Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy.

BACKGROUND: Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy. METHODS: Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16-20 h after inducing fatal sepsis. RESULTS: We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague-Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation. CONCLUSIONS: These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Persistent Cigarette Smoking Attenuates Plaque Stabilization in Response to Lipid-Lowering Therapy: A Serial Optical Coherence Tomography Study.

Objective: This study aimed to investigate the effect of smoking on morphological changes in non-culprit plaques in acute coronary syndrome (ACS) patients at 1 year after percutaneous coronary intervention (PCI), using optical coherence tomography (OCT). Background: Cigarette smoking is an important risk factor for coronary artery disease. However, the reasons for the high risk of re-infarction and worsened health among patients who continue to smoke after PCI remain unclear. Methods: A total of 129 non-culprit plaques were identified from 97 ACS patients who underwent OCT imaging at the time of PCI and at 1-year follow-up. Patients were divided into the following three groups according to their smoking status at 1-year follow-up: persistent smoking group (n = 26), smoking cessation group (n = 29), and nonsmoking group (n = 42). Medical history, serum cholesterol level, coronary angiography data, and OCT-determined plaque morphology were analyzed among the three groups. Results: Relative to baseline levels, the total cholesterol and low-density lipoprotein cholesterol levels significantly decreased in all three groups at 1-year follow-up after statin therapy (p < 0.05). The persistent smoking group had a relatively smaller fibrous cap thickness (FCT) and a higher incidence of thin-cap fibroatheroma (TCFA) than the other two groups at 1-year follow-up (p < 0.05), although the FCT increased and the incidence of TCFA decreased in all three groups. Conclusions: Persistent smoking is associated with an attenuated effect of statin therapy on plaque stabilization in ACS patients.

Predictors of Coronary Plaque Erosion in Current and Non-Current Smokers With ST-Segment Elevation Myocardial Infarction　- An Optical Coherence Tomography Study.

BACKGROUND: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).Methods and Results:A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10-0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16-1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98-5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture. CONCLUSIONS: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

Diagnostic utility of circulating plasma microRNA-101a in severity of coronary heart disease.

BACKGROUND: For evaluating the severity of coronary heart disease (CHD), coronary arteriography may not be available everywhere due to technical limitations. MicroRNA-101a (miR-101a) associated with inflammation and cholesterol homeostasis. However, whether it related to presence and stratification of CHD is still unknown. AIM: We aim to evaluate the value of miR-101a in stratifying CHD patients. METHODS: We enrolled 200 CHD patients and 100 controls, and 200 CHD patients were divided into two groups of low and high SYNTAX score (SYNTAX score ≤ 22 versus SYNTAX score ≥ 33). Intergroup comparisons of miR-101a level were compared among the controls and two groups of low and high SYNTAX score. Correlation between miR-101a and blood lipid profiles was analyzed. The logistic regression analysis were conducted to evaluate the risk factors of CHD. RESULTS: Relative level of miR-101a in the controls, SYNTAX score ≤ 22 and SYNTAX score ≥ 33 group were 4.61 (1.24-8.91), 3.28 (0.58-6.75) and 2.29 (1.04-3.62), respectively (p < 0.001). All lipid profiles significantly associated with miR-101a expression (all p < 0.001). The odds ratio (OR) of miR-101a in univariate analysis was 0.41 (95% CI, 0.33-0.52). After adjusting for the traditional risk factors, such as blood profiles and history of smoking, the odds ratio of miR-101a was 0.63 (95% CI, 0.47-0.43), which closely associated with CHD (p = 0.002). CONCLUSIONS: Circulating miR-101a may be considered as a novel biomarker for evaluating the presence and severity of CHD.

Predictors of non-stenting strategy for acute coronary syndrome caused by plaque erosion: four-year outcomes of the EROSION study.

