Efficacy and Safety of SIKD1977 in Combination with Standard Treatment for Postherpetic Neuralgia: Study Protocol for a Double Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Clinical Trial.

Purpose: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster, associated with poor quality of life and increased patient and healthcare resource expenditure. This randomized controlled trial aims to evaluate the efficacy and safety of SIKD1977 (Sogeonjungtang) in combination with standard treatment and estimate an effective dose for treating PHN. Patients and Methods: This is a protocol for a randomized, placebo-controlled, double-blind, multicenter trial. A total of 90 eligible participants with PHN will be recruited from three hospitals and randomly allocated to high-dose group, low-dose group, or placebo group in a 1:1:1 ratio. The trial will involve a 6-week oral administration of SIKD1977/placebo, and a 1-week follow-up period. The primary outcome will be the weekly average change in average daily pain score (ADPS) from baseline to the end of treatment. The secondary outcomes will include the weekly average changes in ADPS from baseline to week 2, 4, and 7, differences in Short-Form McGill Pain Questionnaire, Visual analogue scale, 5-level EuroQol-5 dimensions, Patient Global Impression of Change, and consumption of rescue drugs. All adverse events will be assessed during the trial. Conclusion: This study will provide evidence for the efficacy and safety of SIKD1977, and an effective dose for PHN. Trial Registration: This protocol has been registered in the Clinical Research Information Service with the identification code KCT0007939.

Inappropriate empirical antibiotic therapy does not adversely affect the clinical outcomes of patients with acute pyelonephritis caused by extended-spectrum ß-lactamase-producing Enterobacteriales.

Extended-spectrum ß-lactamase-producing Enterobacteriales (ESBL-PE) are often associated with inappropriate empirical therapy (IAT). The aim of this study was to investigate whether IAT of acute pyelonephritis (APN) caused by ESBL-PE is related to adverse outcomes. A retrospective cohort study was performed at a tertiary-care hospital from 2014 through 2016. Patients who had APN caused by ESBL-PE and were definitely treated with appropriate antibiotics for at least 7 days were enrolled. IAT was defined as when inappropriate empirical antibiotics were given 48 h or longer after initial diagnosis of APN. Primary endpoint was treatment failure defined as clinical and/or microbiologic failure. Secondary endpoints were length of hospital stay and recurrence of APN. Propensity score matching was used to adjust heterogeneity of each group. Among 175 eligible cases, 59 patients received IAT and 116 patients received appropriate empirical antimicrobial therapy (AT). Treatment failure was observed in five (8.4%) patients and nine (7.8%) patients in each group, respectively. After matching, the treatment failure rate was similar between both groups (adjusted odd ratio [aOR] 1.05; 95% confidence index [CI] 0.26-4.15). The length of hospital stay (median 11 days in the IAT group versus 11 days in the AT group; P = 0.717) and absence of recurrence within 2 months (90.3% in IAT and 86.7% in AT; P = 0.642) were also similar. IAT did not adversely affect the clinical outcome. In this regard, clinicians should be more cautious about indiscriminate prescription of broad-spectrum antibiotics such as carbapenem empirically for treatment of APN possibly caused by ESBL-PE.

Investigation of Iron Metabolism for Regulating Megakaryopoiesis and Platelet Count According to the Mechanisms of Anemia.

