Changes in health and sleep quality after anti-retroviral treatment modification in Japanese people living with HIV.

BACKGROUND: Anti-retroviral treatment (ART) modification for treatment simplification is performed in virologically controlled people living with Human Immunodeficiency Virus (PLWH). However, studies on the impact of these stable treatment modifications on health-related quality of life (HRQoL) measured using patient-reported outcomes (PROs) in clinical practice are scarce; this was the focus of this study. METHODS: PLWH who visited Teikyo University Hospital between October 2019 and March 2021, and whose ART was changed to a newly recommended single-tablet regimen for treatment simplification, were included in the study. HRQoL and sleep quality were evaluated using the Short-Form (SF) 8 and Pittsburgh Sleep Quality Index (PSQI) global score, respectively, at two time points: before and after treatment modification. Comorbidities, duration of Human Immunodeficiency Virus diagnosis, ART initiation, ART regimens, and blood test data before and after treatment were assessed. The SF-8 was used to calculate the physical component summary (PCS) and mental component summary (MCS) scores. RESULTS: Forty-nine patients (all male) were included into the study. There was no change in the PCS score before and after ART modification. The MCS score significantly improved from 48.50 ± 6.56 to 50.76 ± 4.37 (p = 0.0159). Thirteen patients' ARTs were changed to dolutegravir/lamivudine. Their HRQoL and sleep quality changes were further analyzed. Their MCS and PSQI scores had improved significantly. Thirty patients' ARTs were changed to bictegravir/tenofovir alafenamide/emtricitabine; however, there were no significant changes in their HRQoL or PSQI score. CONCLUSION: ART modification for treatment simplification based on PROs may improve the HRQoL of PLWH.

Staphylococcus haemolyticus attenuates the antibacterial effect of teicoplanin via aggregates and biofilms.

OBJECTIVES: This study aimed to determine the inhibitory and bactericidal effects of teicoplanin (TEC) on TEC-susceptible Staphylococcus haemolyticus isolated from a patient with cancer in whom infection persisted despite TEC therapy. We also focused on the biofilm-forming ability of the isolate in vitro. METHODS: S. haemolyticus clinical isolate (strain 1369A) and its control strain, ATCC 29970 were cultured in Luria-Bertani (LB) broth with TEC. The inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of these strains were analyzed by using a biofilm formation/viability assay kit. The expression of biofilm-related genes was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Biofilm formation was determined by using scanning electron microscopy (SEM). RESULTS: The clinical isolate of S. haemolyticus had enhanced ability to bacterial growth, adherence, aggregation, and biofilm formation, thus the inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of the isolate were attenuated. Additionally, TEC induced cell aggregation, biofilm formation, and some biofilm-related gene expression of the isolate. CONCLUSION: The clinical isolate of S. haemolyticus is resistant to TEC treatment due to cell aggregation and biofilm formation.

Enterococcus casseliflavus Infection: A Review of Clinical Features and Treatment.

Some Enterococcus species, including Enterococcus faecalis and E. faecium, are increasingly becoming a common cause of nosocomial infections, accounting for the majority of human enterococcal infections, while other species, such as E. casseliflavus, have also been shown to be pathogenic to humans due to the increase in immunocompromised patients. These infections vary widely in their mode of transmission, symptoms, and other characteristics. Treatment is difficult in some cases because enterococci are resistant to numerous antimicrobial agents. Enterococcus faecalis and E. faecium are the best-known opportunistic pathogens, but others, including E. casseliflavus, occasionally cause opportunistic infections. This review summarizes the clinical features of E. casseliflavus infections and discusses effective therapeutic strategies. Bacteremia was the most common form of E. casseliflavus infections. Because E. casseliflavus carries the VanC gene, which confers resistance to vancomycin, less resistant drugs such as ampicillin were found more effective in treating the bacteremia. The second most common form of E. casseliflavus infection was trauma-induced endophthalmitis. This was commonly reported in active young to middle-aged patients. Vitreoretinal surgery and local or systemic administration of sensitive antimicrobial agents seem to be key to successful treatment. Other conditions such as infective endocarditis, meningitis, peritonitis, and pyothorax have also been reported as forms of E. casseliflavus infection. This review clarifies the clinical features of E. casseliflavus infection and provides important insights into its treatment.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of adult pyelonephritis.

