Tokyo Dental College Ichikawa General Hospital

Background: Pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs), a life-threatening congenital heart defect (CHD), is frequently associated with abnormal pulmonary blood flow and vascular remodeling, causing hypoxia and heart failure. Segmental pulmonary hypertension (PH), a distinct PH type, may exist in some patients. Pulmonary vasodilators have been considered for treatment; however, evidence of their efficacy and safety remains lacking. Methods: A systematic review was conducted using PubMed, MEDLINE, The Cochrane Library, and Ichushi Web, encompassing studies from inception to May 2023. Inclusion criteria focused on patients with PA/VSD/MAPCAs treated with PH medications. Results: Of 86 studies screened, 6 met the inclusion criteria, including 1 cohort study and 5 case reports, comprising 22 patients. The most frequently administered medications were sildenafil (14 cases) and bosentan (12 cases), with 16 patients receiving monotherapy. Clinical improvements were observed in pulmonary vascular resistance (8/8 patients), oxygen saturation (8/19 patients), and symptoms (19/21 patients). Adverse effects were noted in five patients, including treatment discontinuation in two. Conclusions: PH medications may benefit some patients with PA/VSD/MAPCAs; however, the extremely limited sample size (n = 22) and substantial heterogeneity in anatomy, age, surgical status, and treatment regimens severely limit interpretability and clinical applicability. Considering the potential benefits and risks associated with these medications, their use should be considered cautiously and restricted to specialized centers with expertise in CHD and PH management.

We describe a technique for repairing Crawford type IV thoracoabdominal aortic aneurysms using a midline abdominal incision with left transverse extension, performed in the supine position without thoracotomy. Six patients (median age, 73 years) underwent this approach for true aneurysms, chronic dissection, or aortoduodenal fistula. Aortic reconstruction was performed with four-branched or bifurcated grafts under selective visceral perfusion. All patients were discharged home; one required reoperation for bleeding, and one developed an abdominal wall incisional hernia. This approach provided sufficient exposure for proximal and distal anastomoses and facilitated concurrent abdominal procedures while minimizing respiratory complications.

Abstract Glioblastoma patients in Japan can receive bevacizumab (Bev) from the time of initial diagnosis—a unique clinical strategy rarely adopted worldwide. This enables sequential molecular analyses using paired tumor samples from same patients obtained before, during, and after Bev exposure. To investigate resistance mechanisms to anti-angiogenic therapy, we performed qPCR-based gene expression analysis for Annexin A2 (ANXA2), metalloproteinase-2 (MMP2), metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinases-1 (TIMP1) and plasminogen activator inhibitor-1 (PAI-1) using RNA extracted from 68 Formalin-fixed Paraffin-embedded tumor samples from 33 patients with glioblastoma, including 32 paired specimens (initial surgery and refractory samples). We first focused on the paired analysis. In patients who received neoadjuvant Bev (Effective Bev) before initial surgery, comparison between primary and refractory tumors revealed significantly elevated PAI-1 expression in refractory specimens (p = 0.005), with a trend toward TIMP1 upregulation (p = 0.129). This molecular shift was not observed in pairs without neoadjuvant Bev exposure (Naïve Bev). ANXA2 and MMP9 expression negatively correlated with Bev cycle number (ρ = -0.456, p = 0.009; ρ = -0.395, p = 0.026). ANXA2 expression was higher in tumors treated with fewer than 15 Bev cycles (p = 0.037), and MMP9 was upregulated in T2 circumscribed MRI pattern (p = 0.030). Moreover, it was statistically shown that the expression level of MMP9 influences PFS (0.008). These findings suggest that prolonged Bev exposure might affect resistance by inducing invasive gene expression and distinct imaging phenotypes. Paired analyses further revealed that these molecular changes were more evident in patients who received neoadjuvant Bev. Integrating paired molecular profiles with treatment and imaging data may inform future therapeutic strategies for recurrent glioblastoma by identifying biomarkers of resistance and tailoring duration for anti-angiogenic treatment.

ABSTRACTEndoscopic ultrasound‐guided rendezvous (EUS‐RV) is an alternative technique for patients in whom selective bile duct cannulation (SBDC) has failed during endoscopic retrograde cholangiopancreatography (ERCP). However, EUS‐RV has several challenging steps. Herein, we present a method for troubleshooting the EUS‐RV using a nasobiliary drainage tube (NBD) in a patient with a large periampullary diverticulum (PAD) and severe gastroptosis. An 80‐year‐old woman presented with nausea. Contrast‐enhanced computed tomography revealed a common bile duct (CBD) stone. Although ERCP was performed twice, the ampulla of Vater (AV) could not be identified due to the large PAD. Therefore, EUS‐RV was performed. The CBD was punctured from the descending part of the duodenum. Although a guidewire was advanced through the AV, the PAD hindered guidewire insertion to the anal side of the duodenum. During the switch to duodenoscopy, the guidewire was withdrawn due to gastroptosis. A subsequent attempt to puncture the CBD through the duodenal bulb resulted in guidewire entrapment. To manage the prolonged procedure, a 5‐French NBD was temporarily placed in the CBD. An NBD was subsequently inserted into the duodenum via the PAD using esophagogastroduodenoscopy under fluoroscopic guidance after 1 week. After switching to duodenoscopy, SBDC was successful along the NBD that was not withdrawn, and the stone was removed. NBD use in EUS‐RV may be effective in difficult cases of guidewire manipulation into the distal duodenum due to PAD and guidewire maintenance due to gastroptosis. Further, NBD is a readily available device, making its use convenient.

