Recyclable Tough Adhesive Sheets with Movable Cross-Links for Sustainable Use.

Acrylic adhesive sheets have been used for many applications, from popular seal materials to high-end electrical devices. One of the basic and critical design features of adhesives is effective covalent cross-linking for superior adhesive properties. On the other hand, covalent cross-linking prevents reuse or recycling of the adhesive. This makes the adhesive sheets insoluble and poorly workable. For development of sustainable adhesives, we investigated the adhesive sheets based on acrylic elastomers with "Movable Cross-links" (M-PEA-CD (0.5)) copolymerized with 0.5 mol % cyclodextrin monomers. The peel strength and creep resistance of M-PEA-CD (0.5) were greater than those of adhesives (N-PEA) without any cross-links. M-PEA-CD (0.5) was recyclable via dissolution in ethyl acetate. Furthermore, the recycled M-PEA-CD (0.5) from solution exhibited the same adhesion properties as virgin M-PEA-CD (0.5). Spectroscopic and mechanical measurements indicated that topological cross-linking with Cyclodextrin (CD) moieties generated novel recyclable adhesive sheets without restricting the polymer main chains, unlike covalent cross-linking (CC-PEA). The movable cross-links were maintained in both the solid state and in solution, which allowed recycling of the elastomer via simple methods.

Efficacy and safety of atezolizumab plus bevacizumab in patients with portal hypertension for unresectable hepatocellular carcinoma.

AIM: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. METHODS: A total of 146 patients with u-HCC and Child-Pugh Scores of 5-7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score-matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score-matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). RESULTS: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression-free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3-4 AEs between patients without and with PH. CONCLUSIONS: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

Impact of MAFLD criteria on postoperative recurrence of non-B, non-C HCC.

BACKGROUND: This study aimed to clarify the population in whom the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) especially contributes to recurrence after liver resection for non-B, non-C hepatocellular carcinoma (NBNC-HCC). METHODS: Of the 199 patients who underwent liver resection for NBNC-HCC, those who exceeded Milan criteria and with pathologically proven vascular invasion, intrahepatic metastasis, and positive resection margins were excluded, and the remaining 94 were eligible for this study. We explored factors contributing to postoperative recurrence in populations with and without advanced liver fibrosis. RESULTS: Independent factors contributing to postoperative recurrence in the study population were male sex ( P  = 0.023) and presence of type 2 diabetes (DM) ( P  = 0.006) and advanced liver fibrosis ( P  < 0.001). Factors in cases with advanced liver fibrosis (n = 43) were non-overweight ( P  = 0.02), type 2 DM ( P  = 0.006), and preoperative alpha-fetoprotein level of 8.2 ng/ml or higher ( P  = 0.021). In cases without advanced liver fibrosis (n = 51), only presence of all three MAFLD criteria was related to recurrence. CONCLUSION: Liver fibrosis is a strong factor contributing to postoperative recurrence of NBNC-HCC, as previously reported. In patients with advanced liver fibrosis, presence of type 2 DM was the only factor associated with recurrence among MAFLD criteria. On the other hand, in patients without advanced liver fibrosis, the combination of all MAFLD criteria, rather than a specific criterion alone, contributed to recurrence. MAFLD criteria were found to have utility as predictors of postoperative recurrence in NBNC-HCC.

Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab.

INTRODUCTION: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. METHODS: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. RESULTS: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. CONCLUSION: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Improvement in Cohesive Properties of Adhesion Systems Using Movable Cross-Linked Materials with Stress Relaxation Properties.

