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A 70-year-old man with hypertensive heart disease underwent catheter ablation of persistent atrial fibrillation. After completing the pulmonary vein isolation, atrial burst pacing induced an annular atrial tachycardia (AT). Overdrive pacing exhibited constant fusion, indicating a macroreentrant mechanism of the AT. However, the CARTO3 activation map created using the Octaray catheter (both Biosense Webster, Irvine, CA) exhibited a centrifugal spread with the earliest activation site at the 4 o'clock position of the tricuspid annulus. In contrast, the Ripple map revealed a clear reentrant circuit with its isthmus located at the 4–6 o'clock position of the tricuspid annulus. The local electrograms in these areas recorded systolic and diastolic potentials simultaneously, and the misannotation of the large far-field potentials caused this discrepant result. Handling low-amplitude complex fractionated electrograms remains a challenge in creating a precise activation mapping. The Ripple map, especially when combined with the Octaray catheter, was effective in dynamically visualizing all these electrograms and accurately delineating the reentrant circuit.

Abstract This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p

Abstract Background and purpose The ANNEXA‐4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. Methods Thirty patients were randomly selected from the ANNEXA‐4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty‐eight different ANNEXA‐4 subjects were also randomly selected to assess intra‐rater reliability of total ICrH volume measurement change at baseline and 12‐h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA‐4. Results Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. Conclusion Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Abstract Objectives Flexible endoscopy does not have a system that can automatically evacuate surgical smoke generated in the gastrointestinal lumen. We aimed to investigate the feasibility and potential usefulness of automatic smoke evacuation systems in flexible endoscopy. Methods [Bench] After surgical smoke generated in the stomach was evacuated by the evacuator, the degree of residual smoke and gastric luminal collapse were evaluated to optimize the evacuator settings. [Animal] Insufflation, suction, and total operation time to complete the protocol of 10 cauterizations of the gastric mucosa were measured in three groups: “manual suction only,” “manual suction with automatic evacuation (50% force),” and “manual suction with automatic evacuation (70% force).” The stability of endoscopic visualization and operability was evaluated by 10 endoscopists blinded to those suction settings, and the number of manual suctions, insufflations, and total operation time were measured. Results [Bench] The degree of residual smoke and gastric luminal collapse were inversely correlated. [Animal] When the automatic evacuator was partially used, there was no difference in the insufflation time, but the suction time (vs 50%; p = 0.011, vs. 70%; p = 0.011) and total operation time (vs. 50%; p = 0.012, vs. 70%; p = 0.036) were significantly reduced compared to manual operation only. Furthermore, manual suction with automatic evacuation (50% force) significantly improved the stability of endoscopic visualization and operability compared to manual operation only (p = 0.041, p = 0.0085). Conclusions The automatic smoke evacuation in flexible gastrointestinal endoscopy was potentially feasible and useful by improving the device setting.

Abstract Background and aims In our previous study, we visualized and systematically evaluated gas leakage from the forceps plug of the gastrointestinal endoscope system using the Schlieren system. In order to minimize the potential risk of infection from gas leakage from the gastrointestinal endoscope, the development of a new forceps plug was considered urgent. In this study, we analyzed the structure of commercially available forceps plugs and attempted to develop new forceps plugs with improvements. Methods Microfocus computed tomography was used to nondestructively analyze the structural changes that occur when forceps are inserted into a commercially available forceps plug. Based on the findings, the basic structure of the newly developed forceps plug was set. We examined the airtightness of these newly developed plugs using the Schlieren system and also compared their fractional resistance with those of commercially available plugs. Results As a result of the nondestructive analysis, all of the commercially available plugs had a single valve, and the cleavage created in the valve during forceps, insertion was large in the case of plugs with slit‐type entrances. In the newly developed forceps plugs, all four types of plugs showed less gas leakage and similar or better usability compared to the commercially available plugs. Conclusions The structural weaknesses of the existing gastrointestinal endoscopic forceps plugs were identified. Based on the findings, we froze the design of a prototype of a new forceps plug that was airtight and not inferior in usability compared to commercially available plugs.