BACKGROUND: The EROSION study demonstrated that patients with an acute coronary syndrome (ACS) caused by plaque erosion could be treated with antithrombotic therapy without stenting. However, the long-term prognosis of this strategy is still unclear. AIMS: The aim of this study was to test whether a non-stenting antithrombotic strategy was still effective at four-year follow-up and to explore potential predictors of long-term prognosis. METHODS: This study was a long-term follow-up of the EROSION study. Follow-up was conducted by phone call or clinical visit. Patients were divided into two groups - those with target lesion revascularisation (the TLR group), and the non-TLR group. RESULTS: Out of 55 patients who completed one-month follow-up, 52 patients finished four-year follow-up. The median duration was 4.8 years (range, 4.2-5.8 years). The majority of patients remained free from events, and all patients were free from hard endpoints (death, myocardial infarction, stroke, bypass surgery, or heart failure). Only one patient had gastrointestinal bleeding, and 11 patients underwent TLR. Patients in the non-TLR group had more optical coherence tomography (OCT) thrombus reduction from baseline to one month; 95% of patients in the non-TLR group versus 45% in the TLR group (p=0.001) met the primary endpoint (thrombus volume reduction >50%). Angiographic results showed that the TLR group had less improvement in diameter stenosis (p=0.014) at one month compared with the non-TLR group. CONCLUSIONS: Four-year follow-up findings reconfirmed the safety of an antithrombotic therapy without stenting for ACS caused by erosion. Patients with better response to antithrombotic therapy in the first month were less likely to require stent implantation during the next four years.

Characteristics and etiology of hospitalized pediatric community-acquired pneumonia in Taiwan.

BACKGROUND/PURPOSE: The purpose of this study was to determine the pathogens and to estimate the incidence of pediatric community-acquired pneumonia (CAP) in Taiwan. METHODS: This prospective study was conducted at eight medical centers from November 2010 to September 2013. Children aged 6 weeks to 18 years who met the radiologic criteria for pneumonia were enrolled. To detect classical and atypical bacteria and viruses, blood and pleural fluids were cultured, and respiratory specimens were examined by multiple conventional and molecular methods. RESULTS: At least one potential pathogen was identified in 705 (68.3%) cases of 1032 children enrolled, including bacteria in 420 (40.7%) cases, virus in 180 (17.4%) cases, and mixed viral-bacterial infection in 105 (10.2%) cases. Streptococcus pneumoniae (31.6%) was the most common pathogen, followed by Mycoplasma pneumoniae (22.6%). Adenovirus (5.9%) was the most common virus. RSV was significantly associated with children aged under 2 years, S. pneumoniae in children aged between 2 and 5 years, and M. pneumoniae in children aged >5 years. The annual incidence rate of hospitalization for CAP was highest in children aged 2-5 years (229.7 per 100,000). From 2011 to 2012, significant reduction in hospitalization rates pertained in children under 5 years of age, in pneumonia caused by pneumococcus, adenovirus or co-infections and complicated pneumonia. CONCLUSION: CAP related pathogens have changed after increased conjugated pneumococcal vaccination rates. This study described the latest incidences and trends of CAP pathogens, which are crucial for prompt delivery of appropriate therapy.

Co-inhibition of BCL-XL and MCL-1 with selective BCL-2 family inhibitors enhances cytotoxicity of cervical cancer cell lines.

