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OBJECTIVE The major concern about ruptured arteriovenous malformations (rAVMs) is recurrent hemorrhage, which tends to preclude stereotactic radiosurgery (SRS) as a therapeutic modality for these brain malformations. In this study, the authors aimed to clarify the role of SRS for rAVM as a stand-alone modality and an adjunct for a remnant nidus after surgery or embolization. METHODS Data on 410 consecutive patients with rAVMs treated with SRS were analyzed. The patients were classified into groups, according to prior interventions: SRS-alone, surgery and SRS (Surg-SRS), and embolization and SRS (Embol-SRS) groups. The outcomes of the SRS-alone group were analyzed in comparison with those of the other two groups. RESULTS The obliteration rate was higher in the Surg-SRS group than in the SRS-alone group (5-year cumulative rate 97% vs 79%, p < 0.001), whereas no significant difference was observed between the Embol-SRS and SRS-alone groups. Prior resection (HR 1.78, 95% CI 1.30–2.43, p < 0.001), a maximum AVM diameter ≤ 20 mm (HR 1.81, 95% CI 1.43–2.30, p < 0.001), and a prescription dose ≥ 20 Gy (HR 2.04, 95% CI 1.28–3.27, p = 0.003) were associated with a better obliteration rate, as demonstrated by multivariate Cox proportional hazards analyses. In the SRS-alone group, the annual post-SRS hemorrhage rates were 1.5% within 5 years and 0.2% thereafter and the 10-year significant neurological event–free rate was 95%; no intergroup difference was observed in either outcome. The exclusive performance of SRS (SRS alone) was not a risk for post-SRS hemorrhage or for significant neurological events based on multivariate analyses. These results were also confirmed with propensity score–matched analyses. CONCLUSIONS The treatment strategy for rAVMs should be tailored with due consideration of multiple factors associated with the patients. Stand-alone SRS is effective for hemorrhagic AVMs, and the risk of post-SRS hemorrhage was low. SRS can also be favorably used for residual AVMs after initial interventions, especially after failed resection.

Oxidative stress has been reported to play an important role in the pathogenesis of skin fibrosis in systemic sclerosis (SSc). We previously identified that botulinum toxin (BTX) injection suppresses pressure ulcer formation in a cutaneous ischemia-reperfusion injury mouse model by regulation of oxidative stress. However, the therapeutic possibility of BTX administration for preventing skin fibrosis in SSc is unclear. The objective of this study was to investigate the effect of BTX-B on skin fibrosis in a murine model of SSc and determine the underlying mechanism. We found that BTX-B injection significantly reduced dermal thickness and inflammatory cell infiltration in bleomycin-induced skin fibrosis lesion in mice. We also identified that the oxidative stress signal detected through bioluminescence in OKD48 mice after bleomycin injection in the skin was significantly decreased by BTX-B. Additionally, mRNA levels of oxidative stress associated factors (NOX2, HO-1, Trx2) were significantly decreased by BTX-B. Apoptotic cells in the lesional skin of bleomycin-treated mice were significantly reduced by BTX-B. Oxidant-induced intracellular accumulation of reactive oxygen species in SSc fibroblasts was also inhibited by BTX-B. In conclusion, BTX-B might improve bleomycin-induced skin fibrosis via the suppression of oxidative stress and inflammatory cells in the skin. BTX-B injection may have a therapeutic effect on skin fibrosis in SSc.

Background Several literature reviews have suggested that pregnancy may trigger the formation of dural arteriovenous fistulae (DAVF). However, few case reports have described DAVF discovered during pregnancy, and treatment strategies remain largely unknown. Case description: A 28-year-old primigravid woman without any medical history of note presented to our hospital for natural twin conception. She started to feel left-sided pulsatile tinnitus in 23 weeks of gestation. Magnetic resonance imaging of the head raised suspicion of left cavernous sinus DAVF with leptomeningeal venous drainage. Considering the risk of intracerebral hemorrhage due to the increased cardiac output in the third trimester of a twin pregnancy, we performed transarterial embolization for the DAVF, which was successfully achieved without complications in 28 weeks of gestation. Tinnitus resolved immediately after the procedure, and the postoperative course proved uneventful. Both fetuses were safely delivered by cesarean section on 37 1/7 weeks of gestation. Conclusions We encountered a case of cavernous sinus DAVF during a twin pregnancy. This case suggests that hemodynamic shift due to pregnancy has potential to cause higher shunt flow in an arteriovenous fistula. The timing of treatment should be determined in consideration of the hemodynamic change in the course of pregnancy. If X-ray exposures and iodine contrast media are appropriately managed, endovascular intervention is one treatment option, even during pregnancy.

