Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases.

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.

Epidemiology of postoperative bleeding after endoscopic nasal and sinus surgery and factors associated with bleeding.

PURPOSE: Endoscopic nasal and sinus surgery is a surgical procedure frequently performed by otolaryngologists. Postoperative bleeding is detrimental to both healthcare providers and patients. We investigated the epidemiology of postoperative bleeding during endoscopic nasal and sinus surgery and explored possible bleeding triggers. METHODS: We evaluated the patients who underwent endoscopic nasal and sinus surgery. Data regarding the age, sex, presence of hypertension, and abnormal coagulability, including oral anticoagulants, diagnoses, operative procedures, intraoperative use of drills and blood loss, and postoperative antimicrobial administration of eligible patients, were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and eighty-six patients underwent endoscopic nasal or sinus surgery during the study period, and postoperative bleeding occurred in 9 patients (4.8%). Posterior nasal neurotomy (PNN) was the procedure most likely to cause postoperative bleeding (4 surgeries, 13.3%). Postoperative antimicrobial administration significantly reduced the incidence of postoperative bleeding (p = 0.04). CONCLUSIONS: Postoperative bleeding requiring intervention occurs in 4.8% of cases, and PNN is associated with a high risk of postoperative bleeding. Wound infection is a potential cause of postoperative bleeding, and antimicrobial administration should be considered in addition to local treatment.

Propriety of various examinations for subjective symptoms of olfactory disorders.

PURPOSE: In Japan, two types of tests for diagnosing olfactory disorders, T and T (T&T) olfactometry and intravenous olfactory tests, are covered by insurance and performed on patients with olfactory disorders. This study examined the validity of these olfactory tests and whether psychophysical or morphological tests are more helpful in evaluating olfactory disorders. METHODS: We evaluated patients who visited our department and underwent two types of olfaction tests and sinus computed tomography (CT). Data regarding the age, sex, peripheral blood eosinophil percentage, presence of bronchial asthma, diagnoses, olfactory symptom score, results of the two olfactory tests, and CT findings in eligible patients were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and sixty-three patients underwent all tests during the study period. The results of the T&T olfactometry and intravenous olfactory tests were significantly correlated. However, only the results of T&T olfactometry and olfactory cleft opacification on CT were statistically significant predictors of the olfactory symptom scores. CONCLUSION: T&T olfactometry and CT evaluations of olfactory cleft opacification helped evaluate olfactory dysfunction. It is important to note that intravenous olfactory tests are best performed with careful control and not blindly to assess olfactory disorders.

Dosimetric impact of the respiratory motion of the liver dome in stereotactic body radiotherapy for spine metastasis: A planning study.

PURPOSE: This study aimed to clarify the dosimetric impact of the respiratory motion of the liver on stereotactic body radiation therapy (SBRT) for spine metastasis and examine the utility of introducing beam avoidance (beam-off at specific gantry angles). METHODS: A total of 112 consecutive patients who underwent SBRT for spine metastasis between 2018 and 2024 were examined. Overall, 15 patients who had lesions near the liver dome were included in this study. Retrospective treatment plans were generated using computed tomography (CT) images acquired during inhalation and exhalation to evaluate the dosimetric impact of respiratory motion of the liver. The dose difference (DD) and relative value (DD%) were evaluated using the dose-volume histogram (DVH) metrics, planning target volume Dmax, D95%, spinal cord D0.035 cc, and esophagus D2.5 cc. The magnitude of the liver movements was evaluated based on differences of liver size Lave at the isocentric axial plane between the inspiratory and expiratory CT images. RESULTS: The DD in almost all DVH metrics tended to increase when the liver moved away from the target during inhalation: For example, Mean ± $ \pm $ a standard deviation (SD) DD in PTV D95% for the treatment plan incorporating beam avoidance and those without beam avoidance was 0.5 ± $\pm$ 0.3 and 0.9 ± $ \pm $ 0.6 Gy, respectively. The spinal cord D0.035 cc for those shows 0.4 ± $ \pm $ 0.2 and 0.7 ± $ \pm $ 0.7 Gy, respectively. The treatment plans without beam avoidance also showed moderate or strong correlations between Lave and DD for almost all DVH metrics. No correlation was seen in the beam avoidance plan. The spinal cord D0.035 cc revealed approximately 1 Gy or +4% in DD when Lave was < -4 cm. CONCLUSIONS: Respiratory motion of the liver dome can cause substantial dosimetric discrepancies in the dose delivered to the spinal cord, although the extent depends on patient variables. Dose assessment should be performed for determining the appropriate means of respiratory management, such as breath-hold. Alternatively, beam avoidance effectively mitigates the impact.