Abstract The reproducibility of longitudinal strain measured by 2D speckle tracking echocardiography (2DSTE) may be affected by ultrasound settings. This study investigated the effect of transmit ultrasound frequency on global longitudinal strain (GLS) by 2DSTE. Apical, 2- and 4-chamber, and long-axis views were obtained in consecutive 162 patients using Philips ultrasound devices. Three different frequency presets were used sequentially: high resolution (HRES, 1.9 to 2.1 MHz), general (HGEN, 1.6 to 1.8 MHz), and penetration mode (HPEN, 1.3 to 1.6 MHz). GLS values were determined for each preset using the Philips Q-station software, resulting in GLS-HRES, GLS-HGEN, and GLS-HPEN. Among the 151 patients with successfully measured GLS, a significant difference in GLS was observed among the three presets (p

Abstract Background A diaphragmatic hernia is a prolapse of the abdominal organs into the thoracic cavity through a hole in the diaphragm. Traumatic diaphragmatic injuries are rare and usually occur after blunt or penetrating thoracic or abdominal traumas. Blunt diaphragmatic rupture rarely accounts for immediate mortality and may go clinically silent until complications occur which can be life threatening. It usually present late with intrathoracic herniation of abdominal viscera and carry a high mortality rate. We experienced a very rare case who showed repeated colon incarcerations 7 years after injury. And, we operated laparoscopically. Case presentation A 64-year-old man presented with multiple left rib fractures that occurred during an accident. After 7 years, he visited the emergency department with the chief complaint of left shoulder pain and epicardial pain after eating. He was diagnosed with transverse colon incarceration due to a left diaphragmatic hernia by computed tomography (CT) and X-ray imaging. Surgical repair was recommended, but he refused as the symptoms improved. Fourteen months later, the patient revisited the hospital in similar symptoms and improved spontaneously. He consulted our hospital for the surgical indication. We recommended that he undergo surgery, showing images of the X-ray and CT when his transverse colon was obstructed and he felt pain and when symptoms improved. Finally, he decided to undergo surgery. We performed diaphragmatic hernia repair with laparoscopic direct suturing in good view. The patient experienced an uneventful postoperative recovery period. The absence of diaphragmatic herniation recurrence was confirmed seven months after surgery. Conclusions We experienced a traumatic diaphragmatic hernia with repeated colon incarcerations 7 years after injury and performed surgical repair laparoscopically.

Abstract Background Severe scoliosis can cause reflux esophagitis, and is a risk factor for Barrett's adenocarcinoma of the esophagus. Severe scoliosis is associated with respiratory dysfunction, impaired operative tolerance, and anatomical difficulty in surgical manipulation, and is, therefore, considered a high surgical risk. In this report, we describe the case of a young patient with Barrett's esophageal adenocarcinoma with severe scoliosis who underwent salvage surgery after radical chemoradiotherapy. Case presentation The patient was a 39-year-old male. Although he had severe scoliosis and paraplegia of both lower limbs since childhood, he was independent in activities of daily living. His previous doctor, who diagnosed the esophageal cancer, determined that surgery was not indicated due to the coexistence of severe scoliosis, so he underwent chemoradiotherapy with curative intent. After chemoradiotherapy, the patient was referred to our hospital for a second opinion because of a tumor remnant. After various additional examinations, thoracoscopic and laparoscopic subtotal esophagectomy for esophageal cancer was performed, along with ante-thoracic route reconstruction using a narrow gastric tube. Although the patient had symptoms associated with postoperative reflux, he recovered well overall and was discharged home about 4 weeks after surgery. Conclusions We report the case of an esophageal cancer patient with severe scoliosis at high surgical risk who underwent successful minimally invasive esophagectomy.

Abstract Background Familial gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the digestive tract caused by germline gain-of-function mutations in the KIT gene or platelet-derived growth factor receptor alpha gene (PDGFRA). These mutations cause not only multiple GISTs but also diffuse hyperplasia of interstitial cells of Cajal (ICCs), which is related to esophageal motility disorder. Case presentation A 53-year-old man was referred to our hospital because of anemia and dysphagia. Fifteen years earlier, he had undergone a laparoscopic partial gastrectomy for multiple gastric GISTs with a germline mutation in exon 17 of the KIT gene. An upper gastrointestinal endoscopy revealed that the patient had multiple gastric GISTs and a large esophageal diverticulum directly above the esophagogastric junction. The largest gastric tumor was 7 cm, with a delle that might cause bleeding. Because the patient presented with dysphagia, we performed video-assisted thoracic esophagectomy and laparoscopic-assisted proximal gastrectomy simultaneously. The patient had survived without metastasis for 4 years after surgery and dysphagia had improved. Conclusions This is the first report of successful laparoscopic–thoracoscopic surgery for a patient with familial gastric GISTs accompanied with a large esophageal diverticulum.

Background Ischemic stroke is an important cause of death in the world. The malignant middle cerebral artery infarction (MMCAI) has mortality as high as 80% when clinically treated. In this setting, decompressive craniectomy is a life-saving measure, in spite of high morbidity among survivors.

