[Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors].

Objective: To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes. Results: A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment (P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions: The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189.

BACKGROUND: In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. PATIENTS AND METHODS: Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators' choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed-platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. RESULTS: After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed-platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed-platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed-platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed-platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed-platinum and 66.8% of patients receiving placebo plus pemetrexed-platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. CONCLUSIONS: Pembrolizumab plus pemetrexed-platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed-platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous NSCLC.

Perioperative outcomes of women with and without class III obesity undergoing hysterectomy for endometrioid endometrial cancer: A population-based study.

OBJECTIVE: Population-based data on perioperative complications among women with endometrial cancer and severe obesity are lacking. We evaluated 30-day complication rates among women with and without class III obesity (body mass index ≥ 40 kg/m2) undergoing primary surgical management for endometrioid endometrial cancer (EEC), and how outcomes differed according to surgical approach (open vs. minimally invasive). METHODS: We performed a retrospective population-based cohort study of women with EEC undergoing hysterectomy in Ontario, Canada, between 2006 and 2015. We evaluated perioperative complications in the whole cohort, and in a 1:1 matched analysis using hard and propensity score matching to ensure similar distributions of patient, tumour, provider and institution-level factors between women with and without class III obesity (identified using a surgical billing code). The primary outcome of interest was the 30-day perioperative complication rate. RESULTS: 12,112 women met inclusion criteria; 2697 (22.3%) had class III obesity. We matched 2320 (86%) women with class III obesity to those without. The composite complication rate was significantly higher among women with class III obesity (23.2% vs. 18.4%, standardized mean difference [SMD] = 0.12), primarily due to wound infection/disruption (12.1% vs. 6.2%). There was no difference in outcomes for women with and without class III obesity when a minimally invasive approach was used. CONCLUSIONS: Wound infection/disruption was increased for women with class III obesity compared to women without. Otherwise, perioperative complications were similar between the matched pairs. When minimally invasive approaches were used, women with class III obesity had a similar risk of complications as women without obesity.

Rhamnus prinoides (gesho) stem extract prevents co-culture biofilm formation by Streptococcus mutans and Candida albicans.

Streptococcus mutans and Candida albicans exhibit a symbiotic relationship to form polymicrobial biofilms that exacerbate oral infections including early-childhood caries, periodontitis and candidiasis. Rhamnus prinoides (gesho) has traditionally been used for the treatment of a variety of illnesses and was recently found to inhibit Gram-positive bacterial biofilm formation. We hypothesized that Rhamnus prinoides extracts have anti-biofilm activity against S. mutans and C. albicans mono- and dual-species biofilms. Ethanol extracts were prepared from gesho stems and leaves; then anti-biofilm activity was assessed using crystal violet, resazurin and XTT staining. Ethanol extracts significantly inhibited Streptococcus mutans and Candida albicans mono-species biofilm formation up to 97 and 75%, respectively. The stem ethanol extract disrupted S. mutans and C. albicans co-culture synergism, with 98% less polymicrobial biofilm formation than the untreated control. Additionally, this extract inhibited planktonic S. mutans cell growth and decreased biofilm polysaccharide production up to 99%. The reduction in polysaccharide production is likely a contributing factor in the anti-biofilm activity of GSE. These findings indicate that gesho or gesho-derived compounds may have potential as additives to oral hygiene products. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral Streptococcus mutans and Candida albicans biofilms are associated with a variety of illnesses. When occurring together, the resulting infections are especially challenging to treat due to enhanced biofilm formation and antibiotic resistance. More therapeutics that can effectively prevent polymicrobial biofilm formation and disrupt interspecies synergism are needed. Rhamnus prinoides ethanol extracts significantly inhibited dual-species biofilm formation and disrupted interspecies synergism.

[Current status and research progress of third-line treatment for patients with gastric cancer in China].

