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Objective 11C-PHNO is a PET radioligand most specific to dopamine D3 receptor (D3R). The long scan duration of 120 min used in quantification of 11C-PHNO binding to D3R in previous studies is challenging to subjects. The main objective of this study was to investigate the effects of shorter scan times on the binding of 11C-PHNO to D3R and test–retest reliability using the latest digital whole-body PET system. Methods Two 120-min 11C-PHNO brain scans were performed in 7 healthy subjects using a digital whole-body PET/CT. The binding potential relative to non-displaceable tracer in the tissue (BPND) of D3R-rich regions: the pallidum, ventral striatum (VST), substantia nigra (SN) and hypothalamus, were quantified using the simplified reference tissue model. The bias, correlation, and test–retest reliability of BPND, which includes the test–retest variability (TRV) and intraclass correlation coefficient (ICC), were evaluated and compared between scans of shorter durations (40–110 min post-injection) and the original 120-min scan acquisitions. Results Progressively, shorter scan durations were associated with underestimation of BPND, slightly decreased correlation with 120-min derived BPND, and decrease in test–retest reliability. The BPND values of the pallidum, VST and SN from the shortened 90-min scans showed excellent correlation with those derived from the 120-min scans (determination coefficients > 0.98), and the bias within 5%. The test–retest reliability of BPND in these regions derived from 90-min scan (TRV of 3% in the VST and pallidum, 7% in the SN and the ICC exceeded 0.88) was comparable to those obtained in previous 120-min studies using brain-dedicated PET scanners. In the hypothalamus, the BPND values obtained from scan-time less than 110 min showed bias larger than 5% and the TRV more than 9%. Conclusion The scan-time shortening causes bias and decreasing test–retest reliability of 11C-PHNO BPND. However, in the whole-body PET system, 90-min scan duration was sufficient for estimating the 11C-PHNO BPND in the D3R-rich striatum and SN with small bias and at the test–retest reliability comparable to those derived from 120-min scans using the brain-dedicated PET systems.

An 82-year-old man with fever and back pain was referred to our hospital and was thus found to be thrombocytopenic. A bone marrow biopsy revealed the diffuse infiltration of poorly differentiated neuroendocrine carcinoma (NEC). Computed tomography revealed a large hepatic mass. Considering the risk of bleeding due to thrombocytopenia, a needle biopsy was not performed. The patient rapidly deteriorated and died 10 days after presentation. An autopsy confirmed the diagnosis of primary hepatic NEC, with diffuse metastasis to the spleen, bone marrow, and systemic lymph nodes. This is an extremely rare case of NEC presenting with thrombocytopenia due to extensive bone marrow and splenic infiltration.

The management of cervical spine injuries in the elderly is often complicated by the presence of multiple medical comorbidities, and it is not uncommon for preoperative testing to reveal other conditions that require the postponement of surgery. However, the factors that affect the waiting time from injury to surgery have not been clarified. The purpose of this multicenter database study was to analyze the clinical features and identify the factors affecting the number of days waited between injury and surgery in elderly patients with a cervical spine injury.We retrospectively reviewed the case histories of 1512 Japanese patients with a cervical spinal injury, who were seen at 33 institutions. After excluding patients who were not initially receiving a surgery for cervical spinal injury, 694 patients were ultimately analyzed. Based on a multivariate mixed model, we determined the factors related to the number of days from injury to surgery.The mean time from injury to surgery was 12.3 days. Multivariate analysis revealed delays of 10.7 days for a renal disorder, 7.3 days for anticoagulant use, and 15.2 days for non-surgical thoracolumbar fracture as factors prolonging wait time. In contrast, a C3 or lower spine injury was significantly associated with a shortening of 9.5 days to surgery.This multicenter database study identified several factors influencing the time between injury and cervical spine surgery in elderly patients. While renal impairment, anticoagulant use, and non-surgical thoracolumbar fracture may increase the number of days to surgery, trauma to C3 or lower may expedite surgical treatment.

In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma.The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well.Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases.This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.

