diagnosis and structured reporting of COVID-19 on computed tomography imaging.

Because of the widespread use of CT in the diagnosis of COVID 19, indeterminate presentations such as single, few or unilateral lesions amount to a considerable number. We aimed to develop a new classification and structured reporting system on CT imaging (COVID-19 S) that would facilitate the diagnosis of COVID-19 in the most accurate way. Our retrospective cohort included 803 patients with a chest CT scan upon suspicion of COVID 19. The patients' history, physical examination, CT findings, RT PCR, and other laboratory test results were reviewed, and a final diagnosis was made as COVID 19 or non-COVID 19. Chest CT scans were classified according to the COVID 19 S CT diagnosis criteria. Cohen's kappa analysis was used. Final clinical diagnosis was COVID-19 in 98 patients (12%). According to the COVID-19 S CT diagnosis criteria, the number of patients in the normal, compatible with COVID 19, indeterminate and alternative diagnosis groups were 581 (72.3%), 97 (12.1%), 16 (2.0%) and 109 (13.6%). When the indeterminate group was combined with the group compatible with COVID 19, the sensitivity and specificity of COVID-19 S were 99.0% and 87.1%, with 85.8% positive predictive value (PPV) and 99.1% negative predictive value (NPV). When the indeterminate group was combined with the alternative diagnosis group, the sensitivity and specificity of COVID-19 S were 93.9% and 96.0%, with 94.8% PPV and 95.2% NPV. COVID-19 S CT classification system may meet the needs of radiologists in distinguishing COVID-19 from pneumonia of other etiologies and help optimize patient management and disease control in this pandemic by the use of structured reporting.

Vertebra Plana in Children May Result from Etiologies Other Than Eosinophilic Granuloma.

Vertebra plana in children is a diagnostic dilemma for orthopaedic surgeons. This radiographic finding sometimes has been said to be pathognomonic for eosinophilic granuloma (Langerhans cell histiocytosis); however, vertebra plana may also be caused by a range of other conditions. We sought to determine whether vertebra plana can be associated with malignancies other than eosinophilic granuloma. (1) To report the underlying diagnoses for children with vertebra plana and determine how frequently these patients were found to have eosinophilic granuloma as opposed to an underlying malignant process, (2) to evaluate the occurrence of nondiagnostic results on biopsy, and (3) to determine whether the presenting characteristics of spinal lesions were associated with the ultimate clinical diagnosis. As part of a retrospective review, our institutional electronic medical record was searched for all patients younger than 18 years between 1976 and 2017 whose clinical record included the term vertebra plana. Patients with trauma were excluded. Twenty-seven patients met the inclusion criteria (mean [range] age 9 years [0 to 18]; 12 girls). To address our first research purpose about the underlying diagnoses of patients with vertebra plana, we reviewed the final clinical diagnosis. To address our second research purpose about the utility of biopsy, we reviewed which patients underwent a biopsy and whether it had been diagnostic. To address our third research purpose about the radiographic criteria, we classified the radiographs and compared this to the clinical diagnosis. Vertebral collapse was described as less than 50% collapse, 50% to 100% collapse, symmetrical, and asymmetrical. The location of each lesion was noted. Twelve of 27 patients had a diagnosis of eosinophilic granuloma. Six of 27 had other neoplastic etiologies, including acute lymphoblastic leukemia, primary germ cell tumor, giant cell tumor, rhabdomyosarcoma and teratoma. Seventeen of 27 patients underwent biopsy to confirm the diagnosis; six biopsies were consistent with eosinophilic granuloma, six for other etiologies, and five were nondiagnostic. With the limited patient numbers available, there was no difference in the frequency of less than 50% loss of height or 50% to 100%, or symmetric and asymmetric loss of height, and location of the lesion among patients with eosinophilic granuloma and those with other diagnoses. Eosinophilic granuloma or Langerhans cell histiocytosis is a common cause of vertebra plana, but other causes must be considered in children presenting with this radiographic finding. Six of 27 of patients presenting to our center with vertebra plana had an underlying neoplasm other than eosinophilic granuloma. With the limited patient numbers available, pain, spinal location, and the degree and symmetry of collapse were not associated with a diagnosis of eosinophilic granuloma in this series. Thus, patients presenting with vertebral plana and back pain need a comprehensive work-up and potentially tissue biopsy to determine diagnosis and appropriate treatment. Level IV, diagnostic study.

