A pilot study to profile salivary angiogenic factors to detect head and neck cancers.

BACKGROUND: Early diagnosis of head and neck squamous cell carcinoma (HNSCCs) is an appealing way to increase survival rates in these patients as well as to improve quality of life post-surgery. Angiogenesis is a hallmark of tumor initiation and progression. We have investigated a panel of angiogenic factors in saliva samples collected from HNSCC patients and controls using the Bio-Plex ProTM assays. METHODS: We have identified a panel of five angiogenic proteins (sEGFR, HGF, sHER2, sIL-6Ra and PECAM-1) to be elevated in the saliva samples collected from HNSCC patients (n = 58) compared to a control cohort (n = 8 smokers and n = 30 non-smokers). RESULTS: High positive correlations were observed between the following sets of salivary proteins; sEGFR:sHER2, sEGFR:HGF, sEGFR:sIL-6Rα, sHER2:HGF and sHER2:sIL6Ra. A moderate positive correlation was seen between FGF-basic and sEGFR. CONCLUSION: We have shown that angiogenic factor levels in saliva can be used as a potential diagnostic biomarker panel in HNSCC.

HIV-associated neurocognitive disorder in HIV-infected Koreans: the Korean NeuroAIDS Project.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND. METHODS: HIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment (MoCA)-K were also assessed as potential tools for screening for HAND. RESULTS: Among the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin (Hb) level ≤ 13 g/dL (P = 0.046) and current use of a protease inhibitor-based regimen (P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS (P < 0.001) and MoCA-K (P < 0.001) were both useful for screening for HAND. Among NP tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2 and 72.0%, and those of the Wisconsin Card Sorting Test were 61.2 and 84.4%, respectively. CONCLUSIONS: HAND is a prevalent comorbidity in HIV-infected Koreans. Active screening and diagnosis with effective tools, such as the IHDS, MoCA-K and Grooved Pegboard Test, could be used to identify this important complication.

Viral load dynamics in adult patients with A(H1N1)pdm09 influenza.

SUMMARY The dynamics of influenza A viral load in respiratory samples collected from adult A(H1N1)pdm09 influenza patients were investigated. Three respiratory specimens were obtained every 2-4 days and clinical findings were recorded at the time each specimen was collected. A total of 105 serial specimens were collected from 35 patients. Viral clearance was more rapid in patients aged 15-29 years than patients aged 30-49 years (P < 0.01) or ≥ 50 years (P < 0.01). Hospitalized patients showed slow viral clearance compared to outpatients (P < 0.01). Resolution of cough and headache was correlated with viral load reduction in respiratory specimens. Viral shedding was found in 17 patients (48.6%) 5 days after symptom onset. Time to hospital visit after symptom onset was significantly correlated with prolonged viral shedding (odds ratio 9.0, 95% confidence interval 1.56-51.87, P = 0.01). These findings will contribute to infection control aspects with respect to managing patients with influenza virus infections.

Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab.

BACKGROUND AND PURPOSE: Vaccination against infection becomes important in patients with neuromyelitis optica spectrum disorder (NMOSD) because they are at an increased risk of infection due to long-term immunosuppressive therapy. However, it is unclear whether NMOSD patients under immunosuppression therapy show proper antibody formation after vaccination. Thus the antibody formation after influenza A (H1N1) vaccination in patients with NMOSD receiving rituximab was evaluated. METHODS: The study enrolled 26 patients with NMOSD, nine with multiple sclerosis and eight healthy controls. The enrolled patients had been treated with rituximab (n = 16), mycophenolate mofetil (n = 5), azathioprine (n = 6) and interferon-ß (IFN-ß) (n = 8). Antibodies against the H1N1 influenza virus were measured in the serum drawn just before (T0) and between 3 and 5 weeks after (T1) vaccination. The immunization states for hepatitis B virus surface antigen, measles and tetanus during the treatment period were also tested. RESULTS: The rituximab group showed significantly lower geometric mean titer, seroprotection rate and mean fold increase than the azathioprine group, IFN-ß group and healthy controls, and a lower seroconversion rate than the IFN-ß group. This decrease in vaccination efficacy was also shown in patients receiving mycophenolate mofetil. The immunization state for hepatitis B virus surface antigen, measles and tetanus remained the same during the treatment period with each drug, suggesting that these treatments do not affect previously formed immunity. CONCLUSION: This study shows a severely hampered humoral immune response to H1N1 influenza vaccine in patients with NMOSD treated with rituximab, although the vaccination itself is safe in these patients.

