Obstruction Group Research Articles

Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

Long-term administration of alpha-1 blocker can reverse the micturition pattern in a bladder outlet obstruction murine model.

To investigate the effect of chronic administration of an alpha-1 blocker on micturition patterns in long-term partial bladder outlet obstruction. Mice were divided into three groups: a normal group, in which animals were fed a standard diet; a partial bladder outlet obstruction group, in which the proximal urethra was tied and animals were fed a standard diet; and a partial bladder outlet obstruction+naftopidil group, in which the proximal urethra was tied and animals were fed a standard diet containing naftopidil. Micturition behavior was evaluated in all groups for 6months after partial bladder outlet obstruction surgery. The parameters evaluated included voided volume, time per void, urination frequency and total urine volume. Quantitative assessment of gene expression was also carried out. Total urine volume, as well as total and average voided volume during night, was significantly decreased in partial bladder outlet obstruction+naftopidil mice compared with partial bladder outlet obstruction animals. The levels of transcripts encoding 5-hydroxytryptamine2A and tissue inhibitor of metalloproteinase2 were significantly decreased in the partial bladder outlet obstruction+naftopidil group compared with the partial bladder outlet obstruction group. Long-term administration of an alpha-1 blocker seems to reverse the disturbance of the micturition pattern caused by partial bladder outlet obstruction. Mechanistically, this effect might be mediated by changes in the expression of a serotonin receptor and/or in the activity of the fibrogenesis pathway.

A new perspective on imaging of olfactory dysfunction: Does size matter?

PurposeThis study assesses the diagnostic utility of olfactory nerve and bulb morphologies in addition to volumetric analysis in classification of different olfactory dysfunction etiologies. Methods106 patients presenting with olfactory loss and 17 control subjects were included. Based on detailed anamnesis, smell test and ear-nose-throat examination; patients were categorized into four groups as post-viral, post-traumatic, idiopathic, and obstructive olfactory dysfunction. Olfactory region was imaged with paranasal sinus CT and MRI dedicated to olfactory nerve. Olfactory bulb volume and olfactory sulcus depths were calculated on MRI. The olfactory bulb was assessed for morphology, contour lobulations and T2-signal intensity; and olfactory nerve for uniformity and clumping. ResultsVolumetric analysis showed decreased olfactory bulb volume in idiopathic and obstructive group compared to control subjects. Olfactory sulci were shallower in post-viral, post-traumatic, idiopathic, and obstructive group compared to the control group.In post-viral group; olfactory bulbs had lobulated contour and focal T2-hyperintense regions in 67 % of cases, and olfactory nerves had a clumped and thickened appearance in 66 % of cases. In idiopathic group, olfactory bulbs were rectangular shaped with minimally deformed contours, and olfactory nerves were thin and hard to delineate. No specific olfactory bulb or nerve pattern was identified in obstructive and post-traumatic groups, however closed olfactory cleft and siderotic frontobasal changes were helpful clues in obstructive and post-traumatic groups, respectively. ConclusionIn addition to olfactory cleft patency, olfactory sulcus depth and olfactory bulb volume; bulb and nerve morphologies may provide diagnostic information on different etiologies of olfactory dysfunction.

Can urinary biomarkers detect obstruction defined by renal functional loss in antenatal hydronephrosis?

Diagnosing obstruction and thus, assessment of need for surgery in the management of antenatal hydronephrosis may be challenging. Current diagnostic tests are not capable of indicating which patients are at risk for obstructive nephropathy. Biomarkers may play an important role in distinguishing these patients. The aim of this study is to evaluate if urinary biomarkers could differentiate obstruction (OBS) from non-obstructive dilation (NOD) in patients with antenatal hydronephrosis (AH) that underwent pyeloplasty due to loss of differential renal function (DRF). Children with a history of AH and postnatal anteroposterior (AP) diameter ≥15mm were included in this study of prospectively collected data between 2010 and 2018. The OBS group included patients who underwent pyeloplasty due to solely ≥10% subsequent decrease in DRF on a MAG-3 scan during follow-up. Patients with stable or improving hydronephrosis with no significant reduction in ipsilateral DRF (<10%) during follow-up formed the NOD group. Healthy children with no history of AH and a normal urinary ultrasound were taken as the control group. Urinary IP-10, MCP-1, KIM-1, NGAL, and Ca19-9 levels using ELISA were measured. In the OBS group, urine samples were obtained preoperatively and at 3rd post operative-month whereas in the NOD and control groups, samples were collected at the time of enrollment. There were 24 children in the OBS and 27 children in the NOD groups. The control group consisted of 27 healthy children. The pre-operative bladder urine levels of biomarkers of the OBS group were significantly higher than in the NOD and control group (p<0.05, for all). In terms of differentiating OBS from NOD, results of ROC analyses for the given cut-off values were as follows: 135.06 ng/mgCr (sensitivity 75%; specificity 66%, AUC=0.735) for IP-10, 0.89 ng/mgCr (sensitivity 79.2%; specificity 88%, AUC=0.802) for KIM-1, 367.65 pg/mgCr (sensitivity 62.5%; specificity 52%, AUC=0.660) for MCP-1, 16.15 ng/mgCr (sensitivity 70.8%; specificity 70.4%, AUC=0.669) for NGAL, and 55.5 U/mgCr (sensitivity 75%; specificity 66%, AUC=0.676) for Ca 19-9. Moreover, when KIM-1 was combined with IP-10 and Ca19-9, sensitivity and specificity levels were 83% and 85% (AUC=0.919), respectively. In this novel study, which focused on scintigraphic DRF loss, KIM-1 was the most successful among all the biomarkers evaluated. Combination of IP-10, Ca19-9 and KIM-1 resulted increased diagnostic ability.

