Prognostic value of 1,5-anhydro-D-glucitol incorporating syntax score in acute coronary syndrome.

The utility of adding information on 1,5-anhydro-D-glucitol (1,5-AG), a marker for postprandial hyperglycemia, to a pre-existing scoring system in acute coronary syndrome (ACS) patients is unknown. This retrospective cohort study included 266 ACS patients. The end point was major adverse cardiac and cerebral events (MACCE) through 5 years of follow-up. To evaluate incremental benefits of combining 1,5-AG with the syntax score, we applied time-dependent receiver operating curve (ROC) analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA). Temporal changes to the area under time-dependent ROC curves showed that addition of 1,5-AG parameters to syntax score did not provide any incremental value (area under the curve for syntax alone, 0.673 (95% confidence interval (CI), 0.599-0.747) vs. with 1,5-AG combined, 0.671 (95%CI 0.596-0.746; Delong p = 0.65). Incorporating 1,5-AG into syntax score yielded a significant NRI of 0.291 (95%CI 0.015-0.567) and IDI of 0.055 (95%CI 0.018-0.093), while DCA analysis showed the limited net benefit in combination with 1,5-AG and syntax score. 1,5-AG values exhibited significant discriminatory utility for detecting MACCE within the ACS population. However, 1,5-AG levels contributed limited utility beyond syntax score based on time-dependent ROC and DCA analyses.Trial registration: UMIN000023837.

Relationship of body mass index to clinical outcomes after percutaneous coronary intervention.

BACKGROUND: Elevated body mass index (BMI) demonstrates lower all-cause and cardiovascular mortalities compared with normal-weight or lean patients in chronic diseases. This study investigated relationships between BMI and clinical outcomes following percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients, together with the sex-specific impacts of BMI on mortality. METHODS: We reviewed 1104 CAD patients who underwent PCI between 2006 and 2015. Patients were divided by BMI into three groups: lean, <18.5 kg/m2 ; normal, 18.5-24.9 kg/m2 ; and overweight/obese, ≥25 kg/m2 . The primary endpoint was all-cause mortality, and the secondary endpoint was 3-point major adverse cardiovascular events (MACE). RESULTS: Kaplan-Meier survival analysis demonstrated risks of all-cause death, and 3-point MACE were higher in lean patients compared with normal-weight and overweight/obese subjects (log-rank p < .001). Cox proportional hazard modelling showed overweight/obese was significantly associated with all-cause death (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.48-0.95; p = .03), and lean was significantly associated with 3-point MACE (HR 2.02, 95% CI 1.15-3.53; p = .01). Cox proportional hazard analysis with restricted cubic spline showed non-linear associations between BMI and both all-cause mortality and 3-point MACE (p for effect = .002 and = .003, respectively). No significant interaction was evident between sex and BMI for all-cause mortality (p for interaction = .104) or 3-point MACE (p for interaction =0.122). CONCLUSIONS: Lean category was associated with adverse outcomes among CAD patients. An obesity paradox regarding the independent association of elevated BMI with reduced mortality after PCI is evident in both males and females.

Relationships between sodium levels, haemodynamics and metalloproteinases in heart failure patients.

To estimate the associations between dysnatraemia and inflammatory marker [including interleukin-6 (IL-6)], and tissue remodelling marker [matrix metalloproteinase (MMP)-9 and tissue inhibitor of MMP (TIMP)-1], the pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (PAP), and left ventricular end-diastolic pressure (EDP), and the prognostic relevance in patients with heart failure. The serum sodium level and circulating levels of IL-6, MMP-9, and TIMP-1 were measured in 173 heart failure patients. Dual heart catheterisation was performed to measure PCWP, mean PAP, and EDP. All-cause mortality was assessed during the follow-up period (mean 88 ± 49 months). Restricted cubic spline (RCS) regression showed a U-shaped association of serum sodium level with TIMP-1, with the lowest values in the 138-140 mmol/L range (P for effect = 0.042, P for non-linearity = 0.017). IL-6 and MMP-9 levels showed non-significant associations with serum sodium level. U-shaped associations of serum sodium level with PCWP (P for effect = 0.004, P for non-linearity = 0.001) and mean PAP (P for effect = 0.042, P for non-linearity = 0.017) were found with the RCS regression model. The random forest model revealed that TIMP-1, MMP-9, and IL-6 were important predictors for serum sodium levels. Restricted cubic spline Cox regressions demonstrated that TIMP-1 levels indicated a U-shaped, concaved, non-linear association with all-cause mortality (P for effect = 0.011, P for non-linearity = 0.022). Dysnatraemia is an index of TIMP-1 aggravation and elevated PCWP, mean PAP; hence, it is associated with worsening all-cause mortality.Clinical Trial Registration: UMIN000023840.

Estimated excretion and clearance of uric acid as optimal surrogate indices for daily urinary uric acid excretion.

