Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A.

Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.

Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Gordonibacter faecis sp. nov., producing urolithin C from ellagic acid, isolated from feces of healthy Korean subjects.

A Gram-stain-positive, anaerobic, motile, and short rod-shaped bacterium, designated KGMB12511T, was isolated from the feces of healthy Koreansubjects. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KGMB12511T was closely related to Gordonibacter pamelaeae 7-10-1-bT (95.2%). The draft genome of KGMB12511T comprised 33 contigs and 2,744 protein-coding genes. The DNA G + C content was 59.9% based on whole-genome sequences. The major cellular fatty acids (>10%) of strain KGMB12511T were C18:1 cis9, C18:1 cis9 DMA (dimethylacetal), and C16:0 DMA. The predominant polar lipids included a diphosphatydilglycerol, four glycolipids, and an unidentified phospholipid. The major respiratory quinones were menaquinone 6 (MK-6) and monomethylmenaquinone 6 (MMK-6). Furthermore, HPLC analysis demonstrated the ability of strain KGMB12511T to convert ellagic acid into urolithin. Based on a comprehensive analysis of phenotypic, chemotaxonomic, and phylogenetic data, strain KGMB12511T represents a novel species in the genus Gordonibacter. The type strain is KGMB12511T (= KCTC 25343T = NBRC 116190T).

MRI imaging features for predicting macrotrabecular-massive subtype hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To identify significant MRI features associated with macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), and to assess the distribution of Liver Imaging Radiology and Data System (LI-RADS, LR) category assignments. METHODS: PubMed and EMBASE were searched up to March 28, 2023. Random-effects model was constructed to calculate pooled diagnostic odds ratios (DORs) and 95% confidence intervals (CIs) for each MRI feature for differentiating MTM-HCC from NMTM-HCC. The pooled proportions of LI-RADS category assignments in MTM-HCC and NMTM-HCC were compared using z-test. RESULTS: Ten studies included 1978 patients with 2031 HCCs (426 (20.9%) MTM-HCC and 1605 (79.1%) NMTM-HCC). Six MRI features showed significant association with MTM-HCC: tumor in vein (TIV) (DOR = 2.4 [95% CI, 1.6-3.5]), rim arterial phase hyperenhancement (DOR =2.6 [95% CI, 1.4-5.0]), corona enhancement (DOR = 2.6 [95% CI, 1.4-4.5]), intratumoral arteries (DOR = 2.6 [95% CI, 1.1-6.3]), peritumoral hypointensity on hepatobiliary phase (DOR = 2.2 [95% CI, 1.5-3.3]), and necrosis (DOR = 4.2 [95% CI, 2.0-8.5]). The pooled proportions of LI-RADS categories in MTM-HCC were LR-3, 0% [95% CI, 0-2%]; LR-4, 11% [95% CI, 6-16%]; LR-5, 63% [95% CI, 55-71%]; LR-M, 12% [95% CI, 6-19%]; and LR-TIV, 13% [95% CI, 6-22%]. In NMTM-HCC, the pooled proportions of LI-RADS categories were LR-3, 1% [95% CI, 0-2%]; LR-4, 8% [95% CI, 3-15%]; LR-5, 77% [95% CI, 71-82%]; LR-M, 5% [95% CI, 3-7%]; and LR-TIV, 6% [95% CI, 2-11%]. MTM-HCC had significantly lower proportion of LR-5 and higher proportion of LR-M and LR-TIV categories. CONCLUSIONS: Six MRI features showed significant association with MTM-HCC. Additionally, compared to NMTM-HCC, MTM-HCC are more likely to be categorized LR-M and LR-TIV and less likely to be categorized LR-5. CLINICAL RELEVANCE STATEMENT: Several MR imaging features can suggest macrotrabecular-massive hepatocellular carcinoma subtype, which can assist in guiding treatment plans and identifying potential candidates for clinical trials of new treatment strategies. KEY POINTS: • Macrotrabecular-massive hepatocellular carcinoma is a subtype of HCC characterized by its aggressive nature and unfavorable prognosis. • Tumor in vein, rim arterial phase hyperenhancement, corona enhancement, intratumoral arteries, peritumoral hypointensity on hepatobiliary phase, and necrosis on MRI are indicative of macrotrabecular-massive hepatocellular carcinoma. • Various MRI characteristics can be utilized for the diagnosis of the macrotrabecular-massive hepatocellular carcinoma subtype. This can prove beneficial in guiding treatment decisions and identifying potential candidates for clinical trials involving novel treatment approaches.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Phocaeicola acetigenes sp. nov., producing acetic acid and iso-butyric acid, isolated faeces from a healthy human.

