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OBJECTIVE Chronic subdural hematoma (CSDH) is a common neurological disease with a significant postoperative recurrence rate. There are numerous reported studies of the development of CSDH. In recent years, fibrinolysis, angiogenesis, and inflammation have all been identified as relevant factors in the development of CSDH. While several authors have reported risk factors associated with CSDH recurrence, differential blood count of leukocytes has not yet been discussed. Therefore, in this study the authors aimed to retrospectively investigate the association between differential blood leukocyte count and the rate of CSDH recurrence. METHODS The authors retrospectively reviewed 476 patients with 529 CSDHs who underwent surgery at a single institution between January 2011 and December 2021. After exclusion of patients who had not undergone a differential blood test of leukocytes preoperatively, CSDHs in 517 cerebral hemispheres of 466 patients were included in the study. Peripheral blood eosinophil counts ≥ 100/µL were considered eosinophil rich. RESULTS CSDHs in 494 cerebral hemispheres of 445 patients were followed up postoperatively for at least 3 months or until resolution indicated by CSDH disappearance. Postoperative recurrence of CSDH was observed in 46 cerebral hemispheres (9.3%). Among the preoperative differential blood counts of all leukocytes, eosinophils alone were significantly associated with CSDH recurrence (median [IQR] 76/µL [30–155/µL] vs 119/µL [39–217/µL]; p = 0.03). Multivariable regression analysis showed thrombocytopenia (adjusted OR [aOR] 5.23, 95% CI 1.85–14.79; p = 0.002), use of anticoagulant drugs (aOR 2.51, 95% CI 1.17–5.38; p = 0.02), hematoma volume (10 mL per increase) (aOR 1.08, 95% CI 1.00–1.16; p = 0.04), and eosinophil-rich peripheral blood (aOR 2.22, 95% CI 1.17–4.23; p = 0.02) were all independent predictors for CSDH recurrence. CONCLUSIONS This study showed that preoperative peripheral blood eosinophil count was an independent risk factor for CSDH recurrence. Therefore, patients with CSDH who have elevated eosinophils preoperatively in peripheral blood require careful follow-up.

Microorganisms often live in symbiosis with their hosts, and some are considered mutualists, where all species involved benefit from the interaction. How free-living microorganisms have evolved to become mutualists is unclear. Here we report an experimental system in which non-symbiotic Escherichia coli evolves into an insect mutualist. The stinkbug Plautia stali is typically associated with its essential gut symbiont, Pantoea sp., which colonizes a specialized symbiotic organ. When sterilized newborn nymphs were infected with E. coli rather than Pantoea sp., only a few insects survived, in which E. coli exhibited specific localization to the symbiotic organ and vertical transmission to the offspring. Through transgenerational maintenance with P. stali, several hypermutating E. coli lines independently evolved to support the host’s high adult emergence and improved body colour; these were called ‘mutualistic’ E. coli. These mutants exhibited slower bacterial growth, smaller size, loss of flagellar motility and lack of an extracellular matrix. Transcriptomic and genomic analyses of ‘mutualistic’ E. coli lines revealed independent mutations that disrupted the carbon catabolite repression global transcriptional regulator system. Each mutation reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that single carbon catabolite repression mutations can make E. coli an insect mutualist. These findings provide an experimental system for future work on host–microbe symbioses and may explain why microbial mutualisms are omnipresent in nature.