Development of resistance to chemo- and radiotherapy in patients suffering from advanced cervical cancer narrows the therapeutic window for conventional therapies. Previously we reported that a combination of the selective BCL-2 family inhibitors ABT-263 and A-1210477 decreased cell proliferation in C33A, SiHa and CaSki human cervical cancer cell lines. As ABT-263 binds to both BCL-2 and BCL-XL with high affinity, it was unclear whether the synergism of the drug combination was driven either by singly inhibiting BCL-2 or BCL-XL, or inhibition of both. In this present study, we used the BCL-2 selective inhibitor ABT-199 and the BCL-XL selective inhibitor A1331852 to resolve the individual antitumor activities of ABT-263 into BCL-2 and BCL-XL dependent mechanisms. A-1210477 was substituted for the orally bioavailable S63845. Four cervical cancer cell lines were treated with the selective BCL-2 family inhibitors ABT-199, A1331852 and S63845 alone and in combination using 2-dimensional (2D) and 3-dimensional (3D) cell culture models. The SiHa, C33A and CaSki cell lines were resistant to single agent treatment of all three drugs, suggesting that none of the BCL-2 family of proteins mediate survival of the cells in isolation. HeLa cells were resistant to single agent treatment of ABT-199 and A1331852 but were sensitive to S63845 indicating that they depend on MCL-1 for survival. Co-inhibition of BCL-2 and MCL-1 with ABT-199 and S63845, inhibited cell proliferation of all cancer cell lines, except SiHa. However, the effect of the combination was not as pronounced as combination of A1331852 and S63845. Co-inhibition of BCL-XL and MCL-1 with A1331852 and S63845 significantly inhibited cell proliferation of all four cell lines. Similar data were obtained with 3-dimensional spheroid cell culture models generated from two cervical cancer cell lines in vitro. Treatment with a combination of A1331852 and S63845 resulted in inhibition of growth and invasion of the 3D spheroids. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer.

A rare case of septic cavernous sinus thrombosis as a complication of sphenoid sinusitis.

Isolated sphenoid sinusitis is a rare disorder and may present with severe complications due to its proximity to the orbital and intracranial areas. We report a 13-year-old boy hospitalized for septic shock with fever of unknown origin. Facial palsy was later noted. Brain magnetic resonance imaging showed a sphenoid mass and right cavernous sinus and internal jugular vein thrombosis. Biopsy revealed chronic rhinosinusitis. Complete recovery followed by an incision/drainage procedure and antibiotic treatment. Acute sphenoid sinusitis should be included in the differential diagnosis of septic manifestations mimicking central nervous system infection or cranial nerve palsy.

In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction: a clinical, angiographical, and intravascular optical coherence tomography study.

Aims: Plaque erosion is a significant substrate of acute coronary thrombosis. This study sought to determine in vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: A prospective series of 822 STEMI patients underwent pre-intervention optical coherence tomography. Using established diagnostic criteria, 209 had plaque erosion (25.4%) and 564 had plaque rupture (68.6%). Plaque erosion was more frequent in women <50 years when compared with those ≥50 years of age (P = 0.009). There was a similar, but less striking, trend in men (P = 0.011). Patients with plaque erosion were more frequently current smokers but had fewer other coronary risk factors (dyslipidaemia, hypertension, chronic kidney disease, and diabetes mellitus) than those with plaque rupture. There was a preponderance of plaque erosion in the left anterior descending artery (LAD; 61.2%), whereas plaque rupture was more equally distributed in both the LAD (47.0%) and right coronary artery (43.3%). Despite the similar spatial distribution of erosions and ruptures over the lengths of the coronary arteries, plaque erosion occurred more frequently near a bifurcation (P < 0.001). In the multivariable analysis, age <50 years, current smoking, absence of other coronary risk factors, lack of multi-vessel disease, reduced lesion severity, larger vessel size, and nearby bifurcation were significantly associated with plaque erosion. Nearby bifurcation and current smoking were especially notable in men, while age <50 years was most predictive in women. Conclusions: Plaque erosion was a predictable clinical entity distinct from plaque rupture in STEMI patients, and gender-specific role of risk factors in plaque erosion should be considered.

Iron-Catalyzed Regiospecific Intermolecular Radical Cyclization of Anilines: Strategy for Assembly of 2,2-Disubstituted Indolines.

The first regiospecific catalytic intermolecular assembly of 2,2-disubstituted indolines has been developed. This protocol is based on a ligand and directing group free, iron-catalyzed radical [3 + 2] process, allowing efficient coupling of different N-sulfonylanilines with various α-substituted styrenes. Preliminary mechanistic studies elucidated the radical mechanism involving a reactive and versatile anilino radical and the importance of iron complex as a Lewis acid, rendering both the reactivity and regiospecificity of this transformation.