A Study on the Role and Mechanism of Fenofibrate in Mice Renal Fibrosis Induced by Unilateral Ureteral Obstruction

To investigate the role and mechanism of fenofibrate in renal fibrosis induced by unilateral ureteral obstruction in mice, and to provide a potential therapeutic target for renal fibrosis. 31 adult male C57BL/6J mice were randomly divided into Sham operation group (Sham, n=9), unilateral ureteral obstruction group (UUO, n=10) and unilateral ureteral obstruction+ fenofibrate group (UUO+Feno, n=12). Mice in both the UUO group and UUO+Feno groups were ligated with left ureter, and the the mice in Sham group freed the left ureter without ligation. From the second day after the operation, the UUO+Feno group was daily intragastrically administrated with 10 mg/kg of fenofibrate normal saline solution (final concentration was 0.08 mg/mL) for 15 d, and the other two groups were intragastrically administrated with the same amount of normal saline solution. At 15 th day postoperation after intragastric administration, mice were sacrificed, and the concentration of serum creatinine and blood urea nitrogen were detected, the kidney tissues were performed HE staining, Masson dyeing and Sirius Red staining, and the content of renal tissue hydroxyproline were determined. Besides, immunohistochemical staining was used to explore the expressions of α-smooth muscle actin (α-SMA), Collegan-Ⅰ (COL Ⅰ) protein in renal tissue, Western blot was carried out to observe the changes of the expression levels of kidney α-SMA and COL Ⅰ proteins, and real-time fluorescent quantitative (RT)-PCR method was performed to detect the changes of mRNA expression levels of renal tissue fibrosis related genes matrix metalloproteinase (MMP)2, MMP9, COLⅠA1, COLⅠA2, tissue inhibitors of metalloproteinases (TIMP)-1, transforming growth factor (TGF)-β1, α-SMA. Compared with the Sham group, the serum creatinine and blood urea nitrogen levels of UUO group increased (P<0.05); compared with UUO group, the serum creatinine and blood urea nitrogen levels of UUO+Feno group were significantly lower (P<0.05). The results of HE staining, Masson staining, Sirius Red staining and renal hydroxyproline content indicated that the collagen deposition in UUO+Feno group was significantly reduced compared with that in UUO group. Immunohistochemical staining results showed that, compared with UUO group, the expression levels of α-SMA, COL Ⅰin kidney tissues of UUO+Feno group were significantly reduced; Western blot and RT-PCR results showed that compared with the UUO group, the mRNA and protein expression levels of fibrotic factors were significantly reduced in the UUO+Feno group (P<0.05). Fenofibrate reduced mice renal fibrosis caused by unilateral ureteral obstruction and its mechanism may be relate to its regulation effect on the expressions of renal tissue fibrosis related genes.

The value of brain natriuretic peptide in the prosthetic valve thrombosis.

: We aimed to investigate how prosthetic valve thrombosis (PVT) affects brain natriuretic peptide (BNP) levels and how BNP changes following thrombolytic therapy. The study included 70 consecutive patients with left-sided mechanical PVT who received thrombolytic therapy. The patients were divided into two groups, namely obstructive thrombus (n = 42) and nonobstructive thrombus (NOT, n = 28). BNP levels of patients were assessed before and after thrombolytic therapy. BNP levels were higher in obstructive thrombus group than NOT group in whole study population, in patients with mitral PVT and in patients with aortic PVT [325.0 (189.5-496.0) vs. 84.0 (44.5-140.0), P < 0.001, 323.0 (193-449.0) vs. 59.0 (37.0-131.0), P < 0.001 and 321.0 (132.0-525.0) vs. 99.0 (60.5-173.0), P < 0.001]. BNP levels were positively correlated with transmitral and transaortic mean gradients, and negatively correlated with mitral valve area (r: 0.374, P = 0.013; r: 0.432, P = 0.035 and; r: -0.642, P < 0.001, respectively). BNP values above 165 pg/ml may predict the presence of obstructive thrombus with a sensitivity of 88.0%, and a specificity of 79.0% (AUC = 0.928, 95% confidence interval: 0.871-0.986, P < 0.001). Following thrombolytic therapy, BNP levels (pg/ml) significantly decreased from 325.0 (189.5-496.0) to 137.0 (101.7-224.5), P < 0.001, in all patients with obstructive thrombus, from 323.0 (193.0-449.0) to 129.0 (98.0-223.0), P < 0.001, in patients with only mitral obstructive thrombus and from 321.0 (132.0-525.0) to 181.0 (99.0-217.5), P < 0.001, in patients with only aortic obstructive thrombus. BNP levels are significantly higher in prosthetic valve patients with obstructive thrombus than in those with NOT and decrease in patients with obstructive thrombus after thrombolytic therapy. A cut off value of BNP of at least 165.0 pg/ml was found to discriminate obstructive thrombus from NOT.

Self-expandable metal stent of esophagogastric junction versus pyloric area obstruction in advanced gastric cancer patients

Upper gastrointestinal stenting is a palliative treatment for relieving symptoms such as nausea, vomiting, and dietary intake in patients with obstruction due to inoperable advanced stomach cancer. Self-expandable metal stent (SEMS) implantation for malignant obstruction has recently become more effective, safer, and less expensive than operative modality. It also has better short-term outcomes, particularly a shorter hospital stay and a more rapid return to oral intake, than surgical treatment. However, there is no comparative analysis regarding the efficacy, side effects, and survival rate of stenting between the esophagogastric junction (EGJ) and pyloric obstructions.To compare the prognoses and complications after SEMS implantation between EGJ and pyloric obstructions in advanced gastric cancer.Among advanced gastric cancer patients with gastrointestinal obstruction diagnosed from January 2008 to December 2017 at the Gastroenterology Department of Chungnam National University Hospital, 42 and 76 patients presented with EGJ (EGJ obstruction group) and gastric pyloric obstructions (pyloric obstruction group), respectively. We retrospectively reviewed the survival period, changes in food intake, and complications of these patients before and after SEMS placement.The prevalences of aspiration pneumonia were 11.9% (5/42) and 2.6% (2/76) in the EGJ and pyloric obstruction groups, respectively, before SEMS placement (P value: .041). Other symptoms associated with gastric malignant obstruction were not statistically different between the groups. Success rate and adverse events did not significantly differ between the EGJ and pyloric obstruction groups. There was no difference in frequency of stent reinsertion procedures performed owing to reobstruction, but the reprocedure average period was statistically significantly longer in the EGJ obstruction group [EGJ obstruction: 158.3 days (±42.4); pyloric obstruction: 86.0 days (±29.1)] (P value: .022). As an index of improved dietary status, the Gastric Outlet Obstruction Scoring System score was not significantly different between the groups before and after SEMS placement.The EGJ and pyloric obstruction groups did not significantly differ in prognosis or complication rates. However, EGJ stent was more stable than pyloric stent when reobstruction was considered.

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study.

Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score = 0, uninjured coronaries and with no obstructive CHD (no critical stenosis, NCS) were considered as control subjects (n = 18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p = 0.05) of HLA-G gene in CHD patients compared to control group; 2) the hypomethylation level of one specific fragment of 161bp (+616/+777) positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups evaluated and was predictive for disease severity. Reduced levels of circulating HLA-G molecules could derive from epigenetic marks. Epigenetics phenomena induce hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive non critical stenosis vs coronary stenosis individuals.

Respiratory functional phenotypes of severe asthma in cohort of 130 patients

Asthma is a heterogeneous disease divided into clusters that do not consider the type of respiratory functional impairment. The objective was to investigate the association between respiratory functional impairment and main asthma phenotypes. We conducted a retrospective, observational, monocentric study including patients with severe asthma who first consulted at Croix Rousse Hospital, Hospices Civils de Lyon, between January 2015 and June 2018. Patients were divided into 4 respiratory functional groups: reversible proximal airway obstruction (Group 1); fixed proximal airway obstruction (Group 2); exclusive small airway involvement (Group 3); no functional impairment (Group 4). The distribution of these 4 functional groups was analyzed within the main clinical and biological phenotypes of severe asthma: TH2 high allergic, TH2 high eosinophil, mixed TH2 allergic/eosinophil, hypersensitivity to aspirin, and TH2 low. Among 130 patients, 28 patients were included in group 1 (22%), 51 patients in group 2 (39%), 27 patients in group 3 (21%), and 24 patients in group 4 (18%). The distribution of clinical phenotypes was significantly different between the groups (p=0.004). TH2 high eosinophil phenotype patients were higher in groups 1 and 2, compared to other phenotypes (p=0.014), and TH2 allergic phenotype patients were higher in groups 3 and 4, compared to other phenotypes (p=0.0003). Other phenotypes of severe asthma were not associated with a respiratory functional signature. We found heterogenous pulmonary functional impairment in severe asthma. Some functional characteristics are associated to allergic and eosinophilic phenotypes. More studies are needed to determine prognostic or therapeutic value of the functional impairment.

Are reduced internal nasal dimensions a risk factor for obstructive sleep apnea syndrome?

IntroductionObstructive sleep apnea syndrome is a high-prevalence disorder found in the population. Studies have shown a possible association between nasal obstruction and obstructive sleep apnea syndrome, but the existence of a association between the degree of nasal obstruction and obstructive sleep apnea syndrome severity has not yet been proven. ObjectiveTo evaluate the internal nasal dimensions of adults with primary snoring and obstructive sleep apnea syndrome by acoustic rhinometry and to correlate the findings with obstructive sleep apnea severity. MethodsTwenty-one male Caucasian subjects with complaints of snoring and/or respiratory pauses during sleep, aged between 18 and 60 years of age, were evaluated. After clinical evaluation, otorhinolaryngological examination and flexible nasopharyngolaryngoscopy, all patients underwent type III polysomnography. The participants were divided into two groups according to symptom severity: group 1, primary snoring and/or mild obstructive sleep apnea syndrome(n = 9) and group 2, moderate/severe obstructive sleep apnea syndrome (n = 12). Internal nasal dimensions were measured by acoustic rhinometry, analyzing minimum cross sectional area (CSA) and three nasal segment volumes. ResultsThe respiratory event index corresponded to 8.1 ± 4.0 in group 1 and 47.5 ± 19.1 in group 2. In group 1, the cross-sectional areas values, in cm2, corresponded to: CSA 1 = 1.1 ± 0.4; CSA 2 = 2.1 ± 0.9; CSA 3 = 3.5 ± 1.8 and, in group 2: CSA 1 = 1.2 ± 0.3, CSA 2 = 2.0 ± 0.5; CSA 3 = 2.8 ± 0.7. In group 1, volumes (V), in cm3, corresponded to: V1 = 3.5 ± 1.0; V2 = 9.3 ± 5.0; V3 = 40.2 ± 21.5 and in group 2 a: V1 = 3.6 ± 0.5; V2 = 7.6 ± 1.5; V3 = 31.5 ± 6.7. Cross-sectional area and volume ​​did not differ between groups. ConclusionThere were no significant differences in the cross-sectional areas and nasal volumes between individuals with primary snoring-mild obstructive sleep apnea syndrome and moderate-severe obstructive sleep apnea syndrome. Differently to the raised hypothesis, our results suggest that there is no association between internal nasal dimensions and severity of obstructive sleep apnea syndrome.

Use of diffusion-weighted imaging in the noninvasive diagnostic of obstructed biliary ducts.

This study sought to evaluate the role of diffusion-weighted imaging (DWI) in differentiation between obstructed and unobstructed bile ducts in patients undergoing magnetic resonance imaging (MRI). Eighty-four patients, 40 males and 44 females (mean age: 56.4 ± 15.1years), undergoing MRI with DWI (0-50-500-700) were evaluated and divided into two groups: 58 with abnormal laboratory tests (obstructed group) and 26 with normal laboratory values (unobstructed group). Laboratory tests were total bilirubin, alkaline phosphatase, and gamma-glutamyltransferase. Median ADC values were calculated and correlated with laboratory tests and degree of bile-duct dilatation (absent, moderate, or severe). The persistence of signal on DWI (b500 and b700) in the biliary tract was evaluated. Bilirubin values were tested for correlation with bile-duct ADC values and persistence of b700 signal. For statistical analysis, Student t test, chi-square test and Wilcoxon-Mann-Whitney test were used. ADC maps were plotted for three levels of the biliary tree, and a receiver operating characteristic (ROC) curve was calculated. In the obstructed group, 15 patients had severe dilatation, 24 had moderate dilatation, and 19 had no appreciable dilatation; 38 patients had persistent signal on b700 images. In the unobstructed group, 23 patients had no dilatation and 3 had moderate dilatation; 4 patients had persistent signal on b700 images. Correlation was found between degree of bile-duct dilatation, bilirubin levels, persistence of b700 signal, and ADC map values. The calculated ADC map cutoff value (353 10-6 mm2/s) was able to differentiate the obstructed and unobstructed groups with 92.3% sensitivity, 81% specificity, and 91.9% accuracy. DWI is able to distinguish patients with obstructed versus unobstructed bile ducts, regardless of the degree of dilatation, correlating with clinical and laboratory findings.

