Background: Anemia has negative effects on long-term outcomes of rectal cancer patients; however, its status as a risk factor for severe complications is disputed. Perioperative risks may differ based on the severity of pre-surgical anemia; nonetheless, no previous study has investigated these differences. This study identified risks of severe postoperative complications in rectal cancer patients based on severity of their pre-surgical anemia. Materials and Methods: This study enrolled patients who underwent low anterior resection for rectal cancer and were registered in the Japanese National Clinical Database (NCD) between 2017 and 2019. Anemia severity was categorized into three levels: mild, moderate, and severe. A logistic regression model was applied to calculate the risk-adjusted odds ratio (OR) of severe complications after surgery. Results: This study analyzed a cohort of 51 765 rectal cancer patients who underwent low anterior resection. Results showed that severe complications occurred in 10.9% of patients and were significantly more frequent in patients with anemia (13.6%) than those with normal hemoglobin levels (9.2%). Risk-adjusted ORs of severe complications in the severe, moderate, and mild anemia groups versus the normal group for males were 1.19 (95% confidence interval [CI]: 0.89-1.58), 1.47 (1.34-1.62), and 1.21 (1.12-1.31), respectively. Those for females were 1.39 (0.90-2.15), 1.64 (1.37-1.97), and 1.36 (1.16-1.58), respectively. Conclusions: According to this large cohort study, pre-surgical anemia significantly increases the risk of severe postoperative complications in rectal cancer patients. Even mild anemia presents a significant risk.
OBJECTIVE: The efficacy of pembrolizumab in patients with microsatellite instability (MSI)-high cancers has been reported; however, the differences in efficacy according to the subtypes of MSI-high endometrial cancers (ECs) remain unclear. MSI-high ECs are classified into at least 3 groups based on their molecular characteristics: MLH1 hypermethylated, Lynch-like syndrome (LLS)-associated, and Lynch syndrome (LS)-associated cancers. This study aimed to investigate whether the efficacy of pembrolizumab differs among these 3 groups, and if so, whether EPM2AIP1 immunohistochemistry (IHC), which correlates with MLH1 promoter methylation, can be used to rule out MLH1 methylation cases. METHODS: This study included 12 patients with MSI-high EC who received pembrolizumab treatment. Patients were categorized into 3 groups based on MLH1 methylation analysis and the Amsterdam Criteria: MLH1 hypermethylated (sporadic [SP]), LLS-associated, and LS-associated. Patients' medical records were retrospectively reviewed, and the efficacy of treatment was evaluated based on the response rate using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: The overall response rate was 75% (3/4) in the SP group, while it was 100% including one complete response patient in the LLS-associated and the LS-associated group, respectively. The sensitivity and positive predictive value of EPM2AIP1 IHC for MLH1 methylation were 100% and 66.7%, respectively. CONCLUSION: Pembrolizumab may be more effective in LLS and LS-associated groups. EPM2AIP1 IHC was less predictive than MLH1 methylation analysis; however, it may be useful for ruling out MLH1 methylation cases due to its high sensitivity. Further studies are needed to determine whether EPM2AIP1 IHC can predict pembrolizumab efficacy.
OBJECTIVE: Trophoblast Cell Surface Antigen 2 (Trop-2) is a transmembrane glycoprotein that is overexpressed in various cancers, with immunological significance as a target for tumor-reactive T-cells. We aimed to investigate the association between the expression of Trop-2 and the tumor immune microenvironment in cervical cancer. METHODS: The study included 123 patients with cervical cancer who underwent primary surgery between 2000 and 2020 in our hospital. Trop-2 expression was evaluated using anti-Trop-2 monoclonal antibody clone MAB650. Immune biomarkers, including PD-L1 (22C3), CD3 (PS1), and CD8 (4B11), were also evaluated. Trop-2 and PD-L1 positivity were defined by an H-score ≥ 10 and a combined positive score (CPS) ≥1, respectively. Tumor-infiltrating lymphocytes (TILs) were assessed in the five selected independent areas. The correlation between Trop-2 expression and immune biomarkers was analyzed. RESULTS: The cohort comprised patients with squamous cell carcinoma (SCC) (54.5%) and non-SCC (45.5%). Trop-2 was positive in 84.6% of samples and more commonly expressed in SCC (SCC vs. non-SCC; 97.0% vs. 69.6%, p < 0.001). Intratumoral CD3+ and CD8 + TILs were significantly more common in Trop-2-positive cases (CD3, Mann-Whitney U = 383, p < 0.0001; CD8, U = 442, p < 0.0001). Additionally, significant positive correlations were found between the Trop-2H-score and immune markers (CD3 + TILs, r = 0.295, p < 0.001; CD8 + TILs, r = 0.267, p = 0.001; PD-L1 CPS, r = 0.178, p = 0.025). No significant associations were detected between TILs and other clinicopathological features, including prognosis. CONCLUSION: Expression of Trop-2 in cervical cancer is associated with increased levels of intratumoral TILs, indicating the potential of Trop-2 targeted therapy alone or in combination with immune checkpoint inhibitors.
