Stability between single and segmental maxillary osteotomies in bimaxillary surgery for cleft-associated class III deformity: a CBCT study.

OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.

Adiponectin-leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance.

BACKGROUND: Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. MATERIALS AND METHODS: A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. RESULTS: The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). CONCLUSIONS: The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3]Key messagesThe prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.

Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination.

BACKGROUND/PURPOSE: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited. METHODS: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose. RESULTS: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks. CONCLUSION: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).

Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome.

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 µg/L, 1043.45 ± 306.36 µg/L, and 1246.83 ± 538.13 µg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35-10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25-3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24-3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

Intensive care utilization in patients with end-stage liver disease: A population-based comparative study of cohorts with and without comorbid hepatocellular carcinoma in taiwan.

BACKGROUND: End-of-life intensive care may be futile and can be a cause of distress to both patients and their families. This study aimed to understand the utilization of intensive care and its associated factors in patients with End-stage liver disease (ESLD) during terminal hospitalization. METHODS: Population-based retrospective cohort study using the National Health Institute Research Database of Taiwan. All adult patients with ESLD who died during their hospitalization in 2010-2013 were included. FINDINGS: Of the 14,247 patients with ESLD, the majority (60·8%) was comorbid with hepatocellular carcinoma (HCC). Patients with ESLD only were younger, more deprived, more alcohol-related, and less likely to receive palliative care prior to terminal hospitalization (6·0% vs 29·2% with HCC). Compared to patients with comorbid HCC, relatively more patients without HCC were admitted to ICU (59·6% vs 22·3%), receiving CPR (11·1% vs 4·3%) and mechanical ventilation (36·3% vs 12·5%) during terminal hospitalization. Etiology of alcoholic hepatitis, esophageal varices, septicemia, pneumonia and respiratory failure, and renal failure were associated with a higher probability of ICU admission (adjusted rate ratio (aRR) range: 1·09-2·09). Prior palliative care was associated with lower probability of ICU admission (aRR range: 0·24-0·38). INTERPRETATION: The intensive care utilization by patients with ESLD in their terminal hospitalization was substantial in Taiwan. Those who are not comorbid with HCC need more attention, especially in terms of their palliative care needs, choices regarding intensive care, and their healthcare utilization. FUNDING: National Institute of Health Research Health Applied Research Collaboration (ARC) South London.

Intrarenal Transplantation of Hypoxic Preconditioned Mesenchymal Stem Cells Improves Glomerulonephritis through Anti-Oxidation, Anti-ER Stress, Anti-Inflammation, Anti-Apoptosis, and Anti-Autophagy.

To confer further therapeutic potential and prevent some adverse effects by the mesenchymal stem cells (MSCs) transplantation, we explored the effects of locally intrarenal arterial administration of hypoxic preconditioned MSCs in the anti-Thy1.1 induced rat glomerulonephritis. Proteinuria, histochemical staining, and western blotting were used to explore the therapeutic effects and mechanisms. Locally intrarenal arterial MSCs transplantation successfully implanted the fluorescent or CD44 labeled MSCs in the nephritic glomeruli, ameliorated proteinuria, and glomerulosclerosis in nephritic rats. Hypoxic preconditioning significantly upregulated hypoxic inducible factor-1α/VEGF (HIF-1α/VEGF) in the MSCs and was more efficient than normoxic MSCs in reducing the degree of urinary protein, glomerulosclerosis, fibrosis, macrophage/monocyte infiltration, GRP78 mediated endoplasmic reticulum stress, Beclin-1/LC3-II mediated autophagy, and Bax/Bcl-2/caspase 3 mediated apoptosis. Hypoxic MSCs could further promote intranuclear nuclear factor (erythroid-derived 2, Nrf2) and reduce nuclear factor kappa B expression in nephritic kidneys. As compared to normoxic MSCs, hypoxic MSCs transplantation significantly upregulated the renal expression of anti-oxidative response elements/enzymes including glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione peroxidase, catalase, Mn, and Cu/Zn superoxide dismutase. In summary, intrarenal hypoxic preconditioning MSCs transplantation was more effective to activate hypoxic inducible factor-1α/VEGF/Nrf2 (HIF-1α/VEGF/Nrf2) signaling, preserve anti-oxidant proteins and anti-oxidative responsive element proteins, and subsequently reduce glomerular apoptosis, autophagy, and inflammation.

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.

Addition of one session with a specialist counselor did not increase efficacy of a family physician-led smoking cessation program.

Objective Higher-intensity counseling sessions increase the smoking abstinence rate. However, counselors are limited in Taiwan. This study was performed to determine whether the addition of one session with a specialist counselor increases the efficacy of a family physician-led smoking cessation program. Methods Participants opted to either visit a family physician for brief counseling and pharmacotherapy (Po) or visit a specialist counselor for an initial session followed by a family physician for brief counseling sessions with pharmacotherapy (P+). The 7-day point prevalence (PP) rate was evaluated at weeks 12 and 24. Results In total, 356 patients were enrolled. In the intention-to-treat analysis, the PP rate at week 12 was higher in the Po than P+ group, but there was no significant difference at week 24. In the per-protocol analysis, the PP rates at weeks 12 and 24 were not significantly different between the Po and P+ groups. The adjusted odds ratios also revealed no significant differences in either the intention-to-treat analysis or the per-protocol analysis between the two groups. Conclusion The addition of one session with a specialist counselor had no benefit over the provision of counseling through a family physician at either 12 or 24 weeks of follow-up.

High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance.

OBJECTIVE: Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. RESEARCH DESIGN AND METHODS: This was a hospital-based case-control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. RESULTS: After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). CONCLUSIONS: We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation.

Association of Non-alcoholic Fatty Liver Disease with Metabolic Syndrome Independently of Central Obesity and Insulin Resistance.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease that may lead to liver cirrhosis and hepatocellular carcinoma. We aimed to determine the association between the prevalence of metabolic syndrome (MetS) and NAFLD severity using semi-quantitative ultrasonography (US). A total of 614 participants were recruited from the community. NAFLD was evaluated according to the ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Insulin resistance was estimated with the homeostasis model assessment index for insulin resistance (HOMA-IR). NAFLD and MetS were found in 53.7 and 17.3% of the participants, respectively. Linear relationships were found between the severity of NAFLD and waist circumference, fasting glucose, HOMA-IR, triglycerides, HDL-C and blood pressure. After adjusting for confounding factors, i.e., body mass index and HOMA-IR, the odds ratios for MetS were 3.64 (95% confidence interval (CI): 1.5-8.83) for those with mild NAFLD and 9.4 (95% CI: 3.54-24.98) for those with moderate-to-severe NAFLD compared to those without NAFLD. The combination of the HOMA-IR and US-FLI scores better differentiated MetS than the HOMA-IR alone. In addition to obesity, the severity of NAFLD and the HOMA-IR both play important roles in MetS. Whether NAFLD is a component of MetS warrants further research.

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.

Effects of a multimodule curriculum of palliative care on medical students.

BACKGROUND/PURPOSE: The objective of this study was to investigate the effects of educational intervention using a multimodule curriculum of palliative care on medical students, and to explore significant factors that influence improvement in beliefs of ethical decision-making. METHODS: A total of 259 medical students enrolled in the "Family, Society and Medicine" course, and accepted a multimodule palliative care curriculum that included a 1-hour lecture, 1 hour of patient contact, 1 hour of literature reading, and 1 hour of discussion. A questionnaire was administered before and after the course to evaluate improvements in medical students' knowledge (principles and clinical management) of palliative care and their beliefs concerning ethical decision-making in palliative care. RESULTS: The students showed significant improvements after the course in their knowledge of the principles of palliative care (pretest 58.4% vs. posttest 73.1%; p less than 0.01) and clinical management of palliative care (pretest 58.8% vs. posttest 67.9%; p less than 0.01). Although their beliefs about ethical decision-making were also improved after the course, the medical students did not have a positive belief of "artificial nutrition and hydration is not always beneficial for terminal cancer patients", with a mean score of only 3.15 and 3.51 (pretest and posttest, respectively; range, 1-5). The logistic regression model showed that improvement in knowledge of either principles or clinical management did not significantly improve beliefs about ethical decision-making. CONCLUSION: A multimodule curriculum of palliative care for medical students can significantly improve their knowledge on principles of clinical management and beliefs about ethical decision-making in palliative care. As for changes in beliefs about ethical decision-making in palliative care, continued ethical and clinical training is required.