Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury.

Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.

Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Butyricimonas is a key gut microbiome component for predicting postoperative recurrence of esophageal cancer.

BACKGROUND: Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer. METHODS: We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained. RESULTS: Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown. CONCLUSION: Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers.

STM/TERS observation of (M)-type diphenyl[7]thiaheterohelicene on Ag(111).

The chiral recognition of a self-assembled structure of enantiopure (M)-type 2,13-diphenyl[7]thiaheterohelicene ((M)-Ph-[7]TH) was investigated on a Ag(111) substrate by scanning tunnelling microscopy (STM) and tip-enhanced Raman spectroscopy (TERS). In contrast to previous research of thiaheterohelicene and its derivatives showing zigzag row formation on the Ag(111) substrate, the hexagonal ordered structure was observed by STM. The obtained TERS spectra of (M)-Ph-[7]TH were consistent with the Raman spectra calculated on the basis of density functional theory (DFT), which suggests that (M)-Ph-[7]TH was adsorbed on the substrate without decomposition. The sample bias voltage dependence of STM images combined with the calculated molecular orbitals of (M)-Ph-[7]TH indicates that a phenyl ring was observed as a protrusion at +3.0 V, whereas the helicene backbone was observed at +0.5 V. From these results, a possible model of the hexagonal structure was proposed. Owing to the phenyl ring, the van der Waals interaction between (M)-Ph-[7]TH and the substrate becomes strong. This leads to the formation of the hexagonal structure with the same symmetry as the substrate.

Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. METHODS: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. RESULTS: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. CONCLUSION: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.

How I do it: Sternocleidomastoid sparing approach for the right vertebral artery to common carotid artery transposition.

BACKGROUND: Direct surgery is an important option to treat vertebral artery (VA) stenosis. METHOD: A patient with symptomatic stenosis at the origin of the right VA underwent transposition of the right VA to the common carotid artery (CCA). Using the sternocleidomastoid sparing approach, the VA was anastomosed to the posterior wall of the CCA by twisting the CCA to expose its posterior wall to face the operative field. CONCLUSION: This approach, consisting of securing the proximal VA and then following it to its distal end, not only preserves the sternocleidomastoid muscle but also protects the sympathetic chains and thoracic duct.

Preoperative evaluation of visceral pleural invasion in peripheral lung cancer utilizing deep learning technology.

PURPOSE: This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction. METHODS: This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation. RESULTS: Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction. CONCLUSION: AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC.

An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma.

Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase-accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss-of-function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS-NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor-promoting pathways were activated in the ELF3 signature-high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor-promoting properties in NEC.

Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial.

AIM: Developing effective adjuvant therapies is essential for improving the surgical outcomes in patients with hepatocellular carcinoma (HCC). Immunotherapy against HCC has become a promising strategy; however, only approximately 30% of all HCC patients respond to immunotherapy. Previously, we generated the novel therapeutic vaccine comprising multi-human leukocyte antigen-binding heat shock protein 70/glypican-3 peptides with a novel adjuvant combination of hLAG-3Ig and poly-ICLC. We also confirmed the safety of this vaccination therapy, as well as its capacity for the effective induction of immune responses in a previous clinical trial. METHODS: In this phase I study, we administered this vaccine intradermally six times before surgery, and 10 times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary end-points of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin-eosin staining and immunohistochemistry for heat shock protein 70, glypican 3, CD8 and programmed death-1. RESULTS: A total of 20 human leukocyte antigen-matched patients received this vaccination therapy with an acceptable side-effect profile. All patients underwent planned surgery without vaccination-related delay. Immunohistochemical analyses revealed that potent infiltration of CD8+ T cells into tumors with target antigen expression was observed in 12 of 20 (60%) patients. CONCLUSIONS: This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC, and has the potential to strongly induce CD8+ T cells infiltration into tumors.

Effect of electromyostimulation training on intramuscular fat accumulation determined by ultrasonography in older adults.