Role of Ultrafast MR Imaging in Stroke Patients.

Objectives The aim of the study is to assess the role of ultrafast (UF) magnetic resonance (MR) sequences in stroke imaging. Material and Methods We prospectively studied 85 patients having clinical suspicion of stroke referred for MR imaging (MRI) during August 2016 to July 2018. These patients were subjected to both conventional and UF MRI sequences. The patients were divided into six categories based on the pathologies encountered. Further subclassification was done based on the size of the lesions as ≤10 mm and >10 mm as seen separately in both UF and conventional MR sequences. The number and visibility of these lesions on conventional and UF MRI were compared. The image quality of all the subjects was also compared based on a scale categorized into excellent, satisfactory, and poor. The findings on conventional and UF imaging sequences were correlated with the final clinical diagnosis arrived at the time of discharge. Results In our study comprising 85 patients, 57 showed pathologies. The patients showing pathologies were assigned into the six categories as acute infarct (34 cases), acute hemorrhagic infarct (six cases), chronic infarct (17 cases), chronic hemorrhagic infarct (four cases), subacute infarct (three cases), and chronic hemorrhage (one case). The number of lesions seen on conventional and UF sequences were the same although there was a slight decrease in the size of the lesions on UF sequences as compared with conventional counterparts. The image quality using UF sequences was better in motion prone patients while conventional imaging showed better image quality in cooperative patients. Conclusion In motion prone patients, UF sequences are a suitable alternative for conventional sequences as they help in arriving at the diagnosis in lesser time, with reasonably good image quality, and without motion artifacts. In cooperative stroke patients, it is better to use conventional MR sequences as the image quality is better.

Lung Ultrasonography as an Accurate Diagnostic Method for the Diagnosis of Community-Acquired Pneumonia in the Elderly Population.

Community-acquired pneumonia (CAP) is one of the most common causes of both hospitalization and death in elderly patients. The chest x-ray (CXR) is nowadays still the imaging method of choice for patients suspected of having pneumonia. However, the sensitivity of CXR, particularly bedside chest radiography, is relatively low. Chest computed tomography, the procedure of higher precision, cannot be conducted routinely for safety, organizational, and economic reasons. Thus, lung ultrasonography (LUS) could be the most accurate diagnostic tool for CAP in the geriatric population.This prospective observational study involving 191 elderly patients (older than 65 years), hospitalized because of suspicion of pneumonia, aimed at comparing the diagnostic accuracy of LUS and CXR to final clinical diagnosis. During the first hours of hospitalization, both CXR and LUS were conducted. At discharge, pneumonia diagnosis was confirmed in 115 patients (60.2% of the study group). Chest x-ray revealed inflammatory lesions in only 65 patients (34% of the study group, 56.5% of the patients with final pneumonia diagnosis), whereas LUS was positive in 114 patients (59.7% of the study group, 99% of the patients with final pneumonia diagnosis). Sensitivity and specificity of LUS in pneumonia diagnosis were, respectively, 99% and 98.7%, whereas CXR sensitivity and specificity were 56.5% and 100%, respectively. The positive and negative predictive values of LUS were 99% and 98.7%, whereas, for CXR, they were 100% and 60.3%, respectively.Lung ultrasonography proved to be more effective at revealing pulmonary inflammatory lesions as compared with CXR in elderly patients suspected of pneumonia.

Additional CTA-Subtraction Technique in Detection of Pulmonary Embolism-a Benefit for Patients or Only an Increase in Dose?

