Diagnostics, Volume 10, Issue 11 (November 2020) – 135 articles

Serological tests offer the potential in order to improve the diagnosis of tuberculosis (TB). Macrophage migration inhibitory factor (MIF) plays a protective role in infection control in TB; however, to date, no studies on antibody responses to MIF have been reported. We measured immunoglobulin (Ig)A and IgG responses to MIF in individuals with either active tuberculosis (ATB; n = 65), latent tuberculosis (LTBI; n = 53), or in non-infected individuals (NI; n = 62). The QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was used in order to screen for LTBI. The level of IgA against MIF was significantly lower in LTBI and ATB patients than in NI individuals, was significantly related to LTBI and ATB diagnosis, and it could discriminate between LTBI and ATB. In contrast, the level of IgG against MIF was significantly lower in LTBI patients than in NI individuals and was significantly related to LTBI diagnosis. Anti-MIF IgG levels were significantly lower in AFB-negative TB, minimal TB, and new ATB patients, than in the NI group. IgA and IgG levels against MIF both showed significant negative correlations with IFN-γ levels, as assessed using the QFT-GIT test. Although none of the antibodies could achieve high diagnostic predictive power individually, our results suggest the possibility of using IgA antibody responses to MIF in the diagnosis of LTBI and ATB. Full article

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO₂; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome. Full article

The opacification of the olfactory cleft (OC) has been associated with birhinal orthonasal olfaction in patients with chronic rhinosinusitis (CRS). The aim of this study was to determine the associations between monorhinal and birhinal orthonasal, and retronasal olfaction with radiological markers of the OC in a cohort of patients with CRS. Results were analyzed in a CRS-cohort including 13 patients with nasal polyposis (CRSwNP) and 12 patients with non-eosinophilic CRS (non-eCRS). Monorhinal and birhinal orthonasal olfactory function, and OC-air volume were higher in non-eCRS compared CRSwNP. OC-opacification was also higher in CRSwNP compared to non-eCRS. In the entire CRS-cohort, those with higher OC-opacification showed significantly lower orthonasal and retronasal olfactory test results compared to those with lower OC-opacification across all three coronal planes. Similarly, higher unilateral OC-opacification was also associated with lower ipsilateral orthonasal olfactory function. Correlation analysis further revealed a positive correlation between monorhinal and birhinal orthonasal olfaction with ipsilateral and overall OC-air volume. Likewise, birhinal and monorhinal orthonasal, and retronasal olfactory test results correlated negatively with the overall and ipsilateral Lund-Mackay scores. Monorhinal and birhinal orthonasal, and retronasal olfactory function were lower in CRS patients with higher ipsilateral and overall OC-opacification compared to those with lower OC-opacification. Full article

Breast density estimation with visual evaluation is still challenging due to low contrast and significant fluctuations in the mammograms’ fatty tissue background. The primary key to breast density classification is to detect the dense tissues in the mammographic images correctly. Many methods have been proposed for breast density estimation; nevertheless, most of them are not fully automated. Besides, they have been badly affected by low signal-to-noise ratio and variability of density in appearance and texture. This study intends to develop a fully automated and digitalized breast tissue segmentation and classification using advanced deep learning techniques. The conditional Generative Adversarial Networks (cGAN) network is applied to segment the dense tissues in mammograms. To have a complete system for breast density classification, we propose a Convolutional Neural Network (CNN) to classify mammograms based on the standardization of Breast Imaging-Reporting and Data System (BI-RADS). The classification network is fed by the segmented masks of dense tissues generated by the cGAN network. For screening mammography, 410 images of 115 patients from the INbreast dataset were used. The proposed framework can segment the dense regions with an accuracy, Dice coefficient, Jaccard index of 98%, 88%, and 78%, respectively. Furthermore, we obtained precision, sensitivity, and specificity of 97.85%, 97.85%, and 99.28%, respectively, for breast density classification. This study’s findings are promising and show that the proposed deep learning-based techniques can produce a clinically useful computer-aided tool for breast density analysis by digital mammography. Full article