BACKGROUND: Iron deficiency anemia (IDA) is characterized by depletion of total body iron stores or a poor supply of plasma iron. By contrast, chronic inflammation makes iron unavailable for hematopoiesis through a cytokinemediated cascade and leads to a condition known as anemia of chronic disease (AOC). However, the laboratory data regarding the regulatory role of iron metabolism on platelet count has not been fully discussed yet. In this study, we investigated the relationship between iron status and platelet production according to different anemic mechanisms representing different iron metabolisms. METHODS: The study included a total of 759 specimens. Blood samples were obtained through venipuncture. The complete blood count was measured using an Advia 2120 (Siemens Healthcare Diagnostics Inc., USA). Biochemical indices including iron level were estimated using a Toshiba chemical analyzer (Toshiba, Japan). RESULTS: In the AOC group, we found a significant relationship between platelet count and serum iron level (p < 0.27), whereas there was no correlation in the IDA group. Moreover, when the AOC patient group was subdivided by serum iron level, a remarkable difference was observed as follows. The platelet count was significantly correlated with serum iron level only in the AOC group with decreased serum iron levels (serum iron < 50 µg/dL) (p < 0.0001), while there was no correlation in the AOC group with normal serum iron levels (serum iron 50 - 100 µg/dL). CONCLUSIONS: Iron deficiency in AOC involves upregulated hepcidin production induced by elevated inflammatory cytokines. This can cause increased iron sequestration in macrophages and decreased iron absorption for bone marrow. The condition of decreased megakaryocytic iron supply makes megakaryocytes with higher ploidy which can release more platelets than lower ploidy. Moreover, reactive thrombocytosis in inflammatory states occurs by cytokine cascades involving interleukin 6 and thrombopoietin in AOC. These two features may enhance thrombocytosis in patients of AOC with decreased iron level. In the future, further study should be performed to elucidate regulating mechanism of iron metabolism for megakaryopoiesis in AOC patients, and guide proper supplemental therapy of iron to decrease thrombotic risk due to reactive thrombocytosis in various kinds of anemia.

Risk Factors for Community-Onset Pneumonia Caused by Levofloxacin-Nonsusceptible Streptococcus pneumoniae.

BACKGROUND: Fluoroquinolones are antibiotics commonly used in the treatment of infections caused by Streptococcus pneumoniae. However, rates of fluoroquinolone resistance are increasing with their frequent use. We designed this study to verify current fluoroquinolone resistance rates and risk factors for community-onset pneumococcal pneumonia. METHODS: A retrospective case-control study was conducted in a tertiary referral hospital. The study population comprised patients admitted for pneumococcal pneumonia between January 2011 and May 2017. The case group included community-onset pneumonia caused by levofloxacin-nonsusceptible S. pneumoniae. The control group consisted of two patients with levofloxacin-susceptible S. pneumoniae who were admitted around the same time as each case. RESULTS: A total of 198 pneumococcal pneumonia cases were identified during the study period. Twenty-five levofloxacin-resistant S. pneumoniae cases and 3 levofloxacin-intermediate S. pneumoniae cases were included in the case group (nonsusceptibility rate = 14.1%). Multivariate analysis showed that healthcare-associated factors (odds ratio [OR] 4.78, 95% confidence interval [CI] 1.39-16.43, p = 0.013), bronchopulmonary disease (OR 3.79, 95% CI 1.07-13.40, p = 0.039), cerebrovascular disease (OR 6.08, 95% CI 1.24-29.75, p = 0.026), and exposure to fluoroquinolones within the previous 3 months (OR 5.89, 95% CI 1.21-28.68, p = 0.028) were associated with nonsusceptibility to levofloxacin. CONCLUSION: Independent risk factors for levofloxacin-nonsusceptible pneumococcal pneumonia were recent hospitalization, bronchopulmonary disease, cerebrovascular disease, and prior antibiotic use within 3 months. Careful selection of empirical antibiotics is thus needed in at-risk patients. Similarly, efforts to prevent the interpersonal spread of drug-resistant pathogens in long-term care facilities and to restrict unnecessary fluoroquinolone prescriptions are important.

Case-control study of the risk factors for acquisition of Pseudomonas and Proteus species during tigecycline therapy.

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

Clinical Features and Treatment Outcomes of Bloodstream Infections Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli Sequence Type 131.

