The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?

BACKGROUND: Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures. METHODS: We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria. RESULTS: Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results. CONCLUSIONS: Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.

Modeling Pancreatic Cancer with Patient-Derived Organoids Integrating Cancer-Associated Fibroblasts.

Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell-CAF interaction in the CIPCO promoted epithelial-mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME.

Positivity rates of mycobacterial culture in patients with tuberculous spondylitis according to methods and sites of biopsies: An analysis of 206 cases.

OBJECTIVES: We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. METHODS: We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. RESULTS: During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13-11.99, P = 0.030). CONCLUSIONS: We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0-85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS.

Circulating Plasmacytoid and Conventional Dendritic Cells Are Numerically and Functionally Deficient in Patients With Scrub Typhus.

Background: Dendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients. Methods: The study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry. Results: Circulating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α. Conclusions: This study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

Prosthetic valve endocarditis by Trichosporon mucoides: A case report and review of literature.

NATIONALE: Trichosporon species are widely distributed in nature and are emerging opportunistic human pathogens. Trichosporon infections are associated with superficial cutaneous involvement in immunocompetent individuals to severe systemic disease in immunocompromised patients. Until now, there is no report in infective endocarditis by Trichosporon mucoides confirmed by molecular diagnostics PATIENT CONCERNS:: A 66-year-old man presented with a fever that had occurred for a period of 6 months. He had undergone aortic valve replacement 10 years prior. Transthoracic echocardiography showed vegetations on the prosthetic aortic valve and native mitral valve. T mucoides was detected in the cultures of blood and vegetations. DIAGNOSIS: DNA sequencing using D/D2 region of rRNA and internal transcribed spacer were performed. INTERVENTIONS: Infections were successfully controlled with valve replacement and voriconazole plus liposomal amphotericin B therapy. OUTCOMES: There has been no sign of recurrence for 18-months after treatment completion. LESSONS: This is the first reported case of infective endocarditis due to T mucoides. Clinicians should consider Trichosporon species as causative agents of endocarditis in patients who have undergone cardiac surgery.

Microbial Etiology of Pyogenic Vertebral Osteomyelitis According to Patient Characteristics.

BACKGROUND: It is difficult to select an appropriate empirical antibiotic treatment regimen for patients with culture-negative pyogenic vertebral osteomyelitis (PVO). Having knowledge of the distribution of microorganisms according to patient characteristics can help clinicians make informed choices regarding empirical antibiotics. The aim of this study was to determine the microbial distribution among individuals with PVO according to their demographic and clinical characteristics. METHODS: We reviewed the medical records of patients admitted to our hospital with culture-confirmed PVO between January 2005 and December 2017 and collected data on demographics, underlying diseases, and radiographic and microbiological results. Statistical analysis was performed to identify associations between specific bacteria and specific patient characteristics. RESULTS: A total of 586 patients were included in the study. The prevalence of Staphylococcus aureus infections was higher in young patients than in old patients, while gram-negative bacterial infections and Enterococcus were more prevalent in older patients. Gram-negative bacterial infections were more common in women than in men (32.1% vs 16.4%; P < .05), in patients with cirrhosis than in those without (32.7% vs 21.1%; P < .05), and in patients with a solid tumor than in those without (31.0% vs 20.7%; P < .05). Methicillin-resistant S. aureus infections were more prevalent in patients with chronic renal disease than in those without (34.4% vs 14.7%; P < .05). CONCLUSIONS: The microbial etiology of PVO varies according to patient characteristics. Patient characteristics should thus be considered when choosing empirical antibiotics in patients with culture-negative PVO.

Lipocalin2 Induced by Bacterial Flagellin Protects Mice against Cyclophosphamide Mediated Neutropenic Sepsis.

Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis. The TLR5 agonist bacterial flagellin derived from Vibrio vulnificus extended the survival of cyclophosphamide-treated mice by reducing the bacterial load in internal organs. The protective effect of flagellin was mediated by the antimicrobial protein lipocalin 2 (Lcn2), which is induced by TLR5-NF-κB activation in hepatocytes. Lcn2 sequestered iron from infecting bacteria, particularly siderophore enterobactin-dependent members of the Enterobacteriaceae family, thereby limiting their proliferation. Lcn2 should be considered for the treatment of neutropenic sepsis and gastrointestinal damage during chemotherapy to prevent or minimize the adverse effects of cancer chemotherapy.