We report the case of a 71-year-old man affected by testicular large B-cell lymphoma (DLBCL), treated with right orchiectomy and first-line chemotherapy (R-CHOP, 8 cycles). A complete remission was obtained after therapy. Twenty-two months after the primary diagnosis the patient suddenly presented dyspnoea and superior vena cava syndrome; thus, he underwent a CT scan that revealed a large mass in the right atrium, expanding to the superior vena cava. A differential diagnosis between a neoplastic mass and a clot was proposed. The subsequent MR did not clarify the nature of the mass; therefore, the patient underwent an 18F-FDG PET/CT scan (PET/CT), after a specific preparation to reduce fluoro-deoxyglucose (FDG) myocardial uptake. PET/CT revealed an intense FDG uptake involving the whole mass (SUVmax 9.4), suggestive for neoplasm and confirmed by the subsequent endocardiac biopsy. The patient was treated with 8 cycles of R-COMP, obtaining a complete remission, as indicated by the PET/CT performed after the seventh cycle of therapy. The case that we are reporting highlights that DLBCL can have an uncommon relapse presentation in the atrium. PET/CT, compared to conventional imaging, can be a valuable tool to detect early and better characterize cardiac lesions in order to improve the poor prognosis of these conditions. Full article

The objective of the study was to describe a case-series of neural tube defects (NTD) with an abnormal intracranial translucency (IT) detected during the first-trimester ultrasound scan, performed on a low-risk obstetric population in Mexico. Certified Fetal Medicine specialists performed all US scans; the IT was assessed using the mid-sagittal view of the fetal head, which is already systematically used for nuchal translucency and nasal bone evaluation. During the study, we were able to find that eight fetuses had an absence of the intracranial translucency, out of which two were reassessed at 14 weeks′ gestation and IT was normal, six of them were later diagnosed to have an NTD that consisted in spina bifida aperta (n = 5) and encephalocele (n = 1). Conclusion: As previous studies have shown, IT evaluation during the first-trimester US routine scan may be a useful screening marker for early detection of NTDs. Full article

In Asian countries, ultrasound has been proposed as a possible alternative for mammography in breast cancer screening because of its superiority in dense breasts, accessibility and low costs. This research aimed to meta-analyze the evidence for the diagnostic performance of ultrasound compared to mammography for breast cancer screening in Asian women. PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched for studies that concurrently compared mammography and ultrasound in 2000–2019. Data extraction and risk of bias were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) statement. The primary outcome was the sensitivity and specificity. Bivariate random models were used to generate pooled estimates of diagnostic parameters and 95% confidence intervals (95% CI). In total, 4424 studies were identified of which six studies met the inclusion criteria with a sample size of 124,425 women. The pooled mean prevalence of the included studies was 3.7‰ (range: 1.2–5.7‰). The pooled sensitivity of mammography was significantly higher than that of ultrasound (0.81 [95% CI 0.71–0.88] versus 0.65 [95% CI 0.58–0.72], p = 0.03), but no significant differences were found in specificity (0.98 [95% CI: 0.94–1.00] versus 0.99 [95% CI: 0.97–1.00], p = 0.65). In conclusion, based on the currently available data on sensitivity alone, there is no indication that ultrasound can replace mammography in breast cancer screening in Asian women. Full article

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers. Full article

Background: Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, such as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: We performed CMR in 49 HCM patients, 30 non-HCM hypertrophy, and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to 25% of diastole. Left ventricular mass, mean, and standard deviation (SD) of WT, maximal WT, minimal WT, and their difference were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating eight hearts with HCM, 10 with coronary artery disease, and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95% CI = 0.89–0.98). This was particularly evident in the female population of HCM (AUC=0.998), with 100% specificity (95% CI = 85–100%) and 96% sensitivity (95% CI = 79–99%). Using this parameter, at PMCMR, all of the eight patients with HCM were correctly identified with no false positives. Conclusions: PMCMR allows identification of HCM as the cause of sudden death using the SD of WT > 2.4 as the diagnostic parameter. Full article

