Efficacy of Tailored Treatment Strategies for Chronic Subdural Hematoma Based on Hematoma Characteristics and Volume: A Retrospective observational Study.

OBJECTIVE: We assessed the effectiveness of a treatment strategy based on hematoma characteristics and volume. METHODS: From September 2022 to December 2023 (the Study period), a two-center retrospective observational study of initial chronic subdural hematoma (CSDH) was performed. The baseline period was from January 2018 to December 2019. Patients were classified into the high and low retreatment rate groups (Groups H and L, respectively). During the Study period, Group H was treated with drainage and middle meningeal artery embolization (MMAE), while Group L was treated with drainage or MMAE alone. During the Baseline period, all the patients were treated with drainage alone. The primary and secondary endpoints were group retreatment rates and severe procedure-related complications requiring surgical intervention and permanent sequelae, respectively. RESULTS: Fifty-two patients were included during the Study period (31 in Group H and 21 in Group L) and 53 during the Baseline period (32 in Group H and 21 in Group L). Three (5.8%) and nine (17.0%) patients required retreatment in the Study and Baseline periods, respectively (p = 0.12). One (3.2%) and nine (28.1%) patients in Group H required retreatment during the Study and Baseline periods, respectively (p = 0.01). Similarly, two patients (9.5%) and no patient in Group L required retreatment during the Study and Baseline periods, respectively (p = 0.49). No severe complications were reported throughout. CONCLUSIONS: CSDH treatment strategies that consider to hematoma volume and characteristics have the potential to identify and reduce treatment rates in cases with high retreatment rates.

Successful surgical resection of a multilobular osteochondrosarcoma arising from the costal cartilage in a cat.

A 10-year-old neutered male cross-bred cat was referred to our clinic for a solid mass tightly fixed to the right side of the thoracic wall from the 2nd to 4th ribs. Computed tomography revealed the mass had remarkable calcifications and arose from the 3rd costal cartilage. After removal, it was diagnosed histopathologically as a multilobular osteochondrosarcoma (MLO). For tumor resection, extremely wide surgical margins included 6 costal cartilages and 3 sternal segments were required; however, the tumor was successfully resected, followed by reconstruction of the thoracic wall using artificial materials. The cat recovered uneventfully and was good in health for ~4 y. This is apparently the first report of surgical resection of MLO from the costal cartilage of a cat. Key clinical message: To our knowledge, this is the first report of MLO from the costal cartilage in a cat, demonstrating aggressive surgical resection despite extremely wide surgical margins.

Résection chirurgicale réussie d'un ostéochondrosarcome multilobulaire provenant du cartilage costal chez un chatUn chat croisé mâle castré de 10 ans a été référé à notre clinique pour une masse solide bien fixée sur le côté droit de la paroi thoracique de la 2e à la 4e côte. La tomodensitométrie a révélé que la masse présentait des calcifications remarquables et provenait du 3e cartilage costal. Après retrait, il a été diagnostiqué histopathologiquement comme un ostéochondrosarcome multilobulaire (MLO). Pour la résection tumorale, des marges chirurgicales extrêmement larges comprenaient 6 cartilages costaux et 3 segments sternaux; cependant, la tumeur a été réséquée avec succès, suivie d'une reconstruction de la paroi thoracique à l'aide de matériaux artificiels. Le chat s'est rétabli sans incident et était en bonne santé pendant environ 4 ans. Il s'agit apparemment du premier rapport de résection chirurgicale de MLO du cartilage costal d'un chat.Message clinique clé:À notre connaissance, il s'agit du premier rapport de MLO du cartilage costal chez un chat, démontrant une résection chirurgicale agressive malgré des marges chirurgicales extrêmement larges.(Traduit par Dr Serge Messier).

Feasibility, efficacy, and safety of mechanical thrombectomy via sheathless transradial access as a first-line strategy: A case series.

