Diagnostics, Vol. 9, Pages 66: In vivo Diagnosis of Primary Cutaneous Amyloidosis —the Role of Reflectance Confocal Microscopy Primary cutaneous amyloidosis (PCA) is a form of localized amyloidosis. It is characterized by the deposition of a fibrillar material in the superficial dermis, without affecting other systems or organs. The diagnosis can be made clinically, but usually a skin biopsy is performed in order to exclude other skin diseases with similar appearance. Reflectance confocal microscopy (RCM) is a novel imaging tool that enables in vivo characterization of various skin changes with a high, quasi-microscopic resolution. This technique might have an important role in the differential diagnosis of cutaneous amyloidosis, by the in vivo assessment of epidermal changes and dermal amyloid deposition. Moreover, it is completely non-invasive and can be safely repeated on the same skin area. However, to date, there is only one published paper presenting the confocal features of primary cutaneous amyloidosis. Hereby, we describe the in vivo RCM features of PCA lesions from a patient with diabetes and correlate them with histologic findings. This strengthens the clinical usefulness of in vivo RCM examination for the non-invasive diagnosis of cutaneous amyloidosis, especially in patients that might associate diseases with impaired wound healing.

Diagnostics, Vol. 9, Pages 65: The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer’s Disease—Review of Literature and Interesting Images Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided.

Diagnostics, Vol. 9, Pages 64: Diagnostics Receives First Impact Factor It is with great pleasure we can announce that Diagnostics has received its first official impact factor, which has just been published in the 2018 edition of the Journal Citation Reports® [...]

Diagnostics, Vol. 9, Pages 63: Decreased CTRP3 Plasma Concentrations Are Associated with Sepsis and Predict Mortality in Critically Ill Patients C1q/ tumor necrosis factor (TNF)-like protein 3 (CTRP3) represents a novel member of the adipokine family that exerts favorable metabolic actions in humans. However, the role of CTRP3 in critical illness and sepsis is currently unknown. Upon admission to the medical intensive care unit (ICU), we investigated CTRP3 plasma concentrations in 218 critically ill patients (145 with sepsis, 73 without sepsis). Results were compared with 66 healthy controls. CTRP3 plasma levels were significantly decreased in critically ill patients, when compared to healthy controls. In particular, low CTRP3 levels were highly associated with the presence of sepsis. CTRP3 levels were neither associated with obesity nor diabetes. In critically ill patients, CTRP3 plasma concentrations were inversely correlated with inflammatory cytokines and classical sepsis markers. Among a wide group of adipokines, CTRP3 only correlated with circulating resistin. Low CTRP3 plasma levels were associated with the overall mortality, and CTRP3 levels below 620.6 ng/mL indicated a particularly increased mortality risk in ICU patients. Our study demonstrates for the first time the role of circulating CTRP3 as a biomarker in critically ill patients that might facilitate diagnosis of sepsis as well as prognosis prediction. The association between low CTRP3 and increased inflammation warrants further pathophysiological investigations.

Diagnostics, Vol. 9, Pages 62: Solid Indeterminate Pulmonary Nodules of Less Than 300 mm3: Application of Different Volume Doubling Time Cut-offs in Clinical Practice In the British Thoracic Society guidelines for incidental pulmonary nodules, volumetric analysis has become the recommended method for growth assessment in solid indeterminate pulmonary nodules (SIPNs) <300 mm3. In these guidelines, two different volume doubling time (VDT) cut-offs, 400 and 600 days, were proposed to differentiate benign from malignant nodules. The present study aims to evaluate the performance of these VDT cut-offs in a group of SIPNs <300 mm3 which were incidentally detected in a routine clinical setting. During a 7-year period, we retrospectively selected 60 patients with a single SIPN <300 mm3. For each SIPN, the volume and VDT were calculated using semiautomatic software throughout the follow-up period, and the performance of the 400- and 600-day VDT cut-offs was compared. In the selected sample, there were 38 benign and 22 malignant nodules. In this group of nodules, the sensitivity, negative predictive value and accuracy of the 600-day VDT cut-off were higher than those of the 400-day VDT cut-off. Therefore, in the management of SIPNs <300 mm3 which were incidentally detected in a clinical setting, the 600-day VDT cut-off was better at differentiating benign from malignant nodules than the 400-day VDT cut-off, by reducing the number of false negatives.