Clinical characteristics of community-acquired acute pyelonephritis caused by ESBL-producing pathogens in South Korea.

OBJECTIVES: The aim of this study was to determine the risk factors and clinical characteristics of community-acquired acute pyelonephritis (CA-APN) caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: From March 2010 to February 2011, patients with CA-APN were recruited in 11 hospitals in South Korea. Clinical and microbiological data were collected prospectively, and the ESBLs and multilocus sequence types of the ESBL-producing Escherichia coli were characterized. Comparison between CA-APN caused by ESBL-producing Enterobacteriaceae and those by non-ESBL-producing organisms was performed. RESULTS: A total of 566 patients were recruited. Enterobacteriaceae were detected in 526 patients. Forty-six isolates (46/526, 8.7 %) were positive for ESBLs. Clinical and microbiological failure did not differ between the two groups, despite there being fewer patients with ESBL-positive isolates provided with appropriate antibiotics initially (19.6 vs. 93.8 %, p < 0.001). However, the duration of hospitalization was longer in the ESBL group (10.5 vs. 7.0 days, p = 0.012). In a logistic regression model, Charlson score ≥1 point [odds ratio (OR) 3.4, 95 % confidence interval (CI) 1.6-7.0, p = 0.001], antibiotics usage during the previous year (OR 3.1, 95 % CI 1.4-7.2, p = 0.008), and urinary catheterization during the previous month (OR 4.4, 95 % CI 1.1-17.6, p = 0.035) were associated with the risks of CA-APN by ESBL producers. CTX-M-15 (48 %) and CTX-M-14 (38 %) were the most common ESBLs. ST131 was the most common clone (7/24, 29.1 %), which was more frequently resistant to cefepime, fosfomycin, and temocillin. CONCLUSIONS: The risk factors for CA-APN by ESBL producers were Charlson score ≥1 point, antibiotics usage during the previous year, and urinary catheterization during the previous month.

Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation.

The aim of this study was to evaluate the potential of tumor-necrosis-factor-related apoptosis-inducing ligand TRAIL to eradicate leukemia cell lines, while sparing normal hematopoietic stem cells. Human Jurkat and Molt-4 cell lines were used to optimize the purging process in umbilical cord blood (UCB) mononuclear cells. The Jurkat cell line was TRAIL sensitive and TRAIL-resistant Molt-4 cell line became sensitive after being treated with TRAIL and a low dose of doxorubicin (0.1 micro M), but UCB mononuclear cells remained resistant. DR4 expression was increased when Jurkat cells were treated with TRAIL, and DR5 expression increased after exposing Molt-4 cells to TRAIL plus a low dose of doxorubicin for 24 h. The expression of DR4 and DR5 in UCB mononuclear cells was unchanged after treatment with TRAIL, a low-dose doxorubicin, or TRAIL plus a low dose of doxorubicin. In TRAIL-sensitive Jurkat cells, caspases 8, 9, 3, and 7 were activated by TRAIL treatment and activation of caspases was augmented by TRAIL plus a low dose of doxorubicin than TRAIL or a low dose of doxorubicin alone in Molt-4 cells. Experiments involving mixture of UCB mononuclear cells and Jurkat or Molt-4 cells showed a marked eradication of leukemia cells and the limiting dilution assay demonstrated an eradication rate of more than 4 logs after 24 h incubation with 100 ng/ml of TRAIL in Jurkat cells. In the case of Molt-4 cells, the eradication rate was about 3 logs when TRAIL was used in combination with a low dose of doxorubicin. No significant decrease in the number of granulocyte-macrophage colony-forming unit) (CFU-GM) colonies was detected when UCB mononuclear cells were treated with TRAIL in combination with a low dose of doxorubicin. These results suggest that TRAIL offers the possibility of being used as an ex vivo purging agent for autologous transplantation in hematologic malignancies.

Nested polymerase chain reaction for detection of Mycobacterium tuberculosis in solitary pulmonary nodules.

