Cerebral foreign body granulomas after mechanical thrombectomy: Two case reports and a review of the literature.

OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

Appropriate tension sensitivity of α-catenin ensures rounding morphogenesis of epithelial spheroids.

The adherens junction (AJ) is an actin filament-anchoring junction. It plays a central role in epithelial morphogenesis through cadherin-based recognition and adhesion among cells. The stability and plasticity of AJs are required for the morphogenesis. An actin-binding α-catenin is an essential component of the cadherin-catenin complex and functions as a tension transducer that changes its conformation and induces AJ development in response to tension. Despite much progress in understanding molecular mechanisms of tension sensitivity of α-catenin, its significance on epithelial morphogenesis is still unknown. Here we show that the tension sensitivity of α-catenin is essential for epithelial cells to form round spheroids through proper multicellular rearrangement. Using a novel in vitro suspension culture model, we found that epithelial cells form round spheroids even from rectangular-shaped cell masses with high aspect ratios without using high tension and that increased tension sensitivity of α-catenin affected this morphogenesis. Analyses of AJ formation and cellular tracking during rounding morphogenesis showed cellular rearrangement, probably through AJ remodeling. The rearrangement occurs at the cell mass level, but not single-cell level. Hypersensitive α-catenin mutant-expressing cells did not show cellular rearrangement at the cell mass level, suggesting that the appropriate tension sensitivity of α-catenin is crucial for the coordinated round morphogenesis.Key words: α-catenin, vinculin, adherens junction, morphogenesis, mechanotransduction.

The force-sensing device region of α-catenin is an intrinsically disordered segment in the absence of intramolecular stabilization of the autoinhibitory form.

Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G. Our molecular dissection study showed that helix bundles F and G are stable in solution in each isolated form, whereas helix bundle E that contains VBS1 is unstable and intrinsically disordered in solution in the isolated form. We successfully identified key residues mediating the autoinhibition and produced mutated α-catenins that display variable force sensitivity and autoinhibition. Using these mutants, we demonstrate both in vitro and in vivo that, in the absence of this stabilization, the helix bundle containing VBS1 would adopt an unfolded form, thus exposing VBS for vinculin binding. We provide evidence for importance of mechanotransduction with the intrinsic force sensitivity for vinculin recruitment to adherens junctions of epithelial cell sheets with mutated α-catenins.

Japanese Internists' Most Memorable Diagnostic Error Cases: A Self-reflection Survey.

Objective The etiologies of diagnostic errors among internal medicine physicians are unclear. To understand the causes and characteristics of diagnostic errors through reflection by those involved in them. Methods We conducted a cross-sectional study using a web-based questionnaire in Japan in January 2019. Over a 10-day period, a total of 2,220 participants agreed to participate in the study, of whom 687 internists were included in the final analysis. Participants were asked about their most memorable diagnostic error cases, in which the time course, situational factors, and psychosocial context could be most vividly recalled and where the participant provided care. We categorized diagnostic errors and identified contributing factors (i.e., situational factors, data collection/interpretation factors, and cognitive biases). Results Two-thirds of the identified diagnostic errors occurred in the clinic or emergency department. Errors were most frequently categorized as wrong diagnoses, followed by delayed and missed diagnoses. Errors most often involved diagnoses related to malignancy, circulatory system disorders, or infectious diseases. Situational factors were the most cited error cause, followed by data collection factors and cognitive bias. Common situational factors included limited consultation during office hours and weekends and barriers that prevented consultation with a supervisor or another department. Conclusion Internists reported situational factors as a significant cause of diagnostic errors. Other factors, such as cognitive biases, were also evident, although the difference in clinical settings may have influenced the proportions of the etiologies of the errors that were observed. Furthermore, wrong, delayed, and missed diagnoses may have distinctive associated cognitive biases.

Coaxial Method of PTA Balloon and Aspiration catheter using the delivery wire of a stent retriever for tandem occlusion: CoMBAt tandem occlusion.

