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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

BACKGROUND/PURPOSE Klebsiella pneumoniae bacteremia-induced sepsis is a clinically important condition with a high mortality rate and various known virulence factors. However, studies on the association of these virulence factors with the occurrence of K. pneumoniae bacteremia-induced sepsis are scarce. We aimed to investigate clinical variables and virulence factors in patients with K. pneumoniae bacteremia-induced sepsis. METHODS We retrospectively reviewed the medical records of 76 patients with K. pneumoniae bacteremia between January 2012 and July 2017. Patients were divided into sepsis (n = 25) and non-sepsis (n = 51) groups. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. We assessed the distribution of virulence factors related to K. pneumoniae, such as mucoviscosity, capsular polysaccharide, and siderophores. Siderophore production levels were determined by measuring the orange halo zone on chrome azurol S agar plate assay. RESULTS There were no intergroup differences in male-to-female ratio and age. Multivariable analysis revealed that siderophore production level (p

BackgroundHealthcare workers (HCWs) who care for patients with the novel coronavirus infectious disease (COVID-19) are at an increased risk and fear contracting the infection themselves. HCWs are chronically exposed to very intense stress, both and physically and mentally. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients. This study aimed to investigate the occupational risk among HCWs of experiencing physical symptoms during the current COVID-19 pandemic.MethodsA twice-weekly questionnaire targeting HCWs who care for COVID-19 patients was performed at Osaka City University Hospital from April 30 to May 31, 2020 using a shareable Research Electronic Data Capture tool. The demographic characteristics of the participants, frequency of exposure to at-risk care, and physical complaints were evaluated.ResultsA total of 35 doctors, 88 nurses, and 35 technicians were engaged in the care of these critically ill COVID-19 patients. 76 HCWs participated in this study, of whom 24 (31.6%) were doctors, 43 (56.6%) were nurses, and 9 (11.8%) were technicians. The frequency of experiencing any physical symptom was 25.0% among HCWs. Exposure to at-risk care was significantly higher among nurses than among doctors (p < 0.001); likewise, the frequency of experiencing physical symptoms was higher among nurses than among doctors (p < 0.01). The multivariate analysis revealed that nurses (odds ratio 8.29; p = 0.01) might be independently at risk of experiencing physical symptoms.ConclusionsOur results indicate that occupational health care at hospitals must be allocated to HCWs who are highly exposed to at-risk care, particularly nurses engaged in the care of COVID-19 patients.

Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function.Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables.EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048).EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Background After the A/H1N1 influenza pandemic in 2009, two new drugs against influenza, namely laninamivir and peramivir, were released in 2010 in Japan. We investigated prescription trends of four neuraminidase inhibitors (NAIs), which are laninamivir, peramivir, oseltamivir, and zanamivir, and assessed clinical data related to influenza for 8 years. Methods Patients living in Osaka Prefecture and diagnosed with influenza responded to a postcard questionnaire that collected data regarding their demographic characteristics, symptoms including fever, prescribed drugs, and influenza type. Results Laninamivir was most prescribed to patients aged ≥ 10 years, and oseltamivir was most prescribed to patients aged, We showed the data of eight seasons and report prescription trends of four neuraminidase inhibitors (NAIs) and time course of fever in patients after taking these inhibitors. Doctors, especially general physicians, should consider how to choose anti‐influenza drugs. This study based on our 8‐year survey should be helpful to them when deciding which NAIs should be chosen in clinical settings and for which patients.

Klebsiella pneumoniae bacteremia is a critical clinical presentation that is associated with high mortality. However, extremely few studies have investigated the virulence factors related to mortality of K. pneumoniae bacteremia in patients. The present study elucidated clinical and virulence factors associated with the 30-day mortality of K. pneumoniae bacteremia at a tertiary hospital. The medical records of 129 patients with K. pneumoniae bacteremia admitted to Osaka City University Hospital between January 2012 and December 2018 were retrospectively reviewed. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. Additionally, virulence factors were assessed using multiplex polymerase chain reaction to elucidate their association with K. pneumoniae. The 30-day mortality was 10.9% in patients with K. pneumoniae bacteremia. The male-to-female ratio, age, and underlying disease did not differ between the non-survivor and survivor groups. Multivariate analysis showed that sepsis (odds ratio (OR), 7.46; p = 0.005) and iutA (OR, 4.47; p = 0.046) were independent predictors associated with the 30-day mortality of K. pneumoniae bacteremia. Despite the relatively low 30-day mortality of patients with K. pneumoniae bacteremia, the treatment of those with sepsis and those infected with K. pneumoniae harboring iutA may require careful management for improving their outcomes.

