Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

[Three-dimensional volume rendering for dynamic characteristics of secundum atrial septal defect during various phases of the cardiac cycle and the impact on occluder selection].

Objective: To investigate the dynamic change of the secundum atrial septal defect (ASD) throughout the cardiac cycle, and assess its impact on occluder selection. Methods: This study retrospectively analyzed 35 patients with ASD who received electrocardiogram-gated coronary CT angiography (CCTA) throughout the cardiac cycle as well as interventional closure therapy in Fuwai Hospital from December 2016 to December 2019. The raw data were reconstructed into 20 phasic images of RR intervals (RRI) ranging from 0 to 95% in an increment of 5% and transmitted to a workstation for postprocessing. For each phase image, CT virtual endoscopy reconstruction technique (CTVE) was used to provide views of ASD. Axial sequence assisted CT volumetric measurement (CTAS) was used to calculate the maximum dimensions in axial planes (Da) and in superior-inferior direction (Db). Using a formula for converting circumference to diameter, the equivalent circle dimensions were calculated (De, De=minor axis+2 (major axis-minor axis)/3). Taking the data of 75% RRI phase, the patients were divided into Da75%RRI≥Db75%RRI group and Da75%RRIDa. Db is basically constant while Da changes significantly during cardiac cycle (10%-90% RRI). Nonetheless, both values peak and maintain the maximum status at end-systolic phase (35%-45% RRI). For patients with huge ASD, occluder selection should be based on the De at 35% RRI phase, which is helpful for the successful intervention.

Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer.

OBJECTIVE: To investigate the correlations of analgesic dosage of morphine with solute carrier family 6 member 4 (SLC6A4) gene polymorphisms in patients with lung cancer. PATIENTS AND METHODS: A total of 200 lung cancer patients without cancer pain were selected as painless group, and another 200 lung cancer patients with cancer pain as cancer pain group. Visual Analogue Scale (VAS) was applied to grade the pain, the patients in cancer pain group were treated with morphine, and the dosage of morphine within 24 h was recorded. Then, the genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood of the research subjects, and the polymorphisms rs1042173 and rs7224199 of SLC6A4 gene were detected. RESULTS: There was a difference in the genotype distribution of SLC6A4 gene rs7224199 between painless group and cancer pain group (p=0.004), and the frequency of GG genotype was remarkably higher in cancer pain group [75 (0.375)]. The frequency of heterozygous model AC of rs1042173 and recessive model GT + TT of rs7224199 in cancer pain group was evidently lower than that in painless group (p=0.048, p=0.043). Besides, the lung cancer patients in cancer pain group had markedly lower frequency of AG haplotype (p=0.000), but notably higher frequency of AT (p=0.000) and CG (p=0.000) haplotypes of SLC6A4 gene rs1042173 and rs7224199 than those in painless group. No significant differences in genotypes of SLC6A4 gene rs1042173 (p=0.241) and rs7224199 (p=0.316) were detected among the degrees of cancer pain in cancer pain group. The analgesic dosage of morphine for the lung cancer patients was prominently correlated with the genotypes of SLC6A4 gene rs1042173 in cancer pain group. Moreover, in cancer pain group, there were significant differences in the dosage within 24 h (p=0.025), at 24 h after weight correction (p=0.001) and at 24 h after correction of weight and body surface area (p=0.000) among the genotypes, and the morphine dosage for the patients with CC genotype was significantly lower. Furthermore, the morphine dosage within 24 h (p=0.047), at 24 h after weight correction (p=0.042) and at 24 h after correction of weight and body surface area (p=0.031) were distinctly associated with the haplotypes of SLC6A4 gene in cancer pain group, of which the patients with CT haplotype were administered with a remarkably lower morphine dosage. CONCLUSIONS: The morphine dosage for analgesia has significant correlations with SLC6A4 gene polymorphisms in patients with lung cancer.

Long-term (2008-2018) aerosol properties and radiative effect at high-altitude sites over western trans-Himalayas.