Abstract Background Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch‐type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea‐hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. Methods This study was conducted under a retrospective, single‐center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal‐AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP‐AHI) to that using PSG (PSG‐AHI). Results The WP‐AHI was 25.9 ± 12.7 and PSG‐AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP‐AHI

Background Massive rotator cuff tears (RCTs) are complicated by muscle atrophy, fibrosis, and intramuscular fatty degeneration, which are associated with postoperative tendon-to-bone healing failure and poor clinical outcomes. We evaluated muscle and enthesis changes in large tears with or without suprascapular nerve (SN) injury in a rat model. Methods Sixty-two adult Sprague-Dawley rats were divided into SN injury (+) and SN injury (–) groups (n=31 each), comprising tendon (supraspinatus [SSP]/infraspinatus [ISP]) and nerve resection and tendon resection only cases, respectively. Muscle weight measurement, histological evaluation, and biomechanical testing were performed 4, 8, and 12 weeks postoperatively. Ultrastructural analysis with block face imaging was performed 8 weeks postoperatively. Results SSP/ISP muscles in the SN injury (+) group appeared atrophic, with increased fatty tissue and decreased muscle weight, compared to those in the control and SN injury (–) groups. Immunoreactivity was only positive in the SN injury (+) group. Myofibril arrangement irregularity and mitochondrial swelling severity, along with number of fatty cells, were higher in the SN injury (+) group than in the SN injury (–) group. The bone-tendon junction enthesis was firm in the SN injury (–) group; this was atrophic and thinner in the SN injury (+) group, with decreased cell density and immature fibrocartilage. Mechanically, the tendon-bone insertion was significantly weaker in the SN injury (+) group than in the control and SN injury (+) groups. Conclusions In clinical settings, SN injury may cause severe fatty changes and inhibition of postoperative tendon healing in large RCTs. Level of evidence Basic research, controlled laboratory study.

Abstract This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p

The use of coercive measures in psychiatric inpatient settings has been an important issue for many years. Nursing interventions based on a strengths model could enable a reduction in the use of these measures. This study aimed to describe the practice of nursing interventions using a strengths model for psychiatric inpatients who have been in seclusion for a long time. We also constructed a nursing model to minimize coercive measures. The participants were eight inpatients who had been in seclusion for a long time. Nursing interventions based on a strengths model were implemented in collaboration with nurses from six long-term care units in three psychiatric hospitals in Japan. For 4 of the 8 participants, the seclusion time decreased by 20–45%. However, for another 2, it increased by about 23–34%. An average decrease of 9.6% was observed, and the open observation time increased by 1.4 h per day on the seclusion days. When using this model, the nurses considered the effects of stimulating strengths. We believe this approach may promote inpatients’ self-insight. Considering the perspective of stimulus adjustment might be useful for maximizing the positive effects of working on strengths.

Abstract Background Workflow interruptions in pharmacies contribute to dispensing errors, a high-priority issue in patient safety, but have rarely been studied from a systemic perspective partly because of the limitations of the conventional reductionistic approach. This study aims to identify a mechanism for the occurrence of interruptions in a hospital pharmacy and find interventional points using a synthetic approach based on resilience engineering and systems thinking, and assess implemented measures for reducing them. Methods At a Japanese university hospital, we gathered information about performance adjustments of pharmacists in the inpatient medication dispensing unit for oral and topical medicines (IMDU-OT) and nurses in the inpatient wards (IPWs) in the medication dispensing and delivery process. Data about the workload and workforce of pharmacists were collected from hospital information systems. Telephone inquiries and counter services in the IMDU-OT, the primary sources of interruptions to pharmacists' work, were documented. The feedback structure between the IMDU-OT and the IPWs was analyzed using a causal loop diagram to identify interventional points. The numbers of telephone calls and counter services were measured cross-sectionally before (February 2017) and four months after implementing measures (July 2020). Results This study found that interruptions are a systemic problem emerging from the adaptive behavior of pharmacists and nurses to their work constraints, such as short staffing of pharmacists, which limited the frequency of medication deliveries to IPWs, and lack of information about the medication dispensing status for nurses. Measures for mitigating cross-system performance adjustments—a medication dispensing tracking system for nurses, request-based extra medication delivery, and pass boxes for earlier pick-up of medicines—were introduced. Following their implementation, the daily median number of telephone calls and counter services was significantly reduced (43 to 18 and 55 to 15, respectively), resulting in a 60% reduction in the total number of interruptions. Conclusion This study found interruptions in the hospital pharmacy as a systemic problem that can be reduced by mitigating difficulties being compensated for by clinicians' cross-system performance adjustments. Our findings suggest that a synthetic approach can be effective for solving complex problems and have implications for methodological guidance for Safety-II in practice.

