Frequency, Characteristics, and Preventability of Adverse Drug Reactions in Perioperative Neurosurgery: Analysis Over 11 Years.

OBJECTIVE: Despite the importance of adverse drug reactions (ADRs), little is known about their role in perioperative neurosurgery. This study aimed to determine the prevalence of ADRs in perioperative neurosurgery and clarify the characteristics, severity, preventability, and risk factors of ADRs. METHODS: Data for all patients who underwent neurosurgical procedures over an 11-year period were analyzed. During the study period, 3648 surgical procedures were performed for 2695 patients. Demographic and clinical information documented included medical history, allergic history, diagnosis, surgical method, suspected drugs, concomitant medications, and drug details. Multivariate logistic regression analyses were performed to identify independent parameters that were correlated with ADRs. RESULTS: In total, 467 ADRs (18.3% ADRs/all neurosurgical procedures) were experienced by 401 patients. Anticonvulsants were associated with the highest number of ADRs (16.0%), followed by antibiotics (14.7%). Patients with ADRs were older than patients without ADRs (P < 0.01). The total number of drugs in patients with ADRs was 8.8 ± 3.6, compared to 5.2 ± 2.4 for patients without ADRs (P < 0.01). There were no significant differences in sex, allergic history, severe renal dysfunction (estimated glomerular filtration rate < 30 ml/min/1.73 m2), hypertension, diabetes, urgency of surgery, and type of surgery. Multivariate analysis showed that a high total number of drugs (odds ratio=3.2; 95% confidence interval 1.9-5.1) and older age (odds ratio=2.1; 95% confidence interval 1.3-3.8) were independent risk factors for ADRs. CONCLUSIONS: The frequency of suspected and severe ADRs was higher than expected. Polypharmacy and older age were independent risk factors for ADRs in perioperative neurosurgery. To decrease ADRs during perioperative neurosurgery, polypharmacy must be discouraged, especially among older adult patients.

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Current-driven fast magnetic octupole domain-wall motion in noncollinear antiferromagnets.

Antiferromagnets (AFMs) have the natural advantages of terahertz spin dynamics and negligible stray fields, thus appealing for use in domain-wall applications. However, their insensitive magneto-electric responses make controlling them in domain-wall devices challenging. Recent research on noncollinear chiral AFMs Mn3X (X = Sn, Ge) enabled us to detect and manipulate their magnetic octupole domain states. Here, we demonstrate a current-driven fast magnetic octupole domain-wall (MODW) motion in Mn3X. The magneto-optical Kerr observation reveals the Néel-like MODW of Mn3Ge can be accelerated up to 750 m s-1 with a current density of only 7.56 × 1010 A m-2 without external magnetic fields. The MODWs show extremely high mobility with a small critical current density. We theoretically extend the spin-torque phenomenology for domain-wall dynamics from collinear to noncollinear magnetic systems. Our study opens a new route for antiferromagnetic domain-wall-based applications.

Pituitary apoplexy in endocrinologically silent adenoma during somatostatin analog administration for pancreatic neuroendocrine tumor: A case report.

A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an 82-year-old patient who suffered from pituitary apoplexy in an endocrinologically silent adenoma during lanreotide administration. The patient was diagnosed with a pancreatic neuroendocrine tumor with lymph node metastasis and treated with lanreotide for two years. An endoscopic endonasal transsphenoidal approach was used for tumor and hematoma removal. The specimen showed growth hormone and prolactin positivity and was diagnosed as pit1-lineage plurihormonal adenoma. The tumor also showed positivity for somatostatin receptor 2. Thus, lanreotide treatment is a risk factor for pituitary apoplexy even in silent adenoma.

Intracerebral Hematoma in Patients With Impella Ventricular Assist Device Placement for Cardiogenic Shock: Report of Three Cases.