OBJECTIVE There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart. However, an improvement in the remaining live AdSCs administered at the injected site while maintaining paracrine factor secretion is desired to achieve effective regenerative medicine. We previously reported the ABA-type tri-block copolymer of poly(ɛ-caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG), exhibiting temperature-responsive sol-to-gel transition as biodegradable injectable polymer (IP) systems. Moreover, we recently reported that the biodegradable temperature-triggered chemically cross-linked gelation systems exhibited longer gel state durations using tri-PCG attaching acryloyl groups and a polythiol derivative. In this study, we explored this IP-mediated AdSC delivery system. We investigated the cell viability, mRNA expression, and cytokine secretion of AdSCs cultured in the physical or chemical IP hydrogels. Both of these IP hydrogels retained a certain number of viable cells, and RT-PCR and ELISA analyses revealed that mRNA expression and secretion of vascular endothelial growth factor of the AdSCs cultured in the chemical hydrogel were higher than the physical hydrogel. Moreover, AdSCs injected with the chemical hydrogel into ischemic heart model mice showed longer retention of the cells at the injected site and recovery from the ischemic condition. The results mean that the IP system is a promising candidate for a stem cell delivery system that exhibits the recovery of cardiac function for myocardial infarction treatment., Graphical Abstract

BACKGROUND Although an anterior cranial fossa dural arteriovenous fistula (ACFdAVF) is thought to have a fistula on the dura near the olfactory groove, the detailed angioarchitecture remains unreported. OBSERVATIONS In case 1, a 65-year-old man was found to have an asymptomatic ACFAVF. His computed tomography angiography (CTA)-maximum intensity projection (MIP) showed the shunt point in the crista galli (CG), with the intradural drainer penetrating the destroyed bone of the CG. In case 2, a 78-year-old man had a past history of intracerebral hemorrhage and was found to have an ACFAVF. The rotational angiography (RA)-MIP showed the intraosseous fistula in the CG with the drainer passing through a tiny bone defect of the CG. In case 3, a 35-year-old man was investigated for epilepsy. The RA-MIP showed an osseous arteriovenous fistula (AVF) in the anterior cranial base, with the drainer penetrating the skull osteolytic site. In case 4, a 73-year-old woman was found to have an asymptomatic ACFAVF. Her RA-MIP showed the osseous AVF with the drainer penetrating the CG with bone erosion. LESSSONS All patients were diagnosed with anterior cranial fossa osseous AVF rather than dAVF, with bone erosion in the CG. These findings should be noted at the time of diagnosis and treatment.

Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 μg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 μg/ml and ≥ 6 μg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 μg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65–98.77; p = 0.02) or ≥ 6 μg/ml (OR, 18.33; 95% CI, 2.32–144.82; p = 0.006) were independent predictors of PR. This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Introduction: Mechanical thrombectomy (MT) for acute ischemic stroke has become a standard therapy, and the recanalization rate has significantly improved. However, some cases of unsuccessful recanalization still occur. We aimed to clarify patient factors associated with unsuccessful recanalization after MT for acute ischemic stroke. Methods: This was a single-center, retrospective study of 119 consecutive patients with anterior circulation acute ischemic stroke who underwent MT at our hospital between April 2015 and March 2019. Successful recanalization after MT was defined as modified Treatment in Cerebral Ischemia (mTICI) grade 2b or 3, and unsuccessful recanalization was defined as mTICI grades 0–2a. Several factors were analyzed to assess their effect on recanalization rates. Results: Successful recanalization was achieved in 88 patients (73.9%). The univariate analysis showed that female sex (38.6 vs. 67.7%, p = 0.007), a history of hypertension (53.4 vs. 83.9%, p = 0.003), and a longer time from groin puncture to recanalization (median 75 vs. 124 min, p < 0.001) were significantly associated with unsuccessful recanalization. The multivariate analysis confirmed that female sex (OR 3.18; 95% CI 1.12–9.02, p = 0.030), a history of hypertension (OR 4.84; 95% CI 1.32–17.8, p = 0.018), M2–3 occlusion (OR 4.26; 95% CI 1.36–13.3, p = 0.013), and the time from groin puncture to recanalization (per 10-min increase, OR 1.22; 95% CI 1.09–1.37, p < 0.001) were independently associated with unsuccessful recanalization. Conclusion: Female sex and a history of hypertension might be predictors of unsuccessful recanalization after MT for anterior circulation acute ischemic stroke. Further studies are needed to fully evaluate predictors of recanalization.