Case report: nosocomial fungemia caused by Candida diddensiae.

BACKGROUND: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases. CASE PRESENTATION: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 µg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements. CONCLUSION: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.

Clinical characteristics and risk factors for complications of candidaemia in adults: Focus on endophthalmitis, endocarditis, and osteoarticular infections.

OBJECTIVES: This study evaluated the incidence, risk factors, and clinical characteristics of complications of candidaemia in adults, with a focus on endophthalmitis, endocarditis, and osteoarticular infections. METHODS: All patients ≥18 years old with candidaemia in two Korean tertiary hospitals from 2007 to 2016 were investigated. Complications of candidaemia were defined as the presence of endophthalmitis, endocarditis, or osteoarticular infections documented in patients with candidaemia. The clinical characteristics and risk factors for candidaemia with complications were analysed in the patients who underwent ophthalmological examinations. RESULTS: Of 765 adult patients with candidaemia, 34 (4.4%) met the definition of complications, including endophthalmitis in 29 (3.8%), endocarditis in 4 (0.5%), and osteoarticular infections in 3 (0.4%). Of the 225 patients who underwent ophthalmological examinations, 29 (12.9%) had endophthalmitis. Candida albicans was an independent risk factor for complicated candidaemia (OR, 5.12; 95% CI, 2.17-12.09; P < 0.001). Although the mortality rate was no higher in complicated candidaemia, the duration of antifungal therapy was longer (23.1 ± 17.6 vs. 16.4 ± 10.8 days, P = 0.042), and 13 patients (39.3%) underwent additional procedures or surgery. CONCLUSIONS: Complications of candidaemia occurred in 4.4% of adult patients. C. albicans was an independent risk factor for complicated candidaemia in adults. Complications of candidaemia might need prolonged treatment and additional procedures or surgery. Therefore, careful evaluation and active treatment of candidaemia with complications should be encouraged.

Comparison of pyogenic postoperative and native vertebral osteomyelitis.

BACKGROUND CONTEXT: Postoperative vertebral osteomyelitis (PVO) after spinal surgery is a clinical challenge. However, there is a paucity of evidence regarding the most likely etiologic organisms to guide the choice of empirical antibiotic therapy, and previous reports of treatment outcomes for PVO are scarce. PURPOSE: To compare the microbiology, clinical characteristics, and outcomes of pyogenic PVO with native vertebral osteomyelitis (NVO). STUDY DESIGN: Retrospective comparative study. PATIENT SAMPLE: Patients with microbiologically proven vertebral osteomyelitis from three university-affiliated hospitals in South Korea between January 2005 and December 2015 with follow-up of at least 12 months after completion of antibiotics or until the patient was transferred. Patients who had a spine operation in the same location within 1 year of diagnosis, and all patients with remnant implants at the time of the vertebral osteomyelitis diagnosis, were defined as having PVO. The remainder of the patients was considered to have NVO. Spinal operations included discectomy, laminectomy, arthrodesis, and instrumentation for stabilization of the spine. OUTCOME MEASURES: Overall mortality, neurologic outcomes, treatment failure, and relapse of infection. METHODS: Demographic data, comorbidities, presenting symptoms, microbiological data, radiographic characteristics, laboratory data (including white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein), surgical treatment, and neurologic outcomes for each patient were reviewed from electronic medical records and analyzed. Mortality rate, treatment failure, and relapse of infection were calculated for the two groups. Factors associated with treatment outcome were evaluated using univariate and multivariate logistic regression analyses. RESULTS: The study evaluated 104 patients with PVO and 441 patients with NVO. In PVO, the most common isolate was Staphylococcus aureus (34%, n=35), followed by coagulase-negative staphylococci (31%, n=32). In NVO, the most common isolates were S. aureus (47%, n=206) and streptococci (21%, n=94). Of the staphylococci, the proportion of methicillin-resistant strains was significantly higher in PVO than that in NVO (75% vs. 39%, p<.001). The proportion of patients with gram-negative bacilli was 14% in PVO and 20% in NVO. Pre-existing or synchronous nonspinal infection was observed more frequently in NVO than in PVO (33% vs. 13%, p<.001). Although the duration of antibiotic use was similar in both groups, surgery for infection control was performed more frequently in PVO. The mortality rate was similar in both groups. However, the treatment failure and relapse rates at 12 months were higher in the PVO group (23% vs. 13%, p=.009; 14% vs. 7%, p=.028, respectively). Methicillin-resistant S.aureus was significantly associated with treatment failure or relapse via logistic regression (odds ratio 3.01, 95% confidence interval [1.71-5.32], p<.001; odds ratio 2.78, 95% confidence interval [1.40-5.49], p=.003). CONCLUSIONS: Coverage of methicillin-resistant staphylococci should be considered when prescribing empirical antibiotics for PVO. Although surgery was performed more often in PVO than NVO, the treatment failure and relapse rates at 12 months were higher in PVO.