A strong, tough, and stable adhesion system used in various environments must be developed. A long-lasting adhesion system should effectively perform in the following five aspects: adhesion strength, toughness, energy dissipation property, self-restoration property, and creep resistance property. However, these properties are difficult to balance using conventional adhesives. Here, a new topological adhesion system using single-movable cross-network (SC) materials [SC(DMAAm) Adh] was designed. 3-(Trimethoxysilyl) propyl acrylate was used as the anchor, N,N-dimethyl acrylamide (DMAAm) was used as the main chain monomer, and γ-cyclodextrin (γ-CD) units acted as movable cross-links. The movable cross-links provided SC(DMAAm) Adh with energy dissipation properties, thereby improving its toughness. The γ-CD units also acted as bulky stoppers that provided a high adhesion strength and self-restoration properties. Moreover, the combination of the movable cross-links and bulky stoppers provided creep resistance to SC(DMAAm) Adh. The performance of the adhesion systems under different mobilities of the polymer chains was examined by adjusting the water content. In proper water-containing states, all mechanical properties of SC(DMAAm) Adh were better than those of the adhesion systems using homopolymers [P(DMAAm) Adh] and polymers with covalent cross-linking points [CP(DMAAm) Adh].

Clinical Outcomes of Switching from Zoledronic Acid to Denosumab for the Management of Severe Bone Metastasis from Hepatocellular Carcinoma: A Single-Center, Open-Label, Prospective Intervention Trial.

Background: Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma. Methods: This prospective study enrolled 10 patients with HCC and bone metastases. The levels of type 1 collagen cross-linked N-telopeptide (NTx) and tumor growth remained abnormal in these patients despite administration of zoledronic acid for over 3 months. We switched from zoledronic acid to 120 mg denosumab every 4 weeks and evaluated the clinical outcomes, including changes in the NTx level, pain level, and activities of daily living, as well as adverse events, after each administration. Results: Urinary NTx clearance was normal in all patients. The average urinary NTx clearance increased from 13.2 to 21.2 nmol BCE/nmol ·â€†Cre (P = 0.54) after the switch to denosumab. Serum NTx levels were abnormal in all cases. The serum NTx level decreased from 142 nmol BCE/L to 126 nmol BCE/L (P = 0.56). The answers to questionnaires on pain and activities of daily living did not change significantly. Some patients showed elevated transaminase levels, but this was not due to the drug switch. Conclusion: Switching to denosumab did not show a significant change of the pain and activity of daily living for the patients with severe bone metastasis from hepatocellular carcinoma, in whom the efficacy of zoledronic acid was limited.

Therapeutic Efficacy and Safety of Lenvatinib after Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months-not reached) and 10.5 months (range, 8.2-12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months-not reached) and 4.0 months (range, 2.5-6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child-Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02-0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003-0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.

Enhancement of the mechanical properties of organic-inorganic hybrid elastomers by introducing movable and reversible crosslinks.

Organic-inorganic materials have been widely utilized in various fields as multifunctional materials. Poly(dimethyl siloxane) (PDMS), a typical inorganic polymer, has industrially appealing functions, such as transparency, biocompatibility, and gas permeability; however, it has poor mechanical properties. We incorporated organic-inorganic hybrid elastomers (PDMS-γCD-AAl⊃P(EA-HEMA) (x)) with movable crosslinks, and we utilized hydrogen bonds as reversible crosslinks. The organic polymer poly ethyl acrylate-r-hydroxy ethyl methacrylate (P(EA-HEMA)) penetrated the cavity of triacetylated γ-cyclodextrin (γCD), which was introduced into the side chains of PDMS, and it compounded with PDMS at the nanoscale. Structural studies involving visual and X-ray scattering measurements revealed that movable crosslinks improved the compatibility levels of PDMS and acrylate copolymers. However, macroscopic phase separation occurred when the number of reversible crosslinks increased. Furthermore, studies on the mobility levels of acrylate copolymers and movable crosslinks indicated that the relaxation behaviour of PDMS-γCD-AAl⊃P(EA-HEMA) (x) changed with changing numbers of reversible crosslinks. Introducing reversible crosslinks improved the Young's modulus and toughness values. The movable and reversible crosslinks between the organic and inorganic polymers contributed to the high elongation properties. The design of PDMS-γCD-AAl⊃P(EA-HEMA) (x) incorporated cooperatively movable and reversible crosslinks to achieve high compatibility of immiscible polymers and to control the mechanical properties.