We evaluated the feasibility and efficacy of four existing interventions to improve adherence to them in migrants living with HIV (MLWH): directly administered antiretroviral therapy (DAART), group medical appointments (GMA), early detection and treatment of psychological distress, and peer support by trained MLWH. At baseline and after the interventions, socio-demographic characteristics, psychosocial variables, and data on HIV treatment adherence were collected. The two questionnaires were completed by 234/301 (78%) MLWH included at baseline. Detectable HIV RNA decreased (from 10.3 to 6.8%) as did internalized HIV-related stigma (from 15 to 14 points), and self-reported adherence increased (between 5.5 and 8.3%). DAART and GMA were not feasible interventions. Screening of psychological distress was feasible; however, follow-up diagnostic screening and linkage to psychiatric services were not. Peer support for and by MLWH was feasible. Within this small intervention group, results on HIV RNA < 400 copies/mL (decrease of 23.6%) and outpatient clinic attendance (up to 20.4% kept more appointments) were promising. Full article

Heated-bone color changes may provide information about temperature of exposure, with interest for anthropologists and forensic experts. The aim of this study was to assess heat-induced color changes by spectrophotometry in cortical and medullar human bones heated at different temperatures and times. CIELAB (International Commission on Illumination-LAB) color parameters (L*, a*, and b*) and whiteness (WI) and yellowness (YI) indexes were obtained by spectrophotometry in the cortical and medullar zones of 36 bone sections exposed at 200, 400, 600, and 800 °C for 30 and 60 min. The accuracy of color-based temperature estimations was evaluated by Receiver Operating Characteristics (ROC) analysis. Chromaticity a* showed the best significant discrimination power with the area under the ROC curve (AUC) values ranged from 0.9 to 1.0 in cortical zones and 0.7 to 1.0 in medullar zones for all temperatures of exposures and both time of exposures. Chromaticity b*, and WI and YI indexes showed an AUC of 1.0 at 400, 600, and 800 °C for 30 and 60 min in the cortical and medullar zones. The spectrophotometric color parameters provided a highly accurate estimation of the temperature of exposure to discriminate between temperatures and exposure times in the cortical and medullar zones. Spectrophotometric bone color measurement in cortical and medullar zones can be an objective and reproducible method to estimate the temperature of exposition, and it can be considered useful for forensic and anthropological purposes. Full article

Interleukin-6 (IL-6) and C-reactive protein (CRP) are being used for diagnosis of sepsis. However, studies have reported varying cut-off levels and diagnostic performance. This study aims to investigate the optimal cut-off levels and performance of IL-6 and CRP for the diagnosis of neonatal sepsis. The study was conducted at the University Hospital of Leipzig, Germany from November 2012 to June 2020. A total of 899 neonates: 104 culture proven sepsis, 160 clinical sepsis, and 625 controls were included. Blood culture was performed using BacT/ALERT 3D system. IL-6 and CRP were analyzed by electrochemiluminescent immunoassay and immunoturbidimetric assay, respectively. Data were analyzed using SPSS 20 statistical software. Among neonates with proven sepsis, the optimal cut-off value of IL-6 was 313.5 pg/mL. The optimal cut-off values for CRP in 5 days serial measurements (CRP1, CRP2, CRP3, CRP4, and CRP5) were 2.15 mg/L, 8.01 mg/L, 6.80 mg/L, 5.25 mg/L, and 3.72 mg/L, respectively. IL-6 showed 73.1% sensitivity, 80.2% specificity, 37.6% PPV, and 94.8% NPV. The highest performance of CRP was observed in the second day with 89.4% sensitivity, 97.3% specificity, 94.5% PPV, and 98.3% NPV. The combination of IL-6 and CRP showed increase in sensitivity with decrease in specificity. In conclusion, this study defines the optimal cut-off values for IL-6 and CRP. The combination of IL-6 and CRP demonstrated increased sensitivity. The CRP 2 at cut-off 8.01 mg/L showed the highest diagnostic performance for identification of culture negative clinical sepsis cases. We recommend the combination of IL-6 (≥313.5 pg/mL) and CRP1 (≥2.15 mg/L) or IL-6 (≥313.5 pg/mL) and CRP2 (≥8.01 mg/L) for early and accurate diagnosis of neonatal sepsis. The recommendation is based on increased sensitivity, that is, to minimize the risk of any missing cases of sepsis. The CRP2 alone at cut-off 8.01 mg/L might be used to identify clinical sepsis cases among culture negative sepsis suspected neonates in hospital settings. Full article