The coronavirus disease 2019 outbreak has made it difficult to hold face-to-face BLS training sessions at university. Even in this limited situation, the effective use of combined online video course and offline training can contribute to gaining participants' confidence in conducting BLS and improving mindset than before.

リファンピシンが粘液活性を減少させ、高病原性肺炎桿菌の病原性を低下させることを見出した。, A recent increase in the incidence of hypervirulent Klebsiella pneumoniae (hvKP) infections, especially those caused by a sublineage of the clonal group CG23 (CG23-I), is raising serious health concerns worldwide. The high virulence of hvKP is, at least in part, attributed to the overproduction of capsular polysaccharide (CPS), which is triggered by a positive regulator of capsular polysaccharide synthesis (cps) genes, named RmpA. Although extensive research has been conducted on the mechanisms ofhvKP virulence, no study has focused on the development of anti-virulence therapeutics....

This study aimed to assess the prognostic factors of patients with bacteremia due to extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-PE) as well as the antimicrobial susceptibility, particularly to piperacillin/tazobactam (PTZ), among ESBL-PE strains. The medical records of 65 patients with ESBL-PE bacteremia divided into the survivor group (n = 52) and nonsurvivor group (n = 13) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, leukocyte count, C-reactive protein level, and treatment did not differ between the 2 groups. Multivariate analysis showed that the independent predictors associated with hospital mortality of ESBL-PE bacteremia were sepsis (P = 0.047) and febrile neutropenia (P = 0.008); thus, early assessment of these conditions is important. Further, the minimum inhibitory concentration values of ESBL-PE isolates in nonsurvivors tended to be higher than those in survivors. PTZ should be used with caution in cases of ESBL-PE strains with low susceptibility to the drug.

Background Smoking predisposes individuals to endothelial dysfunction. Both flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, there are differences in the physiology of vascular beds being tested and in the response of conduit and resistive vessels to RH. Therefore, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and by RH-PAT remains unclear. Purpose We aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT. Methods Thirty-eight consecutive current smokers (mean±standard deviation; age, 65±10 years) who visited our smoking cessation outpatient department and succeeded in smoking cessation with varenicline were enrolled. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. Fifteen current smokers who failed in smoking cessation were enrolled as age- and sex-matched controls. The Spearman's rank correlation coefficient and intraclass correlation coefficient (ICC) for a two-way mixed effects model were performed to assess the agreement of changes in FMD and Ln-RHI. Multivariate logistic regression analysis was performed to examine the associations between the presence of increase in FMD or Ln-RHI and clinical variables. Results FMD significantly improved after smoking cessation (3.42%±1.96% to 4.45%±2.28%; p=0.019), whereas Ln-RHI did not (0.53±0.25 to 0.59±0.21; p=0.223). The Spearman's rank correlation coefficient between changes in FMD and Ln-RHI was −0.013, and the ICC was −0.002 (p=0.506). In the multivariate logistic regression analysis, an increase in FMD or Ln-RHI was predicted based on the baseline FMD (odds ratio = 0.54, p=0.013) or Ln-RHI (odds ratio = 0.36, p=0.012), respectively, after adjusting for age and sex. Conclusions There was significant improvement in the endothelial function assessed by FMD, but not by Ln-RHI, after smoking cessation. In addition, there was disagreement between changes in FMD and those in Ln-RHI. Smoking cessation may have varying effects on the endothelial function of the conduit and digital vessels. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-aid for scientific research from the ministry of education, science and culture of Japan

Smoking predisposes individuals to endothelial dysfunction. Flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and RH-PAT remains unclear. Thus, we aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT and clarify the factors associated with these effects. Fifty-eight consecutive current smokers (mean ± standard deviation; age, 64 ± 11 years) who visited our smoking cessation outpatient department and succeeded with smoking cessation were enrolled. Twenty-one continued smokers were enrolled as age- and sex-matched controls. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. In 58 smokers who succeeded with smoking cessation, FMD significantly improved (3.80 ± 2.24 to 4.60 ± 2.55%; p = 0.013), whereas Ln-RHI did not (0.59 ± 0.28 to 0.66 ± 0.22; p = 0.092). Spearman’s rank correlation coefficient between changes in FMD and Ln-RHI was −0.004, and the intraclass correlation coefficient for a two-way mixed effects model was

