Significance of the autoantibody assay in predicting the development of immune-related adverse events in patients receiving atezolizumab plus bevacizumab combination therapy for unresectable hepatocellular carcinoma.

AIM: Atezolizumab plus bevacizumab (AB) combination therapy is the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). The management of immune-related adverse events (irAEs) is an important issue associated with achieving a good therapeutic response in patients receiving AB therapy. However, few studies have reported irAE development in patients receiving AB therapy. This study focused on the association between irAE development and autoantibodies at baseline in patients receiving AB therapy. METHODS: Sixty-one patients receiving AB therapy were enrolled. For autoantibodies, the following antibodies were tested before the start of AB therapy: antinuclear antibodies, rheumatoid factor (RF), anti-thyroglobulin antibodies, thyroid peroxidase antibodies, anti-thyroid stimulating hormone receptor antibodies, and acetylcholine receptor antibodies. A patient was considered to have pre-existing antibodies if any of the listed antibodies were present at baseline. RESULTS: Ten patients (16%) developed irAEs during the observation period. The irAEs included liver injury, hypothyroidism, adrenal insufficiency, adrenocorticotropic hormone deficiency, and rhabdomyolysis. Patients with irAE (n = 10) were more likely to be positive for any autoantibody (hazard ratio [HR] 3.7, p = 0.047) and RF at baseline (HR 5.4, p = 0.035) and to achieve complete response (HR 5.8, p = 0.027) than those without. The presence of autoantibodies at baseline was an independent factor associated with irAE development. CONCLUSION: In the real world, 16% of patients receiving AB therapy for u-HCC developed irAEs. Patients with autoantibodies at baseline are at high risk of developing irAEs and require cautious follow-up.

The cortical high-flow sign of oligodendroglioma, IDH-mutant and 1p/19q-codeleted: comparison between arterial spin labeling and dynamic susceptibility contrast methods.

PURPOSE: The cortical high-flow sign with the non-enhancing area was reportedly found to be more frequent with oligodendroglioma, IDH-mutant and 1p/19q codeleted (ODG IDHm-codel) than with IDH-wildtype or astrocytoma, IDH-mutant on arterial spin labeling (ASL) in diffuse gliomas. This study aimed to compare the identification rate of the cortical high-flow sign on ASL in patients with ODG IDHm-codel to that on dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). METHODS: Participants consisted of 32 adult ODG IDHm-codel patients with pathologically confirmed. Subtraction images were generated from paired control and label images on ASL. For DSC, dynamic T2*-weighted perfusion weighted images were obtained after pre-bolus of gadolinium-based contrast agent. Regional cerebral blood flow/volume maps were generated based on the concentration-time curve and arterial input function. Tumor-affecting cortices without contrast enhancement on conventional MR imaging were targeted. The identification rate of the cortical high-flow sign was compared between ASL and DSC using the Pearson's Chi-Square test. RESULTS: Frequency of the cortical high-flow sign was significantly higher on ASL (18/32, 56.3%; p < 0.001) than on DSC (5/32, 15.6%). All cases with the positive cortical high-flow sign on DSC were identified on ASL. CONCLUSION: ASL effectively identifies the cortical high-flow sign in ODG IDHm-codel, surpassing DSC in identification rates.

Comparison of diagnostic performance of radiologist- and AI-based assessments of T2-FLAIR mismatch sign and quantitative assessment using synthetic MRI in the differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted.

PURPOSE: This study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method. METHODS: Thirty-three cases (men, 14; women, 19) comprising 19 astrocytomas and 14 oligodendrogliomas were evaluated. Four radiologists independently evaluated the presence of the T2-FLAIR mismatch sign. A 3D convolutional neural network (CNN) model was trained using 50 patients outside the test group (28 astrocytomas and 22 oligodendrogliomas) and transferred to evaluate the T2-FLAIR mismatch lesions in the test group. If the CNN labeled more than 50% of the T2-prolonged lesion area, the result was considered positive. The T1/T2-relaxation times and proton density (PD) derived from SyMRI were measured in both gliomas. Each quantitative parameter (T1, T2, and PD) was compared between gliomas using the Mann-Whitney U-test. Receiver-operating characteristic analysis was used to evaluate the diagnostic performance. RESULTS: The mean sensitivity, specificity, and area under the curve (AUC) of radiologists vs. AI were 76.3% vs. 94.7%; 100% vs. 92.9%; and 0.880 vs. 0.938, respectively. The two types of diffuse gliomas could be differentiated using a cutoff value of 2290/128 ms for a combined 90th percentile of T1 and 10th percentile of T2 relaxation times with 94.4/100% sensitivity/specificity with an AUC of 0.981. CONCLUSION: Compared to the radiologists' assessment using the T2-FLAIR mismatch sign, the AI and the SyMRI assessments increased both sensitivity and objectivity, resulting in improved diagnostic performance in differentiating gliomas.

