Life Expectancy in Pre-Frail and Frail States with and without Disability: 18-Years of Follow-Up Data from the HEPESE Study Using the Markov Chain Method.

We estimated the total life expectancy (TLE), frailty-free life expectancy (FFLE), frail life expectancy (FLE), pre-frail life expectancy (PFLE), and FLE with and without disability among 2,000 Mexican Americans aged ≥67 years over an 18-year period. Frailty was defined as the presence of ≥2 criteria (weight loss, weakness, self-reported exhaustion, slowness). We used the Markov chain method to estimate the TLE, FFLE, FLE, PFLE, and FLE with and without disability by age and gender. TLE at age 67 was 17.49 years (women) and 15.54 years (men); FFLE was 6.50 years (women) and 6.45 years (men); PFLE was 6.48 years (women) and 5.42 years (men); FLE was 4.51 years (women) and 3.67 years (men); and FLE with disability was 2.13 years (women) and 1.13 years (men). In conclusion, Mexican American older women had fewer years of non-frail LE, more pre-frail or frail years, and more years with disability than men.

Comparison of through-the-scope stent insertion with standard stent insertion for the management of malignant colorectal obstruction: a prospective study.

BACKGROUND: The aim of the present study was to compare the feasibility, safety and efficacy of the through-the-scope (TTS) stent technique to that of the standard metallic stent technique for the management of malignant colorectal obstruction. METHODS: Fifty-two patients scheduled to receive stent insertion for the management of acute obstructive colorectal cancer were enrolled in our study and divided into a TTS stent group (n = 24) and a standard stent group (n = 28). The stent insertion procedure was performed under endoscopic and fluoroscopic guidance in all patients. The success rate, complications, fluoroscopic time, and clinical remission rate were recorded and compared. RESULTS: The technique success rate was 100 % (24/24) in the TTS stent group and 78.6 % (22/28) in the standard stent group (p = 0.03). In five patients in the standard stent group, the stent failed to pass through occlusive lesions because of the stiffness of the stent system. Serious bleeding occurred in one patient in the standard stent group. The fluoroscopy time in the TTS stent group was significantly reduced (12.9 ± 6.6 min) compared with that of the standard stent group (24.8 ± 9.8 min; p < 0.01). Silent perforation occurred in 17.9 % (5/28) of the cases in the standard stent group compared with none in the TTS (p = 0.03). Clinical remission was achieved in 97.1 % (23/24) and 78.6 % (22/28) of patients in the TTS and standard stent groups, respectively (p = 0.11). CONCLUSIONS: The TTS stent is safer and more feasible for the management of malignant colorectal obstructions than the standard stent, and the TTS technique provides a higher success rate, a similar clinical remission rate, and a markedly reduced fluoroscopic time.

Clinical significance of hmgb1 expression in human gastric cancer.

High mobility group box 1 (HMGB1) has been proved to be implicated in a variety of cell physiological and pathological behaviors including immune response, inflammation and cancer. Accumulating evidence suggests that HMGB1 plays a critical role in the development and progression of multiple malignancies. However, the clinical significance and prognosis of HMGB1 expression in some cancers remain controversial. The present study aimed to investigate whether overexpression of HMGB1 is an independent prognostic factor in patients with gastric cancer. The correlation of HMGB1 expression with clinicopathologic characteristics and prognosis was assessed by immunohistochemical assay through tissue microarray procedure in 50 primary gastric cancer cases. Our results indicated that the positive expression of HMGB1 was significantly increased in the nucleus of gastric cancer tissues compared with the adjacent non-cancerous tissues (ANCT) (64.0% vs 44.0%, P=0.025), but was not linked to the clinicopathologic features, including the TNM stage (P=0.533) and metastatic lymph node (P=0.771), in patients with gastric cancer. Kapalan-Meier and log-rank analysis demonstrated that overexpression of HMGB1 did not exert significant impact on the overall survival of patients with gastric cancer (P=0.805). Furthermore, Cox regression analysis showed that high HMGB1 protein expression did not represent an independent risk factor for patients with gastric cancer (P=0.677). Taken together, our findings suggest that high expression of HMGB1 is not correlated with the clinicopathologic characteristics of gastric cancer, and cannot serve as an independent prognostic biomarker for patients with gastric cancer.

IL-10 treatment is associated with prohibitin expression in the Crohn's disease intestinal fibrosis mouse model.

Prohibitin, which can inhibit oxidative stress and mitochondrial dysfunction, has been shown to have significant anti-inflammatory activities. Here, we investigate the effects of altering prohibitin levels in affected tissues in the interleukin-10 knockout (IL-10KO) mouse model with intestinal fibrosis. The aim of this study is to investigate the effects of IL-10 on prohibitin and the role of prohibitin in intestinal fibrosis of murine colitis. After the mice were treated with IL-10, prohibitin expression and localization were evaluated in IL-10KO and wild-type (WT, 129/SvEv) mice. The colon tissue was then investigated and the potential pathogenic molecular mechanisms were further studied. Fluorescence-based quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry assays revealed a significant upregulation of prohibitin with IL-10 treatment. Furthermore, IL-10 decreases inflammatory cytokines and TGF-ß1 in the IL-10KO model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. In conclusion, we hypothesize that IL-10 treatment is associated with increased prohibitin and would decrease inflammation and fibrosis in an animal model of Crohn's disease. Interestingly, prohibitin may be a potential target for intestinal fibrosis associated with inflammatory bowel disease (IBD).