OBJECTIVE: Although mechanical thrombectomy (MT) is primarily performed via transfemoral access (TFA), transradial access (TRA) is a potential alternative in older patients or those with tortuous vessels. However, the small radial artery diameter restricts the use of large-bore balloon guides and aspiration catheters, a limitation that may be overcome using the sheathless technique. Thus, we aimed to explore the feasibility, efficacy, and safety of sheathless TRA-MT as a first-line treatment approach for acute ischemic stroke. METHODS: This single-center retrospective case series included patients who underwent TRA-MT as first-line treatment between September 2020 and June 2023. Per our MT protocol, TRA was not the first-line approach in cases of left anterior circulation lesions with a type 3 aortic arch. We evaluated treatment effectiveness based on the successful recanalization rate, puncture-to-recanalization time, and modified first-pass effect; access route effectiveness based on the puncture-to-first-pass time and switch-to-TFA rate; and procedure safety based on procedure-related and severe puncture site complications. RESULTS: Sheathless 8-F guide catheters were used in 68 % and large-bore aspiration catheters in 70 % of the procedures. Successful recanalization was achieved in 98 % of the patients, with a modified first-pass effect in 54 % of them. The median puncture-to-first-pass and puncture-to-recanalization times were 20.5 and 33 min, respectively. The rate of procedure-related complications was low (4 %), with no severe puncture site complications. CONCLUSION: Sheathless TRA-MT enabled the use of large-bore guide and aspiration catheters, providing a swift approach to the target and satisfactory outcomes, and might be an effective first-line treatment for acute ischemic stroke.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037). CONCLUSION: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

Carotid Artery Stenting via Radial Access with Modified Flow Reversal Method: Case Series.

OBJECTIVE: Neuroendovascular treatment via transradial access (TRA) has gained popularity as a minimally invasive technique. However, the flow reversal (FR) system, reported useful in carotid artery stenting (CAS), cannot be applied via TRA because it requires an access route of more than 8 F. Herein, we report the utility of a modified FR system applied via TRA using a sheathless 8-F balloon guide catheter and a 2.6-F balloon catheter. METHODS: In a retrospective analysis of a single-center consecutive case series, patients with CAS and vulnerable plaques who were treated with CAS via TRA using a modified FR system from June 2022 to August 2022 were examined. High-intensity spots were assessed on postprocedural diffusion-weighted magnetic resonance images. Puncture site complications at discharge and cardiovascular events for 1 year after CAS were also evaluated. RESULTS: Ten patients were included in this study. There were no high-intensity spots on diffusion-weighted magnetic resonance images after CAS. No procedure-related complications, including radial artery occlusion or cardiovascular events, were observed. CONCLUSIONS: This study suggests that CAS with FR using our modified system is feasible via TRA and may be an effective technique with a low rate of vascular complications.

Fentanyl sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs: a retrospective case-control study.

This study retrospectively evaluated the fentanyl-sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs. Fentanyl was prepared for intraoperative analgesia in dogs, although proximal RUMM block was performed using 0.5% or 0.25% bupivacaine before surgery in the block group. Dogs without a nerve block were assigned to the control group. The fentanyl dose in the block group [0.8 (0-1.9) µg/kg/hr] [median (interquartile range)] was significantly lower than in the control group [8.4 (7.2-10) µg/kg/hr]. Surgery was performed without fentanyl in >50% of the dogs (5/7), using 0.5% bupivacaine. Ultrasound-guided proximal RUMM block can be useful as an intraoperative analgesic for radial and ulnar fracture repair in dogs.

One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.

The Short-Term Outcome of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma with Mild Symptom: Case Series.

