Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. METHODS: In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. RESULTS: Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. CONCLUSIONS: When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

Depletion of hepatic stellate cells inhibits hepatic steatosis in mice.

BACKGROUND AND AIM: Hepatic stellate cells (HSCs), the main source of extracellular matrix in hepatic fibrogenesis, produce various cytokines, growth factors, and morphogenetic proteins. Among these, several factors are known to promote hepatocyte lipid accumulation, suggesting that HSCs can be efficient therapeutic targets for non-alcoholic steatohepatitis (NASH). This study aimed to investigate the effects of HSC depletion on the development of hepatic steatosis and fibrosis in a murine NASH model. METHODS: C57BL/6 mice were treated with gliotoxin (GTX), an apoptosis inducer of activated HSCs under the feeding of a choline-deficient l-amino acid-defined high-fat diet for 4 weeks. For in vitro study, Hc3716 cells, immortalized human hepatocytes, were treated with fatty acids in the presence or absence of LX2, immortalized HSCs. RESULTS: Choline-deficient l-amino acid-defined high-fat diet increased pronounced hepatic steatosis, which was attenuated by GTX treatment, together with a reduction in the number of activated HSCs. This change was associated with the downregulation of the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream genes, including adipocyte protein 2, cluster of differentiation 36 (CD36), and fatty acid transport protein 1, all of which increase the fatty acid uptake into hepatocytes. As expected, GTX treatment improved hepatic fibrosis. Co-culture of hepatocytes with HSCs enhanced intracellular lipid accumulation, together with the upregulation of PPARγ and CD36 protein expressions. CONCLUSIONS: In addition to the improvement in hepatic fibrogenesis, depletion of HSCs had a favorable effect on hepatic lipid metabolism in a mouse NASH model, suggesting that HSCs are potentially efficient targets for the treatment of NASH.

Endoscopic approach in the diagnosis of high-grade pancreatic intraepithelial neoplasia.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high-grade pancreatic intraepithelial neoplasia (HG-PanIN), whose tumorous lesion is undetectable on cross-sectional images such as computed tomography or magnetic resonance image, long-term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG-PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG-PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG-PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post-ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4-Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early-stage PDAC.

Donor age (≥45 years) and reduced immunosuppression are associated with the recurrent primary sclerosing cholangitis after liver transplantation - a multicenter retrospective study.

The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5- and 10-year patient- and graft survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5- and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (P < 0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (P < 0.001), cyclosporine use (P = 0.012), mono or no immunosuppressive agent (P < 0.001), postoperative biliary complication (P < 0.001), and active intestinal bowel disease after LT (P < 0.001). Among these factors, donor age ≥45 years [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.21-2.69; P = 0.003] and mono or no immunosuppressive agent 1-year after LT (HR, 2.38; 95% CI, 1.23-3.45; P = 0.011) were identified as independent risk factors in the final multivariate Cox regression model. The results were similar in sub-analysis for ABO-identical/compatible adult living donor LT cases.

Periostin antisense oligonucleotide prevents hepatic steatosis and fibrosis in a mouse model of non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation, and hepatocellular injury with varying degrees of fibrosis. There are currently no established treatment approaches for NASH other than lifestyle interventions. Periostin, a matricellular protein required for tissue remodeling and fibrosis, plays an important role in hepatic steatosis and fibrosis and could be a potential target for NASH treatment. Advances in molecular biology and biochemical engineering have led to the development of antisense oligonucleotides (ASOs) that can inhibit target genes with no significant toxic effects. Herein, we investigated the therapeutic effects of periostin-targeting ASO (PNASO) in NASH. METHODS: C57BL/6J mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) to induce NASH with or without intraperitoneal injection of mouse PNASO. To explore the role of periostin in hepatocellular steatosis, Hc3716 cells, an immortalized human hepatocyte line, were treated with recombinant periostin in vitro. RESULTS: The induced periostin expression in the liver of CDAHFD-fed mice was significantly suppressed by PNASO. The deletion of hepatic periostin by PNASO significantly ameliorated hepatic steatosis while restoring the expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its target genes. PNASO also inhibited hepatic fibrosis, reflected by the reduction of alpha-smooth muscle actin, collagen type I, and other fibrotic markers. In vitro experiments demonstrated that treatment with recombinant periostin increased cellular lipid accumulation in Hc3716 cells accompanied with the downregulation of PPAR-α. CONCLUSIONS: Periostin-targeting ASO is a potential therapeutic approach for the efficient treatment of hepatic steatosis and fibrosis in NASH.

Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan.

AIM: Autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) impose a significant burden on public health, and it is important to estimate their prevalence. We carried out a nationwide, hospital-based, epidemiological survey of AIH, PBC, and PSC, and compared the results with those from previous surveys. METHOD: We randomly selected health-care facilities used in the survey from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with AILD who visited the facility in 2016. An identical survey was undertaken for AIH/PBC in 2004 and for PSC in 2007; we carried out a comparative analysis of these data. RESULTS: We selected 1793 departments from health centers all over Japan. Of them, 1078 (60.1%) responded to the questionnaires. The number of reported patients with AIH, PBC, and PSC was 8505, 10 847, and 906, respectively, and point prevalence was 23.9 (95% confidence interval, 23.3-24.5) for AIH (8.7 in 2004), 33.8 (33.0-34.6) for PBC (11.6 in 2004), and 1.80 (1.75-1.85) for PSC (0.95 in 2007) per 100 000 population. Male-to-female patient ratio of AILD was 1:4.3 for AIH (1:6.9 in 2004), 1:3.9 for PBC (1:7.1 in 2004), and 1:0.88 for PSC (1:1.4 in 2007). CONCLUSION: The current study indicates an increasing trend of prevalence as well as male-to-female patient ratio of AILD in Japan.

Long-term outcomes of pediatric-onset primary sclerosing cholangitis: A single-center experience in Japan.

AIM: Primary sclerosing cholangitis (PSC) is very rare in Japan. Although a large-scale cohort study of 781 pediatric-onset PSC patients in Europe and North America showed that the 5-year survival with native liver was 88%, the long-term outcomes of pediatric-onset PSC in Japan are unknown. Here, we evaluated the clinical outcomes of pediatric-onset PSC in Japan. METHODS: We carried out a retrospective cohort study with a medical records review of pediatric PSC patients diagnosed between 1986 and 2017 at a single center. The PSC diagnoses were based on cholangiography, liver histology, and biochemical findings. The patients' survival was analyzed using the Kaplan-Meier method. Prognostic factors were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. RESULTS: We identified 39 pediatric-onset PSC patients (22 boys, 17 girls). The median age at diagnosis was 9 years (interquartile range 6.0-13.5 years). The median follow-up period was 5.5 years (interquartile range 3.4-8.7 years). The phenotypes of PSC-autoimmune hepatitis, PSC-inflammatory bowel disease, and small-duct PSC were diagnosed in 13 (33.3%), 36 out of 38 (94.8%), and three (7.7%) patients, respectively. The 5-year liver transplantation-free survival of the whole cohort was 93.5%. Nine patients underwent liver transplantation, and four of these nine cases resulted in death. Both the univariate and multivariate analyses showed that the phenotype of "PSC-autoimmune hepatitis overlap" was an independent poor prognostic factor. CONCLUSIONS: The overall survival of pediatric-onset PSC in Japan was comparable to those in Western countries. The phenotype of PSC-autoimmune hepatitis was identified as a prognostic factor associated with a poorer long-term outcome.

Geographical distribution of family physicians in Japan: a nationwide cross-sectional study.

BACKGROUND: Geographical maldistribution of physicians, and their subsequent shortage in rural areas, has been a serious problem in Japan and in other countries. Family Medicine, a new board-certified specialty started 10 years ago in Japan by Japan Primary Care Association (JPCA), may be a solution to this problem. METHODS: We obtained the workplace information of 527 (78.4%) of the 672 JPCA-certified family physicians from an online database. From the national census data, we also obtained the workplace information of board-certified general internists, surgeons, obstetricians/gynaecologists and paediatricians and of all physicians as the same-generation comparison group (ages 30 to 49). Chi-squared test and residual analysis were conducted to compare the distribution between family physicians and other specialists. RESULTS: Five hundred nineteen JPCA-certified family physicians and 137,587 same-generation physicians were analysed. The distribution of family physicians was skewed to municipalities with a lower population density, which shows a sharp contrast to the urban-biased distribution of other specialists. The proportion of family physicians in non-metropolitan municipalities was significantly higher than that expected based on the distribution of all same-generation physicians (p < 0.001). CONCLUSIONS: Family physicians distributed in favour of rural areas much more than any other specialists in Japan. The better balance of family physician distribution reported from countries with a strong primary care orientation seems to hold even in a country where primary care orientation is weak, physician distribution is not regulated, and patients have free access to healthcare. Family physicians comprise only 0.2% of all Japanese physicians. However, if their population grows, they can potentially rectify the imbalance of physician distribution. Government support is mandatory to promote family medicine in Japan.