Background: Craniocervical junction arteriovenous fistulas (CCJAVFs) are known to be rare, but variations and clinical behaviors remain controversial. Methods: A total of 11 CCJAVF patients (M: F=9:2, age 54–77 years) were investigated. Based on the radiological and intraoperative findings, they were categorized into three types: dural AVF (DAVF), radicular AVF (RAVF), and epidural AVF (EDAVF). Results: There were four symptomatic patients (subarachnoid hemorrhage in two, myelopathy in one, and tinnitus in one) and seven asymptomatic patients in whom coincidental CCJAVFs were discovered on imaging studies for other vascular diseases (arteriovenous malformation in one, intracranial DAVF in two, ruptured cerebral aneurysm in two, and carotid artery stenosis in two). Of these 11 patients, 2 (18.2%) had multiple CCJAVFs. Of 14 lesions, the diagnoses were DAVF in 5, RAVF in 3, and EDAVF in 6 (C1–C2 level ratio =5:0, 2:1, 3:3). Patients with DAVF/RAVF in four lesions with intradural venous reflux underwent surgery, although an RAVF remained in one lesion after embolization/radiation. Since all six EDAVFs, two DAVFs, and one RAVF had neither feeder aneurysms nor significant symptoms, no treatment was provided; of these nine lesions, one DAVF and one RAVF remained unchanged, whereas six EDAVFs showed spontaneous obliteration within a year. Unfortunately, however, one DAVF bled before elective surgery. Conclusion: CCJAVFs have many variations of shunting site, angioarchitecture, and multiplicity, and they were frequently associated with coincidental vascular lesions. For symptomatic DAVF/RAVF lesions with intradural drainage, surgery is preferred, whereas asymptomatic EDAVFs without dangerous drainage may obliterate during their natural course.

Background Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. Methods We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. Results Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p Conclusion An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Background and Purpose: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. Methods: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. Results: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. Conclusions: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

The combination of pemetrexed and carboplatin is commonly used for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), mainly because it is comparatively effective and less toxic than other platinum-doublet therapies. Using the JMII (JACAL) study, we report the efficacy and safety of this treatment followed by pemetrexed maintenance in the elderly population (≥70 years of age).The JMII study was a multicenter, post-marketing study that assessed the efficacy and safety of carboplatin (AUC6) and pemetrexed (500 mg/mThe study includes younger (70 years, n = 84) and elderly (≥70 years, n = 25) patients who received induction therapy. Median progression-free survival and overall survival from the start of the induction phase were 5.2 (95% CI: 3.5, 8.2) and 16.8 (95% CI: 10.3, NC) months for the elderly patients compared with 5.8 (95% CI: 4.3, 7.4) and 20.5 (95% CI: 16.7, NC) months for the younger patients, respectively. Grade 3/4 hematologic toxicities were more frequent in the elderly patients. Non-hematologic toxicities in the elderly patients were comparable to those in younger patients. Dose reduction was more common in the elderly (44% vs 23%), due to hematologic toxicities.There was no difference in efficacy (evaluated by progression-free survival) between elderly and younger patients. Although grade 3/4 hematologic toxicities were frequently observed in the elderly patients, they were easily managed with dose adjustment.

Carotid revascularization may be considered for severe stenosis, but its use for symptomatic mild stenosis (50%) with vulnerable plaque or ulcer remains uncertain. The characteristics of patients with symptomatic mild stenosis who underwent revascularization are reviewed.The subjects of this study were 18 patients with symptomatic mild stenosis (50%) on angiography from among 175 patients who underwent revascularization in our department. The plaques were evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion without any of the above. Fourteen patients underwent carotid endarterectomy (CEA), and 4 patients underwent carotid artery stenting.The stenosis on angiography was 27.2% ± 10.7 (5%-41%), and the area carotid artery stenosis rate on US was 69.8 ± 14.5% (44.5%-97%). The stenosis rate of these 2 methods was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque by operative findings. In type 2 plaque that underwent CEA, all patients had vulnerable plaque by histopathology. During the follow-up period, none of the patients had restenosis or stroke.The findings of US and BB-MRI in patients with symptomatic mild stenosis (50%) on angiography are important for determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in mild stenosis, surgical treatment may be considered for these patients.