Use of a Sampling Area-Adjusted Adenosine Triphosphate Bioluminescence Assay Based on Digital Image Quantification to Assess the Cleanliness of Hospital Surfaces.

Contaminated surfaces play an important role in the transmission of pathogens. We sought to establish a criterion that could indicate "cleanliness" using a sampling area-adjusted adenosine triphosphate (ATP) assay. In the first phase of the study, target surfaces were selected for swab sampling before and after daily cleaning; then, an aerobic colony count (ACC) plate assay of bacteria and antibiotic-resistant bacteria was conducted. ATP swabs were also tested, and the ATP readings were reported as relative light units (RLUs). The results of the ACC and ATP assays were adjusted according to the sampling area. During the second phase of the study, a new cleaning process employing sodium dichloroisocyanurate (NaDCC) was implemented for comparison. Using the criterion of 2.5 colony-forming units (CFU)/cm², 45% of the sampled sites were successfully cleaned during phase one of the study. During phase two, the pass rates of the surface samples (64%) were significantly improved, except under stringent (5 RLU/cm²) and lax (500 RLU) ATP criteria. Using receiver-operating characteristic curve analysis, the best cut-off point for an area-adjusted ATP level was 7.34 RLU/cm², which corresponded to culture-assay levels of <2.5 CFU/cm². An area adjustment of the ATP assay improved the degree of correlation with the ACC-assay results from weak to moderate.

Lipopolysaccharide-induced proliferation of the vasa vasorum in a rabbit model of atherosclerosis as evaluated by contrast-enhanced ultrasound imaging and histology.

Whether lipopolysaccharide (LPS) can promote vasa vasorum (VV) proliferation for atherosclerosis in vivo is unclear. Eighteen rabbits with atherosclerosis were randomly assigned into one of three groups of six. Group A received biweekly injections of 10 mL saline after 2 weeks of balloon injury. Groups B and C received biweekly intravenous injections of 3.0 µg LPS in 10 mL saline at weeks 10 and 4, respectively, until study termination. LPS significantly increased the levels of triglycerides and C-reactive protein and decreased the level of high-density lipoprotein cholesterol. Group C had significant larger plaques and more macrophages than group A (p = 0.01 and p < 0.001, respectively). Contrast enhancement ultrasound imaging and histological detection demonstrated that plaques in group C had a significantly higher VV density than that in group A (p = 0.009 and p = 0.002, respectively). In summary, VV proliferation for plaque destabilization can be accelerated by LPS-induced systemic inflammation and changes in lipid profiles.

[Study on combined immunization of rAd/MDC-VP1 and pcDNA3/MDC-VP1 against Coxsackievirus B3 challenge in mice].

AIM: To immunize the mice using the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost strategy and observe its immunological effect against Coxsackievirus B3(CVB3). METHODS: BALB/c mice were randomly divided into four groups: PBS group, rAd/MDC-VP1 group, pcDNA3/MDC-VP1 group and rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost group. Mice in each group were immunized intramuscularly. The titers of serum IgG and neutralizing antibody were tested by ELISA and trace neutralization assays respectively. The Lymphocytes proliferation activity and specific CTL cytotoxic activity were tested by CCK-8 assay. The mice in each group were challenged with lethal dose of CVB3, and the serum virus titer was assayed and the protection efficacy against Coxsackievirus infection was observed. RESULTS: It was observed that the titers of CVB3 VP1 specific IgG and neutralizing antibody, non-specific lymphocytic proliferation activity and specific lymphocytic CTL cytotoxic activity of the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost group were much higher than those of the rest groups(P<0.05), what's more, after CVB3 challenged, the serum virus titer of this group was lower and the protection rate(41.67%) was higher (P<0.05). CONCLUSION: Both the cellular and humoral immune responses in mice could be significantly enhanced by the rAd/MDC-VP1 prime-pcDNA3/MDC-VP1 boost strategy and the protection rate after challenged by lethal dose of virus could be increased.

