Spleen stiffness in patients with chronic liver disease evaluated by 2-D shear wave elastography with ultrasound multiparametric imaging.

BACKGROUND: The novel 2-D shear wave elastography (2D-SWE) can measure two ultrasound parameters: shear wave dispersion (SWD) and shear wave speed (SWS). We investigated the ability of 2D-SWE in measuring spleen stiffness using ultrasound multiparametric imaging. METHODS: This cross-sectional study included patients with chronic liver disease who underwent esophagogastroduodenoscopy and ultrasonographic examinations of the spleen between September 2018 and December 2021. In total, 157 patients were enrolled in this study: 81 and 67 patients were included in the pilot set for hepatic venous pressure gradient (HVPG) measurements and validation cohort without HVPG measurements, respectively. To confirm reproducibility between the two examiners, an additional 30 patients were enrolled. RESULTS: The Bland-Altman plots revealed no significant bias in the SWD as measured by two examiners. The splenic SWS (r = 0.752) and SWD (r = 0.444) were correlated with the HVPG. Regarding high-risk varices, as per the Youden index, the cut-off value for splenic SWS was 3.30 m/s, with a sensitivity of 85.7%, specificity of 92.5%, positive predictive value of 85.7%, and negative predictive value of 92.4% in the pilot set. In the validation set, good diagnostic performance by the splenic SWS was observed. However, SWD did not perform as well as SWS. CONCLUSIONS: The splenic SWS, measured using ultrasound multiparametric imaging, was closely correlated with the HVPG. Thus, SWS is a useful predictive marker for high-risk varices.

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.

AIMS: HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. METHODS: A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. RESULTS: Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10  IU/ml (p < 0.05) and -0.2677 log10  IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. CONCLUSIONS: Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Marked Hypertriglyceridemia in a Patient with type 2 Diabetes Receiving SGLT2 Inhibitors.

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis.

Role of severe thrombocytopenia in preventing platelet count recovery in thrombocytopenic patients with chronic liver disease.

BACKGROUND AND AIM: Certain thrombocytopenic patients with chronic liver disease have inadequate platelet count recovery after platelet transfusion or lusutrombopag administration. We aimed to identify the reasons for this phenomenon. METHODS: We investigated 58 and 86 thrombocytopenic patients with chronic liver disease who received lusutrombopag (3 mg orally for up to 7 days) or underwent blood transfusions, respectively. Thirty patients underwent simultaneous hepatic surgery and splenectomy. Factors preventing platelet count recovery above 50 × 103 /µL were identified. RESULTS: The median patient age was 64 years. Eleven, 78, and 55 patients had hepatitis B, hepatitis C, or another etiology, respectively; 59, 69, and 16 had Child-Pugh classes A, B, and C, respectively. The median spleen volume was 432 mL, and a median of 10 blood units were transfused per patient. The median platelet count rose significantly (from 41.5 × 103 /µL to 81.0 × 103 /µL) after lusutrombopag administration but not after blood transfusion before invasive procedures. However, maximum platelet counts in patients who underwent splenectomy before platelet transfusion were markedly improved over those who did not. Increasing platelet counts above 50 × 103 /µL required baseline platelets > 30 × 103 /µL and lusutrombopag administration for all patients. Platelet count recovery was dependent on a spleen volume of < 300 mL and baseline platelets of > 40 × 103 /µL in patients who underwent platelet transfusions, while a baseline platelet count of > 30 × 103 /µL was required for patients administered with lusutrombopag. CONCLUSION: Neither blood transfusion nor lusutrombopag improves thrombocytopenia in patients with severe conditions; however, the degree of platelet count elevation following lusutrombopag administration is higher than that following blood transfusion.

Using ALBI score at the start of sorafenib treatment to predict regorafenib treatment candidates in patients with hepatocellular carcinoma.

