Clinical relevance of procalcitonin values in bacteremia.

INTRODUCTION: The aim of this study was to investigate procalcitonin levels according to the causative pathogens of bacteremia. The relationships between the clinical outcomes and procalcitonin levels were also studied. METHODS: From among 452 patients, 507 cases of positive blood culture were included in the present study. Procalcitonin levels were studied according to the pathogen types. The prevalence of septic shock and the mortality rates were also studied in four groups stratified by the procalcitonin levels (groups 1, 2, 3, and 4 had procalcitonin levels of <0.5 ng/mL, 0.5 ≤ 2.0 ng/mL, 2.0 < 10 ng/mL, and ≥10 ng/mL, respectively). RESULTS: The procalcitonin levels were significantly higher in bacteremia cases with Gram-negative rods (19.50 ng/mL), such as Escherichia coli (32.5 ng/mL), than those with Gram-positive rods (8.45 ng/mL) or Gram-positive cocci (9.21 ng/mL) (p < 0.01). The 28-day mortality rates in groups 1, 2, 3, and 4 were 6.0%, 12.0%, 14.9%, and 19.8%, respectively. The procalcitonin levels of samples taken before or on the same day of blood cultures were significantly lower than those taken one day after blood cultures. Multiple logistic regression analysis showed that C-reactive protein and procalcitonin ≥10 ng/mL were independently associated with a higher risk of mortality within 28 days. CONCLUSIONS: The PCT levels were higher in cases of bacteremia caused by GNR than those caused by GPR or GPC. The 28-day mortality rate increased as the PCT levels increased. Clinical importance of early evaluations and appropriate interpretation of procalcitonin levels for bacteremia were indicated.

Impact on Antifungal Susceptibility Patterns of Previous vs. Revised Clinical and Laboratory Standards Institute Breakpoints for Candida Species Isolated from Candidemia: Experience of Two Tertiary Care Institutions in Japan.

BACKGROUND: Candidemia has a high mortality rate. Identifying prognostic factors of candidemia, based on each regional data, is essential for better management. The Clinical and Laboratory Standards Institute (CLSI) recently revised Candida species-specific breakpoints (R-BP) for antifungal agents. Few studies have investigated the detection performance of resistance in Candida species by comparing the R-BP and previous species non-specific CLSI breakpoint (P-BP) among patients with candidemia. The primary objective was to investigate the impact of the R-BP on the antifungal susceptibility patterns of Candida species, while the secondary objective was to identify the prognostic factors of candidemia. METHODS: A total of 193 Candida species isolated from 187 patients with candidemia between January 2007 and December 2016 were examined. Susceptibility based on CLSI M27-A3 was defined as the P-BP and based on species-specific CLSI M59 or M60 breakpoint was defined as the R-BP. Multivariate Cox's hazard analysis was performed to identify prognostic factors within 30 days of the diagnosis of candidemia. RESULTS: A significant difference was observed in the susceptibility rate to fluconazole (FLCZ) (P-BP; 93.0% vs. R-BP; 79.4%) and to voriconazole (VRCZ) (P-BP; 97.2% vs. R-BP; 91.0%). The susceptibilities of C. parapsilosis, C. glabrata, and C. tropicalis to azole antifungal agents were markedly lower with the R-BP. Based on the R-BP, anti-fungal therapy was regarded as inappropriate for approximately 10% of the patients. The 30-day mortality rate was 29.4%. In a multivariate Cox's hazard analysis, age, lung disease, C. albicans, and the absence of antifungal therapy were associated with a high mortality rate, whereas serum albumin, C. parapsilosis, surgical wards, the removal of central venous catheter (CVC), and follow-up blood culture tests to confirm the clearance of Candida species were associated with a lower mortality rate. CONCLUSIONS: Early initiation of antifungal therapy, removal of CVC, and follow-up blood culture tests are essential for improving the outcome. The R-BP efficiently detected non-susceptible strains to FLCZ and VRCZ, particularly in non-albicans Candida species. The present results support the importance of antifungal susceptibility tests and interpretations based on the R-BP among patients with candidemia.

Anti-E Detected in a 7-Month-Old Infant with Acute Lymphoblastic Leukemia after Transfusion.