Three-micrometer-diameter needle electrode with an amplifier for extracellular in vivo recordings.

Microscale needle-electrode devices offer neuronal signal recording capability in brain tissue; however, using needles of smaller geometry to minimize tissue damage causes degradation of electrical properties, including high electrical impedance and low signal-to-noise ratio (SNR) recording. We overcome these limitations using a device assembly technique that uses a single needle-topped amplifier package, called STACK, within a device of ∼1 × 1 mm2 Based on silicon (Si) growth technology, a <3-µm-tip-diameter, 400-µm-length needle electrode was fabricated on a Si block as the module. The high electrical impedance characteristics of the needle electrode were improved by stacking it on the other module of the amplifier. The STACK device exhibited a voltage gain of >0.98 (-0.175 dB), enabling recording of the local field potential and action potentials from the mouse brain in vivo with an improved SNR of 6.2. Additionally, the device allowed us to use a Bluetooth module to demonstrate wireless recording of these neuronal signals; the chronic experiment was also conducted using STACK-implanted mice.

Prediction of Therapeutic Response Using Contrast-Enhanced Ultrasound in Japanese Patients Treated with Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Atezolizumab and bevacizumab (AB) therapy was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). However, the predictive marker of therapeutic response that can be easily used in clinical practice is still unknown. We prospectively investigated the utility of time-intensity curve (TIC) analysis using contrast-enhanced ultrasound (CEUS) as a predictive indicator of therapeutic response after the start of AB therapy. METHODS: Thirty-five patients who received AB therapy for u-HCC were included in this study. TIC analysis was performed in 28 patients who were able to undergo CEUS before and 3-7 days after administration. We analyzed prognostic factors related to the initial therapeutic response and long progression-free survival (PFS). RESULTS: The initial therapeutic response using dynamic computed tomography or Gd-EOB magnetic resonance imaging at 8-12 weeks after administration was partial response/stable disease/progressive disease (PD) in 14/12/9 cases (40/34/26%). Cases with PD (n = 9) had more cases without decreased blood flow in TIC analysis compared with cases with non-PD (100 vs. 18%, p = 0.001). Cases without decreased blood flow in TIC analysis (n = 10) had more cases with PD compared with cases with decreased blood flow (60 vs. 0%, p = 0.001). PFS in patients without decreased blood flow early after the administration was shorter than that in those with decreased blood flow (9.1 vs. 28 weeks, p = 0.0051). CONCLUSION: Early evaluation by TIC analysis using CEUS may be useful in predicting the therapeutic response in patients treated with AB therapy for u-HCC.

