Applying a multi-faceted infection control strategy to improve hospital environmental cleaning quality.

Background: Along with existing infection control policies, repeated education and training of environmental service workers (ESWs) improves their compliance and ultimately reduces hospital-associated infection (HAI) rates. However, only limited studies have explored the health behavioral determinants of ESWs regarding their cleaning performance after implementing an educational intervention with multi-faceted infection control strategy. Objective: To determine whether an educational intervention with multi-faceted infection control strategy improves the health behavioral determinants associated with ESWs' cleaning performance. Methods: Twenty-eight ESWs who received an educational intervention with multi-faceted hospital infection control strategy were included. ESWs' knowledge, perceived benefits and barriers, self-efficacy, health literacy, and cleaning performance were evaluated at pre-intervention, post-intervention, and 3-month follow-up. Results: HAI-related adenosine triphosphate (ATP) levels decreased significantly at post-intervention and 3-month follow-up compared with pre-intervention levels (all p < 0.05). All post-intervention ATP levels met the standard criterion after the 2nd environmental cleaning, with a median score of 267 (range, 71-386). High baseline ATP levels (odds ratio [OR] = 4.195, 95%CI 2.500-7.042, p < 0.05) were positively associated with qualified post-intervention ATP levels, while high education (OR = 0.480, 95%CI 0.276-0.833, p < 0.05) and high baseline knowledge scores (OR = 0.481, 95%CI 0.257-0.903, p = 0.023) were negatively associated with qualified post-intervention ATP levels. Conclusion: Educational intervention using a multi-faceted infection control strategy improves health behavioral determinants (baseline education, knowledge scores and ATP levels) associated with ESWs' hospital cleaning performance. Receiving an educational intervention may increase HAI knowledge of environmental cleaning among ESWs with high education or low baseline HAI knowledge.

Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin.

Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203-1.967, p < 0.05) higher than that in the non-pioglitazone controls. Compared to patients without both insulin and pioglitazone, higher cumulative risk of developing AD was found in patients receiving both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702-2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398-1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125-1.572), respectively (all p < 0.05). A similar observation also found in the evaluation the use of diabetic drugs with a cumulative defined daily dose (cDDD). No interaction between pioglitazone and major risk factors (comorbidities) of AD was observed. In conclusion, alternative drug therapies may be an effective strategy for reducing risk of developing AD in T2DM patients.

Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming.

The nucleotide-binding and oligomerization domain, leucine-rich repeats, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC-0160 or pioglitazone, increased NLRP3 inflammasome activation and IL-1ß secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP-associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC-itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU-induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3-related autoinflammatory diseases.

Association between trichomoniasis and prostate and bladder diseases: a population-based case-control study.

Trichomonas vaginalis infection is one of the most widespread sexually transmitted infections in the world. There are approximately 276 million cases worldwide. Most men remain undiagnosed and untreated because they are asymptomatic. The chronic inflammation induced by persistent infection may increase the risk of developing genitourinary cancers. In this study, we aimed to investigate the association between trichomoniasis and benign prostate hyperplasia (BPH), prostate cancer (PCa), and bladder cancer (BC) in Taiwan. We designed a case-control study by using the database of the National Health Insurance program in Taiwan. We used the International Classification of Diseases, 9th Revision classifications to classify all the medical conditions in the case and control groups. All odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using multivariable logistic regression to adjust for all comorbidities and variables. From 2000 to 2015, we enrolled a total of 62,544 individuals as the case group and 187,632 as the control group. Trichomoniasis exposure had a significant association with BPH and PCa (adjusted OR: BPH = 2.685, 95% CI = 1.233-4.286, P = 0.013; PCa = 5.801, 95% CI = 1.296-26.035, P = 0.016). The relative risk was much higher if patients had both trichomoniasis and depression (adjusted OR = 7.682, 95% CI = 5.730-9.451, P < 0.001). Men with trichomoniasis had a significantly higher risk of developing BPH and PCa than those without. Healthcare professionals should not only pay more attention to disease treatment, but also to public health education.

Trichomonas infection in pregnant women: a nationwide cohort study.

