Neurologic Manifestations of COVID-19.

Neurological manifestations of novel coronavirus disease (COVID-19) are reported to occur in as much as 37% of the affected patients. These manifestations range from headache and dizziness to altered mental status and consciousness, anosmia, ageusia, sensory disturbances, and stroke. The mechanisms by which the neurological symptoms arise are not yet determined but may either proceed as an indirect consequence of systemic hyperinflammation or result from the direct invasion of the virus to neural and glial cells. The neural invasion can explain both the retrograde pathway of encephalitis and the early manifestation of anosmia by invading the olfactory bulb. Moreover, in the case of attacking the brain stem, it may take part in the early apnea manifestation reported by patients. Additionally, neurotropism of the virus could be the cause of acute hemorrhagic encephalitis. Hyperinflammation can have acute and prolonged effects in the nervous system, such as acute demyelination and predisposition to multiple sclerosis. Moreover, the pro-inflammatory state contributes to hypercoagulation, which in turn could result in cerebrovascular injuries in COVID-19 patients. This chapter would discuss that the neurologic manifestations of the COVID-19 are to be looked at as a multifactorial entangled phenomenon.

Baseline 3D-ADC outperforms 2D-ADC in predicting response to treatment in patients with colorectal liver metastases.

OBJECTIVES: To examine the value of baseline 3D-ADC and to predict short-term response to treatment in patients with hepatic colorectal metastases (CLMs). METHODS: Liver MR images of 546 patients with CLMs (2008-2015) were reviewed retrospectively and 68 patients fulfilled inclusion criteria. Patients had received systemic chemotherapy (n = 17), hepatic trans-arterial chemoembolization or TACE (n = 34), and 90Y radioembolization (n = 17). Baseline (pre-treatment) 3D-ADC (volumetric) of metastatic lesions was calculated employing prototype software. RECIST 1.1 was used to assess short-term response to treatment. Prediction of response to treatment by baseline 3D-ADC and 2D-ADC (ROI-based) was also compared in all patients. RESULTS: Partial response to treatment (minimum 30% decrease in tumor largest transverse diameter) was seen in 35.3% of patients; 41.2% with systemic chemotherapy, 32.4% with TACE, and 35.3% with 90Y radioembolization (p = 0.82). Median baseline 3D-ADC was significantly lower in responding than in nonresponding lesions. Area under the curve (AUC) of 3D-ADC was 0.90 in 90Y radioembolization patients, 0.88 in TACE patients, and 0.77 in systemic chemotherapy patients (p < 0.01). Optimal prediction was observed with the 10th percentile of ADC (1006 × 10-6 mm2/s), yielding sensitivity and specificity of 77.4% and 91.3%, respectively. 3D-ADC outperformed 2D-ADC in predicting response to treatment (AUC; 0.86 vs. 0.71; p < 0.001). CONCLUSION: Baseline 3D-ADC is a highly specific biomarker in predicting partial short-term response to treatment in hepatic CLMs. KEY POINTS: • Baseline 3D-ADC is a highly specific biomarker in predicting response to different treatments in hepatic CLMs. • The prediction level of baseline ADC is better for90Y radioembolization than for systemic chemotherapy/TACE in hepatic CLMs. • 3D-ADC outperforms 2D-ADC in predicting short-term response to treatment in hepatic CLMs.

Prognostic value of baseline volumetric multiparametric MR imaging in neuroendocrine liver metastases treated with transarterial chemoembolization.

OBJECTIVES: To determine whether baseline multiparametric MR imaging can predict overall survival (OS) and hepatic progression-free survival (HPFS) in patients with neuroendocrine liver metastases (NELMs) treated with transarterial chemoembolization (TACE). METHODS: This retrospective study included 84 NELMs patients treated with TACE. Tumor volume and volumetric measurements of arterial enhancement (AE), venous enhancement (VE), and apparent diffusion coefficient (ADC) were performed on baseline MR imaging. A maximum of one, two, and five index lesions were selected in each patient. OS was the primary endpoint and HPFS was the secondary endpoint. Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS considering a maximum of one, two, and five index lesions were assessed. RESULTS: Prognostic values of volumetric multiparametric MR parameters for predicting OS and HPFS were similar regardless of the maximum number of index lesions. Multivariate survival analysis showed that baseline dominant tumor volume ≥ 73 cm3, volumetric mean AE ≥ 45%, and mean VE ≥ 73% were independent prognostic factors for OS (HR 2.73; 95% CI 1.45, 5.15; HR 0.32; 95% CI 0.17, 0.63; HR 0.35; 95% CI 0.17, 0.72, respectively) and HPFS (HR 2.30, 95% CI 1.38, 3.84; HR 0.46, 95% CI 0.25, 0.84; HR 0.36, 95% CI 0.19, 0.57, respectively). OS and HPFS were similar in patients with low and high volumetric mean ADC. CONCLUSION: Volumetric enhancement values and tumor volume of the dominant lesion on baseline MR imaging may act as prognostic factors for OS and HPFS in NELMs patients treated with TACE. KEY POINTS: • High volumetric mean AE and VE, and low tumor volume of the dominant lesion on baseline MR imaging were associated with favorable OS and HPFS in NELMs patients treated with TACE. • Evaluation of multiple lesions does not provide additional information as compared to single lesion evaluation.

Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms.

OBJECTIVES: To evaluate the added value of diffusion-weighted imaging (DWI) on MRI in differentiating serous from mucin-producing pancreatic cystic neoplasms (PCNs). METHODS: One hundred seventeen patients with PCN measuring ≥ 10 mm were included. Three readers independently evaluated MRI with and without the use of apparent diffusion coefficient (ADC). Logistic regression was used to analyze whether confidence scores were different with the use of different image sets. Diagnostic performance with and without ADC was compared. RESULTS: DWI/ADC improved confidence in 44.8%, 73.6%, and 78.2% of patients by the three readers in distinguishing serous from mucin-producing PCNs. The use of ADC increased the probability of a higher confidence in the differentiation as compared to morphological imaging for all three readers (p < 0.001). Odds ratio for increase in the diagnostic confidence with the use of ADC for the three readers with decreasing years of experience were 5.8, 6.8, and 12.7. The diagnostic accuracy of morphological MRI with ADC was higher than that without ADC for two of three readers with lesser experience (87.2% vs. 80.8%; 91.5% vs. 80.8%). CONCLUSION: DWI may have added value as a complementary tool to conventional morphological MRI in differentiating between serous and mucin-producing PCNs with possibly greater value for readers with less experience in reading abdominal MRI. KEY POINTS: • Optimal management of PCNs requires differentiation of serous from mucin-producing PCNs. • ADC measurements allow increased confidence in differentiating serous from mucin-producing PCNs. • ADC measurements increase the accuracy in diagnosing serous versus mucin-producing PCNs.

Utility of volumetric contrast-enhanced and diffusion-weighted MRI in differentiating between common primary hypervascular liver tumors.

BACKGROUND: Differentiating between hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) is usually achievable by MRI. However, in some cases with atypical imaging findings accurate diagnosis may be difficult. PURPOSE: To assess the diagnostic value of volumetric contrast-enhanced (CE) and volumetric diffusion-weighted imaging (DWI) in differentiating between HCC, FNH, and HCA. STUDY TYPE: Retrospective. SUBJECTS: In all, 143 patients (206 lesions): 42 HCA (81 lesions), 51 FNH (65 lesions), and 50 HCC (60 lesions). FIELD STRENGTH/SEQUENCE: 1.5T MRI, T1 -T2 WI, DWI. ASSESSMENT: Patients underwent CE-MRI and DWI (b = 0, 750 mm2 /s). Volumetric assessment of lesions' contrast enhancement and apparent diffusion coefficient (ADC) was performed with semiautomatic software after 3D image registration and segmentation by an observer and compared between three lesion groups. The diagnosis of lesions was based on histopathology, typical MRI findings, and/or follow-up. STATISTICAL TESTS: Independent t-test was used to compare parameters between two groups, one-way analysis of variance (ANOVA) between three groups, and receiver operator characteristic curve (ROC) analysis to define under-curve area and optimal cutoff. RESULTS: Mean values (±standard deviation) for HCC, FNH, and HCA, respectively, were: 1) arterial enhancement (%), 40.5 ± 13.2, 88.6 ± 32.6, 69.6 ± 25.1; 2) venous enhancement (%) 72.4 ± 22.1, 95.2 ± 30.9, 80.7 ± 30.6; and 3) ADC (10-6 mm2 /s) 1404.5 ± 168.1, 1413.4 ± 232.1, 1070.1 ± 232.1. ADC was the best differentiator of HCA from FNH (at 1211 × 10-6 mm2 /s; sensitivity 80.4%, specificity 71.7%) and arterial enhancement was the best differentiator of HCC from both HCA (at 48%; sensitivity 80.0%, specificity 80.5%) and FNH (at 52%; sensitivity 85.7%, specificity 85.4%). A combination of arterial enhancement and ADC (at 50% and 1227 × 10-6 mm2 /s) differentiated three types of tumors with high specificity (87.9%). DATA CONCLUSION: Volumetric CE-MRI and volumetric DWI can help to differentiate between HCC, FNH, and HCA. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1080-1090.

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort.