OBJECTIVE: A few reports have demonstrated the efficacy of middle meningeal artery embolization (MMAE) alone for mildly symptomatic chronic subdural hematoma (CSDH); however, the clinical course in the early posttreatment period remains unclear. The purpose of this study was to analyze the short-term outcomes of this technique at our center. METHODS: This study was based on a retrospective analysis of a single-center consecutive case series. Patients with mildly symptomatic CSDH treated with MMAE alone between July 2020 and June 2022 were examined. Neurological examinations and head computed tomography scans were performed before treatment and 1, 7, 14, and 28 days after treatment. The clinical course of the patients was analyzed. In particular, symptom improvement within 1 week from treatment or rescue evacuation and the factors associated were evaluated. RESULTS: Fifteen patients were included in this study. No procedure-related complications occurred. Partial or complete recovery within the first week from treatment was observed in 10 cases (66.7%), and the symptoms resolved completely in a median of 26 (6.5-33.5) days. Rescue evacuation was needed in 3 cases (20.0%). The hematoma volume and midline shift gradually decreased from baseline, with a significant improvement within the first week (P = 0.030 and 0.0032, respectively). CONCLUSIONS: MMAE alone provides relatively early improvement in cases of mildly symptomatic CSDH and may be a potential alternative to surgical evacuation or medical therapy.

Feasibility and Challenges of Transradial Approach in Neuroendovascular Therapy: A Retrospective Observational Study.

Objective: Transradial approach (TRA) is increasingly used as a viable alternative to the traditional transfemoral approach (TFA) in neuroendovascular therapy (NET) owing to its potential anatomical benefits and lower puncture-site complication rates. However, the real-world challenges of implementing TRA-NET have not been thoroughly studied, particularly those related to guide catheter (GC) placement. In this study, we aimed to explore the feasibility and challenges of TRA-NET, with a specific focus on GC placement. Methods: This retrospective observational study included patients who underwent NET at our institution between December 2019 and May 2022. Procedural success was defined as the successful placement of a GC in the target vessel. Cases in which a Simmons-shaped GC was used or the approach was changed to TFA were classified as difficult. Safety was assessed based on the rate of severe puncture-site complications requiring either blood transfusion or surgical intervention. Results: Among the 310 patients who underwent NET during the study period, 222 (71.6%) with a median age of 74 years were selected for TRA-NET. The target vessel was in the left anterior circulation (LtAC) in 101 (45.5%) patients, and 8-F GCs were the most frequently used (40.1%). TRA-NET achieved a 95.0% success rate, with a switch to TFA required in 5.0% of the cases. Procedural challenges occurred in 42 (18.9%) patients, primarily in those with LtAC lesions. Specifically, a type III aortic arch (p <0.0001) and age ≥80 years (p = 0.01) were significantly associated with procedural difficulties. Radial artery evaluation was confirmed in 66 cases (29.7%), revealing one instance (1.5%) of radial artery occlusion. No severe puncture-site complications were observed. Conclusion: TRA-NET may provide substantial therapeutic benefits without significant limitations in device use. However, it may be challenging, particularly in older patients and those with a type III aortic arch with LtAC lesions. Consequently, careful selection of the approach route is imperative.

Establishment and characterization of urothelial carcinoma cell lines with and without BRAF mutation (V595E) in dogs.

Each 5 urothelial carcinoma (UC) cell lines with and without the v-Raf murine sarcoma virus oncogene homolog B (BRAF) gene mutation (V595E) were established and examined V595E-related tumorigenic characteristics in dogs. No typical morphological features were observed in cloned cells with and without V595E. The cell proliferation of both cloned cells showed logarithmic growth curve and those doubling time were 24.9 ± 4.1 h in V595E ( +) and 29.3 ± 11.3 h in V595E ( -). On the growth curve of xenotransplanted tumor in severe combined immunodeficiency mice, 3 out of 5 V595E ( +) and 2 out of 5 V595E ( -) cloned cells revealed gradually and remarkably increasing curve, indicating clearly tumorigenicity. The xenotransplanted tumors with V595E ( +) showed typical features of UC, such as solid proliferation of pleomorphic tumor cells, formation of papillary structure, and glandular structure. Additionally, various vascular formation was observed, probably indicating an advanced growth phase of UC. In mitogen-activated protein kinase (MAPK) signaling pathway, cytoplasmic phosphorylated-BRAF (pBRAF) and cytoplasmic and nuclear phosphorylated-ERK1/2 (pERK1/2) were detected in all 4 tumors with V595E ( +), whereas only cytoplasmic and nuclear pERK1/2 was detected in tumors with V595E ( -). Since V595E can directly activate MAPK signaling pathway, coincidence of V595E with pBRAF (phosphor Thr598/Ser601) indicates acquired resistance to BRAF inhibitors. These established UC cell lines, especially V595E ( +) cell lines, are useful tool for understanding pathophysiological states and controlling therapeutic manners of UC in dogs.