Background. Childhood obesity is becoming a major health issue and contributes to increasing the risk of cardiovascular disease in adulthood. Since dysregulated metabolism of bile acids (BAs) plays a role in progression of obesity-related disorders, including steatosis and hypertension, this study aimed to investigate BAs profiles in obese children with and without steatosis and hypertension, as well as exploring the interplay between BAs profile and vascular function. Methods. BAs concentrations were quantified with liquid chromatography-tandem mass spectrometry in 69 overweight/obese children and adolescents (mean age, 11.6 ± 2.5 years; 30 females). Liver steatosis was defined with abdomen ultrasonography, whilst hypertension was defined according to the current European guidelines. Vascular function was assessed with ultrasound technique, by measuring carotid intima media thickness (cIMT) and common carotid artery distensibility (cDC). Results. Total and individual glycine-conjugated BAs concentrations were found to be significantly higher in males compared to females, as well as in pre-pubertal compared to pubertal stage (p < 0.05 for both). No difference in BAs concentration was observed between hypertensive and normotensive subjects. Total BAs and glycine conjugated BAs were significantly higher in participants with steatosis compared to those without (p = 0.004 for both). The values of total glycine-conjugate acids were positively correlated with cDC and this association remained significant in linear regression after adjusting for sex, age, pubertal stage, body mass index and aspartate aminotransferase. Conclusion. The results suggest a possible role of BAs in the pathogenesis of liver and/or vascular damage in children and adolescent. Further studies are hence needed to validate these preliminary findings. Full article

In this review, we will evaluate how high-density lipoprotein (HDL) and the reverse cholesterol transport (RCT) pathway are critical for proper cardiovascular–renal physiology. We will begin by reviewing the basic concepts of HDL cholesterol synthesis and pathway regulation, followed by cardiorenal syndrome (CRS) pathophysiology. After explaining how the HDL and RCT pathways become dysfunctional through oxidative processes, we will elaborate on the potential role of HDL dysfunction in CRS. We will then present findings on how HDL function and the inducible antioxidant gene heme oxygenase-1 (HO-1) are interconnected and how induction of HO-1 is protective against HDL dysfunction and important for the proper functioning of the cardiovascular–renal system. This will substantiate the proposal of HO-1 as a novel therapeutic target to prevent HDL dysfunction and, consequently, cardiovascular disease, renal dysfunction, and the onset of CRS. Full article

Background: In patients with primary hyperparathyroidism (PHPT) locating hyperfunctioning glands (HPGs) is crucial when planning minimally invasive surgery. Dual-isotope subtraction scintigraphy with ^99mTc-MIBI/¹²³Iodide using SPECT/CT and planar pinhole imaging (Method A) has previously shown a sensitivity >93%. However, the method is costly and time consuming and entails a high radiation dose. ¹¹C-Choline PET/CT (Method B) is an appealing candidate method unencumbered by these disadvantages. Methods: Sixty patients with newly diagnosed PHPT participated and were scanned using both methods prior to parathyroidectomy. We investigated whether sensitivities of Method A and Method B are similar in a method-to-method comparison when using surgical findings as the true location. Results: At the patient level, sensitivities were (A) 0.98 (95% CI: 0.90–1.00) and (B) 1.00 (95% CI: 0.93–1.00). At the gland level, sensitivities were (A) 0.88 (95% CI: 0.78–0.94) and (B) 0.87 (95% CI: 0.76–0.92). With a non-inferiority margin of ∆ = −0.1, we found a 1-sided p-value < 0.001. Conclusion: Our methods comparison study found that sensitivity of Method B was not inferior to Method A. We suggest that ¹¹C-Choline PET/CT is a clinically relevant first-choice candidate for preoperative imaging of PHPT and that Method B can likely replace Method A in the near future. Full article