A standard approach to the diagnosis of dry eye disease across eye care practitioners is critical to reassuring the patient, providing consistency between practitioners and informing governments as to the true prevalence and resulting healthcare needs. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III has reviewed the evidence-base since their previous reports published in 2017 and revised the definition to "Dry eye is a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and/or ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities are etiological factors." Key features from the definition include that dry eye disease is multifactorial, is a disease and not a syndrome and is always symptomatic. Differential diagnosis and ocular examination guidance is given along with the risk factors that should be discussed with the patient. The recommended screening questionnaire is the OSDI-6 with a cut-off score ≥4. A positive result together with a non-invasive breakup time <10s or alternatively tear film hyperosmolarity (≥308mOsm/L in either eye or an interocular difference >8mOsm/L) or alternatively >5 corneal fluorescein and/or >9 conjunctival lissamine green punctate spots and/or lid margin lissamine green staining of ≥2mm length & ≥25 % width, gives a diagnosis of dry eye. Subclassification was separated into tear film deficiencies (lipid, aqueous and mucin/glycocalyx), eyelid anomalies (blink/lid closure and lid margin) and ocular surface abnormalities (anatomical misalignment, neural dysfunction, ocular surface cell damage/disruption and primary inflammation/oxidative stress) components, with appropriate clinical tests and cut-offs provided to identify these etiological drivers in an individual, to inform appropriate management and therapy.

To improve the explainability of a YOLOv5-based model for anterior segment disease diagnosis by combining gradient-weighted class activation mapping ++ (Grad-CAM++) and cut-and-paste validation and evaluate the influence of extracorneal information on diagnostic accuracy. In total, 1039 slit-lamp photographs across nine diagnostic categories were analyzed using a previously developed YOLOv5 model. Grad-CAM++ was implemented to visualize the attention patterns across key network layers. To quantitatively assess clinical relevance, attention maps were compared against expert-delineated lesion boundaries using Intersection over Union (IoU). Furthermore, cut-and-paste validation was performed by systematically swapping the corneal regions with different backgrounds to probe the reliance of the model on contextual information. Grad-CAM++ analysis revealed hierarchical attention focus, progressing from broad in the early layers to highly localized in the final layers, with layer 23 showing distinct disease-specific patterns. Cut-and-paste validation demonstrated that model accuracy was highly dependent on the background context for certain diseases; for instance, the accuracy for infectious keratitis and acute primary angle closure dropped significantly upon background alteration. Critically, the clinical relevance of the attention maps measured by the IoU against expert annotations was significantly higher for correct predictions than for incorrect predictions, linking the model's visual explanation to its diagnostic reliability. Combining Grad-CAM++ with cut-and-paste validation provided a robust framework for evaluating the explainability of the YOLOv5 model. This dual approach reveals layer-specific attention dynamics and quantifies the model's reliance on clinically relevant extracorneal features, thereby enhancing the transparency and trustworthiness of artificial intelligence-based diagnostic systems in ophthalmology.

This retrospective cohort study aimed to emulate the ADVANCE trial population and directly compare the Endurant and Excluder using propensity score matching. Patients were included if endovascular aneurysm repair was performed for abdominal aortic aneurysm using either Endurant or Excluder at 10 hospitals in Japan between January 2012 and July 2022. Cases were selected according to the modified ADVANCE trial inclusion and exclusion criteria. To minimize selection bias and simulate a randomized controlled trial setting, propensity score matching was performed using patient and anatomical characteristics. The primary outcome measure was the proportion of patients with sac regression ≥ 5mm at 1year. The secondary outcome measures were rates of freedom from late complications, T1aEL, sac enlargement ≥ 5mm, and overall survival. Outcomes were first analyzed in patients within the instructions for use (IFU) and then in all matched patients including outside IFU patients. After matching, the within-IFU group included 124 pairs and the total cohort of 266 pairs. The primary outcome measures for Endurant and Excluder were met in 38.9% and 36.6% (p = 0.74) in the within-IFU group and 33.5% and 35.0% (p = 0.74) in the total cohort, respectively. No significant differences were observed in any secondary outcome measures. However, T2EL and use of additional proximal cuff were significantly more frequent for Excluder in both the within-IFU and total cohort. Furthermore, T1b and T5ELs occurred significantly more for Endurant in the total cohort. There were no significant differences in all clinical outcome measures between Endurant and Excluder. Level IV, multicenter retrospective cohort study.

<title>Abstract</title> Limbal stem cell deficiency (LSCD) is a debilitating condition that impairs corneal transparency and visual function due to damage of the limbal niche. Traditional treatments often fall short in bilateral cases or severe opacity. Cultivated oral mucosal epithelial transplantation (COMET) has recently emerged as a novel regenerative approach to restore the ocular surface in LSCD. Here we show that COMET leads to significant improvements in visual acuity and reduction of corneal surface irregularities. Using anterior segment optical coherence tomography (OCT), we evaluated corneal reflectivity in the epithelial, stromal, and endothelial layers over time. We found early reduction in epithelial opacity, while stromal reflectivity showed a persistent correlation with visual outcomes. Higher-order aberrations also decreased postoperatively and were significantly associated with better vision. These findings demonstrate the clinical potential of COMET to improve both structural and optical quality of the cornea and highlight the value of quantitative OCT imaging in evaluating therapeutic response. This study provides new insight into visual rehabilitation mechanisms in patients with severe LSCD and supports broader application of cultivated epithelial cell therapies in ocular surface reconstruction.