The relationship between noncontrast computed tomography (CT) markers, which predict the expansion of spontaneous intracerebral hemorrhage (sICH) under conservative treatment, and postoperative rebleeding (PR) after treatment by directly removing the sICH is unknown. This study investigated the relationship between noncontrast CT markers and PR in patients with sICH treated by endoscopic surgery.The study population included 92 patients with available data who underwent endoscopic surgery for sICH at our institution from January 2010 to September 2018. The correlations between PR and preoperative noncontrast CT markers, including the blend sign, hypodensities, black hole sign, heterogeneous density, and island signs, were retrospectively evaluated.In 5 of the 18 patients (27.8%) with the blend sign, PR developed, whereas only 5 of 74 patients (6.8%) without the blend sign developed PR. In the univariate regression analyses, manifestation of hydrocephalus (odds ratio [OR], 8.75; 95% confidence interval [CI], 2.15-35.68; P = 0.002), presence of the blend sign (OR, 5.31; 95% CI, 1.34-20.97; P = 0.02), and insertion of external ventricular drainage (OR, 13.88; 95% CI, 3.22-59.77; P0.001) were significant risk factors. The other radiographic markers were not associated with PR. In a multivariate analysis, the presence of the blend sign (OR, 22.07; 95% CI, 2.18-223.60; P = 0.009) was the only independent predictor of PR.The blend sign is likely to be a strong predictor for PR in patients who undergo endoscopic surgery for sICH. To improve the prognosis of patients with sICH, further studies are needed to establish new treatment strategies and surgical procedures.

Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single-arm open-label phase 1 study of prexasertib consisted of 2 dose levels, 80 mg/m2 and the global-recommended dose based on a US study of 105 mg/m2 , administered intravenously once every 14 days (n = 6 for each dose). Transition to the higher dose proceeded if the frequency of dose-limiting toxicity observed in cycle 1 was

Background and Importance. Subependymoma occurs very rarely in the spinal cord. We report another case of spinal subependymoma along with a review of the literature and discussion of a radiological finding that is useful for preoperative diagnosis of this tumor.Clinical Presentation. A 51-year-old man presented with a 2-year history of progressive muscle weakness in the right lower extremity. Sagittal magnetic resonance imaging (MRI) showed spinal cord expansion at the Th7–12 vertebral level. Surgical resection was performed and the tumor was found to involve predominantly subpial growth. Histological diagnosis was subependymoma, classified as Grade I according to criteria of World Health Organization. We made an important discovery of what seems to be a characteristic appearance for spinal subependymoma on sagittal MRI. Swelling of the spinal cord is extremely steep, providing unusually large fusiform dilatation resembling a bamboo leaf. We have termed this characteristic MRI appearance as the “bamboo leaf sign.” This characteristic was apparent in 76.2% of cases of spinal subependymoma for which MRI findings were reported.Conclusion. The bamboo leaf sign on spinal MRI is useful for differentiating between subependymoma and other intramedullary tumors. Neurosurgeons encountering the bamboo leaf sign on spinal MRI should consider the possibility of subependymoma.