Background With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long‐term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once‐daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. Methods APeX‐J is a phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group, 3‐part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run‐in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert‐confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs., APeX‐J is a phase 3, placebo‐controlled trial conducted in Japan to assess the efficacy and safety of oral berotralstat in patients with HAE. Patients were randomized 1:1:1 to receive once‐daily berotralstat 110 mg, berotralstat 150 mg, or placebo. Berotralstat 150 mg significantly reduced the frequency of HAE attacks compared with placebo, supporting its use as a prophylactic therapy. Abbreviation: HAE, hereditary angioedema.

Background Skull base chordomas will occasionally penetrate the clival dura mater and extend into the prepontine cistern, involving the basilar artery. Few reports have described cases of skull base chordoma accompanying a dissecting aneurysm of the basilar artery, and the treatment strategies have remained largely unknown. Case Description A 28-year-old man was referred to our hospital with a complaint of severe headache. A skull base chordoma involving a basilar artery dissecting aneurysm was diagnosed. We initially performed endovascular surgery for the dissecting aneurysm after dual antiplatelet therapy before surgical resection of the tumor, which was successfully achieved without complications. Follow-up angiography 3 months after endovascular surgery disclosed obliteration of the dissecting aneurysm. We then stopped the dual antiplatelet therapy, and performed judicious resection using an endoscopic transclival approach. The residual tumor was treated with radiosurgery. At the last follow-up examination, the patient was stable, and the tumor remained sufficiently controlled. Conclusions We have reported a case of a dissecting aneurysm of the basilar artery with clival chordoma. Our findings suggest that chordoma with intradural vascular encasement has the potential to invade the vessel wall. To avoid rupture of those critical vascular structures, treatment strategies that minimize stress on the involved arteries and offer safe and sufficient surgical resection should be considered.

Background Ventriculoperitoneal shunt placement is a common standard treatment for hydrocephalus, and these shunts function appropriately in the presence of a pressure gradient between the ventricular and abdominal cavities. Case Description We encountered 2 cases of shunt malfunction that was due to an increase in intra-abdominal pressure, mainly caused by constipation and excessive accumulation of enteric gas. Although aggressive bowel regimens were implemented, this management failed in both patients. Careful physical examination revealed unusually elevated tonus of the anus sphincter muscle, and a fecal incontinence catheter was inserted into the rectum. Following this procedure, constipation rapidly improved together with a marked reduction in enteric gas, leading to a normalization of ventricular size on imaging and neurologic improvements. Both patients were able to avoid unnecessary surgical exploration or shunt revision. Conclusions Constipation is one of the differential diagnoses of ventriculoperitoneal shunt malfunction, and bowel regimens are the first-line treatment. However, some cases can prove resistant to medical therapy, and mechanical tube placement can provide an alternative or additional solution. Before proceeding to surgical exploration, the intra-abdominal environment should be properly assessed and every option should be explored to address underlying causes of shunt failure to avoid unnecessary intervention.

OBJECTIVESpinal arteriovenous shunts are rare vascular lesions and are classified into 4 types (types I–IV). Due to rapid advances in neuroimaging, spinal epidural AVFs (edAVFs), which are similar to type I spinal dural AVFs (dAVFs), have recently been increasingly reported. These 2 entities have several important differences that influence the treatment strategy selected. The purposes of the present study were to compare angiographic and clinical differences between edAVFs and dAVFs and to provide treatment strategies for edAVFs based on a multicenter cohort.METHODSA total of 280 consecutive patients with thoracic and lumbosacral spinal dural arteriovenous fistulas (dAVFs) and edAVFs with intradural venous drainage were collected from 19 centers. After angiographic and clinical comparisons, the treatment failure rate by procedure, risk factors for treatment failure, and neurological outcomes were statistically analyzed in edAVF cases.RESULTSFinal diagnoses after an angiographic review included 199 dAVFs and 81 edAVFs. At individual centers, 29 patients (36%) with edAVFs were misdiagnosed with dAVFs. Spinal edAVFs were commonly fed by multiple feeding arteries (54%) shunted into a single or multiple intradural vein(s) (91% and 9%) through a dilated epidural venous plexus. Preoperative modified Rankin Scale (mRS) and Aminoff-Logue gait and micturition grades were worse in patients with edAVFs than in those with dAVFs. Among the microsurgical (n = 42), endovascular (n = 36), and combined (n = 3) treatment groups of edAVFs, the treatment failure rate was significantly higher in the index endovascular treatment group (7.5%, 31%, and 0%, respectively). Endovascular treatment was found to be associated with significantly higher odds of initial treatment failure (OR 5.72, 95% CI 1.45–22.6). In edAVFs, the independent risk factor for treatment failure after microsurgery was the number of intradural draining veins (OR 17.9, 95% CI 1.56–207), while that for treatment failure after the endovascular treatment was the number of feeders (OR 4.11, 95% CI 1.23–13.8). Postoperatively, mRS score and Aminoff-Logue gait and micturition grades significantly improved in edAVFs with a median follow-up of 31 months.CONCLUSIONSSpinal epidural AVFs with intradural venous drainage are a distinct entity and may be classified as type V spinal vascular malformations. Based on the largest multicenter cohort, this study showed that primary microsurgery was superior to endovascular treatment for initial treatment success in patients with spinal edAVFs.