Despite the clear benefits of Impella in patients with cardiogenic shock, bleeding is a possible complication. Herein, we report three cases of intracerebral hemorrhage in patients with Impella implantation for cardiogenic shock, which were treated with hematoma evacuation. We present the clinical features, diagnosis, and management (hematoma evacuation) of patients with the Impella device (Abiomed, Danvers, Massachusetts) who developed intracerebral hemorrhage. Case one was a 56-year-old man who presented with chest pain and loss of consciousness, was diagnosed with acute myocardial infarction, and underwent urgent percutaneous coronary intervention and Impella placement. After eight days, the patient developed anisocoria. Computed tomography revealed a left intracerebral hemorrhage. An emergency hematoma evacuation was successfully performed (intraoperative blood loss: 2600 mL). Case two was a 54-year-old male who presented with persistent chest pain and loss of consciousness, was diagnosed with acute myocardial infarction, and underwent an emergency percutaneous coronary intervention with Impella implantation and venoarterial extracorporeal membrane oxygenation. The patient developed intracerebral hemorrhage after 26 days. Hematoma evacuation was successfully performed (intraoperative blood loss: 380 mL). Case three was a 52-year-old male who presented with dyspnea and hypotension, was diagnosed with dilated cardiomyopathy, and underwent Impella implantation and venoarterial extracorporeal membrane oxygenation, followed by which the patient developed subcortical hematoma. An emergency hematoma evacuation was performed (intraoperative blood loss: 3205 mL). The patient died 14 days after admission. Intracerebral hemorrhage is a potential cause of morbidity associated with Impella placement. Although hematoma evacuation is optimal, the bleeding tends to increase.

Impact of system approach and personal performance on preventable morbidity and mortality events in neurosurgery patients.

PURPOSE: Adverse events in neurosurgery are a serious problem. The approach for seeking solutions for adverse events has shifted from a personal approach to a systemic approach. However, to some extent, preventable morbidity events could be related to personal performance. This study aimed to clarify the impact of personal performance and systematic failure on the occurrence of morbidity and mortality events in neurosurgery patients. METHODS: All morbidity and mortality conference data stored within our department over a 9-year period were analyzed. There were 4580 admitted patients and 3262 surgical procedures performed. We performed a three-step classification of morbidity and mortality events based on the possibility of prevention, root of the event, and personal or systemic issues. RESULTS: As a result of the first step, 214 preventable and 278 unpreventable events were identified. Of the preventable events, two mortality and 212 morbidity events were analyzed. In the second step, 155 (72.4%), 34 (15.9%), 13 (6.1%), and 12 (5.6%) events were categorized as technical complications, critical events, judgment errors, and human factors, respectively. There were 179 events (83.6%) classified as personal performance issues and 35 events (16.4%) as systemic issues. The ratio of personal performance to systemic issues varied widely, with significant differences among the four categories (P < 0.01). CONCLUSIONS: Among neurosurgery patients who have preventable morbidity, issues related to personal performance were more frequent than systemic issues. Efforts to improve systems should be unwavering. However, the personal responsibility of neurosurgeons to avoid preventable complications should not be ignored.

A case of intestinal perforation with a residual shunt tube placed during childhood: should we remove the non-functioning tube?

We report a 22-year-old man who had abdominal shunt tube migration into colon. He was diagnosed with pilocytic astrocytoma at optic-chiasm to hypothalamus at age of 7, and treated by resection, chemotherapy, and irradiation. He developed hydrocephalus and had multiple ventriculo-peritoneal shunt surgery. At age of 19, he fell in coma due to the subarachnoid and intra-ventricular hemorrhage due to the aneurysm rupture. The ventricle tube was removed, leaving the shunt valve and abdominal tube. The new shunt system was reconstructed at the contralateral side. He was at bed rest after this episode. At age of 20, he had high fever unable to control with antibiotics. The abdominal computed tomogram showed the shunt tube migration in the descending colon. The tube was removed under laparoscopy, and the inflammation was cured. The abandoned peritoneal shunt tube should be removed in patients with high tube migration risks.

Giant field-like torque by the out-of-plane magnetic spin Hall effect in a topological antiferromagnet.

