Blood cultures should be collected for acute cholangitis regardless of severity.

BACKGROUND: Despite the high frequency of bacteremia in acute cholangitis, the indications for blood cultures and the relationship between the incidence of bacteremia and severity of acute cholangitis have not been well established. This study examined the association between the 2018 Tokyo Guidelines (TG18) severity grading for acute cholangitis and incidence of bacteremia to identify the need for blood cultures among patients with acute cholangitis in each severity grade. METHODS: Patients with acute cholangitis who visited our emergency department between 2019 and 2020 were retrospectively investigated. Patients administered antibiotics within 48 h of hospital arrival, whose prothrombin time-international normalized ratios were not measured, or who were suspected of false bacteremia were excluded. RESULTS: Out of the included 358 patients with acute cholangitis, blood cultures were collected from 310 (87%) patients, of which 148 (48%) were complicated with bacteremia. As the TG18 severity grading increased, the frequency of bacteremia increased (Grade I, 35% [59/171]; Grade II, 59% [48/82]; Grade III, 74% [42/57]; P <0.001). Agreement with the TG18 diagnostic criteria (unfulfilled, suspected, or definite) was not different between patients with and without bacteremia; however, 36% (14/39) of the patients with "unfulfilled" criteria were complicated with bacteremia. CONCLUSIONS: As the severity of acute cholangitis increased, the frequency of bacteremia increased; however, the incidence of bacteremia was high even in mild cases and cases that did not meet the TG18 diagnostic criteria. Blood cultures should be collected regardless of the severity of acute cholangitis for patients who visit the emergency department.

Clinical prediction rule is more useful than qSOFA and the Sepsis-3 definition of sepsis for screening bacteremia.

BACKGROUND: Clinical guidelines recommend blood cultures for patients suspected with sepsis and bacteremia. Sepsis-3 task force introduced the new definition of sepsis in 2016; however, the relationship between the Sepsis-3 definition of sepsis and bacteremia remains unclear. This study aimed to investigate how to detect patients who need blood cultures. METHODS: Consecutive patients who visited the emergency department in our hospital with suspected symptoms of bacterial infection and with collected blood culture were retrospectively examined between April and September 2019. The relationship between bacteremia and Sepsis-3 definition of sepsis, and the relationship between bacteremia and clinical scores (quick-Sequential Organ Failure Assessment [qSOFA], systematic inflammatory response syndrome [SIRS], and Shapiro's clinical prediction rule) were investigated. In any scores used, ≥2 points were considered positive. RESULTS: Among the 986 patients who met the inclusion criteria, 171 (17%) were complicated with bacteremia and 270 (27%) were patients with sepsis. Sepsis was more frequent (61% vs. 20%, P < 0.001) and all clinical scores were more frequently positive in patients with bacteremia than in those without (qSOFA, 23% vs. 9%; SIRS, 72% vs. 58%; Shapiro's clinical prediction rule, 88% vs. 49%; P < 0.001). Specificity to predict bacteremia was high in sepsis and positive qSOFA (0.80 and 0.91, respectively), whereas sensitivity was high in positive SIRS and Shapiro's clinical prediction rule (0.72 and 0.88, respectively); however, no clinical definitions and scores had both high sensitivity and specificity. The area under the receiver operating characteristic curves were 0.59 (95% confidence interval, 0.55-0.64), 0.60 (0.56-0.65), and 0.78 (0.74-0.82) in qSOFA, SIRS, and Shapiro's clinical prediction rule, respectively. CONCLUSION: Blood cultures should be obtained for patients with sepsis and positive qSOFA because of its high specificities to predict bacteremia; however, because of low sensitivities, Shapiro's clinical prediction rule can be more efficiently used for screening bacteremia.

Intravenous lobular capillary haemangioma presenting as neck discomfort associated with neck anteflexion.

Lobular capillary haemangioma, also known as pyogenic granuloma, is a benign vascular tumour that usually originates in the skin and mucosal membrane. It sometimes derives from the lumen of a vein and the clinical presentations are various and non-specific. A 72-year-old woman complained of a sensation of pressure in her left neck for 1 month when cooking. Her left cephalic vein was enlarged with no signs of oedema, and cervical ultrasound revealed a space-occupying lesion in the left subclavian vein. Contrast-enhanced CT and MRI revealed an intravascular tumour. This tumour was removed with operation, and histopathological examination revealed intravascular capillary haemangioma. Intravascular lobular capillary haemangioma is a rare condition that occurs in the veins of the neck and upper extremities. Intravascular tumours could cause a unique symptom, such as neck discomfort associated with neck anteflexion.