Background Rhododendrol (RD) is cytotoxic to melanocytes and can cause leukoderma at the application site. Patients with RD-induced leukoderma usually recover after discontinuation of application (improved cases). However, occasionally lesions may expand or new lesions may develop in unapplied sites (aggravated cases). Objective To understand the pathomechanism of RD-induced leukoderma in aggravatedcases. Methods We performed immunohistochemical study to compare the expression of the catalytic subunit of glutamate cysteine ligase (GCLC), E-cadherin, and mast cell tryptase in 22 improved cases, 16 aggravated cases, and 39 normal controls. Results GCLC expression in melanocytes surrounding leukoderma was higher in improved cases than in normal controls and aggravated cases. E-cadherin expression in melanocytes was upregulated both in improved and aggravated cases and increased levels of degranulated mast cells were observed in aggravated cases. Conclusion Our results indicate that downregulation of GCLC expression due to low levels of glutathione along with reduced melanocyte migration and increased E-cadherin expression can aggravate RD-induced leukoderma. Additionally, increased degranulation of mast cells may prolong the persistence of RD-induced leukoderma.

Background Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and “biological downstaging” in chemoradiation therapy (CRT) for pancreatic cancer (PC). Methods A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. “Biological downstaging” was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). Results The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). Conclusions Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated “biological downstaging” in b-BR in the preoperative CRT strategy.

Background Although the embolization of lenticulostriate artery feeders is often warranted in the treatment of brain arteriovenous malformations, it is technically challenging due to steep and repeated angulations. Here, we describe our novel technique of navigating a flow-guided microcatheter into lenticulostriate artery feeders using the strong support provided by an S-shaped distal access catheter. Methods We reviewed our retrospective cohort of brain arteriovenous malformations, in which lenticulostriate artery feeders were attempted to embolize. Result During the study period, endovascular embolization was performed in 25 arteriovenous malformations cases. Of these, eight lenticulostriate artery feeders were present in six cases (24%). In two cases, lenticulostriate artery feeder catheterization was avoided from the beginning due to the small diameters of the feeders. After all, microcatheter navigation for lenticulostriate artery feeders were attempted in four cases with six lenticulostriate artery feeders. In all the six feeders, the S-shaped distal access catheter was successful in supporting the microcatheter to advance distally to the lenticulostriate artery feeders, even if other approaches were unsuccessful. Of the six catheterized lenticulostriate artery feeders, four were embolized. Symptomatic infarction in the lenticulostriate artery territory and mild vasospasm occurred in two cases each, but they did not result in permanent neurological deficits. Conclusion Although some potential complications need to be considered, the S-shaped distal access catheter technique appears to be an effective alternative approach to gaining access to difficult feeders of arteriovenous malformations.

The rigid method of identifying the rupture site in cases of subarachnoid haemorrhage (SAH) with multiple intracranial aneurysms (MIAs) is still unclear. Here we present a reliable method by using a combination of six predictors.Concerning the 48 SAH patients with MIAs who visited the Showa General Hospital during the period from January 2005 to March 2016, several predictors of rupture site such as the aneurysm-related morphologic features (size, aspect ratio, shape, bleb), aneurysm location, and the distribution of SAH were investigated. Compared with other coexisting aneurysms in each predictor, each aneurysm was categorized into 'suspicion' or 'non-suspicion', and we analyzed the association between 'suspicion' and rupture.In the first analysis, all variables were associated with rupture and included in the multivariate logistic regression analysis. The presence of bleb (OR, 20.7; CI, 2.3-186;Our results suggest that the predictive score may be an excellent parameter to identify the rupture site in cases of SAH with MIAs.