Gastric cancer (GC) is one of the most common malignant tumors in the world. The prognosis of advanced GC is extremely poor, characterized by the high recurrence or disease progression rate after the first-line chemotherapy, and the extremely low long-term survival rate. Meanwhile, the options for subsequent treatment are limited. Studies have shown that the third-line therapy can provide significant survival benefits for selected patients with advanced GC. Currently, a series of randomized controlled trials and real-world studies related to chemotherapy, targeted therapy, and immunotherapy are conducted. In addition, the explorations of combination therapy, and screening the optimal clinical features or predictive biomarkers for the suitable population who might benefit from the third-line regimens are the hot spots for researchers. This article will provide a detailed overview of the current status and progress of the third-line treatment for advanced GC, and to illustrate the characteristics of Chinese GC treatment.

Expression Patterns of Three Genes Under Short and Long Term Cold Exposure in Thitarodes pui (Lepidoptera: Hepialidae), A Host of Ophiocordyceps sinensis.

　　BACKGROUND: Thitarodes larvae are the host of the caterpillar fungus Ophiocordyceps sinensis. Low temperature is the main environmental limitation for larvae growth. OBJECTIVE: To better understand the cold adaption process in T. pui larvae, the expression patterns of trehalose-6-phosphate synthase (TpTPS), heat shock protein 70 (TpHSP70), and heat shock protein 90 (TpHSP90) were investigated upon short and long-term exposure to 0°C. MATERIALS AND METHODS: The 6th instar T. pui larvae were collected in July 2013. TpTPS was firstly sequenced and expression patterns of TpTPS, TpHSP70 and TpHSP90 were investigated using quantitative PCR. RESULTS: Full-length cDNA of TpTPS was 3,012 bp, with an open reading frame of 2,472 bp and an encoding protein of 823 amino acids. TpTPS up-regulation was induced by cold exposure. TpHSP70 expression is altered by cold exposure, but remained low. TpHSP90 expression was obviously up regulated in long-term cold stimulation. CONCLUSION: All three genes (TpTPS, TpHSP70 and TpHSP90) have likely contributed to cold tolerance in T. pui larvae, TpTPS and TpHSP90 potentially being more important.

[Second-line treatment for metastatic or locally advanced gastric cancer].

Gastric cancer is one of the major causes of cancer-related deaths. Many patients with metastatic gastric cancer after first-line chemotherapy received salvage chemotherapy in routine clinical practice. Recent phase Ⅲ trials demonstrated substantial prolongation of overall survival to support this chemotherapy or targeted therapy as a second-line treatment. Both ramucirumab monotherapy and ramucirumab plus paclitaxel were approved by FDA in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. In addition, paclitaxel, irinotecan, or docetaxel monotherapy is also recommended for preferred regimens. This review will summarize chemotherapy or targeted therapy as a second-line treatment in advanced gastric cancer.

[Clinical value of T-cell interferon releases detection of tuberculosis infection assay in quick diagnosis of spinal tuberculosis].

OBJECTIVE: To evaluate the value of T-cell interferon releases detection of tuberculosis infection(T-SPOT.TB)assay in quick diagnosis of spinal tuberculosis. METHODS: From January 2012 to June 2015, a group of 122 diagnosed patients with spinal tuberculosis in the Qingdao Municipal Chest Hospital and a group of 86 patients suspected with spinal tuberculosis in Department of Orthopaedic, the Qingdao Third People's Hospital were accepted to undergone TB-DOT, T-SPOT.TB and TB-DNA PCR tests Department of Clinical Laboratory. RESULTS: The sensitivity of TB-DOT, T-SPOT.TB and TB-DNA PCR tests were 69.7%, 86.1% and 56.6%, respectively.The sensitivity of T-SPOT.TB was significantly higher than TB-DOT and TB-DNA PCR tests (χ(2)=9.51, P<0.05; χ(2)=25.96, P<0.05). The specificity of TB-DOT, T-SPOT.TB and TB-DNA PCR tests were 62.8%, 88.3% and 91.9%, respectively.The specificity of T-SPOT.TB was significantly higher than TB-DOT test (χ(2)=15.25, P<0.05). CONCLUSIONS: T-SPOT.TB assay possesses high sensitivity and specificity in quick diagnosis of patients with spinal tuberculosis, which is valuable in diagnosis of spinal tuberculosis.