BACKGROUND: Pyelonephritis is a common infection at any age. Urine neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute renal failure, is related to pyelonephritis in pediatric patients, although the significance of this urine biomarker in adult patients are not clear. We investigated the relationship between urine NGAL of pyelonephritis and non-pyelonephritis. PATIENTS AND METHODS: We prospectively enrolled adult patients who were hospitalized due to pyelonephritis or non-pyelonephritis. Pyelonephritis was diagnosed in patients with fever and bacteriuria, with no any other infection focuses. Non-pyelonephritis was diagnosed in patients who had fever and another infection focus without bacteriuria. Urine samples were collected on days 0, 3 and 7. Urine NGAL levels were measured by ELISA. RESULTS: There were 35 patients in the pyelonephritis group and 19 patients in the non-pyelonephritis group. Urine NGAL level were significantly higher in the pyelonephritis group than the non-pyelonephritis group on day 0 (median 302 ng/mL vs 25 ng/mL, p = 0.006). The area under the receiver operating characteristic curve of NGAL was 0.78 (p = 0.006). Urine NGAL level had a specificity of 66.7% and sensitivity of 87.0% at the cut-off level of 250 ng/mL for diagnosing pyelonephritis. CONCLUSIONS: Urine NGAL level at the diagnosis of infection are elevated in adult patients with pyelonephritis, but not in those with non-pyelonephritis. Urine NGAL might be a supportive biomarker for the diagnosis of pyelonephritis.

Relationship of sleep disorders with long-term complications and health-related quality of life in people with well-controlled human immunodeficiency virus.

ABSTRACT: Although sleep disorders are common in patients with human immunodeficiency virus (HIV) infection, they have not been adequately evaluated under currently advanced treatments, mainly with integrase strand transfer inhibitors. However, the relationship of sleep disorders with long-term complications and quality of life (QOL) status in patients infected with HIV is still poorly understood. Such associations are important in the management of outpatients with HIV. Hence, this study aimed to evaluate these associations.This cross-sectional observational study assessed the QOL changes of patients with HIV before and after the treatment regimen change. Male patients with well-controlled HIV who attended our hospital and changed HIV medications for reasons other than treatment failure between October 2019 and September 2021 were included. At the time of regimen change, sleep disorder status was assessed according to the Pittsburgh sleep quality index (PSQI), and health-related QOL (HRQOL) was assessed using the medical outcomes study 8-item short form health survey. In addition, we collected information on age, blood tests, and long-term comorbid conditions present during the evaluation. The HIV treatment regimen was also reviewed.Out of 45 male Japanese patients with HIV that were included in this study, 24 (53.3%) and 21 (46.7%) were classified into the sleep disorder group and nonsleep disorder group, respectively, according to their PSQI scores. The sleep disorder group had a significantly lower HRQOL mental component summary (P = .0222) than the nonsleep disorder group. The prevalence rates of hypertension, dyslipidemia, and diabetes mellitus were not significantly different between the 2 groups. In addition, a significant correlation was observed between PSQI scores and the HRQOL status (mental component summary, P = .0450; physical component summary, P = .0350).Sleep disorders remain common in patients with well-controlled HIV infection receiving current treatment. Sleep disorder is significantly associated with a low HRQOL in these patients. Hence, sleep status evaluation is necessary to improve HIV management.

Osteomyelitis and pyomyositis due to Staphylococcus aureus in an osteomalacic adult with multiple fractures.