PURPOSE: Electromyostimulation (EMS) induces a short-term change in muscle metabolism, and EMS training induces long-term improvements of muscle atrophy and function. However, the effects of EMS training on intramuscular fat in older adults are still poorly known. The purpose of this study was to examine whether the intramuscular fat index and biochemical parameters change with EMS training of the quadriceps femoris muscles in older adults. METHODS: Nineteen non-obese older men and women performed EMS training of the quadriceps femoris for 12 weeks (3 times/week; single session for 30 min). The intramuscular fat content index was estimated by echo intensity of the vastus lateralis and rectus femoris muscles on ultrasonography, and muscle thickness was also measured. Muscle strength was assessed as the maximal voluntary contraction during isometric knee extension. Echo intensity, muscle thickness, and muscle strength were measured before and after EMS training. A rested/fasting blood samples were collected before and after EMS training for measuring plasma glucose, insulin, free fatty acid, triglyceride, and interleukin-6 concentrations. To examine the acute effect of a single-EMS session on biochemical parameters, blood samples were taken before and after the EMS session. RESULTS: EMS training did not significantly change echo intensity in muscles, muscle thickness, muscle strength, or biochemical parameters. Regarding the acute effect on blood lipid concentrations, a single-EMS session increased free fatty acid and glucose concentrations. CONCLUSION: EMS sessions had an acute effect of increasing free fatty acid and glucose concentrations, but EMS training intervention did not improve intramuscular fat content.

Increased Medial Elbow Torque Is Associated With Ball Velocity Rather Than a History of Medial Elbow Injuries in Youth Baseball Pitchers.

PURPOSE: This study compared medial elbow torque in youth baseball pitchers with and without a history of medial elbow injuries to determine the relationship between medial elbow torque during pitching and having a history of medial elbow injuries. METHODS: We recruited 171 youth baseball pitchers aged 9 to 12 years old. The exclusion criteria included current pain with pitching, history of surgery on the tested extremity, or osteochondritis dissecans of the humeral capitellum. The participants were grouped into 3 groups: injury <1-year, injury >1-year, and control, based on ultrasonographic abnormalities of the elbow and the presence of elbow pain. Pitchers pitched 3 fastballs while wearing a sensor sleeve that recorded the medial elbow torque, arm speed, and shoulder rotation. Ball velocity was measured using a radar gun. RESULTS: The final analysis included 164 pitchers. Thirty were assigned to the injury <1-year group, 34 to the injury >1-year group, and 100 to the control group. The medial elbow torque was significantly greater in the injury <1-year group compared with the control group (18.6 ± 3.6 Nm vs 16.2 ± 4.8 Nm, P = .023). A multiple regression analysis revealed that ball velocity (B = 0.282, P < .001) and body weight (B = -0.224, P < .001) were significantly associated with medial elbow torque, but not with the history of medial elbow injuries. CONCLUSIONS: Increased medial elbow torque was associated with greater ball velocity regardless of the history of medial elbow injuries. Youth baseball pitchers with a history of medial elbow injuries within one year had greater medial elbow torque during pitching; however, having a history of medial elbow injuries was not an independent factor in increasing medial elbow torque. Limiting the ball velocity can reduce medial elbow torque and may prevent elbow injuries in youth baseball pitchers. LEVEL OF EVIDENCE: Level II, prospective comparative prognostic investigation with the patients enrolled at different time point.

[Rehabilitation Therapy for Acute Brain Disease].

Early mobilization and rehabilitation therapy are becoming more critical in acute stroke, traumatic brain injury, and neurological disorder. Better functional prognosis for patients are obtained by performing comprehensive early mobilization and rehabilitation by a multidisciplinary team, generally within 48 hours after the onset. Early and frequent mobilization and rehabilitation therapy are recommended unless systemic management is paramount, such as hemodynamic instability, increased intracranial pressure, or active bleeding. Future considerations to be verified include implementation of rehabilitation in the very early phase(e.g., within 24 hours after the onset), selection of patients(e.g., when to start rehabilitation for each disease type), amount of exercise load in the intensive care unit(ICU), and content of training at the early stage. In addition, there are still few established methods for evaluating motor activity that can be performed in bed. It is also necessary to consider the nature of the rehabilitation team and leadership that were poorly addressed.

Effect of a multicomponent programme based on reality orientation therapy on the physical performance and cognitive function of elderly community-dwellers: a quasi-experimental study.