OBJECTIVES: Daily uric acid excretion is an essential index for patients with gout/hyperuricemias. We identified alternative indices most correlated with 24-hour uric acid clearance (Cua 24h) and 24-hour uric acid excretion (Eua 24h) using data from the reference interval of urinary clearance and excretion of urate study. METHODS: The subjects were indoor workers aged 20 to 65 who met the Clinical and Laboratory Standards Institute Guidelines C28-A3c. Alternative indices using spot urine were urine uric acid creatinine ratio, uric acid clearance - creatinine clearance ratio (Cua/Ccr), uric acid excretion - creatinine clearance ratio (Eua/Ccr), estimated uric acid clearance (eCua), and estimated uric acid excretion (eEua). eCua and eEua are the values obtained by multiplying Cua/Ccr and Eua/Ccr by the estimated glomerular filtration rate. RESULTS: The final number of subjects analyzed was 739. Among the indices using spot urine, eCua and eEua showed the highest correlation with Cua 24h and Eua 24h, respectively. Compared with Cua 60min and Eua 60min obtained from 60-minute urine collection, eCua and eEua showed lower root means squared error, lower bias, and significantly higher accuracy of within 30% and within 15%. CONCLUSIONS: The newly proposed eCua and eEua may be appropriate from a practical perspective.

Associations between cachexia and metalloproteinases, haemodynamics and mortality in heart failure.

BACKGROUND: Addressing cachexia in chronic heart failure (CHF) patients is an urgent issue in Japan, the most aged country in the world. We investigated the possible relationships between cachexia and, metalloproteinases and haemodynamics assessed by the cardiac catheterization. We also clarified the prognostic value of cardiac cachexia in the Japanese CHF population. METHODS AND RESULTS: A total of 370 participants (median age, 69 years; 35% women) were included. The haemodynamic effects of cachexia were analysed by right heart catheterization. The serum levels of matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP), as myocardial collagen turnover markers, were also assessed. Cachexia was present in 88 patients (31%). Overall, 59 patients (16%) had all-cause death. Serum MMP-2 and TIMP-2 levels were higher in cachectic patients than in noncachectic patients (797.5 [649.0-1066.8] vs 610.0 [461.8-756.8] ng/mL; P = .004 and 39.0 [28.0-49.0] vs 24.0 [19.0-37.0] ng/mL; P = .008, respectively). Cachectic patients had greater values of pulmonary vascular resistance (PVR) (161.9 [119.4-225.4] vs 127.8 [90.7-164.8] dynes/sec/cm-5 , P = .020). Kaplan-Meier survival analysis demonstrated higher probabilities of all-cause death in the cachexia group (log-rank P = .010). Cox proportional hazards modelling showed cachexia was an independent predictor of mortality (hazard ratio, 1.89; 95% confidence interval, 1.06-3.37; P = .029). The random forest model showed that C-reactive protein, age, haemoglobin, PVR and MMP-2 were predictors of cardiac cachexia. CONCLUSIONS: Cachexia, applying the globally accepted definition, was associated with adverse outcomes in the Japanese CHF population and accompanied by increased activity of MMP species and PVR.

False positive results in severe acute respiratory coronavirus 2 (SARS-CoV-2) rapid antigen tests for inpatients.

Severe acute respiratory syndrome coronavirus 2 rapid antigen detection (RAD) test kits are widely used as primary screening test in Japan because rapid diagnosis of coronavirus disease 2019 (COVID-19) is critical for infection control. We report cases with RAD test false-positive results in a ward for patients with disabilities. RAD tests potentially evoke hospital operational risk. It is desirable that performing PCR test appropriately when patients admitted to a medical treatment ward with COVID-19 symptoms instead of RAD test.

Polymicrobial bloodstream infection involving Oligella urethralis and Trueperella bernardiae: a case report and literature review.

Oligella urethralis and Trueperella bernardiae are rare causes of bacteremia. A 96-year-old female nursing home resident with diabetes presented with polymicrobial bloodstream infection comprising these organisms and obstructive urinary tract infection. O. urethralis identified from blood cultures was resistant to fluoroquinolones and non-fourth-generation cephalosporins. Cases must be accumulated to define the clinical features of these organisms for infection control.

Tracheostomy wound myiasis in a patient with hypoxic encephalopathy.

•Tracheostomy wound myiasis is rarely observed in unconscious and immobile patients.•Maggots in the vicinity of the tracheostomy site should be closely monitored.•Controlling myiasis in hospitals requires fly control and patient fluid management.

Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series.

OBJECTIVES: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study. METHODS: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups. RESULTS: The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4. CONCLUSIONS: Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.

Acute hyperglycemia causes microvascular damage, leading to poor functional recovery and remodeling in patients with reperfused ST-segment elevation myocardial infarction.