Trichomoniasis is the most prevalent sexually transmitted infection worldwide, and is associated with adverse pregnancy outcomes. However, Trichomonas vaginalis (TV) has received little public health attention, and only limited data are available on prevalence of TV and other Trichomonas-associated syndromes in pregnant women. This study aimed to determine associations between pregnancy and incident trichomoniasis-related diseases. Data of pregnant women were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. The pregnant cohort included 113,781 women, and cases were randomly matched by age, and index year with those of non-pregnant women (n = 113,781). Risk of incident trichomoniasis-related diseases was also not significantly different between pregnant and non-pregnant women. However, after stratifying by age or level of care, the younger subgroup among pregnant women had a higher risk of incident trichomoniasis-related diseases than did the younger subgroup in non-pregnant women, while the elder subgroup among pregnant women had a lower risk of incident trichomoniasis-related diseases than did the same subgroup in non-pregnant women (all p < 0.05). The higher level of care (medical center) subgroup among pregnant women had a lower risk of incident trichomoniasis-related diseases than did the same subgroup in non-pregnant women. In conclusions, although pregnancy is not significantly associated with risk of trichomoniasis-related diseases, data of the present study support an enhanced high level of medical care for pregnant women, emphasizing the potential of high medical care in reduced incidence of trichomoniasis-related diseases. This may be an effective strategy for reducing various pregnancy complications associated with trichomoniasis-related diseases.

Associations between Diabetes Mellitus and Nontuberculous Mycobacterium-Caused Diseases in Taiwan: A Nationwide Cohort Study.

Patients with diabetes mellitus (DM) are at greater risk of developing active tuberculosis and other intracellular bacterial infections, although the risk of acquiring infections from nontuberculous Mycobacterium (NTM) remains undefined. This study evaluated associations between DM and incidence of NTM infection-caused pulmonary and cutaneous diseases. Data for DM patients were extracted from the National Health Insurance Research Database of Taiwan. The DM cohort included 136,736 patients, and cases were matched randomly by age, gender, and index year with non-DM patients. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios of incident NTM-caused diseases in the DM cohort compared with non-DM control subjects. The frequency of incident NTM-caused diseases was significantly greater in DM patients (0.12%) than in non-DM patients (0.08%) (P < 0.05), including patients with type 1 DM (0.12%) and type 2 DM (0.12%) (all P < 0.05). Adjusted multivariate Cox regression analysis revealed that the incidence of NTM-caused diseases in DM patients was 1.43-fold greater than that in non-DM patients overall (P < 0.05), particularly in pulmonary (1.13-fold), other specific (excluding pulmonary, cutaneous, and disseminated diseases; 3.88-fold), and unspecific (atypical NTM infection; 1.54-fold) diseases (all P < 0.05). In conclusion, both type 1 DM and type 2 DM patients have high risk of NTM-caused diseases, suggesting that physicians need to pay more attention to this issue concerning the high risk of NTM-caused infection in DM patients.

Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation.

Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis - lactic acid fermentation and pyruvate oxidation-in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1ß maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.

Infection with Toxoplasma gondii increases the risk of psychiatric disorders in Taiwan: a nationwide population-based cohort study.

This study aimed to evaluate associations between toxoplasmosis and psychiatric disorders in Taiwan based on the National Health Insurance Research Database, Taiwan (1997-2013). Patients newly diagnosed with toxoplasmosis formed the case group (n = 259), and the control group included propensity-score matched patients without toxoplasmosis (n = 1036). The primary outcome was incidence of psychiatric disorders. Cox proportional hazards regression and stratified analyses were performed to examine risk of developing specific psychiatric disorders between patients with and without toxoplasmosis. Patients with toxoplasmosis had significantly higher incidence of psychiatric disorders than those without toxoplasmosis (P = 0.016). A significant difference was found in numbers of psychiatric disorders between the two groups during 14 years of follow-up (log-rank P < 0.001). Those with toxoplasmosis had significantly higher risk of bipolar disorder [adjusted hazard ratio (aHR = 3.60, 95% confidence interval (CI) = 2.07, 7.26), depression (aHR = 4.94, 95% CI = 2.15, 11.80) and anxiety (aHR = 5.36, 95% CI = 2.98, 25.88), but no significant between-group differences were found for schizophrenia and other psychiatric disorders. In conclusion, the present nationwide population-based analysis revealed that Toxoplasma gondii infection in Taiwan significantly increases the risk for developing bipolar disorder, depression and anxiety, but not for schizophrenia and other psychiatric disorders.

Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance.

BACKGROUND: Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue. METHODS: We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation. RESULTS: A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility. CONCLUSIONS: We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis.

