The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: The second phase of the archive of digital records.

A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes' monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form.

Can transbronchial lung cryobiopsy benefit adaptive treatment strategies in connective tissue disease-associated interstitial lung disease?

BACKGROUND: Some patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies. METHODS: We analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing. RESULTS: Among the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren's syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents. CONCLUSIONS: TBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.

Systematic clustering algorithm for chromatin accessibility data and its application to hematopoietic cells.

The huge amount of data acquired by high-throughput sequencing requires data reduction for effective analysis. Here we give a clustering algorithm for genome-wide open chromatin data using a new data reduction method. This method regards the genome as a string of 1s and 0s based on a set of peaks and calculates the Hamming distances between the strings. This algorithm with the systematically optimized set of peaks enables us to quantitatively evaluate differences between samples of hematopoietic cells and classify cell types, potentially leading to a better understanding of leukemia pathogenesis.

Mid-Term Results of Thoracic Endovascular Aneurysm Repair with Intentional Celiac Artery Coverage for Crawford Type I Thoracoabdominal Aortic Aneurysms with the TX2 Distal Component Endograft.

BACKGROUND: Anatomically suitable Crawford type I (C-I) thoracoabdominal aortic aneurysm (TAAA) can be treated by thoracic endovascular aneurysm repair (TEVAR) with intentional celiac artery (CA) coverage to ensure distal seal. We report on mid-term results of TEVAR with intentional CA coverage for C-I TAAA. METHODS: Between August 2010 and July 2017, we treated 16 cases of C-I TAAA by TEVAR with intentional CA coverage using the Zenith TX2 Thoracic Distal Component Endograft. The primary end point was aneurysm shrinkage. Secondary end points were technical success, aneurysm-related death (ARD), and major adverse events (MAEs) including stroke, paraplegia, visceral ischemia, endoleak, and secondary intervention. RESULTS: The preoperative mean aneurysm size was 57.7 ± 8.0 mm. The technical success rate was 100%. There was no aneurysm-related mortality; however, one patient suffered from superior mesenteric artery embolization, which required an open laparotomy. The mean observational period was 40.5 months, and aneurysm shrinkage of >5 mm was observed in 10 cases (62.5%). At 12, 36, and 60 months after the procedure, freedom from ARD was 100%, 100%, and 100%, respectively, whereas freedom from MAE including secondary intervention was 86.7%, 86.7%, and 77.0%, respectively. CONCLUSIONS: Mid-term results of TEVAR with intentional CA coverage for C-I TAAA were acceptable.

Nintedanib allows retreatment with atezolizumab of combined non-small cell lung cancer/idiopathic pulmonary fibrosis after atezolizumab-induced pneumonitis: a case report.

BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that efficiently slows the progression of idiopathic pulmonary fibrosis (IPF) and has an acceptable tolerability profile. In contrast, immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death ligand 1 inhibitors have shown clinical activity and marked efficacy in the treatment of non-small cell lung cancer. However, it is unclear whether nintedanib reduces the risk of ICI-induced pneumonitis in IPF. CASE PRESENTATION: A 78-year-old man with squamous cell lung carcinoma in IPF underwent second-line treatment with pembrolizumab. He was diagnosed as having pembrolizumab-induced pneumonitis after two cycles. He was administered prednisolone (PSL) and then improved immediately. Thereafter, his lung cancer lesion enlarged despite treatment with TS-1. Atezolizumab was then administered as 4th-line chemotherapy, but he immediately developed atezolizumab-induced pneumonitis after 1 cycle. The re-escalated dosage of PSL improved the pneumonitis, and then nintedanib was started as additional therapy. Under careful observation with nintedanib, atezolizumab was re-administered on day 1 of an every-21-day cycle. After three cycles, it remained stable without exacerbation of drug-induced pneumonitis. CONCLUSION: This case indicates the possibility that the addition of nintedanib to ICI therapy might prevent drug-induced pneumonitis or acute exacerbation of IPF. However, whether anti-fibrotic agents such as nintedanib are actually effective in preventing ICI-induced pneumonitis in ILD remains unknown and additional research is greatly needed to identify effective therapies for ILD combined with lung cancer.

Clinical Outcomes of Total Endovascular Aneurysm Repair for Aortic Aneurysms Involving the Proximal Anastomotic Aneurysm following Initial Open Repair for Infrarenal Abdominal Aortic Aneurysm.