Abstract Background Exon 18 D842V, which is a point mutation from aspartic acid to valine at codon 842, is the most frequent mutation in Platelet-Derived Growth Factor Receptor alpha (PDGFRA)-mutated gastrointestinal stromal tumor (GIST). In the Japanese GIST guidelines, no standard systematic therapy is available for this type of GIST, which is refractory after recurrence. Recently, pimitespib (PIMI), a novel heat shock protein 90 (HSP90) inhibitor, was approved for the treatment of advanced GIST in a phase III study. This report presents a case of a long-term response to PIMI in GIST with PDGFRA D842V mutation. Case presentation A 55-year-old woman was diagnosed with primary GIST of the stomach and underwent partial gastrectomy. Eight years after the operation, recurrent GISTs were identified as multiple recurrent peritoneal GISTs in the upper right abdomen and pelvic cavity. We administered tyrosine kinase inhibitors, but they achieved poor effects. After failure of the standard treatment, PIMI was administered and achieved a partial response in the patient. The highest reduction rate was 32.7%. After PIMI failed, we performed multiplex gene panel testing, which revealed the PDGFRA D842V mutation. Conclusions We report the first case of long-term response to PIMI in PDGFRA D842V mutant GIST. Pimitespib may be effective for treating GIST harboring this mutation by inhibiting HSP90.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most severe cancers and is characterized by chemotherapy resistance and poor prognosis associated with epithelial-mesenchymal transition (EMT). In a previous study, a low mitochondrial DNA (mtDNA) copy number was associated with poorer prognosis and induced EMT in ESCC. However, the detailed mechanism related to mtDNA copy number and EMT is unclear. The aim of this study was to clarify the mechanism by which a change in mtDNA copy number contributes to EMT and to examine treatment of chemotherapy resistance in ESCC. Methods The association between low mtDNA copy number and chemotherapy resistance was investigated using specimens from 88 patients who underwent surgery after neoadjuvant chemotherapy. Then, the mtDNA content of human ESCC cell lines, TE8 and TE11, was depleted by knockdown of mitochondrial transcription factor A expression. The present study focused on modulation of mitochondrial membrane potential (MMP) and DNA methylation as the mechanisms by which mtDNA copy number affects EMT. mRNA and protein expression, chemotherapy sensitivity, proliferation, MMP and DNA methylation were evaluated, and in vitro and in vivo assays were conducted to clarify these mechanisms. Results ESCC patients with decreased mtDNA copy number who underwent R0 resection after neoadjuvant chemotherapy had significantly worse pathological response and recurrence-free survival. Additionally, low mtDNA copy number was associated with resistance to chemotherapy in vitro and in vivo. mtDNA controlled MMP, and MMP depolarization induced EMT. Depletion of mtDNA and low MMP induced DNA methylation via a DNA methylation transcription factor (DNMT), and a DNMT inhibitor suppressed EMT and improved chemotherapy sensitivity in mtDNA-depleted ESCC cells, as shown by in vitro and in vivo assays. Conclusion This study showed that decreased mtDNA copy number induced EMT via modulation of MMP and DNA methylation in ESCC. Therapeutic strategies increasing mtDNA copy number and DNMT inhibitors may be effective in preventing EMT and chemosensitivity resistance.

Summary: Introduction: Peripherally inserted central venous catheter (PICC) has a risk of causing phlebitis and thrombus occlusion. We coated the surfaces of the PICC with a specialized coating material (SEC-1) which may prevent thrombogenicity and phlebitis. This study aimed to evaluate SEC-1 coating PICCs using big animal. Methods: SEC-1 coating was used to both the internal and external surface of the catheter. In internal coating evaluation, the swine blood was filled up to 10 cm from the tip of the catheter into both non-coated and SEC-1-coated PICC (4Fr). Then we attempted to release the catheter occlusion at 5, 15 and 30 min while measuring the occlusion pressure by a digital pressure gauge. In external coating evaluation, after optimizing the phlebitis model using milk vein in swine, both PICCs inserted at a depth of 15 cm in the vein were forcibly withdrawn a distance of 5 cm and re-inserted 100 times. After 2days, we assessed inflammatory cell infiltration by histological evaluation. Result: The catheter occlusion release pressure at 5 min was measured at the non-coated: 2 and SEC-1-coated PICC:2 kPa. At 15 min, 7 and 4 kPa (p=0.38). At 30 min, 30 and 4 kPa (p=0.01). In external coating evaluation, there was no clear difference between the non-coated and the SEC-1-coated PICC in terms of inflammatory cell infiltration. Conclusion: The results of this study suggest that antithrombotic coating (SEC-1 coating) of PICC catheters may inhibit thrombogenicity. However, we were unable to confirm that it was effective in the control of phlebitis.