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy.

BACKGROUND: Autologous chimeric antigen receptor (CAR) T cell therapy is a promising therapeutic strategy for treating hematologic malignancies. A spectrum of serious complications caused by CAR-T cells has caught great attention. We developed a novel CAR against CD19 namely UWC19, consisting anti-CD19 single-chain variable fragment (scFv) hinged with 4-1BB and CD3z signaling domains. In this study, preclinical assessments of UWC19 were conducted to evaluate the safety and efficacy in vitro and in vivo. METHODS: To evaluate the binding activity of UWC19 cells to CD19, we measured the saturation degree of CAR with human CD19 molecules using flow cytometry in vitro. The antitumor efficacy of UWC19 cells was determined by in vitro cytotoxicity assay against CD19 positive cells and in vivo using a xenograft mouse model. Cross tissue reactivity of UWC19 cells was examined by co-culturing with cell lines from difference human tissues. Tumorigenicity was determined by subcutaneously injecting UWC19 in immunodeficient mice. Persistence was analyzed using quantitative PCR. RESULTS: We showed that UWC19 CAR T cells exerted highly specific binding affinity and cytotoxicity against CD19+ cells in vitro. In vivo, UWC19 CAR T cells are able to fully control disease progression in a Raji-xenografted immunodeficient mouse model. UWC19 exerted no obvious effects on the mean body mass and graft versus host disease were observed in surviving mice. We showed that UWC19 cells specifically recognized and eliminated CD19 positive cells, whereas CD19 negative cells were much less affected. No tumorigenicity of UWC19 in immunodeficient mice was observed. CONCLUSIONS: UWC19 treatment effectively eliminated CD19 positive tumor cells with favorable toxicity profile. The findings suggest encouraging clinical prospects for its use in patients with CD19 positive B cell malignancies. Our study presented an alternative evaluation strategy for CAR-T cell products.

Infection with Trichomonas vaginalis increases the risk of psychiatric disorders in women: a nationwide population-based cohort study.

BACKGROUND: Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis and annually infects approximately 276 million people worldwide. We observed an ambiguously higher probability of trichomoniasis in patients from the psychiatric department of Tri-Service General Hospital. Herein, we aimed to investigate the association between trichomoniasis and the risk of developing psychiatric disorders. METHODS: The nationwide population-based study utilized the database of the National Health Insurance (NHI) programme in Taiwan. A total of 46,865 subjects were enrolled in this study from 2000-2013, comprising 9373 study subjects with trichomoniasis and 37,492 subjects without trichomoniasis as the control group. Cox proportional hazards regression analysis was performed to calculate the hazard ratio (HR) of psychiatric disorders during the 14 years of follow-up. RESULTS: Of the study subjects with trichomoniasis, 875 (9.34%) developed psychiatric disorders compared with 1988 (5.30%) in the control group (P < 0.001). The adjusted hazard ratio (aHR) of overall psychiatric disorders in the study subjects was 1.644 (95% confidence interval, CI: 1.514-1.766; P < 0.001). More specifically, the study subjects had a higher risk for developing an individual psychiatric disorder, including depression, anxiety, bipolar disorder, schizophrenia and substance abuse. Although metronidazole treatment reduced the risk for developing several subgroups of psychiatric disorders, significant reduction was detected for depression only. Furthermore, refractory trichomoniasis (trichomoniasis visits ≥ 2) enhanced the risk of psychiatric disorders. CONCLUSIONS: We show herein that T. vaginalis infection increases the overall risk for psychiatric disorders. The novel role of T. vaginalis in developing psychiatric disorders deserves more attention, and the control of such a neglected pathogen is of urgent public health importance.

Piperacillin-tazobactam induced bicytopenia in low cumulative treatment doses.

We present the case of infected wet gangrene of right foot in the setting of poorly controlled type 2 diabetes in a 71-year-old woman. This patient presented with improved infection condition after intravenous piperacillin-tazobactam (PTZ) 2.25 gm every 6 hours treatment and below knee amputation surgery on day 3. However, neutropenia and thrombocytopenia developed on day 13. We consulted a haematologist and performed a series of examinations. However, no significant findings were noted thereafter. PTZ was suspected to be the most likely cause of neutropenia and thrombocytopenia and was hence terminated on day 14 (cumulative dose of PTZ: 126 g) following stabilisation of the infection condition. A transfusion was performed with two units of single donor platelets on day 14 and treated with intravenous dexamethasone 5 mg every 8 hours from day 14 to 16. Her white blood cell and platelet counts increased on day 15 and continued to recover thereafter.

