Narrowing of the Parent Artery Angle Is Associated With Intracranial Aneurysm Growth.

OBJECTIVE: Although risk factors for intracranial aneurysm growth have been reported, studies investigating the influence of the parent artery angle are limited. In this study, we examined the relationship between intracranial aneurysm growth and parent artery angle narrowing by analyzing long-term follow-up magnetic resonance angiography data. METHODS: We retrospectively reviewed data of patients with untreated aneurysms and those treated by simple coil embolization, who were followed up by magnetic resonance angiography for over 24 months at the Steel Memorial Yawata Hospital between August 2007 and March 2023. We investigated the relationship of aneurysm growth with parent artery angle narrowing, age, sex, follow-up duration, previous subarachnoid hemorrhage, hypertension, smoking, aneurysm location, aneurysm type, maximum size, and neck size. RESULTS: A total of 180 aneurysms of 162 patients (women, n=113; untreated, n=136) were included. The median age at aneurysm diagnosis was 71 (63.8-76) years and the median follow-up duration was 69 (45-120) months. Among the 180 aneurysms, 41 (untreated, n=30; treated by simple coil embolization, n=11) showed growth during the follow-up period, with a risk of 4.4%/patient-year. In the univariable analysis, the parent artery angles on the initial and last follow-up images and angle change were significantly associated with aneurysm growth. However, in the multivariable analysis, the association remained significant only for angle change (odds ratio, 2.21; 95% confidence interval, 1.42-3.45). The cutoff value of parent artery angle change for intracranial aneurysm growth was -3.4°. CONCLUSION: Parent artery angle narrowing was significantly associated with intracranial aneurysm growth. This parameter may be useful for the monitoring of patients with unruptured intracranial aneurysms and may contribute to discerning the mechanism of intracranial aneurysm growth.

SARS-CoV-2 is localized in cardiomyocytes: a postmortem biopsy case.

A 72-year-old patient was admitted to the intensive care unit due to acute respiratory distress syndrome caused by COVID-19. On day 20, the patient experienced shock. The electrocardiogram showed ST segment elevation in leads V3-V6 and severe left ventricular dysfunction with an ejection fraction of 35%-40%. The left ventricle showed basal hypokinesis and apical akinesis, while the creatine kinase level was normal, indicating Takotsubo cardiomyopathy. On day 24, the patient died of multiple organ failure. In post-mortem biopsy, SARS-CoV-2 antigen was detected in cardiomyocytes by immunostaining. Moreover, SARS-CoV-2 RNA was detected in heart tissue. We need to further analyse the direct link between SARS-CoV-2 and cardiomyocytes.

Coronavirus disease (COVID-19) associated delayed-onset fulminant myocarditis in patient with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

A healthy 35-year-old man was admitted to a rural hospital with coronavirus disease (COVID-19). During 14 days of hospitalization, he had no symptoms and was not given supplemental oxygen. About 3 weeks after discharge, he was re-admitted to the same hospital with new-onset continuous fever and general weakness. At the time of his second admission, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RT-PCR was performed on a retro-nasal swab and the result was negative. Four days after admission, the patient was transferred to our intensive care unit (ICU) following deterioration of his respiratory and haemodynamic conditions, where he received mechanical ventilation, intra-aortic balloon pumping, and veno-arterial extracorporeal membrane oxygenation. A nasopharyngeal swab was obtained again at ICU admission, but RT-PCR was negative for SARS-CoV-2. All antibody titres measured against other viruses were low. Blood cultures were negative, and no bacteria were observed in sputum samples. However, SARS-CoV-2 RNA was detected by RT-PCR from sections obtained by myocardial biopsy. The patient's final diagnosis was delayed-onset SARS-CoV-2-induced fulminant myocarditis (FM). We strongly suggested that one of the proposed mechanisms of COVID-19-related myocardial injury will be the direct invasion of SARS-CoV-2 into cardiomyocytes even if delayed-onset. And this is the first case of delayed-onset FM in which diagnosis of active myocarditis was proven by pathological examination following endomyocardial biopsy and SARS-CoV-2 was detected in the myocardium by RT-PCR.

Trauma-induced coagulopathy and critical bleeding: the role of plasma and platelet transfusion.