Clinical Features, Response to Treatment, and Outcomes of IgG4-Related Sclerosing Cholangitis.

BACKGROUND & AIMS: Immunoglobulin G4 sclerosing cholangitis (IgG4-SC) is a biliary tract manifestation of IgG4-related systemic disease. We investigated the demographics, clinical features at presentation, treatment response, and outcomes of IgG4-SC using data from a large-scale survey in Japan. METHODS: We performed a retrospective cohort study of 527 patients with IgG4-SC (436 female; median age, 66.2 years; range, 23-89 years) in Japan from 2000 to 2015. Data on patient demographics, presentation, treatment response, and outcomes were collected from questionnaires given to patients at 211 referral centers in Japan in 2015. Patients were diagnosed with IgG4-SC based on the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Patients were followed for a median of 4.1 ± 3.1 years. Survival was assessed using the Kaplan-Meier curve and log-rank test. RESULTS: Symptoms at presentation included jaundice (35% of patients) and pruritus (13% of patients); 28% of patients were asymptomatic. It was extremely rare for patients with IgG4-SC to present with symptoms of decompensated cirrhosis. At presentation, serum levels of IgG4 were increased (>135 mg/dL) in 84% of patients. Response to prednisolone was excellent in 90% of patients. No patients received liver transplants, and cholangiocarcinoma was found in only 4 patients (0.7%). Restenosis of bile ducts was observed in 19% of patients but did not affect overall survival. CONCLUSIONS: In a retrospective cohort study of 527 patients with IgG4-SC in Japan, we found the disease to be benign. Most patients (90%) respond to treatment with prednisolone and few develop decompensated cirrhosis or cholangiocarcinoma.

[Emergency care by Japan Primary Care Association certified family physician].

The Japan Primary Care Association has certified family physicians to play a key role in emergency care. During the family medicine program, family physicians train how to treat mild to moderate emergency symptoms for at least three months at a hospital in which more than one thousand patients are transported by ambulance a year. After the three-year program, they can provide not only emergency care for citizens but also emergency care education for trainee doctors. There will be a greater need for certified family physicians because they have a vital mission to protect the health of local communities by associating with several departments, including the emergency department.

Clinical evaluation of ezetimibe on bile lithogenicity in humans: Use of transnasal endoscopy for bile sampling.

AIM: Ezetimibe inhibits cholesterol absorption by blocking Niemann-Pick C1-like 1 proteins (NPC1L1) expressed in the small intestine. Because NPC1L1 is also expressed in human liver, ezetimibe conceivably alters biliary lipid compositions. Here, we performed a clinical trial investigating the effect of ezetimibe on biliary lipids using transnasal endoscopy for bile collection. METHODS: Eight patients with dyslipidemia enrolled in this study completed blood and bile sampling before and at 3 months after ezetimibe treatment (10 mg/day), and the samples are analyzed. RESULTS: Endoscopic bile sampling was performed safely and painlessly. Serum sterol-based biomarkers declared decreased cholesterol absorption and increased synthesis. On analysis of biliary lipids, four of the eight patients showed relative decrease of cholesterol and increase of bile acids with improved lithogenicity while the remainder exhibited the symmetrical changes. CONCLUSION: Our data suggests that biliary lithogenicity is not worsened by ezetimibe. The regulation of biliary cholesterol is presumably multifactorial such as body cholesterol pool size and biliary cholesterol reabsorption by NPC1L1 in the liver.

Clinical features of hepatolithiasis: analyses of multicenter-based surveys in Japan.