Potential role of autophagy in proteolysis in Trichomonas vaginalis.

BACKGROUND: Autophagy has been shown to be involved in the pathogenesis of several protists, offering prospects for the developments of new drugs targeting autophagy. However, there is no evidence illustrating functional autophagy in the deep-branching trichomonads. The human parasitic protist Trichomonas vaginalis has been predicted to possess reduced autophagic machinery, with only autophagy-related protein 8 (Atg8) conjugation system required for autophagosome formation. METHODS: The recombinant protein of TvAtg8 (rTvAtg8) and the polyclonal antibody against rTvAtg8 were generated. The expression and localization of TvAtg8 was monitored upon autophagy induction by glucose restriction (GR) compared with glucose-rich cultivation. The role of TvAtg8 in proteolysis was clarified. RESULTS: Here, we report that T. vaginalis Atg8 (TvAtg8) is upregulated and conjugated to autophagosome-like vesicles upon autophagy induction by GR. Moreover, we investigate, for the first time, the role of autophagy in T. vaginalis. Proteasome inhibition (PI)-induced autophagy compensates for the removal of polyubiquitinated proteins under glucose-rich condition. GR-induced autophagy is a major proteolytic system in T. vaginalis. These results suggest that autophagy is vital for proteolysis in T. vaginalis with an impaired ubiquitin-proteasome system or under glucose-limited environment. CONCLUSION: Our findings unveiled previously unidentified functions of autophagy in proteostasis in trichomonads, advancing our understanding of this highly conserved process in the ancient eukaryote.

Compact spectrometer system based on a gradient grating period guided-mode resonance filter.

We demonstrate a compact spectrometer system by using a gradient grating period guided-mode resonance filter-mounted on a linear photodetector array-that exhibits spatially dependent resonance characteristics; a specific incident wavelength is reflected such that the underlying array pixels measure minimum intensity. A precalibrated transmission efficiency matrix is used to determine each pixel's transmission efficiency for specific wavelengths. Unknown spectral information can be calculated from the measured intensity. Grating periods of 250-388 nm in 2-nm increments are used in each 100-cycle period. Device length is 2.23 mm. Spectral range of 506-700 nm is measurable with 1-nm resolution.

Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic blood hematopoietic stem cell transplantation recipients-A retrospective analysis of a single medical center in Taiwan.

BACKGROUND/PURPOSE: The efficacy and safety of posaconazole compared to fluconazole as antifungal prophylaxis in patients receiving allogeneic blood hematopoietic stem cell transplantation (allo-HSCT) during the early neutropenic phase without graft-versus-host disease (GVHD) was uncertain. METHODS: The medical records of allo-HSCT recipients from a single institution, who received oral fluconazole (from January 2005 to June 2011) or oral posaconazole (from June 2011 to December 2013) during the early neutropenic phase (until engraftment), were retrospectively reviewed. RESULTS: There were 52 allo-HSCT recipients, two of whom were younger than 18 years of age. Twelve cases received posaconazole and 40 cases received fluconazole as primary antifungal prophylaxis. The two groups had similar transplant characteristics, conditioning, and GVHD prophylaxis regimens. The fluconazole group had a higher risk for development of invasive fungal infections within 90 days after allo-HSCT (43% vs. 8.3%, p = 0.039). Kaplan-Meier analysis indicated that the cumulative incidence of invasive fungal infection for 90 days after allo-HSCT was higher in the fluconazole group (log rank test, p = 0.047). Early discontinuation of antifungal prophylaxis for intolerance was significantly lower in the posaconazole group (8.3% vs. 50%, p = 0.017). Both groups had similar rates of impaired liver function. CONCLUSION: Analysis of primary fungal prophylaxis during the early neutropenic phase following allo-HSCT indicated that posaconazole was more effective and was better tolerated than fluconazole. Both drugs had similar safety profiles.

Regulator of the mucoid phenotype A gene increases the virulent ability of extended-spectrum beta-lactamase-producing serotype non-K1/K2 Klebsiella pneumonia.