Characteristics of pneumonia with negative chest radiography in cases confirmed by computed tomography.

Background: Chest radiography is commonly used for diagnosing community-acquired pneumonia (CAP). Computed tomography (CT) is not routinely recommended for initial assessment of CAP patients but is more sensitive and more specific than chest radiography. Objectives: To investigate characteristics of pneumonia with negative chest radiography in cases confirmed by CT. Methods: We included patients diagnosed with CAP in the emergency department, and chest radiography and CT were performed and sputum cultures were collected. The CR- group was defined as patients for whom infiltration of pneumonia was detected only on CT. The CR+ group was defined as patients for whom infiltration was detected on both chest radiography and CT. Data were collected retrospectively from medical records. Results: A total of 138 patients were included, with 58 patients in the CR- group and 80 patients in the CR+ group. Mean age was higher in the CR- group than in the CR+ group, and white blood cell counts and C-reactive protein (CRP) levels were lower in the CR- group than in the CR+ group (8.4 × 103/µL vs 12.4 × 103/µL, p = 0.01; 4.7 mg/dL vs 15.6 mg/dL, p < 0.001, respectively). Laterality of the infiltrated lungs differed between groups (right:left:bilateral = 14:30:14 vs 48:20:12, p = 0.006). Multivariate logistic analysis identified leukocytosis, elevated CRP levels (odds ratio (OR) 3.57, p = 0.003), laterality (OR 2.16, p = 0.006) as predictors of pneumonia in the CR- group. Conclusion: In pneumonia with negative chest radiography in cases confirmed by CT, milder inflammation and infiltration in the left lung tended to be seen.

Serum Levels of Fibroblast Growth Factor 23 in People Living with HIV.

BACKGROUND: Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports related to FGF23 in PLWH have been published. METHODS: Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled in the study. In addition to serum FGF23 measurements, the clinical factors assessed included age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis were performed to determine factors significantly associated with FGF23. RESULTS: In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the median CD4 count was 529 cells/µL, and the median serum FGF23 level was 36.0 pg/mL. Based on correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P = 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704). CONCLUSION: Factors significantly associated with elevated serum FGF23 levels included poor virologic control and ABC/3TC use.

Efficacies of atovaquone, pentamidine, and trimethoprim/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients on steroid therapy for connective tissue diseases. The standard agent for primary PCP prophylaxis is trimethoprim/sulfamethoxazole (TMP-SMX), although this agent can cause common adverse reactions, including myelosuppression and renal toxicity, that result in cessation. Aerosolized pentamidine and oral atovaquone are alternatives for PCP prophylaxis. The efficacies of atovaquone, pentamidine, and TMP-SMX to prevent PCP in patients with connective tissue diseases have never been compared. METHODS: Hospitalized patients with connective tissue diseases who started steroid therapy and PCP prophylaxis were enrolled. PCP prophylaxis regimens were oral TMP-SMX, aerosolized pentamidine, or oral atovaquone. Information was retrospectively collected from medical records about laboratory findings, duration of PCP prophylaxis, and reasons for terminating PCP prophylaxis. RESULTS: Ninety-six patients received PCP prophylaxis. All of them were initially treated with TMP-SMX, but this was replaced during the study period with pentamidine in 33 patients and with atovaquone in 7. Forty-one (43%) patients discontinued TMP-SMX because of adverse events, and 5 (15%) also discontinued pentamidine. None of the patients discontinued atovaquone. The most frequent causes of TMP-SMX and pentamidine cessation were cytopenia (N = 15) and asthma (N = 2). The rates of continuing treatment with TMP-SMX, pentamidine, and atovaquone at one year after starting PCP prophylaxis were 55.3%, 68.6%, and 100%, respectively (P = 0.01). None of the patients developed PCP. CONCLUSION: Although TMP-SMX for PCP prophylaxis had to be discontinued in 43% of patients with connective tissue diseases, pentamidine and atovaquone were well tolerated.