Analysis of the climatology of aerosol properties is performed over Hanle (4500 m) and Merak (4310 m), two remote-background sites in the western trans-Himalayas, based on eleven years (2008-2018) of sun/sky radiometer (POM-01, Prede) measurements. The two sites present very similar atmospheric conditions and aerosol properties allowing us to examine them as continuous single-data series. The annual average aerosol optical depth at 500 nm (AOD500) is 0.04 ± 0.03, associated with an Ångström exponent (AE440-870) of 0.58 ± 0.35 and a single scattering albedo (SSA500) of 0.95 ± 0.05. AOD500 exhibits higher values in May (~0.07) and lower in winter (~0.03), while AE400-870 minimizes in spring, indicating influence by coarse-mode dust aerosols, either emitted regionally or long-range transported. The de-convolution of AOD500 into fine and coarse modes justifies the aerosol seasonality and sources, while the marginal diurnal variation in all aerosol properties reveals a weak influence from local sources, except for some few aerosol episodes. The aerosol-volume size distribution presents a mode value at ~10 µm with secondary peaks at accumulation (~ 2 µm) and fine modes (~0.03 µm) and low variability between the seasons. A classification of the aerosol types based on the fine-mode fraction (FMF) vs. SSA500 relationship reveals the dominance of aerosols in the FMF range of 0.4-0.6, characterized as mixed (39%), followed by fine aerosols with high scattering efficiency (26%), while particles related to dust contribute ~21%, with low fractions of fine-absorbing aerosols (~13%). The aerosol radiative forcing (ARF) estimates reveal a small cooling effect at the top of the atmosphere (-1.3 Wm-2), while at the surface, the ARF ranges from -2 Wm-2 to -6 Wm-2 on monthly basis. The monthly-mean atmospheric radiative forcing (~1 to 4 Wm-2) leads to heating rates of 0.04 to 0.13 K day-1. These ARF values are higher than the global averages and may cause climate implications over the trans-Himalayan region.

Overexpression of miRNA-410-3p protects hypoxia-induced cardiomyocyte injury via targeting TRAF5.

OBJECTIVE: This study aims to clarify the influence of microRNA-410-3p (miRNA-410-3p) on hypoxia-induced injury in cardiomyocytes. MATERIALS AND METHODS: MiRNA-410-3p level, apoptotic rate, and cell viability in AC16 cells undergoing normoxia or hypoxia preconditioning were assessed. The regulatory effects of miRNA-410-3p and TRAF5 on the proliferative and apoptotic abilities of AC16 cells were evaluated. The binding relationship between miRNA-410-3p and TRAF5 was verified by Dual-Luciferase Reporter Gene Assay. RESULTS: Hypoxia preconditioning triggered apoptosis and inhibited the viability in AC16 cells. MiRNA-410-3p was downregulated in cardiomyocytes under the hypoxic environment. The overexpression of miRNA-410-3p stimulated proliferation and inhibited apoptosis in hypoxia preconditioning AC16 cells. TRAF5 was proved to be the target of miRNA-410-3p. TRAF5 level was negatively regulated by miRNA-410-3p. The silence of TRAF5 could reverse viability and apoptosis changes in hypoxic AC16 cells overexpressing miRNA-410-3p. CONCLUSIONS: MiRNA-410-3p protects hypoxia-induced proliferation suppression and apoptosis stimulation in cardiomyocytes via targeting TRAF5.

Metformin and tuberculosis risk in elderly patients with diabetes mellitus.

SETTING: Tuberculosis (TB) and diabetes mellitus (DM) remain global health concerns. Metformin has recently received attention for its anti-tuberculosis effects.OBJECTIVE: To evaluate the risk of TB development in elderly DM patients treated with metformin compared with sulfonylureas.DESIGN: We performed a retrospective cohort study using the National Health Insurance Service-Senior database. The participants were type-2 DM (T2DM) patients aged ≥60 years between 1 January 2003 and 31 December 2013. We matched each metformin user to a sulfonylurea user using a propensity score. A Cox proportional hazards model was used to compare the risk of TB in metformin and sulfonylurea users.RESULTS: After propensity score matching, 12,582 patients were in each group. The TB incidence was 280.2/100 000 person-years (py) for metformin users and 394.5/100 000 py for sulfonylurea users. Metformin users had a lower risk of TB development than sulfonylurea users (adjusted hazard ratio 0.74, 95%CI 0.58-0.95), and the results were stronger for male participants. A dose-response relationship between metformin use and TB development was found in both sexes.CONCLUSION: Metformin use was associated with a decreased risk of TB development among elderly T2DM patients compared with sulfonylurea use.

Association between use of proton pump inhibitors and tuberculosis risk: a systematic review.

SETTING: A comprehensive systematic review on whether proton pump inhibitors (PPIs) are associated with tuberculosis (TB) incidence is lacking.OBJECTIVE: To conduct a systematic review to elucidate if there is an association between PPI use and TB risk.DESIGN: We searched the MEDLINE, EMBASE, and Cochrane Library databases from their inception through 14 February 2018. Risk of Bias Assessment tool for Non-randomised Studies (ROBANS) was used to estimate the quality of each study. We could not undertake a meta-analysis because of the small number of studies and the diversity of outcome measures. All results of included studies are described narratively.RESULTS: Five studies were identified. In three case-control studies, compared with non-PPI use, PPI use was associated significantly with TB incidence, a 1.2-to-1.7-fold increased risk (adjusted OR 1.29; 95%CI 1.29-1.30, OR 1.31; 95%CI 1.22-1.41, adjusted hazard ratio 1.71; 95%CI 1.17-2.50). A cohort study reported that ≥3 months of PPI treatment was not associated significantly with TB incidence compared PPI treatment of <3 months. One cohort study reported that lansoprazole use decreased TB development significantly when compared with omeprazole/pantoprazole use.CONCLUSION: Compared with non-PPI use, PPI use was associated significantly with TB risk but the studies were heterogeneous.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Optimal maintenance treatment with calcipotriol/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris: a multicentre randomized, controlled clinical trial.

BACKGROUND: There is a lack of response data for topical treatments for psoriasis vulgaris in Asian patients. OBJECTIVES: To determine the optimal maintenance regimen for topical treatment with calcipotriol monohydrate/betamethasone dipropionate gel in Korean patients with psoriasis vulgaris, by comparing the efficacy of three 8-week maintenance regimens. METHODS: This was a multicentre, prospective, randomized, controlled, parallel-group, open-label, phase 4 clinical trial, conducted in South Korea. Patients with psoriasis vulgaris on the limbs/trunk received once-daily treatment with calcipotriol monohydrate (50 µg/g)/betamethasone dipropionate (500 µg/g) gel for 8 weeks (induction phase). Responders (defined as an Investigator's Global Assessment of Disease Severity (IGA) grade of 'clear' or 'almost clear') were then randomized to receive 8 weeks' maintenance treatment with Xamiol® gel once daily as needed [pro re nata (PRN Group)], once daily every day (Continuous group), or twice weekly - on Saturday and Sunday (Weekend group). The primary endpoint was the percentage of IGA responders at week 16. RESULTS: At the end of the induction phase, 62.18% of patients were IGA responders. At the end of the maintenance phase (week 16), the responder rate was 63.89% for the PRN group, 67.5% for the Continuous group and 31.43% for the Weekend group. The PRN and Continuous groups were statistically superior to the Weekend group (P = 0.0109 and P = 0.0015), but the PRN and Continuous groups did not differ statistically. The incidence of adverse events did not differ significantly between the groups. CONCLUSION: Among Korean patients with psoriasis vulgaris, maintenance treatment with calcipotriol monohydrate/betamethasone dipropionate using a continuous daily regimen or an 'as needed' daily regimen provided similar efficacy, whereas a twice-weekly regimen was significantly less efficacious than either of these regimens.

Do volar locking plates fit the volar cortex of the distal radius?

The purpose of this study was to measure the volar cortical angles of the commercially available volar locking plates and evaluate how well they fit the distal radius. We measured the volar cortical angles of the radial and intermediate columns of eight volar locking plates and compared them with the volar cortical angles of 90 cadaver distal radii. The mean radial and intermediate column volar cortical angles of the wider plates were significantly larger than those of narrower plates. The mean radial and intermediate column volar cortical angles were significantly larger in wider radii than narrower radii. The width of the distal radius did not correlate well with the mean volar cortical angles of the radial and intermediate columns. LEVEL OF EVIDENCE: IV.

A randomised controlled trial comparing a dietary antiplatelet, the water-soluble tomato extract Fruitflow, with 75 mg aspirin in healthy subjects.

BACKGROUND/OBJECTIVES: Increasing numbers of food ingredients are gaining acknowledgement, via regulated health claims, of benefits to human health. One such is a water-soluble tomato extract, Fruitflow (FF), a dietary antiplatelet. We examined relative platelet responses to FF and to 75 mg aspirin (ASA) in healthy subjects. SUBJECTS/METHODS: A total of 47 healthy subjects completed a double-blinded randomised controlled trial following a crossover design. Acute and 7-day treatments with 75 mg ASA were compared with control with and without concomitant FF, over a 5-h timecourse. Platelet aggregation response agonist, platelet thromboxane A2 release, plasma clotting times and time to form a primary haemostatic clot (PFA-100 closure time, TTC) were measured. RESULTS: Administration of all treatments lowered platelet function and thromboxane A2 generation, and extended the TTC, relative to baseline (P<0.001) and to control (P<0.001). Plasma clotting times were not affected. A single 75 mg dose of ASA showed approximately equal efficacy to a dose of FF, whereas daily 75 mg ASA was approximately three times as effective after 7 days (P=0.002). Platelet responses were heterogenous with distinct weak and strong responder groups. Weak ASA responders retained a functional platelet response to collagen agonist and were responsive to FF. Concomitant FF and ASA did not lead to significant additive effects. CONCLUSIONS: The suppression of platelet function observed after consuming FF is approximately one-third that of daily 75 mg ASA. The reversible action of FF renders it less likely to overextend the time to form a primary haemostatic clot than ASA, an important safety consideration for primary prevention.

Supplementation with nutrients modulating insulin-like growth factor-1 negatively correlated with changes in the levels of pro-inflammatory cytokines in community-dwelling elderly people at risk of undernutrition.

BACKGROUND: Suboptimal nutrition accompanied by chronic low-grade increases in circulating cytokine levels is more common in elderly people. We explored the improvement in nutritional status, especially in the level of insulin-like growth factor-1 (IGF-1) and its relationship with changes in circulating cytokine levels, after providing extra protein and energy content to community-dwelling older adults at risk of undernutrition. METHODS: Sixty nondiabetic subjects, aged ≥65 years and living independently in a community for elderly people, with a serum pre-albumin level ≤30 mg dL-1 and a body mass index <25 kg m-2 , were recruited. The subjects were followed for a 2-week pre-intervention period, during which they maintained routine dietary habits. This was followed by an intervention period, during which they received oral nutritional supplementation for 2 weeks. RESULTS: Following 2 weeks of intervention, there were significant increases in total lymphocyte count (TLC) and insulin-like growth factor (IGF)-1, pre-albumin and transferrin compared to baseline. Body weight and mid-arm circumference significantly increased without alteration of tricep skinfold thickness at the end of the intervention. There was a significant reduction in interleukin (IL)-6 levels and a trend toward a decrease in the tumor necrosis factor (TNF)-α levels. At baseline, age was negatively correlated with IGF-1 levels and positively correlated with IL-6 and TNF-α levels. The change (▵, from baseline) in IGF-1 level was positively correlated with age and negatively correlated with ▵IL-6 and ▵TNF-α. CONCLUSIONS: A 2-week intervention with oral nutritional supplementation improved nutritional status and decreased circulating cytokine levels. Specifically, ▵IGF-1 was negatively correlated with changes in pro-inflammatory cytokine levels in community-dwelling elderly people at risk of undernutrition. (Clinicaltrials.gov: NCT02656186).

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Expression and prognostic influence of NF-κB and EGFR in esophageal cancer.

The goal of this study was to investigate the expression profiles of nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) in esophageal cancer and to determine their association with tumor prognosis. This study included 40 esophageal cancer patients [22 men and 18 women; average age = 62.7 ± 3.9 years; tumor-node-metastasis (TNM) staging: 12 patients with stage I, 13 patients with stage II, and 15 patients with stage III disease]. Tumor tissues and tumor-adjacent tissue specimens were collected during radical resections at our hospital. Immunohistochemical staining was used to examine these tissues for NF-κB and EGFR expression. Follow-up of all patients included gathering information such as the 3-year survival rate. We found that NF-κB and EGFR expression was significantly higher in tumor tissues compared to tumor-adjacent normal tissues. Expression was not related to gender or age, but was positively associated with the degree of tumor infiltration. NF-κB and EGFR expression levels gradually increased with higher TNM stage, but this difference was not significant. Follow-up results showed that patients with higher NF-κB and EGFR levels had a lower survival rate and unfavorable prognosis. In conclusion, we found that NF-κB and EGFR expression was significantly elevated during the occurrence and development of esophageal carcinoma, and expression of these factors appears to be correlated with cancer progression. Higher expression of both genes is associated with an unfavorable prognosis.

Efficacy and complications of enteral feeding tube insertion after liver transplantation.

BACKGROUND: Adequate nutritional support for patients undergoing major surgery significantly affects postoperative recovery. Data on enteral feeding after liver transplantation (LT) are scarce. The aim of this work was to determine the efficacy and complications of feeding tubes inserted with the use of fluoroscopic assistance, endoscopic assistance, or transperitoneal jejunostomy in patients who underwent LT. METHODS: From January 2008 to August 2013, 2,058 LTs were performed at Asan Medical Center, Seoul, Korea. Enteral feeding tubes were inserted in 155 patients (7.5%) after LT: with the use of fluoroscopic placement in 81 (52%), endoscopic placement in 49 (32%), and transperitoneal jejunostomy in 25 (16%). We retrospectively analyzed the efficacy and complications of enteral feeding tubes. RESULTS: The median age was 55 years (interquartile range [IQR] 49-60). Enteral feeding indications were a high risk of gastric aspiration (n = 90), gastric stasis (n = 27), pneumonia (n = 23), gastrointestinal bleeding (n = 12), and bowel rest (n = 3). Median enteral feeding durations were 14.5 days (IQR 8.0-30.7) for fluoroscopic placement, 20.0 days (IQR 8.0-40.0) for endoscopic placement, and 37.5 days (IQR 18.2-86.2) for transperitoneal jejunostomy. Times to establishment of oral feeding were 13.0 days (IQR 6.2-25.7) for fluoroscopic placement, 24.0 days (IQR 10.5-43.5) for endoscopic placement, and 37.0 days (IQR 17.0-64.2) for transperitoneal jejunostomy. After tube insertion, tube dislocation and blockage occurred in 34 patients (22%) and 16 patients (25%), respectively. CONCLUSIONS: Enteral feeding tube insertion in patients who can not maintain a nasogastric tube or start oral intake for a long time is important for nutritional support after LT. Proper feeding method selection according to patient condition can help patients by improving nutritional support after major operations such as LT.

Temperature-dependent rheological property changes of thermoplastic gutta-percha root filling materials.