BACKGROUND: Although acute hyperglycemia (AHG) is associated with poor outcomes in ST-segment elevation myocardial infarction (STEMI) patients, underlying mechanisms have not been fully elucidated. We investigated the influence of AHG on myocardial microcirculation in reperfused STEMI patients. METHODS AND RESULTS: Thirty-four STEMI patients were divided into 2 groups according to the presence (Group H, n 5 11) or the absence (Group L, n 5 23) of AHG. Myocardial blood flow (MBF) and myocardial flow reserve (MFR) in the infarct-related area were compared between 2 groups, using ¹³N-ammonia positron emission tomography. Wall motion abnormality scores (WMASs) and end-diastolic volume indices (EDVI) were also assessed at 1 and 6 months after the onset. Although resting MBF was similar, MFR was lower in Group H than in Group L (1.69 ± 0.37 vs 2.39 ± 0.56, P = .001). WMAS was greater in Group H than in Group L at both 1 month (7.4 ± 3.7 vs 3.7 ± 3.0, P = .011) and 6 months (7.3 ± 3.9 vs 3.1 ± 3.4, P = .015). EDVI tended to be greater in Group H than in Group L at 6 months (103.8 ± 42.9 vs 73.9 ± 16.0 mL/m2, P = .071). Multivariate analysis showed AHG to be independently associated with low MFR. CONCLUSIONS: In STEMI patients, AHG impaired myocardial microcirculation, leading to poor functional recovery and remodeling despite successful reperfusion.

Aseptic Meningitis after Amenamevir Treatment for Herpes Zoster in the First Branch of the Trigeminal Nerve.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.

[A case of bacterial aneurysm complicated by severe infectious endocarditis].

We report a case of bacterial aneurysm complicated by severe infectious endocarditis. A 34-year-old man developed idiopathic fever and general fatigue persisting for a month. He was admitted to our institution, and examinations revealed severe bacterial endocarditis with vegetation at the mitral valve and mitral incompetence. Right after admission, he suddenly developed acute cardiac infarction and cardiac arrest due to occlusion of the coronary artery by emboli from vegetation of the mitral valve. After achieving a good recovery, magnetic resonance (MR) imaging demonstrated an unruptured bacterial aneurysm at the distal branch of the left middle cerebral artery (MCA) supplying the left parietal lobe 5 days after admission, and T2* weighted images demonstrated multiple signal loss lesions, which were suspected of being thrombosed bacterial micro-aneurysms or micro-vasculitis. Although there was a risk of aneurysm rupture, we decided to proceed with mitral valve replacement by an artificial heart valve made of carbon, and repeatedly observed an unruptured bacterial aneurysm by serial MR imaging and angiography. Due to the preceding cardiac surgery, we were able to completely cure the severe infection and prevent new embolic showers. Under administration of antibiotics, the bacterial cerebral aneurysm did not increase over a period of 4 weeks, and finally the aneurysm disappeared about 6 weeks after admission. Although the timing of treatment of an unruptured bacterial aneurysm and cardiac surgery for infectious endocarditis associated with a bacterial cerebral aneurysm are controversial, we think that proceeding with cardiac surgery and observing the unruptured bacterial aneurysm by repeated MR imaging and angiography under administration of antibiotics was an appropriate strategy in this case.

Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure.

AIMS: Matrix metalloproteinase (MMP) is up-regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP-9 and tissue inhibitors of MMP-1 (TIMP-1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF. METHODS AND RESULTS: Plasma levels of MMP-9, TIMP-1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow-up (median 109 months). MMP-9 and TIMP-1 levels and the MMP-9/TIMP-1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP-9 than those without HF events (P = 0.004). Kaplan-Meier analysis demonstrated a higher probability of HF events with high MMP-9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP-9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03-13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20-11.02; P = 0.023) among patients with high MMP-9 values compared with patients with low BNP and low MMP-9 values. CONCLUSIONS: MMP-9 and TIMP-1 levels correlate with the severity of chronic HF. MMP-9 is a strong predictor of HF events, suggesting that a disparity between MMP-9 and TIMP-1 levels and increased MMP-9 levels may help predict HF events.

A precise pharmacodynamic study showing the advantage of a marked reduction in cardiotoxicity in continuous infusion of doxorubicin.

We have already shown that the antileukemic activity of daunorubicin that had been reported to be dependent on the area under the concentration - time curve (AUC) was actually peak concentration (Cmax) dependent. The antitumor activity of doxorubicin (DXR) has also been reported to be dependent on AUC, whereas its cumulative cardiotoxicity has been reported to be Cmax dependent. In this study, we evaluated whether the antileukemic and cardiotoxic effects of DXR were AUC or Cmax dependent, and compared their cytotoxic effects, utilizing the computer-controlled in vitro pharmacokinetic simulation system or a conventional culture system for a leukemic cell line and measuring the intracellular ATP amount or the proportion of beating cells for the cardiotoxicity. In leukemic cells, the cytotoxic rate decreased as the simulated infusion time or exposure time increased with the same AUC value in the simulation and conventional culture system (P < 0.05 and <0.01, respectively). The intracellular ATP and proportion of beating cells also increased with prolonged DXR exposure time with the same constant concentration - time product value (P < 0.05 and <0.0001, respectively) in heart cells. These results indicated that both the antileukemic effects and the cardiotoxicity were Cmax dependent. However, a comparison of the two showed that cardiotoxicity was more Cmax dependent than the antileukemic effect. These results suggested that the continuous infusion treatment schedule of DXR may have the clinical advantage of reducing cardiotoxicity more markedly than the antileukemic effect.