BACKGROUND: To evaluate initial and midterm clinical outcomes of aortic aneurysms involving the proximal anastomotic aneurysm (AAPAAs) following initial open repair for infrarenal abdominal aortic aneurysm. METHODS: Between July 2006 and August 2015, 24 patients underwent elective endovascular repair for the treatment of AAPAAs at our institution. AAPAA classification has been categorized as 3 types. Type I AAPAA is the most extensive, extending from the descending aorta to the prior proximal anastomosis as similar to Crawford type II or III thoracoabdominal aortic aneurysm. Type II AAPAA is limited to the aortic aneurysm below the diaphragm including the abdominal visceral arteries. Finally, similar to pararenal abdominal aortic aneurysm, type III AAPAA involves the renal origins, but does not extend to the celiac and superior mesenteric arteries. Total endovascular aneurysm repair (t-EVAR) consisted of fenestrated EVAR (f-EVAR), multibranched EVAR (t-Branch), and snorkel EVAR (s-EVAR) were performed for patients with high-risk open surgical repair. We retrospectively analyzed 24 cases, which were categorized with 3 types of AAPAA. RESULTS: F-EVAR, t-Branch, and s-EVAR for AAPAAs were performed in 15 patients (62.5%), 5 patients (20.8%), and 4 patients (16.7%), respectively. Type I and type II AAPAA were identified in 13 patients (54.2%) and 7 patients (29.2%), and type III AAPAA was identified in 4 patients (16.7%). Technical success was 95.8%, and clinical success was 79.2% with t-EVAR. Spinal cord ischemia was identified in 2 patients (8.3%) of type I AAPAA, the 30-day mortality rate was 4.2% (n = 1, type I AAPAA). Type II and III endoleaks occurred in 1 (4.2%, type III AAPAA) and 3 patients (12.5%, each case of type I, II, and III AAPAA), respectively. There was no open conversion or aneurysm rupture in the late follow-up period. The estimated overall survival rates of t-EVAR after 1 and 3 years were 95.6% and 76.2%, respectively. Rates of freedom from aneurysm-related death and secondary intervention of t-EVAR at 3 years were 90.1% and 89.7%, respectively. Finally, rates of target vessel patency at 1 and 3 years were 95.3% and 88.8%, respectively. CONCLUSIONS: Our initial to midterm results of t-EVAR for the treatment of AAPAA were generally good with low rates of perioperative mortality and aneurysm-related death. However, more attentions should be paid for the treatment of type I AAPAA with high incidence of major adverse events.

Clinical Outcomes of Spinal Cord Ischemia after Fenestrated and Branched Endovascular Stent Grafting during Total Endovascular Aortic Repair for Thoracoabdominal Aortic Aneurysms.

BACKGROUND: In this single-center study, we assessed the clinical outcomes of fenestrated endovascular aortic repair (f-EVAR) and branched EVAR on morbidity and mortality during total endovascular aortic repair for thoracoabdominal aortic aneurysms (TAAAs). METHODS: Between July 2006 and June 2015, elective f-EVAR and multibranched EVAR (t-Branch) for TAAAs were performed in 99 patients at our institution (Crawford classification types I [7], II [13], III [6], IV [55], and V [18]). We retrospectively analyzed 44 patients, excluding those with Crawford type IV TAAAs, and compared 30 patients treated with f-EVAR and 14 treated with t-Branch. Multivariate analysis was performed to determine the factors associated with perioperative spinal cord ischemia (SCI). RESULTS: Technical success was 96.7% with f-EVAR and 100% with t-Branch, and the 30-day mortality rate was 3.3% with f-EVAR and 7.1% with t-Branch (P = 0.646). The incidences of perioperative SCI were higher with t-Branch (n = 5, 35.7%) than those with f-EVAR (n = 2, 6.7%; P = 0.04). Endoleaks were more prevalent with f-EVAR (n = 9, 30.0%) than with t-Branch (n = 1, 7.1%; P = 0.046). Rates of freedom from aneurysm-related death after 1 year for f-EVAR and t-Branch were 96.7 and 92.9%, respectively, and those after 3 years were 88.8 and 92.9% (P = 0.982), respectively. The risk of SCI remarkably increased in the presence of risk factors such as procedure (t-Branch), maximum short axis of ≥65 mm, coverage length of ≥360 mm, internal iliac artery occlusion, and ≥ 5 sacrificed intercostal arteries. CONCLUSIONS: Our initial to mid-term results of f-EVAR and t-Branch were good with low rates of perioperative mortality and high rates of freedom from aneurysm-related death. SCI incidence with t-Branch was significantly high; it is important to develop additional SCI prevention methods for patients with high-risk factors.

Intra-arterial catheter system to repeatedly deliver mesenchymal stem cells in a rat renal failure model.