Long-term Consequences on Soil Fungal Community Structure: Monoculture Planting and Natural Regeneration.

Understanding the regeneration and succession of belowground communities, particularly in forests, is vital for maintaining ecosystem health. Despite its importance, there is limited knowledge regarding how fungal communities change over time during ecosystem development, especially under different forest restoration strategies. In this study, we focused on two restoration methods used in northern Japan: monoculture planting and natural regeneration. We examined the responses of the fungal community to monoculture plantations (active tree planting) and naturally regenerated (passive regeneration) forests over a 50-year chronosequence, using natural forests as a reference. Based on DNA metabarcoding, we assessed the richness of fungal Operational Taxonomic Units (OTUs) and their dissimilarity. Our findings revealed that soil fungal richness remained stable after natural regeneration but declined in monoculture plantations, from 354 to 247 OTUs. While the compositional dissimilarity of fungal assemblages between monoculture plantations and natural forests remained consistent regardless of the time since tree planting, it significantly decreased after natural regeneration, suggesting recovery to a state close to the reference level. Notably, the composition of key functional fungal groups-saprotrophic and ectomycorrhizal- has increasingly mirrored that of natural forests over time following passive natural regeneration. In summary, our study suggests that monoculture plantations may not be effective for long-term ecosystem function and service recovery because of their limited support for soil fungal diversity. These results underscore the importance of natural regeneration in forest restoration and management strategies.

Subclonal accumulation of immune escape mechanisms in microsatellite instability-high colorectal cancers.

BACKGROUND: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH. METHODS: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed. RESULTS: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment. CONCLUSIONS: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.

Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.

BACKGROUND: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity. METHODS: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39-77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability. RESULTS: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of 'Val Leu Ile degradation pathway'. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival. CONCLUSIONS: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.

Impact of right ventricular reserve on exercise capacity and quality of life in patients with left ventricular assist device.

Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (V̇o2) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median ΔRVSWI (change from rest to peak exercise). Patients with lower ΔRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/dt than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD (r = 0.59, P = 0.003) and peak V̇o2 (r = 0.56, P = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS (r = 0.44, P = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD (r = -0.34, P = 0.88), peak V̇o2 (r = 0.074, P = 0.74), or EQ-VAS (r = 0.127, P = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD.NEW & NOTEWORTHY The change in right ventricular stroke work index (RVSWI) during exercise, not RVSWI at rest, was associated with exercise capacity and HRQoL. Our findings suggest that the assessment of change in RVSWI during exercise as a surrogate of RV reserve function may aid in risk stratification of patients with LVAD.

Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). METHODS: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. RESULTS: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). CONCLUSION: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 days after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e. proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

Liver stiffness assessed by magnetic resonance elastography predicts clinical outcomes in patients with heart failure and without chronic liver disease.