Independent gait following stroke is ultimate goal of rehabilitation. Non-invasive neuromodulation achieving it has never been reported. A 74-year-old woman suffered from subarachnoid haemorrhage, followed by hydrocephalus. Both were treated successfully. Even 1 year after the ictus, ambulation was difficult due to truncal instability with lateropulsion mainly to the left side. Transcranial direct current stimulation (tDCS) was applied to the parietal area (2mA for 20 min/day; anode on left side, cathode on right) for 16 days. The intervention improved her truncal instability and she achieved independent gait. tDCS of the parietal area could be a novel treatment option for gait disturbance due to postural instability following stroke.

Supplementary Methods

Table S1. Canine cohort metadata Table S2. Canine library preparation, amplification, and complexity Table S3. COSMIC Cancer Gene Census genes Table S4. Summary of canine RNA-seq data Table S5. RNA-seq validation Table S6. RNA-seq survey Table S7. Enrichment of protein domains in hemangiosarcoma and angiosarcoma Table S8. Canine somatic copy number aberrations by oaCGH Table S9. Comparison of top SCNAs in human Angiosarcoma Project data with canine oaCGH data Figure S1 - Canine exome sequencing workflow Figure S2 - Canine SMGs called in normal vs. overamplified libraries Figure S3 - Mutational landscape of entire canine cohort Figure S4 - Mutational landscape: FFPE vs Frozen Figure S5 - Mutational landscape: Canine Tumor Location Figure S6 - FFPE vs Frozen exome SCNA data clustering

Supplemental Table 7

Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease.Implications:We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.

Ion channels at the nodes of Ranvier (NRs) are believed to play essential roles in intrinsic electrophysiological properties and saltatory conduction of action potentials (AP) at the NRs of myelinated nerves. While we have recently shown that two-pore domain potassium (K2P) channels play a key role at the NRs of Aβ-afferent nerves, K(+) channels and their functions at the NRs of mammalian motor nerves remain elusive. Here we addressed this issue by using ex vivo preparations of lumbar spinal ventral nerves from both male and female rats and the pressure-patch-clamp recordings at their NRs. We found that depolarizing voltages evoked large noninactivating outward currents at NRs. The outward currents could be partially inhibited by voltage-gated K(+) channel blockers, largely inhibited by K2P blockers and cooling temperatures. Inhibition of the outward currents by voltage-gated K(+) channel blockers, K2P blockers, or cooling temperatures significantly altered electrophysiological properties measured at the NRs, including resting membrane potential, input resistance, AP width, AP amplitude, AP threshold, and AP rheobase. Furthermore, K2P blockers and cooling temperatures significantly reduced saltatory conduction velocity and success rates of APs in response to high-frequency stimulation. Voltage-gated K(+) channel blockers reduced AP success rates at high-frequency stimulation without significantly affecting saltatory conduction velocity. Collectively, both K2P and voltage-gated K(+) channels play significant roles in intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. The effects of cooling temperatures on saltatory conduction are at least partially mediated by K2P channels at the NRs. SIGNIFICANCE STATEMENT Ion channels localized at the NRs are believed to be key determinants of saltatory conduction on myelinated nerves. However, ion channels and their functions at the NRs have not been fully studied in different types of mammalian myelinated nerves. Here we use the pressure-patch-clamp recordings to show that both K2P and voltage-gated K(+) channels play significant roles in intrinsic electrophysiological properties and saltatory conduction at NRs of lumbar spinal ventral nerves of rats. Furthermore, cooling temperatures exert effects on saltatory conduction via inhibition of ion channels at the NRs. Our results provide new insights into saltatory conduction on myelinated nerves and may have physiological as well as pathologic implications.