Relationship between Plasma IP-10/CXCL10 Levels and the Initial Therapeutic Response in Patients Treated with Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Atezolizumab plus bevacizumab combination therapy (AB) was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). IFN-γ-induced protein 10 (IP-10/CXCL10) is a chemokine to inhibit HCC proliferation by promoting the migration of cytotoxic T cells. We focused on the relationship between plasma IP-10/CXCL10 levels and the initial therapeutic response in patients receiving AB therapy. METHODS: Forty-six patients receiving AB therapy were enrolled. Plasma IP-10/CXCL10 levels were measured at baseline, 3-7 days, 3 weeks, 6 weeks, and 8-12 weeks after the start of AB therapy. The initial therapeutic response was evaluated at 8-12 weeks. RESULTS: The baseline IP-10/CXCL10 levels of partial response (PR) group was higher than that of stable disease (SD) or progressive disease (PD) group. Patients with the baseline IP-10/CXCL10 of 84 pg/mL or higher were likely to present PR than patients below (71 vs. 35%, p = 0.031), but prediction of PD using the baseline IP-10/CXCL10 levels was difficult. In contrast, IP-10/CXCL10 ratio of the PR group was lower than that of the SD/PD group at 3, 6, and 8-12 weeks. Patients with the 3, 6, and 8-12 weeks IP-10/CXCL10 ratio of 1.3, 0.4, and 0.4 or lower were likely to present PR than patients with ≥1.3, 0.4, and 0.4 (88, 35, 35 vs. 30, 3.8, 0%, p < 0.001, 0.011, 0.002). In other hand, the 3, 6, and 8-12 weeks IP-10/CXCL10 ratio for PD group was higher than that for non-PD group. Patients with the 3, 6, and 8-12 weeks IP-10/CXCL10 ratio of 1.3, 1.7, and 1.9 or higher were likely to present PD than patients below (85, 62, 57 vs. 32, 23, 14%, p = 0.002, 0.034, 0.009). CONCLUSION: High baseline IP-10/CXCL10 levels may be associated with better outcome, and high IP-10/CXCL10 ratio after 3-12 weeks may be associated with worse outcome in u-HCC patients receiving AB therapy.

Impact of Renal Function on the Prognosis of Patients Receiving Atezolizumab/Bevacizumab Combination Therapy and Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Several studies have reported kidney injury caused by immune checkpoint inhibitors, and proteinuria caused by vascular endothelial growth factor inhibitors for unresectable hepatocellular carcinoma (u-HCC). We investigated the relationship between renal function and prognosis in patients with u-HCC receiving atezolizumab and bevacizumab (AB) and lenvatinib (LEN) therapy. METHODS: Fifty-one patients who received AB and 50 patients who received LEN therapy were included. We analyzed prognostic factors related to the overall survival (OS), and characteristics related to renal function. RESULTS: In patients with AB therapy, OS was shorter in patients with baseline proteinuria of 1+ or higher, as assessed by urine dipstick test, compared to those with -/± (p = 0.024). There were many cases with two or more drugs with a high risk of renal dysfunction (p = 0.019) in patients with 1+ or higher. Furthermore, OS was shorter in the group with estimated glomerular filtration rate (eGFR) grade deterioration without urinary protein-creatinine ratio (UPCR) of 2 g/g·Cre or higher than in the other groups (p = 0.027). In the group where eGFR worsened without an increase in UPCR, there were many cases with a daily salt intake of 10 g or more (p = 0.027), three or more drugs with a high risk of renal dysfunction (p = 0.021), and a history of arteriosclerosis (p = 0.021). On the other hand, in patients with LEN therapy, OS tends to be shorter in patients with proteinuria of ± or higher, compared to those without (p = 0.074). There were many cases with a daily salt intake of 10 g or more in patients with ± or higher (p = 0.002). CONCLUSION: In patients receiving AB and LEN therapy, baseline proteinuria was associated with OS. Renal function deterioration without proteinuria was associated with a poor prognosis in AB therapy. Excessive salt intake, preexisting atherosclerotic disease, and drug with a high risk of renal dysfunction were risk factors for renal deterioration.

Arterial Spin Labeling-Based MR Angiography for Cerebrovascular Diseases: Principles and Clinical Applications.

Arterial spin labeling (ASL) is a noninvasive imaging technique that labels the proton spins in arterial blood and uses them as endogenous tracers. Brain perfusion imaging with ASL is becoming increasingly common in clinical practice, and clinical applications of ASL for intracranial magnetic resonance angiography (MRA) have also been demonstrated. Unlike computed tomography (CT) angiography and cerebral angiography, ASL-based MRA does not require contrast agents. ASL-based MRA overcomes most of the disadvantages of time-of-flight (TOF) MRA. Several schemes have been developed for ASL-based MRA; the most common method has been pulsed ASL, but more recently pseudo-continuous ASL, which provides a higher signal-to-noise ratio (SNR), has been used more frequently. New methods that have been developed include direct intracranial labeling methods such as velocity-selective ASL and acceleration-selective ASL. MRA using an extremely short echo time (eg, silent MRA) or ultrashort echo-time (TE) MRA can suppress metal susceptibility artifacts and is ideal for patients with a metallic device implanted in a cerebral vessel. Vessel-selective 4D ASL MRA can provide digital subtraction angiography (DSA)-like images. This review highlights the principles, clinical applications, and characteristics of various ASL-based MRA techniques. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Efficacy of a Gastroscope for Cecal Intubation during Colonoscopy in Patients with Severe Sigmoid Adhesion.