The indirect corticopontine pathway relays perioral sensory signals to the cerebellum via the mesodiencephalic junction.

In the cerebro-cerebellar loop, outputs from the cerebral cortex are thought to be transmitted via monosynaptic corticopontine gray (PG) pathways and subsequently relayed to the cerebellum. However, it is unclear whether this pathway is used constitutively for cerebro-cerebellar transduction. We examined perioral sensory pathways by unit recording from Purkinje cells in ketamine/xylazine-anesthetized mice. Infraorbital nerve stimulations enhanced simple spikes (SSs) with short and long latencies (first and second peaks), followed by SS inhibition. The second peak and SS inhibition were suppressed by muscimol (a GABAA agonist) injections into not only the PG but also the mesodiencephalic junction (MDJ). The pathway from the secondary somatosensory area (SII) to the MDJ, but not the cortico-PG pathway, transmitted the second peak signals. SS inhibition was processed in the SII and primary motor area. Thus, the indirect cortico-PG pathway, via the MDJ, is recruited for perioral sensory transduction.

Sodium-glucose cotransporter-2 inhibitors improve FibroScan-aspartate aminotransferase scores in patients with nonalcoholic fatty liver disease complicated by type 2 diabetes.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by excessive lipid accumulation in the liver, and its global incidence is increasing. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are oral antidiabetes drugs that promote glucose excretion into the urine and have been reported to exert therapeutic effects in NAFLD, but liver stiffness measurements (LSMs) determined by transient elastography are inconsistent. In addition, the effects of SGLT2is on the FibroScan-aspartate aminotransferase (FAST) scores have not been reported. We evaluated the effect of SGLT2is on patients with NAFLD complicated by type 2 diabetes using biochemical tests, transient elastography, and FAST scores. METHODS: Fifty-two patients with type 2 diabetes complicated by NAFLD who started SGLT2i treatment between 2014 and 2020 at our hospital were selected from the database. Pre- and post-treatment serum parameters, transient elastography, and FAST scores were compared. RESULTS: After 48 weeks of SGLT2i treatment, body weight, fasting blood glucose, hemoglobin A1c, AST, alanine aminotransferase, gamma-glutamyltransferase, uric acid, fibrosis-4 index, and AST to platelet ratio index improved. Median LSM decreased from 7.0 kPa to 6.2 kPa ( P  = 0.023) and the median controlled attenuation parameter decreased from 304 dB/m to 283 dB/m ( P  = 0.022). Median FAST score decreased from 0.40 to 0.22 ( P  < 0.001), and the number of cases with a cutoff value of ≥0.35 decreased from 15 to 6 ( P  = 0.001). CONCLUSION: SGLT2i use not only improves weight loss and blood glucose levels but also improves hepatic fibrosis by ameliorating hepatic steatosis and inflammation.

The Analysis of Muscle Volume Measured by Bioelectrical Impedance in Patients with Hepatocellular Carcinoma Treated with First-Line Atezolizumab plus Bevacizumab Combination Therapy or First-Line Lenvatinib.

INTRODUCTION: Measurements of body composition, such as the skeletal muscle index (SMI), are useful for predicting prognosis in hepatocellular carcinoma (HCC). This study aimed to analyze the relationship between skeletal muscle changes during therapy with atezolizumab plus bevacizumab (Atezo + Beva) or lenvatinib (Len) and the association between SMI and prognosis. METHODS: Patients with advanced HCC and Child-Pugh A status received Atezo + Beva or Len as first-line systemic chemotherapy. We assessed prognosis and body composition obtained by bioelectrical impedance analysis. RESULTS: A total of 109 patients received treatment (Atezo + Beva, n = 47; Len, n = 62). During treatment, the arm SMI was reduced in the Len group and maintained in the Atezo + Beva group. The extracellular water to total body water ratio (ECW/TBW) increased significantly in both groups during treatment. In the Atezo + Beva group, no factor was associated with prognosis. Multivariate analysis showed that in the Len group, the arm SMI (hazard ratio [HR], 0.5; 95% CI: 0.26-0.89; p = 0.02), ECW/TBW (HR: 2.7; 95% CI: 1.21-6.01; p = 0.01), and Child-Pugh score (HR: 2.3; 95% CI: 1.31-6.13; p = 0.004) were associated with progression-free survival. CONCLUSION: Assessing body composition with BIA before Atezo + Beva and Len treatment may be useful.