Case report: dual primary AIDS-defining cancers in an HIV-infected patient receiving antiretroviral therapy: Burkitt's lymphoma and Kaposi's sarcoma.

BACKGROUND: The incidence of AIDS-defining cancers (ADCs) has decreased markedly in the era of highly active antiretroviral therapy (HAART). The occurrence of two ADCs is rare in people living with HIV or AIDS (PWHA) who are severely immunosuppressed or have incomplete virologic suppression. CASE PRESENTATION: We report a case of dual primary ADCs, especially NHL followed by KS, in a 70-year-old HIV-infected man who was on antiretroviral therapy and had successful virologic suppression. During HAART, he presented with generalized myalgia and abdominal pain. Multiple liver masses were detected and a biopsy revealed Burkitt's lymphoma. After three cycles of anticancer chemotherapy with a favorable response, he was diagnosed with cytomegalovirus retinitis and the anti-cancer chemotherapy was discontinued. Despite successful virologic suppression with HAART, human herpes virus-8 associated Kaposi's sarcoma was diagnosed in his right thigh. He underwent radiation therapy. CONCLUSION: These findings suggest that multiple ADCs can occur in PWHA who are receiving HAART and have successful virologic suppression. Healthcare providers caring for PWHA should maintain vigilance for the development of a broad spectrum of cancers.

A Risk-Scoring System for Predicting Methicillin Resistance in Community-Onset Staphylococcus aureus Bacteremia in Korea.

AIMS: We aimed to develop a simple scoring system to predict risk for methicillin resistance in community-onset Staphylococcus aureus bacteremia (CO-SAB) by identifying the clinical and epidemiological risk factors for community-onset methicillin-resistant S. aureus (MRSA). METHODS: We retrospectively analyzed data from three multicenter cohort studies in Korea in which patient information was prospectively collected and risk factors for methicillin resistance in CO-SAB were identified. We then developed and validated a risk-scoring system. RESULTS: To analyze the 1,802 cases of CO-SAB, we included the four most powerful predictors of methicillin resistance that we identified in the scoring system: underlying hematologic disease (-1 point), endovascular infection as the primary site of infection (-1 point), history of hospitalization or surgery in ≤1 year (+0.5 points), and previous isolation of MRSA in ≤6 months (+1.5 points). With this scoring system, cases were classified into low (less than -0.5), intermediate (-0.5-1.5), and high (≥1.5) risk groups. The proportions of MRSA cases in each group were 24.7% (22/89), 39.0% (607/1,557), and 78.8% (123/156), respectively, and 16.7% (1/6), 33.8% (112/331), and 76.9% (10/13) in a validation set. CONCLUSIONS: This risk-scoring system for methicillin resistance in CO-SAB may help physicians select appropriate empirical antibiotics more quickly.

Predictive Value of Procalcitonin for Bacterial Infection after Transarterial Chemoembolization or Radiofrequency Ablation for Hepatocellular Carcinoma.