Latest advantages in computed tomography (CT) come with enhanced diagnostic imaging and also sophisticated dose reduction techniques. However, overall exposure to ionizing radiation of patients in Germany rises slightly, which is mainly based on the growing number of performed CT scans. Furthermore, new possibilities in modern imaging, including 4D scans or perfusion protocols, offer new medical insights but require additional scans.In this study, we reevaluated data sets from patients undergoing CT examinations because of suspected pulmonary embolism and compared doses and diagnostic results of the standard protocol to the additional modern CT subtraction technique. Two groups of single-blinded radiologists were provided with CT data sets from 50 patients. One group (G1) had access to full datasets including CT subtraction with perfusion map. The other group (G2) only evaluated conventional CT angiography. Results were compared to final clinical diagnosis. Dose length product (DLP) of CT angiography was compared to CT subtraction technique, which consists of an additional non-contrast-enhanced scan and perfusion map. Effective dose was calculated using a Monte Carlo simulation-based software tool (ImpactDose). Inter-rater agreement of both groups was strong in G1 with κ = .896 and minimal in G2 (κ = .307). Agreement to final diagnosis was strong in both groups (G1, κ = .848; G2, κ = .767). Doses applied using the CT subtraction technique were 34.8% higher than for CT angiography alone (G1 DLP 337.6 ± 171.3 mGy x cm; G2 DLP 220.2 ± 192.8 mGy x cm; p < .001). Calculated effective dose was therefore significantly higher for G1 (G1 4.82 ± 2.20 mSv; G2 3.04 ± 1.33 mSv; p < .001). Our results indicate a benefit of the CT subtraction technique for the detection of pulmonary embolisms in clinical routine, accompanied by an increase in the dose administered. Although CT protocols should always be applied carefully to specific clinical indications in order to maximize the potential for dose reduction and keep the administered dose as low as reasonably achievable, one should never lose sight of the diagnostic benefit, especially in vital clinical indications.

Differential diagnosis of parkinsonian syndromes: a comparison of clinical and automated - metabolic brain patterns' based approach.

Differentiation among parkinsonian syndromes may be clinically challenging, especially at early disease stages. In this study, we used 18F-FDG-PET brain imaging combined with an automated image classification algorithm to classify parkinsonian patients as Parkinson's disease (PD) or as an atypical parkinsonian syndrome (APS) at the time when the clinical diagnosis was still uncertain. In addition to validating the algorithm, we assessed its utility in a "real-life" clinical setting. One hundred thirty-seven parkinsonian patients with uncertain clinical diagnosis underwent 18F-FDG-PET and were classified using an automated image-based algorithm. For 66 patients in cohort A, the algorithm-based diagnoses were compared with their final clinical diagnoses, which were the gold standard for cohort A and were made 2.2 ± 1.1years (mean ± SD) later by a movement disorder specialist. Seventy-one patients in cohort B were diagnosed by general neurologists, not strictly following diagnostic criteria, 2.5 ± 1.6years after imaging. The clinical diagnoses were compared with the algorithm-based ones, which were considered the gold standard for cohort B. Image-based automated classification of cohort A resulted in 86.0% sensitivity, 92.3% specificity, 97.4% positive predictive value (PPV), and 66.7% negative predictive value (NPV) for PD, and 84.6% sensitivity, 97.7% specificity, 91.7% PPV, and 95.5% NPV for APS. In cohort B, general neurologists achieved 94.7% sensitivity, 83.3% specificity, 81.8% PPV, and 95.2% NPV for PD, while 88.2%, 76.9%, 71.4%, and 90.9% for APS. The image-based algorithm had a high specificity and the predictive values in classifying patients before a final clinical diagnosis was reached by a specialist. Our data suggest that it may improve the diagnostic accuracy by 10-15% in PD and 20% in APS when a movement disorder specialist is not easily available.

MDCT in the Setting of Suspected Colonic Diverticulitis: Prevalence and Diagnostic Yield for Diverticulitis and Alternative Diagnoses.