Evaluation of Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma Using the Combination of Response Evaluation Criteria in Solid Tumors and Alpha-Fetoprotein.

Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is currently positioned as the first-line therapy for unresectable hepatocellular carcinoma (u-HCC). It may be difficult to decide whether to continue this treatment if radiological response is assessed as stable disease (SD). Therefore, the relationship between radiological response and prognosis was analyzed. A total of 109 patients with u-HCC and Child-Pugh Score of 5-7 received this treatment. Radiological response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at the first and second evaluations. Of SD patients (n = 71) at the first RECIST evaluation, partial response, SD, and progressive disease (PD) were seen in 10, 55, and 6 patients, respectively, at the second evaluation. On multivariate analysis, in patients with SD at the first RECIST evaluation, a 25% or greater increase in the alpha-fetoprotein (AFP) value from initiation of treatment (odds ratio, 7.38; p = 0.037) was the independent factor for PD at the second evaluation. In patients with SD (n = 59) at the second RECIST evaluation, decreased AFP from initiation of treatment (hazard ratio, 0.46; p = 0.022) was the independent factor related to progression-free survival on multivariate analysis. AFP trends could help decide the Atezo + Beva treatment strategy.

Effectiveness of Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma-Consideration of the Locations of Target Lesions.

The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.

Efficacy and safety of chemoradiation therapy using one-shot cisplatin via hepatic arterial infusion for advanced hepatocellular carcinoma with major macrovascular invasion: a single-arm retrospective cohort study.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) who receive systemic chemotherapy have a poor prognosis. This study aimed to determine if one-shot cisplatin (CDDP) chemotherapy via hepatic arterial infusion (HAI) combined with radiation therapy (RT) prior to systemic chemotherapy could improve the outcomes of these patients. METHODS: This study consisted of 32 HCC patients with the following eligibility criteria: (i) portal vein invasion 3/4 and/or hepatic vein invasion 2/3; (ii) received one-shot CDDP via HAI; (iii) received RT for MVI, (iv) a Child-Pugh score ≤ 7; and (v) an Eastern Clinical Oncology Group Performance Status score of 0 or 1. To determine the therapeutic effect, we collected information on patient characteristics and took contrast-enhanced computed tomography at the start of the therapy and every 2 to 4 months after the start of therapy. We evaluated the overall response of the tumor and tumor thrombosis according to modified Response Evaluation Criteria in Solid Tumors. We assessed patient data using the Mann-Whitney U and Fisher exact tests and evaluated overall survival and progression-free survival using the log-rank test. RESULTS: The overall response rate at the first evaluation performed a median of 1.4 weeks after HAI was 16% for the main intrahepatic tumor and 59% for the MVI. The best responses were the same as those of the first-time responses. The duration of median survival was 8.6 months, and progression-free survival of the main intrahepatic tumor was 3.2 months. Predictive factors for overall survival were the relative tumor volume in the liver and the first therapeutic response of MVI. There were no severe adverse events or radiation-induced hepatic complications. CONCLUSIONS: One-shot CDDP via HAI and RT were well tolerated and showed immediate and favorable control of MVI. Thus, this combination shows potential as a bridging therapy to systemic chemotherapy.

Interfacial Selective Study on the Gelation Behavior of Aqueous Methylcellulose Solution via a Quartz Crystal Microbalance.