An obligately anaerobic, non-motile, Gram-stain-negative, and rod-shaped strain KGMB11183T was isolated from the feces of healthy Koreans. The growth of strain KGMB11183T occurred at 30-45 °C (optimum 37 °C), at pH 6-9 (optimum pH 7), and in the presence of 0-0.5% NaCl (optimum 0%). Strain KGMB11183T showed 16S rRNA gene sequence similarities of 95.4% and 94.2% to the closest recognized species, Phocaeicola plebeius M12T, and Phocaeicola faecicola AGMB03916T. Phylogenetic analysis showed that strain KGMB11183T is a member of the genus Phocaeiocla. The major end products of fermentation are acetic acid and isobutyric acid. The major cellular fatty acids (> 10%) of this isolate were C18:1 cis 9, anteiso-C15:0, and summed feature 11 (iso-C17:0 3-OH and/or C18:2 DMA). The assembled draft genome sequences of strain KGMB11183T consisted of 3,215,271 bp with a DNA G + C content of 41.4%. According to genomic analysis, strain KGMB11183T has a number of genes that produce acetic acid. The genome of strain KGMB11183T encoded the starch utilization system (Sus) operon, SusCDEF suggesting that strain uses many complex polysaccharides that cannot be digested by humans. Based on the physiological, chemotaxonomic, phenotypic, and phylogenetic data, strain KGMB11183T is regarded a novel species of the genus Phocaeicola. The type strain is KGMB11183T (= KCTC 25284T = JCM 35696T).

Connecting the S2 alar-iliac screw head to the satellite rod for surgical correction of degenerative sagittal imbalance.

PURPOSE: The S2AI screw technique has several advantages over the conventional iliac screw fixation technique. However, connecting the S2AI screw head to the main rod is difficult due to its medial entry point. We introduce a new technique for connecting the S2AI screw head to a satellite rod and compare it with the conventional method of connecting the S2AI screw to the main rod. METHODS: Seventy-four patients who underwent S2AI fixation for degenerative sagittal imbalance and were followed up for ≥ 2 years were included. All the patients underwent long fusion from T9 or T10 to the pelvis. The S2AI screw head was connected to the satellite rod (SS group) in 43 patients and the main rod (SM group) in 31 patients. In the SS group, the satellite rod was placed medial to the main rod and connected by the S2AI screw and domino connectors. In the SM group, the main rod was connected directly to the S2AI screw head and supported by accessory rods. Radiographic and clinical outcomes were evaluated in both groups. RESULTS: There were no significant differences in postoperative complications, including proximal junctional failure, proximal junctional kyphosis, rod breakage, screw loosening, wound problems, and infection between the two groups. Furthermore, the correction power of sagittal deformity and clinical results in the SS group were comparable to those in the SM group. CONCLUSION: Connecting the S2AI screw to the satellite rod is a convenient method comparable to the conventional S2AI connection method in terms of radiological and clinical outcomes.

Can We Control Lateral Shoulder Balance Through Proximal Thoracic Curve Correction in Lenke Type 2 Adolescent Idiopathic Scoliosis?