OBJECTIVES: Evaluation of liver stiffness (LS) by magnetic resonance elastography (MRE) is useful for estimating right atrial pressure (RAP) in patients with heart failure (HF). However, its prognostic implications are unclear. We sought to investigate whether LS measured by MRE (LS-MRE) could predict clinical outcomes in patients with HF. METHODS: We prospectively examined 207 consecutive HF patients between April 2018 and May 2021 after excluding those with organic liver disease. All patients underwent 3.0-T MRE. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF. RESULTS: During a median follow-up period of 720 (interquartile range [IQR] 434-1013) days, the primary outcome occurred in 44 patients (21%), including 15 (7%) all-cause deaths and 29 (14%) hospitalisations for HF. The patients were divided into two groups according to median LS-MRE of 2.54 (IQR 2.34-2.82) kPa. Patients with higher LS-MRE showed a higher incidence of the primary outcome compared to those with lower LS-MRE (p < 0.001). Multivariable Cox regression analyses revealed that LS-MRE value was independently associated with the risk of adverse events (hazard ratio 2.49, 95% confidence interval 1.46-4.24). In multivariable linear regression, RAP showed a stronger correlation with LS-MRE (ß coefficient = 0.31, p < 0.001) compared to markers related to liver fibrosis. CONCLUSIONS: In patients without chronic liver disease and presenting with HF, elevated LS-MRE was independently associated with worse clinical outcomes. Elevated LS-MRE may be useful for risk stratification in patients with HF and without chronic liver disease. KEY POINTS: • Magnetic resonance elastography (MRE) is an emerging non-invasive imaging technique for evaluating liver stiffness (LS) which can estimate right atrial pressure. • Elevated LS-MRE, which mainly reflects liver congestion, was independently associated with worse clinical outcomes in patients with heart failure. • The assessment of LS-MRE would be useful for stratifying the risk of adverse events in heart failure patients without chronic liver disease.

Differences in blood flow dynamics between balloon- and self-expandable valves in patients with aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR). METHODS: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR. RESULTS: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups. CONCLUSIONS: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Risk Stratification of Patients with Marginal Hepatic Functional Reserve Using the Remnant Hepatocyte Uptake Index in Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for Safe Liver Surgery.

BACKGROUND: This study aimed to explore the efficacy of gadoxetic acid-enhanced (Gd-EOB) magnetic resonance imaging (MRI) in surgical risk estimation among patients with marginal hepatic function estimated by indocyanine green (ICG) clearance test. METHODS: This analysis focused on 120 patients with marginal hepatic functional reserve (ICG clearance rate of future liver remnant [ICG-Krem] < 0.10). Preoperative Gd-EOB MRI was retrospectively reviewed, and the remnant hepatocyte uptake index (rHUI) was calculated for quantitative measurement of liver function. The predictive power of rHUI for posthepatectomy liver failure was compared with several clinical measures used in current risk estimation before hepatectomy. RESULTS: Receiver operating curve analysis showed that rHUI had the best predictive power for posthepatectomy liver failure among the tested variables (ICG-R15, ICG-Krem, albumin + bilirubin score, and albumin + ICG-R15 score). Cross-validation showed that a threshold of 925 could be the best cut-off value for estimating the postoperative risk of liver failure with sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 0.689, 0.884, 5.94, and 0.352, respectively. CONCLUSION: rHUI could be a sensitive substitute measure for posthepatectomy liver failure risk estimation among patients with marginal hepatic functional reserve.

Fragmented QRS on 12-lead electrocardiogram predicts long-term prognosis in patients with cardiac sarcoidosis.

Fragmented QRS (fQRS) on a 12-lead electrocardiogram is a known marker of fatal arrhythmias or cardiac adverse events in ischemic and non-ischemic cardiomyopathy patients. Nonetheless, the association between fQRS and clinical outcomes in patients with cardiac sarcoidosis (CS) remains unclear. Herein, we investigated whether fQRS is associated with long-term clinical outcomes in CS patients. A total of 78 patients who received immunosuppressive therapy (IST) for clinically diagnosed CS were retrospectively examined. Patients were classified into two groups according to the presence (n = 19) or absence (n = 59) of fQRS on electrocardiogram before IST. The primary outcome was the composite event of all-cause death, ventricular tachyarrhythmias (VTs), and hospitalization for heart failure. Results of late gadolinium enhancement on cardiac magnetic resonance imaging were also analyzed. During a median follow-up period of 3.7 years (interquartile range: 1.6-6.2 years), the primary outcome occurred more frequently in patients with fQRS than in those without (47% vs. 13%, log-rank p = 0.002). Multivariable Cox regression analyses showed that fQRS was an independent determinant of the primary outcome. The incidence of VTs, within 12 months of IST initiation, was comparable between the two groups; however, late-onset VTs, defined as those occurring ≥ 12 months after IST initiation, occurred more frequently in the fQRS group (21% vs. 2%, log-rank p = 0.002). The scar zone and scar border zone were greater in patients with fQRS than in those without it. In conclusion, our analysis suggests that fQRS is an independent predictor of adverse events, particularly late-onset VTs, in patients with CS.