Background Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well-known for preventing cardiovascular disease. Among n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play key roles in preventing cardiovascular diseases. However, the effects of n-3 PUFAs have been examined under conditions of simultaneous administration of EPA and DHA in the majority of clinical investigations and the effect of purified EPA is still controversial. EPA has been reported to improve endothelial dysfunction. Although several mechanisms underlying the effects of EPA on endothelial function have been demonstrated such as the modulation of lipid metabolism including increases in high-density lipoprotein (HDL) and/or decreases in triglyceride (TG) levels, decreases in cytokine production, and inhibition of inflammatory processes, the main mechanisms ameliorating endothelial function have not been fully determined. Purpose We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. Methods Fifty-one consecutive patients with hypertriglyceridemia (mean ± SD age, 60±13 years) with no evidence of coronary artery disease (CAD) were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-eight patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables such as body mass index, HbA1c, fasting glucose level, HDL, low-density lipoprotein, TG, systolic blood pressure, diastolic blood pressure, heart rate, interleukin-6, baseline diameter of the brachial artery, intima-media thickness of the brachial artery, and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed to examine the associations between FMD changes and clinical variables. Results FMD was significantly improved from 4.16% ± 1.88% to 6.30% ± 2.24% (p Conclusions EPA treatment improves endothelial dysfunction in patients with hypertriglyceridemia without evidence of CAD. The change in FMD was associated with the change in EPA/AA ratio alone. These finding suggest that a direct effect of EPA on the endothelium may be the predominant factor ameliorating endothelial function. Acknowledgement/Funding This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (15K08649).

A 42‐year‐old man with schizophrenia was referred to our hospital after 2 weeks of worsening fatigue. His hemoglobin level was 2.8 g/dL owing to folic acid deficiency stemming from alcohol abuse and consumption of unbalanced meals. We induced behavioral changes in the patient by motivational interviewing. We had direct methodical conversations with medical staff involved with the patient as well as his family, and established new social support for him as well as public assistance. These have resulted in the patient maintaining a favorable lifestyle ever since.

Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli). Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated. Results The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL E. coli bacteremia and non-ESBL E. coli bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL E. coli bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL E. coli bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p=0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL E. coli bacteremia. Conclusion Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL E. coli in mind.

This study aimed to assess the predictive factors of bacteremia due to hypermucoviscous Klebsiella pneumoniae (hvKP), as well as the mortality. The medical records of 114 patients with K. pneumoniae bacteremia who were divided into the hvKP (n = 24) and non-hvKP (n = 90) groups and were retrospectively reviewed. The male-to-female ratio, age, and underlying disease did not differ between the 2 groups. Mortality was higher among patients in the hvKP bacteremia group than in the non-hvKP bacteremia group (29.2% vs 6.7%). Multivariate analysis showed that the independent predictors associated with hvKP bacteremia were abscess (P = 0.01) and no antibiotic exposure (P = 0.02); thus, early assessment of these conditions is important. For patients with a history of abscess and no antibiotic exposure, it is necessary to administer treatment while keeping the risk of hvKP in mind.

Background Detecting and treating dementia at an early stage are important. Although the Revised Hasegawa Dementia Scale (HDS-R) is commonly used to detect dementia, it takes about 10 min to complete. In contrast, the 1-min animal test (OMAT) takes only 1 min to complete and may be a helpful screening test for general practitioners in deciding whether to proceed with administering further diagnostic tests such as the HDS-R. We sought to examine the relationship between the OMAT and HDS-R scores, and determine the cut-off OMAT score that balanced the sensitivity and specificity in identifying HDS-R-positive patients. Methods A total of 122 consecutive patients with diabetes who visited the outpatient clinic at the Fujiidera Municipal Hospital were enrolled. The patients underwent the OMAT and HDS-R on the same day. Tests were conducted in a single-blinded manner. The relationship between the OMAT and HDS-R scores was examined using Spearman’s rank correlation. Receiver operating characteristic curve analysis was performed to identify the optimal cut-off score of OMAT that will determine whether to proceed with further diagnostic tests. Results A strong positive correlation between the OMAT and HDS-R scores was observed (r = 0.70). The sensitivity and specificity of OMAT using cut-off scores of 12/13, 13/14, and 14/15 for HDS-R-positive patients were 0.87 and 0.66, 1.00 and 0.51, and 1.00 and 0.40, respectively among all the subjects. Similar results were obtained in a subgroup of subjects aged ≥ 65 years. Conclusions A cut-off score of 13/14 on the OMAT balanced the sensitivity closest to 1.00 and allowed for the highest specificity for the HDS-R not only among all the patients, but also among just the patients aged ≥ 65 years. The OMAT may be an optimal screening test to determine whether to proceed with further diagnosis using HDS-R. Trial registration UMIN UMIN000025260. This study is retrospectively registered on December 13th, 2016

Enterococcus faecium has high levels of resistance to multiple antibiotics, and the mortality due to E. faecium bacteremia is high. Accordingly, E. faecium strains with low susceptibility to daptomycin are a concern in clinical practice. This study assessed the predictive factors and prognosis of patients with bacteremia due to E. faecium as well as the antimicrobial susceptibility, particularly to daptomycin, among E. faecium isolates. The medical records of patients admitted to Osaka City University Hospital with E. faecalis (n = 60) and E. faecium (n = 48) bacteremia between January 2011 and March 2016 were retrospectively reviewed. The E. faecalis group (mean age: 62.0 years) included 22 women, and the E. faecium group (mean age: 59.1 years) included 19 women. Predictive factors for infection, prognosis, and isolate antimicrobial susceptibilities were evaluated. The mean Sequential Organ Failure Assessment score and mortality rate did not differ between the two groups. The independent predictors of E. faecium bacteremia in multivariate analysis included quinolone use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p = 0.016). Cardiovascular disease was associated with a reduced risk of E. faecium bacteremia (p = 0.015). Notably, the percentage of E. faecium isolates with low daptomycin susceptibility was higher than that of E. faecalis (8.5% vs. 0%, p = 0.036). Thus, E. faecium should be considered when administering antibiotic therapy to patients with a history of these predictors. Furthermore, the use of daptomycin should be avoided in case of E. faecium with low susceptibility to daptomycin.

Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli). Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated. Results The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL E. coli bacteremia and non-ESBL E. coli bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL E. coli bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL E. coli bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p=0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL E. coli bacteremia. Conclusion Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL E. coli in mind.

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

Objective Smoking is associated with gastroesophageal reflux disease (GERD). Varenicline, a nicotinic receptor partial agonist, is used to aid smoking cessation. The purpose of this study was to prospectively examine the long-term benefits of smoking cessation on GERD and health-related quality of life (HR-QOL). Methods Patients treated with varenicline were asked to fill out a self-report questionnaire about their smoking habits, gastrointestinal symptoms, and HR-QOL before and 1 year after smoking cessation. The prevalence of GERD, frequency of symptoms, and HR-QOL scores were compared. We also investigated associations between clinical factors and newly-developed GERD. Results A total of 141 patients achieved smoking cessation (success group) and 50 did not (failure group) at 1 year after the treatment. The GERD improvement in the success group (43.9%) was significantly higher than that in the failure group (18.2%). The frequency of reflux symptoms significantly decreased only in the success group. There were no significant associations between newly developed GERD and clinical factors including increased body mass index and successful smoking cessation. HR-QOL significantly improved only in the success group. Conclusions Smoking cessation improved both GERD and HR-QOL. Smoking cessation should be recommended for GERD patients.

Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers.Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 μg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement.Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed.Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.

A 23-year-old Japanese man was admitted with a chief complaint of abdominal pain. He was previously healthy, and his past medical history was unremarkable. Local tenderness and rebound tenderness at McBurney's point were elicited. Abdominal roentgenography was non-diagnostic. Ultrasonography and computed tomography showed a tumor with a central core. Based on a diagnosis of appendicitis with omental inflammation or an omental tumor, laparotomy performed. Intraoperatively, no site of gastrointestinal perforation was detected; however, a 5-cm omental granuloma was identified that proved to have a fishbone nucleus on pathological examination. The postoperative course was uneventful, and upper gastrointestinal endoscopy and barium enema were unremarkable. A large solitary omental pseudotumor is rare, and the clinical course in this case was atypical compared with the usual course of intestinal perforation by a foreign body and formation of an intra-abdominal granuloma.

Interferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC.Risk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response).According to a univariate analysis, large tumor (2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery.An anatomic resection with an appropriate surgical margin (or = 5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.