BACKGROUND: Differential diagnosis of solitary pulmonary nodules (SPNs) can be difficult in areas, such as Korea, where tuberculosis is endemic. Nested polymerase chain reaction (PCR) is a widely used method to test a very small amount of pathogen and to detect Mycobacterium tuberculosis from fine needle aspirates. OBJECTIVES: The usefulness of nested PCR for the detection of M tuberculosis from tuberculous SPN and for the differential diagnosis of SPN was evaluated. METHODS: Thirty-three patients in whom a diagnosis of SPN was made based on a CT scan of the chest were enrolled in this study. Included were 17 malignant and 16 benign SPNs. Nested PCR was carried out for the detection of M tuberculosis by using TB-1, TB-2, TB-28, and TB-29C on fine needle aspirates from the nodule in all 33 cases. RESULTS: Aspirates from malignant neoplasms, pneumonia, and sequestration were all negative on nested PCR for tuberculosis. One of the three radiologically suspected tuberculous nodules without response to anti-tuberculosis drugs (uncertain) yielded positive results on nested PCR for the detection of M tuberculosis. In contrast, 7 out of 8 (87.5%) aspirates from proven tuberculous nodules showed positive results on nested PCR. Nested PCR could be used to detect M tuberculosis in fine needle aspirates from tuberculous SPNs with good sensitivity (87.5%) and specificity (96.0%). CONCLUSION: Nested PCR for the detection of M tuberculosis in fine needle aspirates may be useful in the differential diagnosis of SPNs.

Clinical characteristics predicting early clinical failure after 72 h of antibiotic treatment in women with community-onset acute pyelonephritis: a prospective multicentre study.

In patients with community-onset acute pyelonephritis (CO-APN), assessing the risk factors for poor clinical response after 72 h of antibiotic treatment (early clinical failure) is important. The objectives of this study were to define those risk factors, and to assess whether early clinical failure influences mortality and treatment outcomes. We prospectively collected the clinical and microbiological data of women with CO-APN in South Korea from March 2010 to February 2012. The numbers of cases in the early clinical success and early clinical failure groups were 840 (79.1%) and 222 (20.9%), respectively. Final clinical failure and mortality were higher in the early clinical failure group than in the early clinical success group (14.9% vs 2.3%, p <0.001; 6.8% vs 0.1%, p 0.001, respectively). In a multiple logistic regression model, the risk factors for early clinical failure among the total 1062 patients were diabetes mellitus (OR 1.5; 95% CI 1.1-2.1), chronic liver diseases (OR 3.3; 95% CI 1.6-6.7), malignancy (OR 2.2; 95% CI 1.1-4.4), Pitt score ≥2 (OR 2.5; 95% CI 1.6-3.8), presence of azotaemia (OR 1.8; 95% CI 1.2-2.7), white blood cell count ≥20 000/mm(3) (OR 2.5; 95% CI 1.6-4.0), serum C-reactive protein level ≥20 mg/dL (OR 1.7; 95% CI 1.2-2.4), and history of antibiotic usage within the previous year (OR 1.5; 95% CI 1.1-2.2). Analysing the subgroup of 743 patients with CO-APN due to Enterobacteriaceae, fluoroquinolone resistance of the uropathogen was another factor associated with early clinical failure (OR 1.7; 95% CI 1.1-2.5). Simple variables of underlying diseases, previous antibiotic usage and initial laboratory test outcomes can be used to decide on the direction of treatment in CO-APN.

Clarithromycin and amikacin vs. clarithromycin and moxifloxacin for the treatment of post-acupuncture cutaneous infections due to Mycobacterium abscessus: a prospective observational study.

An outbreak of post-acupuncture cutaneous infections due to Mycobacterium abscessus occurred in Ansan, Korea, from November 2007 through to May 2008. During this time a prospective, observational, non-randomized study was conducted involving 52 patients that were diagnosed with cutaneous M. abscessus infection. We compared the clinical response between patients treated with clarithromycin plus amikacin regimen and those treated with clarithromycin plus moxifloxacin regimens with regard to time to resolution of the cutaneous lesions. Among the 52 study patients, 33 were treated with clarithromycin plus amikacin, and 19 were treated with clarithromycin plus moxifloxacin. The baseline characteristics for the treatment groups were not significantly different, except for initial surgical excision (n = 27 vs. 6, respectively, p = 0.001). The median time (weeks) to resolution of the lesions in the clarithromycin plus moxifloxacin-treated subjects was significantly shorter than that in the clarithromycin plus amikacin-treated subjects (17 ± 1.1 vs. 20 ± 0.9, respectively, p = 0.017). With adjustments for age, location of lesions, prior incision and drainage, and excision during medical therapy, clarithromycin plus moxifloxacin-treated subjects were more likely to have resolved lesions (hazard ratio, 0.387; 95% confidence interval, 0.165-0.907; p = 0.029). The frequency of drug-related adverse events in the two treatment groups was not significantly different (n = 18 vs. 14, respectively; p = 0.240). The most common adverse event was gastrointestinal discomfort. The results of our study showed that the combination regimen of clarithromycin and moxifloxacin resulted in a better clinical response than a regimen of clarithromycin plus amikacin when used for treatment of cutaneous M. abscessus infection.