BACKGROUND: Effects of a multicomponent exercise programme have an impact on the physical, cognitive, and psychological domains in elderly community-dwellers. However, some individuals aged 65 years or more have not shown positive effects after the intervention as reported in similar research. The objective of this quasi-experimental study was to clarify the effectiveness of a multicomponent programme based on reality orientation therapy (ROT) on the physical performance, cognitive ability, and psychological state in the elderly. METHOD: Participants were recruited from the general public in 20 areas of Akita Prefecture, Japan, and they took part in each exercise programme for 90 min a day, once every 2 weeks, for 3 months, according to the group classification using cluster randomization into 20 cohorts in Akita. Physical, cognitive, and geriatric depression assessments were performed at baseline and after the 3-month intervention in both the ROT-based intervention group and the control group. RESULT: The final samples for analysis consisted of 31 participants in the control group and 30 participants in the intervention group. The results of the statistical analysis comparing the two groups showed that the 5-repetition sit-to-stand test was performed significantly faster (P < 0.05) and that the results of the word list memory (WM) test and the Symbol Digit Substitution Task also had significantly improved (P < 0.05) after the intervention in both groups. The WM score did not show an interactive effect between the group and time factors, but it had a significant main effect on time in both groups (P < 0.05). CONCLUSION: The results of our quasi-experimental study indicated that the multicomponent programme based on the ROT would be as effective as the original multicomponent programme combined with aerobic exercise and cognitive tasks, as highlighted in the WM.

ASCL1 regulates super-enhancer-associated miRNAs to define molecular subtypes of small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with dismal prognosis. Recently, molecular subtypes of SCLC have been defined by the expression status of ASCL1, NEUROD1, YAP1, and POU2F3 transcription regulators. ASCL1 is essential for neuroendocrine differentiation and is expressed in the majority of SCLC. Although previous studies investigated ASCL1 target genes in SCLC cells, ASCL1-mediated regulation of miRNAs and its relationship to molecular subtypes remain poorly explored. Here, we performed genome-wide profiling of chromatin modifications (H3K27me3, H3K4me3, and H3K27ac) by CUT&Tag assay and ASCL1 knockdown followed by RNA sequencing and miRNA array analyses in SCLC cells. ASCL1 could preferentially regulate genes associated with super-enhancers (SEs) defined by enrichment of H3K27ac marking. Moreover, ASCL1 positively regulated several SE-associated miRNAs, such as miR-7, miR-375, miR-200b-3p, and miR-429, leading to repression of their targets, whereas ASCL1 suppressed miR-455-3p, an abundant miRNA in other molecular subtypes. We further elucidated unique patterns of SE-associated miRNAs in different SCLC molecular subtypes, highlighting subtype-specific miRNA networks with functional relevance. Notably, we found apparent de-repression of common target genes of different miRNAs following ASCL1 knockdown, suggesting combinatorial action of multiple miRNAs underlying molecular heterogeneity of SCLC (e.g., co-targeting of YAP1 by miR-9 and miR-375). Our comprehensive analyses provide novel insights into SCLC pathogenesis and a clue to understanding subtype-dependent phenotypic differences.

Prediction of non-muscle invasive bladder cancer recurrence using machine learning of quantitative nuclear features.

Non-muscle invasive bladder cancer (NMIBC) generally has a good prognosis; however, recurrence after transurethral resection (TUR), the standard primary treatment, is a major problem. Clinical management after TUR has been based on risk classification using clinicopathological factors, but these classifications are not complete. In this study, we attempted to predict early recurrence of NMIBC based on machine learning of quantitative morphological features. In general, structural, cellular, and nuclear atypia are evaluated to determine cancer atypia. However, since it is difficult to accurately quantify structural atypia from TUR specimens, in this study, we used only nuclear atypia and analyzed it using feature extraction followed by classification using Support Vector Machine and Random Forest machine learning algorithms. For the analysis, 125 patients diagnosed with NMIBC were used; data from 95 patients were randomly selected for the training set, and data from 30 patients were randomly selected for the test set. The results showed that the support vector machine-based model predicted recurrence within 2 years after TUR with a probability of 90% and the random forest-based model with probability of 86.7%. In the future, the system can be used to objectively predict NMIBC recurrence after TUR.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population.

INTRODUCTION: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. RESULTS: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. DISCUSSION/CONCLUSION: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

The relationship between coronary stent strut thickness and the incidences of clinical outcomes after drug-eluting stent implantation: A systematic review and meta-regression analysis.

