IL-10 Enhances the Inhibitory Effect of Adipose-Derived Stromal Cells on Insulin Resistance/Liver Gluconeogenesis by Treg Cell Induction.

The modulation of cellular phenotypes within adipose tissue provides a potential means for therapeutic intervention for diabetes. Endogenous interleukin-10 (IL-10) protects against diet-induced insulin resistance. We examined the effects and mechanisms of action of IL-10-treated adipose-derived stromal cells on diabetes-induced insulin resistance and liver gluconeogenesis. We harvested stromal vascular fractions (SVFs) from the adipose tissue of diabetic (Leprdb/db) mice and treated them with IL-10 in vitro. SVFs treated with 10 or 100 ng of IL-10 were injected into the inguinal adipose tissue of Leprdb/db mice. IL-10 treatment suppressed the mRNA expression of IL-6, IL-33, CCL2, TNF-α, and IL-1ß. Additionally, it suppressed the protein expression of IL-6, pmTOR, pJNK, and pNF-κB but enhanced Foxp3 mRNA expression in SVFs from diabetic mice. Meanwhile, IL-10 treatment repressed CCL2 and PDGFRα expression in adipose tissue macrophages (ATMs) and IL-6 expression in non-ATMs but increased the Foxp3 and IL-10 mRNA expression of ATMs from diabetic mice. Injection of IL-10-treated SVFs decreased the IL-6, IL-33, CCL2, IL-1ß, and CCL2 but enhanced the Foxp3 and IL-10 mRNA expression of adipose tissue from Leprdb/db mice. Furthermore, injection of IL-10-treated SVFs increased CD4+ regulatory T cells (Tregs) in SVFs and adipose IL-10 levels and suppressed plasma adiponectin levels and DPP4 activity in diabetic mice. Injection of IL-10-treated SVFs decreased hepatic G6PC and PCK1 mRNA expression and increased Akt activation, STAT3 phosphorylation in the liver, and glucose tolerance in diabetic mice. Our data suggest that IL-10 treatment decreases inflammation in adipose SVFs of diabetic mice. Injection of IL-10-treated SVFs into the adipose tissue decreased diabetes-induced gluconeogenesis gene expression, DPP4 activity, and insulin resistance by enhancing Treg cells in diabetic mice. These data suggest that IL-10-treated adipose stromal vascular cells could be a promising therapeutic strategy for diabetes mellitus.

Hemodynamic and Clinical Profiles of Pulmonary Arterial Hypertension Patients with GDF2 and BMPR2 Variants.

Asians have a higher carrier rate of pulmonary arterial hypertension (PAH)-related genetic variants than Caucasians do. This study aimed to identify PAH-related genetic variants using whole exome sequencing (WES) in Asian idiopathic and heritable PAH cohorts. A WES library was constructed, and candidate variants were further validated by polymerase chain reaction and Sanger sequencing in the PAH cohort. In a total of 69 patients, the highest incidence of variants was found in the BMPR2, ATP13A3, and GDF2 genes. Regarding the BMPR2 gene variants, there were two nonsense variants (c.994C>T, p. Arg332*; c.1750C>T, p. Arg584*), one missense variant (c.1478C>T, p. Thr493Ile), and one novel in-frame deletion variant (c.877_888del, p. Leu293_Ser296del). Regarding the GDF2 variants, there was one likely pathogenic nonsense variant (c.259C>T, p. Gln87*) and two missense variants (c.1207G>A, p. Val403Ile; c.38T>C, p. Leu13Pro). The BMPR2 and GDF2 variant subgroups had worse hemodynamics. Moreover, the GDF2 variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL, p = 0.002) in comparison to the value in the non-BMPR2/non-GDF2 mutant group (267.8 ± 185.8 pg/mL). The BMPR2 variant carriers had worse hemodynamics compared to the patients with the non-BMPR2/non-GDF2 mutant group. Moreover, there was a significantly lower GDF2 value in the GDF2 variant carriers compared to the control group. GDF2 may be a protective or corrected modifier in certain genetic backgrounds.

Performance of Prehospital ECG and Impact on Prehospital Service Time: Comparison between EMT-II and EMT-P Teams.

Background: Prehospital electrocardiogram (PHECG) shortens door-to-balloon time in patients with ST-elevation myocardial infarction. However, it may increase the prehospital service time, thus offsetting the benefits gained. The performance of PHECG could be influenced by the proficiency of the emergency medical technicians (EMTs). Objectives: To investigate whether there are differences in the performance of PHECG between EMT-II and EMT-paramedics (EMT-P). Methods: This prospectively designed, retrospectively analyzed study of PHECG was conducted in Taipei from February 2019 to April 2021. Comparisons were made between EMT-II and EMT-P teams. The primary outcomes were the acceptance of PHECG suggestions and prehospital service time. The secondary outcomes were gender disparities in the primary outcomes. Results: A total of 2,991 patients were included, of whom 2,617 received PHECG. For the primary outcomes, the acceptance of PHECG was higher in those approached by EMT-P (99.6% vs. 71.5%, p < 0.001). The scene time and scene-to-hospital time showed no significant differences. For gender disparities, the acceptance of PHECG in female patients was significantly lower in those approached by EMT-II (59.3% vs. 99.2%, p < 0.001). The scene time and scene-to-hospital time were generally longer in the female patients, especially in the younger and middle age groups. Compared to EMT-P, both were significantly longer in the female patients approached by EMT-II. Conclusions: The acceptance of PHECG was lower in those approached by EMT-II, especially in females. Although there were generally no significant differences between EMT-II and EMT-P, the scene time and scene-to-hospital time were significantly longer in female patients, especially in those aged < 75 years approached by EMT-II.

Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells.

Adipogenesis has emerged as a new therapeutic target for regulating metabolism and achieving anti-inflammatory and anti-atherosclerotic effects via the release of adiponectin. However, at present, the effects and mechanism of action of dipeptidyl peptidase 4 (DPP4) stimulation on adiponectin production and adipogenesis have not been clarified. Here, we investigated the effects of DPP4 stimulation with monocyte chemoattractant protein-1 (MCP-1) on platelet-derived growth factor receptor alpha (PDGFRα) expression in adipose tissue and blood adiponectin levels. Stromal vascular fractions (SVFs) purified from human subcutaneous adipose tissue and inguinal adipose tissue of obese and diabetic (Leprdb/db) mice were treated with 50 ng of MCP-1 and plasma from control (Lepr+/+) mice supplemented with 10 ng or 50 ng of MCP-1. Treatment of SVFs from human subcutaneous adipose tissues with 50 ng of MCP-1 significantly increased AdipoQ, DPP4, peroxisome proliferator-activated receptor gamma (PPARγ), fatty-acid-binding protein (FABP4), and SERBF1 mRNA expression. MCP-1-supplemented plasma increased adiponectin, CCAAT-Enhancer-binding protein alpha (C/EBPα), DPP4, IL-33, and PDGFRα mRNA expression and adiponectin and DPP4 protein expression, while decreasing the expression of IL-10 mRNA in SVFs compared with the levels in the plasma treatment group. MCP-1-supplemented plasma was shown to increase PPARγ, PPARγ2, adiponectin, DPP4, and FABP4 and decrease IL-10 mRNA expression in PDGFRα cells from adipose tissue. Meanwhile, MCP-1-supplemented plasma increased MCP-1, PDGFRα, TNFα, adiponectin, and IL-1ß and decreased IL-10 and FOXP3 mRNA expression in DPP4 cells. Moreover, the injection of MCP-1-supplemented plasma into adipose tissue increased the proportion of DPP4+ cells among PDGFRα+ cells from adipose tissue and plasma adiponectin levels of Leprdb/db mice compared with the levels in the plasma injection group. Our results demonstrate that DPP4+ cells are important adipose progenitor cells. Stimulation of DPP4 with MCP-1 increases adipogenesis-related gene expression and the population of DPP4+ cells among PDGFRα+ cells in SVFs and blood adiponectin levels. DPP4 stimulation could be a novel therapy to increase local adipogenesis and systemic adiponectin levels.

Prognostic Role of Subsequent Thrombocytopenia in Necrotizing Fasciitis Without Liver Disease.

BACKGROUND: Necrotizing fasciitis (NF) is a life-threatening disease with a fulminant presentation. Although early diagnosis can be aided by combining physical examination, the Laboratory Risk Indicator for Necrotizing Fasciitis score, and computed tomography, a mortality rate of 30% is still reported. In the modern times, an economical and efficient biomarker for predicting mortality in NF patients is still lacking. Platelet count is typically measured in routine blood tests and aids in predicting disease severity. We aimed to clarify the role of platelet count as a predictive factor for aspects of prognosis, such as mortality and surgical outcomes, in patients with NF. METHODS: We identified 285 patients with NF between 2018 and 2020 in a single medical center in southern Taiwan. Medical records were collected for the evaluation of patients with thrombocytopenia. Univariate and multivariate analyses were performed for different outcomes. RESULTS: We included 115 patients with confirmed diagnoses of NF. Twelve patients died with a mortality rate of 10.4%. Patients with thrombocytopenia exhibited a higher mortality rate (20.9% vs 4.2%, P = 0.006), more shock episodes (51.2% vs 11.1%, P < 0.001), higher intensive care unit admission rate (46.5% vs 13.9%, P < 0.001), and longer hospital length of stay (37.49 ± 24.12 days vs 28.82 ± 14.63 days, P = 0.037) than those without thrombocytopenia. All patients infected with Vibrio species exhibited thrombocytopenia. In multivariate analysis, independent risk factors for mortality were thrombocytopenia (odds ratio, 4.57; 95% confidence interval, 1.08-19.25) and single gram-negative bacterial culture from the wound (odds ratio 6.88; 95% confidence interval, 1.58-29.96). CONCLUSIONS: In patients with NF and subsequent thrombocytopenia, a higher mortality rate, greater numbers of shock episodes, higher demand for intensive care unit, and longer hospital length of stay were observed than in those without thrombocytopenia. In patients with NF, platelet count is a valuable and economic indicator of prognosis. Once thrombocytopenia developed in patients with necrotizing fasciitis, aggressive antibiotic treatment and surgical management are required to improve the chances of recovery.

Mechanical ventilation enhances Acinetobacter baumannii-induced lung injury through JNK pathways.

BACKGROUND: Patients in intensive care units (ICUs) often received broad-spectrum antibiotic treatment and Acinetobacter baumannii (A.b.) and Pseudomonas aeruginosa (P.a.) were the most common pathogens causing ventilator-associated pneumonia (VAP). This study aimed to examine the effects and mechanism of mechanical ventilation (MV) on A.b.-induced lung injury and the involvement of alveolar macrophages (AMs). METHODS: C57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1-/-) mice received MV for 3 h at 2 days after nasal instillation of A.b., P.a. (1 × 106 colony-forming unit, CFU), or normal saline. RESULTS: Intranasal instillation of 106 CFU A.b. in C57BL/6 mice induced a significant increase in total cells and protein levels in the bronchoalveolar lavage fluid (BALF) and neutrophil infiltration in the lungs. MV after A.b. instillation increases neutrophil infiltration, interleukin (IL)-6 and vascular cell adhesion molecule (VCAM) mRNA expression in the lungs and total cells, IL-6 levels, and nitrite levels in the BALF. The killing activity of AMs against A.b. was lower than against P.a. The diminished killing activity was parallel with decreased tumor necrosis factor-α production by AMs compared with A.b. Inducible nitric oxide synthase inhibitor, S-methylisothiourea, decreased the total cell number in BALF on mice receiving A.b. instillation and ventilation. Moreover, MV decreased the A.b. and P.a. killing activity of AMs. MV after A.b. instillation induced less total cells in the BALF and nitrite production in the serum of JNK1-/- mice than those of WT mice. CONCLUSION: A.b. is potent in inducing neutrophil infiltration in the lungs and total protein in the BALF. MV enhances A.b.-induced lung injury through an increase in the expression of VCAM and IL-6 levels in the BALF and a decrease in the bacteria-killing activity of AMs. A lower inflammation level in JNK1-/- mice indicates that A.b.-induced VAP causes lung injury through JNK signaling pathway in the lungs.

Bisphosphonate-Related Osteonecrosis of the Jaw.

OBJECTIVES: Antiresorptive agents for bone pain were widely used to treat patients with advanced osteoporosis, multiple myeloma, and bone metastatic cancer. In recent years, however, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been a rare but major complication of this therapy. Most patients with BRONJ undergo dental procedures during treatment with antiresorptive agents. However, BRONJ may also occur spontaneously. This study reports 13 BRONJ patient cases at Kaohsiung Veterans General Hospital, Taiwan, and their related treatments. We also compare patients with cancer with patients with osteoporosis in treatment outcomes. METHODS: Thirteen symptomatic patients with BRONJ were reviewed between 1985 and 2018 at Kaohsiung Veterans General Hospital. We included patients at advanced stage who were hospitalized for infection control of osteonecrosis of the jaw and excluded asymptomatic patients at stage 0 and stage 1. Four multiple myeloma, 3 patients with bone metastatic breast cancer and 6 patients with advanced osteoporosis (average ages, 63.57 ± 14.54 years in cancer patients and 79.5 ± 9.31 years in osteoporosis patients; average drug durations, 25.86 ± 27.23 months in cancer patients and 58.33 ± 23.87 months in osteoporosis patients; average follow-up times, 22.71 ± 14.46 months in cancer patients and 28.08 ± 36.35 months in osteoporosis patients) were included. RESULTS: Seven patients were defined as having stage 3 (53.8%) and 6 as having stage 2 (46.2%) medication-related osteonecrosis of the jaw, according to the American Association of Oral and Maxillofacial Surgeons classification. The complete response rate with totally healed mucosa was 61.5%. Four cancer patients received free fibular flap (FFF) reconstruction with a high complete response rate (100%). All of them had a relatively better performance status, and the average age was also younger than osteoporosis patients. CONCLUSION: Free fibular flap with a high complete response rate may improve pain relief and infection control for patients with BRONJ. Younger age is seemed to be a great indicator for FFF, but poor self-care ability (Eastern Cooperative Oncology Group status >3) is not suitable for these surgical treatments.

Haematogenous Klebsiella pneumoniae osteomyelitis.

OBJECTIVES: Klebsiella pneumoniae infection has been associated with alcoholic and diabetic patient populations, especially in Asian populations. K. pneumonia wound infection is common, but K. pneumonia without wound osteomyelitis (OM) is relatively rare. However, the pathogenesis of haematogenous K. pneumonia without open wound OM still unclear until now. In our research, we are trying to collect patients with haematogenous K. pneumonia osteomyelitis (K.p OM) at our hospital and to evaluate their contributing factors. METHODS: We compiled a retrospective database of haematogenous K. pneumonia osteomyelitis (K.p OM) from 1990 to 2019 at our hospital. Patients' bone cultures without K. pneumonia infection were excluded. Sixteen patients with haematogenous K.p OM were recruited. Patients' basic information, comorbidities, wound history, the biochemical examination of the blood, bacterial blood, bone, urine, and liver abscess cultures, the location of OM, corresponding treatments, and post operation K.p wound infection history were reviewed retrospectively. The collected data were analyzed using SPSS software. RESULTS: Unwounded haematogenous K.p OM had a statistically significant and positive correlation with liver insufficiency (P = .037; OR = 2.200), advanced age (≥ 65 years) (P = .037; OR = 2.200) and male gender (P = .03; OR = 1.833). DM, hypertension, steroid usage, GI or GU tract K.p infection, post operation K.p wound infection, hypoalbuminemia, and the location of K.p OM had no significant relationship to outcomes. CONCLUSION: Male patients of advanced age (> 65 years) and patients with liver insufficiency, including liver cirrhosis and hepatitis, have a strong correlation with unwounded haematogenous K.p OM.

Osteomyocutaneous Free Fibula Flap Prevents Osteoradionecrosis and Osteomyelitis in Head and Neck Cancer Reconstruction.

BACKGROUND: Osteoradionecrosis (ORN) is one of the most severe complications of free fibula reconstruction after radiotherapy. The gold standard treatment of osteomyelitis involves extensive debridement, antibiotics, and sufficiently vascularized muscle flap coverage for better circulation. Therefore, we hypothesized that free fibula flap with muscle could decrease the risk of ORN. METHODS: This study consisted of 85 patients who underwent reconstruction with free fibula flap in head and neck cancer by a single reconstructive surgeon at Kaohsiung Veterans General Hospital over a period of 19 years (1998-2016). Patients with postoperative adjuvant radiotherapy were included in the study and were grouped by either free fibula osteocutaneous flap or free fibula osteomyocutaneous flap (with flexor hallucis longus muscle), and the incidence of ORN was compared. RESULTS: Of the 85 patients, 15 were reconstructed with osteocutaneous fibula flap and 70 were with osteomyocutaneous fibula flap. The rate of ORN or osteomyelitis was significantly lower in the muscle group (18.6%, n = 13/70 vs. 46.7%, n = 7/15, p = 0.020, Chi-square test). CONCLUSION: Vascularized muscle transfer increases perfusion of surrounding tissues and the bone flap, thereby decreasing the incidence of osteomyelitis or osteonecrosis.

Risk of Free Flap Failure in Head and Neck Reconstruction: Analysis of 21,548 Cases From A Nationwide Database.

BACKGROUND: Head and neck reconstruction is complicated and is made even more challenging by free flap failure. We identified risk factors associated with free flap failure in records extracted from a nationwide database of a 23 million populations. METHODS: We used International Classification of Diseases, Ninth Version, codes 140 to 149 and 161 to identify patients in Taiwan's National Health Insurance Research Database with head and neck cancer between 2000 and 2013. Patient's age, sex, neoadjuvant treatment, comorbidities, and anticoagulation use were also retrieved. Free flap reconstruction twice, or free flap and pedicle flap reconstructions during the same hospitalization were recorded as free flap failure. Logistic regression was used to identify factors that increased risk of free flap failure. RESULTS: A total of 21,548 patients with head and neck cancer were identified; 883 (4.1%) experienced free flap failure. Use of aspirin, clopidogrel, urokinase, prostaglandin (PGE1), low-molecular-weight heparin, and operation time were associated with free flap failure. However, some potential confounders could not be identified from the database. CONCLUSIONS: Several statistically significant findings were prone to influence by potential confounders. The clinically applicable result was that longer operation time and preoperative chemotherapy could increase the likelihood of free flap failure. On the other hand, several factors were proved to be irrelevant to free flap failure.

Clinical Importance and Risk Factors for Postoperative Late-Onset Pneumonia After Major Oral Cancer Surgery With Microvascular Reconstruction.

BACKGROUND: Pulmonary complications are common among patients who have undergone major oral cancer surgery with microvascular reconstruction. Current literatures focused on early-onset pneumonia in the postoperative acute stage. In contrast, we are aiming to identify the clinical importance and the risk factors associated with late-onset pneumonia in oral cancer patients after acute stage. METHODS: In total, 195 patients were included from May 2014 to December 2016 and followed up for up to 1 year after surgery. Their medical histories were reviewed to identify the risk factors of late-onset pneumonia and outcome. Primary outcome was late-onset pneumonia. Other outcome measures included early-onset pneumonia, tumor recurrence, and death within 1 year after surgery. RESULTS: Patients with late-onset pneumonia have demonstrated a significantly higher rate of tumor recurrence (P < 0.001) and death within 1 year (P < 0.001). Independent risk factors of late-onset pneumonia identified were age (P = 0.031), previous radiotherapy (P = 0.017), postoperative radiotherapy (P = 0.002), flap size (P = 0.001), flap type other than osteocutaneous fibula flap (P = 0.009), and tumor recurrence (P < 0.001). CONCLUSIONS: Late-onset pneumonia can act as a warning sign for oral cancer patients who have received microsurgical reconstruction, for its high correlation with tumor recurrence and mortality rate.

Pioglitazone reversed the fructose-programmed astrocytic glycolysis and oxidative phosphorylation of female rat offspring.

Excessive maternal high-fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant's brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that determines cellular metabolism. Astrocytes, a nonneuronal cell type in the brain, are considered to support the high-energy demands of neurons by supplying lactate. In this study, the effects of maternal HFD on astrocytic glucose metabolism were investigated using hippocampal primary cultures of female infants. We found that glycolytic capacity and mitochondrial respiration and electron transport chain were suppressed by maternal HFD. Mitochondrial DNA copy number and mitochondrial transcription factor A expression were suppressed by maternal HFD. Western blots and immunofluorescent images further indicated that the glucose transporter 1 was downregulated whereas the insulin receptor-α, phospho-insulin receptor substrate-1 (Y612) and the p85 subunit of phosphatidylinositide 3-kinase were upregulated in the HFD group. Pioglitazone, which is known to increase astrocytic glucose metabolism, effectively reversed the suppressed glycolysis, and lactate release was restored. Moreover, pioglitazone also normalized oxidative phosphorylation with an increase of cytosolic ATP. Together, these results suggest that maternal HFD impairs astrocytic energy metabolic pathways that were reversed by pioglitazone.

Aryl hydrocarbon receptor ligands enhance lung immunity through intestinal IKKß pathways.

BACKGROUND: Infection by antibiotic-resistant microorganisms is common in intensive care units and has become a global problem. Here, we determined the effect of aryl hydrocarbon receptor (AhR) stimulation on antibiotics-induced systemic defense impairment and its mechanisms. METHODS: C57BL/6 wild-type (WT) mice received combined antibiotics with or without Ahr ligands (tryptophan and indole), or dead Lactobacillus plantarum supplementation. The defense mechanisms against Pseudomonas aeruginosa infection in the lung were examined. RESULTS: Antibiotic treatments decreased the phagocytic activity, physiological activity, and the peroxynitrite production of alveolar macrophage (AMs). It also enhanced P. aeruginosa pneumonia-induced bacterial counts in the lung. Tryptophan and dead L. plantarum supplementation reversed antibiotic-induced intracellular adhesion molecule (ICAM) as well as IL-6 expression, and increased P. aeruginosa pneumonia-induced bacterial counts in the lung and increased phagocytic activity and peroxynitrite production of AMs. Moreover, these treatments reversed the antibiotics-induced reduction of Ahr expression, antibacterial proteins, reactive oxygen species (ROS) production, and NF-κB DNA binding activity of the intestinal mucosa and plasma IL-6 levels. P. aeruginosa counts increased and phagocytic activity of AMs and myeloperoxidase (MPO) activity decreased in intestinal IKKß depleted mice. Antibiotics, antibiotic with tryptophan feeding, or antibiotic with dead L. plantarum feeding treatments did not change the phagocytic activity and peroxynitrite production of AMs, plasma IL-6 levels, and the expression of Ahr of intestine in intestinal IKKß depleted mice. CONCLUSION: Antibiotic treatment impairs lung immune defenses by decreasing Ahr expression in the intestine and peroyxnitrite production of the AMs. Ahr ligands reverses antibiotic-induced lung defense against bacterial infection through intestinal ROS production and NF-κB activation. The gut is critical in maintaining lung defense mechanism through the intestinal IKKß pathways.

The safety and benefit of using oxidized regenerated cellulose to position free flap pedicle in head and neck reconstruction.

BACKGROUND: Oxidized regenerated cellulose (ORC; Surgicel®; Ethicon, Neuchâtel, Switzerland) is an absorbable hemostatic agent used for hemostasis in operation, although some surgeons use it to position free flap pedicles. The increasing risk of vessel compromise is a huge concern. However, no scientific data to date demonstrate the safety and benefit of using ORC in microvascular surgery. In the present study, we compared the outcome of microvascular head and neck reconstruction with and without pedicle placement using ORC. MATERIALS AND METHODS: From January 2015 to December 2017, we reviewed patients undergoing microvascular surgery with free fibular osteocutaneous flap in our hospital. The patients were divided into the ORC group and non-ORC group and their baseline characteristics and outcomes were compared. RESULTS: In total, there were 27 patients in the ORC group and 67 in the non-ORC group. The non-ORC group had significantly higher cigarette consumption (70.4% vs. 89.6%; p = .022). The outcome of the ORC group was better regarding arterial thrombosis (0% vs. 3%), flap failure (0% vs. 4.5%), hematoma (7.4% vs. 10.4%), and wound complications (25.9% vs. 44.8%). The ORC group had a worse result than the non-ORC group for vein thrombosis (7.4% vs. 4.5%) and duration of hospitalization (24.111 days vs. 23.627 days). However, none of above results was significant. CONCLUSIONS: Though this study was underpowered to detect the differences, the results showed a trend toward better outcomes of flaps and wounds in the ORC group. It seems that using ORC in this field is safe and beneficial.

Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis.

Diet-associated insulin resistance (IR) is intimately correlated with the progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has been applied to enhance insulin sensitivity. With limited permeability to blood-brain-barrier, it is unclear that whether oral PIO available to cure both the peripheral IR and the impairment in the hippocampus. We evaluated the levels of peripheral and hippocampal IR via the homeostatic model assessment of insulin resistance and hippocampal IRS-1/Akt phosphorylation, respectively, of Wistar Kyoto rats fed with a regular chew or high fructose diet (HFD) for 12weeks. Gavage with PIO (30mg/kg/day, 2weeks) significantly reduced the peripheral IR and reversed the level of hippocampal PPARγ. Moreover, HFD-activated microglia and astrocyte were effectively relieved by PIO. The suppressed brain-derived neurotrophic factor, CaMKIIα, and postsynaptic density protein 95 in the hippocampus were effectively reversed by PIO. However, the hippocampal IR and inhibition of adult neurogenesis in dentate gyrus were not restored by PIO. Together, PIO oral application may reverse the HFD-induced peripheral IR and maintain the existed neuronal circuit by ameliorating glial activation and enhancing synaptic density through BDNF but failed to restore adult neurogenesis in the hippocampus.

Lactobacillus salivarius reverse antibiotic-induced lung defense impairment in a ventilator model.

BACKGROUND: Widespread use of antibiotics in the intensive care unit is a potential cause of the emergence of hospital-acquired pneumonia. This study determined whether Lactobacillus salivarius feeding could reverse antibiotic-induced lung defense impairment in a ventilator model. METHODS: C57BL/6 wild-type (WT) mice received mechanical ventilation for 3 h after intramuscular antibiotic treatment for 6 days. Treatment with dead Lactobacillus salivarius and fructo-oligosaccharides (FOS) feeding were used to stimulate antibacterial protein expression in the intestine. Reactive oxygen species (ROS) in the intestinal mucosa was detected using 2'7'-dichlorofluorescein diacetate. The peroxynitrite production of alveolar macrophages (AMs) was measured using dihydrorhodamine 123 oxidation assay. N-acetylcysteine (NAC), an ROS scavenger, was orally administered to mice receiving antibiotics with FOS feeding. RESULTS: Antibiotic treatment decreased Pseudomonas aeruginosa (PA) phagocytic activity and activity of AMs and protein expression of regenerating islet-derived protein 3ß (Reg3ß) as well as Toll-like receptor 4 (TLR4) in the intestinal mucosa in the ventilator model. Antibiotic treatment also decreased ROS production in the intestinal mucosa, peroxynitrite production of AMs, and RELMß expression as well as NF-κB DNA binding activity of the intestinal mucosa in WT mice but not in MyD88-/- mice. Treatment with dead L. salivarius or FOS feeding increased ROS production, bacterial killing activity, and protein expression of Reg3ß as well as TLR4 in the intestinal mucosa and reversed the inhibitory effects of antibiotics on PA phagocytic activity of AMs. CONCLUSION: Taken together with the finding that ablation of FOS-induced intestinal ROS using NAC decreased peroxynitrite production as well as PA phagocytic activity of AMs and protein expression of CRP-ductin, IL-17, Reg3ß, and RELMß in the intestinal mucosa, we conclude that commensal microflora plays a key role in stimulating lung immunity. Intestinal ROS plays a role as a predictive indicator and modulator of pulmonary defense mechanisms. Antibiotic treatment reduces lung defense against PA infection through the decrease in intestinal Reg3ß and TLR4 expression. Treatment with dead L. salivarius or FOS feeding reverses the antibiotic-induced lung defense impairment through the intestinal ROS/MyD88 pathways.

Comparison of dexmedetomidine versus propofol on hemodynamics in surgical critically ill patients.

BACKGROUND: Sedation with dexmedetomidine and propofol may cause hypotension or bradycardia. This study aimed to compare the effects of dexmedetomidine and propofol on hemodynamics and clinical outcomes in surgical intensive care unit (ICU) patients after major abdominal surgery. MATERIALS AND METHODS: Enrolled patients were randomly allocated to the dexmedetomidine or propofol group. Cardiac index was measured using a continuous noninvasive cardiac output monitor on the basis of chest bioreactance. Heart rate, blood pressure, opioid requirement, urine output, delirium incidence, ICU length of stay, and total hospital length of stay were compared between the two groups. The incidences of bradycardia, hypotension, and severe low cardiac index were compared. RESULTS: We enrolled 60 patients. Heart rate and mean arterial pressure were significantly lower in the dexmedetomidine group than in the propofol group. Cardiac index did not differ significantly between the two groups (dexmedetomidine group 3.1 L/min/m2, [95% confidence interval {95% CI} 2.8-3.3] versus propofol group 3.2 L/min/m2 [95% CI 2.9-3.5], P = 0.578). The incidences of bradycardia, hypotension, and severe low cardiac index did not differ significantly between the two groups. CONCLUSIONS: Cardiac index did not differ significantly between the dexmedetomidine and propofol groups in surgical ICU patients after major abdominal surgery.

Relationship Between Xanthelasma Palpebrarum and Hyperlipidemia.

BACKGROUND: Xanthelasma palpebrarum is a common periorbital lesion that occurs in middle-aged woman. Dyslipidemia was strongly associated with the occurrence of xanthelasma. Different treatment methods for xanthelasma were applied with comparable results. MATERIALS AND METHODS: This was a retrospective chart review series performed at a single institute. The surgical pathology of 69 patients who received surgical excision from 1994 to 2012 was obtained. In addition, International Classification of Diseases, Ninth Revision, Clinical Modification code of xanthelasma (374.51) of 44 patients who underwent nonsurgical treatment at an outpatient department was acquired from 2006 to 2012. The serum lipid levels, comorbidities, recurrence, and treatment methods were obtained and analyzed with Statistical Analysis System (SAS) 9.4. RESULTS: Of a total of 113 identified patients, 50 had lipid profile data. Of these 50 patients, 25 (50%) had dyslipidemia, which is higher than general population in Taiwan. The recurrence rate was 17.5%, and there was no statistical difference in the recurrence rate between the different treatment methods. CONCLUSIONS: Xanthelasma was found to be associated with dyslipidemia. Thus, we recommend patients with xanthelasma to check their lipid profile and receive diet control and lipid-lowering medications for lipid abnormalities.

Contributing Factors for Complications and Outcomes in Patients With Snakebite: Experience in a Medical Center in Southern Taiwan.

OBJECTIVES: Snakebite usually results in various complications, such as significant soft tissue damage, infection, hematological, and neurological deficit. Surgical intervention, usually, is indicated in patients with tissue necrosis, infection, and compartment syndrome. To identify the contributing factors for complications and outcomes in different patients with snakebite so that outcomes can be evaluated and treatment of such patients can be initiated at the earliest. METHODS: Information was collected regarding age, sex, underlying disease, species of snake, and the course of treatment of the victims of snakebite who visited the emergency department of a medical center in southern Taiwan between 2004 and 2014. The data obtained were analyzed using SPSS 20.0. RESULTS: The bites from Taiwan cobra (Naja naja atra) significantly resulted in more complications than those from other snakes and required surgical intervention. The use of antivenin and antibiotics, immediate presentation to the hospital, and the location of the bite also were significant contributing factors. CONCLUSIONS: Taiwan cobra significantly results in higher possibility of prolonged hospitalization, operation, tissue necrosis, infection, and necrotizing fasciitis. Location of the bite, immediate presentation to the hospital, and use of antivenin and antibiotics affect the outcome of snakebite. Knowledge of these factors will help in a better management of patients with snakebite.

Double-paddle peroneal flap for extensive lip defect reconstruction.

INTRODUCTION: Today, reconstructive surgeons offer an array of options to reconstruct the lip defects. Herein we present our experience of using free double-paddle peroneal flaps for extensive lip defect reconstruction. PATIENTS AND METHODS: From 1996 to 2014, 16 patients with extensive lip defects after tumor ablation were included. Free double-paddle peroneal flaps were used for reconstructions. In terms of flap design, one skin paddle superiorly placed on the lateral lower leg was used to reconstruct intraoral defects, whereas the other was inferiorly located and was used to reconstruct extraoral defects. A part of the inner skin paddle was everted, and the suture line with the outer skin paddle became the new vermilion border. A portion of the outer skin paddle could be de-epithelized and tucked into the fold of the inner skin paddle, leading to greater fullness of the new lip. RESULTS: Skin paddle sizes were 10-15 cm × 3-13 cm and 4-10.5 cm × 2.5-10.5 cm. Venous thrombosis occurred in one patient but was salvaged, and one flap had superficial necrosis over the outer paddle that was conservatively treated. In the 0.5-33 month follow-up period, all patients were able to close their mouths without obvious drooling. CONCLUSION: Free double-paddle peroneal flap transfer could augment lip definition, deepen the labial vestibule, and provide an acute-angle oral commissure, leading to satisfactory oral competency and improved cosmetic results. Therefore, this technique may be considered a viable option for extensive lip defect reconstruction.