BACKGROUND: Proximal thoracic curve (PTC) correction has been considered to prevent lateral shoulder imbalance in Lenke Type 2 adolescent idiopathic scoliosis (AIS) patients; however, postoperative shoulder imbalance (PSI) commonly occurs despite these strategies with PTC correction. We investigated the hypothesis that PTC correction would not directly affect PSI in the majority of Lenke type 2 AIS cases. Furthermore, we investigated the risk factors for lateral PSI after corrective surgery. METHODS: This study examined the records for AIS patients with Lenke type 2 who underwent corrective surgery and followed up for >2 years. Patients were categorized into PSI (-); radiologic shoulder height (RSH)<15 mm, and PSI (+); RSH≥15 mm. Repeated measures analysis of variance was performed at preoperatively, postoperatively, 1 month, and final follow-up. Postoperative lateral shoulder imbalance was predicted by the identification of univariate analysis and multivariate analysis. RESULTS: Among the 151 patients reviewed, 29 (19.2%) showed PSI at final follow-up. Lateral shoulder balance parameters showed different directionalities between PSI (-) and (+) groups at postoperatively, 1 month, and final follow-up ( P <0.01 each). Preoperative PTC, middle thoracic curve (MTC) curve and MTC correction showed strong correlations with the RSH ( P =0.01, 0.03, and 0.04, respectively). However, PTC correction did not show a significant correlation with the RSH. Moreover, only a smaller MTC curve and larger MTC correction rate were related to lateral PSI in multivariate analysis. CONCLUSIONS: In Lenke type 2 AIS curves, the MTC curve and its correction predominantly influence lateral shoulder imbalance after corrective surgery, irrespective of the PTC correction extent. Consequently, overemphasizing the correction of the PTC curve may not necessarily lead to an improved lateral shoulder balance. When MTC curve is smaller, surgeons should be more careful for MCT overcorrection leading to a lateral shoulder imbalance. LEVEL OF EVIDENCE: Level III.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Association Between Metabolic Syndrome and the Risk of Colorectal Cancer Diagnosed Before Age 50 Years According to Tumor Location.

BACKGROUND & AIMS: The increasing prevalence of obesity at younger ages is concurrent with an increased earlier-onset colorectal cancer (CRC) (before age 50 years) incidence, particularly left-sided colon cancer. We investigated whether obesity and metabolic syndrome (MetS) are associated with increased earlier-onset CRC risk according to tumor location. METHODS: Our nationwide population-based cohort study enrolled 9,774,081 individuals who underwent health checkups under the Korean National Health Insurance Service from 2009 to 2010, with follow-up until 2019. We collected data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), blood pressure, and laboratory findings. A multivariate Cox proportional hazards regression analysis was performed. RESULTS: A total of 8320 earlier-onset and 57,257 later-onset CRC cases developed during follow-up. MetS was associated with increased earlier-onset CRC (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27), similar to later-onset CRC (adjusted hazard ratio, 1.19; 95% CI, 1.17-1.21). The adjusted hazard ratios for earlier-onset CRC with 1, 2, 3, 4, and 5 MetS components were 1.07 (95% CI, 1.01-1.13), 1.13 (95% CI, 1.06-1.21), 1.25 (95% CI, 1.16-1.35), 1.27 (95% CI, 1.15-1.41), and 1.50 (95% CI, 1.26-1.79), respectively (P for trend < .0001). We found that higher body mass index and larger waist circumference were significantly associated with increased earlier-onset CRC (P for trend < .0001). These dose-response associations were significant in distal colon and rectal cancers, although not in proximal colon cancers. CONCLUSIONS: MetS and obesity are positively associated with CRC before age 50 years with a similar magnitude of association as people diagnosed after age 50 years. Thus, people younger than 50 years with MetS require effective preventive interventions to help reduce CRC risk.

Effectiveness of US Surveillance of Hepatocellular Carcinoma in Chronic Hepatitis B: US LI-RADS Visualization Score.