BACKGROUND: To determine whether the presence of a capsule regulator gene [i.e., regulator of mucoid phenotype A (rmpA) gene] contributes to virulence on extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-KP) with serotype non-K1/K2 strains. METHODS: Twenty-eight ESBL-KP and non-ESBL-KP isolates were collected from the Tri-Service General Hospital (Taipei, Taiwan). The impact of the virulent rmpA gene in different capsular polysaccharide serotypes on ESBL-KP and non-ESBL-KP isolates was studied by a neutrophil phagocytosis reaction, a serum bactericidal assay, and an animal survival model. RESULTS: Resistance to broad spectrum antibiotics was more prevalent in ESBL-KP strains than in non-ESBL-KP strains (p < 0.01). The ESBL-KP strains had different molecular patterns from non-ESBL-KP strains, based on pulsed-field gel electrophoresis. The frequency of serum-resistant isolates was the highest among ESBL-KP strains with rmpA (i.e., rmpA(+)) [71.4% (5/7)] than among of non-ESBL-KP rmpA(+) strains [42.8% (6/14)], ESBL-KP strains without rmpA (rmpA(-)) [33.3% (7/21)], and non-ESBL-KP rmpA(-) strains [14.2% (2/14)]. The most significant increase in neutrophil resistance occurred in the ESBL-KP rmpA(+) strains in comparison to the non-ESBL-KP rmpA(+), ESBL-KP rmpA(-), and non-ESBL-KP rmpA(-) strains (p < 0.01). The results of the animal survival model were compatible with the neutrophil phagocytosis reaction and serum bactericidal assay. CONCLUSION: We conclude that the pathogenic potential is greater in rmpA(+) ESBL-KP strains than in rmpA(-) ESBL-KP and non-ESBL-KP strains.

Comparisons between patients with trimethoprim-sulfamethoxazole-susceptible and trimethoprim-sulfamethoxazole-resistant Stenotrophomonas maltophilia monomicrobial bacteremia: A 10-year retrospective study.

BACKGROUND/PURPOSE: The impact of bacteremia due to the resistance of Stenotrophomonas maltophilia to trimethoprim-sulfamethoxazole (TMP-SXT) is uncertain. This study compared the clinical characteristics and outcomes of patients with TMP-SXT-susceptible (TSSSM) and TMP-SXT-resistant S. maltophilia (TSRSM) monomicrobial bacteremia. METHODS: The medical records of adult patients with TSSSM and TSRSM monomicrobial bacteremia from January 2004 to December 2013 were reviewed and classified into two groups, namely, TSSSM and TSRSM. RESULTS: There were 184 patients with monomicrobial S. maltophilia bacteremia. The mean age was 68.3 years. Most patients were males (72.8%), had high Charlson Comorbidity Index scores, previously prescribed antimicrobial agents, and indwelling medical devices. The 14-day and in-hospital mortality rates were 23.9% and 47.2%, respectively. There were 128 patients (69.6%) with TSSSM and 56 (30.4%) with TSRSM. The incidence of TSSSM bacteremia increased during the study period. The TSSSM and TSRSM groups had similar demographic and clinical characteristics and no significant differences in 14-day and in-hospital mortality (24.2% vs. 23.2%, p = 0.833; 50.0% vs. 41.1%, p = 0.264, respectively). Patients with TSSSM bacteremia had an increased risk of septic shock (p = 0.044) and neutropenia (p = 0.028) at bacteremia onset. Logistic regression analysis indicated that acquisition of TMP-SXT resistance was an independent risk factor for prolonged hospitalization (p = 0.018) and catheter-related S. maltophilia bacteremia was inversely associated with prolonged hospitalization after bacteremia (p = 0.032). CONCLUSION: There were no significant differences in mortality for patients with TSSSM and TSRSM bacteremia, but patients with TSRSM bacteremia were associated with prolonged hospitalization after bacteremia onset.

Comparison of the effectiveness and antibiotic cost among ceftriaxone, ertapenem, and levofloxacin in treatment of community-acquired complicated urinary tract infections.