BACKGROUND: Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure. METHODS: First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days. RESULTS: Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days. CONCLUSION: Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells.

Body weight loss is a simple and useful indicator of prognosis and predictive tolerability in the first year of nintedanib therapy in patients with interstitial lung disease.

BACKGROUND: Nintedanib is generally safe and well tolerated and can improve prognosis in patients with various interstitial lung diseases (ILDs). Appropriate management of adverse events of nintedanib is important to ensure its long-term persistent use. Weight loss is a routinely assessed adverse event in clinical practice. This study aimed to elucidate whether body weight change in the first year of nintedanib therapy can indicate prognosis and predict tolerability in patients with ILD. METHODS: We analysed 245 consecutive ILD patients treated with nintedanib. We calculated the slope of body weight change using baseline weight and that recorded closest after the first year and then categorized percent change in body weight at this time. Significant weight loss was defined as that ≥5%. RESULTS: Subjects included 67 patients with idiopathic pulmonary fibrosis (IPF) and 76 with non-IPF progressive fibrosing-ILD including fibrotic hypersensitivity pneumonitis (n = 16), unclassifiable (n = 35), connective tissue disease-ILD (n = 21), and nonspecific interstitial pneumonia (n = 4). Older age, low body weight at initial examination, significant weight loss, and lower %FVC were significant predictors of discontinuation of nintedanib. Patients with weight loss ≥5% over the first year showed worse survival than those with weight loss <5% regardless of whether IPF existed or BMI indicated obesity. CONCLUSIONS: Careful monitoring of body weight change might suggest useful information for predicting long-term use of nintedanib and mortality risk in ILD patients treated with nintedanib. Appropriate body weight management is needed to prevent adverse events of nintedanib itself.

Emergent centrality in rank-based supplanting process.

We propose a stochastic process of interacting many agents, which is inspired by rank-based supplanting dynamics commonly observed in a group of Japanese macaques. In order to characterize the breaking of permutation symmetry with respect to agents' rank in the stochastic process, we introduce a rank-dependent quantity, overlap centrality, which quantifies how often a given agent overlaps with the other agents. We give a sufficient condition in a wide class of the models such that overlap centrality shows perfect correlation in terms of the agents' rank in the zero-supplanting limit. We also discuss a singularity of the correlation in the case of interaction induced by a Potts energy.

A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber.

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3-8 min). Mean infarct volume was 388 mm3 (IQR, 354-420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke.

Clinical significance of para-carinal air cysts in patients with pleuroparenchymal fibroelastosis: The relationship with pneumomediastinum and pneumothorax.

BACKGROUND: Para-tracheal or para-carinal air cysts (PACs) are often asymptomatic and usually detected incidentally by methods such as computed tomography. Their clinical significance is unclear in patients with pleuroparenchymal fibroelastosis (PPFE). METHODS: We evaluated the clinical significance of PACs in PPFE and their relationship with pneumomediastinum or pneumothorax. RESULTS: In total, 50 patients had PPFE and 34 (68%) had PACs. Most PACs were para-carinal (n = 30). A para-tracheal air cyst was detected in only nine patients, which included five patients having both para-carinal and para-tracheal air cysts. Overall median survival was 24.7 months. Survival was not significantly different between the patients with [PACs(+)] and without PACs (P = 0.268). A high frequency (64%) of the complication of pneumomediastinum or pneumothorax occurred in the overall population during follow-up. Pneumomediastinum/pneumothorax occurred significantly more frequently in patients with PACs(+) than in those without (76.5% vs. 37.5%; P = 0.012). PACs(+) was the only significant risk factor for pneumomediastinum/pneumothorax. CONCLUSIONS: Our data showed that PACs commonly occur in patients with PPFE, and most PACs were para-carinal air cysts. Additionally, PACs(+) was a significant risk factor for pneumomediastinum/pneumothorax; therefore, clinicians should be more aware of these complications during follow-up examination, particular in PACs(+) patients with PPFE.

Patient background and prognosis of chronic pulmonary aspergillosis in fibrosing interstitial lung disease.

Several previous reports have shown interstitial lung disease (ILD) to be a predictor of poor prognosis in patients with chronic pulmonary aspergillosis (CPA). However, there is a lack of clarity regarding patient background and the prognostic factors in CPA associated with ILD (CPA-ILD). Therefore, we assessed these points to obtain valuable information for clinical practice. We retrospectively surveyed and collected data from 459 patients who had serum examination for anti-Aspergillus antibody. Of these patients, we extracted and investigated CPA-ILD patients. We ultimately analyzed 32 CPA-ILD patients. Patient background factors more frequently showed the patients to be older (mean: 74.9 years), male (75.0%), and to have a smoking history (71.9%). Median survival time from the diagnosis of ILD was 76.0 months, whereas that from the diagnosis of CPA-ILD was 25.5 months. No significant differences in survival were found in regard to each ILD pattern and the presence of idiopathic pulmonary fibrosis. A higher level of C-reactive protein was a significant predictor of mortality by Cox regression analysis. CPA complicating ILD is associated with poor prognosis. ILD patients with older age, male sex, and smoking history should be aware of the potential for the development of CPA in ILD. If such patients have elevated markers of inflammation, prompt induction of antifungal treatment may improve their prognosis. Clinicians should be aware of which complications of CPA may lead to a poor prognosis for any ILD not just those limited to idiopathic pulmonary fibrosis or usual interstitial pneumonia pattern.

Impact of progressive fibrosing interstitial lung disease (ILD) in ILD patients complicated with secondary spontaneous pneumothorax.

BACKGROUND: Secondary spontaneous pneumothorax (SSP) in interstitial lung disease (ILD) may influence prognosis of any ILD, and SSP onset predicts poor outcome in idiopathic pulmonary fibrosis (IPF). Recently, progressive fibrosing ILD (PF-ILD) has rapidly acquired importance. OBJECTIVE: We hypothesized that PF-ILD would strongly influence the prognosis of patients with any ILD complicated with SSP. METHODS: We retrospectively surveyed and collected data from patients hospitalized for SSP from January 2016 to June 2020. PF-ILD was defined as the following occurring within 24 months before SSP develops: relative decline in %forced vital capacity (FVC) ≥10% or two of the following: relative decline in %FVC between 5% and 10%, worsening respiratory symptoms, or increased extent of fibrosis on high-resolution computed tomography. RESULTS: We analyzed 32 patients hospitalized for SSP in ILD. This study comprised 18 patients with PF-ILD and 14 patients with non-PF-ILD. PF-ILD patients had lower body mass index (BMI) and %FVC. No significant differences in survival regarding follow-up period from the time of ILD diagnosis and hospitalization for SSP were observed between the PF-ILD and non-PF-ILD patients. Older age and lower BMI were significant predictors of mortality by multivariate Cox regression analysis. ROC analysis showed BMI ≤17.8 kg/m2 to reliably predict poor prognosis. CONCLUSIONS: Regardless of whether patients have PF-ILD, older age and lower BMI in patients with ILD places them at higher risk of developing SSP, and prognosis is poor if SSP develops. Therefore, clinical management of physique is important to improve the prognosis of ILD patients.

Utilizing Dynamic Phosphorous-31 Magnetic Resonance Spectroscopy for the Early Detection of Acute Compartment Syndrome: A Pilot Study on Rats.

INTRODUCTION: Disasters, including terrorism and earthquakes, are significant threats to people and may lead to many people requiring rescue. The longer the rescue takes, the higher the chances of an individual contracting acute compartment syndrome (ACS). ACS is fatal if diagnosed too late, and early diagnosis and treatment are essential. OBJECTIVE: To assess the ability of dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) in the early detection of muscular damage in ACS. MATERIALS AND METHODS: Six ACS model rats were used for serial 31P-MRS scanning (9.4 Tesla). Skeletal muscle metabolism, represented by the levels of phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP), was assessed. The PCr/(Pi + PCr) ratio, which decreases with ischemia, was compared with simultaneously sampled plasma creatine phosphokinase (CPK), a muscle damage marker. RESULTS: The PCr/(Pi + PCr) ratio significantly decreased after inducing ischemia (from 0.86 ± 0.10 to 0.18 ± 0.06; p < 0.05), while CPK did not change significantly (from 89 ± 29.46 to 241.50 ± 113.28; p > 0.05). The intracellular and arterial pH index decreased over time, revealing significant differences at 120 min post-ischemia (from 7.09 ± 0.01 to 6.43 ± 0.13, and from 7.47 ± 0.03 to 7.39 ± 0.04, respectively). In the reperfusion state, the spectra and pH did not return to the original values. CONCLUSIONS: The dynamic 31P-MRS technique can rapidly detect changes in muscle bioenergetics. This technique is a promising non-invasive method for determining early muscular damage in ACS.

Marmoset angiography just by percutaneous puncture of the caudal ventral artery.