This study aimed to examine whether the combination of excimer laser coronary atherectomy (ELCA) and drug-coated balloon (DCB) angioplasty can provide feasible clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) with 8-month and 2-year scheduled follow-up angiography.Intracoronary thrombus elevates the risk of interventional treatment in patients with STEMI and hampers drug absorption into the vasculature released from DCB.Sixty-two patients with STEMI within 24 h after the onset of symptoms were enrolled in this prospective, single-center, single-arm study.The laser catheter was successfully crossed distal to the culprit lesion in all cases. No ELCA-related adverse events occurred. Bail-out stenting was required in two patients (3.2%) after adjunctive ballooning; thus, the remaining 60 patients were completed with DCB angioplasty without stenting. Scheduled angiography at 8 months and 2 years was completed in 100% and 85.2%, respectively, and minimal lumen diameters were 3.4 ± 0.5, 3.4 ± 0.6, and 3.4 ± 0.5 mm after the procedure, at 8 months and at 2 years, respectively. Binary restenosis was observed in five patients (8.1%) in whom target lesion revascularization was performed. The duration of dual antiplatelet therapy was 2.3 ± 2.2 months, and neither abrupt vessel closure, reinfarction, cardiac death nor major bleeding was observed.A combination of DCB angioplasty with ELCA is a feasible therapeutic option for STEMI.

Background Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis that affects the aorta and its major branches, eventually leading to the development of aortic aneurysm and vascular stenosis or occlusion. This retrospective and prospective study aimed to investigate whether the gut dysbiosis exists in patients with TAK and to identify specific gut microorganisms related to aortic aneurysm formation/progression in TAK. Methods We analysed the faecal microbiome of 76 patients with TAK and 56 healthy controls (HCs) using 16S ribosomal RNA sequencing. We examined the relationship between the composition of the gut microbiota and clinical parameters. Results The patients with TAK showed an altered gut microbiota with a higher abundance of oral-derived bacteria, such as Streptococcus and Campylobacter, regardless of the disease activity, than HCs. This increase was significantly associated with the administration of a proton pump inhibitor used for preventing gastric ulcers in patients treated with aspirin and glucocorticoids. Among patients taking a proton pump inhibitor, Campylobacter was more frequently detected in those who underwent vascular surgeries and endovascular therapy for aortic dilatation than in those who did not. Among the genus of Campylobacter, Campylobacter gracilis in the gut microbiome was significantly associated with clinical events related to aortic aneurysm formation/worsening in patients with TAK. In a prospective analysis, patients with a gut microbiome positive for Campylobacter were significantly more likely to require interventions for aortic dilatation than those who were negative for Campylobacter. Furthermore, patients with TAK who were positive for C. gracilis by polymerase chain reaction showed a tendency to have severe aortic aneurysms. Conclusions A specific increase in oral-derived Campylobacter in the gut may be a novel predictor of aortic aneurysm formation/progression in patients with TAK.

Streptococcus mutans, a major cariogenic bacterium, expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, resulting in the impairment of blood brain barrier integrity followed by cerebral bleeding. We here examined the association of Cnm-positive S. mutans with cerebral microbleeds (CMBs) in acute stroke patients selected from a single-center registry database. Of 428 patients who received oral bacterial examinations among 3154 stroke patients, 326 patients who harbored S. mutans were identified. After excluding four patients without imaging data, we compared 72 patients with Cnm-positive S. mutans and 250 with Cnm-negative S. mutans. Deep, lobar and infratentorial CMBs were observed in 46 (63.9%), 36 (50.0%), 25 (34.7%) patients with Cnm-positive S. mutans and 144 (57.6%), 114 (45.6%), 101 (40.4%) with Cnm-negative S. mutans. Possession of Cnm-positive S. mutans was related to higher numbers of both deep and lobar, but not infratentorial, CMBs (risk ratios 1.57 [1.07‒2.30], deep; 5.44 [2.50‒11.85], lobar). Statistical significance persisted after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy (risk ratios 1.61 [1.14‒2.27], deep; 5.14 [2.78‒9.51], lobar). Our study indicated that reduction of Cnm-positive S. mutans may serve as a therapeutic approach for improving the prognosis of stroke patients.

Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010–2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients.

Additional file 1.