Pulsed cathodic arc-plasma deposition was employed to create a few nanometre-thick Pt overlayer on a 50 µm-thick Fe-Cr-Al metal (SUS) foil, resulting in an effective NH3 oxidation catalyst fabrication. This catalyst exhibited a turnover frequency (TOF) exceeding 100 times that of Pt nanoparticles. In this study, Pt overlayer catalysts with varying degrees of surface roughness were fabricated using different metal foil substrates: mirror-polished (Pt/p-SUS), unpolished (Pt/SUS) and roughened by the formation of a surface oxide layer (Pt/Al2O3/SUS). The nanoscale roughness was comprehensively analysed using electron microscopy, laser scanning confocal microscopy and chemisorption techniques. NH3 oxidation activity, measured at 200 °C, followed an increasing trend in the order of Pt/Al2O3/SUS < Pt/SUS < Pt/p-SUS, despite a decrease in the apparent Pt surface area in the same order. Consequently, the calculated TOF was markedly higher for Pt/p-SUS (267 min-1) compared to Pt/SUS (107 min-1) and Pt/Al2O3/SUS (≤22 min-1). The smooth Pt overlayer surface also favoured N2 yield over N2O at this temperature. This discovery enhances our fundamental understanding of high-TOF NH3 oxidation over Pt overlayer catalysts, which holds significance for the advancement and industrial implementation of selective NH3 oxidation processes.
BACKGROUND: Numerous epidemiological studies have shown that hypertriglyceridemia is a significant risk factor for cardiovascular diseases (CVD). However, large clinical studies on triglyceride-lowering therapy have yielded inconsistent results. In the current review, we reassess the importance of triglyceride-lowering therapy in preventing CVD based on previous literature and the recently published findings of the PROMINENT trial. METHODS: This narrative review is based on literature and public documents published up to November 2023. RESULTS: Meta-analyses of trials on peroxisome proliferator-activated receptor α agonists and triglyceride-lowering therapy, including the PROMINENT trial, have indicated that triglyceride-lowering therapy can reduce CVD events. Mendelian randomization studies have also indicated that triglyceride is indeed a true risk factor for coronary artery disease, leaving no doubt about its relationship to CVD. Meanwhile, the negative results from the PROMINENT trial were likely due to the insufficient triglyceride-lowering effect, slight increases in low-density lipoprotein cholesterol and apolipoprotein B, and the inclusion of mostly high-intensity statin users as target patients. It is unlikely that adverse events counteracted the effectiveness of pemafibrate on outcomes. Additionally, pemafibrate has shown positive effects on non-alcoholic fatty liver disease and peripheral artery disease. CONCLUSION: Although the PROMINENT trial did not demonstrate the significance of pemafibrate as a triglyceride-lowering therapy in a specific population, it does not necessarily negate the potential benefits of treating hypertriglyceridemia in reducing CVD events. It is necessary to explore appropriate populations that could benefit from this therapy, utilize data from the PROMINENT trial and other databases, and validate findings in real-world settings.
Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with a dismal prognosis; however, the mechanism underlying OCCC chemoresistance is not well understood. To explore the intracellular networks associated with the chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell analyses and spatial transcriptomics. We find that a chemoresistant OCCC subpopulation with elevated HIF activity localizes mainly in areas populated by cancer-associated fibroblasts (CAFs) with a myofibroblastic phenotype, which is corroborated by quantitative immunostaining. CAF-enhanced chemoresistance and HIF-1α induction are recapitulated in co-culture assays, which show that cancer-derived platelet-derived growth factor (PDGF) contributes to the chemoresistance and HIF-1α induction via PDGF receptor signaling in CAFs. Ripretinib is identified as an effective receptor tyrosine kinase inhibitor against CAF survival. In the co-culture system and xenograft tumors, ripretinib prevents CAF survival and suppresses OCCC proliferation in the presence of carboplatin, indicating that combination of conventional chemotherapy and CAF-targeted agents is effective against OCCC.