BACKGROUND: Although sorafenib-regorafenib sequential therapy improves the prognosis of patients with hepatocellular carcinoma (HCC), many patients abandon sequential therapy due to worsening hepatic reserve function. Thus, it is important to clarify which patients can be treated using regorafenib. The albumin-bilirubin score is a good biomarker for hepatic reserve function. The aim of this study was to determine whether patient albumin-bilirubin scores at the start of sorafenib treatment could be used to identify candidates for subsequent regorafenib therapy. METHODS: This is a retrospective cohort study. From 2009 to 2017, 267 hepatocellular carcinoma patients treated with sorafenib were enrolled. After sorafenib therapy, 138 progressive disease patients were analyzed. The patients were divided in two groups: (i) regorafenib candidate group (Child-Pugh class A, Eastern Cooperative Oncology Group Performance Status ≤1, and maintained sorafenib tolerance); and (ii) regorafenib non-candidate group. The primary endpoint was the albumin-bilirubin score. We assessed retrospectively whether albumin-bilirubin scores were useful for predicting regorafenib treatment regimen candidacy. RESULTS: For the 138 analyzed patients, the median overall survival duration was 15.6 months in the regorafenib candidate group and 6.8 months in the regorafenib non-candidate group (P < 0.01). Using univariate analysis, etiology, aspartate aminotransferase ≥40 IU/L, prothrombin time ≥85% and albumin-bilirubin score <-2.53 at the start of sorafenib treatment were identified as predictors. Using multivariate analysis, albumin-bilirubin score <-2.53 was the only significant predictor. CONCLUSIONS: Based on the multivariate analysis results, albumin-bilirubin score at the start of sorafenib therapy is a useful marker for identifying candidate patients for starting regorafenib therapy.

Efficacy of chemotherapy in elderly patients with unresectable pancreatic cancer: a multicenter review of 895 patients.

BACKGROUND: The efficacy of chemotherapy for unresectable pancreatic cancer has improved. However, it is occasionally difficult to make treatment decisions for elderly patients. We reviewed the outcomes of elderly patients with unresectable pancreatic cancer by using a large cohort and evaluated whether they had received chemotherapy and the reason why. METHODS: Data for 895 pancreatic cancer patients who were treated using chemotherapy or best supportive care were analyzed considering demographics, clinical stage, treatment, and outcome. Data were analyzed using the chi-square test, Student t-test, or Mann-Whitney U-test, as appropriate. Outcomes were analyzed using the Kaplan-Meier method. Differences in survival were analyzed using the log-rank test. RESULTS: The median survival time was significantly shorter in elderly patients (≥65 years) than in younger patients (<65 years) (181 vs. 263 days, P = 0.0001). The median survival time of patients treated with chemotherapy was not significantly different between the elderly and the younger group (274 days vs. 333 days, P = 0.09), and nor was that of patients choosing best supportive care (84 days vs. 78 days, P = 0.83). These results held true even when the age cut-off between younger and elder patients was increased to 70, 75, and 80 years. Elderly patients treated with chemotherapy had a significantly longer median survival time than those choosing best supportive care (274 vs. 86 days, P < 0.0001); a significantly greater proportion of elderly patients chose best supportive care compared to younger patients (47.8 vs. 25.8%, P < 0.0001). The reason for choosing best supportive care was established in 261 elderly patients (82.9%); 133 (51.0%) met the eligibility criteria for chemotherapy, but of these, 78 (58.6%) were not informed about their disease. The treatment preferences of elderly patients were not always considered; they often received only best supportive care per family members preference (N = 65, 48.8%) or because the physician based their treatment decision only on the patient's age (N = 68, 51.1%). CONCLUSIONS: Chemotherapy appears effective for elderly pancreatic cancer patients with unresectable disease, but treatment needs to be optimized to improve prognosis.

Comparison between real-time tissue elastography and vibration-controlled transient elastography for the assessment of liver fibrosis and disease progression in patients with primary biliary cholangitis.

AIM: Assessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real-time tissue elastography (RTE) and vibration-controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC. METHODS: The study participants were 44 patients with PBC. We assessed hepatic and splenic elasticity using RTE and VCTE and measured serum markers related to fibrosis and hepatic and splenic blood flow using Doppler ultrasonography. We then compared RTE and VCTE for diagnostic accuracy. Patients with asymptomatic PBC were followed every 1-3 months. RESULTS: Both RTE and VCTE performed well and had superior diagnostic accuracy compared with biochemical markers. The areas under the receiver operating characteristic curve for RTE and VCTE were 0.92 and 0.92, 0.95 and 0.91, and 0.97 and 0.91 for F ≥ 2, F ≥ 3, and F = 4, respectively. During follow-up, nine patients (25.0%) developed liver-related symptoms. Multivariate analysis revealed that splenic elasticity assessed using RTE was a significant independent factor for the development of liver-related symptoms (odds ratio, 2.19; P = 0.024). CONCLUSIONS: Real-time tissue elastography offered better diagnostic accuracy for severe fibrosis and cholangitis than VCTE. Splenic elasticity determined using RTE is a useful parameter for evaluating liver-related symptoms and an effective predictive marker of disease progression in patients with asymptomatic PBC.