Evaluation of biodegradable paclitaxel-eluting nanofibre-covered metal stents for the treatment of benign cardia stricture in an experimental model.

BACKGROUND: Benign strictures at the cardia are troublesome for patients and often require repeated endoscopic treatments. Paclitaxel can reduce fibrosis. This study evaluated a biodegradable paclitaxel-eluting nanofibre-covered metal stent for the treatment of benign cardia stricture in vitro and in vivo. METHODS: Drug release was investigated in vitro at pH 7·4 and 4·0. Eighty dogs were divided randomly into four groups (each n = 20): controls (no stent), bare stent (retained for 1 week), and two drug-eluting stent (DES) groups with retention for either 1 week (DES-1w) or 4 weeks (DES-4w). Lower oesophageal sphincter pressure (LOSP) and 5-min barium height (5-mBH) were assessed before, immediately after stent deployment, at 1 week, and 1, 3 and 6 months later. Five dogs in each group were killed for histological examination at each follow-up point. RESULTS: Stent migration rates were similar (0 bare stent versus 2 DES; P = 0·548). The percentage and amount of paclitaxel released in vitro was higher at pH 4·0 than at pH 7·4. After 6 months, LOSP and 5-mBH were both improved in the DES-1w (P = 0·004 and P = 0·049) and DES-4w (both P < 0·001) groups compared with the bare-stent group, with better relief when the stent was retained for 4 weeks (P = 0·004 and P = 0·007). The DES was associated with a reduced peak inflammatory reaction and less scar formation compared with bare stents, especially when inserted for 4 weeks. CONCLUSION: The DES was more effective for the treatment of benign cardia stricture than bare stents in a canine model. Retention of the DES for 4 weeks led to a better clinical and pathological outcome than 1 week.

Biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent placement to reduce fibroblast proliferation in experimental stricture in a canine model.

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess whether placement of the biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent is followed by less fibroblast proliferation and tissue hyperplasia compared with bare stents in experimental stricture in a dog model. METHODS: A total of 80 dog models of stricture were randomly divided into a control group (n = 20, no stent insertion), a bare stent group (BSG, n = 20, 1-week retention), and two drug-eluting stent sub-groups (DESG-1w, n = 20, 1-week retention; DESG-4w, n = 20, 4-week retention). Lower esophageal sphincter (LES) pressure, 5-minute barium height (5-mBH), and cardia diameter were assessed before, immediately after the procedure, and regularly thereafter for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. RESULTS: Stent insertion was well tolerated, with similar migration rates (0 % in BSG vs. 7.5 % in DESGs; P = 0.5441). At 6 months, LES pressure and 5-mBH improved in DESG-1w (26.70 ± 5.02 mmHg and 6.50 ± 2.98 cm) and DESG-4w (20.16 ± 5.50 mmHg and 1.54 ± 0.98 cm) compared with BSG (39.94 ± 5.22 mmHg and 11.1 ± 5.46 cm) (P < 0.05), with DESG-4w being more stable than DESG-1w (P < 0.05). The cardia maintained greater patency in the DESGs (7.10 ± 3.09 mm in DESG-1w; 9.16 ± 3.77 mm in DESG-4w) than in the BSG (1.86 ± 2.45 mm; P < 0.05). Reduced peak inflammatory reactions and scarring occurred in DESGs compared with the BSG (P < 0.05), with a better outcome in DESG-4w than in DESG-1w (P < 0.05). CONCLUSIONS: In this experimental stricture model, rapamycin-eluting stents were more effective than bare stents for the reduction of fibroblast proliferation and tissue hyperplasia after stent placement. Furthermore, 4-week retention of the drug-eluting stent led to a better outcome than 1-week retention.

Identification of differentially-expressed proteins between early submucosal non-invasive and invasive colorectal cancer using 2D-DIGE and mass spectrometry.