Coincidence of v-raf murine sarcoma viral oncogene homolog B mutation (V595E) with phosphorylated v-raf murine sarcoma viral oncogene homolog B in urothelial carcinoma in dogs.

Expression of phosphorylated v-raf murine sarcoma viral oncogene homolog B (pBRAF) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) were investigated in urothelial carcinoma (UC) in dogs with or without the BRAF gene mutation (V595E). Among the 10 cases of UC with V595E (-), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was reported in 8, with 7 displaying moderate reactivity and 1 displaying intense reactivity. Nuclear immunoreactivity against pBRAF was detected in 5 cases; however, these reactivities were non-specific, due to pBRAF being limited in the cytoplasm. In addition, positive cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in 7 cases and nuclear immunoreactivity against ERK1/2 was detected in 6 cases. Among the 13 cases of UC with V595E (+), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pBRAF was detected in 10 cases; however, the nuclear immunoreactivity was non-specific. Cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pERK1/2 was also detected in all cases. As nuclear pERK1/2 indicates a progressive signaling process in the mitogen-activated protein kinase pathway, V595E (+) UC might be in its growing stage. Probable phosphorylated sites of pBRAF at Thr598/Ser601, detected in this study, are major and essential sites of the upstream rat sarcoma viral oncogene homolog (RAS) signaling pathway. In human cancers, the BRAF mutation never coincides with oncogenic RAS. To our knowledge, this is the first report on the simultaneous occurrence of the BRAF mutation (V595E) and pBRAF expression (at Thr598/Ser601) in dogs with UC with V595E (+).

L'expression de l'homologue B de l'oncogène viral du sarcome murin phosphorylé v raf (pBRAF) et de la kinase1/2 régulée par le signal extracellulaire phosphorylé (pERK1/2) ont été étudiées dans le carcinome urothélial (CU) chez des chiens avec ou sans la mutation du gène BRAF (V595E). Parmi les 10 cas de CU avec V595E (−), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été rapportée chez huit, sept présentant une réactivité modérée et un présentant une réactivité intense. L'immunoréactivité nucléaire contre pBRAF a été détectée dans cinq cas; cependant, ces réactivités n'étaient pas spécifiques, car pBRAF était limité dans le cytoplasme. De plus, une immunoréactivité cytoplasmique positive contre pERK1/2 des cellules néoplasiques a été détectée dans sept cas et une immunoréactivité nucléaire contre ERK1/2 a été détectée dans six cas. Parmi les 13 cas de CU avec V595E (+), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été détectée dans les 13 cas et une immunoréactivité nucléaire contre pBRAF a été détectée dans 10 cas; cependant, l'immunoréactivité nucléaire était non spécifique. L'immunoréactivité cytoplasmique contre pERK1/2 des cellules néoplasiques a été détectée dans les 13 cas et l'immunoréactivité nucléaire contre pERK1/2 a également été détectée dans tous les cas. Comme le pERK1/2 nucléaire indique un processus de signalisation progressif dans la voie de la protéine kinase activée par les mitogènes, V595E (+) UC pourrait être dans sa phase de croissance. Les sites phosphorylés probables de pBRAF à Thr598/Ser601, détectés dans cette étude, sont des sites majeurs et essentiels de la voie de signalisation de l'oncogène viral (RAS) du sarcome de rat en amont. Dans les cancers humains, la mutation BRAF ne coïncide jamais avec le RAS oncogène. À notre connaissance, il s'agit du premier rapport sur la survenue simultanée de la mutation BRAF (V595E) et de l'expression de pBRAF (à Thr598/Ser601) chez des chiens atteints de CU avec V595E (+).(Traduit par Docteur Serge Messier).