Background US is a standard surveillance tool of hepatocellular carcinoma (HCC), but its effectiveness varies depending on the degree of fibrosis or steatosis and the etiologies of liver disease. Purpose To evaluate the detection power of US and the occurrence of HCC according to the US Liver Imaging Reporting and Data System (LI-RADS) visualization score in chronic hepatitis B (CHB). Materials and Methods Consecutive patients with CHB undergoing regular US surveillance of HCC at a tertiary referral hospital were retrospectively included in this study. During the follow-up, all patients underwent regular HCC surveillance mainly with US and, in some cases, alternative CT or MRI. Outcomes of interest included cumulative incidence of HCC and false-negative rate of US in the optimal (LI-RADS visualization A) versus suboptimal groups (visualization B or C). Cox regression analysis was conducted to calculate the hazard ratio (HR) of HCC occurrence. Results A total of 2002 patients (median age, 54 years [IQR, 46-60 years]; 1192 men) were included: 972 and 1030 in the optimal and suboptimal groups, respectively. Causes of suboptimal visualization included parenchymal heterogeneity from advanced cirrhosis (n = 489), limited penetration from fatty liver (n = 200), and limited window from overlying organ shadow (n = 341). During a median follow-up of 75 months (IQR, 69-77 months), 163 patients developed HCC. Compared with the optimal group, the suboptimal group had a higher risk of HCC (2.38% per year vs 0.48% per year: hazard ratio, 4.93; 95% CI: 3.28, 7.41; P < .001) and higher odds of a false-negative rate of US (43.9% vs 16.7%: odds ratio, 3.90; 95% CI: 1.02, 15.00; P = .04). Conclusion Among patients with CHB, those with suboptimal US LI-RADS visualization of B or C had a higher risk of HCC and higher odds of false-negative rates of US for detecting HCC than those with optimal visualization of A. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barr and Scoutt in this issue.

Spiral-phase-objective for a compact spiral-phase-contrast microscopy.

Spiral-phase-contrast imaging, which utilizes a spiral phase optical element, has proven to be effective in enhancing various aspects of imaging, such as edge contrast and shadow imaging. Typically, the implementation of spiral-phase-contrast imaging requires the formation of a Fourier plane through a 4f optical configuration in addition to an existing optical microscope. In this study, we present what we believe to be a novel single spiral-phase-objective, integrating a spiral phase plate, which can be easily and simply applied to a standard microscope, such as a conventional objective. Using a new hybrid design approach that combines ray-tracing and field-tracing simulations, we theoretically realized a well-defined and high-quality vortex beam through the spiral-phase-objective. The spiral-phase-objective was designed to have conditions that are practically manufacturable while providing predictable performance. To evaluate its capabilities, we utilized the designed spiral-phase-objective to investigate isotropic spiral phase contrast and anisotropic shadow imaging through field-tracing simulations, and explored the variation of edge contrast caused by changes in the thickness of the imaging object.

Abbreviated MRI for Secondary Surveillance of Recurrent Hepatocellular Carcinoma After Presumed Curative Treatment.