Obstructive colon cancers at endoscopy are associated with advanced tumor stage and poor patient outcome. A retrospective study on 398 patients.

The detection of obstructive colorectal cancer (CRC) masses during endoscopic examination hindering the passage of endoscope and precluding complete examination is not uncommon. The significance and implications of this finding on patients' prognosis and outcomes were not fully investigated and will be addressed in this study. In this retrospective cohort study, we reviewed endoscopy, surgery, pathology and oncology reports of patients diagnosed with CRC over a 10-year period (2007-2016). We compared surgical stages, histologic grades and overall survival between patients with subclinical obstructive tumors at endoscopy to those with nonobstructive tumors. We performed multivariate analysis to identify independent risk factors associated with advanced CRC stage at diagnosis. A total of 144 patients had obstructive colonic tumors while 254 had nonobstructive tumors and constituted the control group. Obstructive CRC group was significantly associated with advanced tumor stage at diagnosis (69 vs. 42%, OR = 3.018, 95% CI, 1.951-4.670; P < 0.01) and had prominently higher rates of moderate to poorly differentiated tumors (64.5 vs. 38.4%; P < 0.001) when compared to non-obstructive controls. Patients with obstructive tumors were significantly associated with decreased five years overall survival (53.4 vs. 67.3% vs.; P < 0.01). Increased overall mortality was observed in survival curves of patients with obstructive tumors along all follow-up periods. Even in the absence of clinical sequela, obstructive CRC at endoscopic level may be associated with higher stage at diagnosis and reduced overall survival. Further prospective studies are warranted to confirm these findings and address their implication on patients' management.

MRI in the evaluation of the azoospermic male.

PURPOSE We aimed to show the usefulness of magnetic resonance imaging (MRI) in the evaluation of infertile men and its ability to distinguish obstructive from nonobstructive azoospermia. METHODS Between April 2015 and February 2018, 45 azoospermic men underwent scrotal MRI. We evaluated the images with an emphasis on signal characteristics of the testis and morphologic changes typical for obstruction. Testicular volume (TV), apparent diffusion coefficient (ADC) value, T1 and T2 signal ratios (testis/muscle) were measured for every testis. On the basis of histologic results, patients were divided into two groups: obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). RESULTS Testes of patients in the OA group had significantly lower ADC values (mean 0.876±101 ×10-3 mm2/s) than in the NOA group (mean, 1.114±147 ×10-3 mm2/s). TV was significantly higher in patients with OA (median, 17.61 mL; range, 11.1-38.4 mL) than in those with NOA (median, 10.5 mL; range, 5.2-22.2 mL). ROC analysis showed that both TV and ADC values were highly predictive for distinguishing between OA and NOA patients, with an area under the ROC curve of 0.82 and 0.92 respectively. A cutoff value of ≥12.4 mL could distinguish obstructive from nonobstructive azoospermia with a sensitivity of 92% and specificity of 63%, whereas for ADC measurements a cutoff value of ≥0.952 ×10-3 mm2/s exhibited a sensitivity of 81% and specificity of 90% There was no statistically significant difference in T1 and T2 signal ratios between both groups. Abnormalities typical for obstruction of the male reproductive tract (e.g., dilatation of ejaculatory ducts, prostatic or seminal vesicle cysts) were found in 78% of patients (14/18) in the obstructive group. CONCLUSION Scrotal MRI is a very effective tool for the evaluation of azoospermic men and may provide important information facilitating interventional treatment of infertility.

Trends in the Surgical Management and Outcomes of Complicated Peptic Ulcer Disease.

Older data indicate that less patients undergo surgery for complicated peptic ulcer disease (PUD). We evaluated contemporary trends in the surgical management and outcomes of patients with complicated PUD. The National Inpatient Sample (2005-2014) was queried for patients with complicated PUD (hemorrhage, perforation, or obstruction). Trend analyses were used to evaluate changes in management and outcomes. There were 1 570 696 admissions for complicated PUD during the study period. Majority (87.0%) presented with hemorrhage, 10.6% presented with perforation, and 2.4% had an obstruction. The average age was 67 years. Overall, admissions with complicated PUD decreased from 180 054 in 2005 to 150 335 in 2014. The proportion of patients managed operatively decreased from 2.5% to 1.9% in the hemorrhage group, 75.0% to 67.4% in the perforation group, and 26.0% to 20.2% in the obstruction group (all P-trend < .05). Overall, among patients managed operatively, the use of acid-reducing procedures decreased from 25.9% to 13.9%, mortality decreased from 11.9% to 9.4% (both P-trend < .001), while complications remained stable (10.4% to 10.3%, P-trend = .830). There are fewer admissions with complicated PUD and more patients are treated nonoperatively. Despite subtle improvements, significant proportions of patients still die from complicated PUD indicating the need for improved preoperative optimization and postoperative care among these patients.

A study on the end criteria of forced vital capacity curve in adults

Objective: To explore the end criteria of forced vital capacity(FVC) curve in adults. Methods: A multicenter cross-sectional study was performed in Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Fujian Medical University, and the Third Affiliated Hospital of Inner Mongolia Medical University from January 2017 to August 2017. A consecutive sample of subjects who completed the spirometry test and FVC curves met end criteria of no volume change (<0.025 L) for ≥ 1 s were qualified in this study. Subjects were divided into a normal group (n=610), an obstructive group (n=536), and a restrictive group(n=306) according to pulmonary function test results. The FET values in different groups were compared. The side effects in the 3 groups and the diagnostic accuracy, specificity and security of different FET in the obstructive group were assessed. Results: The FET values of the normal group, the obstructive group, and the restricted group were (4.00±1.07) s, (8.08±1.56) s and (2.97±0.76) s respectively, and the 95% CI of FET in the 3 groups were between 3.88-4.12s, 7.02-10.14 and 2.21- 3.73s (F=2 263.80, P<0.01). When the exhalation platform was used as the standard of FVC curve, the adverse reaction rate in the normal group and the restricted group were 1.1% and 1.3% respectively, lower than the rate of 17.2% in the obstructive group (χ(2)=92.73, χ(2)=48.49 respectively; all P<0.05). In the obstructive group, 7 s as the ending criterion had similar incidence of adverse reactions to 6 s (χ(2)=0.01, P=0.93). With further extension of expiration time, the incidence of adverse reactions increased significantly. In the obstructive group, the sensitivity of FEV(1)/FEV(7) was 99.25%, higher than that at FEV(1)/FEV(6) (χ(2)=4.06, P=0.04), and the specificity of diagnosis was very similar and 100%. Conclusions: FET was variable in subjects with different lung function status. It is not appropriate to use a fixed FET≥ 6 s as the end criterion of spirometry for adults. For patients with normal lung function or restrictive lung function defect, exhalation platform should be used as the end of exhalation standard. For patients with obstructive lung function defect, an FET of up to 7 s is appropriate.

Mo1706 OBSTRUCTIVE COLON CANCER AT ENDOSCOPY AS AN INDEPENDENT RISK PREDICTOR OF ADVANCED TUMOR STAGE AND REDUCED SURVIVAL

It is still debatable whether a colorectal cancer tumor size affects patients' prognosis and outcome. A more clinically relevant and frequently encountered scenario is the presence of subclinical obstructive mass during endoscopic exam hindering the passage of endoscope and precluding complete exam. The significance and implications of this finding were not fully investigated, and will be addressed in this study. In this retrospective cohort study we reviewed endoscopy, surgery, pathology and oncology reports of patients diagnosed with colorectal cancer over a 10-year period (2007-2016). Data on patients' demographics and ethnicities were documented. Patients with a finding of obstructive tumors at endoscopy were compared to a control group of patients with non-obstructive tumors. We compared surgical stages, histologic grades and overall survival between both groups. We performed multivariate analysis to identify independent risk factors associated with advanced CRC stage and grade at diagnosis. 144 patients had obstructive colonic tumors while 254 had non-obstructive tumors and constituted the control group. Obstructive colon cancer group was significantly associated with advanced tumor stage (Stage 3 or above) at diagnosis compared to the non-obstructive controls (69% Vs. 42%, P<0.01) (Table 1). Likewise, in terms of histologic grade, more patients in the obstructive group were classified as moderate to poorly differentiated compared to controls (64.5 % vs. 38.4%; P<0.001). In multivariate analysis obstructive tumor finding was associated with increased risk of advanced CRC stage at diagnosis (odds ratio=3.018, p<0.0001 and 95%CI=1.951-4.670). A prominent difference of overall survival curves was also noted as obstructive colon cancer was significantly associated with decreased one (77.8% vs. 86%; P=0.01), three (63.6% vs.77.4%; P<0.01) and five years (53.4% vs. 67.3% vs.; P<0.01) survival (Figure 1). Even in the absence of clinical sequela, obstructive colorectal cancer at endoscopic level may be associated with higher stage at diagnosis and reduced overall survival. Further prospective studies are warranted to confirm these findings and address their implication on patients' management.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mo1688 LOCAL PHOTOTHERMAL THERAPY USING NANO FUNCTIONALIZED SELF EXPANDABLE METAL STENT IN AN ORTHOTOPIC MOUSE MODEL OF HUMAN COLON CANCER