PURPOSE: Tandem occlusion, in which the intracranial artery is obstructed along with proximal carotid occlusive or stenotic lesions, occurs in 10-15% of patients with large vessel occlusion. Our study introduces a novel technique for tandem occlusion treatment that involves the simultaneous coaxial deployment of a percutaneous transluminal angioplasty balloon and aspiration catheters with the delivery wire of a stent retriever. After percutaneous transluminal angioplasty of the carotid lesion with a thin balloon catheter, the aspiration catheter was advanced over the balloon to eliminate the ledge between the catheter tip and delivery wire. After balloon removal, intracranial thrombectomy was performed using an aspiration catheter and stent retriever. This study aimed to evaluate the safety and efficacy of this approach. MATERIALS AND METHODS: Medical records of patients with acute stroke due to tandem occlusion treated using our technique were analyzed for its effectiveness and safety. The puncture-to-recanalization time, modified thrombolysis in cerebral infarction (mTICI) grade, functional prognosis and incidence of hyperperfusion were assessed. RESULTS: Seven patients were included in this study. In all patients, mTICI 2b-3 recanalization was achieved after smooth delivery of the aspiration catheter from the carotid lesion to the intracranial thrombus. The median puncture-to-recanalization time was 52 min. Ninety days post-stroke onset, six of seven patients had a modified Rankin Scale score of 0-2, and none of the patients had perioperative hyperperfusion syndrome. CONCLUSION: Our technique allows simultaneous treatment of carotid and intracranial lesions, leading to faster recanalization. Furthermore, percutaneous transluminal angioplasty with a thin balloon may reduce the risk of hyperperfusion.

Visual suppression of vestibulo-ocular reflex in patients treated with carotid artery revascularization: A potential biomarker for cerebral perfusion.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for ischemic stroke prevention in patients with carotid artery stenosis. However, the beneficial effects of CEA/CAS for cerebral hypoperfusion due to carotid artery stenosis have yet to be fully established. As dizziness is a common symptom in patients with carotid artery stenosis, we aimed to evaluate the effects of CEA/CAS on cerebral function in patients with carotid artery stenosis, using equilibrium function tests. METHODS: This prospective observational cohort study included 50 patients who had carotid artery stenosis and were scheduled to undergo CEA or CAS. Before CEA/CAS, we quantitatively evaluated the vestibulo-ocular reflex (VOR) and vestibular evoked myogenic potential (VEMP), as indicators of brainstem/inner ear functions related to balance, and visual suppression of VOR, as an indicator of cerebral control over the brainstem reflex related to balance. These were then compared with supratentorial cerebral blood flow (CBF). Changes in VOR, VEMP, visual suppression of VOR, CBF, and dizziness after CEA/CAS were also evaluated. RESULTS: The visual suppression rates of VOR correlated with supratentorial CBFs before CEA/CAS (correlation coefficient = 0.47, p = 0.003). The visual suppression rates of VOR (p < 0.001) and supratentorial CBFs (p = 0.003) were improved by CEA/CAS, while VOR and VEMP did not change. Symptoms of dizziness improved after CEA/CAS. CONCLUSIONS: Our results suggest that visual suppression of the VOR may be a novel and practical marker for the beneficial effects of CEA/CAS on supratentorial cerebral function.

Efficacy and safety of thrombectomy for acute ischaemic stroke in patients with pre-stroke mRS scores of 2-3: Real-world evaluation from an open-label, prospective, multicentre, observational study.

BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

Increased door-to-puncture time during off-duty hours results in poor treatment outcomes for acute ischemic stroke: A subanalysis of the K-NET registry.