Clinical utility of multipolar ablation with a 3-D simulator system for patients with liver cancer.

BACKGROUND AND AIM: The aim of this study is to confirm the efficacy of multipolar ablation with a new simulator system, three-dimensional (3-D) sim-Navigator, for patients with hepatocellular carcinoma by assessing relapse-free survival and shape of the ablation volume under clinical conditions. METHODS: All participants provided written, informed consent, and study protocols were approved by the institutional ethics committee. Twenty-seven patients with 27 nodules were treated by no-touch ablation using the new simulator system. Another 21 patients with 21 nodules treated without the simulator system were enrolled as controls. Tumor progression and shape of ablation volume were assessed. Predictors of tumor progression were assessed by Cox proportional hazard model. RESULTS: No significant differences in clinical characteristics were seen between groups. Mean sphericity was 0.48 ± 0.07 with 3-D sim-Navigator and 0.37 ± 0.07 without 3-D sim-Navigator (P < 0.001). Median surface-to-volume ratio and compactness were also significantly closer to those of a sphere with 3-D sim-Navigator (P = 0.017, P < 0.001). Relapse-free survival rates at 1 and 1.5 years were 94.1% and 82.4%, respectively, with 3-D sim-Navigator, compared with 83.2% and 55.5% without (P = 0.056). The only independent factor predicting relapse-free survival was use of 3-D sim-Navigator (hazard ratio, 0.12; 95%CI, 0.01-0.87; P = 0.035). CONCLUSIONS: Ideal ablation area was acquired by this simulation and navigation system in clinics. This system improved local tumor progression by facilitating appropriate insertion of multiple electrodes.

A case of an unruptured hepatic aneurysm on the common hepatic artery at the junction of the gastroduodenal and proper hepatic arteries treated with transcatheter arterial embolization.

Hepatic aneurysms are rare, but can prove fatal once they rupture. Transcatheter arterial embolization (TAE) is performed as a prophylactic treatment. The position of the aneurysm determines the degree of difficulty of TAE. Maintaining blood flow to the liver can become difficult, particularly when the aneurysm is at an arterial junction. The patient was a 72-year-old man diagnosed with a hepatic aneurysm. The aneurysm was situated on the common hepatic artery at the junction of the gastroduodenal and proper hepatic arteries. TAE was performed with framing, followed by coil embolization. Blood flow to the liver was maintained via the gastroduodenal artery. Appropriate framing is important for safe and efficient TAE.

Hypophosphatemia in patients with hepatitis B virus infection undergoing long-term adefovir dipivoxil therapy.

AIM: The purpose of this study was to clarify the frequency of hypophosphatemia and other clinical features in patients with hepatitis B undergoing long-term therapy with adefovir dipivoxil (ADF). METHODS: Seventeen hepatitis B patients treated with a combination of lamivudine and ADF were analyzed. They were divided into two groups: patients who developed hypophosphatemia (P < 2.5 mg/dL) (group A) and those who did not (group B). The frequency of hypophosphatemia and other clinical features were retrospectively analyzed. RESULTS: There were six patients (35.3%) in group A. The treatment period was 57.3 ± 15.6 and 61.8 ± 25.7 months in groups A and B, respectively. No differences were found between the groups prior to treatment. Among the six patients in group A, osteomalacia was observed in two, while a pathological fracture of the scapula was found in one. Decreases in phosphate (96 weeks after starting ADF), estimated glomerular filtration rate (eGFR) (48 weeks) and uric acid (24 weeks) levels, and increases in creatinine and alkaline phosphatase were noted in group A. CONCLUSION: Hypophosphatemia occurred in 35% of the patients under the long-term treatment with ADF. Although it was not possible to predict the decrease in phosphate before ADF therapy, decreases in uric acid and eGFR may be the early events relating to low phosphatemia.

Real-time tissue elastography: non-invasive evaluation of liver fibrosis in chronic liver disease due to HCV.