This prospective observational study aimed at investigating the role of procalcitonin (PCT) in diagnosing bacterial infection and guiding antibiotic therapy for hepatocellular carcinoma (HCC) patients with fever after transarterial chemoembolization (TACE) and/or radiofrequency ablation (RFA). Ninety-seven cases (84 patients) were enrolled. Serum PCT, C-reactive protein (CRP), and white blood cell (WBC) counts were measured on the day of fever onset (day 0) and days 1, 3, 5, and 7 of fever. Empirical antibiotics were initiated only if PCT was ≥0.5 ng/mL or specific infection foci were suspected. An infectious cause was found in nine cases. PCT on day 0 of fever was significantly higher in patients with bacterial infection than in those without infection (P = 0.035). The area under the receiver operating characteristic curve for PCT was 0.715 (95% confidence interval, 0.538-0.892) and was higher than that for CRP (0.598 (0.368-0.828)) or WBC counts (0.502 (0.307-0.697)). In patients undergoing TACE and/or RFA, a significantly lower number of antibiotics were prescribed during the study period than during the prestudy period (P < 0.001). In conclusion, PCT might be a biomarker for diagnosing infection and guiding antibiotic treatment to reduce unnecessary antibiotic use in patients with fever after TACE and/or RFA.

Factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures.

This study aimed to identify clinical or microbiological factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures. A total of 64 isolates from 51 patients identified as C. striatum by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were assessed. More than two blood cultures were positive in 25 (48.1%) patients. Diabetes, solid tumor, and a history of previous exposure to antibiotics were more common in patients with multiple positive blood cultures. Charlson comorbidity scores were also higher, and more isolates were recovered after 48 hours of hospital stay in patients with multiple positive blood cultures. Strains recovered from patients with multiple positive blood cultures produced significantly more biofilm. Based on multilocus sequence typing (MLST), sequence type (ST) 20 (31.3%) was the most dominant, followed by ST2 (20.3%) and ST23 (10.9%). There was no relationship between the number of positive blood culture sets and sequence typing. In multivariate analyses, Carlson comorbidity score (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.09-3.36; P = 0.03) and biofilm formation were associated with multiple positive blood cultures (OR, 17.43; 95% CI, 3.71-81.91; P = 0.03). This study provides evidence that the biofilm phenotype could contribute to determining the clinical significance of C. striatum in patients with severe underlying conditions. The predominance of certain STs suggests the relatedness of C. striatum infection and the nosocomial environment.

Disseminated Invasive Mycobacterium marinum Infection Involving the Lung of a Patient with Diabetes Mellitus.

Mycobacterium marinum infection in humans occurs mainly as a granulomatous infection after exposure of traumatized skin to contaminated water. It is usually confined to the skin and soft tissue. Disseminated disease involving other organs rarely occurs in immunocompetent patients. Here, we report a case of disseminated M. marinum infection involving not only the cutaneous tissue, but also the lung of a male patient with uncontrolled diabetes and a previous history of steroid injection who was employed by a deep-water fishery.

Successful Treatment of Protothecal Tenosynovitis in an Immunocompetent Patient using Amphotericin B Deoxycholate.

Protothecosis is an uncommon human infection caused by achlorophyllic algae of the genus Prototheca, especially P. wickerhamii. The skin is the most frequently involved organ and cases of protothecal tenosynovitis are very rare. A 71-year-old woman without prior medical history except hypertension presented with painful swelling of her right hand that did not improve despite receiving antibiotic treatment. She underwent tenosynovectomy and drainage. Histopathologic examination revealed necrotizing granulomatous inflammation and numerous spherical or morula-like organisms with a spoked wheel appearance. P. wickerhamii was identified from tissue culture. The lesion did not improve with empirical fluconazole therapy. Conventional amphotericin B was administered according to antifungal susceptibility tests and the lesion completely resolved. Protothecosis should be considered in the differential diagnosis for chronic tenosynovitis that does not respond to conventional antibacterial treatment; tissue biopsy with culture is required for diagnosis.

Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression. CONCLUSIONS: This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.

Branched multipeptide immunotherapy for glioblastoma using human leukocyte antigen-A*0201-restricted cytotoxic T-lymphocyte epitopes from ERBB2, BIRC5 and CD99.