OBJECTIVE. The purpose of this study was to determine the prevalence and demographic distribution of colonic diverticulitis (CD) and alternative diagnoses (AD), as well as the diagnostic accuracy of MDCT in patients with suspected CD. MATERIALS AND METHODS. This study retrospectively included 1069 patients (560 women) undergoing MDCT for the evaluation of suspected CD. The prevalence of CD and AD was determined and the diagnostic accuracy of MDCT calculated. The final clinical diagnosis derived from the discharge report served as the standard of reference. Prevalence of diagnoses by age, sex, and admission status were compared using Cochran-Armitage, chi-square, and Fisher exact tests. RESULTS. Prevalence of CD was 52.5% (561/1069) and of AD was 39.9% (427/1069). In the remaining 7.6% (81/1069) no final clinical diagnosis was established. The most frequent AD were appendicitis (12.6%, 54/427), infectious colitis (10.5%, 45/427), infectious gastroenteritis (8.2%, 35/427), urolithiasis (6.1%, 26/427), and pyelonephritis (4.9%, 21/427). The prevalence of diverticulitis and AD varied statistically significantly according to both age (p < 0.001) and admission status (p < 0.001). Also, the prevalence of the 10 most frequent specific AD varied statistically significantly according to sex (p = 0.022). CT had a sensitivity and specificity of 99.1% and 99.8% for diagnosing CD and 92.7% and 98.8% for AD, respectively. CONCLUSION. In about 40% of patients with suspected diverticulitis a broad spectrum of AD is causative for symptoms. MDCT provides high diagnostic accuracy in the diagnosis of diverticulitis and AD. The prevalence of diagnoses is related to admission status and demographic data; in particular age-related AD have to be considered in patients with clinically suspected diverticulitis.

The clinical application of nigrosome 1 detection on high-resolution susceptibility-weighted imaging in the evaluation of suspected Parkinsonism: The real-world performance and pitfalls.

PurposeTo evaluate the real-world diagnostic performance of high-resolution susceptibility-weighted imaging (HR-SWI) and investigate whether the reader’s predictions can be used to find cases where HR-SWI finding and final clinical diagnosis matched.MethodsThis retrospective study enrolled patients with suspected Parkinsonism (n = 48) or volunteers with other intracranial pathologies (n = 31) who underwent brain magnetic resonance imaging (MRI) including HR-SWI, which was used to evaluate nigrosome 1 (NG1). All patients with suspected Parkinsonism underwent N-3-fluoropropyl-2-carbomethoxy-3-4-iodophenyl nortropane (FP-CIT) positron emission tomography and a clinical diagnosis was made by a neurologist. The HR-SWI data were qualitatively analyzed by two independent reviewers. A consensus reading was performed and a diagnostic confidence score was assigned. According to final clinical diagnosis, diagnostic sensitivity, specificity, and accuracy were calculated. Receiver operating characteristic (ROC) curve analysis was used to examine whether the diagnostic confidence score could be used to identify HR-SWI finding—final clinical diagnosis matched cases.ResultsOf the 48 patients with suspected Parkinsonism, 31 were diagnosed with idiopathic Parkinson’s disease, and three with multiple system atrophy. The remaining 14 patients were included in the disease control group. Of the 31 volunteers, 10 subjects were excluded due to possibility of nigrostriatal degeneration and finally 21 subjects were enrolled as controls with non-Parkinsonism pathology (non-PD control). After consensus reading, 25 subjects were classified as true positive and 28 as true negative, according to HR-SWI findings. The calculated diagnostic sensitivity, specificity, and accuracy were 73.5%, 80.0%, and 76.8%, respectively. With using diagnostic concordance score, the area under the ROC curve for the detection of concordance case was 0.83 (95% CI: 0.72–0.91, p < 0.05).ConclusionThe diagnostic performance of NG1 detection using HR-SWI with 3T MRI was within acceptable range. Using the reader's diagnostic confidence could be helpful to find cases which HR-SWI finding and final clinical conclusion match. So HR-SWI may be of added value in the evaluation of suspected Parkinsonism.

Neuropathological correlates of parkinsonian disorders in a large Dutch autopsy series

