The Absorb GT1 Bioresorbable Vascular Scaffold System　- 5-Year Post-Market Surveillance Study in Japan.

BACKGROUND: The 1-year clinical outcomes of the Absorb GT1 Japan post-market surveillance (PMS) suggested that an appropriate intracoronary imaging-guided bioresorbable vascular scaffold (BVS) implantation technique may reduce the risk of target lesion failure (TLF) and scaffold thrombosis (ST) associated with the Absorb GT1 BVS. The long-term outcomes through 5 years are now available.Methods and Results: This study enrolled 135 consecutive patients (n=139 lesions) with ischemic heart disease in whom percutaneous coronary intervention (PCI) with the Absorb GT1 BVS was attempted. Adequate lesion preparation, imaging-guided appropriate sizing, and high-pressure post-dilatation using a non-compliant balloon were strongly encouraged. All patients had at least 1 Absorb GT1 successfully implanted at the index procedure. Intracoronary imaging was performed in all patients (optical coherence tomography: 127/139 [91.4%] lesions) and adherence to the implantation technique recommendations was excellent: predilatation, 100% (139/139) lesions; post-dilatation, 98.6% (137/139) lesions; mean (±SD) post-dilatation pressure, 18.8±3.5 atm. At 5 years, the follow-up rate was 87.4% (118/135). No definite/probable ST was reported through 5 years. The cumulative TLF rate was 5.1% (6/118), including 2 cardiac deaths, 1 target vessel-attributable myocardial infarction, and 3 ischemia-driven target lesion revascularizations. CONCLUSIONS: Appropriate intracoronary imaging-guided BVS implantation, including the proactive use of pre- and post-balloon dilatation during implantation may be beneficial, reducing the risk of TLF and ST through 5 years.

Enhancing Long-Term Durability of Electrochemical Reactors Producing Formate from CO2 and Water Designed for Integration with Solar Cells.

Artificial photosynthetic cells producing organic matter from CO2 and water have been extensively studied for carbon neutrality, and the research trend is currently transitioning from proof of concept using small-sized cells to large-scale demonstrations for practical applications. We previously demonstrated a 1 m2 size cell in which an electrochemical (EC) reactor featuring a ruthenium (Ru)-complex polymer (RuCP) cathode catalyst was integrated with photovoltaic cells. In this study, we tackled the remaining issue to improve the long-term durability of cathode electrodes used in the EC reactors, demonstrating high Faradaic efficiencies exceeding 80% and around 60% electricity-to-chemical energy-conversion efficiencies of a 75 cm2 sized EC reactor after continuous operation for 3000 h under practical conditions. Introduction of a pyrrole derivative containing an amino group in the RuCP coupled with UV-ozone treatment to create carboxyl groups on the carbon supports effectively reduced the detachment of the RuCP catalyst by forming a strong amide linkage. A newly developed chemically resistant graphite adhesive prevented the carbon supports from peeling off of the conductive substrates. In addition, highly durable anodes composed of IrOx-TaOy/Pt-metal oxide/Ti were adopted. Even though the EC reactor was installed at an inclined angle of 30°, which is approximately the optimal angle for receiving more solar energy, the crossover reactions were sufficiently suppressed because the porous separator film impeded the transfer of oxygen gas bubbles from the anode to the cathode. The intermittent operation improved the energy-conversion efficiency because the accumulated bubbles were removed at night.

Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products.

INTRODUCTION: An investigation of the suitability of reagents for measuring FVIII products in a one-stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII-deficient plasma (F8DP), even though the APTT-based OSA is comprised of APTT reagents and factor-deficient plasma. AIM: A single-centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. METHODS: FVIII:C in nine types of FVIII product-spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. RESULTS: F8DP-dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP-3). This lower TR was not observed with alternative manufacturing lots of F8DP-3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP-3. CONCLUSION: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.

Effects of Extended Fixation on Advanced Gastric Cancer HER2 Status Assessment Using IHC and FISH.