BACKGROUND: For patients who undergo endovascular treatment for acute ischemic stroke, the total time for treatment may increase during off-duty hours leading to worse outcomes. The present study compared endovascular treatment outcomes for on-duty and off-duty hours and examined factors that could be responsible for the prolonged treatment of patients in a multicenter registry. METHODS: The study group comprised 1571 patients listed in the multicenter stroke registry (K-NET) who had undergone endovascular treatment between January 2018 and June 2020. The modified Rankin Scale (mRS), evaluated at 90 days after stroke onset, was utilized as the primary outcome. Patients were divided into on-duty and off-duty patients based on admission time. Multivariate logistic regression analysis was used to identify the independent factors that increased the time from admission to puncture during the off-duty period. RESULTS: The mean mRS score at 90 days after stroke onset was 2.9, similar in both on-duty and off-duty patients, with no significant difference (p = 0.77); however, significant differences were observed in time from door-to-puncture (74.7 vs. 88.8, p < 0.01). Additionally, the mRS score at 90 days worsened significantly for door-to-puncture time >60 min in the off-duty period. Multivariate logistic regression analysis revealed that a low National Institute of Health Stroke Scale (NIHSS) score, high pre-mRS score, posterior circulation, and diabetes were independent indicators of door-to-puncture time >60 min during the off-duty period. CONCLUSION: Door-to-puncture time >60 min during off-duty hours was associated with poor outcomes related to low NIHSS, high pre-mRS, posterior circulation, and diabetes.

Cognitive Bias and Diagnostic Errors among Physicians in Japan: A Self-Reflection Survey.

This cross-sectional study aimed to clarify how cognitive biases and situational factors related to diagnostic errors among physicians. A self-reflection questionnaire survey on physicians' most memorable diagnostic error cases was conducted at seven conferences: one each in Okayama, Hiroshima, Matsue, Izumo City, and Osaka, and two in Tokyo. Among the 147 recruited participants, 130 completed and returned the questionnaires. We recruited primary care physicians working in various specialty areas and settings (e.g., clinics and hospitals). Results indicated that the emergency department was the most common setting (47.7%), and the highest frequency of errors occurred during night-time work. An average of 3.08 cognitive biases was attributed to each error. The participants reported anchoring bias (60.0%), premature closure (58.5%), availability bias (46.2%), and hassle bias (33.1%), with the first three being most frequent. Further, multivariate logistic regression analysis for cognitive bias showed that emergency room care can easily induce cognitive bias (adjusted odds ratio 3.96, 95% CI 1.16-13.6, p-value = 0.028). Although limited to a certain extent by its sample collection, due to the sensitive nature of information regarding physicians' diagnostic errors, this study nonetheless shows correlations with environmental factors (emergency room care situations) that induce cognitive biases which, in turn, cause diagnostic errors.

Survey of potentially inappropriate prescriptions for common cold symptoms in Japan: A cross-sectional study.

BACKGROUND: Common cold is among the main reasons patients visit a medical facility. However, few studies have investigated whether prescriptions for common cold in Japan comply with domestic and international evidence. OBJECTIVE: To determine whether prescriptions for common cold complied with domestic and international evidence. METHODS: This cross-sectional study was conducted between October 22, 2020, and January 16, 2021. Patients with cold symptoms who visited the two dispensing pharmacies and met the eligibility criteria were interviewed. MAIN OUTCOME MEASURE: The pharmacists at each store and a physician classified the patients into two groups: the potentially inappropriate prescribing group and the appropriate prescribing group. RESULTS: Of the 150 selected patients, 14 were excluded and 136 were included in the analysis. Males accounted for 44.9% of the total study population, and the median patient age was 34 years (interquartile range [IQR], 27-42). The prevalence rates of potentially inappropriate prescriptions and appropriate prescriptions were 89.0% and 11.0%, respectively and the median drug costs were 602.0 yen (IQR, 479.7-839.2) [$5.2 (IQR, 4.2-7.3)] and 406.7 yen (IQR, 194.5-537.2) [$3.5 (IQR, 1.7-4.7)], respectively. The most common potentially inappropriate prescriptions were the prescription of oral cephem antibacterial agents to patients who did not have symptoms of bacterial infections (50.4%) and ß2 stimulants to those who did not have respiratory symptoms due to underlying disease or history (33.9%). CONCLUSIONS: Approximately 90% of prescriptions for common cold symptoms in the area were potentially inappropriate. Our findings could contribute to the monitoring of the use of medicines for the treatment of common cold symptoms.