OBJECTIVE: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. METHODS: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. RESULTS: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. CONCLUSIONS: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.
PURPOSE: Emergency surgery (ES) for complicated appendicitis (CA) is associated with high morbidity. Interval appendectomy (IA) decreases this rate; however, nonoperative management (NOM) is not always successful. Some patients require unplanned ES due to NOM failure (IA failure: IA-F). This study aimed to verify the benefits of IA and to evaluate the risk factors for NOM failure. METHODS: Patients diagnosed with CA who underwent surgery between January 2012 and December 2021 were included in this study. We compared the surgical outcomes of the ES group with those of the IA success (IA-S) and IA-F groups. We also analyzed 14 factors that predicted NOM failure. RESULTS: Among 302 patients, the rate of severe complications (Clavien-Dindo grade ≥ III) was significantly higher in the ES group (N = 165) than in the IA-S group (N = 102). The rates were equal between the ES (N = 165) and IA-F (N = 35) groups. NOM was successful in 110 patients and failed in 27. Lack of abscesses, comorbidities, high WBC count, and free air were independent risk factors for NOM failure. CONCLUSIONS: Considering the benefits of IA and the non-inferior surgical outcomes of IA-F compared to ES, IA is a good therapeutic strategy for CA. However, in patients exhibiting four independent risk factors for NOM failure, careful monitoring of unplanned ES is necessary.
In the spinel framework, copper (Cu) in two distinct coordination states exhibits catalytic activity for NO reduction through different mechanisms. However, detailed exploration of their respective catalytic properties, such as the redox behavior of Cu and substrate molecule adsorption, has been challenging due to difficulties in their separate formation. In this study, we present the controlled formation of pseudospinel CuAl2O4, containing exclusively tetrahedrally or octahedrally coordinated Cu, achieved by manipulating aging temperature and O2 concentration. Through these materials, we observed that in the CO-NO reaction, the step primarily determining the rate differs: NO reduction dominates with octahedrally coordinated Cu, whereas carbon monoxide (CO) oxidation is prominent with tetrahedrally coordinated Cu. The lower coordination number of Cu significantly benefits NO reduction but negatively impacts the CO-NO reaction, albeit positively influencing NO reduction in three-way catalytic reactions.
Cap expansion in agaricoid mushroom species is an important event for sexual reproduction because meiosis occurs in basidia under the cap, and basidiospores can be released by opening the cap. However, molecular mechanisms underlying cap expansion in basidiomycetes remain poorly understood. We aimed to elucidate the molecular mechanisms of cap expansion in basidiomycetes by analyzing the unique cap-expansionless UV mutant #13 (exp2-1) in Coprinopsis cinerea. Linkage analysis and consequent genome sequence analysis revealed that the gene responsible for the mutant phenotypes encodes a putative transcription factor with two C2H2 zinc finger motifs. The mutant that was genome-edited to lack exp2 exhibited an expansionless phenotype. Some of the genes encoding cell wall degradation-related enzymes showed decreased expression during cap expansion and autolysis in the exp2 UV and genome-edited mutant. The exp2 gene is widely conserved in Agaricomycetes, suggesting that Exp2 homologs regulate fruiting body maturation in Agaricomycetes, especially cap expansion in Agaricoid-type mushroom-forming fungi. Therefore, exp2 homologs could be a target for mushroom breeding to maintain shape after harvest for some cultivating mushrooms, presenting a promising avenue for further research in breeding techniques.
Agaricales , Basidiomycota , Fruiting Bodies, Fungal/genetics , Agaricales/genetics , Zinc Fingers/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism
PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.
The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5-year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (p = 0.27). In the MMRd without LS group, the 5-year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log-rank test; p = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.
Colorectal Neoplasms, Hereditary Nonpolyposis , DNA-Binding Proteins , Endometrial Neoplasms , MutS Homolog 2 Protein , Tumor Suppressor Protein p53 , Humans , Female , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Middle Aged , Tumor Suppressor Protein p53/genetics , Aged , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Adult , MutS Homolog 2 Protein/genetics , Prognosis , DNA-Binding Proteins/genetics , DNA Mismatch Repair/genetics , MutL Protein Homolog 1/genetics , Mismatch Repair Endonuclease PMS2/genetics , Aged, 80 and over , Epithelial Cell Adhesion Molecule/genetics , Epithelial Cell Adhesion Molecule/metabolism , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Neoplastic Syndromes, Hereditary/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/mortality , Japan/epidemiology
A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.
