Reduced risk of pneumonia and influenza infection after bariatric surgery: a retrospective cohort study among patients with nondiabetic obesity in Taiwan.

BACKGROUND: Bariatric surgery is associated with significant improvements in immunity in individuals with obesity, but the exact efficacy in reducing pneumonia and influenza infections is unclear. OBJECTIVE: To investigate the association between bariatric surgery and the risk of pneumonia and influenza infection. SETTING: Nondiabetic patients who underwent bariatric surgery and matched controls were identified from the National Health Insurance Research Database of Taiwan. METHODS: We identified 1648 nondiabetic patients who underwent bariatric surgery from the National Health Insurance Research Database of Taiwan in 2001-2009. These patients were matched by propensity score with 4881 nondiabetic patients with obesity who did not undergo bariatric surgery. We followed the surgical and control cohorts until death, any diagnosis of pneumonia or influenza, or December 31, 2012. The Cox proportional hazards regression model was used to calculate the relative risk of pneumonia and influenza infection in those who underwent bariatric surgery compared with those who did not. RESULTS: Overall, there was a .87-fold (95% CI, .78-.98) reduced risk of pneumonia and influenza infection in the surgical group versus the control group. Four years after bariatric surgery, a sustainable effect of the surgery was observed, and the risk of pneumonia and influenza infection was .83-fold reduced in the surgical group (95% CI, .73-.95). Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals. CONCLUSION: Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

Impact of a home health care program for disabled patients in Taiwan: A nationwide population-based cohort study.

The aim of this study was to evaluate the impact of home health care (HHC) for disabled patients.We conducted a nationwide population-based retrospective cohort study. A total of 5838 disabled patients with HHC were identified to match by propensity score with 15,829 disabled patients without HHC receiving tube or catheter care (tracheostomy tube, nasogastric tube, urinary catheter, cystostomy tube, nephrostomy tube) or stage 3 or 4 pressure sore care from the Taiwanese National Health Insurance Research Database between 2005 and 2009. After 1:1 matching, 2901 subjects in the HHC group and 2901 subjects in the non-HHC group were selected and analyzed. Generalized estimating equations (GEEs) were used to compare the risk of health outcomes (rate of hospitalization and emergency services use) and the healthcare expenditure between the 2 groups.Compared to those in the non-HHC group, the patients in the HHC group had significantly higher risk for hospitalization (odds ratio [OR] = 18.43, 95% confidence interval [CI]: 15.62-21.75, P < .001) and emergency services use (OR = 3.72, 95% CI: 3.32-4.17, P < .001) 1 year before the index date. However, 1 year after the index date, the risk for hospitalization (OR = 1.6, 95% CI: 1.41-1.83, P < .001) and emergency services use (OR = 1.16, 95% CI: 1.04-1.30, P < .05) attenuated significantly. Regarding the comparison of total healthcare expenditure 1 year before and after the index date, our study showed an insignificant decrease of US$1.5 per person per day and a significant increase of US$5.2 per person per day (P < .001) in the HHC and non-HHC groups, respectively.The HHC for disabled patients has a potential role to reduce hospitalization and emergency services use. Besides, the improvement of healthcare quality through HHC was not accompanied by increased healthcare expenditure. The clinical impact of HHC emphasizes the importance for public health officials to promote HHC model to meet the needs of disabled patients.

Increased risk for major depressive disorder in severely obese patients after bariatric surgery - a 12-year nationwide cohort study.

BACKGROUND: Bariatric surgery is associated with a significant improvement in depressive mood in the initial postoperative years, but the maintenance of the improvement is under debate. AIM: To explore the association between bariatric surgery and major depressive disorder (MDD) in a 12-year nationwide cohort study. METHOD: Using the National Health Insurance Research Database of Taiwan, we identified 2302 patients who underwent bariatric surgery in 2001-2009. These patients were matched by propensity score to 6493 obese patients who did not receive bariatric surgery. We followed the surgical and control cohorts until death, any diagnosis of MDD or 31 December 2012. We used Cox proportional hazard regression models to calculate the relative risk of MDD in those who received bariatric surgery. RESULTS: Overall, there was a 1.70-fold (95% CI: 1.27-2.27) higher risk of MDD in the surgical group. Subjects receiving malabsorptive procedures showed a higher risk of MDD (3.01, 95% CI: 1.78-5.09) than those receiving restrictive procedures (1.51, 95% CI: 1.10-2.07). Stratified by follow-up period, there was a higher risk of MDD in the surgical group (2.92, 95% CI: 1.75-4.88) than in the restrictive group four years after bariatric surgery. CONCLUSIONS: Bariatric surgery was significantly associated with an elevated risk of MDD. KEY MESSAGES Bariatric surgery is associated with a significant improvement in depressive mood in the initial postoperative years, but the improvement is not maintained. Less is known about the relationship between bariatric surgery and risk of major depressive disorder. This was the first nationwide cohort study which found that bariatric surgery was significantly associated with an elevated risk of MDD (aHR: 1.70; CI: 1.27-2.27), mainly with malabsorptive procedures (aHR: 3.01; CI: 1.78-5.09) and at time points more than four years after surgery (aHR: 2.92; CI: 1.75-4.88) compared with the risk in matched controls. These findings imply an association between long-term malabsorption and the postoperative incidence of MDD. Long-term malabsorption might be related to the incidence of major depressive disorder after bariatric surgery. The possible causal relationship between nutritional deficiency after bariatric surgery and major depressive disorder warrants further investigation.

Improving the regenerative potential of olfactory ensheathing cells by overexpressing prostacyclin synthetase and its application in spinal cord repair.

BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent. RESULTS: Cultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10-12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40-60% of AdPGIS-OEC transplanted SCI rats. CONCLUSIONS: Enhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Cationic amphiphile in phospholipid bilayer or oil-water interface of nanocarriers affects planktonic and biofilm bacteria killing.

A cationic amphiphile, soyaethyl morpholinium ethosulfate (SME), immobilized in liposomes or nanoemulsions, was prepared in an attempt to compare the antibacterial activity between SME intercalated in the phospholipid bilayer and oil-water interface. Before antibacterial assessment, the size of the liposomes and nanoemulsions was respectively recorded as 75 and 214 nm. The data of minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) and live/dead cell count demonstrated a superior antimicrobial activity of nanoemulsions compared to liposomes against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Staphylococcus epidermidis. Nanoemulsion incubation reduced biofilm thickness by 2.4-fold, whereas liposomes showed a 1.6-fold decrease in thickness. SME insertion in the oil-water phase was found to induce bacterial membrane disruption. SME nanosystems were nontoxic to keratinocytes. In vivo topical application of the cationic nanosystems reduced skin infection, MRSA load, and inflammation in mice. The deteriorated skin barrier function evoked by MRSA was recovered by nanoemulsion treatment.

Fracture Risk After Bariatric Surgery: A 12-Year Nationwide Cohort Study.

Bariatric surgery has been shown to impair bone health. This study aimed to investigate the fracture risk in patients after bariatric surgery versus propensity score-matched controls. The authors used the National Health Insurance Research Database of Taiwan and identified 2064 patients who underwent bariatric surgery during 2001 to 2009. These patients were matched to 5027 obese patients who did not receive bariatric surgery, using propensity score matching accounting for age, sex, Charlson Comorbidity Index, diabetes, hypertension, hyperlipidemia and the year morbid obesity was diagnosed. The authors followed the surgical and control cohorts to death, any diagnosis of fracture, or December 31, 2012, whichever occurred first. Cox proportional hazard regression models were used to calculate relative rates of fractures in the surgical group and control group. At the end of the 12-year study period, there were 183 fractures in the surgical group (mean follow-up 4.8 years) and 374 fractures in the matched control group (mean follow-up 4.9 years). Overall, there was a 1.21-fold [95% confidence interval (CI): 1.02-1.43] significantly increased risk of fracture in the surgical group compared with the control group. Stratified by surgical procedures, malabsorptive procedures showed a significantly higher fracture risk (1.47, 95% CI: 1.01-2.15). The Kaplan-Meier estimated fracture rates were 1.60% at 1 year, 2.37% at 2 years, 1.69% at 5 years, and 2.06% after 5 years for the surgical patients, compared with 1.51%, 1.65%, 1.53%, and 1.42%, respectively, for the matched controls. Adjusted analysis showed a trend towards an increased fracture risk, 1 to 2 years after bariatric surgery. (1.42, 95% CI: 0.99-2.05). Bariatric surgery was significantly associated with an increased risk of fractures, mainly with malabsorptive procedures, with a trend of an increased fracture risk 1 to 2 years after surgery. These results provide further evidence for the adverse effects of bariatric surgery on the risk of fractures.

Trend and factors associated with healthcare use and costs in type 2 diabetes mellitus: a decade experience of a universal health insurance program.

BACKGROUND: Little is known about how a universal National Health Insurance program with cost-containment strategies affect costs and quality of diabetes care. OBJECTIVES: To examine the trends of healthcare use and costs for patients with type 2 diabetes mellitus (T2DM) in Taiwan over the last decade, and to identify factors associated with high healthcare cost and poor diabetes care. RESEARCH DESIGN: We delineated the pattern of healthcare use and costs for T2DM in 2000-2010. Generalized linear and logistic regression models were used to identify factors associated with medical costs and diabetes care. SUBJECTS: Representative adult T2DM patients and age-matched and sex-matched nondiabetes individuals were selected from the 2000, 2005, and 2010 National Health Insurance Research Databases. MEASURES: Healthcare use included physician visits, hospital admissions, and antidiabetic drug prescriptions. Indicators of diabetes management included completeness of recommended diabetes tests and medication adherence, assessed using medication possession ratio. RESULTS: The total healthcare cost per diabetes patient was approximately 2.8-fold higher than that for nondiabetes individual. The growth of healthcare cost per diabetes patient was significantly contained by about 3694 New Taiwan dollars (3.6%) between 2005 and 2010, but diabetes care improved over the decade. Diabetes duration, income, place of residence, continuity of care, and enrollment to a pay-for-performance program were associated with healthcare costs and diabetes management. Some public health measures implemented to support diabetes care were also discussed. CONCLUSIONS: Healthcare costs could be controlled without sacrificing the quality of diabetes care by implementing pay-for-performance programs and effective health policies favorable for diabetes care.

Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells.

Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil.

Rejuvenation of aged pig facial skin by transplanting allogeneic granulocyte colony-stimulating factor-induced peripheral blood stem cells from a young pig.

Following a stroke, the administration of stem cells that have been treated with granulocyte colony-stimulating factor (GCSF) can ameliorate functional deficits in both rats and humans. It is not known, however, whether the application of GCSF-mobilized peripheral blood stem cells (PBSCs) to human skin can function as an antiaging treatment. We used a Lanyu pig (Sus scrofa) model, since compared with rodents, the structure of a pig's skin is very similar to human skin, to provide preliminary data on whether these cells can exert antiaging effects over a short time frame. GCSF-mobilized PBSCs from a young male Lanyu pig (5 months) were injected intradermally into the cheek skin of aged female Lanyu pigs, and tissues before and after the cell injections were compared to determine whether this treatment caused skin rejuvenation. Increased levels of collagen, elastin, hyaluronic acid, and the hyaluronic acid receptor CD44 were observed in both dermal and subcutaneous layers following the injection of PBSCs. In addition, the treated skin tissue was tighter and more elastic than adjacent control regions of aged skin tissue. In the epidermal layer, PBSC injection altered the levels of both involucrin and integrin, indicating an increased rate of epidermal cell renewal as evidenced by reductions in both cornified cells and cells of the spinous layers and increases in the number of dividing cells within the basal layer. We found that the exogenous PBSCs, visualized using fluorescence in situ hybridization, were located primarily in hair follicles and adjacent tissues. In summary, PBSC injection restored young skin properties in the skin of aged (90 months) pigs. On the basis of our preliminary data, we conclude that intradermal injection of GCSF-mobilized PBSCs from a young pig can rejuvenate the skin in aged pigs.

Effect of enhanced prostacyclin synthesis by adenovirus-mediated transfer on lipopolysaccharide stimulation in neuron-glia cultures.

Prostacyclin (PGI2) is known as a short-lived, potent vasodilator and platelet anti-aggregatory eicosanoid. This work attempts to selectively augment PGI2 synthesis in neuron-glia cultures by adenoviral (Ad) gene transfer of PGI synthase (PGIS) or bicistronic cyclooxygenase 1 (COX-1)/PGIS and examines whether PGI2 confers protection against lipopolysaccharide (LPS) stimulation. Cultures released low levels of eicosanoids. Upon Ad-PGIS or Ad-COX-1/PGIS infection, cultures selectively increased prostacyclin release. Both PGIS- and COX-1/PGIS-overexpressed cultures contained fewer microglial numbers. Further, they significantly attenuated LPS-induced iNOS expression and lactate, nitric oxide, and TNF-alpha production. Taken together, enhanced prostacyclin synthesis in neuron-glial cultures reduced microglia number and suppressed LPS stimulation.