OBJECT Endoscopic surgery was performed for acute or subacute subdural hematoma (SDH), and its effectiveness and safety in elderly patients were evaluated. METHODS Between September 2007 and November 2013, endoscopic surgery was performed in 11 elderly patients with acute SDH (8 patients) and subacute SDH (3 patients). The criteria for surgery were as follows: 1) the presence of clinical symptoms; 2) age older than 70 years; 3) no brain injury (intracerebral hematoma, brain contusion); 4) absence of an enlarging SDH; and 5) no high risk of bleeding. Hematoma evacuation was performed with a 4-mm rigid endoscope with a 0° lens and a malleable irrigation suction cannula. RESULTS Endoscopic surgery was performed under local anesthesia. The mean age of the patients was 82.6 years (range 73–91 years). There were 5 female and 6 male patients. The mean preoperative Glasgow Coma Scale score was 12, and 5 patients had been receiving antithrombotic drug therapy. The mean operation time was 85 minutes. Only 1 patient had rebleeding, and reoperation with the same technique was performed uneventfully in this individual. A total of 7 patients had a good recovery (modified Rankin Scale Score 0–2) at discharge. CONCLUSIONS Endoscopic hematoma evacuation of acute and subacute SDH is a safe and effective method of clot removal that minimizes operative complications. This technique may be a less invasive method for treating elderly patients with acute and subacute SDHs.

The synthesis and the solution/solid-state fluorescence properties of pyrimidine-based monoboron complexes differing in terms of the substituents [either two fluorine atoms (BF2 complex) or two phenyl groups (BPh2 complex)] on the boron atom are reported herein. Unrestricted C-Ar intramolecular rotation in the non-, trifluoromethyl-, and cyano-substituted derivatives resulted in negligible fluorescence in solution. On the other hand, methoxy- and dimethylamino-substituted analogues caused the restriction of the C-Ar intramolecular rotation and consequently resulted in relatively strong fluorescence in solution. The non-, trifluoromethyl-, and cyano-substituted derivatives showed a pronounced aggregation-induced emission enhancement effect. Dimethylamino-substituted derivatives exhibited solvatochromism in the fluorescence spectra. Substitution with BPh2 effectively enhanced the fluorescence quantum yield compared to the corresponding BF2 complexes in the solid-state.

A 70-year-old woman presented with a 4-year history of painless conjunctival congestion and proptosis of the right eye. Computed tomography and magnetic resonance imaging revealed a 48-mm lesion in the right medial orbit. As the symptoms progressed, the tumor was resected by performing fronto-orbital craniotomy. Histopathological examination revealed a vascular tumor surrounded by smooth muscle fibers and immunohistochemistry demonstrated tumor positivity for smooth muscle actin and desmin. The tumor was diagnosed as an angioleiomyoma, and no recurrence has been observed as of 5 years postoperatively. Angioleiomyomas in the orbit are extremely rare;thus, we have reported this case with reference to the literature.

Here, we report biodegradable temperature-triggered covalent gelation systems exhibiting a longer and controllable duration time of the gel state by a “mixing strategy” utilizing a thiol–ene reaction. We synthesized a tri-block copolymer of poly(caprolactone-co-glycolic acid) and PEG (tri-PCG) as a temperature-responsive injectable polymer (IP) and attached acryloyl groups on both termini (tri-PCG-Acryl). A tri-PCG micelle solution containing hydrophobic hexa-functional polythiol (Solution-A) and a tri-PCG-Acryl micelle solution (Solution-B) were mixed together. After mixing, the solution was still in the sol state at r.t., but exhibited an irreversible sol-to-gel transition in response to temperature. The duration time of the gel state while soaking in PBS could be altered from 1 day to 93 days by changing the mixing ratio of Solution-A/B. The physical strengths of the hydrogels were also controllable by changing the mixing ratio. The IP system showed good biocompatibility and a long duration time of the gel state after subcutaneous implantation.