BACKGROUND: Cecal intubation during colonoscopy is difficult to achieve in patients with severe sigmoid adhesions. This retrospective observational study assessed the efficacy of using a gastroscope for colonoscopy in patients with severe sigmoid adhesions. Furthermore, the ability of computed tomography (CT) to predict the possibility of cecal intubation using a gastroscope was examined. METHODS: A total of 1,626 patients who underwent colonoscopy for total colon observation by one endoscopist were enrolled. Cecal intubation rate and other procedure-related outcomes were evaluated. We also investigated whether identification of the sigmoid colon pathway by CT was involved in cecal intubation rate using a gastroscope. RESULTS: Of the enrolled patients, cecal intubation by colonoscope was not feasible in 19 patients (1.2%) because of severe sigmoid adhesions. Cecal intubation was possible in 13 patients (68.4%) using a gastroscope, and the cecal intubation rate of peritoneal carcinomatosis (0%, p < 0.01) was significantly lower than that of other causes such as a diverticulum (100%) and history of gynecologic surgery (80%). The identifiable case of the sigmoid colon pathway by horizontal section on CT showed significantly higher cecal intubation rate compared to those of unidentifiable cases (92.3% vs. 16.7%, p < 0.01). CONCLUSION: Using a gastroscope is effective in performing cecal intubation during colonoscopy in patients with severe sigmoid adhesions. However, in patients with sigmoid adhesions caused by peritoneal carcinomatosis, cecal intubation may be difficult, even when a gastroscope is used. The ability of CT to identify the sigmoid colon pathway may predict success of cecal intubation.

Alanine aminotransferase levels as therapeutic targets after nucleotide/nucleoside analog therapy in patient with chronic hepatitis B.

AIM: Alanine aminotransferase (ALT) is a criterion for the introduction of nucleotide/nucleoside analog (NA), and ALT levels are decreased by NA treatment. However, the association between post-treatment ALT levels and hepatocellular carcinoma (HCC) risk remains unclear. To fill this gap, we aimed to establish a target value of ALT level during NA treatment. METHODS: In total, 413 patients with chronic hepatitis B who received entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate were enrolled. The subsequent development of HCC was examined and a target value of ALT level during NA treatment as a risk marker for HCC was evaluated. RESULTS: The median follow-up duration was 5.1 years, during which time 27 patients (8.6%) developed HCC. ALT level at the start of treatment was not associated with HCC development (p = 0.08). When stratified by ALT at 1 year after NA initiation, the cumulative 3- and 5-year rates of HCC for patients with ALT ≥21 IU/L were 11.5% and 18.1%, and those with ALT <21 IU/L was 2.3% and 6.5%, respectively. Patients with ALT <21 IU/L had a significantly lower risk of HCC development compared with patients with ALT ≥21 IU/L (p = 0.002). In multivariable analysis adjusting age, sex, and platelet counts, ALT ≥21 IU/L was an independent risk factor of HCC development with hazard ratio of 4.5 (95% confidence interval: 1.01-20.4). CONCLUSIONS: ALT <21 IU/L at 1 year after NA initiation has a lower risk of HCC and could be used as a target value for NA treatment.

Predicting TERT promoter mutation status using 1H-MR spectroscopy and stretched-exponential model of diffusion-weighted imaging in IDH-wildtype diffuse astrocytic glioma without intense enhancement.