Supplemental Material for Epidemiology of Cervical Fracture/cervical Spinal Cord Injury and Changes in Surgical Treatment Modalities in elderly Individuals During a 10-year Period: A Nationwide Multicenter Study in Japan by Philipp Pieroh, Ulrich J.A. Spiegl, Anna Völker, Sven Märdian, Nicolas H. von der Höh, Georg Osterhoff, Christoph-E. Heyde; Spine Section of the German Society for Orthopaedics and Trauma in Global Spine Journal

Primary repair was carried out in a neonate with an atypical form of double outlet right ventricle; with a non-committed ventricular septal defect and lack of the outlet septum between the semilunar valves. The aortic arch was right-sided. The procedure required a right ventricular incision. Intraventricular rerouting could be achieved concomitantly with the arterial switch maneuver. Retrospectively, several strategies were contemplated to seek whether any other approach could have been superior to our present choice.

Objectives. We evaluated the thrombus-vaporizing effect of excimer laser coronary angioplasty (ELCA) in patients with ST-segment elevation myocardial infarction (STEMI) by optical coherence tomography (OCT). Background. Larger intracoronary thrombus elevates the risk of interventional treatment and mortality in patients with STEMI. Methods. A total of 92 patients with STEMI who presented within 24 hours from the onset and underwent ELCA following manual aspiration thrombectomy (MT) were analyzed. Results. The mean baseline thrombolysis in myocardial infarction flow grade was 0.4 ± 0.6, which subsequently improved to 2.3 ± 0.7 after MT ( p < 0.0001 ) and 2.7 ± 0.5 after ELCA ( p = 0.0001 ). The median residual thrombus volume after MT was 65.7 mm3, which significantly reduced to 47.5 mm3 after ELCA ( p < 0.0001 ). Plaque rupture was identified by OCT in only 22 cases (23.9%) after MT, but was distinguishable in 36 additional cases after ELCA (total: 58 cases; 63.0%). Ruptured lesions contained a higher proportion of red thrombus than nonruptured lesions (75.9% vs. 43.3%, p = 0.001 ). Significantly larger thrombus burden after MT (69.6 mm3 vs. 56.3 mm3, p < 0.05 ) and greater thrombus reduction by ELCA (21.2 mm3 vs. 11.8 mm3, p < 0.01 ) were observed in ruptured lesions than nonruptured lesions. Conclusions. ELCA effectively vaporized intracoronary thrombus in patients with STEMI even after MT. Lesions with plaque rupture contained larger thrombus burden that was frequently characterized by red thrombus and more effectively reduced by ELCA.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease that causes arteriovenous thrombosis and death. Valvular heart disease is one of its symptoms. Recurrent cerebral infarction caused by valvular heart disease is an indication for surgery; however, standard treatment, including perioperative anticoagulation, has not yet been established, and surgical mortality is high.Case presentation: A 41-year-old man had a cerebral infarction six years ago and was positive for antiphospholipid antibodies and lupus anticoagulants. He was diagnosed with primary APS and treated with anticoagulation therapy with warfarin. He had another episode of cerebral infarction four months ago. Transesophageal echocardiography revealed a mass attached to the mitral valve. He underwent steroid therapy and was continued on anticoagulant therapy; however, the mass did not shrink, and surgery was performed. Intraoperative rapid histopathology showed that the mass was an old thrombus, and because of the high degree of mitral valve degeneration, we considered that regurgitation control by the valve platy was difficult. Mitral valve replacement was performed using an On-X mechanical valve. Intraoperatively, the activated clotting time was measured every 30 minutes, and no tendency for thrombus formation was observed. He was continued on warfarin therapy after the surgery and did not experience any recurrence of thromboembolism after two years of surgery. Conclusions: We encountered a patient with APS, recurrent cerebral infarction, and mitral valve thrombus who underwent mitral valve replacement and continued postoperative anticoagulation therapy without recurrence of thromboembolism.