Hemorrhage is responsible for 30 to 40% of all trauma-related mortality. Among adult trauma patients, 94% of hemorrhage-related deaths occur within 24 h and approximately 60% of these deaths within 3 h of hospital admission. Therefore, appropriate initial fluid resuscitation for bleeding is crucial to avoid preventable trauma-related death. In particular, the resuscitation strategy must be designed to complement prompt correction of anemia, coagulopathies, and thrombocytopenia. Conventional damage control resuscitation (DCR) of patients with severe trauma and massive hemorrhage is usually begun with rapid infusion of 1000 to 2000 mL of crystalloid fluids with subsequent transfusion of type O or uncross-matched red blood cells (RBCs) without plasma such as fresh frozen plasma (FFP) or platelets (PLTs). However, this DCR technique often leads to several adverse events such as abdominal compartment syndrome, acute respiratory distress syndrome, multiple organ failure, and dilutional coagulopathy. Simultaneous transfusion of FFP and PLTs along with the first units of RBCs while minimizing crystalloid infusion was recently recommended as a renewed DCR strategy. This aggressive RBC transfusion with FFP and PLTs is not only essential for the correction of coagulopathies and thrombocytopenia but also has the potential to ensure a good outcome in trauma patients. Additionally, it is important to maintain the resuscitation ratios of FFP/RBC and PLT/RBC. Most recently, DCR has been advocated for rapid hemorrhage control through early administration of a mixture of FFP, PLTs, and RBCs in a balanced ratio of 1:1:1.

A case of vitamin B12 deficiency with involuntary movements and bilateral basal ganglia lesions.

An 86-year-old woman with a one-year history of dementia was admitted to our hospital complaining of loss of appetite, hallucinations, and disturbance of consciousness. She gradually presented with chorea-like involuntary movements of the extremities. Diffusion-weighted magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals in the basal ganglia. The serum vitamin B12 level was below the lower detection limit of 50 pg/ml. The homocysteine level was markedly elevated at 115.8 nmol/ml. Anti-intrinsic factor and anti-parietal cell antibody tests were positive. Gastrointestinal endoscopy revealed atrophic gastritis. The patient was diagnosed with encephalopathy due to vitamin B12 deficiency caused by pernicious anemia. Involuntary movements and MRI abnormalities improved with parenteral vitamin B12 supplementation. Bilateral basal ganglia lesions are rare manifestations of adult vitamin B12 deficiency. The present case is considered valuable in identifying the pathophysiology of involuntary movement due to vitamin B12 deficiency.

Effect of pre-injury anticoagulant and antiplatelet agents on blood loss in elderly patients with severe trauma.

Aim: It has been widely reported that pre-injury use of anticoagulant and antiplatelet agents can affect traumatic brain injury and the associated risk of mortality, however, the effect of these agents on non-head injury site-related blood loss remains unclear. Therefore, we investigated the effects of pre-injury anticoagulant and antiplatelet agents on the transfusion amount and the need for massive transfusion in elderly patients with severe trauma. Methods: We retrospectively reviewed a cohort of elderly patients with severe trauma (age, ≥65 years; Injury Severity Score, ≥16) between September 2006 and March 2014. The selected patients were subsequently divided into patients who were: only taking warfarin, aspirin, or clopidogrel; taking various combinations of these agents; and a control group who were not taking any of these agents. Results: During the study period, 67 patients (20%) were taking anticoagulant and antiplatelet agents and 272 patients were included in the control group. Among these patients, 10 were receiving only warfarin, 28 were receiving only aspirin, 14 were receiving only clopidogrel, and 13 were receiving various combinations of these medications. The amount of red cell concentrate and need for massive transfusions were only significantly increased in the warfarin group (P < 0.05). Furthermore, the warfarin group had a significantly higher risk of needing a massive transfusion with multivariate logistic regression analysis (odds ratio, 5.03; 95% confidence interval, 1.25-20.20; P < 0.05). Conclusion: Patients who were receiving only warfarin before their injury had an increased risk of bleeding due to non-head injuries.

Limaprost reduces motor disturbances by increasing the production of insulin-like growth factor I in rats subjected to spinal cord injury.

Calcitonin gene-related peptide (CGRP) released from sensory neurons increases the production of a neuroprotective substance insulin-like growth factor I (IGF-I), and sensory neuron stimulation contributes to a reduction of spinal cord injury (SCI) by inhibiting inflammatory responses in rats. Because receptors for prostaglandin E2 (EP receptors) are present on sensory neurons, it is possible that prostaglandin E1 analog limaprost reduces SCI by increasing IGF-I production through sensory neuron stimulation. We examined this possibility in rats subjected to compression-trauma-induced SCI. Limaprost increased the CGRP release from dorsal root ganglion (DRG) neurons isolated from rats, and this increase was reversed by pretreatment with the EP4 receptor antagonist ONO-AE3-208. Spinal cord tissue levels of CGRP and IGF-I were increased after the induction of SCI, peaking at 2 h postinduction. The intravenous administration of limaprost enhanced increases of spinal cord tissue levels of CGRP, IGF-I, and IGF-I mRNA at 2 h after the induction of SCI. Increases of spinal cord tissue levels of tumor necrosis factor, caspase-3, myeloperoxidase, and the number of apoptotic nerve cells were inhibited by the administration of limaprost. Motor disturbances of hind legs in animals subjected to the compression-trauma-induced SCI were reduced by the administration of limaprost. These effects of limaprost were reversed completely by pretreatment with a specific transient receptor potential vanilloid 1 inhibitor SB366791 and by sensory denervation. These observations strongly suggest that limaprost may increase the IGF-I production by stimulating sensory neurons in the spinal cord, thereby ameliorating compression-trauma-induced SCI through attenuation of inflammatory responses.