Hepatitis C virus (HCV)-induced inflammation contributes to progressive liver disease. The chemoattractant protein chemerin is associated with systemic inflammation. We hypothesized that chemerin is a biomarker that predicts the severity of liver disease in HCV patients. Furthermore, we investigated whether serum chemerin levels change during the course of HCV treatment using direct-acting antivirals (DAAs). Therefore, we measured serum concentration of chemerin in a cohort of 82 HCV-infected patients undergoing DAA treatment. Serum chemerin was positively associated with leukocyte count and negatively with markers of hepatic function and the model of end-stage liver disease (MELD) score. Low circulating chemerin levels significantly correlated with advanced liver fibrosis and cirrhosis as measured by the fibrosis-4 (FIB-4) score, the aminotransferase/platelet (AST/PLT) ratio index (APRI) score and the non-alcoholic fatty liver disease (NAFLD) score. Chemerin did not correlate with viral load or viral genotype. Treatment with DAAs did not improve MELD score and leukocyte count within the observation period, up to three months after the end of DAA treatment. Accordingly, chemerin levels remained unchanged during the treatment period. We conclude that low circulating chemerin is a noninvasive biomarker for hepatic dysfunction and advanced liver fibrosis and cirrhosis in HCV infection. Full article

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions. Full article

It is widely believed that cooperation between clinicians and machines may address many of the decisional fragilities intrinsic to current medical practice. However, the realization of this potential will require more precise definitions of disease states as well as their dynamics and interactions. A careful probabilistic examination of symptoms and signs, including the molecular profiles of the relevant biochemical networks, will often be required for building an unbiased and efficient diagnostic approach. Analogous problems have been studied for years by physicists extracting macroscopic states of various physical systems by examining microscopic elements and their interactions. These valuable experiences are now being extended to the medical field. From this perspective, we discuss how recent developments in statistical physics, machine learning and inference algorithms are coming together to improve current medical diagnostic approaches. Full article

Neurosurgeons often neglect the sphenoid sinus due to its deep location and difficulties in accessing during surgical interventions. Disease of the sphenoid sinus is difficult to diagnose since its presenting symptoms are difficult to recognize. Moreover, compared with other paranasal sinuses, the sphenoid sinus is considered the most variable air sinus in terms of its degree of pneumatization, number and position of inter-sinus septa, and its relationship with the surrounding anatomical structures. Anatomical variations of the sphenoid sinus are significant from a neurosurgical point of view. Understanding of these variations and its relationships with surrounding structures such as the internal carotid artery, optic nerve, and pituitary gland are clinically relevant to minimize injuries associated with surgical procedures that involve sphenoid sinus. We implemented principles of imaging using computed tomography to elucidate any anatomical variations of the sphenoid sinus in the Ethiopian population. We conducted a prospective study in 200 patients with ages 18–79, who underwent scans of the sphenoid sinus at the Tikur Anbessa Referral Teaching Hospital in 2017–2018. Our findings revealed an incidence of anatomographical variations in terms of pneumatization that varied between 2–50%. These variants include 2% conchal, 25.5% presellar, 50% sellar, and 22.5% postsellar pneumatization. We also demonstrated anatomographic variants in terms of septation, 77.5% single complete septa, 11.5% single incomplete, 10% double septa, and 1% absence of septa. In summary, the sellar pneumatization was found to be the most clinically relevant anatomographic variant among Ethiopians participating in the study, of which 90% were tomographically single septated. These variants must be taken into consideration during trans-sphenoidal surgery and knowledge of the variations has clinical implication in minimizing injuries during invasive surgical procedures involving the sphenoid sinus. Full article

This study evaluated whether deep learning frameworks trained in large datasets can help non-dermatologist physicians improve their accuracy in categorizing the seven most common pigmented skin lesions. Open-source skin images were downloaded from the International Skin Imaging Collaboration (ISIC) archive. Different deep neural networks (DNNs) (n = 8) were trained based on a random dataset constituted of 8015 images. A test set of 2003 images was used to assess the classifiers’ performance at low (300 × 224 RGB) and high (600 × 450 RGB) image resolution and aggregated data (age, sex and lesion localization). We also organized two different contests to compare the DNN performance to that of general practitioners by means of unassisted image observation. Both at low and high image resolution, the DNN framework differentiated dermatological images with appreciable performance. In all cases, the accuracy was improved when adding clinical data to the framework. Finally, the least accurate DNN outperformed general practitioners. The physician’s accuracy was statistically improved when allowed to use the output of this algorithmic framework as guidance. DNNs are proven to be high performers as skin lesion classifiers and can improve general practitioner diagnosis accuracy in a routine clinical scenario. Full article