Silicone allergy associated with intraocular silicone ball prosthesis in a dog.

A 13-year-old, male Pomeranian dog was presented for scleral rupture with intraocular hemorrhage and retinal detachment in the right eye. After intrascleral silicone ball prosthesis, recurrent swelling and granulomatous blepharitis were observed for 140 d and finally melting keratitis developed. Although an intraorbital prosthesis was implanted, recurrent, serious, erosive, and ulcerative blepharitis developed with high plasma C-reactive protein concentrations. Since the blepharitis could not be controlled, the silicone ball was removed and the affected orbit was debrided. The blepharitis resolved rapidly, and the orbit healed routinely. Positive allergic reactions to silicone were discovered through a patch test. Key clinical message: To the authors' knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions to silicone in the patch test.

Allergie au silicone associée à une prothèse intraoculaire en boule de silicone chez un chien. Un chien poméranien mâle de 13 ans a été présenté pour rupture sclérale avec hémorragie intraoculaire et décollement de la rétine de l'oeil droit. Après l'implantation intrasclérale d'une boule de silicone comme prothèse, un gonflement récurrent et une blépharite granulomateuse ont été observés pendant 140 jours et une kératite fondante s'est finalement développée. Bien qu'une prothèse intra-orbitaire ait été implantée, une blépharite récurrente, grave, érosive et ulcéreuse s'est développée, avec des concentrations plasmatiques élevées de protéine C réactive. Comme la blépharite ne pouvait pas être contrôlée, la boule de silicone a été retirée et l'orbite affectée a été débridée. La blépharite s'est résolue rapidement et l'orbite a guéri normalement. Des réactions allergiques positives au silicone ont été découvertes grâce à un test cutané.Message clinique clé :À la connaissance des auteurs, il s'agit du premier rapport sur une allergie au silicone chez un chien ayant des réactions allergiques positives au silicone lors du test cutané.(Traduit par Dr Serge Messier).

An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency.

Dengue virus (DENV), from the genus flavivirus of the family flaviviridae, causes serious health problems globally. Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. Here, we generated eight HuMAb clones from an Indonesian patient infected with DENV. These HuMAbs exhibited the typical characteristics of weak neutralizing antibodies including high cross-reactivity with other flaviviruses and targeting of the fusion loop epitope (FLE). However, one of the HuMAbs, 3G9, exhibited strong neutralization (NT50 < 0.1 µg/ml) and possessed a high somatic hyper-mutation rate of the variable region, indicating affinity-maturation. Administration of this antibody significantly prolonged the survival of interferon-α/ß/γ receptor knockout C57BL/6 mice after a lethal DENV challenge. Additionally, Fc-modified 3G9 that had lost their in vitro ADE activity showed enhanced therapeutic potency in vivo and competed strongly with an ADE-prone antibody in vitro. Taken together, the affinity-matured FLE-targeting antibody 3G9 exhibits promising features for therapeutic application including a low NT50 value, potential for treatment of various kinds of mosquito-borne flavivirus infection, and suppression of ADE. This study demonstrates the therapeutic potency of affinity-matured FLE-targeting antibodies.

Distal Transradial Approach in Mechanical Thrombectomy: Technical Note.