The prevalence of low serum free testosterone and the short-term effect of anti-retroviral therapy in male Japanese treatment-naïve HIV patients.

OBJECTIVES: The prevalence of hypogonadism in HIV patients is still a matter of debate. Today, serum free testosterone (fTST) is thought to be more important than serum testosterone in the diagnosis of hypogonadism in patients with HIV. This study aimed to determine the prevalence of low fTST levels and the effects of anti-retroviral therapy (ART) on fTST levels in treatment-naïve male Japanese patients with HIV. METHODS: Patients who visited Teikyo University Hospital, Japan between 2010 and 2016 were enrolled. Patients' fTST levels were evaluated twice with a radioimmunoassay in the morning, at the onset of ART and one year later. Clinical factors were also reviewed. The patients were divided into two groups ('hypogonadism' and 'normal') based on Japanese criteria. To determine factors related to low fTST in treatment-naïve patients, the Mann-Whitney U test and a multiple-regression analysis were used. Changes in fTST levels after ART initiation were evaluated with a paired t-test. RESULTS: Data from 25 patients were collected. Their median age was 36.0 years, and the median fTST level was 8.00 pg/ml in the treatment-naïve state. Thirteen patients (52%) were in the hypogonadism group. Low levels of fibroblast growth factor 23 were significantly related to low fTST levels. After the start of ART, fTST levels increased significantly (median 8.00 interquartile range [6.40-9.70] to 9.60 [7.60-13.10] pg/ml, p = 0.0081). CONCLUSIONS: Subnormal fTST levels occurred frequently among the present study patients in treatment-naïve settings. Free testosterone levels in patients with HIV were significantly increased one year after the start of ART.

Inhibition of osteoblast differentiation by ritonavir.

Osteoporosis is one of the chronic complications seen in human immunodeficiency virus (HIV)-infected patients, and affects patients at high prevalence. The causes of osteoporosis in HIV-infected patients are multiple, and include chronic HIV infection, living habits such as smoking and alcohol consumption, and antiretroviral drug use. Among antiretroviral drugs, protease inhibitors have been reported to be associated with osteoporosis. However, it remains to be determined how anti-HIV drugs affect osteoblast differentiation. In the current study, MC3T3-E1 cells, a mouse osteoblastic cell line, were cultured in osteoblast differentiation medium with or without different protease inhibitors (ritonavir, lopinavir, darunavir or atazanavir), and alkaline phosphatase (ALP) activity and the expression of Runt-related transcription factor 2 (Runx2) were analyzed. The ALP activity in MC3T3-E1 cells cultured with ritonavir was significantly reduced compared with that in cells in only osteoblast inducer reagent, indicating that ritonavir inhibited osteoblast differentiation. Meanwhile, ALP activity was not reduced in cells cultured with any of the other inhibitors. In addition, ritonavir inhibited the expression of Runx2, a key regulator of osteoblast differentiation, in the early period of osteoblast differentiation. To the best of our knowledge, this is the first study to demonstrate that ritonavir inhibits osteoblast differentiation in vitro. The present findings may explain the mechanism of osteopenia induced by combination antiretroviral therapy involving protease inhibitors.

Short Communication: The Clinical Value of Cystatin C as a Marker of Renal Function in HIV Patients Receiving Dolutegravir.

Dolutegravir (DTG) is an integrase strand transfer inhibitor that is used for the treatment of HIV infection. DTG inhibits organic cation transporter 2 on the basolateral side of proximal tubule cells of the kidney and leads to increased serum creatinine levels without true renal function deterioration. In HIV patients who receive DTG, an alternative test to serum creatinine measurement is needed to determine the correct renal function. We retrospectively evaluated 18 HIV-infected men who had received combination antiretroviral therapy (cART), including DTG, and who had available data on serum creatinine and cystatin C levels. We used paired t-test to assess the changes in estimated glomerular filtration rate (eGFR) calculated by serum creatinine or cystatin C level, after the start of cART. In all 18 patients, only 2 cases were naive, whereas 16 cases switched treatment. Based on serum creatinine level, eGFR significantly changed from 67.9 (61.2-95.7) ml/min per 1.73 m2 [medians and interquartile ranges ] to 63.6 (55.5-83.7) ml/min per 1.73 m2 (p = .0004). Conversely, eGFR was almost unchanged [79.8 (77.7-82.5) to 80.0 (77.1-82.5) ml/min per 1.73 m2; p = .132] when serum cystatin C level was used for estimation. In HIV patients receiving DTG, measurement of serum cystatin C as an alternative renal function test might be clinically valuable because it is not affected by DTG administration.