It is important to understand the interfacial structure and physical properties of a polymer material to improve its function. In this study, we used a quartz crystal microbalance (QCM) and neutron reflectivity (NR) measurements to evaluate the viscoelasticity and structure of an aqueous methylcellulose solution near the gold interface. The apparent shear modulus, which was calculated from the complex frequency, was used to assess gelation behavior. The apparent shear modulus determined via the QCM suggested high-frequency rheological properties that reflected the relaxation of skeletal stretching and rotational motion of polymer segments, as well as cooperative motion of the various functional groups. The gelation temperature was found to be lowered at the interface in comparison with that of the bulk. It is suggested that the QCM can evaluate the shear modulus accompanying the gelation near the interface. The interfacial segregation on the gold substrate caused by the surface free energy and long-range van der Waals interaction was observed from NR measurements.

The importance of body composition assessment for patients with advanced hepatocellular carcinoma by bioelectrical impedance analysis in lenvatinib treatment.

BACKGROUND AND AIMS: The aim of this study was to investigate the relationship between body composition before lenvatinib treatment and prognosis in patients with hepatocellular carcinoma (HCC). We also assessed the relationship between the rate of change in body composition after lenvatinib treatment and prognosis. METHODS: Eighty-one patients with advanced HCC who were treated with lenvatinib were enrolled. We assessed prognosis, various clinical data, body composition parameters obtained by bioelectrical impedance analysis (BIA), and handgrip strength. RESULTS: Multivariate analysis showed that an extracellular water to total body water ratio (ECW/TBW) ≤ 0.400 at treatment initiation was associated with longer overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) (OS: hazard ratio [H0R], 4.72; 95% CI, 12.03-11.00; P < 0.001; PFS: HR, 2.66; 95% CI, 1.33-5.34; P = 0.0057; PPS: HR, 3.08; 95% CI, 1.32-7.18; P = 0.0093). Multivariate analysis also showed that the skeletal muscle mass index (SMI) of the arm at treatment initiation was associated with a longer PFS (HR, 2.12; 95% CI, 1.23-3.64; P = 0.0069). In the group with an ECW/TBW ≤ 0.400 before lenvatinib treatment, univariate analysis showed that the rate of change in only the arm SMI was associated with a longer OS and PFS. CONCLUSION: Body composition assessment by BIA before and after lenvatinib treatment is useful in predicting prognosis in lenvatinib-treated patients with HCC.

Clinicopathological assessment of steatohepatitic hepatocellular carcinoma.

AIM: To compare the clinicopathological features of typical steatohepatitic HCC (SH-HCC) with other HCCs. METHODS: Subjects were 486 patients with untreated HCC who underwent hepatectomy at our hospital from January 2015 to December 2020. We compared patient backgrounds, preoperative laboratory data, imaging findings (ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI]), and postoperative pathological findings (tumor and background of liver). The Liver Imaging Reporting And Data System (LI-RADS) was used to examine CT and MRI findings. RESULTS: Typical SH-HCCs were significantly different from other HCCs with respect to age, hepatitis B virus (HBV) infection, and nonalcoholic steatohepatitis (NASH). Diabetes and hyperlipidemia were also significantly more common. Regarding histopathology, tumor size and background steatosis were significantly different between groups. Although ultrasonography, CT, and MRI could each alone diagnose SH-HCCs with a diameter < 20 mm in ≥ 50% of patients, the combined use of these tests improved diagnostic accuracy. By LI-RADS, 87% of SH-HCC cases were classified as LR-5, which are considered to be malignant tumors. CONCLUSIONS: It seems possible to diagnose SH-HCC by combining ultrasonography, CT, and MRI.

Evaluation of cold snare polypectomy for small pedunculated (Ip) polyps with thin stalks: a prospective clinical feasibility study.