Spin-orbit torques (SOT) enable efficient electrical control of the magnetic state of ferromagnets, ferrimagnets and antiferromagnets. However, the conventional SOT has severe limitation that only in-plane spins accumulate near the surface, whether interpreted as a spin Hall effect (SHE) or as an Edelstein effect. Such a SOT is not suitable for controlling perpendicular magnetization, which would be more beneficial for realizing low-power-consumption memory devices. Here we report the observation of a giant magnetic-field-like SOT in a topological antiferromagnet Mn3Sn, whose direction and size can be tuned by changing the order parameter direction of the antiferromagnet. To understand the magnetic SHE (MSHE)- and the conventional SHE-induced SOTs on an equal footing, we formulate them as interface spin-electric-field responses and analyzed using a macroscopic symmetry analysis and a complementary microscopic quantum kinetic theory. In this framework, the large out-of-plane spin accumulation due to the MSHE has an inter-band origin and is likely to be caused by the large momentum-dependent spin splitting in Mn3Sn. Our work demonstrates the unique potential of antiferromagnetic Weyl semimetals in overcoming the limitations of conventional SOTs and in realizing low-power spintronics devices with new functionalities.

Cauda equina schwannoma presenting with subarachnoid and subdural hemorrhage: Its underlying mechanism.

BACKGROUND: A patient presented with a spinal subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) attributed to a spinal schwannoma at the T12-L1 level. CASE DESCRIPTION: A 67-year-old male acutely presented with severe back pain and L1 paraparesis/sensory loss, with urinary incontinence. CT/MR studies showed a spinal SAH and SDH within a likely T12-L1 schwannoma. At surgery, the hemorrhage within the tumor was continuous through the lower pole of the tumor into the subarachnoid and subdural spaces; tumor was dissected away from the surrounding tissues and totally removed. The postoperative course was uneventful, and the preoperative neurological deficits gradually resolved. Histopathologically, the lesion was a schwannoma with intratumoral hemorrhage. CONCLUSION: This case demonstrates the rare acute presentation of a T12-L1 schwannoma with an accompanying intratumoral hemorrhage resulting in both a SDH/SAH.

X-ray study of ferroic octupole order producing anomalous Hall effect.

Recently found anomalous Hall, Nernst, magnetooptical Kerr, and spin Hall effects in the antiferromagnets Mn3X (X = Sn, Ge) are attracting much attention for spintronics and energy harvesting. Since these materials are antiferromagnets, the origin of these functionalities is expected to be different from that of conventional ferromagnets. Here, we report the observation of ferroic order of magnetic octupole in Mn3Sn by X-ray magnetic circular dichroism, which is only predicted theoretically so far. The observed signals are clearly decoupled with the behaviors of uniform magnetization, indicating that the present X-ray magnetic circular dichroism is not arising from the conventional magnetization. We have found that the appearance of this anomalous signal coincides with the time reversal symmetry broken cluster magnetic octupole order. Our study demonstrates that the exotic material functionalities are closely related to the multipole order, which can produce unconventional cross correlation functionalities.

Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging-A controversy.

BACKGROUND: Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion? METHODS: Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI). RESULTS: A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI. CONCLUSION: CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