Objective: We report a case of mechanical thrombectomy (MT) via the distal transradial approach (dTRA) and technical tips. Case Presentation: An 89-year-old woman was transferred to our hospital due to back pain after a fall and sudden-onset left hemiparesis. We performed MT because three-dimensional computed tomography angiography (3D-CTA) revealed right middle cerebral artery (MCA) occlusion. The access route was Type 3 aortic arch. The abdominal aorta and common iliac artery were tortuous and partially dissected, and she had a lumbar vertebra fracture. We selected dTRA in consideration of safety, ease of access, and less postoperative postural restriction. The first pass resulted in complete recanalization using an aspiration catheter and stent retriever. Her symptoms rapidly improved and she was discharged with a modified Rankin Scale score of 1. Conclusion: dTRA in MT may be a treatment option.

Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo.

In a secondary dengue virus (DENV) infection, the presence of non-neutralizing antibodies (Abs), developed during a previous infection with a different DENV serotype, is thought to worsen clinical outcomes by enhancing viral production. This phenomenon is called antibody-dependent enhancement (ADE) of infection, and it has delayed the development of therapeutic Abs and vaccines against DENV, as they must be evaluated for the potential to induce ADE. Unfortunately, limited replication of DENV clinical isolates in vitro and in experimental animals hinders this evaluation process. We have, therefore, constructed a recombinant chimeric flavivirus (DV2ChimV), which carries premembrane (prM) and envelope (E) genes of type 2 DENV (DENV-2) R05-624 clinical (Thai) isolate in a backbone of Japanese encephalitis virus (Nakayama strain). DENV E-protein is the most important viral target, not only for neutralizing Abs, but also for infection-enhancing Abs. In contrast to DENV-2 R05-624, DV2ChimV replicated efficiently in cultured mammalian cells and was lethal in interferon-α/ß-γ-receptor double-knockout mice. With DV2ChimV, we were able to perform neutralization assays, in vitro and in vivo ADE assays, and in vivo protection assays. These results suggest that the chimeric virus is a powerful tool for evaluation of Abs against DENV.

Poor prognostic factors in elderly patients aged 75 years old or older with mild traumatic brain injury.

The incidence of traumatic brain injury (TBI) in elderly patients is increasing. We retrospectively investigated the poor prognostic factors at discharge in elderly patients aged 75 years or older admitted to hospital with mild TBI. We continuously enrolled 83 patients aged 75 years or older with mild TBI, in a private general Japanese hospital. The Glasgow Coma Scale scores on admission were within the range of 13-15. Patients with good recovery or moderate disability were included in the "good outcome" group, and those with severe disability, in a persistent vegetative state, or who died were included in the "poor outcome" group. We performed statistical analyses using 8 parameters. We conducted a univariate analysis on each item. Next, we conducted a logistic regression analysis on variables where the p < 0.20 in the univariate analysis. Elderly patients had a poor prognosis when they had dementia (odds ratio [OR]: 20.357, 95% confidence interval [CI]: 2.075-199.683, p = 0.010), cancer (OR: 14.005, 95% CI: 1.262-154.444, p = 0.032), or a history of antithrombotic therapy before admission (OR: 6.673, 95% CI: 1.072-41.526, p = 0.042). When elderly patients aged 75 years or older with mild TBI have the 3 poor prognostic factors of dementia, cancer, or a history of antithrombotic therapy, their outcomes might be worse compared to other elderly patients. Elderly patients who have these factors should be carefully managed.

Establishment and characterization of a novel cell line of medullary thyroid carcinoma from a dog.