"Asymptomatic" Subclavian Steal Syndrome.

The definition of subclavian steal is subclavian artery occlusion or hemodynamically significant stenosis proximal to the origin of the vertebral artery that results in lower pressure in the distal subclavian artery. Although subclavian steal can often remain asymptomatic, if ignored, it can cause syncope or neurological deficits. Detailed routine evaluation of blood pressure and careful physical examination, simultaneously on both sides of patients at high vascular risk (such as those with hypertension, dyslipidemia, and diabetes), can assist in the early detection. Herein, we report the case of an 82-year-old male patient with steal syndrome, who had no subjective symptoms despite severe stenosis of the subclavian artery, with a marked left-right difference in blood pressure.

Antiplatelet Loading Effects Prior to Endovascular Treatment: Carotid Artery Stenosis versus Unruptured Cerebral Aneurysms.

Objective: Carotid artery stenosis and cerebral aneurism may have different platelet functions and antiplatelet responses because these diseases have different etiologies. In this study, we compared the antiplatelet loading effects prior to endovascular treatment between carotid artery stenosis and unruptured cerebral aneurysm (UCA) patients. Methods: Nine patients with asymptomatic carotid artery stenosis (ACS), 14 with symptomatic carotid artery stenosis (SCS), and 20 with unruptured cerebral aneurysms were enrolled in this study. Antiplatelet (aspirin + clopidogrel) loading effects prior to endovascular treatment were evaluated using light transmission aggregometry and platelet aggregate detection methods. Results: Although there are differences in the prevalence of atherosclerosis risk factors, maximum aggregation rates in light transmission aggregometry and platelet aggregation-prone properties were not different in the three disease groups. Conclusion: Preoperative dual antiplatelet therapy with aspirin and clopidogrel may be appropriate for both carotid artery stenosis and cerebral aneurism patients even though their conditions and background factors differ.

A review of food poisoning caused by local food in Japan.

Increasingly popular worldwide, Japanese cuisine includes several raw preparations such as sashimi and sushi; however, limited information on food poisoning from Japanese local food is available in English literature. Without appropriate knowledge, physicians may underdiagnose traveler's diarrhea among people returning from Japan. To provide accurate information to primary care physicians worldwide, we conducted a narrative review on food poisoning research published in Japanese and English over the past four years, considering the frequency and clinical importance of various presentations.

Common and specific risk factors for ischemic stroke in elderly: Differences based on type of ischemic stroke and aging.

BACKGROUND: The risk factors among the types of ischemic stroke (atherothrombotic cerebral infarction: ATI, cardio-embolic infarction: CEI, lacunar infarction: LI) in aged stroke patients have rarely been compared to each other. METHODS: We compared the clinical parameters of 300 elderly patients with ischemic stroke, age 65-98years, to 100 age-matched control patients. RESULTS: Comparison by parametric test and logistic regression analysis between all 300 and 100 control patients showed higher systolic and diastolic blood pressures (p<0.001, p=0.03), lower estimated glomerular filtration rate (eGFR) (p=0.01), larger cardiothoracic ratio (CTR) (p<0.001), smoking (p<0.01) and possibly poor adherence to anti-hypertensive agents in the ischemic stroke patients (p<0.001). Comparisons among three types (n=100 for each) showed the highest atheromatous risk factors for ATI to be hemoglobin A1c (p=0.01) and low-density lipoprotein (p<0.001) and for CEI to be largest cardiac load, indicated by largest left atrial dimension (p<0.001), and CTR (p<0.001). Triglyceride level was found to be a borderline risk factor for LI (p=0.054). Comparison between those aged <74 versus ≥75years (n=150 for each) showed a lower eGFR (p=0.02) and larger right atrial dimension (p<0.001) in patients ≥75. CONCLUSION: The risk factors were quite different among the subtypes and aging.

