Shimane University Hospital

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected.

BACKGROUND: The competence of ChatGPT (Chat Generative Pre-Trained Transformer) in non-English languages is not well studied. OBJECTIVE: This study compared the performances of GPT-3.5 (Generative Pre-trained Transformer) and GPT-4 on the Japanese Medical Licensing Examination (JMLE) to evaluate the reliability of these models for clinical reasoning and medical knowledge in non-English languages. METHODS: This study used the default mode of ChatGPT, which is based on GPT-3.5; the GPT-4 model of ChatGPT Plus; and the 117th JMLE in 2023. A total of 254 questions were included in the final analysis, which were categorized into 3 types, namely general, clinical, and clinical sentence questions. RESULTS: The results indicated that GPT-4 outperformed GPT-3.5 in terms of accuracy, particularly for general, clinical, and clinical sentence questions. GPT-4 also performed better on difficult questions and specific disease questions. Furthermore, GPT-4 achieved the passing criteria for the JMLE, indicating its reliability for clinical reasoning and medical knowledge in non-English languages. CONCLUSIONS: GPT-4 could become a valuable tool for medical education and clinical support in non-English-speaking regions, such as Japan.

Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat ischemia models reduces ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle cerebral artery occlusion (MCAO) ischemia model. At 1 day after transient MCAO, 3 x 10(6) immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotrophic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrophic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain.

A series of 741 consecutive cases of localized hyperplastic lesions of the gingiva were studied. The lesions were reclassified into four groups: pyogenic granuloma, peripheral giant cell granuloma, fibrous hyperplasia and peripheral fibroma with calcification. This study indicates that there are some differences between these groups in age and sex distribution as well as in location and size of the lesion. Fibrous hyperplasia was the most common type, followed in descending order by pyogenic granuloma, peripheral fibroma with calcification and peripheral giant cell granuloma. The peripheral giant cell granuloma showed no sex predilection while fibrous hyperplasia, pyogenic granuloma and peripheral fibroma with calcification were more common in females. Pyogenic granuloma and peripheral fibroma with calcification occur in younger patients more often than fibrous hyperplasia, and thus may represent a stage in the development of fibrous hyperplasia.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a subtype of mature T- and natural killer cell lymphomas characterized by its association with Epstein-Barr virus and extranodal involvement. Although there is geographic variance in the frequency of ENKL, its clinical features are similar between Western countries and endemic areas, such as East Asia. Anthracycline-containing chemotherapy is not recommended to treat ENKL. No standard treatment has been established based on the results of randomized controlled trials. In patients with localized disease, radiotherapy is a core component of the recommended first-line therapy. Radiotherapy administered at 50 to 54 Gy, extended involved-site radiotherapy considering tumor invasiveness, and the use of intensity modulated radiation therapy or volumetric modulated arc therapy are associated with efficacy of radiotherapy. Although the use of concurrent chemoradiotherapy has been supported by the results of clinical trials, accumulating evidence supports the use of sequential chemoradiotherapy with non-anthracycline-containing regimens that include l-asparaginase and/or platinum anticancer agents. l-asparaginase-containing chemotherapy is a key component of first-line treatments for systemic ENKL. Hematopoietic stem cell transplantation is recommended as a front-line consolidation therapy for newly diagnosed advanced-stage ENKL. Newer agents including immune checkpoint inhibitors are being investigated for treating ENKL. In this modern ENKL treatment era, multidisciplinary efforts are needed to identify the best timing and sequencing of radiotherapy, l-asparaginase, platinum, newer agents, and hematopoietic stem cell transplantation.

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

Abstract The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10–90 μg) or placebo for 12 weeks. In Part C, 152 patients were randomized to receive tropifexor 140 µg, tropifexor 200 µg or placebo (1:1:1) for 48 weeks. The primary endpoints were safety and tolerability to end-of-study, and dose response on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic fat fraction (HFF) at week 12. Pruritus was the most common adverse event in all groups, with a higher frequency in the 140- and 200-µg tropifexor groups. Decreases from baseline in ALT and HFF were greater with tropifexor versus placebo at week 12, with a relative decrease in least squares mean from baseline observed with all tropifexor doses for ALT (tropifexor 10–90-μg dose groups ranged from −10.7 to −16.5 U l −1 versus placebo (−7.8 U l −1 ) and tropifexor 140- and 200-μg groups were −18.0 U l −1 and −23.0 U l −1 , respectively, versus placebo (−8.3 U l −1 )) and % HFF (tropifexor 10–90-μg dose groups ranged from −7.48% to −15.04% versus placebo (−6.19%) and tropifexor 140- and 200-μg groups were −19.07% and −39.41%, respectively, versus placebo (−10.77%)). Decreases in ALT and HFF were sustained up to week 48; however, similar trends in AST with tropifexor at week 12 were not observed. As with other FXR agonists, dose-related pruritus was frequently observed. Clinicaltrials.gov registration: NCT02855164