PURPOSE: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated with tumor aggressiveness. The aim of this study was to identify features from MR spectroscopy (MRS) and multi-exponential models of DWI distinguishing wild-type TERT (TERTw) from TERT promoter mutation (TERTm) in IDH-wildtype diffuse astrocytic glioma. METHODS: Participants comprised 25 adult patients with IDH-wildtype diffuse astrocytic glioma. Participants were classified into TERTw and TERTm groups. Point-resolved spectroscopy sequences were used for MRS data acquisition. DWI was performed with 13 different b-factors. Peak height ratios of NAA/Cr and Cho/Cr were calculated from MRS data. Mean apparent diffusion coefficient (ADC), perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), distributed diffusion coefficient (DDC), and heterogeneity index (α) were obtained using multi-exponential models from DWI data. Each parameter was compared between TERTw and TERTm using the Mann-Whitney U test. Correlations between parameters derived from MRS and DWI were also evaluated. RESULTS: NAA/Cr and Cho/Cr were both higher for TERTw than for TERTm. The α of TERTw was smaller than that of TERTm, while the f of TERTw was higher than that of TERTm. NAA/Cr correlated negatively with α, but not with other DWI parameters. Cho/Cr did not show significant correlations with any DWI parameters. CONCLUSION: The combination of NAA/Cr and α may have merit in clinical situation to predict the TERT mutation status of IDH-wildtype diffuse astrocytic glioma without intense enhancement.

Cortical high-flow sign on arterial spin labeling: a novel biomarker for IDH-mutation and 1p/19q-codeletion status in diffuse gliomas without intense contrast enhancement.

This study aimed to investigate whether arterial spin labeling (ASL) features allow differentiation of oligodendroglioma, IDH-mutant and 1p/19q-codeleted (IDHm-codel) from diffuse glioma with IDH-wildtype (IDHw) or astrocytoma, IDH-mutant (IDHm-noncodel). Participants comprised 71 adult patients with pathologically confirmed diffuse glioma, classified as IDHw, IDHm-noncodel, or IDHm-codel. Subtraction images were generated from paired-control/label images on ASL and used to assess the presence of a cortical high-flow sign. The cortical high-flow sign was defined as increased ASL signal intensity within the tumor-affecting cerebral cortex compared with normal-appearing cortex. Regions without contrast enhancement on conventional MR imaging were targeted. The frequency of the cortical high-flow sign on ASL was compared among IDHw, IDHm-noncodel, and IDHm-codel. As a result, the frequency of the cortical high-flow sign was significantly higher for IDHm-codel than for IDHw or IDHm-noncodel. In conclusion, the cortical high-flow sign could represent a hallmark of oligodendroglioma, IDH-mutant, and 1p/19q-codeleted without intense contrast enhancement.

Assessment of cerebral perfusion in moyamoya disease with dynamic pseudo-continuous arterial spin labeling using a variable repetition time scheme with optimized background suppression.

PURPOSE: Accurate assessment of cerebral perfusion in moyamoya disease is necessary to determine the indication for treatment. We aimed to investigate the usefulness of dynamic PCASL using a variable TR scheme with optimized background suppression in the evaluation of cerebral perfusion in moyamoya disease. METHODS: We retrospectively analyzed the images of 24 patients (6 men and 18 women, mean age 31.4 ± 18.2 years) with moyamoya disease; each of whom was imaged with both dynamic PCASL using the variable-TR scheme and 123IMP SPECT with acetazolamide challenge. ASL dynamic data at 10 phases are acquired by changing the LD and PLD. The background suppression timing was optimized for each phase. CBF and ATT were measured with ASL, and CBF and CVR to an acetazolamide challenge were measured with SPECT. RESULTS: A significant moderate correlation was found between the CBF measured by dynamic PCASL and that by SPECT (r = 0.53, P < 0.001). The CBF measured by dynamic PCASL (52.5 ± 13.3 ml/100 mg/min) was significantly higher than that measured by SPECT (43.0 ± 12.6 ml/100 mg/min, P < 0.001). The ATT measured by dynamic PCASL showed a significant correlation with the CVR measured by SPECT (r = 0.44, P < 0.001). ATT was significantly longer in areas where the CVR was impaired (CVR < 18.4%, ATT = 1812 ± 353 ms) than in areas where it was preserved (CVR > 18.4%, ATT = 1301 ± 437 ms, P < 0.001). The ROC analysis showed a moderate accuracy (AUC = 0.807, sensitivity = 87.7%, specificity = 70.4%) when the cutoff value of ATT was set at 1518 ms. CONCLUSION: Dynamic PCASL using this scheme was found to be useful for assessing cerebral perfusion in moyamoya disease.

Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

BACKGROUND: Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. PURPOSE: To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). MATERIAL AND METHODS: Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. RESULTS: In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. CONCLUSION: The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.

Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

BACKGROUND: We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. METHODS: A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. RESULTS: The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6 weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). CONCLUSION: Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

Plasma Renin Activity Predicts Prognosis and Liver Disease-Related Events in Liver Cirrhosis Patients with Ascites Treated by Tolvaptan.

BACKGROUND AND AIMS: A retrospective study was to analyze the association of plasma renin activity (PRA) with overall survival and liver disease-related events in decompensated liver cirrhosis with ascites treated by tolvaptan. METHODS: We included 196 patients with decompensated cirrhosis treated with tolvaptan and for whom hepatic ascites had remained uncontrolled by conventional diuretics. Factors associated with prognosis and appearance of liver disease-related events were investigated, including vasopressin, sympathetic nervous system hormones (adrenaline, noradrenaline, and dopamine), and the renin-angiotensin system (PRA and aldosterone) at the beginning of tolvaptan treatment. RESULTS: Age, history of hepatocellular carcinoma (HCC), and PRA were identified as independent factors for prognosis after tolvaptan treatment. The median survival time in patients with PRA ≥9.5 ng/mL/h at the beginning of tolvaptan treatment was significantly shorter than in patients with PRA <9.5 ng/mL/h (193 vs. 893 days, p < 0.001). PRA and a history of HCC were independent factors for the occurrence of liver disease-related events. The median event-free period in patients with PRA ≥3.2 ng/mL/h was significantly shorter than that of patients with PRA <3.2 ng/mL/h (89 vs. 222 days, p < 0.001). CONCLUSIONS: PRA is an independent predictor of prognosis and appearance of liver disease-related events in patients with decompensated cirrhosis who have started tolvaptan treatment.

Validation of magnetic resonance elastography plus fibrosis-4 for significant fibrosis in nonalcoholic fatty liver disease.

BACKGROUND AND AIM: MEFIB (the combination of magnetic resonance elastography [MRE] ≥ 3.3 kPa and fibrosis-4 (FIB-4) ≥ 1.6) is useful for detecting patients with significant fibrosis (fibrosis stage ≥ 2) having nonalcoholic fatty liver disease (NAFLD). However, age-dependent thresholds of FIB-4 have been proposed, and it remains unclear whether MEFIB could be applied with the same FIB-4 threshold in a different cohort. Therefore, in this study, we examined the best threshold of FIB-4 and validated the utility of MEFIB. METHODS: This study included 105 biopsy-proven NAFLD patients with contemporaneous MRE assessment. The primary outcome was a diagnostic accuracy for significant fibrosis. RESULTS: The median (interquartile range) age was 65 (58-72) years, and significant fibrosis was 76.2% (80/105). FIB-4 of 2.1 was defined as the best threshold for significant fibrosis in the cohort. The area under the receiver operating characteristics curves (AUROCs) of the combination of MRE and FIB-4 (MRE ≥ 3.3 kPa + FIB-4 ≥ 1.6: 0.80, MRE ≥ 3.3 kPa + FIB-4 ≥ 2.1: 0.84) were higher than those of each index alone (MRE ≥ 3.3 kPa: 0.76, FIB-4 ≥ 1.6: 0.72, and FIB-4 ≥ 2.1: 0.77), but AUROCs of MRE ≥ 3.3 kPa + FIB-4 ≥ 1.6 and MRE ≥ 3.3 kPa + FIB-4 ≥ 2.1 were equivalent (P = 0.3). CONCLUSIONS: MEFIB is useful for detecting patients with significant fibrosis and could be utilized in a different cohort without changing the threshold of FIB-4, and it may then be used as a two-step screening strategy.

Right entorhinal cortical thickness is associated with Mini-Mental State Examination scores from multi-country datasets using MRI.