To investigate the clinical course of Japanese patients with early diffuse cutaneous systemic sclerosis (dcSSc) and early SSc with interstitial lung disease (ILD).We prospectively analyzed the clinical features of 207 Japanese patients with early dcSSc (n = 150) and limited cutaneous SSc (lcSSc) with ILD (n = 57) in 10 medical centers every year for 7 consecutive years.Mean modified Rodnan total skin thickness score (mRSS) was 18.3 and 67.4% of the cohort had ILD. Most patients started immunosuppressive therapy and vasodilators during 7 years (83.4% and 87.9%, respectively). Mean value of mRSS of total patients was significantly reduced from the initial registration after the first year. However, other parameters for physical function associated with skin sclerosis including fist closure, hand extension, and oral aperture were not so ameliorated during the study period. Health Assessment Questionnaire-disability index and serum KL-6 levels were constant throughout the course. Percent vital capacity and the presence of ILD, clinically suspected pulmonary arterial hypertension, and digital ulcers were gradually exacerbated during the period.In Japanese early dcSSc patients and SSc patients with ILD, mRSS was continuously reduced during 7 years of follow-up, but there was little improvement of physical disability and organ involvement.

We report the spontaneous emission of vortex rings from turbulence induced by a vibrating wire in superfluid $$^4$$ He, and investigate the statistical behavior of quantum turbulence. Using a set of vibrating wires as a turbulence generator and vortex detectors, we measured the distribution of times of flights between the generator and the detectors for emission directions parallel and perpendicular to the vibration direction of the generator wire. We find that the times exhibit a single exponential distribution for emissions in both directions, indicating temporally random emission of vortex rings with a single mean emission rate. When a limit is set on the detection diameter of the vortex rings, the detection times exhibit a double exponential distribution for the perpendicular direction for ring diameters above 10 $$\upmu \hbox {m}$$ , suggesting that large vortex rings reach the detector with a high rate emission at later times. In the parallel emission direction, the emission rate during an equilibrium state exhibits a power law behavior with a minimum diameter of detected vortex rings, implying that a vortex tangle generated by an oscillating object has a self-similar structure of vortex lines.

Human papillomavirus (HPV) causes cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and oropharyngeal cancer. Squamous cell carcinoma (SCC) in the genital region in particular is recognized to be caused by HPV infection, and intraepithelial lesions of the penis and vulva are termed penile intraepithelial neoplasia and vulvar intraepithelial neoplasia, respectively. Although SCC of the nail apparatus is recognized as being associated with high-risk HPVs, it is not well-known in general medicine, and its analysis has been insufficient. In this article, we reviewed 136 cases of HPV-associated nail SCC and SCC in situ and delineated their clinical characteristics. We found that half of the cases were high-risk HPV-associated. Almost all of the types were high-risk α-HPVs. This disease had a male dominance and left hand digit 3 and right hand digits 1-3 were typically affected. In this review, 24% of the cases of nail SCC had a history of other HPV-associated diseases, suggesting the possibility of genitodigital transmission. We propose that nail SCC is a hidden high-risk HPV-associated reservoir and should be recognized as a sexually transmitted infection.

Background and Aim There are no previous reports describing the prognostic significance of the residual intraductal carcinoma component (carcinoma in situ [CIS]) following preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to investigate the prognostic significance of a minimal residual CIS in cases with complete absence of an invasive component after preoperative treatment for PDAC. Methods Eighty‐one of 594 PDAC patients with preoperative treatment and subsequent surgery in our institute showed remarkable remission in the invasive component, which included 48 patients with the minimal residual invasive component (Min‐inv group) and 33 with absence of an invasive component (No‐inv group). We assessed the survival of these patients in association with the presence or absence of an invasive component and intraductal CIS. Results Five‐year overall survival in the No‐inv group patients was significantly better than that of the Min‐inv group patients (82%/66%, P = .041). Among the 33 patients in the No‐inv group, residual CIS was observed in 16 patients (CIS‐positive group), and the remaining 17 patients had no residual CIS (CIS‐negative group). There was no significant difference in survival between patients in the CIS‐positive and CIS‐negative groups (92%/78%, P = .31). Conclusions Residual CIS in the absence of an invasive component after preoperative treatment does not yield a prognostic impact after receiving perioperative treatment for PDAC. It might be reasonable to define pathological complete response (pCR) from the prognostic standpoint as follows: pCR is the complete absence of an invasive carcinoma component regardless of residual CIS., We investigated the survival outcome of pancreatic ductal adenocarcinoma patients showing complete absence of an invasive component in relation to those with minimal residual carcinoma in situ (CIS) after preoperative therapy; complete regression of the invasive component, regardless of the presence or absence of residual CIS, was a significant indicator for preferable prognosis.