BACKGROUND: Little is known about the performance of abbreviated MRI (AMRI) for secondary surveillance of recurrent hepatocellular carcinoma (HCC) after curative treatment. PURPOSE: To evaluate the detection performance of AMRI for secondary surveillance of HCC after curative treatment. STUDY TYPE: Retrospective. POPULATION: A total of 243 patients (183 men and 60 women; median age, 65 years) who underwent secondary surveillance for HCC using gadoxetic acid-enhanced MRI after more than 2 year of disease-free period following curative treatment, including surgical resection or radiofrequency ablation (RFA). FIELD STRENGTH/SEQUENCE: A 3.0 T/noncontrast AMRI (NC-AMRI) (T2-weighted fast spin-echo, T1-weighted gradient echo, and diffusion-weighted images), hepatobiliary phase AMRI (HBP-AMRI) (T2-weighted fast spin-echo, diffusion-weighted, and HBP images), and full-sequence MRI ASSESSMENT: Four board-certified radiologists independently reviewed NC-AMRI, HBP-AMRI, and full-sequence MRI sets of each patient for detecting recurrent HCC. STATISTICAL TESTS: Per-lesion sensitivity, per-patient sensitivity and specificity for HCC detection at each set were compared using generalized estimating equation. RESULTS: A total of 42 recurred HCCs were confirmed in the 39 patients. The per-lesion and per-patient sensitivities did not show significant differences among the three image sets for either reviewer (P ≥ 0.358): per-lesion sensitivity: 59.5%-83.3%, 59.5%-85.7%, and 59.5%-83.3%, and per-patient sensitivity: 53.9%-83.3%, 56.4%-85.7%, and 53.9%-83.3% for NC-AMRI, HBP-AMRI, and full-sequence MRI, respectively. Per-lesion pooled sensitivities of NC-AMRI, HBP-AMRI, and full-sequence MRI were 72.6%, 73.2%, and 73.2%, with difference of -0.6% (95% confidence interval: -6.7, 5.5) between NC-AMRI and full-sequence MRI and 0.0% (-6.1, 6.1) between HBP-AMRI and full-sequence MRI. Per-patient specificity was not significantly different among the three image sets for both reviewers (95.6%-97.1%, 95.6%-97.1%, and 97.6%-98.5% for NC-AMRI and HBP-AMRI, respectively; P ≥ 0.117). DATA CONCLUSION: NC-AMRI and HBP-AMRI showed no significant difference in detection performance to that of full-sequence gadoxetic acid-enhanced MRI during secondary surveillance for HCC after more than 2-year disease free interval following curative treatment. Based on its good detection performance, short scan time, and lack of contrast agent-associated risks, NC-AMRI is a promising option for the secondary surveillance of HCC. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Can "no-touch" radiofrequency ablation for hepatocellular carcinoma improve local tumor control? Systematic review and meta-analysis.

OBJECTIVES: Percutaneous radiofrequency ablation (RFA) is one of the curative treatments for hepatocellular carcinoma (HCC), but local tumor progression (LTP) has been a main limitation of RFA. This study aims to evaluate the LTP of percutaneous no-touch RFA (NtRFA) for HCC ≤ 5 cm and compare with conventional RFA (intratumoral puncture) through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched for studies on percutaneous NtRFA for HCC ≤ 5 cm. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for LTP after NtRFA were assessed using a random-effects model. For studies comparing NtRFA with conventional RFA, relative risks (RR) and hazard ratios (HR) were meta-analytically pooled with LTP as the outcome. RESULTS: Twelve studies with 900 patients were included. The pooled overall rate of LTP after NtRFA was 6% (95% CI, 4-8%). The pooled 1-, 2-, and 3-year cumulative incidence rates of LTP were 3% (95% CI, 2-5%), 5% (95% CI, 3- 9%), and 8% (95% CI, 6-11%), respectively. Compared to conventional RFA, the pooled RR and HR of LTP were 0.26 (95% CI, 0.16-0.41) and 0.28 (95% CI, 0.11-0.70), respectively (both p < 0.01). Subgroup analysis including only randomized controlled studies also showed better local tumor control of NtRFA with HR of 0.13 (95% CI, 0.14-0.42). CONCLUSIONS: Percutaneous NtRFA is an effective treatment for HCC ≤ 5 cm with an overall LTP rate of 6% and provides lower LTP compared with conventional RFA. KEY POINTS: • The pooled 1-, 2-, and 3-year cumulative incidence rates of local tumor progression after no-touch radiofrequency ablation for HCC ≤ 5 cm were 3% (95% CI, 2-5%), 5% (95% CI, 3-9%), and 8% (95% CI, 6-11%). • No-touch radiofrequency ablation had significantly lower rates of local tumor progression compared to conventional radiofrequency ablation (hazard ratio, 0.28; 95% CI, 0.11-0.70; relative risk, 0.26; 95% CI, 0.16-0.41; p < 0.01, respectively).

Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study.