BACKGROUND: Although the use of cold snare polypectomy (CSP) has spread rapidly, no prospective studies evaluating the safety of CSP for pedunculated (Ip) polyps have been carried out. AIM: We performed this study to provide an accurate evaluation of the safety of CSP for Ip polyps. METHODS: This is a prospective study (UMIN000035687). From January 2019 to February 2021, the safety of CSP for use on Ip polyps <10 mm with thin stalks was evaluated at our hospital. The primary outcome measure was the incidence of bleeding (delayed post-polypectomy bleeding (DPPB) and immediate bleeding). RESULTS: During the study period, 89 consecutive patients (including 92 colonoscopies and 114 polyps) were prospectively enrolled. The en-bloc resection rate was 100%. The rate of DPPB after CSP was 0%, however, DPPB after conversion to HSP occurred in 1 case (33.3% (1/3)). The rate of immediate bleeding during CSP was 28.9% (33/114). Polyps with diameters ≥6 mm (OR (95% CI): 2.77 (1.041-7.376); p = .041) were extracted as independent risk factors for immediate bleeding during CSP for Ip polyps. In all, 104 (91.2%) polyps were low-grade adenomas, and the percentage of cases with negative pathological margins was 96.5% (110/114). CONCLUSIONS: CSP for Ip polyps was safe and had good outcomes. We believe that Ip polyps could be included as an indication for CSP, and that CSP may become the next step in the 'cold revolution.' To confirm our results and verify CSP's inclusion in future guidelines, prospective, randomized studies are necessary.

Spike firing attenuation of serotonin neurons in learned helplessness rats is reversed by ketamine.

Animals suffering from uncontrollable stress sometimes show low effort to escape stress (learned helplessness). Changes in serotonin (5-hydroxytryptamine) signalling are thought to underlie this behaviour. Although the release of 5-hydroxytryptamine is triggered by the action potential firing of dorsal raphe nuclei 5-hydroxytryptamine neurons, the electrophysiological changes induced by uncontrollable stress are largely unclear. Herein, we examined electrophysiological differences among 5-hydroxytryptamine neurons in naïve rats, learned helplessness rats and rats resistant to inescapable stress (non-learned helplessness). Five-week-old male Sprague Dawley rats were exposed to inescapable foot shocks. After an avoidance test session, rats were classified as learned helplessness or non-learned helplessness. Activity-dependent 5-hydroxytryptamine release induced by the administration of high-potassium solution was slower in free-moving learned helplessness rats. Subthreshold electrophysiological properties of 5-hydroxytryptamine neurons were identical among the three rat groups, but the depolarization-induced spike firing was significantly attenuated in learned helplessness rats. To clarify the underlying mechanisms, potassium (K+) channels regulating the spike firing were initially examined using naïve rats. K+ channels sensitive to 500 µM tetraethylammonium caused rapid repolarization of the action potential and the small conductance calcium-activated K+ channels produced afterhyperpolarization. Additionally, dendrotoxin-I, a blocker of Kv1.1 (encoded by Kcna1), Kv1.2 (encoded by Kcna2) and Kv1.6 (encoded by Kcna6) voltage-dependent K+ channels, weakly enhanced the spike firing frequency during depolarizing current injections without changes in individual spike waveforms in naïve rats. We found that dendrotoxin-I significantly enhanced the spike firing of 5-hydroxytryptamine neurons in learned helplessness rats. Consequently, the difference in spike firing among the three rat groups was abolished in the presence of dendrotoxin-I. These results suggest that the upregulation of dendrotoxin-I-sensitive Kv1 channels underlies the firing attenuation of 5-hydroxytryptamine neurons in learned helplessness rats. We also found that the antidepressant ketamine facilitated the spike firing of 5-hydroxytryptamine neurons and abolished the firing difference between learned helplessness and non-learned helplessness by suppressing dendrotoxin-I-sensitive Kv1 channels. The dendrotoxin-I-sensitive Kv1 channel may be a potential target for developing drugs to control activity of 5-hydroxytryptamine neurons.