Ossification of the posterior longitudinal ligament (OPLL) can be complicated cervical spinal cord injury (CSCI) by low energy trauma, which is increasing among the elderly and potentially life-threatening. However, the etiology and neurological outcome of CSCI with OPLL in the elderly remain unknown. Therefore, we conducted this multi-center retrospective cohort study, which identified 1,512 patients aged ≥ 65 years and diagnosed with CSCI on admission from 2010 to 2020. We analyzed the etiology in patients with OPLL. Moreover, we performed propensity score-adjusted analyses to compare the neurological outcomes between patients with and without OPLL. The primary outcome comprised the American Spine Injury Association (ASIA) impairment scale (AIS) grade and ASIA motor score (AMS). In 332 patients with OPLL, the men:women ratio was approximately 4:1. Half of all patients displayed low energy trauma-induced injury, and one-third of the patients had CSCI without a bony injury. The propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between the patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. In summary, OPLL was not associated with neurological recovery in the elderly with CSCI.

Surgical treatment was very urgently carried out in an extremely cyanotic newborn with common pulmonary venous atresia. The diagnosis was confirmed during the procedure, and the common venous chamber was anastomosed to the left atrium through a transverse incision onto the right and the left atria. Unfortunately, pulmonary hypertension persisted during the postoperative course and even got worse gradually. Computed tomography eventually illustrated residual Cor Triatriatum. The initial atriotomy had been entirely above the diaphragm within the left atrium. Consequently, the abnormal structure had been overlooked. The patient is doing well one month after the surgical revision. Pulmonary hypertension disappeared.

Previous immunohistochemical studies have shown the expression of KCNQ2 channels at nodes of Ranvier (NRs) of myelinated nerves. However, functions of these channels at NRs remain elusive. In the present study, we addressed this issue by directly applying whole-cell patch-clamp recordings at NRs of rat lumbar spinal ventral nerves in ex vivo preparations. We show that depolarizing voltages evoke large non-inactivating outward currents at NRs, which are partially inhibited by KCNQ channel blocker linopirdine and potentiated by KCNQ channel activator retigabine. Furthermore, linopirdine significantly alters intrinsic electrophysiological properties of NRs to depolarize resting membrane potential, increase input resistance, prolong AP width, reduce AP threshold, and decrease AP amplitude. On the other hand, retigabine significantly decreases input resistance and increases AP rheobase at NRs. Moreover, linopirdine increases excitability at NRs by converting single AP firing into multiple AP firing at many NRs. Saltatory conduction velocity is significantly reduced by retigabine, and AP success rate at high stimulation frequency is significantly increased by linopirdine. Collectively, KCNQ2 channels play a significant role in regulating intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. These findings may provide insights into how the loss-of-function mutation in KCNQ2 channels can lead to neuromuscular disorders in human patients.

IntroductionThe role of commensal microbiota in systemic diseases, including brain diseases, has attracted increasing attention. Oral infectious diseases, such as dental caries and periodontitis, are also involved in cerebrovascular diseases and cognitive impairment. Cerebral microbleeds (CMBs) and intracerebral hemorrhage due to small vessel disease (SVD), are presumably associated with a high risk of vascular cognitive impairment and stroke. We previously reported that Streptococcus mutans (S. mutans, the main pathogen of dental caries), harboring the cnm gene that encodes the collagen-binding protein Cnm, is associated with the development of hypertensive intracerebral hemorrhage and aggravation of CMBs. We also proposed a mechanism by which the circulating Cnm-expressing S. mutans causes intracerebral hemorrhage or CMBs; it binds to denuded basement membranes mainly composed of collagen IV through damaged tight junctions or it directly invades endothelial cells, resulting in blood-brain barrier injury. In November 2018, we initiated a multicenter, prospective cohort study (RAMESSES: Risk Assessment of Cnm-positive S. mutans in Stroke Survivors; UMIN Clinical Trials Registry: UMIN000045559) to explore the longitudinal association between Cnm-positive S. mutans and CMBs with comprehensive dental findings, which should determine the effect of Cnm-positive S. mutans in the oral cavity on the risk of CMB development and cognitive decline.MethodsFifteen domestic institutes will be enlisted to enroll 230 patients who have at least one CMB in the deep brain area and develop a stroke within the past year. The prevalence of Cnm-positive S. mutans based on oral specimens and dental hygiene will be examined. The primary outcome is the number of newly developed deep CMBs. The secondary outcomes include the new development of lobar, subtentorial, or any type of CMBs; symptomatic intracerebral hemorrhage or ischemic stroke; changes in cognitive function or frailty; major bleeding; all-cause mortality; and antibody titers against periodontal pathogens. The observation period will be 2 years.DiscussionThe 2-year longitudinal prospective cohort study is expected to establish the role of Cnm-positive S. mutans in SVD including CMBs and intracerebral hemorrhage from the perspective of the “brain-oral axis” and provide guidance for novel prophylactic strategies against Cnm-positive S. mutans-induced SVD.