BACKGROUND: Drug-eluting stents (DESs) have been developed with thinner stent struts, and more biocompatible polymers and anti-proliferative drugs to improve the clinical performance. However, it remains unclear whether thinner struts are associated with favorable short- and long-term clinical outcomes such as target lesion revascularization (TLR), periprocedural myocardial infarction (PMI), and stent thrombosis (ST). METHODS: We searched MEDLINE, Embase and other online sources for randomized controlled trials (RCTs) comparing clinical outcomes between a DES and other stent(s), with independent clinical event adjudication. We investigated stent-related events (TLR, PMI, and ST) in 5 years. Each outcome was analyzed with random-effects meta-regression model against strut thickness, then adjusted for DES generation and patient and lesion characteristics. RESULTS: We identified 49 RCTs enrolling 97,465 patients, of which strut thickness ranged from 60 to 140 µm. Incidences of 1-year TLR, PMI, and early ST were reduced with thinner stent struts, when adjusted for stent generation (adjusted relative risk [RR] per 10 µm increase 1.12 [95% CI 1.04-1.21], 1.15 [95% CI 1.05-1.26], and 1.15 [95% CI 1.06-1.25], respectively). Strut thickness was not independently associated with incidences of 5-year TLR, late and very late ST. In addition, early DESs contributed to a higher incidence of very late ST (adjusted RR 2.97 [95% CI 1.36-6.50]). CONCLUSIONS: In this meta-regression analysis, a thinner strut thickness was associated with reduced incidences of early stent-related adverse events (1-year TLR, PMI, and early ST), but not with later events (5-year TLR, late ST, and very late ST).

Programmed cell death ligand 1 expression on monocytes is inversely correlated with tumour response to preoperative chemoradiotherapy for locally advanced rectal cancer.

AIM: The clinical efficacy of chemoradiotherapy (CRT) is largely dependent on host immune status. The aim of this study was to identify possible markers expressed on circulating mononuclear cells to predict tumour response in patients with locally advanced rectal cancer (LARC). METHODS: Peripheral blood samples were obtained from 47 patients diagnosed with LARC before and after CRT. The numbers of lymphocytes and monocyte subsets were analysed using flow cytometry. Based on clinical and pathological findings, patients were classified as high or low responders. RESULTS: Lymphocyte counts were markedly decreased after CRT. Total numbers of lymphocytes (p = 0.030) and CD4(+) T cells (p = 0.041) in post-CRT samples were significantly lower in low responders than in high responders. In contrast, monocyte counts were not reduced and the number of CD14dim (+) CD16(+) nonclassical (patrolling) monocytes were somewhat increased after CRT (p = 0.050). Moreover, the ratios of programmed cell death ligand 1 (PD-L1) (+) cells on patrolling monocytes before and after CRT were significantly higher in low responders than in high responders (p = 0.0046, p = 0.0006). The same trend was observed for classical and intermediate monocytes. The expression of PD-L1 on patrolling monocytes before CRT correlated inversely with the number of T cells and natural killer (NK) cells after CRT. PD-L1(+) ratio in patrolling monocytes was an independent predictor for response to CRT. CONCLUSION: Programmed cell death ligand 1 (PD-L1) expression on patrolling monocytes suppresses cell-mediated immunity in patients receiving CRT which could be related to tumour response, and may be a useful biomarker for decision-making in the management of patients with LARC.

Artificial intelligence predicts lymph node metastasis or risk of lymph node metastasis in T1 colorectal cancer.

BACKGROUND: The treatment strategies for colorectal cancer (CRC) must ensure a radical cure of cancer and prevent over/under treatment. Biopsy specimens used for the definitive diagnosis of T1 CRC were analyzed using artificial intelligence (AI) to construct a risk index for lymph node metastasis. METHODS: A total of 146 T1 CRC cases were analyzed. The specimens for analysis were mainly biopsy specimens, and in the absence of biopsy specimens, the mucosal layer of the surgical specimens was analyzed. The pathology slides for each case were digitally imaged, and the morphological features of cancer cell nuclei were extracted from the tissue images. First, statistical methods were used to analyze how well these features could predict lymph node metastasis risk. A lymph node metastasis risk model using AI was created based on these morphological features, and accuracy in test cases was verified. RESULTS: Each developed model could predict lymph node metastasis risk with a > 90% accuracy in each region of interest of the training cases. Lymph node metastasis risk was predicted with 81.8-86.3% accuracy for randomly validated cases, using a learning model with biopsy data. Moreover, no case with lymph node metastasis or lymph node risk was judged to have no risk using the same model. CONCLUSIONS: AI models suggest an association between biopsy specimens and lymph node metastases in T1 CRC and may contribute to increased accuracy of preoperative diagnosis.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.