Abstract To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1–3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan–Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

Abstract Background We report a case of bilateral pachychoroid disease with type 3 uveal effusion syndrome (UES) in one eye and central serous chorioretinopathy (CSC) in the contralateral eye. Case presentation A 65-year-old man presented to our department because of decreased vision. Visual acuity was 16/20 in the right eye and 2/20 in the left eye, with normal axial lengths. The left eye was diagnosed with CSC and underwent photocoagulation 8 years ago. The right eye showed inferior non-rhegmatogenous retinal detachment and peripheral choroidal detachment. Macular optical coherence tomography showed submacular fluid in the right eye, pachychoroid in both eyes, and choroidal thickness of 565 μm in the right and 545 μm in the left eye. In both eyes, fluorescence angiography showed window defects and mild fluorescence leakage, and indocyanine green angiography showed dilated choroidal vessels, mild choroidal hyperpermeability, and mild dye leakage. The left eye was diagnosed with chronic CSC. Initially, chronic CSC was also suspected in the right eye. However, photodynamic therapy failed, with worsened retinal detachment and visual acuity. Pachychoroid in the peripheral fundus (choroidal thickness 820 μm) was observed only in the right eye. Based on these findings, UES was diagnosed in the right eye. Sclerectomies were performed. The absence of scleral thickening and glycosaminoglycan deposition led to a final diagnosis of type 3 UES. The procedure was not effective, due to connective tissue regeneration at the sclerectomy sites. In the revision surgery, mitomycin-C was used with sclerectomies. One month after surgery, retinal and choroidal detachment disappeared, visual acuity recovered to 8/20, pachychoroid in the macula and peripheral fundus decreased, and choroidal thickness decreased to 352 μm in the macula and 554 μm in inferior peripheral fundus. Conclusions Pachychoroid in the posterior pole was the common finding in type 3 UES and CSC, although extensive pachychoroid in the peripheral fundus may have caused retinal and choroidal detachment in the eye with type 3 UES. Full-thickness sclerectomies with mitomycin-C improved pachychoroid in the peripheral fundus and resolved retinal and choroidal detachment, clearly indicating that the sclera was the main cause of type 3 UES.

Background Reperfusion therapy for acute ischemic stroke efficacy is highly time dependent; therefore, stroke centers are required to further reduce the delays from hospital arrival to treatment efficiently. We developed a visual task management application, Task Calculation Stroke (Task Calc. Stroke: TCS), to facilitate hospital acute ischemic stroke treatment by supporting parallel staff task completion. We evaluated TCS for the reduction of reperfusion therapy delays and improvement of clinical outcomes. Methods In this multicenter cohort study, patients were directly admitted to 4 comprehensive stroke centers in Japan and given intravenous tissue plasminogen activator and/or mechanical thrombectomy from June 2018 to December 2020. The research team visited each facility and instructed the staff on TCS use for acute ischemic stroke (training stage), after which the staff used TCS independently (TCS stage). We then compared door‐to‐needle time for intravenous tissue plasminogen activator, door‐to‐puncture time for mechanical thrombectomy, and clinical outcomes at discharge according to the modified Rankin Scale among patients treated before training (original stage), during the training stage, or the TCS stage. Results During the study period, 316 patients with acute ischemic stroke received reperfusion therapy; of these, 246 received intravenous tissue plasminogen activator and 162 mechanical thrombectomy (including 92 receiving both the treatments). The mean door‐to‐needle time was significantly reduced from 58.0 minutes in the original stage to 54.6 minutes in the training stage (P=0.049) and 47.8 minutes in the TCS stage (P

This retrospective study aimed to clarify the risk of older adults' nursing home placement in terms of basic movements and activities of daily living (ADLs) by analyzing data from a long-term care insurance certification survey in 2016‒2018 in City A. Of the 21,520 people certified as needing care, 16,865 could be followed up until 2018. Data on sex, age, household structure, and level of care required were obtained. Those who lived at home and at nursing homes were categorized as the "Unchanged group" and the "Changed group," respectively. Multivariate binomial logistic regression analysis was performed, with group type as the dependent variable and basic movement and ADL scores as the independent variables. For factor analysis according to care level, participants were classified into support need levels 1 and 2, care need levels 1 and 2, and care need levels 3, 4, and 5. For those categorized into support need levels 1 and 2, standing on one leg and transferring (basic movements) and urination and face cleaning (ADLs) were associated with nursing home placement. For those in care need levels 1 and 2, getting up and transferring (basic movements) and bathing, urination, face cleaning, and hair styling (ADL) were significantly associated with nursing home placement. For those in care need levels 3, 4, and 5, sitting and transferring (basic movements) and self-feeding and defecation (ADL) were significant. Occupational therapists must focus on older adults' declining ADLs and basic movements and relay the necessary information to patients, families, and other healthcare professionals to ensure appropriate and prompt care delivery.