Background: Multiple sclerosis (MS) is an autoimmune, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). To date, there is no definitive imaging biomarker for diagnosing MS. The current diagnostic criteria are mainly based on clinical relapses supported by the presence of white matter lesions (WMLs) on MRI. However, misdiagnosis of MS is still a significant clinical problem. The paramagnetic, iron rims (IRs) around white matter lesions have been proposed to be an imaging biomarker in MS. This study aimed to carry out a systematic mapping review to explore the detection of iron rim lesions (IRLs), on clinical MR scans, and describe the characteristics of IRLs presence in MS versus other MS-mimic disorders. Methods: Publications from 2001 on IRs lesions were reviewed in three databases: PubMed, Web of Science and Embase. From the initial result set 718 publications, a final total of 38 papers were selected. Results: The study revealed an increasing interest in iron/paramagnetic rims lesions studies. IRs were more frequently found in periventricular regions and appear to be absent in MS-mimics. Conclusions IR is proposed as a promising imaging biomarker for MS. Full article

Transient or acoustic radiation force elastography (ARFE) is becoming the most extended technology to assess cervical effacement, additionally to the Bishop test and conventional ultrasound. However, a debate on the fetal safety has been opened due to the high intensity focused beam emitted to produce shear waves. This work is aimed at providing preliminary data to assess clinical effects of fetal exposure. A follow-up study in newborns of 42 women exposed to ARFE during pregnancy was carried out to explore neonatal hypoacusia, Apgar test, and anthropometry. No hypoacusia cases attributable to ARFE were observed. The Apgar test at five minutes scored normally in all the newborns. Comparisons between anthropometric measurements showed no significant statistically differences. The results preclude to state the harmfulness nor the safety of ARFE. However, given the concern on the high level of energy and the potential risk of harmful bioeffects, larger studies are recommended. Full article

Introduction. The acquired muscle paralysis associated with modern critical care can be of neurogenic or myogenic origin, yet the distinction between these origins is hampered by the precision of current diagnostic methods. This has resulted in the pooling of all acquired muscle paralyses, independent of their origin, into the term Intensive Care Unit Acquired Muscle Weakness (ICUAW). This is unfortunate since the acquired neuropathy (critical illness polyneuropathy, CIP) has a slower recovery than the myopathy (critical illness myopathy, CIM); therapies need to target underlying mechanisms and every patient deserves as accurate a diagnosis as possible. This study aims at evaluating different diagnostic methods in the diagnosis of CIP and CIM in critically ill, immobilized and mechanically ventilated intensive care unit (ICU) patients. Methods. ICU patients with acquired quadriplegia in response to critical care were included in the study. A total of 142 patients were examined with routine electrophysiological methods, together with biochemical analyses of myosin:actin (M:A) ratios of muscle biopsies. In addition, comparisons of evoked electromyographic (EMG) responses in direct vs. indirect muscle stimulation and histopathological analyses of muscle biopsies were performed in a subset of the patients. Results. ICU patients with quadriplegia were stratified into five groups based on the hallmark of CIM, i.e., preferential myosin loss (myosin:actin ratio, M:A) and classified as severe (M:A < 0.5; n = 12), moderate (0.5 ≤ M:A < 1; n = 40), mildly moderate (1 ≤ M:A < 1.5; n = 49), mild (1.5 ≤ M:A < 1.7; n = 24) and normal (1.7 ≤ M:A; n = 19). Identical M:A ratios were obtained in the small (4–15 mg) muscle samples, using a disposable semiautomatic microbiopsy needle instrument, and the larger (>80 mg) samples, obtained with a conchotome instrument. Compound muscle action potential (CMAP) duration was increased and amplitude decreased in patients with preferential myosin loss, but deviations from this relationship were observed in numerous patients, resulting in only weak correlations between CMAP properties and M:A. Advanced electrophysiological methods measuring refractoriness and comparing CMAP amplitude after indirect nerve vs. direct muscle stimulation are time consuming and did not increase precision compared with conventional electrophysiological measurements in the diagnosis of CIM. Low CMAP amplitude upon indirect vs. direct stimulation strongly suggest a neurogenic lesion, i.e., CIP, but this was rarely observed among the patients in this study. Histopathological diagnosis of CIM/CIP based on enzyme histochemical mATPase stainings were hampered by poor quantitative precision of myosin loss and the impact of pathological findings unrelated to acute quadriplegia. Conclusion. Conventional electrophysiological methods are valuable in identifying the peripheral origin of quadriplegia in ICU patients, but do not reliably separate between neurogenic vs. myogenic origins of paralysis. The hallmark of CIM, preferential myosin loss, can be reliably evaluated in the small samples obtained with the microbiopsy instrument. The major advantage of this method is that it is less invasive than conventional muscle biopsies, reducing the risk of bleeding in ICU patients, who are frequently receiving anticoagulant treatment, and it can be repeated multiple times during follow up for monitoring purposes. Full article