BACKGROUND/AIMS: We evaluated the diagnostic efficacy for advanced fibrosis of real-time tissue elastography (RTE), is a newly introduced non-invasive method, in hepatitis C virus (HCV) patients. METHODOLOGY: Sixty-six chronic liver diseases with HCV (CLD-HCV) were evaluated by RTE, FIB-4, and APRI, as well as biopsy or hepatectomy findings. Seventeen healthy volunteers, and 1 with elevation of transaminase and 5 with liver tumors within their normal liver were enrolled for normal controls. Severe fibrosis was defined as METAVIR score 3 or 4. The tissue elasticity value was expressed by LF-index created by the program incorporated in the ultrasound device. The percentage of fibrosis area in each specimen (%FA) was determined with a personal computer. A receiver operating characteristic curve (ROC) was calculated for each non-invasive method of estimation of fibrosis. RESULTS: The values for the area under the ROC for LF-index, APRI, and FIB-4 were 0.88, 0.81, and 0.84, respectively. Accuracy, sensitivity, and specificity for prediction of LF-index (>2.8) for severe fibrosis were 86.5%, 78.6%, and 93.6%, respectively, which were better than those of FIB-4 and APRI. LF-index showed a good relationship to %FA (r=0.276, P=0.020). CONCLUSION: RTE is an effective method for predicting severe fibrosis in CLD-HCV.

Spintronic virtual neural network by a voltage controlled ferromagnet for associative memory.

Recently, an associative memory operation by a virtual oscillator network, consisting of a single spintronic oscillator, was examined to solve issues in conventional, real oscillators-based neural networks such as inhomogeneities between the oscillators. However, the spintronic oscillator still carries issues dissipating large amount of energy because it is driven by electric current. Here, we propose to use a single ferromagnet manipulated by voltage-controlled magnetic anisotropy (VCMA) effect as a fundamental element in a virtual neural network, which will contribute to significantly reducing the Joule heating caused by electric current. Instead of the oscillation in oscillator networks, magnetization relaxation dynamics were used for the associative memory operation. The associative memory operation for alphabet patterns is successfully demonstrated by giving correspondences between the colors in a pattern recognition task and the sign of a perpendicular magnetic anisotropy coefficient, which could be either positive or negative via the VCMA effect.

Modification of poly(lactate) via polymer blending with microbially produced poly[(R)-lactate-co-(R)-3-hydroxybutyrate] copolymers.

This study investigated the effect of polymer blending of microbially produced poly[(R)-lactate-co-(R)-3-hydroxybutyrate] copolymers (LAHB) with poly(lactate) (PLA) on their mechanical, thermal, and biodegradable properties. Blending of high lactate (LA) content and high molecular weight LAHB significantly improved the tensile elongation of PLA up to more than 250 % at optimal LAHB composition of 20-30 wt%. Temperature-modulated differential scanning calorimetry and dynamic mechanical analysis revealed that PLA and LAHB were immiscible but interacted with each other, as indicated by the mutual plasticization effect. Detailed morphological characterization using scanning probe microscopy, small-angle X-ray scattering, and solid-state NMR confirmed that PLA and LAHB formed a two-phase structure with a characteristic length scale as small as 20 nm. Because of mixing in this order, the polymer blends were optically transparent. The biological oxygen demand test of the polymer blends in seawater indicated an enhancement of PLA biodegradation during biodegradation of the polymer blends.

Hepatocellular Carcinoma Showing Tumor Shrinkage Due to an Abscopal Effect.

We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.

A case of hepatocellular carcinoma with pseudoaneurysm formation upon lenvatinib administration.

A 79-year-old man received treatment for multiple intrahepatic hepatocellular carcinoma with atezolizumab + bevacizumab. However, he developed lower back pain attributed to spinal metastases upon tumor enlargement; thus, he was admitted to our hospital for a change from atezolizumab + bevacizumab to lenvatinib and radiation therapy for the spinal metastases. On the 11th day after starting lenvatinib treatment, a pulsatile aneurysm appeared in the tumor, detected using abdominal ultrasonography Micro B-flow imaging, which visualized blood flow at a high frame rate; this was diagnosed as a pseudoaneurysm. The patient refused treatment for the pseudoaneurysm; therefore, he was carefully followed up. Fortunately, the pseudoaneurysm disappeared on the 17th day. One month later, the tumor had become completely necrotic. Lenvatinib demonstrated effectiveness in inhibiting angiogenesis in the tumor, as evidenced by a decrease in tumor blood flow. This case report suggests that pseudoaneurysm formation within the tumor occurs early after the administration of lenvatinib; thus, clinicians must be aware of the potential risk of pseudoaneurysm rupture.

