Metabolic Tug-of-War between Glycolysis and Translation Revealed by Biochemical Reconstitution.

Inside cells, various biological systems work cooperatively for homeostasis and self-replication. These systems do not work independently as they compete for shared elements like ATP and NADH. However, it has been believed that such competition is not a problem in codependent biological systems such as the energy-supplying glycolysis and the energy-consuming translation system. In this study, we biochemically reconstituted the coupling system of glycolysis and translation using purified elements and found that the competition for ATP between glycolysis and protein synthesis interferes with their coupling. Both experiments and simulations revealed that this interference is derived from a metabolic tug-of-war between glycolysis and translation based on their reaction rates, which changes the threshold of the initial substrate concentration for the success coupling. By the metabolic tug-of-war, translation energized by strong glycolysis is facilitated by an exogenous ATPase, which normally inhibits translation. These findings provide chemical insights into the mechanism of competition among biological systems in living cells and provide a framework for the construction of synthetic metabolism in vitro.

MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

BACKGROUND: We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS: The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS: Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS: The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

Efficacy of antiviral therapy for the prevention of mother-to-child transmission of hepatitis B virus and the risk of postpartum hepatitis flare after discontinuation of antiviral therapy.

The use of nucleos(t)ide analogs (NAs) is recommended for mothers with a high viral load of hepatitis B virus (HBV) during the second or third trimester of pregnancy. However, postpartum hepatitis flares can occur in some cases. We examined the efficacy of NA administration for the prevention of mother-to-child transmission of hepatitis B virus, and evaluated the risk of postpartum hepatitis flares in mothers after NA discontinuation. Nine pregnant women with a high viral load (HBV DNA ≥5.3 log IU/mL) received tenofovir disoproxil fumarate (TDF) at approximately 28 weeks of gestation, and TDF was discontinued at 4-10 weeks after delivery. We evaluated the virological and biochemical parameters in mothers after TDF discontinuation. Hepatitis flares in mothers were defined as alanine transaminase level ≥60 U/L. None of the infants developed any congenital anomaly or acquired HBV infection during infancy. Hepatitis flares occurred within 6 months after TDF discontinuation in five of seven cases, whereas two cases were lost to follow-up. Furthermore, three cases required the resumption of NA use. NA administration was highly effective against mother-to-child-transmission of HBV in pregnant women with high HBV DNA levels. However, hepatitis flares were commonly observed after NA discontinuation in the postpartum period. Patients should be followed up carefully after NA discontinuation, and NA resumption should be considered based on a comprehensive assessment of virological and biochemical parameters.

Serum angiopoietin-2 levels predict the development of hepatocellular carcinoma following hepatitis C virus eradication using direct-acting antiviral agents.

INTRODUCTION: Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. METHODS: We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥ 2.0 C.O.I. RESULTS: Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; P = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥ 3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥ 2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, P < 0.001). CONCLUSIONS: At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.

Prognostic nutritional index after introduction of atezolizumab with bevacizumab predicts prognosis in advanced hepatocellular carcinoma: A multicenter study.

INTRODUCTION: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. METHODS: One hundred twenty-five HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. RESULTS: During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, P = 0.008 for OS; 12.7 vs. 8.4 months, P = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. CONCLUSIONS: PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy.

Adult-onset Type II Citrullinemia Developed under Dietary Restrictions during Imprisonment.

A 29-year-old man presented with liver damage, and a liver biopsy was performed, but the cause was unclear. Thereafter, he was referred to our hospital. We found that he had been unable to consume carbohydrates in his diet and preferred fried chicken since childhood. In addition, he had shown disturbance of consciousness and abnormal behavior while he had been in prison, where dietary intake had been restricted. A plasma amino acid analysis revealed hypercitrullinemia. Therefore, we suspected adult-onset type II citrullinemia (CTLN2). Genetic testing showed pathologic variations in the SLC25A13 gene, which allowed us to make a definite diagnosis of CTLN2.

Serum inducible protein 10 kDa/C-X-C motif chemokine 10 levels predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

AIM: It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. METHODS: The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively. RESULTS: Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. CONCLUSIONS: Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Multimolecular Competition Effect as a Modulator of Protein Localization and Biochemical Networks in Cell-Size Space.