Diagnostics, Vol. 9, Pages 61: Hand-Held Ultrasound Devices Compared with High-End Ultrasound Systems: A Systematic Review The aim of this study was to review the scientific literature available on the comparison of hand-held ultrasound devices with high-end systems for abdominal and pleural applications. PubMed, Embase, Web of Science and Cochrane were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Original research describing hand-held ultrasound devices compared with high-end systems was included and assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. The search was limited to articles published since 1 January 2012. A total of 2486 articles were found and screened by title and abstract. A total of 16 articles were chosen for final review. All of the included articles showed good overall agreement between hand-held and high-end ultrasound systems. Strong correlations were found when evaluating ascites, hydronephrosis, pleural cavities, in detection of abdominal aortic aneurysms and for use with obstetric and gynaecological patients. Other articles found good agreement for cholelithiasis and for determining the best site for paracentesis. QUADAS-2 analysis suggested few risks of bias and almost no concerns regarding applicability. For distinct clinical questions, hand-held devices may be a valuable supplement to physical examination. However, evidence is inadequate, and more research is needed on the abdominal and pleural use of hand-held ultrasound with more standardised comparisons, using only blinded reviewers.

Diagnostics, Vol. 9, Pages 60: Diagnostic Performance of PET or PET/CT Using 18F-FDG Labeled White Blood Cells in Infectious Diseases: A Systematic Review and a Bivariate Meta-Analysis Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose (18F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic. Methods: A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and diagnostic odds ratio (DOR) of 18F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated. Results: Eight studies on the use of 18F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75–92.9%], specificity 92% (95%CI 79.8–97.1%), LR+ 6.6 (95%CI: 3.1–14.1), LR− 0.2 (95%CI: 0.12–0.33), DOR 43.5 (95%CI: 12.2–155). A statistically significant heterogeneity was not detected. Conclusions: Despite limited literature data, 18F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed.

Diagnostics, Vol. 9, Pages 59: Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression in cutaneous melanoma is still under investigation. In the present study, we analyzed microarray and RNA-Seq data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) using different bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP and -DR, was significantly associated with better overall survival. Furthermore, the expressions of HLA class II genes were most closely associated with survival in cutaneous melanoma as compared with other cancer types. The expression of HLA class II co-expressed genes, which were found to associate with antigen processing, immune response, and inflammatory response, was also positively associated with overall survival in cutaneous melanoma. Therefore, the results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity and related inflammatory response via presenting tumor antigens to the immune system. The expression pattern of HLA class II genes may serve as a prognostic biomarker and therapeutic targets in cutaneous melanoma.

Diagnostics, Vol. 9, Pages 58: Codex (Cognitive Disorders Examination) Decision Tree Modified for the Detection of Dementia and MCI Many cognitive screening instruments are available to assess patients with cognitive symptoms in whom a diagnosis of dementia or mild cognitive impairment is being considered. Most are quantitative scales with specified cut-off values. In contrast, the cognitive disorders examination or Codex is a two-step decision tree which incorporates components from the Mini-Mental State Examination (MMSE) (three word recall, spatial orientation) along with a simplified clock drawing test to produce categorical outcomes defining the probability of dementia diagnosis and, by implication, directing clinician response (reassurance, monitoring, further investigation, immediate treatment). Codex has been shown to have high sensitivity and specificity for dementia diagnosis but is less sensitive for the diagnosis of mild cognitive impairment (MCI). We examined minor modifications to the Codex decision tree to try to improve its sensitivity for the diagnosis of MCI, based on data extracted from studies of two other cognitive screening instruments, the Montreal Cognitive Assessment and Free-Cog, which are more stringent than MMSE in their tests of delayed recall. Neither modification proved of diagnostic value for mild cognitive impairment. Possible explanations for this failure are considered.

Diagnostics, Vol. 9, Pages 57: Detecting Synchronous Parathyroid Adenoma and False-Positive Findings on Technetium-99m MIBI Single Photon-Emission Computed Tomography/Computed Tomography Technetium (Tc)-99m-methoxyisobutylisonitrile (MIBI) single photon-emission computed tomography/computed tomography (SPECT/CT) is now being used increasingly for preoperative localization of parathyroid adenomas. Tc-99m-MIBI scintigraphy in a 52-year-old man with a diagnosis of primary hyperparathyroidism revealed two focal areas with retention of radioactivity in the left lobe of the thyroid gland on the delayed phase of MIBI SPECT/CT but no significant focal radioactive uptake on MIBI planar images. The patient subsequently underwent left partial parathyroidectomy. Histological analysis identified one lesion to be thyroid hyperplasia and the other to be parathyroid adenoma. This case demonstrates the value of MIBI SPECT/CT for localization of a parathyroid lesion when compared with planar images and that false-positive findings can lead to misdiagnosis in a patient with coexisting thyroid disease. An appropriate diagnostic work-up that includes Tc-99m MIBI SPECT/CT in addition to ultrasonography is helpful for an accurate diagnosis in patients with concomitant thyroid disease.