Efficacy and safety of postoperative preemptive use of tolvaptan for patients with cirrhosis undergoing hepatectomy for hepatocellular carcinoma.

PURPOSE: Optimal choice of diuretics in perioperative management remains unclear in enhanced recovery after liver surgery. This study investigated the efficacy and safety of tolvaptan (oral vasopressin V2-receptor antagonist) in postoperative management of patients with liver injury and hepatocellular carcinoma. METHODS: The patients clinically diagnosed with liver cirrhosis were included in this study. Clinical outcomes of 51 prospective cohort managed with a modified postoperative protocol using tolvaptan (validation group) were compared with 83 patients treated with a conventional management protocol (control group). RESULTS: Postoperative urine output were significantly larger and excessive body weight increase were reduced with no impairment in renal function or serum sodium levels in the validation group. Although the total amount of discharge and trend of serum albumin level were not significantly different among the groups, global incidence of postoperative morbidity was less frequent (19.6% vs. 44.6%, P=0.005) and postoperative stay was significantly shorter (8 days vs.10 days, P=0.008) in the validation group compared with the control group. CONCLUSIONS: Tolvaptan could be safely used for the patients with injured liver in postoperative management after hepatectomy and potentially advantageous in the era of enhanced recovery after surgery with its strong diuretic effect and better fluid management.

Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis.

PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.

A Preoperative Imaging Evaluation to Avoid Orbital Complications in Functional Endoscopic Sinus Surgery.

Functional endoscopic sinus surgery has become popular worldwide. However, serious complications have been reported with it. A preoperative imaging evaluation is thus essential to avoid complications. The authors compared 0.5 mm slice computed tomography (CT) images reconstructed from sinus CT data with conventional 2 mm slice CT images. The authors evaluated patients who underwent endoscopic surgery. Data regarding age, sex, history of craniofacial trauma, diagnosis, operative procedure, and CT findings of eligible patients were extracted from medical records and retrospectively reviewed. One hundred twelve patients underwent endoscopic surgery during the study period. Six patients (5.4%) had orbital blowout fractures, and half of them could only be identified by 0.5 mm slice CT images. The authors presented the usefulness of 0.5 mm slice CT images in the preoperative imaging evaluation of functional endoscopic sinus surgery. Surgeons should also recognize that a small number of patients have "stealth" (asymptomatic and unrecognized) blowout fractures.

Dissipative Kerr soliton microcombs for FEC-free optical communications over 100 channels.

The demand for high-speed and highly efficient optical communication techniques has been rapidly growing due to the ever-increasing volume of data traffic. As well as the digital coherent communication used for core and metro networks, intensity modulation and direct detection (IM-DD) are still promising schemes in intra/inter data centers thanks to their low latency, high reliability, and good cost performance. In this work, we study a microresonator-based frequency comb as a potential light source for future IM-DD optical systems where applications may include replacing individual stabilized lasers with a continuous laser driven microresonator. Regarding comb line powers and spectral intervals, we compare a modulation instability comb and a soliton microcomb and provide a quantitative analysis with regard to telecom applications. Our experimental demonstration achieved a forward error correction (FEC) free operation of bit-error rate (BER) <10-9 with a 1.45 Tbps capacity using a total of 145 lines over the entire C-band and revealed the possibility of soliton microcomb-based ultra-dense wavelength division multiplexing (WDM) with a simple, cost-effective IM-DD scheme, with a view to future practical use in data centers.

Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma.

INTRODUCTION: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). METHODS: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in 2 independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. RESULTS: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2A histone family member X and checkpoint kinase 1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. CONCLUSIONS: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.