Subarachnoid hemorrhage (SAH) with multiple intracranial aneurysms is common, but the difficulties often arise in determining treatment strategy in the acute phase. We experienced a case of SAH with distal anterior cerebral artery aneurysm coexisting with middle cerebral artery and anterior communicating artery aneurysms, in which it was difficult to identify the precise rupture site preoperatively, and both pterional approach and interhemispheric approach were required in the acute phase of SAH. However, we could treat whole aneurysms in one stage and obtained an excellent outcome using our surgical procedure with ipsilateral frontotemporal and frontal parasagittal craniotomies through a single skin incision.

Background There is growing evidence that vasculopathy-induced hypoxia and oxidative stress enhance the process of fibrosis in systemic sclerosis (SSc). Kaempferol is a natural flavonoid widely found in various vegetables and fruits, and has been reported to have excellent antioxidant activity. Objective Objective was to elucidate the effect of kaempferol on skin fibrosis and the mechanism of the inhibitory regulation of fibrosis by kaempferol. Methods We assessed the effect of intraperitoneally administered kaempferol on bleomycin-induced dermal fibrosis in mice. The effect of kaempferol on oxidative stress in bleomycin-treated mice and SSc fibroblasts was assessed in vivo and in vitro. Results We identified that kaempferol injection significantly inhibited bleomycin-induced dermal fibrosis in mice. The number of αSMA+ myofibroblasts, CD3+ T-cells, and CD68+ macrophages in lesional skin was significantly decreased by kaempferol injections. Kaempferol administration also significantly suppressed the bleomycin-induced oxidative stress signal in OKD48 mice. Additionally, mRNA levels of oxidative stress-associated factors, such as HO-1 and NOX2, as well as inflammatory and pro-fibrotic cytokines, including IL-6, TGF-β and TNFα in sclerotic skin were significantly decreased by kaempferol. Kaempferol also reduced bleomycin-induced TUNEL+ apoptotic cells in the lesional skin of bleomycin-treated mice. Furthermore, the oxidant-induced intracellular accumulation of reactive oxygen species (ROS) in SSc fibroblasts was inhibited by kaempferol treatment. In addition, the oxidant-induced apoptosis of SSc fibroblasts was decreased by kaempferol in vitro. Conclusion Kaempferol might improve bleomycin-induced fibrosis by reducing oxidative stress, inflammation, and oxidative cellular damage. Administration of kaempferol might be an alternative treatment for skin fibrosis in SSc.

Background Previous studies have indicated that MFG-E8 enhances tumor cell survival, invasion and angiogenesis. However, the role of MFG-E8 in angiosarcoma (AS) has not been clarified. Objective Objective was to elucidate the mechanism of the regulation by MFG-E8 in AS and the association between MFG-E8 and clinicopathological features of AS. Methods The effects of the depletion of MFG-E8 by siRNA on tube formation, migration and proliferation in murine AS cells were examined. The effect of administration of anti-MFG-E8 antibody (Ab) on tumor growth of AS in mice was examined. The associations of MFG-E8 expression and clinicopathological features of human AS were assessed. Results The expressions of MFG-E8 in murine and human AS cells were significantly higher than those in melanoma cells, macrophages and endothelial cells. Depletion of MFG-E8 in murine AS cells by siRNA significantly inhibited the formation of capillary-like structures and migration, but not proliferation. Administration of anti-MFG-E8 Ab significantly inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in AS tumors. Tumor size and the number of TAMs in human AS with high expression of MFG-E8 were significantly increased compared to those of AS with low expression of MFG-E8. Progression-free survival and overall survival time of the patients of AS with high expression of MFG-E8 were significantly shorter than those of AS with low expression of MFG-E8. Conclusions AS-derived MFG-E8 might enhance tumor growth via angiogenesis and the induction of TAMs in autocrine/paracrine manner, and administration of anti-MFG-E8 Ab could be a therapeutic potential for AS.