Patients with organ malperfusion from acute aortic dissection (AAD) have poor outcomes, and the surgical indications for patients with AAD complicated by extensive cerebral infarction have not been established. Here, we report a successfully treated surgical case of a patient with cerebral infarction and Stanford type A, AAD. A 77-year-old man was admitted to the hospital with a chief complaint of left paresis. After confirming that there was no cerebral hemorrhage with a head computed tomography and an incision in the right neck, and the right internal carotid artery was ligated and closed, emergency surgery was performed with a 24 mm Triplex® raft. The ascending aorta was replaced, and a bypass was performed with a prosthetic graft from the right axillary artery. No cerebral hemorrhage or neurological issues were observed postoperatively, which indicates the possibility of surgical intervention as a treatment strategy for this disease.

BACKGROUND: Copeptin, the C-terminal portion of the arginine vasopressin precursor, is a novel candidate biomarker. This study investigated the prognostic value of copeptin levels following cardiac surgery for the occurrence of postoperative acute kidney injury. METHODS: We studied 23 patients who underwent cardiac surgery between January 2018 and December 2019. The primary endpoint was postoperative acute kidney injury onset. Copeptin levels were measured before, right after, and daily for 7 days. The patients were divided into two groups according to the copeptin levels: low (values

ObjectivesTo collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.MethodsFifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.ResultsThe study population comprised 26 males and 24 females aged 0–61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.ConclusionsIn patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

Stroke is the second leading cause of death and a significant cause of disability worldwide. Recent advances in DNA sequencing, proteomics, metabolomics, and computational tools are dramatically increasing access to the identification of host–microbiota interactions in systemic diseases. In this review, we describe the accumulating evidence showing how human microbiota plays an essential role in cerebrovascular diseases. We introduce the symbiotic relationships between microbiota and the mucosal immune system, focusing on differences by anatomical sites. Microbiota directly or indirectly contributes to the pathogenesis of traditional vascular risk factors including age, obesity, diabetes mellitus, dyslipidemia, and hypertension. Moreover, recent studies proposed independent effects of the microbiome on the progression of various subtypes of stroke through direct microbial invasion, exotoxins, functional amyloids, inflammation, and microbe-derived metabolites. We propose the critical concept of gene-microbial interaction to elucidate the heterogeneity of stroke and provide possible therapeutic avenues. We suggest ways to resolve the vast inter-individual diversity of cerebrovascular disease and mechanisms for personalized prevention and treatment.

Background A complex and rare form of persistent truncus arteriosus needs careful attention when choosing the optimal strategy for repair. Aim of the study We herein describe our surgical strategy of a small infant having this malformation concomitantly with right aortic arch, unusual pulmonary artery branching and a left superior vena cava. Methods The patient underwent initially bilateral pulmonary arterial banding followed by the Rastelli type definitive repair. The pulmonary arteries were unified in front of the left superior vena cava, and the right ventricular outflow tract was readily reconstructed. Results The patient is doing well with an excellent hemodynamic status. Conclusions We considered the two-stage approach was sensible in this particular patient.