On clinical application of biodegradable injectable polymer (IP) systems, quick extemporaneous preparation of IP formulations and longer duration time gel state after injection into the body are the important targets to be developed. Previously, we had reported temperature-responsive covalent gelation systems via bio-orthogonal thiol-ene reaction by ‘mixing strategy’ of amphiphilic biodegradable tri-block copolymer (tri-PCG) attaching acryloyl groups on both termini (tri-PCG-Acryl) with reactive polythiol. In other previous works, we found ‘freeze-dry with PEG/dispersion’ method as quick extemporaneous preparation method of biodegradable IP formulations. In this study, we applied this quick preparative method to the temperature-triggered covalent gelation system. The instant formulation (D-sample) could be prepared by ‘freeze-dry with PEG/dispersion’ just mixing of tri-PCG-Acryl micelle dispersion and tri-PCG/DPMP micelle dispersion with PEG, that can be prepared in 30 s from the dried samples. The obtained D-sample showed irreversible gelation and long duration time of gel state, which was basically the same as the formulations prepared by the usual heating dissolution method (S-sample). Interestingly, the D-sample could maintain its sol state for a longer time (24 h) after preparing the formulation at r.t. compared with the S-sample, which became a gel in 3 h after preparing. The IP system showed good biocompatibility and long duration time of the gel state after subcutaneous implantation. These characteristics of D-samples, quick extemporaneous preparation and high stability in the sol state before injection, would be very convenient in a clinical setting.

Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear.A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes.At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P.001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P.001).Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy.

OBJECTIVEAging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system.METHODSThis study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge.RESULTSA total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale [mRS] score 0–2) of cases and poor in 28.4% (mRS score 3–6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%.CONCLUSIONSThis study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.

This study investigated the frequency of poor outcome at discharge of acute subdural hematoma (SDH) patients with and without microbleeds. We retrospectively examined the records of 37 patients with acute SDH who were surgically treated with hematoma removal and received magnetic resonance (MR) imaging within 2 weeks of head injury onset. MR images were used to determine the presence or absence of microbleeds and contusional hemorrhage (CH). Patient outcome was categorized as good (moderate disability or good recovery) or poor (severely disability, vegetative state, or dead) according to the Glasgow Outcome Scale at discharge. Microbleeds were found in 23 patients (62%) and CH was found in 26 patients (70%). Fifteen patients (41%) had both microbleeds and CH. Poor outcome at discharge was more common in SDH patients with both microbleeds and CH than in SDH patients with neither microbleeds nor CH (14/15, 93% vs. 14/22, 64%; p = 0.04). Poor outcome at discharge was more common in SDH patients under 60 years of age with microbleeds (6/8, 75%) than patients under 60 years of age without microbleeds (0/4, 0%; p = 0.03). The location of the microbleed was not related to the outcome at discharge. These results suggest that the presence of microbleeds and CH on MR images may indicate poor prognosis in patients with acute SDH.

The effects of incorporated poly( d -lactic acid) (PDLA) as poly(lactic acid) (PLA) stereocomplex crystallites on the isothermal and non-isothermal crystallization behavior of poly( l -lactic acid) (PLLA) from the melt were investigated for a wide PDLA contents from 0.1 to 10 wt%. In isothermal crystallization from the melt, the radius growth rate of PLLA spherulites (crystallization temperature (Tc)≥125 °C), the induction period for PLLA spherulite formation (ti) (Tc≥125 °C), the growth mechanism of PLLA crystallites (90 °C≤Tc≤150 °C), and the mechanical properties of the PLLA films were not affected by the incorporation of PDLA or the presence of stereocomplex crystallites as a nucleating agent. In contrast, the presence of stereocomplex crystallites significantly increased the number of PLLA spherulites per unit area or volume. In isothermal crystallization from the melt, at PDLA content of 10 wt%, the starting, half, and ending times for overall PLLA crystallization (tc(S), tc(1/2), and tc(E), respectively) were much shorter than those at PDLA content of 0 wt%, due to the increased number of PLLA spherulites. Reversely, at PDLA content of 0.1 wt%, the tc(S), tc(1/2), and tc(E) were longer than or similar to those at PDLA content of 0 wt%, probably due to the long ti and the decreased number of spherulites. This seems to have been caused by free PDLA chains, which did not form stereocomplex crystallites. On the other hand, at PDLA contents of 0.3–3 wt%, the tc(S), tc(1/2), and tc(E) were shorter than or similar to those at PDLA content of 0 wt% for the Tc range below 95 °C and above 125 °C, whereas this inclination was reversed for the Tc range of 100–120 °C. In the non-isothermal crystallization of as-cast or amorphous-made PLLA films during cooling from the melt, the addition of PDLA above 1 wt% was effective to accelerate overall PLLA crystallization. The X-ray diffractometry could trace the formation of stereocomplex crystallites in the melt-quenched PLLA films at PDLA contents above 1 wt%. This study revealed that the addition of small amounts of PDLA is effective to accelerate overall PLLA crystallization when the PDLA content and crystallization conditions are scrupulously selected.