Impact of Perihematomal Edema on Infectious Complications after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hematoma involves two mechanisms leading to brain injury: the mechanical disruption of adjacent brain tissue by the hematoma and delayed neurological injury. Delayed neurological injury involves perihematomal edema (PHE) formation. Infectious complications following intracerebral hemorrhage (ICH) are a significant contributor to post-ICH recovery. We sought to identify a correlation between PHE volumes and infectious complications following ICH. We also sought to explore the clinical impact of this association. MATERIALS AND METHODS: This retrospective study included 143 patients with spontaneous ICH. CT scans were performed on admission, and 3 h, 24 h, and 72 h following admission. Hematoma and PHE volumes were calculated using a semi-automatic method. The absolute PHE volume at each time point and changes in PHE volume (ΔPHE) were calculated. Neutrophil to lymphocyte ratio (NLR) and serum C-reactive protein (CRP) levels were measured from the obtained blood samples. Neurological deterioration (ND) was assessed in all patients. RESULTS: Infectious complications were associated with ΔPHE72-24 (P < 0.01), whereas there was no association between infectious complications and ΔPHE24-3 (P = 0.09) or ΔPHE3-ad (P = 0.81). There was a positive correlation between ΔPHE72-24 and NLR (r = 0.85, 95% CI: 0.79-0.90, P < 0.01) and between ΔPHE72-24 and CRP levels (r = 0.89, 95% CI: 0.84-0.92, P < 0.01). The ND rate in the group of patients with infectious complications comorbid with high ΔPHE72-24 was higher than the other patient groups (P < 0.01). CONCLUSIONS: This study revealed a correlation between ΔPHE72-24 and infectious complications after spontaneous ICH, which was associated with markers of systemic inflammation. This phenotype linkage is a negative cascade that drives ND.

Anomalous transport due to Weyl fermions in the chiral antiferromagnets Mn3X, X = Sn, Ge.

The recent discoveries of strikingly large zero-field Hall and Nernst effects in antiferromagnets Mn3X (X = Sn, Ge) have brought the study of magnetic topological states to the forefront of condensed matter research and technological innovation. These effects are considered fingerprints of Weyl nodes residing near the Fermi energy, promoting Mn3X (X = Sn, Ge) as a fascinating platform to explore the elusive magnetic Weyl fermions. In this review, we provide recent updates on the insights drawn from experimental and theoretical studies of Mn3X (X = Sn, Ge) by combining previous reports with our new, comprehensive set of transport measurements of high-quality Mn3Sn and Mn3Ge single crystals. In particular, we report magnetotransport signatures specific to chiral anomalies in Mn3Ge and planar Hall effect in Mn3Sn, which have not yet been found in earlier studies. The results summarized here indicate the essential role of magnetic Weyl fermions in producing the large transverse responses in the absence of magnetization.

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

Morbidity and Mortality Conference Can Reduce Avoidable Morbidity in Neurosurgery: Its Educational Effect on Residents and Surgical Safety Outcomes.

BACKGROUND: Morbidity and mortality conferences (MMCs) are now widely implemented in clinical hospitals, but their impact on the education for neurosurgeons remains limited. This prospective study was aimed to assess the efficacy and benefit of MMCs on the education for neurosurgeon. METHODS: All morbidity and mortality events were prospectively recorded and were categorized on the basis of 2 viewpoints. First, they were classified into "avoidable" and "unavoidable" events, based on the quality of each event. Simultaneously, they were classified into 3 groups, including the residents, attendant members, or unclassifiable, based on the experience of the neurosurgeon who were most closely related to each event. The information was compared between early (2013-2014) and late (2015-2017) study periods to evaluate the education value of MMCs. RESULTS: During a 5-year study period, 44 mortality (2.1% per patient) and 201 morbidity events (9.7% per patient) were recorded. There were no significant differences in the incidence of mortality between 2 periods (P = 0.52). The incidence of morbidity significantly decreased from 11.5% (83/723) to 8.4% (118/1403; P < 0.04). Of these, "avoidable" events, but not "unavoidable" events significantly decreased from 7.5% (54/723) to 4.2% (59/1403; P = 0.001). The decrease in the incidence of "avoidable" morbidity was more pronounced in the residents than in the attendant members (P = 0.007 and P = 0.04, respectively). CONCLUSIONS: Knowledge acquisition from MMCs can significantly reduce "avoidable" morbidity events in both residents and experienced neurosurgeons. The educational effect was more distinct in the residents.

Repeated Deterioration of Consciousness Resulting from Spontaneous Intracranial Hypotension Associated with Deep Cerebral Vein Stagnation.