AIM: To compare the penetration resistance (PR) of six thermoplastic gutta-percha (GP) materials against needle penetration at different temperatures. METHODOLOGY: The PR of the following materials based on warm gutta-percha techniques, Beefill GP Cartridge (Beefill), GP Obturator-Hard/Medium/Soft (Dia-H, Dia-M, Dia-S), Obtura (Obtura) and Tactendo Gutta (Tactendo), was measured as a function of temperature change (from 30 °C to 200 °C). The PR was measured using a force gauge, mounted on a motor-driven micrometre stage, which pushed the penetration needle against GP in a glass cylinder at the designated temperatures. Data were analysed using Kruskal-Wallis anova and Duncan's multiple range tests at 5% significance. RESULTS: The mean PR values for all assessed materials ranged from 15.55 MPa to 26.02 MPa at 30 °C, decreased to 0.18-1.61 MPa at 60 °C, and finally reached 0.02-0.12 MPa at 200 °C. The Obtura had the highest PR values at most of the measured temperatures. At 40-60 °C, Obtura had the highest PR value (P < 0.05), and Tactendo had the lowest amongst the tested materials. At 70-200 °C, both the mean PR values and melt flow temperature (MFR) of Obtura, Dia-H and Dia-M were significantly higher than those of other materials (P < 0.05). CONCLUSIONS: The PR values were changed by both the heating temperature and the brand or type of GP materials tested. Each material was associated with drastic decreases before reaching 60 °C in different degrees, and Obtura had the highest PR at most of the measured temperatures.

Association of phosphodiesterase 4D gene and interleukin-6 receptor gene polymorphisms with ischemic stroke in a Chinese hypertensive population.

Genetic factors have been shown to be associated with the risk of stroke. However, due to individual differences, the extent of the association between genetic factors and stroke varies widely. Hypertension is considered one of the most important risk factors for stroke, but it remains unknown whether the genetic association with stroke in a hypertensive population is the same as that in a non-hypertensive population. The aim of the present study was to explore the association between the phosphodiesterase 4D gene (PDE4D) and interleukin-6 receptor gene (IL6R) single nucleotide polymorphisms and ischemic stroke in a hypertensive population. The study included 307 ischemic stroke cases with hypertension and 227 controls (simple hypertension). The polymorphic loci rs12188950 and rs918592 in PDE4D, and rs4075015 and rs4537545 in IL6R were selected for analyzing the genotype and allele frequencies between cases and controls. rs12188950 was not found in the study population. In the univariate analysis, the rs918592 polymorphism in PDE4D was found to be significantly associated with ischemic stroke with the recessive model (P = 0.02), whereas no association with ischemic stroke was observed for rs4075015 and rs4537545 in IL6R. Following adjustment for binary logistic regression, the rs918592 polymorphism was not found to be associated with ischemic stroke. While prior studies have found an association between PDE4D and IL6R polymorphisms and ischemic stroke, our results suggest that this association may be different in a hypertensive population. Therefore, the association between PDE4D and IL6R polymorphisms and ischemic stroke among a hypertensive population requires further investigation.

The effect of age on the key parameters in the Chicago classification: a study using high-resolution esophageal manometry in asymptomatic normal individuals.

BACKGROUND: High-resolution manometry using the Chicago classification, which utilizes parameters including integrated relaxation pressure (IRP), distal contractile integral (DCI), and contractile front velocity (CFV), shows better diagnostic ability than previous conventional criteria. However, the current normal cut-off values for the Chicago classification are based on individuals aged 19-48 years and do not include older people. Here, we aimed to assess the normal values for the Chicago classification in individuals aged 20-67 years and compare the parameters across age groups. METHODS: Fifty-four asymptomatic healthy individuals (27 male and 27 female; age range. 20-67 years) were prospectively enrolled. To evaluate the effect of age and sex on manometric profiles, we attempted to enroll equal numbers of male and female subjects for each decade. Manometry was performed in both the supine and sitting positions. KEY RESULTS: The distal latency (DL) was significantly shorter with increasing age in both measurement positions. Furthermore, IRP was significantly higher with increasing age in both positions. Spearman's ranked correlation coefficient analysis indicated that DCI and IRP in both positions were positively correlated with age. CONCLUSIONS & INFERENCES: Age affects the key parameters currently used in the Chicago classification, including IRP, DCI, and DL. Larger prospective studies with older subjects are needed to determine the age-related normal values for the Chicago classification system.