PURPOSE: To discover common biomarkers correlating with the Mini-Mental State Examination (MMSE) scores from multi-country MRI datasets. METHODS: The first dataset comprised 112 subjects (49 men, 63 women; range, 46-94 years) at the National Hospital Organization Kyushu Medical Center. A second dataset comprised 300 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (177 men, 123 women; range, 57-91 years). Three-dimensional T1-weighted MR images were collected from both datasets. In total, 14 deep gray matter volumes and 70 cortical thicknesses were obtained from MR images using FreeSurfer software. Total hippocampal volume and the ratio of hippocampus to cerebral volume were also calculated. Correlations between each variable and MMSE scores were assessed using Pearson's correlation coefficient. Parameters with moderate correlation coefficients (r > 0.3) from each dataset were determined as independent variables and evaluated using general linear model (GLM) analyses. RESULTS: In Pearson's correlation coefficient, total and bilateral hippocampal volumes, right amygdala volume, and right entorhinal cortex (ERC) thickness showed moderate correlation coefficients (r > 0.3) with MMSE scores from the first dataset. The ADNI dataset showed moderate correlations with MMSE scores in more variables, including bilateral ERC thickness and hippocampal volume. GLM analysis revealed that right ERC thickness correlated significantly with MMSE score in both datasets. Cortical thicknesses of the left parahippocampal gyrus, left inferior parietal lobe, and right fusiform gyrus also significantly correlated with MMSE score in the ADNI dataset (p < 0.05). CONCLUSION: A positive correlation between right ERC thickness and MMSE score was identified from multi-country datasets.

Development and performance evaluation of a deep learning lung nodule detection system.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths throughout the world. Chest computed tomography (CT) is now widely used in the screening and diagnosis of lung cancer due to its effectiveness. Radiologists must identify each small nodule shadow from 3D volume images, which is very burdensome and often results in missed nodules. To address these challenges, we developed a computer-aided detection (CAD) system that automatically detects lung nodules in CT images. METHODS: A total of 1997 chest CT scans were collected for algorithm development. The algorithm was designed using deep learning technology. In addition to evaluating detection performance on various public datasets, its robustness to changes in radiation dose was assessed by a phantom study. To investigate the clinical usefulness of the CAD system, a reader study was conducted with 10 doctors, including inexperienced and expert readers. This study investigated whether the use of the CAD as a second reader could prevent nodular lesions in lungs that require follow-up examinations from being overlooked. Analysis was performed using the Jackknife Free-Response Receiver-Operating Characteristic (JAFROC). RESULTS: The CAD system achieved sensitivity of 0.98/0.96 at 3.1/7.25 false positives per case on two public datasets. Sensitivity did not change within the range of practical doses for a study using a phantom. A second reader study showed that the use of this system significantly improved the detection ability of nodules that could be picked up clinically (p = 0.026). CONCLUSIONS: We developed a deep learning-based CAD system that is robust to imaging conditions. Using this system as a second reader increased detection performance.

Unilateral agenesis of internal carotid artery with interparaclinoid and contralateral carotid-anterior cerebral artery anastomoses diagnosed by magnetic resonance angiography: a case report.

PURPOSE: Unilateral agenesis of the internal carotid artery (ICA) is a rare anatomical variant. We identified a case of unilateral ICA agenesis with interparaclinoid and contralateral carotid-ACA anastomoses. METHODS: A 65-year-old female with a long history of depressive episodes underwent MR imaging including MR angiography at National Hospital Organization Kyushu Medical Center. MR imaging was performed using a 3.0-T MR scanner to rule out vascular Parkinsonism, although drug-induced Parkinsonism was suspected from her medical history. RESULTS: The proximal left ICA was not visible on MR angiography, and an anterior communicating artery (ACoA) aneurysm was identified. The left middle cerebral artery was supplied from the right ICA via an interparaclinoid anastomosis. This interparaclinoid anastomosis showed no communication with the basilar, posterior communicating, or posterior cerebral arteries. A communicating artery connecting the interparaclinoid anastomosis and anterior cerebral artery (ACA) branched off from the presumed transition point between the interparaclinoid anastomosis and left ICA. Both right and left ophthalmic arteries (OAs) originated from the clinoid segment of the ICA. The communicating artery connecting the interparaclinoid anastomosis and ACA arose proximal to the left OA, and the communicating artery was identified as the carotid-ACA anastomosis. CONCLUSION: Neuroradiologists, physicians, and neurosurgeons need to be aware of this extremely unusual anatomical variant to determine appropriate treatment strategies in cases of aneurysmal growth or anterior cranial base surgery.