Cells are small, closed spaces filled with various types of macromolecules. Although it is shown that the characteristics of biochemical reactions in vitro are quite different from those in living cells, the role of the co-existence of various macromolecules in cell-size space remains still elusive. Here, using a constructive approach, it is demonstrated that the co-existence of various macromolecules themselves has the ability to tune protein localization for spatiotemporal regulation and a biochemical reaction system in a cell-size space. Both experimental and theoretical analyses reveal that enhancement of interfacial effects by a large surface-area-to-volume ratio facilitates membrane localization of molecules in the cell-size space, and the interfacial effects are alleviated by competitive binding to lipid membranes among multiple proteins even if their membrane affinities are weak. These results indicate that competition for membrane binding among various macromolecules in the cell-size space plays a role in regulating the spatiotemporal molecular organization and biochemical reaction networks. These findings shed light on the importance of surrounding molecules for biochemical reactions using purified elements in small spaces.

Serum CXCL10 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced BCLC stage C hepatocellular carcinoma: A multicenter analysis.

BACKGROUND & AIMS: Relationships of serum C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) levels with hot immune features have been reported in patients with hepatocellular carcinoma (HCC). Therefore, we examined the utility of their levels for predicting the efficacy of atezolizumab plus bevacizumab (Atez/Bev) in patients with HCC. DESIGN: In total, 98 patients with HCC treated with Atez/Bev were enrolled, and their initial responses were evaluated at least once via dynamic computed tomography or magnetic resonance imaging. Serum CCL5 and CXCL10 levels were assessed by enzyme-linked immunosorbent assay before treatment and at the start of the second course of Atez/Bev therapy, and their relationships with treatment efficacy were determined. RESULTS: No analyzed factor was associated with the initial therapeutic response. Among the 56 patients with Barcelona Clinic Liver Cancer (BCLC) stage C, serum CXCL10 levels at the beginning of course two (CXCL10-2c) tended to be higher in responders than in non-responders in the initial evaluation, and its optimal cutoff level of 690 pg/mL could be used to stratify patients regarding overall survival (OS; high vs. low: not reached vs. 17.6 months, p = 0.034) and progression-free survival (high vs. low: 13.6 vs. 5.1 months, p = 0.014). In multivariate analysis, high CXCL10 levels and neutrophil-to-lymphocyte ratios at the start of course two and Child-Pugh stage A at baseline were independent predictive factors of improved OS. CONCLUSIONS: Serum CXCL10-2c levels were predictive of Atez/Bev efficacy in patients with BCLC stage C HCC.

Kinetics of HBcrAg and HBsAg using highly sensitive iTACT assays in chronic hepatitis B patients with HBsAg seroclearance.

Two novel assays have been developed, iTACT-hepatitis B core-related antigen (iTACT-HBcrAg) and iTACT-hepatitis B surface antigen (iTACT-HBsAg) assays. We investigated the longitudinal profiles of iTACT-HBcrAg- and -HBsAg in patients with HBsAg seroclearance (SC) (<0.05 IU/mL). This study comprises 60 HBV-infected patients with HBsAg SC, 27 in chronic hepatitis/liver cirrhosis (CH/LC) group and 33 in inactive carrier (IC) group. Longitudinal profiles of iTACT-HBcrAg and -HBsAg were examined using stored serum samples. The median period from HBsAg SC to iTACT-HBcrAg loss or to the last observation was longer in the CH/LC group than the IC group (39 vs. -3 months, p = 0.004), but this tendency was not observed in that by iTACT-HBsAg. Comparing the times of iTACT-HBcrAg and -HBsAg loss, the rate of patients who lost HBcrAg first was significantly higher in the IC group (p = 0.008). The cumulative incidence rate of iTACT-HBcrAg loss after HBsAg SC was higher in the IC group that the CH/LC group (p = 0.002). Patients in the CH/LC group had higher rates of detectable iTACT-HBcrAg than those in the IC group after HBsAg SC, suggesting that the presence of HBcrAg possibly contribute to the progression of chronic hepatitis B.

Safety and Feasibility of Tele-Cardiac Rehabilitation Using Remote Biological Signal Monitoring System: A Pilot Study.