Background/aim The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). Patients and methods A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. Results The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). Conclusion The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.

Background Zinc deficiency is believed to be a predisposing factor for the development and intractable healing of pressure ulcers (PUs); however, the mechanisms of this association have not been elucidated. Objective Objective was to elucidate the mechanisms of the formation of severe and prolonged PUs under the zinc deficiency condition. Methods We assessed PUs formation after cutaneous ischemia-reperfusion (I/R) injury in mice fed with a zinc-adequate (ZA) or a zinc-deficient (ZD) diet from 2 weeks before I/R injury. Wound size, vascular damage, apoptotic cells, adenosine triphosphate (ATP) amount, and the number of Langerhans cells (LCs) in I/R area were analyzed. We evaluated the extent of oxidative stress in I/R area in OKD48 mice through bioluminescence detection. Results We found that dietary zinc deficiency caused the formation of severe and prolonged PUs in mice. Zinc deficiency increased the vascular disorder, oxidative stress, and apoptosis induced by cutaneous I/R injury. I/R injury-induced oxidative stress signals were significantly higher in ZD OKD48 mice than in ZA OKD48 mice. Additionally, zinc deficiency reduced the number of LCs and increased the amount of ATP in cutaneous I/R-injured skin. Oral supplementation of zinc improved zinc deficiency-associated PUs. Conclusion Zinc deficiency might increase cutaneous I/R injury-induced vascular damages, oxidative stress, and apoptosis, as well as ATP amount in I/R area due to the loss of LCs. These mechanisms might partly account for zinc deficiency-induced formation of severe and prolonged PUs. Oral supplementation of zinc might be a reasonable therapeutic choice for patients with PUs and zinc deficiency.

BACKGROUND Single-session stereotactic radiosurgery (SRS) for large arteriovenous malformations (AVMs) ≥10 mL remains controversial, which is considered as the current size limitation. OBJECTIVE To reconsider the size limitation of SRS for AVMs by profoundly analyzing dose-volume relationship. METHODS Data on 610 consecutive patients with AVM treated with SRS using regular (18-22 Gy) or low (

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by the activated macrophages and acts as a bridge between apoptotic cells and phagocytes. Aside from macrophages, a variety of malignant cells also express MFG-E8. The objective of this study is to elucidate the clinical relevance and significance of MFG-E8 in the tumor microenvironment (TME) of patients with oral squamous cell carcinoma (OSCC). We investigated MFG-E8 expression in 74 patients with OSCC by immunohistochemistry and evaluated the relationship between MFG-E8 expression and various clinicopathological factors including immune cell infiltration. MFG-E8 expression was detected in 34 of 74 (45.9%) patients with OSCC and a significant correlation was observed with levels of infiltrating T cells, macrophages, and immunosuppressive M2 macrophages. Furthermore, MFG-E8 expression was also associated with clinical stage, lymphatic/vascular invasion, and Ki-67+ tumor cells but not with survival. Our results suggest that MFG-E8 may play an important role in shaping the immune suppressive network in TME as well as tumor progression.

Tissue injury/hypoxia and oxidative stress induced-extracellular adenosine triphosphate (ATP) can act as damage-associated molecular pattern molecules, which initiate inflammatory response. Our objective was to elucidate the role of extracellular ATP in skin fibrosis in systemic sclerosis (SSc). We identified that hypoxia enhanced ATP release and that extracellular ATP enhanced IL-6 production more significantly in SSc fibroblasts than in normal fibroblasts. There were no significant differences of P2X and P2Y receptor expression levels between normal and SSc fibroblasts. Nonselective P2 receptor antagonist and selective P2Y2 receptor antagonists, kaempferol and AR-C118925XX, significantly inhibited ATP-induced IL-6 production and phosphorylation of p38 in SSc fibroblasts. ATP-induced IL-6 production was significantly inhibited by p38 inhibitors, SB203580, and doramapimod. Collagen type I production in SSc fibroblasts by ATP-induced IL-6/IL-6 receptor trans-signaling was inhibited by kaempferol and SB203580. The amount of ATP in bleomycin-treated skin was increased, and administration of AR-C118925XX significantly inhibited bleomycin-induced dermal fibrosis in mice. These results suggest that vasculopathy-induced hypoxia and oxidative stress might enhance ATP release in the dermis in SSc and that extracellular ATP-induced phosphorylation of p38 via P2Y2 receptor might enhance IL-6 and collagen type I production in SSc fibroblasts. P2Y2 receptor antagonist therapy could be a treatment for skin sclerosis in patients with SSc.