BACKGROUND: Only a few cases of infantile anti-red blood cell alloantibody production have been reported. METHODS: A 7-month-old girl with acute lymphoid leukemia developed anti-E alloantibody 13 days after transfusion of E-positive red blood cells. Antibody screening was performed before and at 2, 6, 13, 18, 27, 34, and 49 days after red blood cell transfusion. Identification test, direct immunoglobulin test, acid elution, and dithiothreitol test were also performed. RESULTS: Anti-E alloantibody was detected in the blood 13 days after the first transfusion. The detected antibody was IgM and it decreased below detectable levels within 49 days after the first transfusion. CONCLUSIONS: Follow-up testing for the presence of post-transfusion alloantibody at appropriate times is important, even in infants.

Intracellular Storage of Duffy Antigen-Binding Chemokines by Duffy-Positive Red Blood Cells.

BACKGROUND: Duffy antigen/chemokine receptor (DARC) is a non-signaling receptor for multiple chemokines. The role of DARC on red blood cells (RBCs) has remained elusive. The purpose of this study was to analyze selective storage of DARC-binding chemokines in RBCs. METHODS: Peripheral blood from healthy volunteers with DARC-positive blood type was collected in EDTA tubes. The concentration of DARC binding chemokines (i.e., MCP-1, RANTES, eotaxin-1, TARC, and IL-8), DARC nonbinding chemokines (i.e., MIP-1α, IP-10), and several cytokines in the supernatant of purified RBCs before and after hemolysis was measured using Bio-Plex and ELISA assays. Storage of chemokines in RBCs and the expression of DARC were evaluated using flow-cytometry. RESULTS: The levels of all DARC-binding chemokines except TARC and IL-8 increased significantly after hemolysis. There was no significant increase in any of the DARC non-binding chemokines or in the other cytokines after hemolysis. RANTES, eotaxin-1, and MCP-1 were detectable intracellularly but not on the RBC surface. RANTES was absorbed by RBCs. DARC was expressed intracellularly in RBCs as well as on the surface. CONCLUSIONS: These data suggested that DARC-positive RBCs store RANTES, MCP-1 and eotaxin-1. DARC on RBC may be internalized from the surface in the process of chemokine absorption.

Surgical treatment of unruptured distal basilar artery aneurysm: durability and risk factors for neurological worsening.

BACKGROUND: Distal basilar artery aneurysms (DBAs) consist of basilar apex and basilar artery-superior cerebellar artery bifurcation (BA-SCA) aneurysms. The authors aimed to investigate clinical and radiological differences between two locations and to evaluate the 12-month surgical outcome in unruptured DBAs. METHODS: Fifty-six consecutive patients who underwent surgical treatment (37 basilar apex and 19 BA-SCA aneurysms) between April 2012 and February 2016 were retrospectively evaluated. In patients with a preoperative modified Rankin Scale score (mRS) of more than 1, neurological worsening (NW) was defined as an increase in one or more mRS. In patients without symptoms, NW was defined as mRS ≥2. RESULTS: The mean age of the patient population was 64 ± 9.6 years, and 48 (86%) were female. Mean follow-up period was 2.6 ± 0.94 years. An excellent (mRS 0 to 1) outcome was archived in 31 (55%), 45 (82%), and 48 (87%) patients at 30 days, 6 months, and 12 months, respectively. Clinical and radiological characteristics showed no differences between two locations. One early death (1.8%) and one severe morbidity (1.8%) due to rupture were observed. The postoperative annual rupture rate was 1.4% overall (145 patient-years). After adjustment for age and location, large or giant DBA was related to 30-day and 12-month NW [n = 22 (39%) and n = 6 (11%); p = 0.009 and 0.002, respectively], aneurysm localization in the interpeduncular cistern (LIC) and perforator territory infarction were related to 30-day NW (p = 0.002 and 0.002), and DBA that needed bypass surgery and previously treated recurrent DBA were related to NW at 12 months (p = 0.017 and 0.001). Multivariate analysis showed that LIC was significantly related to perforator territory infarction (p = 0.003). CONCLUSIONS: Clinical and radiological characteristics were not different between basilar apex and BA-SCA aneurysms; therefore, they should not be discussed separately. To avoid neurological worsening, results of surgical treatment for unruptured DBAs should be improved.