OBJECTIVES: To investigate the safety and preliminary efficacy of the combined treatment of focused ultrasound (FUS) and chemotherapy (nab-paclitaxel plus gemcitabine, nPac/Gem) for patients with unresectable pancreatic cancer. METHODS: Patients pathologically diagnosed with unresectable pancreatic cancer were included. Low (Isppa = 1.5 kW/cm2), intermediate (2.0 kW/cm2), and high (2.5 kW/cm2) FUS intensity treatment groups were predefined. A 1% duty cycle and the 3+3 scheme were used. Six combined treatments were performed, and adverse events were assessed. Changes in tumor size and tumor response, CA 19-9 level, and patient-reported outcomes at the immediate follow-up (F/U) and/or at the 3-month F/U and survival were evaluated. RESULTS: Three participants were enrolled in each intensity group. No adverse device effect or dose-limiting toxicity occurred in any of the participants. Seven of the nine participants experienced a >15% tumor size decrease at the immediate F/U CT and at the 3-month F/U CT. The CA 19-9 level decreased in all of the participants at the immediate F/U. All participants in the intermediate-intensity treatment group showed a > 30% tumor size decrease, partial response, and a significant decrease in the CA 19-9 level at 3-month F/U and longer survival (p < 0.05). CONCLUSION: FUS with an intensity of 1.5 to 2.5 kW/cm2 was safe in the combined treatment of FUS and nPac/Gem. Considering the results of the change in tumor size, the change in CA 19-9 level, tumor response, and survival, these FUS parameters can be used for subsequent clinical trials. KEY POINTS: • No adverse device effect or dose-limiting toxicity occurred in any of the participants when focused ultrasound with an intensity of 1.5-2.5 kW/cm2 and a low duty cycle of 1% was combined with chemotherapy. • The intermediate-intensity group showed a >30% tumor size decrease, partial response, and a significant decrease in CA 19-9 in all of the participants at the 3-month follow-up and the longest survival. • Any focused ultrasound setting used in this study could be safe and optimal for subsequent clinical trials.

High-resolution pancreatic computed tomography for assessing pancreatic ductal adenocarcinoma resectability: a multicenter prospective study.

OBJECTIVE: This prospective multicenter study aimed to evaluate the diagnostic performance of 80-kVp thin-section pancreatic CT in determining pancreatic ductal adenocarcinoma (PDAC) resectability according to the recent National Comprehensive Cancer Network (NCCN) guidelines. METHODS: We prospectively enrolled surgical resection candidates for PDAC from six tertiary referral hospitals (study identifier: NCT03895177). All participants underwent pancreatic CT using 80 kVp tube voltage with 1-mm reconstruction interval. The local resectability was prospectively evaluated using NCCN guidelines at each center and classified into three categories: resectable, borderline resectable, and unresectable. RESULTS: A total of 138 patients were enrolled; among them, 60 patients underwent neoadjuvant therapy. R0 resection was achieved in 103 patients (74.6%). The R0 resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable disease, respectively, in 78 patients who underwent upfront surgery. Meanwhile, the rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively, in patients who received neoadjuvant therapy. The area under curve of high-resolution CT in predicting R0 resection was 0.784, with sensitivity, specificity, and accuracy of 87.4% (90/103), 48.6% (17/35), and 77.5% (107/138), respectively. Tumor response was significantly associated with the R0 resection after neoadjuvant therapy (odds ratio [OR] = 38.99, p = 0.016). CONCLUSION: An 80-kVp thin-section pancreatic CT has excellent diagnostic performance in assessing PDAC resectability, enabling R0 resection rates of 88.7% and 90.9% for patients with resectable PDAC who underwent upfront surgery and patients with resectable PDAC after neoadjuvant therapy, respectively. KEY POINTS: • The margin-negative (R0) resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable pancreatic ductal adenocarcinoma (PDAC), respectively, on 80-kVp thin-section pancreatic CT in the 78 patients who underwent upfront surgery. • Among the 60 patients who underwent neoadjuvant therapy, the R0 rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively. • Tumor response, along with the resectability status on pancreatic CT, was significantly associated with the R0 resection rate after neoadjuvant therapy.