Colorectal Neoplasms , Polyketides , Humans , Escherichia coli/genetics , Neoplasm Recurrence, Local , Mucous Membrane , Carcinogenesis
Exploring potential spintronic functionalities in resistive switching (RS) devices is of great interest for creating new applications, such as multifunctional resistive random-access memory and novel neuromorphic computing devices. In particular, the importance of the spin-triplet state of cation vacancies in oxide materials, which is induced by localized and strong O-2p on-site Coulomb interactions, in RS devices has been overlooked. d0 ferromagnetism sometimes appears due to the spin-triplet state and ferromagnetic Zener's double exchange interactions between cation vacancies, which are occasionally strong enough to make nonmagnetic oxides ferromagnetic. Here, for the first time, anomalous and colossal magneto-RS (CMRS) with very high magnetic field dependence is demonstrated by utilizing an unconventional RS device composed of a Ge nanochannel with all-epitaxial single-crystalline Fe/MgO electrodes. The device shows colossal and unusual behavior as the threshold voltage and ON/OFF ratio strongly depend on a magnetic field, which is controllable with an applied voltage. This new phenomenon is attributed to the formation of d0 -ferromagnetic filaments by attractive Mg vacancies due to the spin-triplet states with ferromagnetic double exchange interactions and the ferromagnetic proximity effect of Fe on MgO. The findings will allow the development of energy-efficient CMRS devices with multifield susceptibility.
OBJECTIVE: To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. METHODS: This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. RESULTS: Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). CONCLUSION: This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.
Endometrial Neoplasms , Laparoscopy , Female , Humans , Retrospective Studies , Prospective Studies , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Hysterectomy/adverse effects , Laparoscopy/adverse effects , Neoplasm Staging
Extrahepatic portal vein obstruction (EHPVO) is a rare disease. Most EHPVO patients are usually referred to a gastroenterologist for intestinal bleeding and hypersplenic thrombocytopenia; however, hypercoagulative diseases may be occult in these patients and require anticoagulation. The purpose of this study was to elucidate the clinical characteristics of EHPVO. We conducted a retrospective analysis of the hospital database, evaluating the medical records of 15 patients (7 males, 8 females, mean age of onset 42.0 years, range 5-74 years). Thirteen of 15 EHPVO patients (86.7%) had intestinal varices. These included 10 esophageal (66.7%), 12 gastric (80.0%), and 6 ectopic varices (40.0%). Nine (60.0%) of 15 had a history of intestinal bleeding. Regarding comorbidities, 5 of 15 (33.3%) suffered from vascular diseases, including acute myocardial infarction, cerebral infarction, pulmonary embolism, Budd-Chiari syndrome, and mesenteric vein thrombosis. The former 3 vascular commodities manifested at less than 32 years of age. Four patients (26.7%) with JAK2V617F mutation were diagnosed as myeloproliferative neoplasm (MPN). 72.3% of EHPVO patients without MPN experienced thrombocytopenic state. No EHPVO patients with MPN experienced thrombo-leukocytopenia. The elevation of white blood cell and platelet counts, and decrease of protein S were seen in EHPVO with MPN, compared with EHPVO without MPN. EHPVO is frequently associated with underlying hypercoagulative factors, causing a dilemma between thrombotic complications and portal hypertensive bleeding. Most EHPVO patients experience an evident thrombocytopenic state due to severe hypersplenism; however, hypersplenic hematologic changes are eliminated in EHPVO with MPN. MPN should be suspected in EHPVO patients negative for thrombo-leukocytopenia.
Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited. In this study, we explored extracellular long non-coding RNAs (lncRNAs) released from primary sensory neurons as biomarker candidates for oxaliplatin-induced peripheral neuropathy. Because many human-specific lncRNA genes exist, we induced peripheral sensory neurons from human induced pluripotent stem cells. Oxaliplatin treatment changed the levels of many lncRNAs in extracellular vesicles (EVs) released from cultured primary sensory neurons. Among them, the levels of release of lncRNAs that were considered to be selectively expressed in dorsal root ganglia were correlated with those of lncRNAs in plasma EV obtained from healthy individuals. Several lncRNAs in plasma EVs early after the initiation of treatment showed greater changes in patients who did not develop chronic neuropathy that persisted for more than 1 year than in those who did. Therefore, these extracellular lncRNAs in plasma EVs may represent predictive biomarkers for the development of chronic peripheral neuropathy induced by oxaliplatin.
AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.
