Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the ...bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated.
In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed.
20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up.
These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.
Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed new light on the ...involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show differential expression in gastric cancer tissues. Genes coding for these miRNAs have been characterized as novel proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of gastric cancer cells. In this connection, miRNA dysregulation promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Moreover, certain polymorphisms in miRNA genes are associated with increased risks for atrophic gastritis and gastric cancer, whereas circulating levels of miRNAs may serve as biomarkers for early diagnosis. Several miRNAs have also been shown to correlate with gastric cancer progression, and thus may be used as prognostic markers. Elucidating the biological aspects of miRNA dysregulation may help us better understand the pathogenesis of gastric cancer and promote the development of miRNA-directed therapeutics against this deadly disease.
Paxillin (PXN) is required for receptor tyrosine kinase-mediated ERK activation, and the activation of the Raf/MEK/ERK cascade has been linked with Bcl-2 expression. We hypothesized that ...phosphorylation of PXN by the EGFR/Src pathway might contribute to cisplatin resistance via increased Bcl-2 expression. We show that cisplatin resistance was dependent on PXN expression, as evidenced by PXN overexpression in TL-13 and TL-10 cells and PXN knockdown in H23 and CL1-5 cells. Specific inhibitors of signaling pathways indicated that the phosphorylation of PXN at Y118 and Y31 via the Src pathway was responsible for cisplatin resistance. We further demonstrated that ERK activation was also dependent on this PXN phosphorylation. Bcl-2 transcription was upregulated by phosphorylated PXN-mediated ERK activation via increased binding of phosphorylated CREB to the Bcl-2 promoter. A subsequent increase in Bcl-2 levels by a PXN/ERK axis was responsible for the resistance to cisplatin. Animal models further confirmed the findings of in vitro cells indicating that xenograft tumors induced by TL-13-overexpressing cells were successfully suppressed by cisplatin combined with Src or ERK inhibitor compared with treatment of cisplatin, Src inhibitor or ERK inhibitor alone. A positive correlation of phosphorylated PXN with phosphorylated ERK and Bcl-2 was observed in lung tumors from NSCLC patients. Patients with tumors positive for PXN, phosphorylated PXN, phosphorylated ERK and Bcl-2 more commonly showed a poorer response to cisplatin-based chemotherapy than did patients with negative tumors. Collectively, PXN phosphorylation might contribute to cisplatin resistance via activating ERK-mediated Bcl-2 transcription. Therefore, we suggest that Src or ERK inhibitor might be helpful to improve the sensitivity for cisplatin-based chemotherapy in NSCLC patients with PXN-positive tumors.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Summary
Background
The sensitivity of current upper limit of normal (ULN) of serum alanine aminotransferase (ALT) levels for detecting chronic liver disease has been challenged recently.
Aim
To ...identify modulating factors for serum ALT levels and to refine its ULN threshold.
Methods
We enrolled 34 346 consecutive subjects who completed the health check‐up at Taipei Veterans General Hospital from 2002 to 2009. ULN was set for healthy ALT level to the 95th percentile of the reference healthy population.
Results
A group of 21 282 subjects were used as a training set to define an ULN with the highest sensitivity; afterwards, this ULN was validated in another set of 13 064 subjects. A reference healthy population was selected from the training set after excluding subjects with any abnormalities in independent risk factors associated with elevated serum ALT level (>40 IU/L) by multivariate analysis like body mass index, waist circumference, glucose, cholesterol, high‐density lipoprotein‐cholesterol, triglyceride, hepatitis B virus surface antigen, anti‐hepatitis C virus antibody and fatty liver. The new ULN of serum ALT level defined as the 95% percentile in the healthy population were 21 IU/L and 17 IU/L for men and women respectively. These cut‐off values had the highest Youden's index and areas under the corresponding receiver operating curves among four widely applied thresholds in both the training and validation sets.
Conclusions
The suggested threshold of upper limit of normal provides better discrimination between healthy and unhealthy status. Viral hepatitis, metabolic syndrome and fatty liver are the major risk factors of elevated serum alanine aminotransferase levels.
The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor ...pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3–9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3‐β‐d‐glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject’s health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono‐n‐butyl phthalate, and mono‐2‐ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized.
Practical Implications
For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy‐related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) ...was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and ...stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.
Summary
Background
The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results.
Aim
To assess in a meta‐analysis, the ...diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC.
Methods
Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random‐effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac‐based FOBT (gFOBT) and immunochemical‐based FOBT (iFOBT).
Results
Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3–79.4%), 93.6% (95% CI 90.7–95.7%), 11.1 (95% CI 7.8–15.8) and 0.3 (95% CI 0.2–0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9–87.0%), 93.6% (95% CI 90.7–95.7%), 12.6 (95% CI 8.8–18.1) and 0.2 (95% CI 0.1–0.3). The area‐under‐curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC.
Conclusion
Faecal occult blood tests, both guaiac‐ and immunochemical‐based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.
PDF