BACKGROUND: Hepatolithiasis is a calculus disease of the liver with no known cause that is relatively uncommon, and is characterized by a refractory nature and high frequency of recurrence. Hepatolithiasis is one of the diseases listed by the Ministry of Health, Labour and Welfare of Japan under Research on Intractable Diseases, and it requires further research on the pathogenesis as well as the therapeutic strategy. It is also included in the clinical guidelines for cholelithiasis of the Japanese Society of Gastroenterology, which suggest guiding principles for the treatment of hepatolithiasis. METHODS: we performed questionnaire surveys of hepatolithiasis twice in 2010 and in 2012. Verification of the evidence-based clinical practice guidelines a questionnaire survey of 22 facilities in 2010 and 25 facilities in 2012 across Japan that provided cooperation, which enabled us to assess 210 new cases over a two-year period. CONCLUSIONS: Comparison with two surveys that have been carried out previously revealed the main factor associated with hepatolithiasis was a history of biliary tract surgery, which was noted in the majority of cases. In addition, there was an increase of patients in whom balloon endoscopy was performed using transduodenal approach. This method is not included in the treatment options of the current clinical guidelines for cholelithiasis, so there may be a need to take it into consideration when the guidelines are revised.

Assessing outcomes and complications of secondary hepatolithiasis after choledochoenterostomy: A nationwide survey in Japan.

BACKGROUND: This study aimed to evaluate the outcomes and complications of secondary hepatolithiasis following choledochoenterostomy to guide suitable management. METHODS: The study analyzed 127 patients from a 2017 national survey conducted by the Ministry of Health, Labor, and Welfare. The 2023 cohort study assessed residual stones, recurrences, cholangitis, cholangiocarcinoma, and prognosis. RESULTS: The median follow-up duration was 48 months. Balloon endoscopy-assisted endoscopic retrograde cholangiography (BE-ERC) was the most common treatment, achieving complete stone clearance in 84.4% of patients. Anatomical hepatectomy was the most common surgery. Predictors of residual stones were stone number ≥10 (odds ratio [OR], 7.480; p = .028) and stone diameter ≥10 mm (OR, 5.280; p = .020). Predictors of stone recurrence during follow-up were biliary strictures (hazard ratio [HR], 3.580; p = .005) and cholangitis (HR, 2.700; p = .037). Predictors of cholangitis during follow-up were biliary stricture (HR, 5.016; p = .006) and dilatation (HR, 3.560; p = .029). Any treatment for hepatolithiasis reduced cholangitis occurrence (HR, 0.168; p = .042). Balloon dilation combined with stenting for ≥3 months improved biliary strictures in 57.1% of patients. CONCLUSION: This study recommends BE-ERC as the first-choice treatment for secondary hepatolithiasis. Stone removal and relief of biliary strictures and dilatation are crucial to prevent stone recurrence and cholangitis after treatment.

Dietary intervention for adult survivors of cancers other than breast cancer: A systematic review.

INTRODUCTION: Healthy eating and weight control are recommended for cancer survivors; however, dietary interventions are not routinely offered to them. This study aimed to assess the effects of dietary interventions on survival, nutritional status, morbidity, dietary changes, health-related quality of life (QOL), and clinical measures in cancer survivors. METHODS: Searches were conducted from October 1, 2018 to November 21, 2011 in the Medline, EMBASE, CENTRAL, Emcare, and DARE electronic databases. We included randomized controlled trials (RCTs) that involved individuals diagnosed with cancer, excluding conference abstracts, case studies, other reviews, and meta-analyses, and screened the articles. RESULTS: Eight studies were included in this meta-analysis. We observed significant improvements in QOL and clinical data in 3 of 6 studies and in one study, respectively, significant weight loss on anthropometry in 2 of 5 studies, and dietary improvement in 4 of 5 studies of adult cancer survivors. However, we did not observe any benefits of dietary intervention for cancer survivors with undernutrition. DISCUSSION: Dietary interventions for adult cancer survivors might contribute to improving their nutritional status; however, further clarification requires a study that standardizes the intervention method. Furthermore, RCTs are required to determine the effects on cancer survivors with undernutrition.

Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction.

Nutritional factors play a key role in the pathogenesis of biliary diseases such as gallstones and pancreaticobiliary maljunction. Gallstones are primarily classified into cholesterol stone and pigment stone according to the major composition. Cholesterol gallstone formation is very likely based upon supersaturated bile formation, and pigment stones are formed in bile rich in bilirubin. Thus, defects of hepatic metabolism of lipids and organic anions lead to biliary stones. Here, the recent understanding of cholesterol gallstone pathogenesis is elaborated. On the other hand, there is another important link of biliary lipid degradation to serious biliary disease, namely pancreaticobiliary maljunction. Lysophosphatidylcholine (lysoPC), a derivative of phosphatidylcholine hydrolysis by phospholipase A2, is a highly abundant bioactive lipid mediator present in circulation as well as in bile. Increases in bile of lysoPC and phospholipase A2 have been reported in pancreaticobiliary maljunction and considered to be the major risk factor for biliary tract cancers. Further, oxidized fatty acids have been established as a potent ligand for G2A, a member of G protein-coupled receptor family that mediates a diverse array of biological processes including cell growth and apoptosis. Thus, both of lysoPC and free fatty acids are supposed to play an important role through G2A in biliary inflammation and carcinogenesis of pancreaticobiliary maljunction. Taken together, nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases, and such a causal relationship is reviewed by mainly authors' previous publications.