Summary: The effects of various additives: poly(D-lactic acid) (PDLA), talc, fullerene C60, montmorillonite, and various polysaccharides, on the non-isothermal crystallization behavior of poly(L-lactic acid) (PLLA), during both the heating of melt-quenched films from room temperature, and the cooling of as-cast films from the melt, was investigated. When the melt-quenched PLLA films were heated from room temperature, the overall PLLA crystallization was accelerated upon addition of PDLA or the stereocomplex crystallites formed between PDLA and PLLA, the mixtures containing PDLA, and the mixture of talc and montmorillonite. No significant effects on the overall PLLA crystallization were observed for talc, C60, montmorillonite, and the mixtures containing C60. Such rapid completion of the overall PLLA crystallization upon addition of the aforementioned additives can be ascribed to the increased density (number per unit volume or area) of PLLA spherulites. When the as-cast PLLA films were cooled from the melt, the overall PLLA crystallization completed rapidly, upon addition of PDLA, talc, C60, montmorillonite, and their mixtures. Such rapid overall PLLA crystallization is attributable to the increased density of the PLLA spherulites and the higher nucleation temperature for PLLA crystallization. In contrast, the addition of various polysaccharides has no significant effect, or only a very small effect, on the overall PLLA crystallization during heating from room temperature or during cooling from the melt. This finding means that the polysaccharides can be utilized as low-cost fillers for PLLA-based materials, without disturbing the crystallization of the PLLA. The effect of additives in accelerating the overall PLLA crystallization during cooling from the melt, decreased in the following order: PDLA > talc > C60 > montmorillonite > polysaccharides. Polarization optical photomicrographs of pure PLLA, and the PLLA-F film, with the fullerene additive, during cooling from the melt (Process IIB). Both of the photomicrographs were taken at 120 °C.

We investigated the release behavior of glucagon-like peptide-1 (GLP-1) from a biodegradable injectable polymer (IP) hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40)) was observed compared with a reversible (physical gelation) IP formulation (F(P1)). Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

This report describes a mixed germ cell tumor that underwent dramatic size changes. A 12-year-old boy presented to our hospital with a headache that had persisted for two months. Initial magnetic resonance imaging (MRI) revealed a pineal tumor and hydrocephalus. The patient required external ventricular drainage and underwent two endoscopic biopsies. His evaluation involved a total of nine computed tomography (CT) scans prior to the second biopsy;the tumor size had decreased before the second endoscopic biopsy. The tumor consisted of both a germinoma and a teratoma component. The patient was treated with three courses of carboplatin-etoposide (CBDCA-VP) chemotherapy and whole-ventricle radiotherapy (32.1 Gy). However, during the adjuvant therapy, the tumor size increased, necessitating total tumor resection. We speculate that the tumor's initial size reduction was caused by leakage of the cyst component and exposure to the brain CT irradiation. The tumor's subsequent increase in size was due to the recollection of the cystic components and intracranial growing teratoma syndrome (iGTS). Therefore, frequent brain CTs and angiography should be avoided before definitive pathological diagnosis is achieved. Further, the tumor size should be considered, with surgical resection being performed at the optimal time.