Co-Colonization with Neisseria species Is a Risk Factor for Prolonged Colonization with Multidrug-Resistant Acinetobacter baumannii in the Respiratory Tract.

Multidrug-resistant Acinetobacter baumannii (MDRAB) colonization increases the risk of bacterial spread in the hospital setting. The impact of clinical factors, including antibiotic use, on prolongation of MDRAB colonization has not been investigated. Patients with respiratory tract MDRAB detected using culture were enrolled in this study. Long-term colonizers and short-term colonizers were defined as patients whose colonization periods were >30 days or ≤30 days, respectively. Clinical data were abstracted from medical records. MDRAB was isolated in 34 patients. There were 13 long-term colonizers and 9 short-term colonizers. Twelve patients were lost to follow-up and excluded from the study. There were no significant differences in average leukocyte counts, numbers of antibiotic classes administered, duration of antibiotic use in the 30 days following colonization, or rates of central catheterization or mechanical ventilation between the 2 groups. Long-term colonizers carried Neisseria species (spp.) more frequently in the 30 days following colonization than short-term colonizers (7/13 vs 1/9, p = 0.01); however, this was not the case prior to colonization with MDRAB (5/13 vs 1/9, p = 0.33). The 90-day MDRAB colonization rates for Neisseria-negative patients and Neisseria-positive patients were 10.0% and 83.3%, respectively (P < 0.01). Prolonged MDRAB colonization in the respiratory tract was associated with Neisseria spp. co-colonization.

Decreased serum bone specific alkaline phosphatase and increased urinary N-terminal telopeptide of type I collagen as prognostic markers for bone mineral density loss in HIV patients on cART.

OBJECTIVES: Bone mineral density (BMD) loss is a major chronic complication in HIV patients. We performed a prospective study to determine the time course of BMD changes and to find prognostic factors of BMD loss in HIV patients on combination antiretroviral therapy (cART). PATIENTS AND METHODS: Subjects were 54 male Japanese HIV patients who had been on cART ≥1 year with no therapeutic agents for osteoporosis. Patients were observed for ≥1 year (median 3.1 years) and underwent annual BMD analyses using dual energy X-ray absorptiometry. Changes in BMD at lumbar spine and femoral neck were calculated for each person-year of all the patients. Clinical factors were also collected simultaneously with BMD examinations to determine prognostic factors for BMD loss. RESULTS: In total, 173 person-years in 54 patients were observed. One third (19, 35.2%) and slightly over half (30, 55.6%) patients showed BMD decreases at lumbar spine and femoral neck, respectively. However, the median BMD changes at lumbar spine and femoral neck were 0.0% and -0.52% per year, respectively. Monovariant and mixed model analyses determined that decreased serum bone specific alkaline phosphatase (BAP, p = 0.0047) and increased urinary N-terminal telopeptide (uNTx, p = 0.0011) were prognostic factors for BMD loss at lumbar spine and femoral neck, respectively. CONCLUSIONS: BMD at both lumbar spine and femoral neck changed little on average in HIV patients on cART. Decreased serum BAP or increased uNTx may be helpful to predict progressive BMD loss in the following year and to select patients for BMD follow-up or initiation of anti-osteoporosis treatment.

Increase of 25-hydroxyvitamin D levels after initiation of combination antiretroviral therapy.