Background: Cardiac rehabilitation (CR) is categorized as a class I recommendation in the guidelines for the management of patients with cardiovascular disease (CVD). However, the penetration rate of outpatient CR is low in Japan. We designed a pilot study to evaluate the safety and feasibility of tele-CR using a remote biological signal monitoring system. Methods: A total of nine patients (median aged 70.0 (66.0 - 76.0) years (male = 6) with CVD who participated in phase II CR for 1 month under the exercise prescription using the cardiopulmonary exercise test (CPET) were analyzed. They participated in the tele-CR program with a remote biological signal monitoring system (Nipro HeartLineTM, Osaka, Japan, and Duranta, Miyagi, Japan) in the CR room and were instructed by the CR staff from a separate room in the hospital. We evaluated the occurrence and degree of remote biological signal monitoring defects as safety evaluation items, i.e., whether the patients could set the remote biological signal monitoring equipment, as a feasibility evaluation item during a 3-month period. We also performed CPET at the baseline and follow-up. Following the 3-month tele-CR program, a total of 122 remote CR programs were performed using the remote biological signal monitoring system. Results: No patient experienced a lack of remote biological signal monitoring during exercise therapy. Significant improvement was noted in the exercise capacity, as assessed using the cardiopulmonary test (from 19.5 (16.7 - 20.2) mL/kg/min to 21.1 (17.3 - 22.8) mL/kg/min, P = 0.01, age ratio from 86% (75-96%) to 99% (78-104%), P = 0.01). One patient required support using the remote biological signal monitoring system, including information technology literacy. Conclusions: This study suggests the safety and feasibility of tele-CR using the remote biological signal monitoring system. However, further investigations are required to explore the suitability, effects, and cost-effectiveness of tele-CR as an alternative to center-based CR in the future.

Phase-Separated Giant Liposomes for Stable Elevation of α-Hemolysin Concentration in Lipid Membranes.

Staphylococcus aureus α-hemolysin (αHL) is one of the most popular proteins in nanopore experiments within lipid membranes. Higher concentrations of αHL within the lipid membrane are desirable to enhance the mass transport capacity through nanopores. However, the reconstitution of αHL at high concentrations is associated with the problem of membrane lytic disruption. In this study, we present a method that effectively increases αHL concentration while maintaining membrane stability. This method is achieved by using phase-separated giant liposomes, where coexisting liquid-disordered (Ld) and liquid-ordered phases (Lo) are enriched in unsaturated lipids and saturated lipids with cholesterol (Chol), respectively. Fluorescence observation of αHL in liposomes revealed that the presence of Chol facilitates αHL insertion into the membrane. Despite the preferential localization of αHL in the Ld phase rather than the Lo phase, the coexistence of both Lo and Ld phases prevents membrane disruption in the presence of concentrated αHL. We have explained this stabilization mechanism considering the lower membrane tension exhibited by phase-separated liposomes compared to homogeneous liposomes. Under hypertonic conditions, we have successfully increased the local concentration of αHL by invagination of the lipid-only region in the Ld phase, leaving αHL behind. This method exhibits potential for the reconstitution of various nanochannels and membrane proteins that prefer the Ld phase over the Lo phase, thus enabling the production of giant liposomes at high concentrations and the replication of the membrane-crowding condition observed in cells.

The importance of psychosocial support in youth dilated cardiomyopathy patient who underwent cardiac rehabilitation.

Poor health-related quality of life (HR-QOL) and anxiety status in younger patients living with heart failure and dilated cardiomyopathy (DCM) may be caused by the illness itself or the numerous life events that traditionally occur earlier in life, such as establishing a career, meaningful relationships, family, and financial security. The present case involved a 26-year-old man diagnosed with DCM who participated in an outpatient cardiac rehabilitation (CR) program once a week. No cardiovascular events were observed during CR. At follow-up after 12 months, exercise tolerance improved from 18.4 to 24.9 mL/kg/min. Regarding HR-QOL, the Short-Form Health Survey showed that only general health, social function, and physical component summary were improved during follow-up. However, other components showed no significant increasing trend. The State-Trait Anxiety Inventory showed a better improvement in trait anxiety (from 59 to 54 points) than state anxiety (from 46 to 45 points). For young patients with DCM, it is crucial to consider not only physical status but also psychosocial status even with improved exercise tolerance. Learning objective: Younger adults with dilated cardiomyopathy (DCM) had strikingly worse health-related quality of life with both the emotional and physical components of the scale. Beyond physical symptoms alone, living with heart failure and DCM at a younger age negatively impacts role fulfillment, autonomy, perception, and psychological well-being. Cardiac rehabilitation (CR) comprised medical evaluation of patients, exercise therapy, education for secondary prevention, and support for psychosocial factors including counseling and cognitive-behavioral therapy. Therefore, early detection of the psychosocial problem and providing further support by participating in CR is important.

Nutritional Status in Patients Undergoing Phase II Cardiac Rehabilitation by Mini Nutritional Assessment.