Prevalence and trends of multiple antimicrobial resistance of Helicobacter pylori in one tertiary hospital for 20 years in Korea.

BACKGROUND: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).

Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months.

BACKGROUND: The association between Helicobacter pylori (HP) infection and coronary heart disease (CHD) is controversial. This study aimed to investigate the effect of H. pylori eradication on CHD, especially in terms of age and sex. MATERIALS AND METHODS: From May 2003 to March 2022, 4765 subjects with H. pylori infection and without CHD (median follow-up: 51 months) were prospectively enrolled. The participants were categorized into two groups: H. pylori eradication and H. pylori non-eradication. After propensity-score matching (PSM), the effect of H. pylori eradication on CHD was analyzed using Cox proportional hazards. RESULTS: There were no significant differences in age, sex, alcohol consumption, smoking habits, history of diabetes, hypertension, and dyslipidemia, and aspirin intake between the eradication and non-eradication groups (3783 vs. 982) before and after PSM. Multivariate analysis after PSM showed that H. pylori eradication (HR: 0.489, CI: 0.314-0.761, p = .002), age (HR: 1.027, CI: 1.007-1.047, p = .007), hypertension (HR: 2.133, CI: 1.337-3.404, p = 001), dyslipidemia (HR: 1.758, CI: 1.086-2.848, p = .022), and aspirin intake (HR: 2.508, CI: 1.566-4.017, p < .001) were associated with CHD development. H. pylori eradication prevented CHD in males ≤65 years (HR: 0.133, CI: 0.039-0.455, p = .001), but not in those aged >65 years (p = .078) (p for interaction = .022). In contrast, females aged >65 years (HR: 0.260, CI: 0.110-0.615, p = .002) were protected by H. pylori eradication and not those ≤65 years (p = .485) (p for interaction = .003). This preventive effect increased more after PSM, particularly in males ≤65 years and females >65 years. CONCLUSIONS: H. pylori eradication prevented CHD and this effect was different depending on age and sex.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Fusion imaging-guided radiofrequency ablation with artificial ascites or pleural effusion in patients with hepatocellular carcinomas: the feasibility rate and mid-term outcome.

Purpose: To investigate the feasibility rate and the mid-term outcomes of fusion imaging-guided radiofrequency ablation (RFA) with artificial ascites or pleural effusion of hepatocellular carcinomas (HCCs) based on tumor locations.Materials and Methods: In this single-center retrospective study, 456 patients with single HCCs ≤4 cm were referred for RFA from April 2019 to April 2020. The tumor locations were classified into a conventional location (CL) and difficult location (DL, close to the diaphragm/heart/major vessels/bile ducts/gastrointestinal tract/kidneys). This study assessed the feasibility rate of CT/MRI-US fusion system-guided RFA with artificial ascites or pleural effusion and the therapeutic outcomes including technical success, technique efficacy, and local tumor progression (LTP) according to tumor location. Cumulative LTP rates were estimated using the Kaplan-Meier method.Results: 235 of 456 (51.5%) patients had HCCs in DL. Ablation was feasible in 431 of 456 (94.5%) patients. The feasibility rate was significantly lower in DL group than in CL group (89.8% [211/235] vs. 99.5% [220/221], p < 0.001). The technical success and technique efficacy rates were 100% [211/211] vs. 99.5% [219/220] and 98.6% [208/211] vs. 100% [220/220] in DL and CL groups, respectively (p > 0.05). The estimated 1-, 2-, and 3-year cumulative LTP rates in DL group were 1.0%, 2.5%, and 2.5%, respectively, and were not significantly different from the 2.3%, 3.9%, and 3.9% observed in CL group (p = 0.456).Conclusion: Fusion imaging-guided RFA with artificial ascites or pleural effusion could decrease technically infeasible cases and provide comparable LTP rates for HCCs in DL to HCCs in CL.