Although vitamin D deficiency in HIV patients reported worldwide, the mechanisms and the effect of combination antiretroviral therapy (cART) on vitamin D levels are unclear. Patients were 50 male Japanese with HIV who visited Teikyo University Hospital, Tokyo, Japan. Patients were divided into those receiving cART (cART-experienced group, n = 30) and those who had not received cART (cART-naïve group, n = 20). Patients in the cART-experienced group had received treatment with cART for more than one year and those in the cART-naïve group were just about to start cART at study entry. Patients underwent measurement of serum 25-hydroxyvitamin D (25(OH)D) levels and assessment of clinical factors twice at one year intervals. At study entry, 23 (76.7%) in the cART-experienced group and 19 (95.0%) in the cART-naïve group had vitamin D insufficiency or deficiency. Mean 25(OH)D values were significantly higher in the cART-experienced group (25.2 ng/ml vs. 19.3 ng/ml, p = 0.01). However, levels of 25(OH)D at one year increased more in the cART-naïve group (-1.1 ng/ml vs. 5.0 ng/ml, p = 0.01), with mean 25(OH)D values in the cART-naïve group increasing to match those in the cART-experienced group. HIV infected patients who initiated cART showed increases in vitamin D levels in one year.

Characteristics of serum endocan levels in infection.

OBJECTIVES: Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers. METHODS: Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10). RESULTS: A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05). CONCLUSIONS: In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.

Hyaluronic Acid concentration in pleural fluid: diagnostic aid for tuberculous pleurisy.

BACKGROUND: A high concentration of hyaluronic acid in pleural fluid is suggestive of malignant mesothelioma. However, a relatively high concentration of hyaluronic acid was also seen in the pleural fluid of patients with benign inflammatory diseases. To show the utility of measuring hyaluronic acid levels in pleural fluid to diagnose tuberculous pleurisy, we compared the clinical features and levels of hyaluronic acid in the pleural fluid of patients with and without tuberculous pleurisy. METHODS: We enrolled 27 patients with infective pleurisy admitted at Teikyo University Hospital from January 2010 to December 2013. Ten patients were diagnosed with tuberculous pleurisy, and 17 with non-tuberculous pleurisy. We reviewed the clinical features and data of all 27 patients and compared the two groups. We analyzed and compared the concentration of hyaluronic acid and adenosine deaminase in their pleural fluid. RESULTS: Patients with tuberculous pleurisy tended to have significantly higher concentrations of hyaluronic acid and adenosine deaminase in their pleural fluid (tuberculous pleurisy patients vs. other infective pleurisy patients: hyaluronic acid (× 10(3) ng/mL); 42.9 ± 23.3 vs. 16.8 ± 17.9, P = 0.003, adenosine deaminase (IU/L); 89.7 ± 33.3 vs. 74.0 ± 90.9, P = 0.032). Receiver operating characteristic analysis revealed no significant difference in the area under the curve of hyaluronic acid and adenosine deaminase volumes in pleural fluid, suggesting their equivalent value as major diagnostic tools for tuberculosis pleurisy. CONCLUSIONS: Hyaluronic acid concentration in pleural fluid can be a valuable tool for the diagnosis of tuberculous pleurisy.

Clinical efficacy of peramivir in adult patients with seasonal influenza during the winter of 2012 in Japan.

BACKGROUND: Peramivir is an intravenously administered neuraminidase inhibitor for influenza. The clinical efficacy of peramivir remains unclear because it is used in a limited number of countries. We compared the clinical efficacy of peramivir with that of oseltamivir in influenza patients during the 2012-2013 season. METHODS: Thirty-two influenza patients who were hospitalized at Teikyo University Hospital, a teaching hospital in Tokyo, Japan, from October 2012 to March 2013 were enrolled. Among them, 23 and 9 were treated with peramivir and oseltamivir, respectively. The end points of this study were the time to defervescence and survival rate. RESULTS: There were no significant differences in the clinical backgrounds of the two groups. However, patients treated with peramivir tended to have a higher incidence of consciousness disturbance [34.8% (8/23) vs 0.00% (0/9), P = 0.064]. There were no significant differences between the peramivir and oseltamivir groups with respect to the time to defervescence (30.9 ± 18.7 h vs 34.7 ± 18.6 h) or survival rate [95.7% (22/23) vs 100% (9/9), respectively]. CONCLUSIONS: The clinical efficacy of peramivir is non-inferior to that of oseltamivir, although peramivir tended to be used in patients with serious complications. Intravenous administration of peramivir may be useful for patients with serious complications, such as consciousness disturbances.

Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins.

We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of ß-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours.