A comparative phenotypic and genomic analysis of methicillin-resistant Staphylococcus aureus ST45 isolates from cellulitis and from osteomyelitis in Taiwan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics. METHODS: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSAs; n = 6) or osteomyelitis (OM-MRSAs; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and six OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS). RESULTS: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity, and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates. CONCLUSIONS: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health.

A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration.

Matrix metalloproteinases (MMPs), which are proteolytic enzymes, promote blood-brain barrier (BBB) disruption, leading to neuronal damage and neuroinflammation. Among them, MMP-9 upregulation serves as an inflammatory biomarker in the central nervous system (CNS). Currently, the development of marine organism-derived bioactive compounds or metabolites as anti-inflammatory drugs has received considerable attention. The 9,11-secosteroid, 3ß,11-dihydroxy-9,11-secogorgost-5-en-9-one (4p3f), is a novel sterol compound extracted from the soft coral Sinularia leptoclado with potential anti-inflammatory activity. However, the effect of and potential for brain protection of 4p3f on brain astrocytes remain unclear. Herein, we used rat brain astrocytes (RBAs) to investigate the effects and signaling mechanisms of 4p3f on lipopolysaccharide (LPS)-induced MMP-9 expression via zymographic, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence staining, promoter-reporter, and cell migration analyses. We first found that 4p3f blocked LPS-induced MMP-9 expression in RBAs. Next, we demonstrated that LPS induced MMP-9 expression via the activation of ERK1/2, p38 MAPK, and JNK1/2, which is linked to the STAT3-mediated NF-κB signaling pathway. Finally, 4p3f effectively inhibited LPS-induced upregulation of MMP-9-triggered RBA cell migration. These data suggest that a novel sterol from soft coral, 4p3f, may have anti-inflammatory and brain-protective effects by attenuating these signaling pathways of MMP-9-mediated events in brain astrocytes. Accordingly, the soft coral-derived sterol 4p3f may emerge as a potential candidate for drug development or as a natural compound with neuroprotective properties.

The Impact of Cefuroxime Susceptibility on Aeromonas Necrotizing Fasciitis Outcomes.

Despite aggressive antibiotic therapy and surgical debridement, Aeromonas necrotizing fasciitis (NF) can lead to high amputation and mortality rates. Our study compares the different antibiotic minimum inhibitory concentrations (MICs) via Epsilometer tests (E-tests) between non-survivors and survivors of Aeromonas NF of limbs. A prospective review of 16 patients with Aeromonas NF was conducted for 3.5 years in a tertiary coastal hospital. E-tests were conducted for 15 antimicrobial agents to determine the MIC value for Aeromonas species. These patients were divided into non-survival and survival groups. The clinical outcomes, demographics, comorbidities, presenting signs and symptoms, laboratory findings, and microbiological results between the two periods were compared. A total of four patients died, whereas 12 survived, resulting in a 25% mortality rate. A higher proportion of bloodstream infections (100% vs. 41.7%; p = 0.042), monomicrobial infections (100% vs. 33.3%; p = 0.021), shock (100% vs. 33.3%; p = 0.021), serous bullae (50% vs. 0%; p = 0.009), liver cirrhosis (100% vs. 25%; p = 0.009), chronic kidney disease (100% vs. 33.3%; p = 0.021), lower susceptibility to cefuroxime (25% vs. 83.3%; p = 0.028), and ineffective antibiotic prescriptions (75% vs. 16.7%; p = 0.029) was observed in non-survivors. Aeromonas NF is an extremely rare skin and soft-tissue infection that is associated with high mortality, bacteremia, antibiotic resistance, and polymicrobial infection. Therefore, antibiotic regimen selection is rendered very challenging. To improve clinical outcomes and irrational antimicrobial usage, experienced microbiologists can help physicians identify specific pathogens and test MIC.

Bullous skin signs and laboratory surgical indicators can quickly and effectively differentiate necrotizing fasciitis from cellulitis.

OBJECTIVES: The purpose of this prospective study was to investigate the different microorganisms associated with mortality, to evaluate the bullous skin sign, and to identify the positive predictive factors for differentiating necrotizing fasciitis (NF) from cellulitis on initial onset at the emergency department. METHODS: This prospective study was conducted in 145 consecutive patients with NF and 159 patients with cellulitis. Age, sex, comorbidities, infection site, microbiological results, condition of skin lesions, laboratory findings, vital signs, and clinical outcomes were compared between the two groups at the time of admission to the emergency room. RESULTS: A total of 15 patients in the NF group and two patients in the cellulitis group died, resulting in a mortality rate of 10.3% and 1.3%, respectively. The NF group had a significantly higher incidence of white blood cell counts, band form neutrophil, and C-reactive protein than the patients in the cellulitis group. Hemorrhagic bullae presentation appeared to have significantly associated with NF and death. CONCLUSION: The following diagnostic indicators can be effectively used to differentiate NF from cellulitis at the initial onset: presence of hemorrhagic bullae, white blood cell counts >11,000 cells/mm3, band forms >0%, C-reactive protein >100 mg/l, and systolic blood pressure ≤90 mm Hg at the time of consultation.

Exploring the Role of Intraoperative Positive Culture of Allograft Bone in Subsequent Postoperative Infections among Donors and Recipients in Bone Bank Processing.

BACKGROUND: Allografts have been frequently used in orthopedic procedures. The purposes of this study were to evaluate the discard rates and bacterial contamination of a bone bank, and to assess the clinical outcomes of recipients with bacterial culture-positive donor allografts. METHODS: We retrospectively reviewed 1764 allografts which were harvested from living donors and stored in a bone bank from 2018 to 2022. The donors whose allografts displayed bacterial contamination at retrieval of the primary hip or knee arthroplasty were followed for microbiology and subsequent prosthetic joint infection analysis. The infected pathogens, antibiotic treatment and subsequent infection were reviewed for the intraoperative positive culture group. RESULTS: The discard rate was 17%, and the bacterial contamination rate of bone retrieval was 2.15%. Thirty-eight allografts at retrieval displayed confirmed bacterial growth, and 37 patients did not reveal infective signs at 6 months follow-up. A total of 1464 allografts were stored and implanted, among which 28 allografts (1.91%) were confirmed to be positive for bacterial growth and 13 cases (0.89%) were confirmed as surgical site infections. CONCLUSIONS: Our results validate the suggestion that our bone bank system performs good quality monitoring to eliminate the risk of dissemination of viral and bacterial diseases and to decrease surgical site infection after allograft implantation. By ensuring aseptic conditions and contamination-reducing strategies during harvesting and thawing, the allografts can be safely stored and implanted while limiting bacterial contamination. Our findings confirm that the intraoperative positive cultures of allografts did not contribute to subsequent postoperative surgical site infection in donors and recipients.

Protective Effects of Sophoraflavanone G by Inhibiting TNF-α-Induced MMP-9-Mediated Events in Brain Microvascular Endothelial Cells.

The regulation of matrix metalloproteinases (MMPs), especially MMP-9, has a critical role in both physiological and pathological events in the central nervous system (CNS). MMP-9 is an indicator of inflammation that triggers several CNS disorders, including neurodegeneration. Tumor necrosis factor-α (TNF-α) has the ability to stimulate the production of different inflammatory factors, including MMP-9, in several conditions. Numerous phytochemicals are hypothesized to mitigate inflammation, including the CNS. Among them, a flavonoid compound, sophoraflavanone G (SG), found in Sophora flavescens has been found to possess several medicinal properties, including anti-bacterial and anti-inflammatory effects. In this study, mouse brain microvascular endothelial cells (bMECs) were used to explore TNF-α-induced MMP-9 signaling. The effects of SG on TNF-α-induced MMP-9 expression and its mechanisms were further evaluated. Our study revealed that the expression of MMP-9 in bMECs was stimulated by TNF-α through the activation of ERK1/2, p38 MAPK, and JNK1/2 via the TNF receptor (TNFR) with a connection to the NF-κB signaling pathway. Moreover, we found that SG can interact with the TNFR. The upregulation of MMP-9 by TNF-α may lead to the disruption of zonula occludens-1 (ZO-1), which can be mitigated by SG administration. These findings provide evidence that SG may possess neuroprotective properties by inhibiting the signaling pathways associated with TNFR-mediated MMP-9 expression and the subsequent disruption of tight junctions in brain microvascular endothelial cells.

Rational Use of Antibiotics and Education Improved Aeromonas Necrotizing Fasciitis Outcomes in Taiwan: A 19-Year Experience.

BACKGROUND: Aeromonas necrotizing fasciitis (NF) causes high rates of amputation and mortality, even after aggressive surgical debridement and antibacterial therapy. This study investigated the effects of rational use of antibiotics and education by infectious disease (ID) physicians on Aeromonas NF treatment outcomes. METHODS: Retrospective review for conducted for four years (period I, without an ID physician, December 2001 to December 2005) and 15 years (period II, with an ID physician, January 2006 to March 2021). In period II, the hospital-wide computerized antimicrobial approval system (HCAAS) was also implemented. A pretest-posttest time series analysis compared the two periods. Differences in clinical outcomes, demographics, comorbidities, signs and symptoms, laboratory findings, Aeromonas antibiotic susceptibility, and antibiotic regimens were compared between the two periods. RESULTS: There were 19 patients in period I and 53 patients in period II. Patients had a lower rate of amputation or mortality in period II (35.8%) compared with period I (63.2%). Forty-four patients (61.1%) had polymicrobial infections. In the emergency room, the rate of misdiagnosis decreased from 47.4% in period I to 28.3% in period II, while effective empiric antibiotic usage increased from 21.1% in period I to 66.0% in period II. After the ID physician's adjustment, 69.4% received monotherapy in period II compared to 33.3% in period I. CONCLUSIONS: Because Aeromonas NF had a high mortality rate and was often polymicrobial, choosing an antibiotic regimen was difficult. Using the HCAAS by an experienced ID physician can improve rational antibiotic usage and clinical outcomes in Aeromonas NF.

San-Zhong-Kui-Jian-Tang Exerts Antitumor Effects Associated With Decreased Cell Proliferation and Metastasis by Targeting ERK and the Epithelial-Mesenchymal Transition Pathway in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive cancer whose 5-year survival rate remains poor. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used in clinical practice as adjuvant therapy in cancers. However, its therapeutic effects and molecular mechanisms in OSCC remain unclear. METHODS: We investigated the potential therapeutic effects and molecular mechanism of SZKJT in OSCC in tumor cell lines and in tumor xenograft mice and evaluated combined SZKJT and cisplatin treatment efficacy. In vitro-cultured OSCC cells were administered SZKJT at different doses or SZKJT plus cisplatin, and cell proliferation, colony formation assays, and cell cycle analysis were used to assess the effects on cancer cell proliferation and apoptosis. We also analyzed the effects of SZKJT on oral cancer cell line migration, the regulation of mitogen-activated protein kinase (MAPK) signaling, and epithelial-mesenchymal transition (EMT)-associated genes. The antitumor effects of SZKJT plus cisplatin were also tested in vivo using a tumor-bearing NOD/SCID mice model. RESULTS: The results showed that SZKJT effectively inhibited OSCC cell proliferation, induced cell cycle S phase arrest, and induced cell apoptosis. SZKJT also inhibited cell migration by modulating the MAPK signaling and epithelial-mesenchymal transition (EMT) pathway. Further exploration suggested that SZKJT affects OSCC by modulating ERK pathway; downregulating vimentin, fibronectin, and Oct-4; and upregulating E-cadherin. In vivo, SZKJT significantly inhibited tumor growth, and SZKJT and cisplatin exerted synergistic antitumor effects in model animals. CONCLUSIONS: SZKJT exerts antitumor effects in OSCC cells. Additionally, SZKJT and cisplatin exhibit synergy in OSCC treatment. These findings support the clinical usage of Chinese herbal formulas as adjuvant therapy with chemotherapy in cancer treatment.

Rational Use of Ceftriaxone in Necrotizing Fasciitis and Mortality Associated with Bloodstream Infection and Hemorrhagic Bullous Lesions.

Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. The formation of hemorrhagic bullae is a special skin sign of NF. The purposes of this study were to investigate the incidence of hemorrhagic bullae formation and bacteremia associated with different organisms, to appraise the appropriate use of ceftriaxone, and to compare the clinical and laboratory risk indicators of NF patients with Gram-positive and Gram-negative infections on the initial examination. Methods: From March 2018 to December 2020, there were seventy-four NF patients with positive monomicrobial bacterial cultures enrolled based on surgical confirmation, and were categorized into two groups: the Gram-positive group and the Gram-negative group. Ceftriaxone susceptibility tests were carried out using the standard disk diffusion technique. Data, such as demographics, clinical outcomes, microbiological results, presentations of hemorrhagic bullae, and laboratory findings, were compared among these two groups. Results: The Gram-negative group included 52 patients, of whom 6 patients died, resulting in a mortality rate of 11.5%. The Gram-positive group included 22 patients and none died. Patients with bacteremia, hemorrhagic bullae, shock, fever, higher segmented forms and banded forms, and lower platelet counts constituted higher proportions in the Gram-negative group than in the Gram-positive group. The multivariate analysis identified six variables for the differentiation of Gram-negative and Gram-positive NF: the presentation of bacteremia, hemorrhagic bullae, shock at first consultation, fever with body temperature > 38.5 °C, band forms > 0%, and segmented forms ≦ 74%. A total of 66 isolates (89.2%) was susceptible to ceftriaxone. Conclusions: Gram-negative NF patients were significantly associated with hemorrhagic bullae presentation, blood stream infection, and mortality. Physicians should be alert to NF patients with the appearance of bacteremia, shock, fever, higher WBC banded and segmented forms, and lower platelet counts at the emergency department, with patients revealed to more likely have Gram-negative infections. Ceftriaxone with/without other appropriate antibiotics under the supervision of infectious doctors appeared to be clinically effective for the treatment of NF and blood stream infections.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear. The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions. Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd . was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort. The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.

Characterization of Methicillin-Resistant Staphylococcus aureus Isolates from Periprosthetic Joint Infections.

Periprosthetic joint infection (PJI) is a troublesome clinical issue in total joint arthroplasty (TJA). Although methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the most serious pathogen in PJIs, little is known about the genotypic and phenotypic characteristics of MRSA clones isolated from PJI patients. A total of 36 MRSA isolates from PJI patients were collected at the Chang-Gung Memorial Hospital in Taiwan from May 2016 to October 2019. All MRSA isolates were subjected to genome typing. The prevalence of Panton-Valentine leucocidin (PVL), the antibiotic susceptibility profile, and the biofilm formation ability were compared among different MRSA genogroups. Additionally, demographics and clinical manifestations of patients infected with different MRSA genogroups were investigated. Eight sequence types (STs) were identified among 36 isolated from PJIs. According to the incidence of MRSA genotypes in PJIs, in this study, we divided them into four groups, including ST8 (n = 10), ST59 (n = 8), ST239 (n = 11), and other STs (n = 7). For the antibiotic susceptibility testing, we found that all MRSA isolates in the ST239 group were highly resistant to ciprofloxacin, gentamicin trimethoprim-sulfamethoxazole, and levofloxacin. Additionally, ST239 MRSA also had a higher ability to form biofilm than other groups. Importantly, patients with ST239 infection typically had a fever and exhibited higher levels of inflammatory markers, including C-reactive protein (CRP) and white blood cell count (WBC). Epidemiological investigations revealed that knee PJIs were mainly attributed to infection with ST59 MRSA and increasing trends for infection with ST8 and other ST types of MRSAs in PJI patients were observed from 2016 to 2019. The identification of MRSA genotypes in PJIs may be helpful for the management of PJIs.

Monomicrobial Necrotizing Fasciitis and Sepsis Caused by Pseudomonas aeruginosa and Pseudomonas fluorescens: a Series of Ten Cases.

Monomicrobial necrotizing fasciitis caused by Pseudomonas species is a rare infection. This study aimed to elucidate the specific characteristics and clinical outcomes of necrotizing fasciitis caused by Pseudomonas aeruginosa and Pseudomonas fluorescens. Ten patients with monomicrobial necrotizing fasciitis caused by Pseudomonas species were retrospectively reviewed in an 8-year period. Differences in mortality, patient characteristics, clinical presentation, laboratory data, and clinical outcomes were compared between the death and survival groups. Two patients died, showing a mortality rate of 20%. P. aeruginosa was the causative agent in nine patients and P. fluorescens in one patient. The most common comorbidity was type 2 diabetes (n = 5). We found that patients who died had lower albumin levels and higher leukocyte counts than those who survived. Monomicrobial necrotizing fasciitis caused by Pseudomonas species needs emergent surgical intervention and aggressive intensive care due to the high mortality rate. We report the first case of monomicrobial necrotizing fasciitis caused by P. fluorescens. Severe hypoalbuminemia and high leukocyte counts in initial laboratory examinations can be considered poor prognostic factors.

Brain Protective Effect of Resveratrol via Ameliorating Interleukin-1ß-Induced MMP-9-Mediated Disruption of ZO-1 Arranged Integrity.

In the central nervous system (CNS), the matrix metalloproteinase-9 (MMP-9) is induced by several factors and contributes to CNS disorders, including inflammation and neurodegeneration. Thus, the upregulation of MMP-9 has been considered to be an indicator of inflammation. Interleukin-1ß (IL-1ß) is an important proinflammatory cytokine which can induce various inflammatory factors, such as MMP-9, in many inflammatory disorders. Several phytochemicals are believed to reduce the risk of several inflammatory disorders, including the CNS diseases. Among them, the resveratrol, a principal phenolic compound of the grape, blueberry, and mulberry peels and Cassia plants, has been shown to possess several medicinal properties, including antioxidative, anti-inflammatory, and antitumor function. Herein, we used mouse-brain microvascular endothelial cells (bMECs) to demonstrate the signaling mechanisms of IL-1ß-induced MMP-9 expression via zymographic, RT-PCR, Western blot, reactive oxygen species (ROS) detection, immunofluorescence stain, and promoter reporter analyses. Then we evaluated the effects of resveratrol on IL-1ß-induced MMP-9 expression in bMECs and its mechanism of action. We first demonstrated that IL-1ß induced MMP-9 expression in bMECs. Subsequently, IL-1ß induced MMP-9 expression via ROS-mediated c-Src-dependent transactivation of EGFR, and then activation of the ERK1/2, p38 MAPK, JNK1/2, and NF-κB signaling pathway. Finally, we determined that IL-1ß-induced upregulation of MMP-9 may cause the disruption of the arranged integrity of zonula occludens-1 (ZO-1), but this could be inhibited by resveratrol. These data indicated that resveratrol may have antioxidative and brain-protective activities by reducing these related pathways of ROS-mediated MMP-9 expression and tight junction disruption in brain microvascular endothelial cells.

Incidence of different types of subsequent fractures and related mortality in Taiwan.

Hip fracture is the most common type of fracture to occur within 2 years after an initial fracture. Mortality risk increases when a subsequent fracture occurs. The occurrence of subsequent fracture is significantly higher in patients with hip fractures than others. Prevention of subsequent fracture is of paramount important. PURPOSE: Osteoporotic fracture significantly increases risk of subsequent fracture. In this retrospective cohort study, we used the Taiwan National Health Insurance Database (NHIRD) to analyze data on fractures in a group at high risk of osteoporosis. We aimed to distinguish differences in subsequent fracture types and their relationship with mortality. METHODS: We enrolled patients aged ≥ 50 years old who were diagnosed with an initial fracture classified as hip, vertebral, upper end of the humerus, or wrist. Data from 2 years of follow-up were analyzed. Risks of subsequent fracture events and mortality were calculated by Kaplan-Meier estimation and assessed with Cox proportional hazards models. RESULTS: We included 375,836 patients from the 2011-2015 NHIRD. Patients with initial hip fracture had the highest incidence of subsequent fracture at both 1- and 2-year follow-up (7.0% and 10.9%). Subsequent fractures occurred mainly at the hip. Conversely, other patients had a higher proportion of subsequent vertebral fracture. Patients with subsequent fracture classified as hip, vertebral, and upper end of the humerus had significantly higher cumulative mortality rates than that of patients who had no subsequent fracture, with adjusted hazard ratios of 1.64 (95% CI = 1.57-1.71, p < 0.01), 1.06 (95% CI = 1.00-1.12, p = 0.04), 1.31 (95% CI = 1.17-1.46, p < 0.01), respectively. CONCLUSION: Patients who experienced an initial hip fracture are at greatest risk of subsequent fracture, most commonly the hip. Occurrence of subsequent fractures was associated with an increased mortality risk. Thus, there is a need for early intervention following initial hip fractures.

Bacteriology and mortality of necrotizing fasciitis in a tertiary coastal hospital with comparing risk indicators of methicillin-resistant Staphylococcus aureus and Vibrio vulnificus infections: a prospective study.