Despite the remarkable emergence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type 131 (ST131), the clinical features and outcomes of infections caused by ST131 remain poorly described. From 2011 to 2012, we collected ESBL-producing E. coli isolates from patients with bloodstream infections in 13 hospitals in Korea and compared clinical characteristics and outcomes between ST131 and non-ST131 clones. Of the 110 ESBL-producing isolates, the most common ST was ST131 (30.9%). Multivariate analysis showed that recent operation was the only variable associated with the ST131 clone; other comorbid conditions and clinical features were similar between ST131 and non-ST131 clones. CTX-M-14 and CTX-M-15 were the predominant types of ESBLs, and CTX-M-15 was significantly associated with ST131. The rate of nonsusceptibility to ciprofloxacin was higher in ST131 than in non-ST131 clones (94.1% vs. 75.0%). No significant differences in 30-day mortality rates were found between ST131 and non-ST131 clones. Multivariate analysis revealed that older age (odds ratio [OR]=5.39, 95% confidence interval [CI] 1.22-23.89; p=0.027), nosocomial infection (OR=4.81, 95% CI 1.15-20.15; p=0.032), and higher Pitt bacteremia score (OR=7.26, 95% CI 1.41-37.42; p=0.018) were independent risk factors for 30-day mortality. The ESBL-producing E. coli ST131 clone has emerged and disseminated in Korea. Our findings reveal similarities in clinical and demographic characteristics between ST131 and non-ST131 clones. Although a more resistant profile has been detected in ST131, patients with the ST131 clone did not exhibit a higher mortality rate.

Antitumor metastasis activity of pectic polysaccharide purified from the peels of Korean Citrus Hallabong.

A polysaccharide fraction, HBE-III, was successfully purified in a high yield (40.4%) from its crude polysaccharide (HBE-0) which was prepared from pectinase hydrolysates of the peels of the Korean Citrus Hallabong. In experimental lung metastasis studies of Colon 26-M3.1 carcinoma cells, prophylactic administration of HBE-III significantly inhibited lung metastasis in a dose-dependent manner. In an in vitro cytotoxicity analysis, HBE-III (up to 1000 µg/mL) did not affect the growth of Colon 26-M3.1 cells and normal cells. HBE-III enhanced production of IL-6 and IL-12 by murine peritoneal macrophages. In an assay for natural killer (NK) cell activity, HBE-III (1000 µg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells. The depletion of NK cells by injection of mouse anti-asialo GM1 serum abolished the inhibitory effect of HBE-III on lung metastasis of Colon 26-M3.1 cells. These data suggest that HBE-III may inhibit tumor metastasis via activation of macrophages and NK cells.

Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia bacteremia?

A retrospective study was conducted to evaluate the efficacy of levofloxacin in the treatment of Stenotrophomonas maltophilia bacteremia. The 30-day mortality rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and levofloxacin treatment groups. Adverse events related to antibiotics occurred more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to levofloxacin-resistant S. maltophilia strains developed in patients treated with levofloxacin. Our data suggest that levofloxacin can be a useful alternative option for treating S. maltophilia infections.

Mycobacterium chelonae infections associated with bee venom acupuncture.

We report 3 cases of Mycobacterium chelonae infections after bee venom acupuncture. All were treated with antibiotics and surgery. Mycobacterium chelonae infections should be included in the differential diagnosis of chronic skin and soft tissue infections following bee venom acupuncture.

Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo.

A scar is usually developed by an imbalance of collagen synthesis and degradation. It is believed that the flavonoids (quercetin and kaempferol) in onion extract play a role in reducing scar formation through inhibition of fibroblast activities. Even though several commercial products are composed of onion extract, the precise molecular mechanisms of onion extract in reduction of scar formation in skin are still largely unknown. In this study we investigated the effect both of onion extract and quercetin on the proliferation of fibroblasts, expression of type I collagen and matrix metalloproteinase-1 (MMP-1). Our data show that proliferation rates of fibroblasts were decreased in a dose-dependent manner of the onion extract and quercetin. The expression of type I collagen was not markedly changed by the onion extract and quercetin. Interestingly, the expression of MMP-1 was markedly increased by both onion extract and quercetin in vitro and in vivo. Thus, our data indicate that onion extract and quercetin play a role in the anti-scar effect in skin through up-regulation of MMP-1 expression, implying this agent is a promising material for reducing scar formation.