[Construction of the recombinant adenovirus expressing the CVB3 sVP1-C3d3 protein and study on its immunological effects in mice].

AIM: To construct recombinant adenovirus Ad/C3d3-sVP1 and investigate the immune effects against coxsackievirus infection in mouse. METHODS: The recombinant adenovirus Ad/sVP1-C3d3 was constructed and packaged. BALB/c mouse were divided into four groups: Ad/sVP1-C3d3 group, Ad/VP1 group, Ad group and PBS group. The mice in each group were immunized by intramuscular injection. The titers of sera IgG and neutralizing antibody were detected by ELISA method and trace neutralization assay, respectively.The specific CTL cytotoxic activity was detected by CCK-8 assay. The mice in each group were challenged with lethal dose of coxsackievirus, the titers of the sera virus were titrated. RESULTS: The recombinant adenovirus Ad/sVP1-C3d3 was successfully constructed. It's observed that the titers of CVB3 VP1 specific antibody and neutralizing antibody were much higher than those of the other three groups(P<0.01). CTL cytotoxicity activities was much higher than PBS and Ad group(P<0.01), but little higher than Ad/VP1 group(P<0.05).The titer of sera virus was lower than Ad and PBS groups after CVB3 challenged(P<0.05). CONCLUSION: Both the celluar and humoral immune responses in mice could been significantly enhanced by Ad/sVP1-C3d3.

Anticancer, antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel.

This study was designed to examine the anticancer, antioxidant and antimicrobial activities of the essential oil from Lycopus lucidus Turcz. var. hirtus Regel. The essential oil treatment to six human cancer cell lines resulted in a dose-dependent inhibition of cell growth. The cytotoxicity of the essential oil on liver carcinoma and breast cancer cell lines was significantly stronger than on other cell lines. The essential oil can induce apoptosis of the liver carcinoma cell line Bel-7402 and decrease the intracellular GSH level. The antioxidant effect of the essential oil was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH) scavenging assays. The essential oil exhibited moderate antioxidant activity. The antimicrobial activity of the essential oil was evaluated against eight microorganisms using the disc diffusion and broth microdilution methods. The essential oil also showed moderate antimicrobial activity. These suggest that the essential oil could hold a good potential for use in the pharmaceutical industry.

Different clinical characteristics between polymicrobial and monomicrobial Aeromonas bacteremia--a study of 216 cases.

BACKGROUND: Part of Aeromonas bacteremia is polymicrobial infection. However, a clinical comparison of monomicrobial and polymicrobial Aeromonas bacteremia has not hitherto been reported. METHODS: A retrospective analysis of medical records of patients with Aeromonas bacteremia at three large referral hospitals in Taiwan for an 8-year period (2001-2008) was conducted. RESULTS: There were 154 patients with monomicrobial Aeromonas bacteremia and 62 patients with polymicrobial Aeromonas bacteremia. In the polymicrobial infections, E. coli was the most common combined pathogen (42%), followed by Klebsiella spp. (24%) and Enterobacter spp. (16%). Multivariate logistic regression analysis revealed solid cancer as the risk factor for polymicrobial Aeromonas bacteremia, with male gender and cirrhosis as risk factors for monomicrobial Aeromonas bacteremia. However, of all types of solid cancer, hepatoma was associated with monomicrobial Aeromonas bacteremia. APACHE II score was the most important prognostic factor in both groups. CONCLUSION: Aeromonas bacteremia in patients with cirrhosis or male gender tended to be monomicrobial. Polymicrobial Aeromonas bacteremia was associated with solid cancers. In either polymicrobial or monomicrobial Aeromonas bacteremia, prognosis could be predicted according to disease severity measured by APACHE II score.