BACKGROUND: Thrombelastograph analysis (TEG) is used to evaluate blood coagulation. Ideally, whole blood is immediately processed. If impossible, blood may be citrated and assessed after recalcification. No data describe the effect of such treatment and storage on TEG parameters. METHODS: Three studies were performed in 90 surgical patients. In 30 patients, blood was citrated (1:10, 0. 129 M) and recalcified (20 microl 2 M CaCl2 to 340 microl citrated blood), and TEG was performed with native blood and after recalcification after 0, 15, and 30 min of citrate storage. In another 30 patients, TEG was performed with citrated blood recalcified immediately and after 1-72 h storage. In a third study, thrombin-antithrombin complex, prothrombin fragment 1+2, and beta-thromboglobulin were measured (using enzyme-linked immunoabsorbant assay tests) at corresponding time points. Data were compared using repeated-measures analysis of variance and post hocpaired t tests. RESULTS: TEG parameters were different in recalcified citrated blood compared with native blood (P < 0.05) and changed significantly during 30-min (P < 0.025) and 72-h (P < 0.001) citrate storage. TEG parameters measured between 1 and 8 h of citrate storage were stable. Thrombin-antithrombin complex and prothrombin fragment 1+2 values were not elevated in native blood. After 30 min of citrate storage a gradual thrombin activation was observed, as evidenced by increasing thrombin-antithrombin complex and prothrombin fragment 1+2 values (P < 0.05). beta-Thromboglobulin level was increased after 2 and 8 h of citrate storage (P < 0.01). CONCLUSIONS: Analysis of native blood yields the most reliable TEG results. Should immediate TEG processing not be possible, citrated blood may be used if recalcified after 1-8 h.

BACKGROUND AND PURPOSE: The efficacy of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in adult moyamoya disease was evaluated by clinicopathophysiological studies. METHODS: Fifteen patients with cerebral ischemic attacks (ischemia group) and 15 patients with intracranial hemorrhages (hemorrhage group) were investigated. Clinicoangiographic features and regional cerebral blood flow (rCBF) of the MCA territory were preoperatively and postoperatively investigated, and cortical arterial pressure (CAP) and anastomotic blood flow (AF) were intraoperatively measured. RESULTS: In the ischemia group, the preoperative rCBF of 38.4 mL/100 g per minute was significantly increased to 42.1 mL/100 g per minute with a diminution of angiographic moyamoya vessels in 67% of patients after surgery. The mean CAP and AF were 25.6 mm Hg and 34.7 mL/min, respectively. Proximal and distal cerebral vascular resistance (PCVR = [Mean Systemic Arterial Blood Pressure-Mean CAP]/rCBF and DCVR = [Mean CAP/rCBF]) were 1.78 and 0.68, respectively. One patient died perioperatively as a result of intracerebral hemorrhage. During follow-up (mean, 67 months), 12 of 14 patients recovered without neurological deficits, 1 was moderately disabled because of the initial insult, and another patient experienced an intracerebral hemorrhage but recovered fully. In the hemorrhage group, the preoperative rCBF of 38.0 mL/100 g per minute was significantly increased to 42.7 mL/100 g per minute with a diminution of moyamoya vessels in 60% after surgery. The mean CAP and AF were 29.1 mm Hg and 24.1 mL/min, respectively. PCVR and DCVR were 1.72 and 0.77, respectively. One patient became hemiparetic because of perioperative intracerebral hemorrhage. During follow-up (mean, 94 months), 3 patients had fatal intracranial hemorrhages, 10 had good recoveries, and 2 had moderate disabilities. CONCLUSIONS: This study revealed a high PCVR and a very low DCVR in both the ischemia and hemorrhage groups of patients. STA-MCA anastomosis partially normalized cerebral circulation and decreased moyamoya vessels but did not completely prevent rebleeding.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals. METHODS: We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject. RESULTS: MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region. CONCLUSIONS: This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.