Self-expandable stents for obstructing colorectal cancer offer an alternative palliative option to operative management. However, stent obstruction from tumor invasion decreases the stent patency and increases the rates of reintervention. Here, we developed a novel gold nanoparticle (GN) coated self-expandable metal stent (SEMS) for local heating induced suppression of tumor growth. The effectiveness was investigated in an orthotopic mouse model of human colon cancer. GN SEMSs (4 mm in diameter and 8 mm in length) were coated using a two-step synthesis process. The GN SEMS’s wire showed no cytotoxicity to human colon cancer cells (HCT-116) in-vitro. An effective local heating dose (55°C) was achieved under near-infrared laser irradiation (0.8 W/cm2) in ex-vivo studies. Subsequently, a red fluorescent protein (RFP) expressing HCT-116 human colon cancer cells were implanted in the submucosa of the colons of 40 nude mice using a microendoscope (Karl Storz, Germany). Mucosal lifting during the procedure indicated successful implantation. Tumor size was assessed by the degree of lumen obstruction on microendoscopy using a 5 points scale ranging from 1 (just detectable tumor) to 5 (tumor occupying more than half of the lumen). After 2 weeks, 30 mice developed tumors that obstructed 25-50% (grade 4) of the colon lumen (Fig. 1). They were randomly divided into 3 groups of 10 mice each; group A: GN SEMSs without laser irradiation, group B: uncoated SEMSs with laser irradiation (0.8 W/cm2), and group C: GN SEMSs with laser irradiation (0.8 W/cm2). Follow up using microendoscopy and in vivo fluorescence imaging was performed to check the tumor growth rate. The mice were sacrificed after one week and histopathological examination using hematoxylin and eosin staining was performed. SEMSs placement and laser irradiation (group B and C) were technically successful in all mice with no immediate complications. Within one week, seven mice died secondary to colonic obstruction (group A = 3, group B = 3, group C = 1), and one died from micro-perforation in group C. Follow up by microendoscopy after one week showed significantly reduced tumor size in group C (mean ± standard deviation, 1.13 ± .35) compared to group A (2.7 ± .49), and group B (2.6 ± .53); p = <.001. Also, the fluorescent signal intensity was significantly lower in group C (3.07 ± 0.83 × 108 p/s/cm2/sr) compared to group A (5.4 ± 0.80 × 108 p/s/cm2/sr), and group B (5.2 ± 0.24 × 108 p/s/cm2/sr); p = <0.001 (Fig. 2). Histopathological examination showed tumor development in the submucosal layer of the colon with smaller tumor sizes in group C compared to group A and B (Fig. 1). Local photothermal therapy using nano-functionalized stents inhibits tumor growth in an orthotopic mouse model of human colon cancer.Figure 2Representative in-vivo fluorescence images showing lower intensity signals in group C compared to group A and B. Time point 1 = before stent placement, 2= immediately after stent placement, and 3 = one week after stent placement.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

0128 Mild Upper Airway Obstruction Leads to Increased Energy Intake and Growth Retardation that Persists After the Obstruction Removal