Early detection and diagnosis of colorectal cancer (CRC) are closely related to a better therapeutic outcome, and the five-year survival rate of early CRC is over 90 percent. Though endoscopic minimally invasive treatment has become a quick and effective therapy for early CRC, endoscopic biopsies are usually not deep enough to obtain tissues from the submucosal layer and it is difficult to determine whether early CRC has infiltrated into the submucosa. Therefore, in the present study, we constructed tumor models of early submucosal non-invasive CRC (SNICRC) and submucosal invasive CRC (SICRC) in Fischer-344 rats induced by N-methyl-N-nitrosourea (MNU). The differentially-expressed proteins were analyzed and identified in SNICRC, SICRC and normal control (NC) tissues using highly sensitive two dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Proteomic data revealed 132 protein spots between SNICRC and SICRC, 162 protein spots between SICRC and NC and 154 protein spots between SNICRC and NC which were found differentially expressed. These differential spots were picked, in-gel digested and peptide mass fingerprints were obtained by MALDITOF-MS/MS. Finally, five differentially-expressed proteins in SNICRC, SICRC and NC were identified, and increases in Transgelin, peptidylprolyl isomerase A (PPIA) and tropomyosin alpha isoform d were observed, while decreases in carbonic anhydrase 2 (CAII) and an unnamed protein were detected in SICRC compared with SNICRC and NC. Furthermore, Fluorescence-based quantitative polymerase chain reaction (FQ-PCR), Western blotting and immunohistochemistry assays also revealed significant upregulation of Transgelin expression and down-regulation of CAII expression in SICRC tissues. In conclusion, 2D-DIGE is confirmed to be an efficient strategy that enables us to identify differentially expressed proteins between early SNICRC and SICRC. The potential biomarkers such as Transgelin and CAII may be used for the detection of early SICRC.

Temporary self-expanding cardia stents for the treatment of achalasia: an experimental study in dogs.

BACKGROUND: To assess the performance, efficiency and optimal removal time of a newly designed temporary retrievable cardia covered stent (TRC-CS) for the treatment of achalasia in a dog model. METHODS: Eighty-four achalasia-like dog models were randomly divided into seven groups of 12, a control group (CG; no stent insertion), a standard stent control group (NSCG, standard esophageal stent) and five treatment groups (TG, TRC-CS). Stents were retrieved at 4 days after insertion in the NSCG and at 4 days(4 d-TG), 2 weeks(2 w-TG), 1 month(1 m-TG), 3 months(3 m-TG), and 6 months(6 m-TG) in the TGs. Lower esophageal sphincter pressure (LESP) and a timed barium esophagram were assessed before stent insertion, after stent retrieval, and at 1-week, 1-, 3- and 6-month follow-up. Three dogs in NSCG and 4 d-TG were sacrificed for histological examination at each follow-up to investigate the inflammatory reaction after stent insertion. KEY RESULTS: Stent insertion/removal and the follow-up procedures were well tolerated. At 6-month follow-up, the 2 w-TG and 1 m-TG demonstrated an acceptable stent migration (n = 2 in both TGs vs n = 4 in NSCG, n = 4 in 3 m-TG, and n = 6 in 6 m-TG), improved LESP compared to after benzyl-dimethyltetradecylammonium chloride (BAC) injection (P < 0.05), and improved timed barium height (P = 0.0144 and 0.0409). Mouse -proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin staining revealed no inflammatory reaction difference between the NSCG and 4 d-TG at each follow-up. CONCLUSIONS & INFERENCES: The TRC-CS was effective in the treatment of achalasia in a dog model. LESP measurements, timed barium esophagram studies suggest an optimal stent retrieval time of between 2 w∼1 m.

Temporary self-expanding metallic stents and pneumatic dilation for the treatment of achalasia: a prospective study with a long-term follow-up.

The present study compares the efficacy of a self-expanding metallic stent (SEMS, diameter of 30 mm) and pneumatic dilation for the long-term clinical treatment of achalasia. A total of 155 patients diagnosed with achalasia were allocated for pneumatic dilation (n= 80, group A) or a temporary, 30-mm diameter SEMS (n= 75, group B). The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after placement. Data on clinical symptoms, complications, and long-term clinical outcomes were collected, and follow-up observations were performed at 6 months and at 1, 3-5, 5-8, 8-10, and >10 years, postoperatively. Pneumatic dilation and stent placement were technically successful in all of the patients. There were no significant differences in technique success, 30-day mortality, or complications between the two groups. The clinical remission rate in group A was significantly lower than that in group B at 1, 1-3, 3-5, 5-8 and, >10 years (P < 0.05), while the cumulative clinical failure rate in group A (66%, 53/80) was higher than that in group B (92%, 6/75). The mean primary patency in group B was significantly longer than that in group A (4.2 vs 2.1 years, respectively; P < 0.001). A temporary, 30-mm diameter SEMS was associated with a better long-term clinical efficacy in the treatment of patients with achalasia as compared with treatment with pneumatic dilation.

A comparison of enzyme immunoassay and gas chromatography/mass spectrometry in forensic toxicology.

A series of 137 urine samples were analyzed for drugs of abuse by enzyme immunoassay (EMIT) and by gas chromatography/mass spectrometry (GC/MS). Agreement between these methods was excellent and ranged from 93.4% for benzodiazepines to 98.5% for propoxyphene. EMIT false negative were traced to the presence of elevated endogenous lysozyme or other interfering materials. In the case of moderate amounts of lysozyme the use of a blank would lead to correct results. Disagreement in the identification of nine benzodiazepine samples was found to be due to a low recovery of benzodiazepine metabolites from urine. Recovery could be improved by incubation of the urine sample with the enzyme beta-glucuronidase.