Microbial contamination of the Tzu-Chi Cord Blood Bank from 2005 to 2006.

BACKGROUND: In total, 4502 units of cord blood (CB) were collected during a 2-year period from 2005 to 2006 by the Buddhist Tzu-Chi Stem Cells Center. The aim of this study was to analyze the incidence of microbial contamination and type of organism present in the cord blood. The clinical impact of microbial contamination on hematopoietic progenitor cell (HPC) grafts used for HPC transplantation is also discussed. METHODS: First and second specimens were obtained for microbial assessment. These were collected in laboratory after cord blood collection and after cord blood unit manipulation, respectively. The samples were cultured and the results reviewed. RESULTS: The overall incidence of microbiological contamination was 1.8% (82/4502). Three CB units were contaminated with two different organisms. Infectious organisms comprised 9.4% (8/85) of total isolated microbes. These infectious microorganisms were beta-Streptococci group B, Candida tropicalis and Staphylococcus aureus which were isolated in 6, 1 and 1 of CB units respectively. Escherichia coli, Bacteroides fragilis, Lactobacillus spp., Enterococcus, beta-Streptococcus Group B, Bacteroides valgatus, Corynebacterium spp., Klebsiella pneumonia and Peptococcus spp. were the most frequently encountered microorganisms. A higher contamination rate of the CB units was noted after vaginal delivery (2.16%) compared to caesarian section (0.85%) (p < 0.01). CONCLUSIONS: Extensive training in CB collection, good procedures and good protocols can decrease the rate of microbial contamination. The use of a closed collecting system and an ex utero method have the advantage of a lower contamination rate. In our cord blood bank, we use a closed system but an in utero method. Similar to other studies, most of microorganisms reported here as contaminants are non-pathogenic.

Successful treatment of meningitis caused by multidrug-resistant Acinetobacter baumannii with intravenous and intrathecal colistin.

Multidrug-resistant Acinetobacter baumannii is an emergent nosocomial pathogen. A 61-year-old woman developed meningitis caused by MDRAB 27 days after receiving a surgical intervention for invasive meningioma. The patient failed to respond to high doses of meropenem and sulbactam treatment and the organism persisted in the cerebrospinal fluids for two months. The regimen was changed to intravenous and intrathecal colistin for 28 days and the patient responded well. Administration of colistin both intravenously and intrathecally could be a suitable option as a salvage therapy for meningitis due to multidrug-resistant A. baumannii.

Childhood scrub typhus in eastern Taiwan: ten-year experience from a medical center.

BACKGROUND: Scrub typhus, a potentially fatal rickettsial infection, is endemic in western Pacific Rims including Taiwan. Most reports have been concerned about mainly adult patients, whereas serologic surveys suggested that as many as one-half of cases of scrub typhus might be in children. METHODS: We conducted a retrospective study of childhood scrub typhus in our hospital from January 1997 to December 2006. Scrub typhus was diagnosed on the basis of serology tests or polymerase chain reaction (PCR) examination in fifteen children. RESULTS: Fever and chigger bite history were presented in all 15 cases, and eschar lesion was identified in 12 patients (80%). Nine (60%) patients had headache and six (40%) complained of abdominal pain. Three patients (20%) had meningoencephalitis, and two (13%) hemophagocytic syndrome were confirmed by bone marrow biopsy. One patient died of progressive acute respiratory distress syndrome (ARDS) and pulmonary hemorrhage. Myocarditis was revealed in autopsy. All surviving patient responded well to antibiotic therapy, and the average duration to defervescence after treatment was 1.8 days. CONCLUSIONS: We conclude that scrub typhus should be taken into consideration among patients of acute systemic febrile illness, especially those with suspected exposure history and typical skin lesion. Although most patients responded well to treatment, severe complications such as meningoencephalitis, interstitial pneumonia, acute respiratory distress syndrome, hemophagocytic syndrome, and myocarditis might lead to morbidity and mortality.