Abstract Introduction Whereas pediatric obstructive sleep apnea may cause insufficient body weight gain and growth retardation, in some studies, metabolic syndrome and obesity were observed. Interestingly, treatment by adenotonsillectomy can lead to accelerated weight gain by an unclear mechanism. Here, we explored the effects of moderate upper airway obstruction (AO) and mild AO (mAO) and its removal (OR) on ventilation, resting energy expenditure (REE), food intake and growth during the diurnal cycle, from weaning to adulthood. Methods The trachea of 22-day-old rats was surgically narrowed to generate AO, mAO, and OR was performed after two weeks on mAO animals. Minute ventilation was recorded by whole body plethysmography and diurnal food intake, and REE was explored with metabolic cages 12 weeks post surgery. Results Following tracheal narrowing, inspiratory swings in esophageal pressure increased by 177% (p&amp;lt;0.01) and 36% (p&amp;lt;0.01) in AO and mAO rats, respectively, and was similar to the controls in the OR group. REE (Kcal/h/kg) was 3.7±0.1, 5.7±0.12 (p&amp;lt;0.01), 4.1±0.08 (p&amp;lt;0.01), and 3.6±0.15 in the control, AO, mAO, and OR groups, respectively. Increased EE in the AO and mAO groups was associated with up-regulation of ventilation by 133% and 56%, respectively (p&amp;lt;0.01). In all groups, energy intake (EE) was higher during a 12 h active period compared to a sleep period (p&amp;lt;0.01). EE during the lights on of AO and mAO animals increased by 136 % and 126%, respectively, and was similar to the control in the OR group. Active period EE increased by 19% in both obstructed groups (p&amp;lt;0.01). Active period EE was 16.7 % higher in the OR group despite the normalization of ventilation and tracheal diameter to the control value. Increased REE was associated with hindrance of bone elongation (p&amp;lt;0.01), and OR partially improved growth. Conclusion The need to maintain respiratory homeostasis during upper airway obstruction was associated with a persistent increase in energy intake. Surgical intervention may not be sufficient to correct the energy intake elevation, and endocrine regulation of feeding and growth may have greater impacts post intervention. Support This study was supported by the Israel Science Foundation grant no. 164/2018

Standardization for reliable uroflowmetry testing in adults.

To assess if a standard hydration protocol will achieve voided volumes over 150 mL and more reliable uroflowmetry results. This is a single-blinded crossover study of 40 patients with benign prostatic obstruction and 34 healthy volunteers. Subjects were enrolled prospectively between January and March 2019. All subjects performed two randomly ordered uroflowmetry tests. One test was performed when subjects sensed their bladder was full and had the urge to void and another one after emptying the bladder and ingesting 1.5 L of water within 1 hour (prehydration). Uroflowmetry parameters were compared between the benign prostatic obstruction group and the healthy volunteers. Uroflowmetry results were categorized as reliable, residual, and suboptimal with respect to voided volumes. This study has been registered in the UMIN Clinical Trials Registry (UMIN000035446). The benign prostatic obstruction group and the healthy volunteer group presented no difference in respect of uroflowmetry test reliability (P = .459). Uroflowmetry results were reliable in 58 (78.4%) subjects in the prehydrated group and was reliable in 30 (40.5%) subjects in the non-prehydrated group. The difference was statistically significant (P < .05). In the benign prostatic obstruction group and healthy volunteer group, the rate of reliable uroflowmetry tests was significantly higher with prehydration (P < .05). The comparative analysis of uroflowmetry parameters between tests performed with and without prehydration revealed higher values in the prehydrated group (voided volume, maximum flow rate, average flow rate, and postvoiding residual volume; P < .05). Prehydration of patients with 1.5 L of water within 1 hour before uroflowmetry improves uroflowmetry outcomes. By this hydration protocol, the chance to obtain a voided volume over 150 mL is increased significantly.

Lacune is the stroke subtype linked to obstructive sleep apnea.

Each stroke subtype is associated with specific risk factors, and stroke prevention depends solely on the control of the underlying risk factors for each stroke subtype. Obstructive sleep apnea has been established as a major risk factor for stroke and cardiovascular disease. However, information on the stroke subtype linked to obstructive sleep apnea is scarce. This was a single-center, observational case series study conducted on patients who were admitted with acute ischemic stroke to King Khalid University Hospital. The TOAST criteria were used to determine the stroke subtype in each of these patients. The Berlin questionnaire was utilized to assess the presence of obstructive sleep apnea. The proportion of each stroke subtype was then calculated and compared between the group with associated obstructive sleep apnea and the group without associated obstructive sleep apnea. A total of 170 consecutive patients with acute ischemic stroke were admitted between January 2018 and September 2018. Eighty-seven (51%) patients were found to have obstructive sleep apnea. The proportion of small artery disease was significantly greater in the obstructive sleep apnea group (44% vs. 26%, P = 0.02). There was no difference in the distribution of the other stroke subtypes between the two groups. Univariate analysis revealed that small artery disease was associated with body mass index, hypertension, and obstructive sleep apnea. However, in a multivariate logistic analysis, only hypertension was found to be independently associated with small artery disease. Small artery disease is the most common stroke subtype associated with obstructive sleep apnea. Clinicians must vigilantly assess the presence of obstructive sleep apnea in ischemic stroke patients, especially in patients whose stroke is attributed to small artery disease.