Background: Malnutrition impairs quality of life and prognosis of patients with cardiovascular disease. The Mini Nutritional Assessment (MNA) is a screening tool developed for the nutritional assessment of older adults. However, usefulness of MNA for patients undergoing cardiac rehabilitation (CR) has not been fully investigated. Methods: From March 2017 to September 2019, the MNA-short form (MNA-SF) and the MNA total score in patients undergoing phase II CR at the Juntendo University Hospital were evaluated. Results: A total of 336 patients (mean age 70.1 ± 11.4 years; males: 209) were analyzed. In the MNA-SF, 157 patients (47%) were found to be malnourished or at risk of malnutrition. In MNA total score, 168 patients (50%) were found to be malnourished or at risk of malnutrition. The MNA-SF < 12 group had significantly lower body mass index (BMI), hemoglobin level, low MNA scores for protein/water intake, self-evaluation of nutrition and health, and upper arm and calf circumferences compared to the MNA-SF ≥ 12 group. Assuming BMI < 18.5 as malnutrition, the sensitivity and specificity for malnutrition were 100% and 58.9% for MNA-SF, and 96.9% and 54.9% for MNA total score, respectively. Conclusions: MNA is useful in screening for malnutrition in patients undergoing CR. Approximately 50% of them were determined to be malnourished or at risk of malnutrition, suggesting the need for detailed evaluation regarding their food intake and dietary intervention.

Insertion and deletion mutations preserved in SARS-CoV-2 variants.

The insertion/deletion (indel) mutation profiles of SARS-CoV-2 variants, including Omicron, remain unclear. We compared whole-genome sequences from various lineages and used preserved indels to infer the ancestral relationships between different lineages. Thirteen indel patterns from twelve sites were seen in ≥ 2 sequences; six of these sites were located in the N-terminal domain of the viral spike gene. Preserved indels in the coding regions were also identified in the non-structural protein 3 (Nsp3), Nsp6, and nucleocapsid genes. Seven of the thirteen indel patterns were specific to the Omicron variants, four of which were observed in BA.1, making it the most mutated variant. Other preserved indels observed in the Omicron variants were also seen in Alpha and/or Gamma, but not Delta, suggesting that Omicron is phylogenetically more proximal to Alpha. We demonstrated distinct profiles of preserved indels among SARS-CoV-2 variants and sublineages, suggesting the importance of indels in viral evolution.

Trinucleotide Substitutions at Two Locations in the SARS-CoV-2 Nucleocapsid (N) Gene.

The genomes of sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), incorporate mutations with short sequence exchanges based on unknown processes. Currently, the presence of such short-sequence exchanges among the genomes of different SARS-CoV-2 lineages remains uncertain. In the present study, multiple SARS-CoV-2 genome sequences from different clades or sublineages were collected from an international mass sequence database and compared to identify the presence of short sequence exchanges. Initial screening with multiple sequence alignments identified two locations with trinucleotide substitutions, both in the nucleocapsid (N) gene. The first exchange from 5'-GAT-3' to 5'-CTA-3' at nucleotide positions 28,280-28,282 resulted in a change in the amino acid from aspartic acid (D) to leucine (L), which was predominant in clade GRY (Alpha). The second exchange from 5'-GGG-3' to 5'-AAC-3' at nucleotide positions 28,881-28,883 resulted in an amino acid change from arginine and glycine (RG) to lysine and arginine (KR), which was predominant in GR (Gamma), GRY (Alpha), and GRA (Omicron). Both trinucleotide substitutions occurred before June 2020. The sequence identity rate between these lineages suggests that coincidental succession of single-nucleotide substitutions is unlikely. Basic local alignment search tool sequence search revealed the absence of intermediating mutations based on single-base substitutions or overlapping indels before the emergence of these trinucleotide substitutions. These findings suggest that trinucleotide substitutions could have developed via an en bloc exchange. In summary, trinucleotide substitutions at two locations in the SARS-CoV-2 N gene were identified. This mutation may provide insights into the evolution of SARS-CoV-2.

The neutrophil-to-lymphocyte ratio at the start of the second course during atezolizumab plus bevacizumab therapy predicts therapeutic efficacy in patients with advanced hepatocellular carcinoma: A multicenter analysis.

AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is expected to have good therapeutic efficacy for patients with advanced hepatocellular carcinoma (HCC). However, the clinical indicators that predict therapeutic efficacy have not been established. We retrospectively investigated whether the neutrophil-to-lymphocyte ratio (NLR) during Atez/Bev therapy could predict therapeutic efficacy. METHOD: In total, 110 patients with HCC were enrolled; they were treated with Atez/Bev therapy and evaluated for their initial response by dynamic CT or MRI at least once between October 2020 and July 2022. RESULTS: Of the 110 patients with HCC at the initial evaluation, two (2%) showed a complete response (CR), 22 (20%) partial response (PR), 62 (56%) stable disease (SD), and 24 (21%) progressive disease (PD). The NLR at the start of the second course (NLR-2c) increased from CR + PR to SD to PD. There was no significant association between the baseline NLR and the initial therapeutic response. Patients with CR + PR had lower NLR-2c values than those with SD + PD (p < 0.001) and the optimal cut-off value of NLR-2c was 1.97. Patients with NLR-2c <1.97 had better overall survival and progression-free survival (PFS) than those with NLR-2c ≥1.97 (p = 0.005 for overall survival; p < 0.001 for PFS). A multivariate analysis showed that female sex, higher PIVKA-II levels at baseline, and higher values of NLR-2c were significantly associated with poorer PFS. CONCLUSIONS: The NLR-2c value predicts the initial therapeutic response and prognosis of patients with HCC treated with Atez/Bev therapy.

Evaluation of Lung and Liver Tumor Dose Coverage Treated With the CyberKnife Synchrony System With Consideration of Measured Tracking Errors.

BACKGROUND/AIM: Lung and liver tumor dose coverage was evaluated for the CyberKnife synchrony respiratory tracking system (SRTS) with consideration of the motion tracking accuracy measured for motion patterns of individual patients. PATIENTS AND METHODS: Seven treatment plans of six cases treated with the SRTS were evaluated. The motion phantom was moved with the motion data derived from the treatment log files. A laser emitted from the linac head to the moving phantom block was recorded with a webcam, and the tracking accuracy was evaluated. The dose volume histogram (DVH) of planning target volume (PTV) and gross tumor volume (GTV) were calculated by a pencil beam algorithm with shifting the beams with Gaussian random numbers mimicking the measured tracking errors. RESULTS: The tracking errors measured with the motion phantom in the lateral direction were within ±2 mm for 90% of beam-on time. The tracking errors in the longitudinal direction were within ±3.0 mm and ±1.1 mm for 90% and 50% of beam-on time, respectively. Although one case showed a decrease in the dose covering 95% of PTV (D95%) by 1.8%, the change in the dose covering 99% of GTV (D99%) was within 1%. CONCLUSION: This study evaluated the motion tracking errors of the SRTS by a motion phantom moved with the patients' respiration signal, and the impact of the tracking errors on the target coverage was calculated. Even for respiratory patterns with large maximum tracking errors, sufficient GTV coverage is achievable if the beam is accurately delivered for high percentage of beam-on time.

Outcome of nucleos(t)ide analog cessation in patients with treatment for prevention of or against hepatitis B virus reactivation.

AIM: We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after cessation of the NA. METHODS: We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria. RESULTS: A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients. CONCLUSIONS: We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non-hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.

Efficacy of minocycline hydrochloride aspiration sclerotherapy with additional monoethanolamine oleate aspiration sclerotherapy for symptomatic hepatic cysts.

AIM: Minocycline hydrochloride (MINO) aspiration sclerotherapy (AS) has been widely used for treating hepatic cysts (HC). However, cyst recurrence remains problematic. Information on monoethanolamine oleate (EO) AS, another effective HC treatment, is currently limited. We investigated the efficacy of EO on ineffective MINO treatments, and the relationship between MINO AS and cyst fluid pH. METHODS: A total of 22 cases with symptomatic HC underwent AS with 500 mg of MINO from January 2016 to June 2021. Cyst fluid pH was measured before and after MINO injection. Cyst volume ratio (CVR, %) after 2 weeks was calculated as follows:cyst volume 2 weeks after MINO injection / pre-treatment cyst volume × 100. Treatment was completed if CVR after 2 weeks was ≤35% (MINO-group). For patients with CVR >35%, 2 g of EO was added (MINO/EO-group). Cyst volume ratio was measured every 12 months thereafter. RESULTS: There were no recurrence symptoms in any of the patients during follow-up. Of the 22 cases, 21 had CVR ≤20% after 12 months. The MINO/EO-group (n = 8) tended to have smaller CVRs after 12 months than the MINO-group (n = 14). Cyst volume ratio after 2 weeks was correlated to pH change (p = 0.012) and was larger in patients whose pH decreased by <1.5 (p = 0.015). All adverse events were mild, including in elderly patients. CONCLUSION: Adding EO is an effective and safe treatment for symptomatic HC when MINO AS alone is insufficient. Patients with pH decreases of <1.5 should be considered for additional EO treatment.