Radiation costing methods: a systematic review.

OBJECTIVE: Costs for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used. METHODS: A systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as "radiation," "radiotherapy," "neoplasm," "cost," " cost analysis," and "cost benefit analysis" to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars. RESULTS: Most of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%). CONCLUSIONS: Costing methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed.

Molecular cloning and characterization of GbMECT and GbMECP gene promoters from Ginkgo biloba.

Ginkgolides are key pharmaceutical components in Ginkgo biloba. Using the cDNA sequence of the MECP and MECT genes to design primers, we obtained the promoters of these genes from Ginkgo genomic DNA using the genome walking method. The two promoters were 744 and 982 bp in length, respectively. The cis-elements of the GbMECPs and GbMECT promoters were predicted and analyzed using the plant cis-acting regulatory element database. We found major cis-elements in the sequence of the GbMECT and GbMECPs promoters. The GbMECP promoter contains six TATA boxes and eight CAAT boxes. The GbMECT contains five TATA boxes and seven CAAT boxes. Furthermore, some cis-elements in the promoters of GbMECPs and GbMECT included hormone and light-regulated elements, UB-B-induced elements, and stress-related dehydration-responsive elements. Expression analysis results showed that the MECP gene is mainly involved in responses to CCC (cycocel) and UV-B, and that MECT is mainly involved in responses to wounding treatment. These results also showed that the expression model was consistent with the cis-elements present. During the annual growth cycle, the level of GbMECPs was significantly correlated with terpene lactones accumulation in leaves. A fitted quadratic curve showed the best model for correlating GbMECPs with terpene lactones in leaves. These results will help us to understand the transcriptional regulatory mechanisms involved in key gene expression and ginkgolide accumulation in G. biloba.

Functional characterization of the Ginkgo biloba chalcone synthase gene promoter in transgenic tobacco.

The regulative sequence (2273 bp) of the chalcone synthase gene promoter of biloba was cloned by genomic walking. A 2273-bp promoter 5' upstream translation start site of GbCHS was cloned and designated as GbCHSP. pBI121+CHSP:GUS and pBI121-35S:GUS were constructed and transformed into tobacco by LBA4404. We found that GbCHSP could drive transient expression of GUS in tobacco and differentially expressed in root, stem and leaf tissues of this plant. GUS activity regulated by the CHSP promoter were located in tissues (apical meristems) at the growing points of roots and stems. pBI121+CHSP:GUS could be induced by wounding, copper, UV-B, abscisic acid, and ethephon treatments of transgenic seedlings. This activity was weakly inhibited by gibberellin. Deletion analysis of the CHSP promoter in transgenic tobacco showed that CHSP1 complete promoter conferred a GUS expression and activity similar to that of 35 S(CaMV). GUS activity dropped dramatically when there were CHSP4, CHSP5 constructs and was almost totally absent when the CHSP6 construct was present. We conclude that the upstream sequence -1548 to -306 of GbCHSP is the main region for transcriptional regulation of the CHS gene and that it is activated by hormone and stress factors in G. biloba. These results will help us to understand the transcriptional regulatory mechanisms involved in GbCHS expression and flavonoid accumulation in G. biloba.

Dietary Supplementation of Magnesium Sulfate during Late Gestation and Lactation Affects the Milk Composition and Immunoglobulin Levels in Sows.

This experiment was conducted to investigate the effects of dietary supplementation of magnesium sulfate (MgSO4) during late gestation and lactation on sow and litter performance, fecal moisture, blood biochemistry parameters, immunoglobulin levels and milk composition in sows. Forty-eight sows (Yorkshire×Landrace, 4th to 5th parity) were randomly allocated to 1 of 4 dietary treatments supplemented with 0, 200, 400, or 600 mg/kg MgSO4 (n = 12). The experiment started on day 90 of gestation and continued through day 21 of lactation. Blood samples were collected on day 107 of gestation, day 0 (farrowing) and 21 (weaning) of lactation for the analyses of the blood biochemistry parameters and immunoglobulin levels. The colostrum and milk samples were obtained on day 0 and 14 of lactation, respectively. Fecal samples were collected from the sows on day 107 of gestation as well as day 7 and 20 of lactation to determine fecal moisture content. The results showed that the survival percentage of piglets and the litter weight at weaning were decreased linearly (p<0.05) and other parameters of the sow or litter performance were not influenced (p>0.05) by MgSO4 supplementation. The fecal moisture content of the sows were increased (p<0.05) linearly as dietary MgSO4 increased on day 7 and 20 of lactation. Supplementation with MgSO4 increased the plasma magnesium (Mg) level linearly (p<0.05) and had a trend to increase total protein level (p>0.05 and p<0.10). However, an increase in the dietary MgSO4 level resulted in a linear decrease in the colostrum fat content (p<0.05). Dietary MgSO4 supplementation enhanced the immunoglobulin G (IgG) level (linear, p<0.05) in plasma on day of farrowing and immunoglobulin A (IgA) level in colostrum (quadratic, p<0.05) and milk (linear, p<0.05) of the sows. These results indicated that supplementation with MgSO4 during late gestation and lactation may have the potential to prevent sow constipation, but may also result in some negative effects.

Molecular cloning and characterization of GbDXS and GbGGPPS gene promoters from Ginkgo biloba.

Ginkgolides are key pharmaceutical components in Ginkgo biloba leaves. 1-Deoxy-D-xylulose-5-phosphate synthase (GbDXS) and geranylgeranyl pyrophosphate (GbGGPPS) genes are critical genes involved in ginkgolide biosynthesis. In this study, the promoters of GbDXS and GGPPS, with 676 and 570 bp in length, respectively, were cloned by chromosome walking. The cis-elements of GbDXS and GbGGPPS promoters were predicted and analyzed by the plant cis-acting regulatory element (CARE) database. We found some major cis-elements in the sequence of GbDXS and GbGGPPS promoters. The GbDXS promoter has 3 TATA boxes, 10 CAAT boxes, 6 GATA boxes, and 1 I box. The GbGGPPS promoter has 1 TATA box, 6 CAAT boxes, 6 GATA boxes, and 4 I boxes. Furthermore, some stress-related cis-elements in the promoters of GbDXS and GbGGPPS were found to be light-regulated elements, including sequences over-represented in light-induced promoters (SORLIP1- AT), GATA box, and I box, a gibberellin-responsive element (WRKY), salicylic acid-induced (GT-1), cold- and dehydration-responsive (MYC-Core), and copper-inducible (CURE-Core). Further analyses of these cis-elements will aid in elucidating the molecular mechanisms regulating the expression of the GbDXS and GbGGPPS genes during ginkgolide accumulation in G. biloba.

Development of miconazole nitrate containing chitosan microcapsules and their anti-Aspergillus niger activity.

In this article, we report the development of chitosan/miconazole nitrate microcapsules. Four miconazole nitrate ratios including 12.5, 25, 50 and 100 mg were performed in the chitosan-based microencapsulation system. Chitosan microcapsules with the drug input of 25 mg showed the highest encapsulation efficiency (52.47%) and acceptable mean particle size (5.65 µm) when compared with those of 12.5, 50 and 100 mg. Fourier transform infrared spectroscopic spectrum proved the entrapment of miconazole nitrate into chitosan microcapsules. The antifungal result demonstrated that microcapsules containing 75 µg miconazole nitrate possessed comparable anti-Aspergillus niger activity as the commercial ointment. The growth inhibition of miconazole nitrate containing chitosan microcapsules towards human skin keratinocytes was found to be dose dependent. A total of 75 µg of miconazole nitrate containing microcapsules revealed about 25% of growth inhibition while that of 150 µg showed approximately 70% of growth inhibition. Special monitoring should be taken if a higher dose of miconazole nitrate was used to develop the microcapsules.

[Effects of salivary microbiota on tryptophan-aryl hydrocarbon receptor signaling axis in mice with periodontitis].

Objective: To study the effects of salivary microbiota in patients with periodontitis on the tryptophan-aryl hydrocarbon receptor (AhR) signaling axis in mice with periodontitis and to provide theoretical basis as well as new ideas for the influences of periodontitis on systemic metabolism. Methods: Salivary microbiota of 12 healthy individuals and 14 patients with periodontitis were collected in Nanjing Stomatological Hospital, Medical School of Nanjing University from June to December of 2020. According to the random number table method, twenty-four mice were randomly divided into three groups: Sham group (control group), P group (periodontitis patients' salivary microbiota group) and H group (periodontal healthy individuals' salivary microbiota group). The maxillary second molars of all mice were treated with silk thread ligation to induce periodontitis. Phosphate buffer as well as salivary microbiota of periodontal healthy individuals and periodontitis patients were gavaged into periodontitis mice for 2 weeks. The expression of inflammatory factors in mice serum were detected by enzyme linked immunosorbent assay, and the expression of tryptophan and indole metabolites in intestinal tract and serum were detected by liquid chromatography-mass spectrometry. The expression of AhR in intestinal tract of mice was detected by immunohistochemistry and quantitative real time-PCR while gut microbiota constitution was detected by 16S rRNA gene sequencing. The remaining saliva samples of periodontitis patients and periodontal healthy individuals were applied to detect the expression of tryptophan and indole metabolites themselves. Results: The salivary microbiota of periodontitis patients could induce the expression of interleukin-1ß [P group: (162.38±39.46) pg/ml, H group: (82.83±20.01) pg/ml; t=4.40, P=0.001) and tumor necrosis factor-α [P group: (361.16±123.90) pg/ml, H group: (191.66±106.87) pg/ml; t=2.54, P=0.030) in serum of periodontitis mice, and reduce the expression of AhR in colon (P group: 1.18±0.05, H group:1.83±0.47; t=3.09, P=0.015) and ileum (P group: 0.80±0.13, H group: 1.18±0.11; t=4.93, P=0.001). After gavage of salivary microbiota of periodontitis patients to the mice, tryptophan (P group: (18.1±3.8)×107, H group: (26.6±6.6)×107; t=2.49, P=0.037] and indole lactic acid [P group: (1.9±0.7)×107, H group: (3.7±0.6)×107; t=4.49, P=0.002) in serum of periodontitis mice were significantly decreased, but was relatively disorder in intestinal tract. However, the expressions of tryptophan and indole metabolites in saliva of periodontitis patients were higher than those of periodontal healthy individuals. There were significant differences in indole propionic acid [P group: (1 239.39±818.72) nmol/L, H group: (56.96±38.33) nmol/L; t=2.83, P=0.022]. What we find noteworthy was that the expressions of indolelactic acid metabolism in saliva, serum and intestinal were consistent, and salivary microbiota of periodontitis patients could reduce the relative abundance of indolelactic acid-producing bacteria in the gut, suggesting that the salivary microbiota of periodontitis patients might affect the expression of AhR through gut microbiota disorder and indolelactic acid downregulation. Conclusions: Salivary microbiota in patients with periodontitis may affect the systemic inflammatory state through down-regulating the expression of tryptophan-AhR signal axis.

Geographic trends in incidence of hip fractures: a comprehensive literature review.

UNLABELLED: A comprehensive review of literature was conducted to investigate variation in hip fracture incident rates around the world. The original crude incidence rates were standardized for age and sex for comparability. After standardization, the highest rates of hip fracture were found in Scandinavia and the lowest rates in Africa. INTRODUCTION: This study was conducted to investigate the geographic trends of the incidence of osteoporotic hip fractures through a comprehensive review of literature. METHODS: Studies were identified for inclusion in the review by searching the MEDLINE database via PubMed and applying strict inclusion and exclusion criteria. Age-specific incidence rates were extracted from the articles, and in order to provide a common platform for analysis, we used directly age-standardized and age-sex-standardized rates (using the 2005 United Nations estimates of the world population as standard) to complete the analysis. RESULTS: Forty-six full text articles spanning 33 countries/regions were included in the review. For ease of comparison, the results were analyzed by geographic regions: North America, Latin America, Scandinavia, Europe (excluding Scandinavia), Africa, Asia, and Australia. The highest hip fracture rates were found in Scandinavia and the lowest in Africa. We found comparable rates from countries in North America, Australia, and Europe outside of Scandinavia. The diverse makeup of the Asian continent also resulted in quite variable hip fracture rates: ranging from relatively high rates in Iran to low rates, comparable to those from Africa, in mainland China. CONCLUSIONS: Given the aging of populations globally, and in the industrialized countries specifically, hip fractures will become a progressively larger public health burden. The geographic trends observed in hip fracture incidence rates can provide important clues to etiology and prevention.

Changes in first hip fracture rates in British Columbia Canada, 1990-2004.

UNLABELLED: We determined age-standardized first hip fracture rates in British Columbia between 1990 and 2004. We found sex and fracture type rates in keeping with previous reports and that fracture rates have decreased approximately 18% overall in both men and women. INTRODUCTION: To determine whether there have been changes in the age-, sex-, and subtype-specific first hip fracture rates in Canadian province of British Columbia (BC) between 1990 and 2004. METHODS: Records of all persons aged 60 years and older hospitalized with hip fractures in BC between 1985 and 2004 were obtained from the Canadian Institute for Health Information Discharge Abstract Database. Only the first hip fracture records were included, and fractures likely due to causes other than trauma were excluded. Age- and sex-specific rates were calculated using population denominators from Statistics Canada and direct standardization was used. Age-standardized rates allowed for comparison across years with adjustment for age distribution. RESULTS: There were 41,990 records of first hip fracture included, and 73% were in women. Trends in age-specific rates by fracture type were similar to previous reports. Between 1990 and 2004, there has been an age-adjusted 18% decrease in first hip fracture rates in women, and 19% decrease in first hip fracture rates in men. The decrease was statistically significant in femoral neck fractures in women, but not in men. CONCLUSIONS: There has been a decrease in age-adjusted hip fracture rates in BC between 1990 and 2004, which is in contrast to previous projections for hip fracture rates in Canada.

Distinct dysregulation of lipid metabolism by unliganded thyroid hormone receptor isoforms.

Thyroid hormone receptors (TRs) play critical roles in energy homeostasis. To understand the role of TRs in lipid homeostasis in vivo, we adopted the loss-of-function approach by creating knock-in mutant mice with targeted mutation in the TRalpha gene (TRalpha1PV mouse) or TRbeta gene (TRbetaPV mouse). The PV mutation, identified in a patient with resistance to thyroid hormone, exhibits potent dominant-negative activity. Here we show that in contrast to TRalpha1PV mouse, TRbetaPV mice exhibited no significant reduction in WAT but had significant increases in serum free fatty acids and total triglycerides. Moreover, the liver of TRbetaPV mice was markedly increased (33%) with excess lipid accumulation, but the liver mass of TRalpha1PV mouse was decreased (23%) with paucity of lipids. These results indicate that apo-TRbeta and apo-TRalpha1 exerted distinct abnormalities in lipid metabolism. Further biochemical analyses indicate that increased lipogenic enzyme expression, activated peroxisome proliferator-activated receptor gamma (Ppargamma) signaling, and decreased fatty acid beta-oxidation activity contributed to the adipogenic steatosis and lipid accumulation in the liver of TRbetaPV mice. In contrast, the expression of lipogenic enzymes and Ppargamma was decreased in the liver of TRalpha1PV mice. These results suggest that the regulation of genes critical for lipid metabolism by TRs in the liver is isoform dependent. These results indicate that apo-TRbeta and apo-TRalpha1 had different effects on lipid metabolism and that both TR isoforms contribute to the pathogenesis of lipid metabolism in hypothyroidism.