BACKGROUND: Vibrio vulnificus has been reported as the leading causative pathogen of necrotizing fasciitis (NF) and related fatality in the coastal area. Necrotizing fasciitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and V. vulnificus have high mortality rates. The purpose of this prospective study was to clarify the clinical characteristics between death and survival NF patients, to investigate bacteriologic profile and mortality of NF patients, and to compare risk indicators of MRSA and V. vulnificus NF patients. METHODS: This prospective study was conducted in 184 consecutive NF patients over a period of three years in a tertiary coastal hospital. Differences in mortality, laboratory findings, microbiology and clinical outcomes were compared between the death and survival groups, and the V. vulnificus and MRSA subgroups. RESULTS: Twenty patients died, resulting in a mortality rate of 10.9%, and there were 108 patients with a monomicrobial infection (58.7%). The death group had a significantly higher incidence of shock at emergency room and bacteremia than did the survival group. Vibrio species (40 cases) and S. aureus (31 cases) were the two major pathogens. Significant differences with respect to hepatic dysfunction, shock, the event with seawater or seafood contact, bacteremia, C-reactive protein, mean platelet counts, and the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score were observes between V. vulnificus and MRSA groups. CONCLUSIONS: NF patients with both hepatic dysfunction and diabetes mellitus, bacteremia and shock have significantly higher mortality. We should be aware of the increasing incidence of monomicrobial NF and higher mortality rates of Gram-negative pathogens in the warm coastal area. LRINEC score is not a suitable diagnostic indicator for V. vulnificus NF, which is more rapidly progressive and fulminant than MRSA NF. NF needed team works by early suspicion, immediate surgical intervention and aggressive care, which can successfully decrease mortality.

GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells.

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.

The survival outcome of nasopharyngeal cancer patients with traditional Chinese medicine external use: A hospital-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: External-use traditional Chinese medicine (TCM) agents are widely used to relieve the adverse effects of radiation therapy in nasopharyngeal cancer patients. AIM OF THE STUDY: Our study aimed to evaluate the influence of external-use TCM agents to relieve radiotherapy-related adverse effects on the efficacy of radiation therapy and the prognosis of nasopharyngeal cancer patients. MATERIALS AND METHODS: By using the Chang Gung Research Database (CGRD), we analyzed 1823 newly diagnosed nasopharyngeal cancer patients with radiotherapy-related adverse effects between 2001/01 and 2015/12. We used Kaplan-Meier analysis and a Cox regression model to estimate the differences in effects on survival outcomes between two groups, TCM external users and non-TCM external users. RESULTS: We found that TCM external users had significantly better 3-year and 5-year overall survival rates (log-rank test, p = 0.0377 and p = 0.034, respectively) than non-TCM external users. The 3-year and 5-year disease-free survival rates were not statistically significantly different between the groups. We also found a trend of improved 3-year and 5-year overall survival rates in TCM external users with advanced-stage disease, without statistical significance (log-rank test, p = 0.10 and p = 0.089, respectively). The subgroup analysis revealed lower risks of mortality in TCM external users among the nonhypertension, nonhyperlipidemia, nonischemic heart disease, noncirrhosis, and nonchronic kidney disease groups. CONCLUSIONS: Our study showed that TCM agents external use could significantly improve 3-year and 5-year overall survival rates in nasopharyngeal cancer patients with radiotherapy-related adverse effects.

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

The Relationships between Leptin, Genotype, and Chinese Medicine Body Constitution for Obesity.

METHODS: The adults with body mass index (BMI) more than 27 kg/m2 were enrolled in the study. General personal information, physical condition, TCMBC, biochemical, and SNPs were collected for eligible subjects. The body constitution questionnaire (BCQ) was used to evaluate the relationships between TCMBC tendency, biochemical values, and obesity-related SNPs. RESULTS: Obesity patients tended to have a yin deficiency constitution (YinDC) (n = 33, 66.0%); however, TCMBC in combination is not uncommon (30 subjects with more than two TCMBC in combination). For biochemical profiles, leptin was higher among patients with yang deficiency constitution (YangDC) (YangDC versus non-YangDC: 29.7 ± 24.8 versus 15.9 ± 9.9, P=0.020) and YinDC (YinDC versus non-YinDC: 28.8 ± 23.5 versus 14.4 ± 9.6, P=0.020). The leptin level was highest among YangDC subjects. Higher leptin was found among subjects with three-combined TCMBC than balanced TCMBC subjects who were not inclined to any of three TCMBC. For obesity-related SNPs, the adrenergic receptor beta-3 (ADRB3) gene tended to be high expression among YangDC (YangDC versus non-YangDC: 89.7% versus 71.4%, P=0.091) and uncoupling protein 1 (UCP1) tended to be high expression among phlegm-stasis constitution (PSC) (PSC versus non-PSC: 37.9% versus 9.5%, P=0.052). CONCLUSIONS: The relationships between TCMBC, leptin, and SNPs present alternative viewpoints about TCMBC and could be used as a guide to treat obese patients.