We investigated the use of cytotoxic T-lymphocyte (CTL) epitopes in peptide immunotherapy for glioblastoma. Three peptides (ERBB2, BIRC5 and CD99) were selected based on their peptide-T2 cell binding affinities and combined in a multipeptide cocktail or a branched multipeptide synthesized with mini-polyethylene glycol spacers. Dendritic cells (DCs) pulsed with the multipeptide cocktail or branched multipeptide were compared based on their immunophenotype and cytokine secretion. FACS analysis of alpha-type 1 polarized dendritic cells (αDC1s) revealed that both groups highly expressed CD80, CD83 and CD86, indicating that both treatments efficiently generated mature αDC1s with the expected phenotype. Production of IL-12p70, IL-12p40 and IL-10 also increased upon αDC1 maturation in both groups. CTLs stimulated by either αDC1 group ("DC-CTLs") included numerous IFN-γ-secreting cells against T2 cells loaded with the corresponding multipeptides. Large numbers of IFN-γ-secreting cells were observed when human glioblastoma cell lines and primary cells were treated with multipeptide-pulsed DC-CTLs. Both multipeptide-pulsed DC-CTL groups exhibited cytotoxic activity of 40-60% against the U251 cell line and 60-80% against primary cells. Branched multipeptide from ERBB2, BIRC5 and CD99 stably bound with T2 cells, and its cytotoxicity toward target cells was similar to that of the multipeptide cocktail. Thus, branched multipeptides could be promising candidates for immunotherapeutic glioblastoma treatment.

The acceptable duration between occupational exposure to hepatitis B virus and hepatitis B immunoglobulin injection: Results from a Korean nationwide, multicenter study.

BACKGROUND: Postexposure prophylaxis for occupational exposure to hepatitis B virus (HBV) plays an important role in the prevention of HBV infections in health care workers (HCWs). We examined data concerning the acceptable duration between occupational exposure and administration of a hepatitis B immunoglobulin (HBIG) injection in an occupational clinical setting. METHODS: A retrospective analysis was conducted with data from 143 cases of HCWs exposed to HBV in 15 secondary and tertiary teaching hospitals between January 2005 and June 2013. Data were taken from the infection control records of each hospital. RESULTS: Active vaccination after HBV exposure was started in 119 cases (83.2%) and postvaccination testing for hepatitis B antibody showed positive seroconversion in 93% of cases. In 98 cases (68.5%), HBIG was administered within 24 hours after HBV exposure; however, 45 HCWs (31.5%) received an HBIG injection more than 24 hours postexposure and 2 among the 45 received an injection after 7 days. Although 31.5% received an HBIG injection more than 24 hours postexposure, no cases of seroconversion to hepatitis b antibody positivity occurred. CONCLUSIONS: For susceptible HCWs, HBIG administered between 24 hours and 7 days postexposure may be as effective as administration within 24 hours in preventing occupational HBV infection.

Clinical Characteristics and Outcomes of Pyogenic Liver Abscess in Elderly Korean Patients.

BACKGROUND/AIMS: Incidence of pyogenic liver abscess (PLA) has been increasing worldwide, especially in the elderly population. Therefore, the aim of this study is to elucidate the clinical features and outcomes of PLA in elderly patients. METHODS: A total of 602 patients diagnosed with PLA from January 2003 to January 2013 were analyzed retrospectively. The patients were divided according to two age groups;≥ 65 years (n=296) and <65 years (n=306). RESULTS: The mean age was 73.59 ± 5.98 (range, 65-93) years in the elderly group. Significantly higher incidence of females (52.4% vs. 29.1%, p<0.001), hepatobiliary disease (41.2% vs. 24.8%, p<0.001), hepatobiliary procedure (29.4% vs. 13.7%, p<0.001), underlying malignancy (18.2% vs. 4.6%, p<0.001), culture positivity of resistant organism (20.6% vs. 14.4%, p=0.047), occurrence of complication (19.6% vs. 12.8%, p=0.026), and higher white blood cell (13.44 ± 6.56 vs. 12.26 ± 5.89, p=0.021), but lower rates of right lobe abscess (67.2% vs. 80.4%, p<0.001), fever (68.6% vs. 79.3%, p=0.003), and lower CRP (16.79 ± 9.67 vs. 18.80 ± 9.86, p=0.012) was observed in elderly PLA patients, compared to younger patients. Regarding complications, elderly patients had higher incidence of septic shock (8.1% vs. 2.3%, p=0.001) and cardiovascular disease (2% vs. 0%, p=0.014). CONCLUSIONS: More atypical presentations and complications tend to occur in elderly PLA patients compared with younger patients. Clinicians should be aware of these age-related differences in PLA and devise management strategies accordingly.