Multifocal osteomyelitis and pyomyositis usually arise from hematogenous dissemination, especially in patients with immunodeficiency, trauma, or injection drug abuse. We report the case of a 75-year-old man with multifocal pyomyositis and osteomyelitis, which were due to Staphylococcus aureus and were presumably related to multiple fractures. The patient had no risk factors for these hematogenous infections. He was treated with antibiotic therapy for about 80 days and drainage of the abscesses. Regarding the cause of his multipe fractures, he was found to have hypophosphatemia and eventually diagnosed as osteomalacia. To our best knowledge, this case was the first report on multifocal osteomyelitis and pyomyositis around the fracture sites in an osteomalacic adult. Osteomalacia should be considered as one of the differential diagnoses when osteoarticular infection with multifocal fractures is detected.

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.

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.

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.

Clostridium difficile flagellin stimulates toll-like receptor 5, and toxin B promotes flagellin-induced chemokine production via TLR5.

AIMS: Clostridium difficile is an important pathogen in nosocomial infections. Although C. difficile toxins are considered to be major virulence factors, pathogenesis of C. difficile associated diseases remains to be determined. In this study, we investigated whether C. difficile flagellin is involved in the pathogenesis of C. difficile-associated diseases. MAIN METHODS: C. difficile flagellin was extracted from bacterial body by using a combination of ultracentrifugation and low speed centrifugation. Extracted C. difficile flagellin was added to HEK293T cells transiently transfected with pUNO-mcs (empty vector) or pUNO-hTLR5, and NF-kappaB activation was compared by a dual-luciferase assay. The amount of C. difficile flagellin-induced inflammatory mediators such as interleukin-8 and CCL20 was measured by ELISA assay in the culture media of intestinal epithelial cell lines, HT29 cells and Caco-2 cells. Flagellin induced phosphorylation of p38 mitogen-activated protein kinase was examined by Western blotting analysis in Caco-2 cells. The amount of C. difficile flagellin-induced inflammatory mediators in the presence, or absence of C. difficile toxin B was also measured by ELISA assay. KEY FINDINGS: C. difficile flagellin induced activation of NF-kappaB in HEK293T cells via toll-like receptor 5. C. difficile flagellin also induced activation of p38 mitogen-activated protein kinase, and promoted the production of interleukin-8 and CCL20 in intestinal epithelial cells via toll-like receptor 5. Pretreatment with toxin B enhanced flagellin-induced cytokine productions. SIGNIFICANCE: Our results indicate that toxin B promotes flagellin-induced activation of intestinal epithelial cells, and that C. difficile flagellin may play a role in the occurrence of C. difficile-associated diseases.

Liver Abscess With a Markedly High Level of Carbohydrate Antigen 19-9.

Serological tumor markers are useful for detection of malignancies and evaluation of disease progression. However, some markers are rarely elevated in patients with benign diseases and without malignancies. We herein present a case of a liver abscess with a highly elevated carbohydrate antigen (CA 19-9) level in both the serum and abscess fluid. The serological level of CA 19-9 decreased with treatment. Although CA 19-9 is known to be a specific tumor marker, high serum levels of CA 19-9 can be observed in patients with pyogenic liver abscesses. CA 19-9 may also be a marker for treatment response in patients with liver abscesses.

Cryptococcal pleuritis containing a high level of adenosine deaminase in a patient with AIDS: a case report.

Cryptococcal infection is the 4th most common opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). Although pleural effusion alone is an unusual presentation, we present a case of cryptococcal pleuritis in an AIDS patient which was initially difficult to discriminate from tuberculous pleuritis because of the high level of pleural adenosine deaminase (ADA). Cryptococcus neoformans was detected in the culture of the pleural effusion after the initiation of antituberculous treatment. High levels of ADA in the pleural fluid can be observed in patients with cryptococcal pleuritis, and longer incubation of pleural fluid should be performed in all patients who present with pleuritis associated with a high ADA level as the only significant finding.