The clinical diagnosis in patients with parkinsonian disorders can be challenging, and a definite diagnosis requires neuropathological confirmation. The aim of this study was to examine whether a clinical diagnosis of Parkinson’s disease (PD) and atypical parkinsonian disorders predict the presence of Lewy pathology (LP) and concomitant neuropathological lesions.We included 293 donors with a history of parkinsonism without dementia at disease onset, collected by the Netherlands Brain Bank (NBB) from 1989 to 2015. We retrospectively categorized donors according the International Parkinson and Movement Disorder Society clinical diagnostic criteria for PD (MDS-PD criteria) as ‘not PD’, ‘probable PD’ or ‘established PD’. We compared the final clinical diagnosis to presence of neuropathological lesions as defined by BrainNet Europe and National Institute on Aging – Alzheimer's Association guidelines.LP was present in 150 out of 176 donors (85%) with a clinical diagnosis of PD, in 8 out of 101 donors (8%) with atypical parkinsonian disorders and in 4 out of 16 donors (25%) without a definite clinical diagnosis. Independent from age at death, stages of amyloid-β, but not neurofibrillary tau or neuritic plaques, were higher in donors with LP compared to other types of pathology (p = 0.009). The MDS-PD criteria at a certainty level of ‘probable PD’ predicted presence of LP with a diagnostic accuracy of 89.3%. Among donors with LP, ‘established PD’ donors showed similar Braak α-synuclein stages and stages of amyloid-β, neurofibrillary tau and neuritic plaques compared to ‘not PD’ or ‘probable PD’ donors.In conclusion, both a clinical diagnosis of PD as well as MDS-PD criteria accurately predicted presence of LP in NBB donors. LP was associated with more widespread amyloid-β pathology, suggesting a link between amyloid-β accumulation and LP formation.

Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism\u2014comparison with values from healthy volunteers

PurposeIodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers’ data.MethodsFrom a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16–88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses.ResultsAge had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and “normality” limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 ([− 0.019, − 0.011]) for the Flash3D database versus − 0.015 ([− 0.021, − 0.009]) for ENC-DAT. Caudate-to-putamen ratios and asymmetries were not influenced by age or gender.ConclusionThe generated 123I-FP-CIT references values have similar age-related distribution, with no increase in variance due to comorbidities when compared to values from a multi-center study with healthy volunteers. This makes it possible for sites to build their 123I-FP-CIT references from scans acquired during routine clinical practice.

Transcervical sonography and human papillomavirus 16 E6 antibodies are sensitive for the detection of oropharyngeal cancer.

Human papillomavirus 16 (HPV-16) E6 seropositivity is a promising early marker of human papillomavirus-driven oropharyngeal cancer (HPV-OPC), yet more sensitive imaging modalities are needed before screening is considered. The objective of this study was to determine the sensitivity of transcervical sonography (TCS) for detecting clinically apparent HPV-OPC in comparison with computed tomography (CT) and positron emission tomography (PET)/CT. Fifty-one patients with known or suspected HPV-OPC without prior treatment underwent oropharyngeal TCS and blood collection (for HPV multiplex serology testing). Eight standard sonographic images were collected; primary-site tumors were measured in 3 dimensions if identified. Each patient underwent a full diagnostic workup as part of standard clinical care. The pathologic details, HPV status, final staging, and imaging findings were abstracted from the medical record. The sensitivity of each imaging modality was compared with the final clinical diagnosis (the gold standard). Twenty-four base of tongue cancers (47%), 22 tonsillar cancers (43%), and 2 unknown primary cancers (4%) were diagnosed; 3 patients (6%) had no tumors. All p16-tested patients were positive (n=47). Primary-site tumors were correctly identified in 90.2% (95% confidence interval [CI], 78.6%-96.7%) with TCS, in 69.4% (95% CI, 54.6%-81.7%) with CT, and in 83.3% (95% CI, 68.6%-93.0%) with PET/CT. TCS identified tumors in 10 of 14 cases missed by CT and recognized the absence of tumors in 3 cases for which CT or PET/CT was falsely positive. The smallest sonographically identified primary-site tumor was 0.5cm in its greatest dimension; the average size was 2.3cm. Among p16-positive patients, 76.1% (95% CI, 61.2%-87.4%) were seropositive for HPV-16 E6. TCS and HPV-16 E6 antibodies are sensitive for the diagnosis of HPV-OPC.

Multidisciplinary team approach on a case of bilateral interstitial pneumonia

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by exposure to a wide variety of organic particles. In this article, we report a rare case of a 44-year-old male patient with cough and shortness of breath for more than 4 years and exacerbation for 1 month. The findings of lung computed tomography (CT) and pathology supported a diagnosis of chronic HP. The patient had a history of ulcerative colitis for 5 years, and used to take salazosulfapyridine more than 4 years since 2013. We organized domestic and foreign experts to discuss the diagnosis and treatment of this case. The final clinical diagnosis was chronic interstitial pneumonia [related to sulfasalazine or inflammatory bowel disease (IBD) itself], pulmonary infections. It is recommended to discontinuation of sulfasalazine and oral administration of glucocorticoids and required long-term follow-up.

Multiplex bacterial polymerase chain reaction in a cohort of patients with pleural effusion

BackgroundThe identification of the pathogens in pleural effusion has mainly relied on conventional bacterial culture or single species polymerase chain reaction (PCR), both with relatively low sensitivity. We investigated the efficacy of a commercially available multiplex bacterial PCR assay developed for pneumonia to identify the pathogens involved in pleural infection, particularly empyema.MethodsA prospective, monocentric, observational study including 194 patients with pleural effusion. Patients were evaluated based on imaging, laboratory values, pleura ultrasound and results of thoracentesis including conventional microbiology studies during hospitalisation. Multiplex bacterial PCR (Curetis Unyvero p55) was performed in batch and had no influence on therapeutic decisions.ResultsOverall, there were 51/197 cases with transudate and 146/197 with exudate. In 42% (n = 90/214) there was a clinical suspicion of parapneumonic effusion and the final clinical diagnosis of empyema was made in 29% (n = 61/214) of all cases. The most common microorganisms identified in the cases diagnosed with empyema were anaerobes [31] followed by gram-positive cocci [10] and gram-negative rods [4]. The multiplex PCR assay identified more of the pathogens on the panel than the conventional methods (23.3% (7/30) vs. 6.7% (2/30), p = 0.008).ConclusionThe multiplex PCR-based assay had a higher sensitivity and specificity than conventional microbiology when only the pathogens on the pneumonia panel were taken into account. A dedicated pleural empyema multiplex PCR panel including anaerobes would be needed to cover most common pathogens involved in pleural infection.

Direct prospective comparison of 18F-FDG PET and arterial spin labelling MR using simultaneous PET/MR in patients referred for diagnosis of dementia.

18F-FDG PET is routinely used as an imaging marker in the early and differential diagnosis of dementing disorders and has incremental value over the clinical neurological and neuropsychological evaluation. Perfusion MR imaging by means of arterial spin labelling (ASL) is an alternative modality to indirectly measure neuronal functioning and could be used as complement measurement in a single MR session in the workup of dementia. Using simultaneous PET-MR, we performed a direct head-to-head comparison between enhanced multiplane tagging ASL (eASL) and 18F-FDG PET in a true clinical context of subjects referred for suspicion of neurodegenerative dementia. Twenty-seven patients underwent a 20-min 18F-FDG PET/MR and simultaneously acquired eASL on a GE Signa PET/MR. Data were compared with 30 screened age- and gender-matched healthy controls. Both integral eASL and 18F-FDG datasets were analysed visually by two readers unaware of the final clinical diagnosis, either in normal/abnormal classes, or full differential diagnosis (normal, Alzheimer type dementia [AD], dementia with Lewy Bodies [LBD], frontotemporal dementia [FTD] or other). Reader confidence was assessed with a rating scale (range 1-4). Data were also analysed semiquantitatively by VOI and voxel-based analyses. The ground truth diagnosis for the patient group resulted in 14 patients with a neurodegenerative cognitive disorder (AD, FTD, LBD) and 13 patients with no arguments for an underlying neurodegenerative cause. Visual analysis resulted in equal specificity (0.70) for differentiating normal and abnormal cases between the two modalities, but in a higher sensitivity (0.93), confidence rating (0.64) and interobserver agreement for 18F-FDG PET compared with eASL. The same was true for assigning a specific differential diagnosis (sensitivity: and 0.39 for 18F-FDG PET and eASL, respectively). Semiquantitative analyses revealed prototypical patterns for AD and FTD, with both higher volumes of abnormality and intensity differences on 18F-FDG PET. In a direct head-to-head comparison on a simultaneous GE Signa PET/MR, 18F-FDG PET performed better compared with ASL in terms of sensitivity and reader confidence, as well as volume and intensity of abnormalities. However, using pure semiquantitative analysis, similar diagnostic accuracy between the two modalities was obtained. Therefore, ASL may still serve as complement to neuroreceptor or protein deposition PET studies when a single simultaneous investigation is warranted.