TLR4, a member of pattern recognition receptors, is the main receptor of LPS. MD-2 physically associates with TLR4 on the cell surface and confers LPS responsiveness. Helicobacter pylori LPS is one of the major virulence factors for induction of gastritis. We demonstrated in this study the role of MD-2 in TLR4-dependent signaling in H. pylori-associated gastritis. Gastric biopsy samples collected from patients with and without H. pylori infection and four gastric cancer cell lines were used for this study. TLR-4 and MD-2 expression in biopsy specimens and the cell lines was examined by using RT-PCR. Localization of TLR-4 in histological sections was evaluated by immunohistochemistry. For in vitro functional assays, we established stable transfectants of AGS cells expressing TLR4 and MD-2. Cellular distribution of TLR4 was examined by flow cytometry. NF-kappaB activation and activation of IL-8 and MD-2 promoters were assessed by reporter gene assay. H. pylori infection up-regulated the TLR4 and MD-2 expression in gastric mucosa. TLR4 staining was observed predominantly in epithelial cells, located in both the cytoplasm and at the apical surface. MD-2 transfection in AGS cells markedly increased cell surface expression of TLR4 and augmented the activation of NF-kappaB and IL-8 promoter upon stimulation with H. pylori LPS. Live H. pylori also stimulated transcriptional activation of MD-2. This study revealed that MD-2 expression is elevated in gastric epithelial cells during H. pylori infection, suggesting that the TLR4/MD-2 system is a potent receptor complex involved in the response to H. pylori LPS in the stomach.

Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK-positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK-negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK-negative, ALCL-ALK-positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions.

BACKGROUND: Normative alcohol use (or drinking behavior) influences the risk of cardiovascular disease in a multi-faceted manner. To identify susceptibility gene variants for drinking behavior, a 2-staged genome-wide association study was performed in a Japanese population. METHODS AND RESULTS: In the stage-1 scan, 733 cases and 729 controls were genotyped with 456,827 SNP markers. The associated loci without redundancy of linkage disequilibrium were further examined in the stage-2 general population panel comprising 2,794 drinkers (≥ once per week), 1,521 chance drinkers (< once per week), and 1,351 non-drinkers. Along with genome-wide exploration, we aimed to replicate the trait association of a candidate gene SNP previously reported (rs1229984 in ADH1B). A cluster of 12 SNPs on 12q24 were found to significantly (P<5×10(-8)) associate with drinking behavior in stage 1, among which rs671 (a Glu-to-Lys substitution at position 504) in the ALDH2 gene showed the strongest association (odds ratio (OR)=0.16, P=3.6×10(-211) in the joint analysis). The association was also replicated for rs1229984 (OR=1.20, P<3.6×10(-4)). Furthermore, ALDH2 504Lys was associated with several metabolic traits, eg, lower levels of high-density lipoprotein cholesterol and liver enzymes-AST, ALT, and γGTP-by interacting with alcohol intake. CONCLUSIONS: Our results confirm ALDH2 as a major locus regulating drinking behavior in the Japanese, indicating that the ALDH2 504Lys variant exerts pleiotropic effects on risk factors of cardiovascular disease among drinkers.

BACKGROUND: There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). METHODS: We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. RESULTS: With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. CONCLUSIONS: Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

Abstract Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data. Drug sensitivity profiling further demonstrates the role of the JAK-STAT pathway in the pathogenesis of NK-cell malignancies, identifying NK cells to be highly sensitive to JAK and BCL2 inhibition compared to other hematopoietic cell lineages. Our results provide insight into ANKL genetics and a framework for application of targeted therapies in NK-cell malignancies.

MFG-E8 (milk fat globule-epidermal growth factor 8) deficiency is strongly associated with acquisition of immune-mediated disorders due to the loss of tissue homeostasis. However, comparatively little is known regarding its functions in gastrointestinal tract disorders, in which immune homeostasis is a major concern. Herein, we report altered MFG-E8 expression in inflamed colons during the acute phase of murine experimental colitis and found that treatment with recombinant MFG-E8, but not its arginine-glycine-aspartate mutant counterpart, ameliorated colitis by reducing inflammation and improving disease parameters. To reveal the MFG-E8-mediated antiinflammatory mechanism, we employed an in vitro system, which showed the down-regulation of NF-kappaB in an LPS-dependent manner. Additionally, MFG-E8 altered alpha(v)beta(3) integrin-mediated focal adhesion kinase phosphorylation by impeding the binding of one of its potent ligands osteopontin, which becomes activated during colitis. Taken together, our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis.