Possible involvement of reusable towels in the high rate of Bacillus species-positive blood cultures in Japanese hospitals.

BACKGROUND: A number of outbreaks caused by Bacillus species have been reported to date. Outbreaks reported in the last decade have predominantly arisen in Japanese hospitals. AIM: To elucidate factors contributing to these real or pseudo outbreaks by Bacillus species, and to evaluate the rate of Bacillus species-positive blood culture samples in Japan. METHODS: A systematic review of the literature was performed. Reports including data on outbreaks caused by Bacillus species were searched for in PubMed, Google Scholar and Evidence-based Medicine BMJ from inception through 10 Aug 2014. Japanese nationwide data on bacteriological tests were collected from Japan Nosocomial Infections Surveillance. Regional bacteriological data for Akita prefecture were collected using the Akita Regional Network for Infection Monitoring/Control System. FINDINGS: Contamination of reusable towels was suspected as a cause for the high rate of Bacillus-positive blood cultures in Japan. The rate of Bacillus species in blood cultures was much higher in Japan than in reports from other countries. CONCLUSIONS: The high contamination rate of blood culture samples by Bacillus species in Japan is a matter of concern for infection control and medical treatment. Bacteriological investigation of reusable towels should be considered in hospitals with a high frequency of Bacillus-positive blood cultures.

Management strategy for bilateral complex vertebral artery aneurysms.

Bilateral complex vertebral artery aneurysms (BCoVAAns) have no established strategy of management. We retrospectively reviewed five consecutive patients with unruptured BCoVAAns between January 2006 and December 2012. Considering surgical risks of lower cranial nerve (LCN) injuries and eventual growth of an opposite side lesion after unilateral vertebral artery (VA) occlusion, we proposed a strategy of combined open and interventional treatment using revascularization. We applied the following several specific techniques: (1) proximal clipping and occipital artery-posterior inferior cerebellar artery (OA-PICA) and/or superficial temporary artery (STA)-superior cerebellar artery (SCA) bypasses; (2) Distal blood pressure, motor evoked potentials (MEPs), and somatosensory evoked potentials (SEPs) monitoring after parent artery temporary occlusion for safe permanent occlusion of the proximal portions of VA and PICA; (3) V3 to V4 bypass using radial artery (RA) graft with proximal clipping or trapping, two of them combined with OA-PICA bypass; (4) VA fenestration as an opportunity to preserve the flow of the parent artery. Two patients were treated bilaterally and 3 unilaterally, with modified Rankin scale assessed at 39 months postoperatively in average 0 in 2, 1 in 2, and 2 in 1, respectively, and the untreated opposite side lesions without regrowth or bleeding. Two patients with patent V3-RA-V4 bypass complained of dysphagia due to LCN palsies. One of them however suffered a cerebellar infarction due to occlusion of the OA-PICA bypass. When BCoVAAns require surgical treatment, revascularization or preservation of the VA should be considered at the first operation. By doing so, the opposite aneurysm can be effectively occluded by coil embolization, even with VA sacrifice if required.

[Increase in Bacillus spp.-positive Blood Culture Specimens Linked to Inadequate Linen Management].

Bacillus cereus is a gram-positive rod-type bacterium that forms endospores and is distributed throughout various environments. It rarely causes disease in humans except for cases of food poisoning. However, infection with B. cereus in newborns and immunocompromised individuals can cause severe sepsis. Inappropriate catheter insertion and environmental contamination, including that of linen, are thought to be routes of transmission. Pseudo-outbreaks of B. cereus caused by poor hospital linen management have been reported and are important issues in hospitals. The number of Bacillus spp.-positive blood culture specimens increased in "A" ward of our hospital. Consequently, the hospital's infection control team was asked to determine the cause of the increase. We performed environmental research in the "A" ward and the entire hospital. In addition, we investigated the current status of B. cereus derection in five core hospitals in the North Tohoku region. In our hospital, B. cereus was detected in towels before use. When the timeline of contamination was investigated, we found that the towels had already been contaminated at the time they were delivered to our hospital. The linen washing contractor was unconcerned with laundry disinfection. As a result of our findings, disposable towels were introduced. This resulted in a decrease in Bacillus spp.-positive blood culture specimens. Among the five core hospitals in the North Tohoku region, the hospitals outsourcing laundry to contractors without bacteriological monitoring had a significantly higher rate of B. cereus-positive blood cultures than those of three other hospitals with infection control policies for towel management. The increase in Bacillus spp.-positive blood culture specimens in our hospital was a result of towel contamination. Based on these findings, we suggest that proper linen management(including that of towels) is crucial for infection control as well as the quality control of bacteriological tests.