BACKGROUND/AIM: In gastric cancer, accurate determination of human epidermal growth factor receptor type 2 (HER2) status is crucial for treatment decision-making. However, the optimal formalin fixation time of gastric cancer specimens for HER2 status determination remains unestablished. Here, we investigated real-world data on formalin overfixation and its effect on HER2 status determination in gastric cancer. PATIENTS AND METHODS: We comprehensively analyzed HER2 testing results in 228 gastric cancer specimens, including those subjected to formalin overfixation. Subsequently, we divided 52 resected specimens of advanced gastric cancer into three groups and studied the effects of short-term (6-72 h) and long-term (1 and 2 weeks) fixation on HER2 status determination using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: A total of 21.5% (49/228) of the specimens were HER2-positive, whereas 78.5% (179/228) were negative. Among the HER2-negative specimens, no biopsies were overfixed, whereas 12.5% (9/72) of the surgical resection specimens were overfixed. The HER2 status of the 6-72-h group was 82.7% and 76.9% identical to that of the 1- and 2-week groups, when determined using IHC, and 73.1% and 36.5%, when determined using FISH, respectively. However, HER2 determination was not feasible in 26.9% and 63.5% of the specimens in the 1- and 2-week groups, respectively. CONCLUSION: Formalin overfixation may hinder the determination of HER2 status and should be avoided in gastric cancer sample preparation.

High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer.

BACKGROUND: To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. METHODS: This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. RESULTS: Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175-7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. CONCLUSIONS: Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC.

Basement membrane extract potentiates the endochondral ossification phenotype of bone marrow-derived mesenchymal stem cell-based cartilage organoids.

Endochondral ossification is a developmental process in the skeletal system and bone marrow of vertebrates. During endochondral ossification, primitive cartilaginous anlages derived from mesenchymal stem cells (MSCs) undergo vascular invasion and ossification. In vitro regeneration of endochondral ossification is beneficial for research on the skeletal system and bone marrow development as well as their clinical aspects. However, to achieve the regeneration of endochondral ossification, a stem cell-based artificial cartilage (cartilage organoid, Cart-Org) that possesses an endochondral ossification phenotype is required. Here, we modified a conventional 3D culture method to create stem cell-based Cart-Org by mixing it with a basement membrane extract (BME) and further characterized its chondrogenic and ossification properties. BME enlarged and matured the bone marrow MSC-based Cart-Orgs without any shape abnormalities. Histological analysis using Alcian blue staining showed that the production of cartilaginous extracellular matrices was enhanced in Cart-Org treated with BME. Transcriptome analysis using RNA sequencing revealed that BME altered the gene expression pattern of Cart-Org to a dominant chondrogenic state. BME triggered the activation of the SMAD pathway and inhibition of the NK-κB pathway, which resulted in the upregulation of SOX9, COL2A1, and ACAN in Cart-Org. BME also facilitated the upregulation of genes associated with hypertrophic chondrocytes (IHH, PTH1R, and COL10A1) and ossification (SP7, ALPL, and MMP13). Our findings indicate that BME promotes cartilaginous maturation and further ossification of bone marrow MSC-based Cart-Org, suggesting that Cart-Org treated with BME possesses the phenotype of endochondral ossification.

Laparoscopic spleen-preserving distal pancreatectomy: A novel technique with splenic artery resection and splenic vein preservation.

INTRODUCTION: Laparoscopic spleen-preserving distal pancreatectomy (LSDP) is widely performed to treat benign and low-grade malignant diseases. Although preservation of splenic vessels may be desirable considering the risk of postoperative complications, it is sometimes difficult due to tumor size, inflammation, and proximity of the tumor and splenic vessels. Herein, we present the first case of LSDP with splenic artery resection and splenic vein preservation. MATERIALS AND SURGICAL TECHNIQUE: A 40-year-old woman with a pancreatic tumor was referred to our hospital. Contrast-enhanced computed tomography (CT) revealed a tumor in the pancreatic tail that was in contact with the splenic artery and distant from the splenic vein. The splenic artery and vein were separated from the pancreas near the dissection line. The splenic artery was resected after pancreatic dissection using a linear stapler. After the pancreatic tail was separated from the splenic hilum while preserving the splenic vein, the distal side of the splenic artery was resected, and the specimen was removed. The postoperative course was uneventful and the patient was discharged on postoperative Day 9. Four months after surgery, postoperative follow-up CT findings showed neither splenic infarction nor gastric varices. DISCUSSION: This technique is an alternative method of splenic preservation when there is no attachment of the tumor to the splenic vein or uncontrolled expected bleeding of the splenic artery using the Kimura technique.