BACKGROUND: Although the clinical course of spontaneous intracranial hypotension (SIH) is generally benign, in unusual cases it can result in deterioration of consciousness. The exact mechanisms involved have not always been described in previously reported cases. CASE DESCRIPTION: Herein we describe the case of a 36-year-old man who presented complaining of orthostatic headache. Brain magnetic resonance imaging depicted typical findings associated with SIH. He initially underwent conservative treatments, but he subsequently began to exhibit deterioration of consciousness. Magnetic resonance imaging revealed progressive brain sagging, swelling of the brainstem, and focal hyperintensity in the left side of the thalamus on diffusion-weighted imaging. The vein of Galen was stretched downwards, creating a narrow angle between it and the straight sinus. We concluded that deep venous hypertension had occurred due to functional venous stenosis. He underwent epidural blood patch twice and ultimately recovered without any neurologic deficits. CONCLUSIONS: SIH should be recognized as a possible cause of coma as a result of deep cerebral vein stagnation due to severe brain sagging. A change in the vein of Galen/straight sinus angle may be an anatomic marker associated with functional venous stenosis.

Scanning tunneling microscopy on cleaved Mn3Sn(0001) surface.

We have studied in-situ cleaved (0001) surfaces of the magnetic Weyl semimetal Mn3Sn by low-temperature scanning tunneling microscopy and spectroscopy (STM/S). It was found that freshly cleaved Mn3Sn surfaces are covered with unknown clusters, and the application of voltage pulses in the tunneling condition was needed to achieve atomically flat surfaces. STM topographs taken on the flat terrace show a bulk-terminated 1 × 1 honeycomb lattice with the Sn site brightest. First-principles calculations reveal that the brightest contrast at the Sn site originates from the surrounding surface Mn d orbitals. Tunneling spectroscopy performed on the as-cleaved and voltage-pulsed surfaces show a prominent semimetal valley near the Fermi energy.

Publisher Correction: Magnetic and magnetic inverse spin Hall effects in a non-collinear antiferromagnet.

In this Letter, the formatting of some of the crystallographic axes was incorrect. This has been corrected online.

Magnetic and magnetic inverse spin Hall effects in a non-collinear antiferromagnet.

The spin Hall effect (SHE)1-5 achieves coupling between charge currents and collective spin dynamics in magnetically ordered systems and is a key element of modern spintronics6-9. However, previous research has focused mainly on non-magnetic materials, so the magnetic contribution to the SHE is not well understood. Here we show that antiferromagnets have richer spin Hall properties than do non-magnetic materials. We find that in the non-collinear antiferromagnet10 Mn3Sn, the SHE has an anomalous sign change when its triangularly ordered moments switch orientation. We observe contributions to the SHE (which we call the magnetic SHE) and the inverse SHE (the magnetic inverse SHE) that are absent in non-magnetic materials and that can be dominant in some magnetic materials, including antiferromagnets. We attribute the dominance of this magnetic mechanism in Mn3Sn to the momentum-dependent spin splitting that is produced by non-collinear magnetic order. This discovery expands the horizons of antiferromagnet spintronics and spin-charge coupling mechanisms.

Reconstruction of root systems in Cryptomeria japonica using root point coordinates and diameters.

MAIN CONCLUSION: We developed simple algorithms for reconstructing tree root system architecture using only the root point coordinate and diameter, which can be systematically obtained without digging up the root systems. Root system architecture (RSA) is strongly related to various root functions of the tree. The aim of this study was to develop a three-dimensional (3D) RSA model using systematically obtained information on root locations and root diameters at the locations. We excavated root systems of Cryptomeria japonica and systematically obtained XYZ coordinates and root diameters using a 10-cm grid. We clarified the patterns of the root point connections and developed a reconstructed root system model. We found that the root diameters farther from the stump centre are smaller. Additionally, we found that the root lengths of the segments running between the base and the connected root point were smaller than those of other root segments, and the inner angle between the base and the stump and between the base and the connected root point was narrower than for the other pairs. The new RSA model developed according to these results had average accuracies of 0.64 and 0.80 for estimates of total volume and length, respectively. The developed model can estimate 3D RSA using only root point data, which can be obtained without digging up root systems. This suggests a wide applicability of this model in root function evaluation.