Bedside evaluation of smooth pursuit eye movements in acute sensory stroke patients.

BACKGROUND AND PURPOSE: Unilateral saccadic pursuit is reported to be suggestive of a pontine lesion in sensory stroke patients. We attempted to verify this eye sign in just-hospitalized pontine sensory stroke patients. METHODS: Horizontal smooth pursuit eye movements were evaluated upon hospital arrival in 4 pontine sensory stroke patients and were compared with those in 6 thalamic sensory stroke patients. Eye movements were evaluated with the patient lying down on the emergency room or stroke care unit bed by means of a newly developed video-oculography-based eye movement recording system equipped to project a moving laser pointer onto the ceiling. RESULTS: Laterality of horizontal smooth pursuit gain in pontine sensory stroke patients was evident upon arrival; in thalamic sensory stroke patients, horizontal smooth pursuit gain was equal in both directions. These characteristics were easily detected at bedside. CONCLUSION: Unilateral saccadic pursuit in pontine sensory stroke patients may be a practical diagnostic sign that can be detected even in the emergency room. The video-oculography-based recording system equipped to project a moving laser pointer onto the ceiling may be useful for detecting this eye sign.

Gaze palsy and exotropia in internuclear ophthalmoplegia.

BACKGROUND AND PURPOSE: Unilateral gaze palsy associated with internuclear ophthalmoplegia (INO), i.e., one-and-a-half syndrome, is well known. Exotropia can also be associated with INO, but it has been reported only rarely. We sought to determine the frequencies and courses of gaze palsy and exotropia in INO. METHODS: Patients hospitalized with acute-onset INO during the period January 2009 through December 2013 were identified from our clinical registry. Associated gaze palsy and exotropia were evaluated in the identified patients. RESULTS: Twenty-five patients with unilateral INO and 7 patients with bilateral INO were included in this study. Of the 25 patients with unilateral INO, 4 (16.0.0%) had ipsilateral gaze palsy (one-and-a-half syndrome), 8 (32.0%) had exotropia (non-paralytic pontine exotropia), and 6 (24.0%) had both ipsilateral gaze palsy and exotropia (paralytic pontine exotropia). Six (85.7%) of the 7 patients with bilateral INO had exotropia. The gaze palsy persisted more than 1 week in 40.0% of patients, whereas the exotropia disappeared within 1 week in 92.9% of patients when the INO was unilateral. CONCLUSION: Exotropia is not uncommon in the acute stage of INO. However, it is often overlooked because of its short duration.

Isolated unilateral oculomotor paresis in pure midbrain stroke.

BACKGROUND AND PURPOSE: Pure midbrain stroke can cause isolated unilateral oculomotor paresis. We attempted to determine whether there is a difference in the oculomotor paresis pattern between pure midbrain infarction and midbrain hemorrhage. METHODS: Pure midbrain stroke patients who presented with isolated unilateral oculomotor paresis were identified from a group of 2447 consecutive patients hospitalized for acute cerebral infarction or hemorrhage during the period May 2008 through April 2014. Detailed oculomotor findings were evaluated in the identified patients per the cause of the stroke. RESULTS: Five patients with infarct and 1 with hemorrhage became our study subjects. Lesions were located in the paramedian area of the midbrain involving the oculomotor fascicles. The pupillary sphincter and inferior rectus muscles were selectively spared in the infarct patients, whereas these muscles were selectively affected in the hemorrhage patient. CONCLUSION: Fibers in the oculomotor fascicle that innervate the levator palpebrae, superior rectus, and inferior oblique muscles appear to be more susceptible to ischemic damage than those that innervate the pupillary sphincter and inferior rectus muscles. Isolated impairment of the pupillary sphincter and inferior rectus muscles may be suggestive of a non-ischemic process.