Background Developmental venous anomalies are considered benign lesions; however, they can become symptomatic. A capillary stain, which is an atypical angiographical feature of developmental venous anomalies, is reported to be relevant to symptomatic developmental venous anomalies. Case description A 20-year-old man with no pertinent medical history had an epileptic seizure. Magnetic resonance imaging showed severe focal oedema and gadolinium contrast enhancement in the right precentral gyrus and inferior frontal gyrus adjacent to the Sylvian fissure, indicating venous congestion; these presentations had not been observed on magnetic resonance imaging 8 months before. Digital subtraction angiography revealed a developmental venous anomaly with capillary stain. After conservative treatment, the brain oedema resolved spontaneously and contrast enhancement of the lesion reduced significantly. Conclusion We report a rare case of a symptomatic developmental venous anomaly with unique radiological characteristics and its natural and clinical evolution. Despite the presence of a capillary stain, our patient exhibited temporary exacerbations and spontaneous regression, suggesting that the capillary stain was associated with a reversible condition. This is the first report to detail the spatiotemporal changes of a developmental venous anomaly with capillary stain through imaging, suggesting that regular follow-up imaging is warranted in the management of patients with developmental venous anomalies.

Background Increasing restrictions over trainees' working hours and the recent coronavirus disease 2019 pandemic warrant new educational methods of surgical skills. We assessed a novel video-recording system for neuroendovascular skill education, developed with the installation of a hybrid operating room (OR) at our institution. Methods A single-plane angiography unit with a large flat display (FlexVision XL; Philips Medical Systems) was installed in our OR. All media sources in the OR, including live fluoroscopy and ceiling-mounted camcorders, were connected to a video switcher. This video switcher laid up to 8 video images into one big image, which was transferred to the large display and the professional-use Blu-ray recorder. The recording was performed continuously during the procedure. This recording system was evaluated retrospectively with a questionnaire administered to the 5 trainees. Results Using this system, 68 interventional procedures were recorded. Among the potential merits, the trainees assigned the greatest value to the simultaneous recording of the operator's hand motions and the fluoroscopy images. Among the potential limitations of the system, the prolonged time and the increased volume of the video data bothered the trainees the most. The recorded video looked like a live demonstration. Conclusions Our “selfie” video recording system was useful for skill training of neuroendovascular interventions.

Background: Hereditary angioedema (HAE) is a rare but life-threatening condition. HAE types I and II (HAE-1/2) result from C1-inhibitor (C1–INH) deficiency. However, recent genetic analysis has established a new type of HAE with normal C1–INH (HAEnC1-INH). The mutations of factor XII, plasminogen, angiopoietin 1, and kininogen 1 genes may be the cause of HAEnC1-INH. Nevertheless, other causative molecules (HAE-unknown) may be involved. The Japanese therapeutic environment for HAE has been improving owing to the self-subcutaneous injection of icatibant, which was approved for the treatment of acute attack and enables early therapy. Erythema marginatum (EM) is a visible prodromal symptom which occasionally occurs prior to an angioedema attack; hence, recognizing the risk of an acute attack is important for early treatment. However, the detailed characteristics of EM remain unclear. In this study, we first investigated the clinical manifestations of EM in Japanese patients with HAE. Methods: A 20-point survey was developed and distributed to 40 physicians to gather clinical data on EM from patients with HAE. Results: Data on 68 patients with HAE (58 patients with HAE-1/2 and 10 patients with HAE-unknown) were collected. Of the patients with HAE-1/2, 53.4% experienced EM, whereas 43.1% did not. The forearm was the most frequent area of EM (64.5%), followed by the abdomen (29.0%) and upper arm and precordium (19.3%). Of the HAE-1/2 patients with EM, 41.9% always had angioedema following EM, while 29.0% always had colocalization of EM with angioedema. Moreover, 3.2% showed a correlation between the awareness of EM and severity of an angioedema attack. In 60.9% of HAE-1/2 patients with EM, the interval between the awareness of EM and appearance of angioedema was

Background Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis. Objective We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo. Methods The release of neuropeptide was inhibited by injecting Botulinum toxin B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed by PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP8−37) on psoriasis-like dermatitis in IMQ-treated mice. Results BTX-B injection significantly suppressed PSI score and reduced the number of CD4+ T cells, CD11c+ dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5+ nerve fibers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice. Conclusion The suppression of neuropeptide secretion in the skin by BTX injection might inhibit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhibitor could also be applied to the treatment of psoriasis.