Diagnostic accuracy of ultrasound-derived fat fraction for the detection and quantification of hepatic steatosis in patients with liver biopsy.

PURPOSE: This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard. METHODS: Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections. The UDFF cutoff values for histologically proven steatosis grades were determined using the area under the receiver operating characteristic curve (AUROC). RESULTS: The median age of the patients was 66 (interquartile range 54-74) years, and 33 (45%) were females. The UDFF values showed a stepwise increase with increasing steatosis grade (p < .001) and were strongly correlated with the histological fat content (r = .7736, p < .001). The Bland-Altman plot revealed a mean bias of 2.384% (95% limit of agreement, - 6.582 to 11.351%) between them. Univariate regression analysis revealed no significant predictors of divergence. The AUROCs for distinguishing steatosis grades of ≥ 1, ≥2, and 3 were 0.956 (95% confidence interval [CI], 0.910-1.00), 0.926 (95% CI, 0.860-0.993), and 0.971 (95% CI, 0.929-1.000), respectively. The UDFF cutoff value of > 6% had a sensitivity and specificity of 94.8% and 82.3%, respectively, for diagnosing steatosis grade ≥ 1. There was no association between UDFF and the fibrosis stage. CONCLUSION: UDFF shows strong agreement with the histological fat content and excellent diagnostic accuracy for grading steatosis. UDFF is a promising tool for detecting and quantifying hepatic steatosis in clinical practice.

Complete sequence randomness of lactate-based copolymers (LAHBs) with varied lactate monomer fractions employing a series of propionyl-CoA transferases.

Previously, we biosynthesized an evolved version of a bio-based polylactide (PLA) on microbial platforms using our engineered lactate-polymerizing enzyme (LPE). This lactate (LA)-based copolyester, LAHB, has advantages over PLA, including improved flexibility and biodegradability, and its properties can be regulated through the LA fraction. To expand the LA-incorporation capacity and improve polymer properties, in the state of in vivo LAHB production, propionyl-CoA transferases (PCTs) that exhibited enhanced production of LA-CoA than the conventional PCTs were selected. Here, the present study has demonstrated that the LA fraction of LAHB could be altered using various PCTs. Enhanced PCT performance was achieved by balancing polymer production and cell growth. Both events are governed by the use of acetyl-CoA, a commonly shared key metabolite. This could be attributed to the different reactivities of individual PCTs towards acetyl-CoA, which serves both as a CoA donor and a leading compound in the TCA cycle. Interestingly, we found complete sequence randomness in the LAHB copolymers, independent of the LA fraction. The mechanism of LA fraction-independent sequence randomness is discussed. This new PCT-based strategy synergistically combines with the evolution of LPE to advance the LAHB project, and enables us to perform advanced applications other than LAHB production utilizing CoA-linked substrates.

Pseudo-Wet Plasma Mechanism Enabling High-Throughput Dry Etching of SiO2 by Cryogenic-Assisted Surface Reactions.

Manufacturing semiconductor devices requires advanced patterning technologies, including reactive ion etching (RIE) based on the synergistic interactions between ions and etch gas. However, these interactions weaken as devices continuously scale down to sub-nanoscale, primarily attributed to the diminished transport of radicals and ions into the small features. This leads to a significant decrease in etch rate (ER). Here, a novel synergistic interaction involving ions, surface-adsorbed chemistries, and materials at cryogenic temperatures is found to exhibit a significant increase in the ER of SiO2 using CF4/H2 plasmas. The ER increases twofold when plasma with H2/(CF4 + H2) = 33% is used and the substrate temperature is lowered from 20 to -60 °C. The adsorption of HF and H2O on the SiO2 surface at cryogenic temperatures is confirmed using in situ Fourier transform infrared spectroscopy. The synergistic interactions of the surface-adsorbed HF/H2O as etching catalysts and plasma species result in the ER enhancement. Therefore, a mechanism called "pseudo-wet plasma etching" is proposed to explain the cryogenic etching process. This synergy demonstrates that the enhanced etch process is determined by the surface interactions between ions, surface-adsorbed chemistry, and the material being etched, rather than interactions between ion and gas phase, as observed in the conventional RIE.