Association of physical activity with bleeding events and safety in patients with haemophilia A starting emicizumab prophylaxis: an interim analysis of the TSUBASA study.

INTRODUCTION: Little information exists on the relationship between bleeding outcomes and physical activity in patients with haemophilia A (PwHA). AIM: This interim analysis of the TSUBASA study (UMIN-CTR ID: UMIN000037448) evaluated the association of physical activity with bleeding and safety in PwHA starting emicizumab. METHODS: PwHA without factor VIII inhibitors were recruited. Physical activity and bleed data were obtained using an electronic patient-reported outcome application and wearable activity tracker. Adverse events (AEs) were documented. RESULTS: At data cut-off (31-May-2021), 107 PwHA were enrolled, with a median (range) age of 35 (0-73) years. Physical activity data were obtained for 74 participants. Of these, 47 (63.5%) recorded a total of 396 exercise events. The most common exercise events were walking (32.4%), cycling (14.9%), and football (5.4%). Two (0.5%) exercise events in the same individual were associated with bleeding (running, weight training). The safety analysis population consisted of 106 participants treated with emicizumab (median observation period: 241.5 days). Twenty-one (19.8%) participants experienced a total of 39 AEs. Five (4.7%) experienced a serious AE, none of which was emicizumab-related, and three (2.8%) experienced an adverse drug reaction. CONCLUSIONS: PwHA receiving emicizumab in the TSUBASA study experienced minimal bleeding associated with physical activity. TRIAL REGISTRATION: Trial registration: UMIN-CTR ID: UMIN000037448.

Current status of vaccine immunotherapy for gastrointestinal cancers.

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin's lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors.

Impact of Medina classification on clinical outcomes of imaging-guided coronary bifurcation stenting.

Background: Intracoronary imaging improves clinical outcomes after stenting of complex coronary bifurcation lesions (CBLs), but the impact of Medina classification-based CBL distribution on outcomes of imaging-guided bifurcation stenting is unclear. Methods: In this integrated analysis of four previous studies, in which all CBLs were treated with drug-eluting stents under intravascular ultrasound or optical coherence tomography guidance, the distribution of 763 CBLs was assessed using angiographic Medina classification. Major adverse cardiac events (MACE), including target lesion revascularization (TLR), myocardial infarction, stent thrombosis, and cardiac death, were investigated at 1-year follow-up. Results: The most and least prevalent Medina subtypes were 0-1-0 (27.9 %) and 0-0-1 lesions (2.8 %). The most and least frequent MACE/TLR rates were 18.2 %/18.2 % for 0-0-1 lesions and 4.1 %/2.8 % for 0-1-0 lesions. Risks were higher for 0-0-1 lesions than for 0-1-0 lesions for both MACE (hazard ratio [HR]: 4.04, 95 % confidence interval [CI]: 1.21-13.45, p = 0.02) and TLR (HR: 6.19, 95 % CI: 1.69-22.74, p = 0.006). MACE rates were similar for true and non-true CBLs excluding 0-0-1 lesions (8.2 % and 5.9 %, HR 1.54, 95 % CI: 0.86-2.77, p = 0.15), while MACE (HR: 3.25, 95 % CI: 1.10-9.63, p = 0.03) and TLR (HR: 4.24, 95 % CI: 1.38-12.96, p = 0.01) risks were higher for 0-0-1 lesions. Conclusions: This integrated analysis of imaging-guided bifurcation stenting demonstrated similar clinical outcomes in true and non-true CBLs, except for 0-0-1 lesions, which had a significantly higher risk of MACE/TLR.

[A Recurrent Colon Cancer Successfully Treated by Nivolumab plus Ipilimumab with On and Off for Preventing Exacerbation of Skin Disorders].

Here, we report a case in which nivolumab plus ipilimumab combination therapy was significantly effective for MSI-high recurrent colon cancer with acute exacerbation after 5-FU/L-OHP/CPT-11 treatment. At the end of 4 cycles of combination therapy, clinical CR was obtained on diagnostic imaging. At the end of the 2 cycles of transition from combination therapy to monotherapy, eosinophilia was observed in a quadratic function, and exacerbation of skin disorders was observed. Eosinophil counts normalized promptly after discontinuation of treatment, and skin disorders gradually improved. Two months after the discontinuation of treatment, monotherapy was restarted. After the resumption of treatment, an increase in eosinophils and worsening of skin symptoms were observed again, and stopped treatment. We report an interesting case in which immune checkpoint inhibiter were turned on and off according to eosinophil counts for preventing exacerbation of skin disorders, and for maintaining cancer remission by continuing immune checkpoint inhibitor treatment.