Roles considered important for hospitalist and non-hospitalist generalist practice in Japan: a survey study.

BACKGROUND: An increased focus on quality and patient safety has led to the evolution of hospitalists. The number of hospitalists covering ward and outpatient care is on the rise in Japan. However, it is unclear what roles hospital workers themselves consider important in their practice. Therefore, this study investigated what hospitalists and non-hospitalist generalists in Japan consider important for the practice of their specialty. METHODS: This was an observational study that included Japanese hospitalists (1) currently working in a general medicine (GM) or general internal medicine department and (2) working at a hospital. Using originally developed questionnaire items, we surveyed the items important to hospitalists and non-hospitalist generalists. RESULTS: There were 971 participants (733 hospitalists, 238 non-hospitalist) in the study. The response rate was 26.1%. Both hospitalists and non-hospitalists ranked evidence-based medicine as the most important for their practice. In addition, hospitalists ranked diagnostic reasoning and inpatient medical management as the second and third most important roles for their practice, while non-hospitalists ranked inpatient medical management and elderly care as second and third. CONCLUSIONS: This is the first study investigating the roles Japanese hospitalists consider important and comparing those to that of non-hospitalist generalists. Many of the items that hospitalists considered important were those that hospitalists in Japan are working on within and outside academic societies. We found that diagnostic medicine and quality and safety are areas that are likely to see further evolution as hospitalists specifically emphasized on them. In the future, we expect to see suggestions and research for further enhancing the items that hospital workers value and emphasise upon.

Contributions of Japanese Hospitalists During the COVID-19 Pandemic and the Need for Infectious Disease Crisis Management Education for Hospitalists: An Online Cross-Sectional Study.

Introduction: Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists' awareness of crisis management education remain unclear. Material and Methods: We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion. Results: We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that "training of personnel who can provide practical care for emerging infectious diseases is necessary", 78.4% indicated that "the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary", and 74.2% stated that "the establishment of an educational system for responding to emerging infectious diseases is necessary.". Conclusion: In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.

Focal Neurological Symptoms at Initial Presentation Could Be a Potential Risk Factor for Poor Prognosis Among Patients With Multiple Brain Abscesses by Streptococcus anginosus Group: A Case Report With Literature Review.

Streptococcus anginosus group (SAG) is one of the most common microbes of brain abscesses. Brain abscesses caused by SAG have often delayed diagnosis since both blood and cerebrospinal fluid cultures are negative in half of the cases. A 68-year-old man developed persistent fever, headache, and myalgias for two weeks and visited our department. He was treated with oral antibiotics without laboratory work. Although examination showed no focal neurological symptoms, a careful interview revealed a history of unusual behavior for a few minutes on the previous day. Whole body contrast-enhanced computed tomography (CT) and head magnetic resonance imaging (MRI) showed two ring enhancements close to the bilateral ventricles, which were consistent with a diagnosis of the brain abscesses. An emergent surgical puncture for the larger abscess with intravenous antimicrobial therapy quickly improved his condition, and he was discharged on day 36 with no sequelae. We retrospectively reviewed works of literature on cases with multiple brain abscesses by SAG to assess potential prognostic factors for neurological sequelae. Statistical analyses of 12 cases, including 11 cases from the literature review and the current case, were performed between groups with or without poor prognosis. Among potential risk factors of age, sex, focal neurological symptoms, duration from onset to treatment, abscess formation of other organs, presence of surgical drainage, and positive for blood culture, only focal neurological symptoms at the initial presentation were significantly associated with poor prognosis (no poor prognosis, 1/4 cases vs poor prognosis group, 8/8 cases; p=0.01). Careful interviews and detailed examinations should be conducted to assess the possibility of brain abscesses among patients with fever of unknown etiology. Otherwise, a delayed diagnosis might result in poor prognoses such as death or neurological sequelae due to this disease's nature, which has few specific symptoms in the early stages.