PURPOSE: To study characteristics of patients with community-acquired complicated urinary tract infections (cUTIs) and to compare effectiveness and antibiotic cost of treatment with ceftriaxone (CRO), levofloxacin (LVX), and ertapenem (ETP). METHODS: This retrospective study enrolled patients who had community-acquired cUTIs admitted to Division of Infectious Diseases in a single medical center from January 2011 to March 2013. Effectiveness, antibiotic cost, and clinical characteristics were compared among patients treated with CRO, LVX, and ETP. RESULTS: There were 358 eligible cases, including 139 who received CRO, 128 treated with ETP, and 91 with LVX. The most common pathogen was Escherichia coli. The susceptibilities of these three agents were higher and more superior than first-line antibiotics. Treatment with ETP was associated with a significantly shorter time to defervescence since admission (CRO: 39 hours, ETP: 30 hours, and LVX: 38 h; p = 0.031) and shorter hospitalization stay (CRO: 4 days, ETP: 3 days, and LVX: 4 days; p < 0.001). However, the average antibiotic costs in the CRO group were significantly lower than that in the other two groups [CRO: 62.4 United States dollars (USD), ETP: 185.33 USD, and LVX: 204.85 USD; p < 0.001]. CONCLUSION: The resistance of cUTIs isolates to first-line antibiotic is high. Using ETP, CRO, and LVX in the treatment of cUTIs for good clinical response should be suggested. Among the three agents, ETP had better susceptibility than CRO and LVX, reached defervescence sooner, and was associated with shorter hospital stays. However, using CRO in cUTIs was less expensive than the other two agents.

Histopathological assessment of inflammation and expression of inflammatory markers in patients with ketamine-induced cystitis.

The aim of the current study was to evaluate the histopathological features of inflammation and the expression levels of inflammatory markers in tissue samples from patients with ketamine­induced cystitis. Bladder biopsy samples for histological analysis were obtained from 23 patients (18 men and 5 women) with a self­reported history of ketamine use and who were treated for cystitis at the Tri­Service General Hospital of Taipei, Taiwan. Immunohistochemical staining for cyclooxygenase­2 (COX­2), inducible nitric oxide synthase (iNOS), matrix metallopeptidase­9 (MMP­9), mammalian target of rapamycin (mTOR), and phosphorylated 40S ribosomal protein S6 (Phos­S6) was performed. The results revealed urothelial atypia in all patients, and intravascular eosinophil accumulation in 22 patients. Histopathological features included denuded urothelial mucosa, ulceration, collagen deposition, smooth muscle degeneration and vessel proliferation. Tissue samples were immunopositive for all of the inflammation markers, including the urothelium, vessel walls, and smooth muscle. COX­2 staining revealed a significant difference between the inflammatory levels in the urothelium and smooth muscle, and iNOS staining differed significantly between inflammatory levels in smooth muscle (p=0.029). A positive correlation was observed between the percentage of Phos­S6­positive cells and the levels of inflammation in the urothelium. These results add to the descriptive literature on the histopathological aspects of ketamine­induced cystitis, emphasizing the inflammatory nature and a possible role for proteins such as COX­2, iNOS and Phos­S6 in the degree of inflammation.

A case of lung cancer metastasized to the gastrointestinal anastomosis site where the primary gastric cancer was resected 17 years ago.

Metastasis from lung cancer, often found in the adrenal glands, bone, liver, brain, and kidneys, have been thought to be rare in the digestive system. When a metastatic tumor is found in the intestine, it is most commonly metastatic melanoma or carcinoma of the cervix uteri, ovary, or breast. Yet, intestinal metastases have been described in 11% of lung cancers at autopsy. These metastases may induce gastrointestinal perforation, obstruction, or bleeding. Patients with bleeding from small intestinal metastases secondary to lung cancer almost uniformly have poor prognoses. The lung cancer metastasized to the gastrointestinal site or location where a first primary cancer was once resected is never reported in the literature. We report the case of a 76-year-old man with a history of gastric adenocarcinoma treated by subtotal gastrectomy seventeen years ago who presented with lung cancer metastatic to the bone. One month later, he developed persistent melena due to duodenal metastases. Upper gastrointestinal endoscopy showed an ulcerative duodenal mass with bleeding. The pathohistological and immunohistochemical examinations of tissue from the pathologic fracture and the endoscopic biopsy specimen revealed metastatic poorly differentiated adenocarcinoma consistent with lung origin. The diagnosis of metastatic lung cancer can be rendered based on pathologic examination and immunohistochemical analysis, even without access to the primary lung tumor. In this case, the anastomosis site where a gastrectomy for gastric cancer was once performed might be a good niche or microenvironment for cancer cells or tumor stem cells to metastasize to.