A novel cell line of canine medullary thyroid carcinoma (MTC) was established from the neck mass, diagnosed histopathologically and immunohistochemically as ectopic MTC. The neoplastic cells arranging trabecular structures were characterized as pleomorphic cells with eosinophilic cytoplasm and nucleus, containing often clear nucleolus. These tumor cells were immuno-positive for calcitonin gene-related protein (CGRP), somatostatin, and chromogranin A. In addition, 8th passaged cultured cells were also immuno-positive for CGRP, somatostatin, and chromogranin A. The cloned tumor cells showed logarithmic cell growth with a doubling time of 33.3 h. From the results of DNA sequencing of rearranged during transfection (RET) proto-oncogene, the cloned tumor cells had four single base substitution, including exon 5 codon 82, exon 16 codon 750, exon 17 codon 777, and exon 24 codon 1085, all of which were single nucleotide polymorphism reported in RET gene of dogs. After the xenotransplantation into severe combined immunodeficiency (SCID) mice, the cloned cells showed tumorigenicity potentials. The morphological and immunohistochemical features of the xenotransplanted tumor were almost in conformity with those of the original tumor, including positive immunoreactivity for calcitonin, CGRP, and chromogranin A. To our knowledge, this is the first report of canine MTC cell line, which provides useful in vitro tool for understanding oncogenic mechanism and pathophysiological state of MTC in dogs.

Malignant peripheral nerve sheath tumor originating from the adrenal gland in a dog.

A large abdominal mass was found in a dog. Histopathologically, the surface of the mass was covered with compressed adrenal gland tissue. The neoplastic cells showed typical features of malignant peripheral nerve sheath tumor (MPNST), including Antoni type A and type B pattern, and nuclear palisading. Immunohistochemically, these cells were positive for S100 protein, nerve growth factor receptor, nestin and claudin-1. The dog was euthanized because of the developing multiple metastatic lesions. The metastatic cells showed quite similar histopathological and immunohistochemical features as those in the original tumor. Although MPNST can develop at many body sites, this is the first report of MPNST originating from the adrenal gland in a dog.

Human monoclonal antibodies neutralizing influenza virus A/H1N1pdm09 and seasonal A/H1N1 strains - Distinct Ig gene repertoires with a similar action mechanism.

Influenza virus causes acute respiratory infection in humans, and is a major public health concern globally. Antibodies play a central role in host protection against influenza virus. We isolated human monoclonal antibodies (hMAb) 206-2-4 and 201-6-8 by a human hybridoma protocol that neutralized various but distinct influenza virus (IFV) A/H1N1 strains, including 2009 pandemic strains. The half-inhibitory concentration of 206-2-4 and 201-6-8 against A/H1N1pdm09 strains was 2-100ng/mL and 5-20µg/mL, respectively. Prophylactic and therapeutic potencies of 206-2-4 were demonstrated in a mouse model of IFV infection at i.p. dosages of 0.25 and 2.5mg/kg, respectively, suggesting that 206-2-4 is one of the most potent hnMAbs against IFV reported thus far. The Ig genes of 206-2-4 and 201-6-8 were originated from distinct germ line repertoires, and accompanied by 63 and 23 somatic hypermutations, respectively. The hemagglutination inhibitory activity indicated that the mechanism of neutralization was to interfere the virus-receptor interaction. The binding epitope of the two antibodies was mapped to hemagglutinin 1 (HA1) amino acid residues 111-120. Additional interaction between the antibody and the HA1 globular head was necessary for neutralization. Such hnMAbs bearing distinct binding epitope have been rarely reported. The potency is likely due to the coverage of a wide surface area of HA protein by these hnMABs. IFV is a highly variable. Our knowledge on the mechanisms by which these cross-reactive hnMAbs function should help design a novel immunogen for the development of a vaccine effective against broader spectrum of IFV strains.

The Relationship between Functional Outcome and Prehospital Time Interval in Patients with Cerebral Infarction.

BACKGROUND: When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear. METHODS: We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type. RESULTS: In all 122 cases, the BI at the time of discharge was not related to onset time (P = .453) but was significantly related to perception time (P = .026). BI scores at discharge were high for young patients (P = .002) and for patients with short hospital stays (P <.001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short (P = .036). CONCLUSIONS: A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition.