Viral stimulation modulates endotype-related ACE2 expression in eosinophilic chronic rhinosinusitis.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), a receptor targeted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the nasal mucosa. Chronic rhinosinusitis (CRS) shows diverse endotypes and is aggravated by viral infection. Whether viral stimulation and CRS endotype influence ACE2 expression remains unclear. We investigated the expression of ACE2 and the transmembrane protease, serine 2 (TMPRSS2), which mediate the entry of SARS-CoV-2 into cells, and assessed polyinosinic:polycytidylic acid (poly[I:C])-induced changes based on CRS endotype. METHODOLOGY: ACE2 and TMPRSS2 expression was evaluated based on CRS phenotype, endotype, and tissue type. Correlations between ACE2/TMPRSS2 expression and inflammatory mediators in nasal polyps (NP) were examined. Air-liquid interface culture experiments were performed to assess the effects of major cytokines or poly(I:C) stimulation on ACE2/TMPRSS2 expression in primary epithelial cells from healthy nasal mucosa, eosinophilic NP (ENP), and non-eosinophilic NP (NENP). RESULTS: In primary nasal epithelial cells, interleukin (IL)-13 decreased ACE2 expression but increased TMPRSS2. Eosinophilic CRS showed lower ACE2 expression than non-eosinophilic CRS, regardless of CRS phenotype. CRS endotype was an independent factor associated with ACE2/TMPRSS2 expression in NP. Serum and tissue eosinophilic marker levels were inversely correlated with ACE2 expression, whereas tissue neutrophilic marker levels and ACE2 expression were positively correlated in NP. ACE2 expression was suppressed in ENP tissues; however, a combination of poly(I:C) and IL-13 induced ACE2/TMPRSS2 upregulation in ENP. CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.

Non-alcoholic fatty liver diseases and risk of colorectal neoplasia.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with colorectal neoplasia. Yet, NAFLD ranges from simple steatosis to steatohepatitis with advanced fibrosis. AIM: To investigate the risk of colorectal neoplasia according to the presence and severity of NAFLD. METHODS: A total of 26 540 asymptomatic adults who underwent same day first-time colonoscopy and abdominal ultrasonography as a health check-up programme were analysed. NAFLD was diagnosed by ultrasonography. Advanced colorectal neoplasia was defined as an invasive cancer or adenoma that was at least 10 mm in diameter, had high-grade dysplasia, or had villous histological characteristics or any combination thereof. RESULTS: NAFLD patients had a higher prevalence of any colorectal neoplasia (38.0% vs. 28.9%) and advanced colorectal neoplasia (2.8% vs. 1.9%) compared to those without NAFLD. In a multivariable model adjusted for age, sex, smoking, alcohol, body mass index, first-degree family history of colorectal cancer, aspirin use and metabolic factors, the odd ratios comparing patients with NAFLD to those without were 1.10 [95% confidence interval (CI): 1.03-1.17] for any colorectal neoplasia and 1.21 (95% CI: 0.99-1.47) for advanced colorectal neoplasia. When NAFLD patients were further stratified according to the non-invasive parameters of liver disease severity, the risk of any colorectal neoplasia or advanced colorectal neoplasia was higher for those with severe liver diseases than those with mild liver diseases. CONCLUSIONS: The presence and severity of NAFLD were closely associated with any colorectal neoplasia and advanced colorectal neoplasia, suggesting that clinicians should be aware of the increased risk of colorectal neoplasia in patients with NAFLD.

Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease: a nationwide population-based study in South Korea.

BACKGROUND: The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. AIM: To evaluate the risk of incident TB among IBD patients. METHODS: Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications. RESULTS: The IR, SIR and NNS for TB in IBD patients were 223.9/100 000 person-years, 2.64 (2.30-3.01) and 446.6 (392.8-517.6), respectively. The TB IR in Crohn's disease (CD) patients was significantly higher than that in ulcerative colitis (UC) patients (340.1/100 000 person-years vs. 165.5/100 000 person-years, respectively; P < 0.001). The SIR and NNS for TB among CD patients were 4.00 (3.59-4.45) and 604.2 (506.1-749.6), respectively; those among UC patients were 1.95 (1.66-2.27) and 294.0 (246.9-363.4). The TB IRs in IBD patients did not differ significantly by age or gender (Ptrend  = 0.505 and P = 0.861, respectively). The TB IRs among IBD patients prescribed 5-ASA, corticosteroids, immunomodulators and anti-TNF-α were 143.5, 208.5, 284.6 and 554.1 per 100 000 person-years, respectively. Among IBD patients treated using anti-TNF-α, the TB IR was significantly higher than that among all IBD patients (P < 0.001); the SIR and NNS for TB were 6.53 (5.99-7.09) and 180.5 (144.6-240.1) respectively. CONCLUSION: Clinicians should be aware of the increased risk of active tuberculosis in patients with IBD who are receiving anti-TNF-α therapy.

Establishment of reference interval for immature platelet fraction.

INTRODUCTION: Immature platelet fraction (IPF) is a parameter for reticulated platelets. A high percentage IPF (%-IPF) is indicative of consumptive or recovering thrombocytopenic disorders in contrast to a low %-IPF seen in aplastic states. Absolute IPF (A-IPF) specifically reflects the number of immature platelets in circulation. This study aimed to establish reliable reference intervals for %-IPF and A-IPF. METHODS: Except outliers, platelet counts and IPF were determined in 2152 healthy individuals (1252 men and 900 women) and 133 umbilical cord blood from healthy full-term neonates using XE-2100 hematology analyzer (Sysmex, Kobe, Japan). The reference intervals for %-IPF and A-IPF were defined using nonparametrical percentile methods according to the Clinical and Laboratory Standard Institute (CLSI) guideline. RESULTS: Platelets,%-IPF, and A-IPF all showed nonparametrical distributions. In total individuals, the reference intervals for %-IPF and A-IPF were 0.5-3.3% (0.5-3.1% in men; 0.5-3.4% in women) and 1.25-7.02 × 10(9) /L (1.30-6.80 × 10(9) /L in men; 1.21-7.15 × 10(9) /L in women), respectively. The reference intervals for %-IPF and A-IPF in umbilical cord blood were 0.7-3.8% and 1.93-9.7 × 10(9) /L, respectively. CONCLUSIONS: This study provides the reference interval for IPF, including %-IPF and A-IPF, according to the CLSI guideline. These results could be used as fundamental data for clinical use as well as future researches.

The efficacy of i-SCAN for detecting reflux esophagitis: a prospective randomized controlled trial.

New imaging technologies have been applied in endoscopy to improve the detection and differentiation of subtle mucosal changes using a digital contrast method. Among them, i-SCAN technology is the most recently developed image-enhancing technology. We investigated whether i-SCAN could improve the detection rate of reflux esophagitis. Interobserver agreement between endoscopists was compared with conventional white light (WL) endoscopic examination. We performed a prospective randomized controlled trial. A consecutive series of 514 subjects that underwent an esophagogastroduodenoscopy for health inspection were enrolled and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An esophagogastroduodenoscopy with video recording was used for detecting reflux esophagitis, and reflux esophagitis were categorized by the modified Los Angeles (LA) classification. The total number of reflux esophagitis identified by WL and i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group (30.1%) as compared to the WL group (21.6%). Using the modified LA classification, the detection rate of minimal changes was significantly higher (P = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the detection rates of LA-A and LA-B were not significantly different between the two groups (P = 0.897 and P = 0.311, respectively). After comparison of the interobserver agreement using randomly selected video clips, the i-SCAN group showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473). Compared to WL endoscopy, applying i-SCAN in daily practice can improve the diagnostic yield of reflux esophagitis by detecting more minimal changes in the squamo-columnar junction of the esophagus and can improve the interobserver agreement of the modified Los Angeles classification.

Comparison of transnasal small-caliber vs. peroral conventional esophagogastroduodenoscopy for evaluating varices in unsedated cirrhotic patients.

BACKGROUND AND STUDY AIMS: We aimed to evaluate the accuracy of transnasal small-caliber esophagogastroduodenoscopy (TNSC-EGD) compared with peroral conventional EGD (POC-EGD) for evaluating varices in unsedated patients with liver cirrhosis. The success rate, safety, endoscopist satisfaction, and patient tolerability of TNSC-EGD were also addressed. PATIENTS AND METHODS: One hundred patients with liver cirrhosis participated in this randomized crossover trial, and 84 subjects completed both procedures. Of the 84 patients, 28 had marked bleeding diathesis (platelet count ≤ 50000/mm (3) and/or prothrombin time ≥ 1.7 INR). Endoscopists and patients answered questionnaires using a 100-mm visual analog scale about, respectively, their satisfaction and their tolerance of the procedure. RESULTS: The success rate of TNSC-EGD was comparable to that of POC-EGD (96% vs. 99%). Nasal mucosal hemorrhages induced by TNSC-EGD occurred in 5 patients (6%), but were easily controlled. Compared to the POC-EGD reference test, diagnostic accuracies of TNSC-EGD for detecting esophageal varices, gastric varices, and red color signs were 98%, 98%, and 96%, respectively. Concordance rates on grading esophageal varices and gastric varices were excellent at 93% (κ = 0.85) and 96% (κ = 0.87). Endoscopist satisfaction was not significantly different between TNSC-EGD and POC-EGD, whereas patient tolerance of TNSC-EGD was significantly greater than that of POC-EGD (79.0 ± 14.4 vs. 69.5 ± 16.1; P = 0.001). CONCLUSION: TNSC-EGD without sedation was found to be feasible, safe, and accurate for evaluating esophageal varices, gastric varices, and red color signs in patients with cirrhosis - even in those with marked bleeding diathesis. Furthermore, it was significantly better tolerated by patients, without altering endoscopist satisfaction. Our findings indicate that TNSC-EGD without sedation might be viewed as a potential alternative to POC-EGD for evaluation of varices.

Does this patient have oesophageal motility abnormality or pathological acid reflux?

BACKGROUND AND AIMS: The diagnostic values of particular symptoms centred on oesophagus, among patients with suspected oesophageal motility abnormality or pathological acid exposure, are not yet fully understood. The aim of this study was to determine the predictive accuracy of these symptoms in diagnosis of oesophageal motility disorder or pathological acid exposure. PATIENTS AND METHODS.: A total of 462 patients who had undergone conventional oesophageal manometry and ambulatory 24-h pH monitoring to investigate a clinical suspicion of oesophageal motility disorder and pathological acid exposure were enrolled in this study. According to their principal complaints, the patients were divided into the dysphagia category, the non-cardiac chest pain category, the gastrooesophageal reflux disease-related symptom category and the extraoesophageal symptom category. RESULTS: Two hundred and two (44%) out of 462 patients yielded abnormal findings on manometry and/or pH monitoring. Dysphagia was associated with a likelihood ratio (LR) of 2.11 [95% confidence interval (CI), 1.02-4.00)] in patients exhibiting a combination of oesophageal motility abnormality and pathological acid exposure. During oesophageal manometry, the dysphagia substantially increased the likelihood of classic achalasia (LR, 6.24; 95% CI, 3.32-8.78) and diffuse oesophageal spasm (LR, 3.58; 95% CI, 1.03-7.12). When the patients with dysphagia were divided into two groups according to the severity of their symptoms, classic achalasia was significantly frequent in patients with severe dysphagia (P = 0.016). On the other hand, non-cardiac chest pain was the clinical factor that reduced the likelihood of classic achalasia (LR, 0.22; 95% CI, 0.04-0.93). The distribution of pathological acid exposure was significantly frequent between the groups of patients with and without gastrooesophageal reflux disease-related symptom (P = 0.011). CONCLUSION: A small number of oesophageal symptoms are helpful in predicting the likelihood of abnormal findings on oesophageal tests among patients with a clinical suspicion of oesophageal motility disorder and pathological acid exposure. The most useful finding is a severe dysphagia, which is likely to have classic achalasia.

Overexpression of cysteine-string proteins in Drosophila reveals interactions with syntaxin.

Cysteine-string proteins (CSPs) are associated with secretory vesicles and critical for regulated neurotransmitter release and peptide exocytosis. At nerve terminals, CSPs have been implicated in the mediation of neurotransmitter exocytosis by modulating presynaptic calcium channels; however, studies of CSPs in peptidergic secretion suggest a direct role in exocytosis independent of calcium transmembrane fluxes. Here we show that the individual expression of various CSP isoforms in Drosophila similarly rescues the loss of evoked neurotransmitter release at csp null mutant motor nerve terminals, suggesting widely overlapping functions for each isoform. Thus, the structural difference of CSP variants may not explain the opposing putative functions of CSP in neurotransmitter and peptide exocytosis. Consistently, the individual overexpression of each CSP isoform in wild-type Drosophila shows similar effects such as impaired viability and interference with wing and eye development. The dominant effects caused by the overexpression of CSP are suppressed by the simultaneous overexpression of syntaxin-1A but not by the coexpression of SNAP-25. Although overexpression of CSP itself has no apparent effect on the synaptic physiology of larval motor nerve terminals, it fully suppresses the decrease of evoked release induced by the overexpression of syntaxin-1A. A direct protein-protein interaction of CSP with syntaxin is further supported by coimmunoprecipitations of syntaxin with CSP and by protein binding assays using recombinant fusion proteins. Together, the genetic and biochemical interactions of CSP and syntaxin-1A suggest that CSP may chaperone or modulate protein-protein interactions of syntaxin-1A with either calcium channels or other components of the regulatory machinery mediating depolarization-dependent neurotransmitter exocytosis.

Left subclavian artery bypass graft in complicated arterial switch operation.

We report the successful use of left subclavian artery bypass graft in a newborn infant with complete transposition of the great arteries accompanied by an unusual coronary artery pattern, in whom left coronary artery insufficiency developed after the arterial switch operation. This procedure has shown good clinical results, with interesting follow-up angiographic findings 8 months after the operation.

Surgical treatment of atrial myxomas: a report of 20 cases.

Twenty atrial myxomas were resected in 20 patients with the use of cardiopulmonary bypass, from the beginning of July 1966 through the end of June 1985, at Severance Hospital, Seoul, Korea. Nineteen patients had left atrial myxomas; 1 had a right atrial myxoma. Left atrial myxomas arose from the intra-atrial septum in 17 patients and from the left atrial appendage in 2 patients. The right atrial myxoma arose from the fossa ovalis. The 13 female and 7 male patients ranged in age from 14 to 63 years. Symptoms most often reported on presentation were those associated with mitral valve obstruction; other symptoms were associated with systemic embolization. The 1st 4 patients were tested with angiocardiography alone, and 3 of these were misdiagnosed. The last 16 were tested by angiocardiography, M-mode echocardiography, and 2-dimensional echocardiography, alone or in various combinations, and there were no further misdiagnoses. In our experience, 2-dimensional echocardiography was the most accurate method of diagnosing cardiac tumors. In 19 patients, surgical approach was through a median sternotomy; in the 20th patient, approach was through a left thoracotomy, due to a preoperative misdiagnosis of mitral stenosis. No intraoperative embolizations or deaths occurred. On follow-up of 17 patients during periods ranging from 6 months to 6 years, we had no late deaths, and only 2 patients suffered late complications: 1 had sudden right hemiparesis caused by an embolus 4 months after surgery (this improved upon conservative treatment); and 1 had a recurrence of tumor 3 years after surgery (the new myxoma was successfully resected). We conclude that patients who have undergone complete excision of benign myxomas now have an excellent prognosis, with minimal risk of intraoperative embolization and late recurrence. We conclude also that 2-dimensional echocardiography is an extremely accurate tool both in early diagnosis of intracardiac myxomas and in late follow-up after resection.