The proteinase/proteinase-activated receptor-2/transient receptor potential vanilloid-1 cascade impacts pancreatic pain in mice.

AIMS: Proteinase-activated receptor-2 (PAR2) and transient receptor potential vanilloid-1 (TRPV1) are co-localized in the primary afferents, and the trans-activation of TRPV1 by PAR2 activation is involved in processing of somatic pain. Given evidence for contribution of PAR2 to pancreatic pain, the present study aimed at clarifying the involvement of TRPV1 in processing of pancreatic pain by the proteinase/PAR2 pathway in mice. MAIN METHODS: Acute pancreatitis was created by repeated administration of cerulein in conscious mice, and the referred allodynia/hyperalgesia was assessed using von Frey filaments. Injection of PAR2 agonists into the pancreatic duct was achieved in anesthetized mice, and expression of Fos in the spinal cord was determined by immunohistochemistry. KEY FINDINGS: The established referred allodynia/hyperalgesia following cerulein treatment was abolished by post-treatment with nafamostat mesilate, a proteinase inhibitor, and with capsazepine, a TRPV1 antagonist, in mice. Injection of trypsin, an endogenous PAR2 agonist, or SLIGRL-NH(2), a PAR2-activating peptide, into the pancreatic duct caused expression of Fos protein in the spinal superficial layers at T8-T10 levels in the mice. The spinal Fos expression caused by trypsin and by SLIGRL-NH(2) was partially blocked by capsazepine, the former effect abolished by nafamostat mesilate. SIGNIFICANCE: Our data thus suggest that the proteinase/PAR2/TRPV1 cascade might impact pancreatic pain, in addition to somatic pain, and play a role in the maintenance of pancreatitis-related pain in mice.

Activation of sensory neurons contributes to reduce spinal cord injury in rats.

We previously demonstrated that activation of sensory neurons increases endothelial prostaglandin I(2) (PGI(2)) production by releasing calcitonin gene-related peptide (CGRP). Since PGI(2) reduces post-traumatic spinal cord injury (SCI) by inhibiting tumor necrosis factor (TNF) production, activation of sensory neurons in the spinal cord tissue may ameliorate spinal cord injury. This study examines these possibilities using rat models of compression trauma-induced SCI. Both SB366791, a specific vanilloid receptor antagonist, and CGRP (8-37), a CGRP receptor antagonist, significantly inhibited trauma-induced increases in spinal cord tissue 6-keto-PGF(1alpha) levels. SB366791, CGRP (8-37) and indomethacin (IM) enhanced increases in spinal cord tissue TNF levels at 2h after trauma and exacerbated motor disturbances. Administration of CGRP significantly reduced motor disturbances and inhibited increases in spinal cord tissue TNF levels through enhancement of increases in tissue levels of 6-keto-PGF(1alpha). These observations strongly suggest that activation of sensory neurons might ameliorate compression trauma-induced SCI, inhibiting TNF production through enhancement of endothelial PGI(2) production. Thus, although the spinal cord sensory neurons function as nociceptive neurons, they could also be critically involved in the cytoprotective system that attenuates SCI development and, thus, pharmacological stimulation of spinal cord sensory neurons might contribute to reduce spinal cord injury.

Unicortical transverse osteochondral fracture of the patella: a case report.

Chondral lesions are relatively common and they usually occur as a result of high energy trauma. Chondral fractures of the patella ordinarily occur during an acute dislocation of the patella. Patellar chondral fractures without either a dislocation or a patella fracture are extremely rare. We have treated a 25-year-old male who had a unicortical transverse osteochondral fracture of the patella without a dislocation which was produced by high energy trauma. Chondral fractures of the patella are often overlooked because they are difficult to detect on plain radiographs. A persistent cartilaginous irregularity from either a chondral or osteochondral fracture may lead to the development of secondary osteoarthrosis. In this case, restoration of the articular surface was achieved by elevation of the compressed osteochondral fragment. This case demonstrates that understanding the mechanism of injury can be helpful in the treatment of osteochondral lesions.