OBJECTIVES: To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images. METHODS: Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed. RESULTS: Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm3 and 9.4 cm3, respectively). CONCLUSIONS: Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers. KEY POINTS: • MRI measurements by different radiologists can be used for IPMN follow-up. • Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. • Manual axial measurements show the highest interobserver reproducibility in determining size. • Axial and coronal volume measurements show similar limits of agreement. • Manual axial measurements show the lowest variability in agreement range.

Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen.

OBJECTIVES: To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS). METHODS: Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed. RESULTS: Pancreatic NET had significantly higher absolute ADC (1.431x10-3 vs 0.967x10-3 mm2/s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206x10-3 mm2/s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively. CONCLUSION: Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS. KEY POINTS: • Imaging overlaps between IPASs and pancreatic-NETs lead to unnecessary procedures including pancreatectomy. • Uniquely low ADC of spleen allows differentiating IPASs from pancreatic NETs. • Both absolute-ADC and normalised-ADC (lesion-to-spleen ADC-ratio) demonstrate high accuracy in differentiating IPASs from NETs. • Both methods demonstrate excellent inter-reader reliability.

Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic targets - a review of the current knowledge.

Common variable immunodeficiency (CVID) is characterized by low levels of circulating immunoglobulins and compromised specific antibody response leading to frequent infections. Cytokines play an important role in the orchestration of the antibody response. Several previous studies have attempted to identify distinct cytokines responsible for the inflammatory changes and different manifestations of CVID, but there are conflicting results regarding the cytokine profiles in CVID patients. In light of this, an extensive review regarding the level of various cytokines and their potential therapeutic role in CVID patients was performed. This review delineates the contribution of interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-21, interferons, tumor necrosis factor (TNF)-α, IL-17, APRIL (a proliferation inducing ligand) and BAFF (B cell activating factor) in CVID disease and outline their potential therapeutic implications in these patients.

Association of IL-10 and TGF-beta cytokine gene polymorphisms with autoimmune hepatitis.

BACKGROUND AND AIMS: Autoimmune hepatitis is a chronic immune-mediated liver injury caused by dysregulated immune response to liver antigens. Genetic susceptibility is affected by multiple single nucleotide polymorphisms in immune-related genes. There are few reports on the association of TGF-ß and IL-10 genetic variants with autoimmune hepatitis. METHODS: Allele frequency and genotype status of IL-10 -1082, -819, -592 and TGF-ß +869 and +915 polymorphisms were investigated in 57 unrelated patients with autoimmune hepatitis and 140 healthy controls by polymerase chain reaction with sequence-specific primers. RESULTS: IL-10 -592 and -819 allele frequencies and genotypes were not associated with autoimmune hepatitis in our population, while IL-10 -1082 genotypes were. IL-10 -1082/-819/-592 "high-producing" haplotype GCC was significantly less frequent in patients. TGF-ß +869 "high-producing" allele C and genotype CC were significantly more in autoimmune hepatitis, compared to controls; whereas, TGF-ß +915 "low-producing" allele C and genotype CC were significantly more in autoimmune hepatitis compared to control. TGF-ß +869/+915 haplotype TG was significantly less frequent in patients while CC haplotype was significantly more frequently observed in patients. CONCLUSION: We identified a significant association between IL-10 -1082/-819 and TGF-ß +869/+915 genotypes and haplotypes with autoimmune hepatitis in Iranians.

Correlation between quantitative liver and spleen volumes and disease severity in primary sclerosing cholangitis as determined by Mayo risk score.

OBJECTIVES: To correlate total and lobar liver and spleen volume with disease severity in primary sclerosing cholangitis (PSC) as determined by Mayo risk score. METHODS: This HIPAA-compliant single center retrospective study included 147 PSC patients with available imaging studies (MRCP/CT) and laboratory data between January 2003 and January 2018. Total and lobar (right, left and caudate) liver volume and spleen volume were measured. ANOVA test was performed to assess the differences in volumes between low, intermediate and high-risk groups (Mayo risk score <0, >0 and <2, >2, respectively). Correlations between volumes and Mayo risk score were calculated. ROC analysis was performed to assess the accuracy of the variable with the strongest correlation to PSC severity to predict Mayo risk score. P value <0.05 was considered statistically significant. RESULTS: The mean age of this cohort was 45 ± 17 years; 58% were men. Absolute volumes of left lobe, caudate and spleen and volume ratios of left lobe and caudate to total liver volume of the high-risk group were significantly higher compared to those of low and intermediate risk groups (p < 0.05). Left lobe to total liver volume ratio had the highest correlation to Mayo risk score (Pearson correlation coefficient 0.61, p < 0.05) and on ROC analysis it had 84.4% accuracy in detecting high-risk PSC. CONCLUSIONS: In this single institution large cohort study, the left lobe to total liver volume ratio was the best quantifiable volumetric biomarker to correlate with severity of PSC as identified by Mayo risk score.