Periodontopathic bacteria are known to have a pivotal role in the pathogenesis of periodontitis. The aim of the study was to quantitatively compare bacterial profile of patients with different severity of periodontal disease using samples from mouthwash and the subgingival area. Further analysis was performed to evaluate the correlation between mouthwash and two subgingival sampling methods: paperpoint and gingival retraction cord; 114 subjects enrolled in the study, and were divided equally into three groups according to disease severity. Mouthwash and subgingival sampling were conducted, and the samples were quantitatively analyzed for 11 target periodontopathic bacteria using multiplex real-time PCR. There were statistically significant differences in bacterial counts and prevalence of several species between the study groups. Mouthwash sampling showed significant correlations with two different subgingival sampling methods in regard to the detection of several bacteria (e.g., ρ = 0.793 for Porphyromonas gingivalis in severe periodontitis), implying that mouthwash sampling can reflect subgingival microbiota. However, the correlation was more prominent as disease severity increased. Although bacteria in mouthwash have potential to become a biomarker, it may be more suitable for the diagnosis of severe periodontitis, rather than early diagnosis. Further research is required for the discovery of biomarkers for early diagnosis of periodontitis. Full article

Considerable progress has been made recently in the use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to diagnose intra-luminal gastrointestinal lesions and extra-luminal lesions near the gastrointestinal tract. Numerous reports have indicated that EUS-FNA has high diagnostic performance and safety, which has led to the routine use of EUS-FNA and an increasing number of cases. Thus, while EUS-FNA has a low rate of complications, endoscopists may encounter these complications as the number of cases increases. Infrequent reports have also described life-threatening complications. Therefore, endoscopists should possess a comprehensive understanding of the complications of EUS-FNA, which include hemorrhage, perforation, infection, and acute pancreatitis, as well as their management. This review examines the available evidence regarding the complications associated with EUS-FNA, and the findings will be useful for ensuring that endoscopists perform EUS-FNA safely and appropriately. Full article

Cerebral blood flow (CBF) represents the local blood supply to the brain, and it can be considered a proxy for neuronal activation. Independent component analysis (ICA) can be applied to CBF maps to derive patterns of spatial covariance across subjects. In the present study, we aimed to assess the consistency of the independent components derived from CBF maps (CBF-ICs) across a cohort of 92 healthy individuals. Moreover, we evaluated the spatial similarity of CBF-ICs with respect to resting state networks (RSNs) and vascular territories (VTs). The data were acquired on a 1.5 T scanner using arterial spin labeling (ASL) and resting state functional magnetic resonance imaging. Similarity was assessed considering the entire ASL dataset. Consistency was evaluated by splitting the dataset into subsamples according to three different criteria: (1) random split of age and sex-matched subjects, (2) elderly vs. young, and (3) males vs. females. After standard preprocessing, ICA was performed. Both consistency and similarity were assessed by visually comparing the CBF-ICs. Then, the degree of spatial overlap was quantified with Dice Similarity Coefficient (DSC). Frontal, left, and right occipital, cerebellar, and thalamic CBF-ICs were consistently identified among the subsamples, independently of age and sex, with fair to moderate overlap (0.2 < DSC ≤ 0.6). These regions are functional hubs, and their involvement in many neurodegenerative pathologies has been observed. As slight to moderate overlap (0.2< DSC < 0.5) was observed between CBF-ICs and some RSNs and VTs, CBF-ICs may mirror a combination of both functional and vascular brain properties. Full article