Background High-definition vascular imaging is desirable for treatment planning in Gamma Knife radiosurgery (GKRS; Elekta AB) for brain arteriovenous malformations (BAVMs). Currently, rotational angiography (RA) provides the clearest 3-dimensional visualization of niduses with high spatial resolution; however, its efficacy for GKRS has not been clarified. At our institution, RA has been integrated into GKRS (RA-GKRS) for better treatment planning and outcomes since 2015. Objective To evaluate RA-GKRS outcomes of BAVMs and compare them with conventional GKRS (c-GKRS) outcomes. Methods We retrospectively analyzed the radiosurgical outcomes of 50 BAVMs treated with RA-GKRS compared with the 306 BAVMs treated with c-GKRS. Considering possible differences in the baseline characteristics, we also created propensity score-matched cohorts and compared the radiosurgical outcomes between them to ensure comparability. Results The obliteration time was shorter in the RA-GKRS group (cumulative rate, 88% vs 65% at 4 yr [P = .001]). Multivariate Cox proportional hazards analysis demonstrated that the RA-GKRS group (hazard ratio 2.38, 95% CI 1.58-3.60; P = .001) had a better obliteration rate. The cumulative 4-yr post-GKRS hemorrhage rates were 4.0% and 2.6% in the RA-GKRS and c-GKRS groups, respectively (P = .558). There was a trend toward early post-GKRS signal change in the RA-GKRS group compared with the c-GKRS group (cumulative rate, 38% vs 29% at 2 yr; P = .118). Those results were also confirmed in the matched cohort analyses. Conclusion The integration of RA into GKRS is promising and may provide earlier nidus obliteration.

Pancreaticoduodenectomy (PD) concomitant with portal vein resection (PVR) often develops into digestive varices with an occurrence rate of 30–50%, and the variceal bleeding is sometimes untreatable and results in fatality. Against this issue, splenic artery (SpA) ligation during PD-PVR is emerging as an easy and effective prophylactic surgical option. The aim of this study was to investigate the significance of SpA ligation in the development of digestive varices in patients undergoing PD-PVR. We retrospectively investigated 97 patients with PDAC who received PD-PVR in two hospitals. Vascular reconstruction of the splenic vein (SpV) was not performed in either hospital. We assessed the occurrence rate of digestive varices in these patients in association with the performance of SpA ligation. The occurrence rate of digestive varices was 23%. SpA ligation was the only significant decreasing factor for the development of digestive varices (odds ratio 0.3, p = 0.035). Although SpV resection was not a significant risk factor for the development of digestive varices in all patients, SpV resection was a significant risk factor for the development of digestive varices in patients without SpA ligation, as demonstrated in previous reports. SpA ligation did not increase surgical complications or impair pancreatic function. PD-PVR surgery was accompanied by a 23% incidence of digestive varices, and SpA ligation significantly decreased the development of digestive varices without causing clinically significant complications. No. 18196 (Osaka International Cancer Institute) and no. 19006 (National Hospital Organization Osaka National Hospital)

Recently, the authors succeeded in generating a superfluid suction vortex, which is a giant vortex with a hollow core, driven directly by a cryogenic centrifugal pump. The ultimate goal of this study and related work is to determine the distribution of the local density of the quantum vortex lines as a function of the rotational speed and the magnitude of the suction flow. Although the flow of superfluid helium in a rotating bucket, in which the vortex lines are arranged to form a triangular lattice, is known to show rigid body motion, the vortex line distribution of the suction vortex remains an open question. In this study, the attenuation of the second sound across the suction vortex was measured. As a result, it was found that the damping factors of the second sound increased with increasing rotational speed; however, it was found that the apparent vortex line density is not proportional to the rotational speed despite the fact that the total circulation has been previously shown to be proportional to the rotational speed. A possible picture of the quantum vortex lines around the suction vortex is discussed in this paper.

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer-associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti-TIF1γ Ab-positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti-TIF1γ Ab-positive DM, anti-TIF1γ Ab-negative DM and without DM in order to investigate the pathogenesis of cancer-associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti-TIF1γ Ab. Patients with anti-TIF1γ Ab-positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti-TIF1γ Ab (P < 0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti-TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti-TIF1γ Ab-positive group (P < 0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti-TIF1γ Ab-positive DM (P < 0.01 and