Abstract Background Pulmonary vein (PV) reconnection is the main cause of atrial fibrillation (AF) recurrence. This study aimed to examine the effect of first‐pass PV isolation (PVI) on PV reconnection frequency during the procedure and on AF ablation outcomes. Methods This retrospective study included 446 patients with drug‐refractory AF (370 men, aged 64 ± 10 years) who underwent initial PVI using an open‐irrigated contact force catheter between January 2015 and October 2016. We investigated the effect of first‐pass PVI on PV reconnection during spontaneous PV reconnection and dormant conduction after an adenosine triphosphate challenge. Results First‐pass PVI was achieved in 69% (617/892) of ipsilateral PVs, of which we observed PV reconnection during the procedure in 134 (22%) PVs. This value was significantly lower than that observed in those without first‐pass PVI (50%, 138/275) (P

Individuals with Fanconi anemia (FA), a rare genetic bone marrow failure syndrome, have an increased risk of young‐onset head and neck squamous cell carcinomas (SCCs) and esophageal SCC. The FA DNA repair pathway is activated upon DNA damage induced by acetaldehyde, a chief alcohol metabolite and one of the major carcinogens in humans. However, the molecular basis of acetaldehyde‐induced genomic instability in SCCs of the head and neck and of the esophagus in FA remains elusive. Here, we report the effects of acetaldehyde on replication stress response in esophageal epithelial cells (keratinocytes). Acetaldehyde‐exposed esophageal keratinocytes displayed accumulation of DNA damage foci consisting of 53BP1 and BRCA1. At physiologically relevant concentrations, acetaldehyde activated the ATR‐Chk1 pathway, leading to S‐ and G2/M‐phase delay with accumulation of the FA complementation group D2 protein (FANCD2) at the sites of DNA synthesis, suggesting that acetaldehyde impedes replication fork progression. Consistently, depletion of the replication fork protection protein Timeless led to elevated DNA damage upon acetaldehyde exposure. Furthermore, FANCD2 depletion exacerbated replication abnormalities, elevated DNA damage, and led to apoptotic cell death, indicating that FANCD2 prevents acetaldehyde‐induced genomic instability in esophageal keratinocytes. These observations contribute to our understanding of the mechanisms that drive genomic instability in FA patients and alcohol‐related carcinogenesis, thereby providing a translational implication in the development of more effective therapies for SCCs.

Abstract Background We report a case of bilateral pachychoroid disease manifesting polypoidal choroidal vasculopathy (PCV) with punctate hyperfluorescent spot (PHS) in one eye, and peripheral exudative hemorrhagic choroidal retinopathy (PEHCR) with central serous chorioretinopathy (CSC) and PHS in the contralateral eye. Case presentation : A 51-year-old healthy woman presented with complaint of blurred vision in her right eye. Corrected visual acuity was 20/20 in the right and 24/20 in the left eye. Fundus examination was normal in the left eye. In the right eye, fundus finding of an orange-red nodular lesion and optical coherence tomography (OCT) finding of polypoidal lesions led to a diagnosis of PCV. Four aflibercept intravitreal injections were performed in her right eye. After treatment, indocyanine green angiography (ICGA) confirmed residual polypoidal lesions with branching vascular networks and PHS with choroidal vascular hyperpermeability. OCT showed PHS associated with small sharp-peaked retinal pigment epithelium (RPE) elevation in peripheral fundus and small RPE elevation in posterior fundus. Based on the above findings, PCV with PHS was finally diagnosed in the right eye. Posttreatment corrected visual acuity in the right eye was 20/20. She presented again 32 months later, with complaint of vision loss in her left eye. Left corrected visual acuity was 20/20, and fundus examination showed mild vitreous hemorrhage. Vitrectomy was performed. In temporal midperipheral fundus, fluorescein angiography revealed CSC, and OCT showed pachychoroid. ICGA depicted abnormal choroidal networks and PHS in peripheral fundus. Furthermore, polypoidal lesions were confirmed by OCT. Based on the above findings, PEHCR and CSC with PHS was finally diagnosed in the left eye. Postoperative corrected visual acuity in the left eye was 20/20, and aflibercept intravitreal injection was performed for prevention of recurrence of vitreous hemorrhage. Conclusions This is the first case report of PCV with PHS in one eye, and PEHCR with CSC and PHS in the contralateral eye. This case suggests that PCV, PEHCR, and CSC may be linked pathologies of pachychoroid spectrum disease.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the deadliest of all human squamous cell carcinomas and is characterized by chemotherapy resistance and poor prognosis associated with the epithelial–mesenchymal transition (EMT). A subset of ESCC displays loss‐of‐function mutations in genes encoding Notch receptor family members, including NOTCH3. Although Notch signaling regulates EMT in ESCC cells, the role of NOTCH3 in EMT and chemotherapy resistance remains elusive. This study aimed to examine the role of NOTCH3 in EMT and chemotherapy resistance, and determine whether NOTCH3 expression can be used to predict the response to chemotherapy. Methods In vitro and in vivo assays were conducted to clarify the contribution of NOTCH3 to chemotherapy resistance. Using specimens from 120 ESCC patients treated with neoadjuvant chemotherapy, we compared the expression levels of NOTCH3 and genes involved in EMT according to the degree of chemotherapy sensitivity. Results In ESCC cells, chemotherapy resistance was associated with NOTCH3 downregulation and concurrent activation of EMT. RNA interference to silence NOTCH3 resulted in induction of the EMT marker Vimentin (VIM), leading to chemotherapy resistance in ESCC cells. Conversely, ectopic expression of the activated form of NOTCH3 suppressed EMT and sensitized cells to chemotherapy. Results of chromatin immunoprecipitation assays suggested that NOTCH3 may repress transcription of the VIM. Conclusions Our findings suggest that NOTCH3 may control chemotherapy sensitivity by regulating EMT. NOTCH3 may serve as a novel biomarker to predict better clinical outcomes in ESCC patients.

Abstract Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.

Abstract Aim The aim is to report the long‐term outcomes of preoperative cisplatin and fluorouracil plus docetaxel (DCF) vs Adriamycin (ACF) for resectable esophageal squamous cell carcinoma (ESCC). Previously, this trial showed that DCF is associated with prolonged recurrence‐free survival (RFS). Methods Patients were randomly assigned to two cycles of ACF (35 mg/m2 of Adriamycin, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 7 days) every 4 weeks or DCF (70 mg/m2 of docetaxel, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 5 days) every 3 weeks, followed by surgery. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Results Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, 162 of whom were eligible and randomly assigned to the two groups. The median follow‐up for surviving patients was 69.8 months. The 5‐year RFS was significantly better in the DCF group than in the ACF group (59.9% vs 40.7%, hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.35‐0.86; P = .009) and the 5‐year OS was significantly better in the DCF group than in the ACF group (63.5% vs 49.4%, HR, 0.61; 95% CI, 0.38‐0.96; P = .03). The benefit of DCF chemotherapy on survival was significantly greater in the subgroups with more advanced clinical T and N stage. Conclusions Cisplatin and fluorouracil plus docetaxel are associated with better RFS and OS than ACF in resectable ESCC patients.

Abstract Background Self‐assembling peptides (TDMs) comprise synthetic amphipathic peptides that immediately react to changes in pH and/or inorganic salts to transform into a gelatinous state. The first generation of these peptides (TDM‐621) is currently used as a hemostatic agent in Europe. However, TDM‐621 exhibits slow gel‐formation and low retention capabilities on tissue surfaces. The second generation (TDM‐623) was therefore developed to encourage faster gel‐formation and better tissue‐sealing capabilities. Aim The aim of this study was to verify the efficacy of TDM‐623 in terms of its hemostatic effect in endoscopic surgery. Materials and methods Evaluation of the hemostatic effect in endoscopic surgery (animal study) was performed using eight porcine in spine position. Following systemic heparinization, we established a “bleeding model” by endoscopic grasping forceps on the anterior walls of the stomach and duodenum. In the hemostasis method, an endoscope with a distal hood was brought into contact with the bleeding point, and 1 ml TDM‐623 was applied to the wound. After TDM‐623 gelation, the endoscope was removed, and the acute hemostatic effect (after 2 min) was confirmed. Result In the endoscopic bleeding model, 17 of the 23 cases (74%) showed complete hemostatic effects on the anterior wall of the stomach, and 18 of the 20 cases (80%) on the anterior wall of the duodenum, respectively. None of the applied gels were displaced from the anterior walls of the stomach and duodenum. Conclusion The new self‐assembling peptide (TDM‐623) showed high hemostatic effects. TDM‐623 had potential usefulness for upper gastrointestinal endoscopic surgery.