Background Most cases of disseminated carcinomatosis of the bone marrow (DCBM) arise from gastric cancer. DCBM from pancreatic cancer is very rare. We herein present a case of DCBM from pancreatic cancer. Case presentation A 57-year-old man was referred to our hospital for severe lumbago. Laboratory data indicated that he suffered from disseminated intravascular coagulation (DIC). Non-contrast abdominal computed tomography (CT) revealed multiple bone masses but no other abnormal findings. Left iliac bone marrow biopsy revealed poorly differentiated adenocarcinoma cells. Positron emission tomography (PET)-CT showed diffuse abnormal uptake in the bones and tail of the pancreas. Contrast whole-body CT showed a tumor measuring approximately 28 mm in diameter with poor enhancement in the tail of the pancreas. The patient’s final diagnosis was pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC. His DCBM was thus believed to originate from the pancreatic cancer. He succumbed to the disease approximately 2 months after admission to our hospital. Conclusion We herein describe a case of pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC, which, in our case, was DCBM. Therefore, in cases of DCBM with an unknown primary tumor, pancreatic cancer should be considered during differential diagnosis.

Pancreatoduodenectomy can be difficult in patients with obstruction of the celiac axis because of the development of collateral arteries around the head of the pancreas. Bleeding from a pseudoaneurysm is a rare and serious complication of pancreatoduodenectomy. We report a case of a pseudoaneurysm of an enlarged dorsal pancreatic artery, which formed as a result of obstruction of the celiac axis after pancreatoduodenectomy. We assumed that a weakness in the wall of this dorsal pancreatic artery caused by the dissection led to the formation of the aneurysm. Although transcatheter arterial embolization (TAE) could not treat the aneurysm or stop bleeding from the aneurysm completely, it achieved transient hemostasis, whereby the patient's condition improved, making laparotomy safe. This case demonstrates that the dissection of arteries that have developed around the head of the pancreas must be considered in patients with obstruction of the celiac axis.

The etiologic role of alcoholic liver disease for hepatocellular carcinoma is uncertain. To assess the role of alcoholic liver disease on the development of carcinoma, we examined history of alcohol abuse and viral markers in the sera and/or resected specimens in 454 patients who underwent liver resection for hepatocellular carcinoma. Sera from 20 of the 454 patients were negative for hepatitis B, C, and D viruses. Of the 20 patients, one patient had autoimmune hepatitis, one had primary biliary cirrhosis, two had non-alcoholic steatohepatitis. Of the remaining 16 patients, 8 patients were alcohol abusers and 5 of the 8 patients were heavy alcohol abusers. Hepatitis G virus was not detected in sera form the 16 patients. Although hepatitis B x gene was detected in the cancerous and/or non-cancerous tissues in all three alcohol abusers but not heavy abusers and in 5 of 6 non-alcohol abusers whose surgical specimens were available, the gene was detected in only one of the five heavy alcohol abusers. The five heavy alcohol abusers had advanced hepatic fibrosis and active hepatitis. Alcoholic liver disease with advanced hepatic fibrosis and active hepatitis is a possible cause for the development of hepatocellular carcinoma.

症例は53歳,女性.慢性B型肝炎と肝S7腫瘍に対する経過観察中, 2004年12月のCT像上,同腫瘍径が軽度増大した.副腎皮質ホルモン亢進に伴う症状はなく,血液検査上軽度の肝機能障害が認められるのみであった.単純CT像上,径1.6cm大の境界明瞭な低吸収像, dynamic CT早期相において淡く濃染され,晩期相において造影剤はwash outされていた.右肝動脈造影下CTでは腫瘍の大部分は高吸収域として描出された.以上より肝細胞癌と診断,開腹したところ,右副腎は腫瘍と周囲肝実質と強固に癒着していたため,右副腎合併肝部分切除を施行した.腫瘍割面は径1.6cm,黄色調で被膜は認めないものの周囲との境界は明瞭であった.組織学的に腫瘍は副腎と連続性があり肝を圧排していた.脂肪滴を含んだ泡沫状の明るい胞体をもつ淡明型細胞が認められ,副腎腺腫と診断された.肝内に存在するように描出され,肝動脈から栄養されていたため肝細胞癌との術前鑑別が困難であった副腎非機能腺腫例であった.