A molecular epidemiologic study of methicillin-resistant Staphylococcus aureus infection in patients undergoing middle ear surgery.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections after middle ear surgery has recently increased at our hospital. Most of these infections were thought to be hospital-acquired when medical personnel in contact with an MRSA-infected patient may have inadvertently transmitted the pathogen to other patients. To prevent further transmission it is essential that such sources of MRSA infection and transmission routes be selected out and eradicated. Therefore, it is necessary to determine whether the strains of MRSA isolated from infected patients are identical to those obtained from medical personnel in order to prove a reciprocal transmission of organisms between medical personnel and patients. Surveillance bacterial cultures from the anterior nares and hands of medical personnel working in the Department of Otolaryngology, Korea University Guro Hospital, were performed at two different time points: 6 December 1994 and 17 June 1996. Ribotyping with Southern blot technique was used to compare 12 MRSA strains from medical carriers with 60 strains identified from the otorrhea of MRSA-infected patients undergoing middle ear surgery. As results, six different MRSA strains were identified (types I, II, III, IV, V and VI) from ribotyping with EcoR1. One distinct subtype, type I strain, was the most frequently identified strain in both medical carriers and patients. Results also showed that 6 MRSA isolates from 10 medical carriers and 20 from 30 patients contained type I ribotype at first culture. Two medical carriers' isolates and 13 isolates from 30 patients shared the same type I strain at the second surveillance culture. In all, 41 out of 72 MRSA strains (56.9%) shared an identical ribotype pattern. Postoperative MRSA infection rates after treatment of medical carriers and the application of rigorous preventive procedures decreased from 11.9 to 5.7% after first culture and 9.0 to 7.7% following second cultures. These findings confirm that MRSA transmission can occur between medical personnel and patients and that effective preventive measures can reduce the postoperative infection rate.

Possibility of reciprocal infection of methicillin-resistant Staphylococcus aureus between medical personnel and patients undergoing middle ear surgery.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection after middle ear surgery has recently increased in our hospital. In this study we tried to determine whether the strains of MRSA isolated from infected patients are identical to those obtained from medical personnel, to prove a reciprocal transmission between medical personnel and patients. Surveillance bacterial cultures of medical personnel were performed from the anterior nares and from the fingertip. Molecular epidemiological studies, ribotyping and pulsed-field gel electrophoresis (PFGE) were used to compare the 12 MRSA strains obtained from carriers among medical personnel with the 60 strains identified from patient's otorrhea. Six different MRSA strains were identified from ribotyping, and three subtypes from PFGE. There was a particular subtype which was the most frequently identified strain found in both medical carriers and patients. Postoperative MRSA infection rates after the treatment of medical carriers and application of preventive procedures decreased from 11.9 to 5.7%. These findings suggest that the MRSA transmissions have occurred between medical personnel and patients.

Bacteremia due to quinolone-resistant Escherichia coli in a teaching hospital in South Korea.

Quinolone-resistant Escherichia coli (QREC) strains are being isolated with increasing frequency. From 1993 to 1998, 40 cases of QREC bacteremia were observed in a teaching hospital; 25 episodes (63.5%) were community-acquired. The incidence of QREC bacteremia increased steadily, from 6.7% to 24.6% during 5 years, and correlated with the significantly increased use of fluoroquinolones (P = .003, r = 0.98). When the 40 QREC bacteremic patients were compared with 80 patients with bacteremia due to quinolone-susceptible E. coli, prior fluoroquinolone use was the only independent risk factor for QREC bacteremia (P = .001). A high APACHE II score was the only independent risk factor for death. The rate of multidrug resistance of QREC was much higher (60%) than that of quinolone-susceptible isolates (13.8%). Pulsed-field gel electrophoresis patterns of these isolates were diverse. Therefore, the isolates revealed little evidence of clonal spread and may have emerged in direct response to the selective pressure exerted by prior fluoroquinolone use.

Pylephlebitis associated with appendicitis.

Pylephlebitis usually occurs secondary to infection in the region drained by the portal venous system. A most common antesecent focus of infection is diverticulitis and the most common blood isolate is E. coli (54%), followed by Proteus mirabilis (23%). Overall mortality is 32% and most of the patients who had died had severe sepsis prior to the initiation of antibiotic therapy. We describe a case of pylephlebitis which had appendicitis and consequent septic thrombosis of the portal vein and its branches, with dissemination of infection to the liver. The patient had recovered due to timely antibiotic treatment alone and resulted in complete resolution. Early diagnosis and treatment are basic to a favorable clinical course.