Surgery in humans is continuously evolving and promoted minimally invasive treatment. On the other hand, despite the importance of the 3Rs principles for experimental animals is well documented, no reports describe specific methodologies for implementing "refinement" in practice. Here, we describe a new technique, the "Ohta Method" for caudal arthrocentesis in the pursuit of the 3Rs for animal experiments and the development of innovative methods for investigating systemic organ arteries through minimally invasive procedures. This procedure requires only a percutaneous puncture of the caudal artery without any injury to the limb or body trunk. In addition, it does not cut down the artery, making hemostasis easier and recovering arterial damage easier. We will show multiple organ artery angiographies in marmoset for the first time in the world. The principle described in this paper could also be applied to many other small animals, such as rats. Moreover, using this method, multiple doses of the drug or cells can be administered to the target organ at the time of therapeutic intervention, thereby enabling the establishment of more sophisticated and complex therapeutic intervention studies as translational research.

A reproducible swine model of a surgically created saccular thoracic aortic aneurysm.

A reproducible swine thoracic aortic aneurysm (TAA) model is useful for investigating new therapeutic interventions. We report a surgical method for creating a reproducible swine saccular TAA model. We used eight female swine weighing 20-25 kg (LWD; ternary species). All procedures were performed under general anesthesia and involved left thoracotomy. Following aortic cross-clamping, the thoracic aorta was surgically dissected and the media and intima were resected, and the dissection plane was extended by spreading the outer layer for aneurysmal space. Subsequently, only the adventitial layer of the aorta was sutured. At 2 weeks after these procedures, angiography and computed tomography were performed. After follow-up imaging, the model animals were euthanized. Macroscopic, histological, and immunohistological examinations were performed. All model animals survived, and a saccular TAA was confirmed by follow-up imaging in all cases. The mean length of the shorter and the longer aortic diameter after the procedure were 14.01 ± 1.0 mm and 18.35 ± 1.4 mm, respectively (P<0.001). The rate of increase in the aortic diameter was 131.7 ± 13.8%, and the mean length of aneurysmal change at thoracic aorta was 22.4 ± 1.9 mm. Histological examination revealed intimal tears and defects of elastic fibers in the media. Immunostaining revealed MMP-2 and MMP-9 expressions at the aneurysm site. We report our surgical method for creating a swine saccular TAA model. Our model animal may be useful to investigate new therapeutic interventions for aortic disease.

A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy.

The failure of neuroprotective treatment-related clinical trials may be partially caused by unestablished animal models. Existing animal models are less likely to provide occlusion confined to the middle cerebral artery (MCA), making transarterial intervention difficult. We aimed to develop a novel focal stroke model using a microcatheter and zirconium dioxide that is non-magnetic under fluoroscopic guidance, which can monitor MCA occlusion and can improve hemorrhagic complications. Using male Sprague Dawley rats (n = 10), a microcatheter was navigated from the caudal ventral artery to the left internal carotid artery using an X-ray fluoroscopy to establish local occlusion. All rat cerebral angiographies were successful. No rats had hemorrhagic complications. Eight (80%) rats underwent occlusion of the MCA bifurcation by zirconium dioxide. Accidentally, the left posterior cerebral artery was failure embolized in 2 rats (20%). The median operating time was 8 min. All rats of occlusion MCA revealed an incomplete hemiparesis on the right side with neurological deficit score ranging from 1 to 3 (median 1, interquartile range 1-3) at 24 h after the induction of ischemia. Moreover, 2% 2,3,5-triphenyl tetrazolium chloride staining showed that the median infarct volume (mm3) was 280 (interquartile range 267-333) 24 h after the left MCA bifurcation occlusion. We present a novel rat model for focal stroke using a microcatheter and zirconium dioxide which does not affect the MRI. The model is predictable which is well confined within the territory supplied by the MCA, and reproducibility of this model is 80%. Fluoroscopy was able to identify which the MCA occlusion and model success while creating the model. It permitted exclusion of animals with complications from the experiment.

Delayed onset of severe immune thrombocytopenia associated with COVID-19 pneumonia.

A 72-year-old Japanese man was admitted to our hospital for treatment of severe COVID-19 pneumonia and was started on favipiravir, heparin calcium, and methylprednisolone pulse therapy. He recovered from respiratory failure about one month later. However, he soon developed purpura in his lower limbs and thrombocytopenia, and immune thrombocytopenia was subsequently diagnosed. Although immune thrombocytopenia is one of the early complications of COVID-19, the use of corticosteroids for COVID-19 is thought to be a factor in the late onset of immune thrombocytopenia. In cases of severe COVID-19 for which corticosteroids were used for treatment, autoimmune diseases such as immune thrombocytopenia may manifest themselves late in the disease course.