Abstract Introduction Animal experiments with large living animals are essential for the development of medical devices and the training of surgical procedures. Swine are frequently used in animal experiments due to their similar size and anatomy compared to humans. However, it is well known that swine has less local bleeding than humans. The aim of the study was to verify whether animal models with appropriate local bleeding capability could be established. Methods The activated clotting time (ACT) was measured for eight swine (piglet, 35 kg) under general anesthesia. The flexible endoscope was advanced orally, and the gastric mucosa was intentionally traumatized to bleed by biopsy forceps, and the time until spontaneous hemostasis was obtained (mucosal bleeding time). Then, heparin (50 U/kg) was administered intravenously. After 10 min, the ACT was remeasured, and the gastric mucosa was again damaged to bleed by biopsy forceps. The mucosal bleeding time was remeasured. The above measurements were repeated until the ACT exceeded 200 s. Results The median ACT values (seconds) were 83 (no heparin), 155 (50 U/kg heparin), and 204 (100 U/kg heparin), which were significantly increased. The median mucosal bleeding times (seconds) were 152 (no heparin), 283 (50 U/kg), and 423 (100 U/kg), which were significantly extended. Conclusion A bleeding animal model for surgical and endoscopic training was successfully established by bolus heparin administration.

Abstract Objectives Endoscopic submucosal dissection (ESD) has become popular, but complications such as postoperative bleeding remain an issue. Although some methods of closing a mucosal defect with a snare and clips have been reported to be effective and safe, the snare is not a dedicated device, and the procedure is difficult and time‐consuming. We aimed to find an alternative method for defect closure after ESD by developing a dedicated device. Methods We have improved five prototypes. The load on the stopper when starting to tighten and loosen a loop and the maximum load on the stopper and the movement distance of the thread when sliding the stopper were measured five times for each prototype. With the 5th prototype, we finalized the design and named it FLEXLOOP. Additionally, the material and shape of the outer tube were improved. Then, the usability of FLEXLOOP was evaluated in pigs. The operation time for closing mucosal defects with the snare or FLEXLOOP was measured five times. Results We made FLEXLOOP, which had a lower load when sliding and a higher load when loosening than the snare. The improvement of the outer tube significantly reduced the load on the sheath when sliding it. We confirmed the feasibility of mucosal defect closure with FLEXLOOP in pigs. The median operation time was 563 s (range 340–679 s) with the snare and 355 s (range 303–455 s) with FLEXLOOP (p = 0.047). Conclusions FLEXLOOP can be a promising option for defect closure after ESD.

Abstract Background Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment. Case presentation A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography. Conclusions Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.

Abstract Aim To investigate associations between temperament and professional quality of life among Japanese nurses. Design A descriptive‐correlational study using self‐administered anonymous questionnaires. Methods Questionnaires were collected from 1,267 nurses. We used analysis of covariance to examine associations between tendencies of temperament (depressive, cyclothymic, hyperthymic, irritable and anxious) and professional quality of life subscales (compassion satisfaction, burnout, compassion fatigue) first for all participants and then again after dividing the participants into two groups based on years of experience. Results Nurses’ professional quality of life was associated with innate temperament and years of experience. Nurses with any of depressive, cyclothymic, irritable, or anxious tendencies showed significantly lower compassion satisfaction and higher burnout and compassion fatigue than those without these tendencies. Nurses with hyperthymic tendencies showed significantly higher compassion satisfaction and lower burnout than those without the tendency.

Abstract Background The intestinal epithelial barrier allows absorption of dietary nutrients and prevents passage of pathogens and toxins into the body. Severe insults have a negative impact on the intestinal environment, which may decrease intestinal barrier function and cause bacterial translocation. Bacterial translocation, which can cause infectious complications, is defined as the passage of microbes from the gastrointestinal tract across the mucosal barrier to extraintestinal sites. The aim of this study was to investigate the correlation between concentrations of preoperative fecal organic acids and the occurrence of postoperative infectious complications in patients with esophageal cancer. Methods Fifty-five patients with esophageal cancer who underwent esophagectomy were enrolled in this study. Perioperative synbiotics were administered to all patients. Perioperative clinical characteristics and concentrations of preoperative fecal organic acids were compared between patients with and without postoperative infectious complications. Results Postoperative infectious complications occurred in 10 patients. In patients with complications, the concentrations of acetic acid and propionic acid were significantly lower than in patients without complications (p = 0.044 and 0.032, respectively). The concentration of butyric acid was nonsignificantly lower in patients with complications, while the concentration of lactic acid was nonsignificantly higher. The calculated gap between the concentrations of fecal acetic acid plus propionic acid plus butyric acid minus lactic acid was significantly lower in patients with complications. Multivariate analysis revealed that a low gap between acetic acid plus propionic acid plus butyric acid minus lactic acid was an independent risk factor for postoperative infectious complications (p = 0.027). Conclusions Preoperative fecal concentrations of organic acids had a clinically important impact on the occurrence of postoperative infectious complications in patients with esophageal cancer. To reduce postoperative infectious complications, it may be useful to modulate the intestinal environment and maintain concentrations of fecal organic acids before surgery.