We investigated the correlation between serum concentrations of type IV collagen 7s domain (7s collagen) and changes in the volume of the nonembolized liver lobe after subsequent portal vein embolization (PVE).The relationship between the pre-embolization results of laboratory tests and the increase in the left lobe volume was evaluated in 32 patients who underwent preoperative PVE via the right portal vein.By 2 weeks after PVE, the mean volume of the left lobe had increased significantly (P0.001). The percent increase in the left lobe volume correlated negatively with the pre-embolization serum concentration of 7s collagen (r = -0.472, P = 0.0063). In three of four patients with high serum concentrations (8 ng/ml), the percent increase was less than 100% and right lobectomy was not performed. The serum 7s collagen concentration correlated with the histologic activity score (r = 0.469, P = 0.0061) and the histologic fibrosis score (r = 0.425, P = 0.0145).The serum concentration of 7s collagen may predict the efficacy of PVE. Performing PVE before right lobectomy may not be indicated in patients with high serum concentrations of 7s collagen because the increases in left lobe volume may be insufficient.

Background The prognosis of hepatocellular carcinoma originating in or mainly involving the caudate lobe (caudate HCC) is generally poor. We reviewed the clinicopathologic findings of patients who underwent liver resection of caudate HCC and correlated the outcome with the surgical strategy. Methods Records of 402 patients who underwent liver resection for HCC were reviewed. The patients were divided into 2 groups. One group consisted of 15 patients who underwent liver resection for caudate HCC. The other group included 387 patients with HCC in a site other than the caudate lobe. Results Anatomic resection of Couinaud segment I or IX (a partial caudate lobectomy), conforming to portal anatomy, was performed in 13 patients with caudate HCC, and segmentectomies of segments I and IX (a total caudate lobectomy) were performed in 2 patients with caudate HCC. The incidence of postoperative complications was similar in the caudate HCC group and HCC in other sites group, with no operative deaths in the caudate HCC group. Tumor-free survival and cumulative survival were similar in the 2 groups. However, among patients with caudate HCC, tumor-free and cumulative survival were lower in patients with than without microscopic portal venous involvement ( P Conclusions Partial caudate lobectomy (anatomic resection of segment I or IX) along the portal system is an appropriate procedure for caudate HCC, especially in patients with impaired liver function or a small HCC. Patients with caudate HCC who have microscopic portal venous involvement may require adjuvant therapy as early recurrence is likely.

To determine the predictive value of the preoperative serum concentration of type IV collagen 7s domain (7s collagen) for postoperative hepatic failure in patients undergoing liver resection for hepatocellular carcinoma.Clear and reliable criteria for predicting hepatic failure after liver resection are needed. The serum 7s collagen concentration correlates with the histologic degree of active hepatitis and hepatic fibrosis and may predict the regenerative potential of the liver.Potential risk factors for postoperative hepatic failure, including the serum 7s collagen concentration, were evaluated in 251 patients who underwent liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses.Hepatic failure developed postoperatively in 25 patients, 4 of whom died. The serum 7s collagen concentration correlated with the histologic degree of hepatitis activity and hepatic fibrosis. The serum 7s collagen concentration was a risk factor for postoperative hepatic failure by univariate analysis and was the only risk factor on multivariate analysis. No patient with a serum 7s collagen concentration12 ng/mL died of postoperative hepatic failure, and all 4 patients who died had a serum 7s collagen concentrationor=12 ng/mL.The preoperative serum 7s collagen concentration correlated independently with hepatic failure following liver resection for hepatocellular carcinoma. Patients whose serum 7s collagen isor=12 ng/mL are poor candidates for hepatic resection.

To better understand how benign hepatocellular tumors acquire nutrient vessels, we investigated the angioarchitecture of the smallest vessels in hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH). In biopsy or resection specimens, microscopic angioarchitecture was characterized in terms of intratumoral fibrous septa and portal tract. Immunohistochemistry for CD34, factor-VIII-related antigen (F-VIII), type IV collagen (collagen IV), α-smooth muscle actin (α-SMA), and CD68 was performed. HA had no portal tract in fibrous septa although FNH showed portal tract in fibrous septa. The smallest vessels in HA stained diffusely for CD34, and arterial segments of the smallest vessels were stained for F-VIII, and collagen IV. Pericyte surrounding the smallest vessels in HA were stained for α-SMA. The smallest vessels in all but one FNH specimen stained for CD34, F-VIII, collagen IV, and α-SMA along portal tract or the artery. Both HA and FNH stained for CD68, as did normal liver. The results indicate that the smallest vessels in HA and FNH are incomplete capillaries, that have both characters of sinusoid and capillaries morphologically and phenotypically, i.e., capillarized sinusoid as in chronic hepatitis or early well-differentiated hepatocellular carcinoma. Benign hepatocellular tumors such as HA and FNH would acquire new vessels gradually by sinusoidal capillarization, not by rapid arterial angiogenesis.