Maxillofacial osteosynthetic surgeries require stable fixation for uneventful boney healing and optimal remodeling. Although conventional titanium plates and screws for osteofixation are considered the gold standard for rigid fixation in maxillofacial surgeries, bioresorbable implants of plates and screw systems are commonly used for various maxillofacial osteosynthetic surgeries such as orthognathic surgery, maxillofacial fractures, and reconstructive surgery. Titanium plates are limited by their palpability, mutagenic effects, and interference with imaging, which may lead to the need for subsequent removal; the use of a biologically resorbable osteofixation system could potentially address these limitations. However, several problems remain including fundamental issues involving decreased mechanical strength and stability, slow biodegradation, complex procedures, and the available bioresorbable implant materials. Major advances in bioresorbable plate systems have been made with the use of bioactive/resorbable osteoconductive materials and an accelerator of bioresorption, such as polyglycolic acid. This report presents an overview of currently available resorbable implant materials and their applications, with a focus on recent innovative advances and new developments in this field.

We sought to clarify the role of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN). We retrospectively identified 25 BPDCN patients (allo-HSCT, n = 14; auto-HSCT, n = 11) from registry data of the Japan Society for Hematopoietic Cell Transplantation and analyzed clinicopathologic data and clinical outcomes after transplantation. The median age at HSCT was 58 years (range, 17-67 years). All 11 patients who underwent auto-HSCT were in the first complete remission (CR1). With a median follow-up of 53.5 months, the overall survival rates at 4 years for patients who underwent auto-HSCT and allo-HSCT were 82% and 53% (P = .11), respectively, and progression-free survival rates were 73% and 48% (P = .14), respectively. Auto-HSCT for BPDCN in CR1 appears to provide promising results and deserves further evaluation in the setting of prospective trials.

BACKGROUND AND PURPOSE: Estimation of the actual incidence rate of subarachnoid hemorrhage and evaluation of the treatment require the inclusion of all patients in a defined geographic area. METHODS: During 1987 through 1992 in Izumo City, Japan, we estimated the incidence rate of subarachnoid hemorrhage by including dead-on-arrival patients and by further adding the results obtained after reviewing all death certificates registered in this city in the corresponding period. In addition, we compared the management and surgical outcomes in hospitalized patients from 1987 through 1992 with outcomes from 1980 through 1986. RESULTS: During 1987 through 1992, we diagnosed 123 patients as having subarachnoid hemorrhage. The crude and the age- and sex-adjusted incidence rates using the 1990 population statistics for Japan were 25 (95% confidence interval, 21 to 30) per 100,000/y and 23 (95% confidence interval, 19 to 28) per 100,000/y for all ages, respectively; these occurrences are the highest among those reported to date. Of these patients, 8% died before receiving medical attention, 27% in the first week, and 39% at 1 month. The survival curve for 2 years improved significantly from 1980-1986 to 1987-1992 in patients with admission grades 4 and 5 (P = .035) and in operated patients with preoperative grades 1 through 3 (P = .036). However, there was little improvement in the overall management results (P = .168), possibly because patients with high risk and/or old age were admitted and/or diagnosed more often in the latter period. CONCLUSIONS: The incidence rate of subarachnoid hemorrhage is much higher than that reported so far in the literature, and despite improvement of management and surgical therapy, the actual case-fatality rate is still high, mainly because of the high mortality rate directly associated with the primary bleeding.

The oral and maxillofacial region has a complicated anatomy with critical contiguous organs, including the brain, eyes, vital teeth, and complex networks of nerves and blood vessels. Therefore, advances in basic scientific research within the field of intraoperative oral and maxillofacial surgery have enabled the introduction of the features of these techniques into routine clinical practice to ensure safe and reliable surgery. A navigation system provides a useful guide for safer and more accurate complex in oral and maxillofacial surgery. The effectiveness of a navigation system for oral and maxillofacial surgery has been indicated by clinical applications in maxillofacial trauma surgery including complex midfacial fractures and orbital trauma reconstruction, foreign body removal, complex dentoalveolar surgery, skull base surgery including surgery of the temporomandibular joint (TMJ), and orthognathic surgery. However, some fundamental issues remain involving the mobility of the mandible and difficulty in updating images intraoperatively. This report presents an overview and feasible applications of available navigation systems with a focus on the clinical feasibility of the application of navigation systems in the field of oral and maxillofacial surgery and solutions to current problems.