Efficacy of Staging Laparoscopy in Patients With Pancreatic Cancer: A Single Center Prospective Cohort Study.

BACKGROUND/AIM: Staging laparoscopy (SL) for pancreatic cancer (PC) is considered useful to improve accuracy of staging and resectability. However, given the current accuracy of preoperative imaging, the routine application of SL remains unclear. Therefore, we aimed to investigate the importance of SL in patients with PC without radiological distant metastasis. PATIENTS AND METHODS: This was a prospective, cohort, observational study. SL was performed in all patients with PC without radiological distant metastasis before pancreatectomy or chemotherapy at the Yamaguchi University Hospital. RESULTS: Between July 2020 and March 2023, 55 patients underwent SL with peritoneal cytology. The median age was 71, with 53% male patients. SL revealed occult metastasis in six (11%) patients including positive peritoneal cytology (n=6), and peritoneal dissemination (n=1). The resectability of unresectable locally advanced (UR-LA) was associated with a significantly increased risk of occult metastasis (p=0.0211). The median operative time was 40 min, and the median volume of blood loss was 3 ml. There were no severe complications (Clavien-Dindo III or higher). CONCLUSION: SL with peritoneal cytology regardless of previous abdominal surgery is safe and effective to determine accurate staging. Therefore, SL with peritoneal cytology should be considered for patients with PC without radiological distant metastasis, especially in those with UR-LA.

Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data.

INTRODUCTION: With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. AIM: This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. METHODS: The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. RESULTS: Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. CONCLUSION: This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients' quality of life.

A novel prediction model of pancreatic fistula after pancreaticoduodenectomy using only preoperative markers.

BACKGROUND: Since clinically relevant postoperative pancreatic fistula (CR-POPF) can cause intra-abdominal hemorrhage and abscesses, leading to surgery-related deaths after pancreaticoduodenectomy (PD), its preoperative prediction is important to develop strategies for surgical procedures and perioperative management. This study aimed to establish a novel prediction model for CR-POPF using preoperative markers. METHODS: On a training set of 180 patients who underwent PD at the Yamaguchi University Hospital, a combination of CR-POPF predictors were explored using the leave-one-out method with a unique discrete Bayes classifier. This predictive model was confirmed using a validation set of 366 patients who underwent PD at the Osaka University Hospital. RESULTS: In the training set, CR-POPF occurred in 60 (33%)　of 180 patients and 130 (36%)　of 366 patients in the validation set using selected markers. In patients with pancreatic ductal adenocarcinoma (PDAC), the main pancreatic duct (MPD) index showed the highest prognostic performance and could differentiate CR-POPF with 87% sensitivity and 81% specificity among 84 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index-based model for 130 PDAC samples were 93% and 87%, respectively. In patients with non-PDAC, the MPD index/body mass index (BMI) combination showed the highest prognostic performance and could differentiate CR-POPF with 84% sensitivity and 57% specificity among 96 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index/BMI-based model for 236 non-PDAC samples were 85% and 53%, respectively. CONCLUSION: We developed a novel prediction model for pancreatic fistulas after PD using only preoperative markers. The MPD index and MPD index/BMI combination will be useful for CR-POPF assessment in PDAC and non-PDAC samples, respectively.

Prediction of Slow-Flow Phenomenon After Stent Implantation Using Near-Infrared Spectroscopy in Patients With Acute and Chronic Coronary Syndrome.

BACKGROUND: The slow-flow phenomenon is associated with worse clinical outcomes after percutaneous coronary intervention (PCI), so our goal for this study was to see how predictive how near-infrared spectroscopy (NIRS) could be.Methods and Results: We enrolled 179 lesions from 152 patients who had de novo coronary stent implantation guided by NIRS-intravascular ultrasound (IVUS) (male: 69.1%, mean age: 74.3±11.5 years, acute coronary syndrome: 65.1%, diabetes: 42.1%). NIRS automatically determined the maximum 4-mm lipid core burden index (maxLCBI4 mm) value at pre- and post-PCI procedures. The slow-flow phenomenon was defined as the deterioration of TIMI (Thrombolysis in Myocardial Infarction) flows on angiography during the PCI procedure in the absence of mechanical obstruction. The slow-flow phenomenon occurred in 13 (7.3%) lesions, and the slow-flow phenomenon group had a significantly higher maxLCBI4 mm(740±147 vs. 471±223, P<0.001). The best maxLCBI4 mmcutoff point in both acute and chronic coronary syndrome was 578 and 480, with sensitivity of 100%, for predicting the slow-flow phenomenon. In the receiver-operating characteristics analysis, the area under the curve for acute and chronic coronary syndrome was 0.849 and 0.851, respectively. CONCLUSIONS: The results of this study support the utility of NIRS-IVUS-guided PCI for the prediction of the slow-flow phenomenon.

Impact of coronary bifurcation angle on stent malapposition in a randomized comparison between proximal optimization technique followed by side branch dilatation and kissing balloon inflation.

Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 µm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p < 0.05). In the POT-SBD group, worsening ISA after SBD was prominent at the distal bifurcation. The BA was an independent predictor of major ISA (odds ratio 1.04, 95% confidence interval 1.00-1.07, p < 0.05) with a cut-off value of 59.5° (p < 0.05). However, the cases treated with optimal POT in the short BA (<60°) indicated the lowest incidence of major ISA. In the KBT group, BA had no significant impact. Conclusion: A wide BA has a potential risk for the occurrence of major ISA after POT followed by SBD in coronary bifurcation stenting.

A Deep Learning-Based Model for Classifying Osteoporotic Lumbar Vertebral Fractures on Radiographs: A Retrospective Model Development and Validation Study.

Early diagnosis and initiation of treatment for fresh osteoporotic lumbar vertebral fractures (OLVF) are crucial. Magnetic resonance imaging (MRI) is generally performed to differentiate between fresh and old OLVF. However, MRIs can be intolerable for patients with severe back pain. Furthermore, it is difficult to perform in an emergency. MRI should therefore only be performed in appropriately selected patients with a high suspicion of fresh fractures. As radiography is the first-choice imaging examination for the diagnosis of OLVF, improving screening accuracy with radiographs will optimize the decision of whether an MRI is necessary. This study aimed to develop a method to automatically classify lumbar vertebrae (LV) conditions such as normal, old, or fresh OLVF using deep learning methods with radiography. A total of 3481 LV images for training, validation, and testing and 662 LV images for external validation were collected. Visual evaluation by two radiologists determined the ground truth of LV diagnoses. Three convolutional neural networks were ensembled. The accuracy, sensitivity, and specificity were 0.89, 0.83, and 0.92 in the test and 0.84, 0.76, and 0.89 in the external validation, respectively. The results suggest that the proposed method can contribute to the accurate automatic classification of LV conditions on radiography.

Clinical course and prognosis of patients with hepatocellular carcinoma and haemophilia.

INTRODUCTION: Although patients with haemophilia are known to develop hepatocellular carcinoma (HCC) at a lower age than patients without, there are few reports on the clinical course and prognosis of HCC. AIM: We aimed to investigate the clinical course and prognosis of patients with HCC and haemophilia. METHODS: Twenty-two patients with haemophilia, who were initially diagnosed with HCC between 2003 and 2021, were included. Their clinical courses and prognoses were retrospectively analysed. The results were compared with those of the 24th Nationwide Follow-up Survey of Primary Liver Cancer. RESULTS: All 22 patients were male; of these, 20 patients had haemophilia A, and 2 had haemophilia B. The mean age of diagnosis was 63 years (range 45-78 years) which is lower than the mean of 72 years reported in the Nationwide Survey. The mean diameter of the largest tumour was 30 mm (range 11-70 mm), and 18 tumours (82%) were solitary at the initial diagnosis. Standard treatments for HCC were performed in all patients. Sixty-one transarterial chemoembolisation, 28 RFA, 10 hepatectomies, and 2 radiation treatments were performed, and molecular-targeted agents were administered to 5 patients during their clinical courses. No deaths were associated with complications of HCC treatments. The median survival time after initial treatment was 6.4 years (range 0.9-18.7 years) which did not differ much from the median survival time of 5.8 years in the Nationwide Survey. CONCLUSION: Standard treatment for HCC could improve the prognosis of patients with HCC and haemophilia.