Role of G-protein-coupled estrogen receptor in the pathogenesis of chronic asthma.

BACKGROUND AND AIM: G protein-coupled estrogen receptor (GPER) is an estrogen receptor located on the plasma membrane. We previously reported that the administration of G-1, a GPER-specific agonist, suppressed development of acute ovalbumin (OVA)-induced asthma in a mouse model. Herein, we evaluate the involvement of GPER in a mouse model of chronic OVA asthma. METHODS: G-1 or saline was administered subcutaneously to BALB/c mice with chronic OVA asthma, and pathological and immunological evaluation was performed. In addition, Foxp3-expressing CD4-positive T-cells in the spleen and ILC2 in the lungs were measured using flow cytometry. RESULTS: We observed a significant decrease in the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) in the G-1 treated group. In the airways, inflammatory cell accumulation, Th2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and epithelial cytokine TSLP were suppressed, while in the BALF, anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. Furthermore, in splenic mononuclear cells, Foxp3-expressing CD4-positive T-cells were increased in the G-1 group, whereas treatment with G-1 did not change the percentage of ILC2 in the lungs. CONCLUSION: G-1 administration suppressed allergic airway inflammation in mice with chronic OVA asthma. GPER may be a potential therapeutic target for chronic allergic asthma.

Multiple Blood Culture Sampling, Proper Antimicrobial Choice, and Adequate Dose in Definitive Therapy Supported by the Antimicrobial Stewardship Team Could Decrease 30-Day Sepsis Mortality Rates.

Objective: This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use. Methods: Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation. Results: The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased. Conclusion: Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.

[Role of university hospitals in regional infection control network].

Activities and the understanding of infection control in healthcare facilities have improved in the past decade since a certification system for medical personnel, such as infection control nurse and infection control doctor, were introduced in Japan. These specialists are distributed among tertiary general hospitals, while many small and mid-scale hospitals have no infection control specialists. In 2012, the Japanese Ministry of Health, Labour and Welfare launched a new strategy for further improvement of infection control by supporting a regional network of infection control activities. Through the infection control network, small or mid-scaled hospitals can utilize infection control specialists in tertiary general hospitals, enter educational programs on infection control and consult in cases of nosocomial infection outbreaks. As part of the regional infection control network, we established an information network system, named ReNICS, to share the bacteriological test results of the hospitals in Akita prefecture. ReNICS offers epidemiological data on bacteria identified in the region. We can identify the spread of multi-drug resistant bacteria and can roughly estimate the quality of infection control activities in each facility. As a similar information network is being prepared in Hirosaki University Hospital Infection Control Center in Aomori, a prefecture neighboring Akita, we discussed the roles of university hospitals for a regional infection control network.

Serum 3-Hydroxybutyrate is Expected to Serve as One of the Supportive Diagnostic Markers of Persistent Idiopathic Dentoalveolar Pain (PDAP).

Background: Persistent idiopathic dentoalveolar pain (PDAP), previously referred to as atypical odontalgia, is a chronic dental pain that occurs without signs of pathology. PDAP is considered a diagnosis of exclusion, and its definition is currently under refinement and remains ambiguous. The metabolite known as 3-hydroxybutyrate (3HB) has garnered significant interest as a potential indicator for both depression and chronic psychogenic pain. We investigated the characteristics of patients with PDAP and hypothesized that serum 3HB could support the diagnosis of PDAP. Subjects and Methods: Forty-one patients with PDAP and 167 patients with odontogenic toothache were investigated regarding depression and anxiety scales in addition to the general dental evaluation. Blood tests including high-sensitivity CRP, HbA1c, and 3HB were performed for all patients. Associations between PDAP and patients' varying characteristics were investigated using hierarchical multivariate logistic regression analyses. Results: There were more females, current smokers, patients with orofacial pain (such as temporomandibular joint pain, glossalgia, and headache), and people with elevated 3HB levels among patients with PDAP than among control participants. Multivariate logistic regression analyses predicting patients with PDAP identified the female sex (odds ratio [OR]: 4.16), current smoking (OR: 14.9), glossalgia (OR: 19.8) a high CES-D score (≥16) (OR: 5.98), and elevated serum 3HB (≥80 µmol/L) (OR: 18.4) factors significantly associated with PDAP. Conclusion: Our results demonstrated that serum 3HB levels could be elevated in patients with PDAP compared to other types of odontogenic pain, although 3HB was not specific to PDAP. Based on our findings, five factors - female sex, current smoking, depressive tendencies, chronic orofacial pains, and high serum 3HB levels - could be useful for diagnosing PDAP.

Chorioamnionitis and maternal sepsis caused by AmpC ß-lactamase-producing Escherichia coli infection: A case report.

INTRODUCTION: Multidrug resistant bacteria have increasingly become a concern regarding infection treatment. The clinical course of chorioamnionitis (CAM) caused by multidrug-resistant bacteria is not well understood. PRESENTATION OF CASE: We report a case of CAM caused by AmpC-type ß-lactamase (AmpC)-producing Escherichia coli (E. coli), a multidrug-resistant bacterium. A 35-year-old primipara was hospitalized with preterm membrane rupture at 36 weeks of gestation and was started on oral ampicillin. On the fourth day after admission, the patient was diagnosed with CAM owing to high fever development and uterine tenderness; therefore, an emergency cesarean section was performed. AmpC-producing E. coli were detected in blood and amniotic fluid cultures. Post-operation, the patient received treatment for septic shock and was discharged on the 15th post-operative day. DISCUSSION: The patient initially had no symptoms of infection but later experienced fever and uterine pain. She underwent an emergency cesarean section, and both mother and baby were successfully treated with broad-spectrum antibiotics. CAM associated with multidrug-resistant bacteria is more challenging to manage compared to infections in other parts of the body, as it occurs in unique environments such as the uterus, during pregnancy, and in the presence of compromised immunity. CONCLUSION: The development of new diagnostic criteria and effective biomarkers is needed to improve early detection, and adherence to standard precautions can help prevent the acquisition of multidrug-resistant bacteria in healthcare settings.

Impact of polymorphisms of pharmacokinetics-related genes and the inflammatory response on the metabolism of voriconazole.

The effects of inflammatory responses and polymorphisms of the genes encoding cytochrome P450 (CYP) (CYP2C19 and CYP3A5), flavin-containing monooxygenase 3 (FMO3), pregnane X receptor (NR1I2), constitutive androstane receptor (NR1I3), and CYP oxidoreductase (POR) on the ratio of voriconazole (VRCZ) N-oxide to VRCZ (VNO/VRCZ) and steady-state trough concentrations (C0h ) of VRCZ were investigated. A total of 56 blood samples were collected from 36 Japanese patients. Results of multiple linear regression analyses demonstrated that the presence of the extensive metabolizer CYP2C19 genotype, the dose per administration, and the presence of the NR1I2 rs3814057 C/C genotype were independent factors influencing the VNO/VRCZ ratio in patients with CRP levels of less than 40 mg/L (standardized regression coefficients (SRC) = 0.448, -0.301, and 0.390, respectively; all p < .05). With regard to the concentration of VRCZ itself, in addition to the above factors, the presence of the NR1I2 rs7643645 G/G and rs3814055 T/T genotypes were found to be independent factors influencing the VRCZ C0h in these patients (SRC = -0.430, 0.424, -0.326, 0.406 and -0.455, respectively; all p < .05). On the contrary, in patients with CRP levels of at least 40 mg/L, no independent factors were found to affect VNO/VRCZ and VRCZ C0h . Inflammatory responses, and CYP2C19 and NR1I2 polymorphisms may be useful information for the individualization of VRCZ dosages.

Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori, Japan.

BACKGROUND: Spread of vancomycin-resistant Enterococcus (VRE) is a global concern as a significant cause of healthcare-associated infections. A series of VRE faecium (VREf) outbreaks caused by clonal propagation due to interhospital transmission occurred in six general hospitals in Aomori prefecture, Japan. METHODS: The number of patients with VREf was obtained from thirty seven hospitals participating in the local network of Aomori prefecture. Thirteen hospitals performed active screening tests for VRE. Whole genome sequencing analysis was performed. RESULTS: The total number of cases with VREf amounted to 500 in fourteen hospitals in Aomori from Jan 2018 to April 2021. It took more than three years for the frequency of detection of VRE to return to pre-outbreak levels. The duration and size of outbreaks differed between hospitals according to the countermeasures available at each hospital. Whole genome sequencing analysis indicated vanA-type VREf ST1421 for most samples from six hospitals. CONCLUSIONS: This was the first multi-jurisdictional outbreak of VREf sequence type 1421 in Japan. In addition to strict infection control measures, continuous monitoring of VRE detection in local medical regions and smooth and immediate communication among hospitals are required to prevent VREf outbreaks.

Clinical characteristics and treatment outcomes of carbapenem-resistant Enterobacterales infections in Japan.

OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Serum 3-Hydroxybutyrate in Patients with Psychogenic Somatoform Symptoms May Be a Predictor of the Effectiveness of Sertraline and Venlafaxine.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are often used to treat outpatients with psychogenic somatoform symptoms but prove ineffective in some cases. The metabolite 3-hydroxybutyrate (3HB) is currently attracting attention as a marker of the severity of depression. We investigated whether serum 3HB levels in patients with psychogenic somatoform symptoms can predict the effectiveness of sertraline and venlafaxine. PATIENTS AND METHODS: Physical and psychiatric problems were assessed in 132 outpatients, and symptomatic response and serum 3HB concentrations were examined before and after treatment with sertraline (50 mg/day) or venlafaxine (75 mg/day). RESULTS: In 30.3% of patients with psychogenic symptoms, serum 3HB was above the upper limit of normal (<80 µmol/L). According to multiple logistic regression analysis, only episodes of suicidal ideation showed a significant positive association with elevated 3HB (odds ratio 10.2; 95% confidence interval (CI) 2.46-42.2). The sensitivity of 3HB for the effectiveness of sertraline or venlafaxine for psychosomatic symptoms was 44.6%, but specificity was 93.9%. Hierarchical multiple logistic regression analysis identified 3HB as a better predictor of the effectiveness of medication (odds ratio 10.0; 95% CI, 2.49-40.3) than episodes of suicidal ideation. CONCLUSION: The present findings suggest that high serum 3HB levels in patients with psychogenic somatoform symptoms may be associated with suicidal ideation and the effectiveness of sertraline and venlafaxine at low to intermediate doses. The 3HB level may be a good predictor of the effectiveness of medication. Examination of serum 3HB levels may lead to earlier and more appropriate administration of sertraline and venlafaxine.

Impact of Geographical Variations on the Prevalence of Multidrug-Resistant Organisms in Japan.

Emergence and spread of multidrug-resistant organisms (MDRO) is an urgent social and public health problem. Here, we carried out an epidemiological survey to clarify the geographical characteristics and factors influencing the prevalence of MDRO. Data on the prevalence of MDRO in 47 prefectures in Japan were extracted from the Japanese Nosocomial Infection Surveillance, a nationwide database for infection control. Potential factors for MDRO were analyzed using data selected from the pharmacological, medical service, infection control, environmental, social, and food-related categories, based on the characteristics of each organism and the correlations between them and MDRO prevalence. Statistical data for potential factors were obtained from public domains. The use of antibiotics was found to be correlated with the prevalence of penicillin-resistant Streptococcus pneumoniae, 3rd-generation cephalosporin- and fluoroquinolone-resistant Escherichia coli, and methicillin-resistant Staphylococcus aureus. Negative correlation between the consumption of food such as kelp and fermented soybeans that facilitate the growth of lactic acid bacteria and the prevalence of 3rd-generation cephalosporin- and fluoroquinolone-resistant E. coli suggested an association between the intestinal microflora and MDRO colonization. In addition to the use of antibiotics, lifestyle, food culture, and social factors such as tobacco smoking, average atmospheric temperature, prevalence of three-generation households, ratio of elderly population, average duration of tourist stay, chicken and fermented soybean consumption, and the competency of healthcare services may also affect MDRO prevalence.

Morphological parameters as factors of 12-month neurological worsening in surgical treatment of patients with unruptured saccular intracranial aneurysms: importance of size ratio.

OBJECTIVE: It is well known that larger aneurysm size is a risk factor for poor outcome after surgical treatment of unruptured saccular intracranial aneurysms (USIAs). However, the authors have occasionally observed poor outcome in the surgical treatment of small USIAs and hypothesized that size ratio has a negative impact on outcome. The aim of this paper was to investigate the influence of size ratio on outcome in the surgical treatment of USIAs. METHODS: Prospectively collected clinical and radiological data of 683 consecutive patients harboring 683 surgically treated USIAs were evaluated. Dome-to-neck ratio was defined as the ratio of the maximum width of the aneurysm to the average neck diameter. The aspect ratio was defined as the ratio of the maximum perpendicular height of the aneurysm to the average neck diameter of the aneurysm. The size ratio was calculated by dividing the maximum aneurysm diameter (height or width, mm) by the average parent artery diameter (mm). Neurological worsening was defined as an increase in modified Rankin Scale score of 1 or more points at 12 months. Clinical and radiological variables were compared between patients with and without neurological worsening. RESULTS: The median patient age was 64 years (IQR 56-71 years), and 528 (77%) patients were female. The median maximum size, dome-to-neck ratio, aspect ratio, and size ratio were 4.7 mm (IQR 3.6-6.7 mm), 1.2 (IQR 1.0-1.4), 1.0 (IQR 0.76-1.3), and 1.9 (IQR 1.4-2.8), respectively. The size ratio was significantly correlated with maximum size (r = 0.83, p < 0.0001), dome-to-neck ratio (r = 0.69, p < 0.0001), and aspect ratio (r = 0.74, p < 0.0001). Multivariate logistic regression analysis showed that the specific USIA location (paraclinoid segment of the internal carotid artery: OR 6.2, 95% CI 2.6-15, p < 0.0001; and basilar artery: OR 8.4, 95% CI 2.8-25, p < 0.0001), size ratio (OR 1.3, 95% CI 1.1-1.6, p = 0.021), and postoperative ischemic lesion (OR 9.4, 95% CI 4.4-19, p < 0.0001) were associated with neurological worsening (n = 52, 7.6%), and other characteristics showed no significant differences. CONCLUSIONS: The present study showed that size ratio, and not other morphological parameters, was a risk factor for 12-month neurological worsening in surgically treated patients with USIAs. The size ratio should be further studied in a large, prospective observational cohort to predict neurological worsening in the surgical treatment of USIAs.

Analysis for risk factors of 12-month neurological worsening in patients with surgically treated small-to-moderate size unruptured intracranial aneurysms.

The risk associated with surgical treatment for small-to-moderate size unruptured intracranial aneurysms (SMUIAs, defined as <15 mm) has not been well characterized. Authors aimed to investigate risk factors for poor outcome in surgical treatment of SMUIAs. The data of prospectively collected 801 consecutive patients harboring 971 surgically treated SMUIAs was evaluated. Neurological worsening (NW) was defined as an increase in 1 or more modified Rankin Scale at 12-month. Clinical and radiological characteristics were compared. Neurological worsening was observed in 45 (4.6%). In multivariate analysis, only perforator territory infarction (PTI) on postoperative diffusion-weighted imaging (odds ratio (OR), 13; 95% confidence interval (CI), 4.9-32, p < 0.0001), and aneurysm locations (paraclinoid (OR, 6.9; 95% CI, 3.1-15, p < 0.0001), basilar artery (OR, 4.5; 95% CI, 1.5-14, p = 0.008), vertebral artery (OR, 11; 95% CI, 3.3-34, p < 0.0001)) were related to neurological worsening. Multivariate analysis showed that statin use (OR, 12; 95% CI, 3.8-39, p < 0.0001) and aneurysm locations (internal carotid artery-posterior communicating artery (OR, 3.9; 95% CI, 1.8-8.2, p < 0.0001) and basilar artery (OR, 6.3; 95% CI, 2.3-17, p = 0.008)), and aneurysm size >10 mm (OR, 5.3; 95% CI, 1.8-15, p = 0.003) were related to PTI. Although all SMUIAs should be carefully considered whether to be treated, those with statins, specific locations, and larger sizes should perhaps be more meticulously contemplated, and neurosurgeons should continue to avoid PTI.