Although traumatic cervical spine injuries in older adults are commonly caused by minor traumas, such as ground-level falls, their prognosis is often unfavorable. Studies examining the clinical characteristics of cervical spine injuries in older adults according to the external cause of injury are lacking. This study included 1512 patients of ≥ 65 years of age with traumatic cervical spine injuries registered in a Japanese nationwide multicenter database. The relationship between the external causes and clinical characteristics, as well as factors causing unfavorable outcomes at the ground-level falls, were retrospectively reviewed and examined. When fall-induced cervical spine injuries were categorized and compared based on fall height, the patients’ backgrounds and injury statuses differed significantly. Of note, patients injured from ground-level falls tended to have poorer pre-injury health conditions, such as medical comorbidities and frailty, compared with those who fell from higher heights. For ground-level falls, the mortality, walking independence, and home-discharge rates at 6 months post-injury were 9%, 67%, and 80%, respectively, with preexisting medical comorbidities and frailty associated with unfavorable outcomes, independent of age or severity of neurological impairment at the time of injury.

Background The 1-year mortality and functional prognoses of patients who received surgery for cervical trauma in the elderly remains unclear. The aim of this study is to investigate the rates of, and factors associated with mortality and the deterioration in walking capacity occurring 1 year after spinal fusion surgery for cervical fractures in patients 65 years of age or older. Methods Three hundred thirteen patients aged 65 years or more with a traumatic cervical fracture who received spinal fusion surgery were enrolled. The patients were divided into a survival group and a mortality group, or a maintained walking capacity group and a deteriorated walking capacity group. We compared patients’ backgrounds, trauma, and surgical parameters between the two groups. To identify factors associated with mortality or a deteriorated walking capacity 1 year postoperatively, a multivariate logistic regression analysis was conducted. Results One year postoperatively, the rate of mortality was 8%. A higher Charlson comorbidity index (CCI) score, a more severe the American Spinal Cord Injury Association impairment scale (AIS), and longer surgical time were identified as independent factors associated with an increase in 1-year mortality. The rate of deterioration in walking capacity between pre-trauma and 1 year postoperatively was 33%. A more severe AIS, lower albumin (Alb) and hemoglobin (Hb) values, and a larger number of fused segments were identified as independent factors associated with the increased risk of deteriorated walking capacity 1 year postoperatively. Conclusions The 1-year rate of mortality after spinal fusion surgery for cervical fracture in patients 65 years of age or older was 8%, and its associated factors were a higher CCI score, a more severe AIS, and a longer surgical time. The rate of deterioration in walking capacity was 33%, and its associated factors were a more severe AIS, lower Alb, lower Hb values, and a larger number of fused segments.

Retrospective multicenter study.To investigate the neurological outcomes of older individuals treated with surgery versus conservative treatment for cervical spinal cord injury (CSCI) without bone injury.Thirty-three medical institutions in Japan.This study included 317 consecutive persons aged ≥65 years with CSCI without bone injury in participating institutes between 2010 and 2020. The participants were followed up for at least 6 months after the injury. Individuals were divided into surgery (n = 114) and conservative treatment (n = 203) groups. To compare neurological outcomes and complications between the groups, propensity score matching of the baseline factors (characteristics, comorbidities, and neurological function) was performed.After propensity score matching, the surgery and conservative treatment groups comprised 89 individuals each. Surgery was performed at a median of 9.0 (3-17) days after CSCI. Baseline factors were comparable between groups, and the standardized difference in the covariates in the matched cohort was10%. The American Spinal Injury Association (ASIA) impairment scale grade and ASIA motor score (AMS) 6 months after injury and changes in the AMS from baseline to 6 months after injury were not significantly different between groups (P = 0.63, P = 0.24, and P = 0.75, respectively). Few participants who underwent surgery demonstrated perioperative complications such as dural tear (1.1%), surgical site infection (2.2%), and C5 palsy (5.6%).Conservative treatment is suggested to be a more favorable option for older individuals with CSCI without bone injuries, but this finding requires further validation.