Clinical evaluation of a fully automated and high-throughput molecular testing system for detection of influenza virus.

INTRODUCTION: We investigated the performance of the cobas® 6800 system and cobas SARS-CoV-2 & Influenza A/B, a fully automated molecular testing system for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This enabled an assay in a batch of 96 samples in approximately 3 h. METHODS: An assay was performed using the cobas SARS-CoV-2 & Influenza A/B on the cobas 6800 system for samples collected in four facilities between November 2019 and March 2020 in our previous study. The results were compared with those obtained using the reference methods. RESULTS: Of the 127 samples analyzed, the cobas SARS-CoV-2 & Influenza A/B detected influenza A virus in 75 samples, of which 73 were positive using the reference methods. No false negative results were observed. The overall positive and negative percent agreement for influenza A virus detection were 100.0% and 96.3%, respectively. There were no positive results for the influenza B virus or SARS-CoV-2. CONCLUSION: The cobas 6800 system and cobas SARS-CoV-2 & Influenza A/B showed high accuracy for influenza A virus detection and can be useful for clinical laboratories, especially those that routinely assay many samples.

Multicenter evaluation of molecular point-of-care testing and digital immunoassays for influenza virus A/B and respiratory syncytial virus in patients with influenza-like illness.

INTRODUCTION: Digital immunoassays (DIAs) and molecular point-of-care (POC) tests for influenza were recently developed. We aimed to evaluate and compare the positive rate with molecular POC tests and DIAs in detecting influenza virus A, B and respiratory syncytial virus (RSV). METHODS: A prospective observational study was conducted in 2019-2020. Nasopharyngeal swab samples were collected from adult outpatients with influenza-like illness who visited four hospitals and clinics in Japan. DIAs were performed at each facility. The clinical diagnosis was determined based on the findings of DIAs, history taking, and physical assessment. Molecular POC test and reverse transcription polymerase chain reaction (RT-PCR) were performed later. RESULTS: A total of 182 patients were evaluated. The positive rate for influenza virus with molecular POC test was significantly higher than that with DIAs (51.6% versus 40.7%, p = 0.046). In patients who tested positive for influenza virus with only molecular POC test, the presence of influenza virus was confirmed by RT-PCR. In a comparison between the patients who were positive for influenza virus with only molecular POC test and those with both molecular POC test and DIA, the percentage of patients who sought consultation within 18 h after the onset of symptoms was significantly higher in the molecular POC test only group than in the both methods group (70.0% versus 43.2%, p = 0.044). CONCLUSIONS: A molecular POC test could contribute to the accurate diagnosis of influenza in patients with influenza-like illness, especially those who visited a hospital immediately after the onset of symptoms.

Palladium-catalyzed Z-selective oxidative amination of ortho-substituted primary anilines with olefins under an open air atmosphere.

The Pd-catalyzed oxidative amination of olefins with primary anilines has been achieved using molecular dioxygen as the sole oxidant. The use of ortho-substituted primary anilines such as ortho-toluidine was the key to the successful development of this reaction, providing the corresponding N-alkenyl substituted anilines in high yields with unusually high levels of Z-selectivity.

Effectiveness of concomitant enteral nutrition therapy and infliximab for maintenance treatment of Crohn's disease in adults.

BACKGROUND: One of the problems associated with infliximab (IFX) treatment for Crohn's disease (CD) is loss of response during maintenance therapy. AIMS: The aim of this multicenter, retrospective, cohort study was to determine whether enteral nutrition (EN) added to the IFX therapy regimen is effective for maintaining remission in adult CD patients. METHODS: Patients with CD who had started IFX therapy between April 2003 and March 2008 at any one of the seven participating medical centers and who met the following inclusion criteria were enrolled in the study: remission after triple infusions of IFX followed by IFX maintenance therapy every 8 weeks, and follow-up data available for ≥ 1 year. Remission was defined as a C-reactive protein (CRP) level of <0.3 mg/dL, and recurrence was defined as an increase in CRP to ≥ 1.5 mg/dL or shortening of the IFX interval. Patients were classified by EN dosage into two groups (EN group and non-EN group). The cumulative remission period and related factors were analyzed. RESULTS: Of the 102 adult CD patients who met the inclusion criteria, 45 were in the EN group and 57 were in the non-EN group. The cumulative remission rate was significantly higher in the EN group than in the non-EN group (P = 0.009). Multivariate analysis revealed that EN was the only suppressive factor for disease recurrence (P = 0.01). CONCLUSIONS: The results demonstrate that among this CD patient cohort, EN combined with IFX maintenance treatment was clinically useful for maintaining remission.

Proximal extension of backwash ileitis in ulcerative-colitis - associated colon cancer.

BACKGROUND: Extension of the inflammatory process into the terminal ileum in ulcerative colitis is termed backwash ileitis. Ulcerative colitis patients with pancolitis and backwash ileitis may be at increased risk of colorectal carcinoma. A case of ulcerative colitis-associated cancer with backwash ileitis, which extended proximally over time, is described. CASE REPORT: A 67-year-old man was diagnosed with pancolitis; despite prednisolone and mesalazine treatment, he showed no improvement. Although initial endoscopic examination showed no abnormalities in the terminal ileum, a repeat colonoscopy 4 months later revealed erythema, absence of the vascular pattern, mucosal friability, and erosions within 30 cm of the terminal ileum in a continuous fashion from the cecum, and a flat, elevated lesion was found in the transverse colon. On histopathologic examination, the patient had nonspecific, active, chronic inflammation of the ileal mucosa, consistent with backwash ileitis, and colonic adenocarcinoma. Despite additional treatment with leukocytapheresis, the backwash ileitis progressed, with increased severity of mucosal inflammation and extensive erosions, 20 cm proximal to the primarily affected site of the ileum on repeat colonoscopy 2 months later. The patient underwent a proctocolectomy and excision of the terminal ileum with an ileostomy. CONCLUSIONS: Histopathology of the surgical specimen revealed marked backwash ileitis and submucosal, well-differentiated adenocarcinoma. The patient has remained well for 5 years after surgery.

Magnifying endoscopic observation with narrow band imaging for specialized intestinal metaplasia in barrett's esophagus with special reference to light blue crests.

AIM: Barrett's esophagus (BE) with specialized intestinal metaplasia (SIM) is at high risk of esophageal adenocarcinoma. Magnified endoscopy with narrow band imaging (ME-NBI) can be useful for detecting this condition. In addition to pit patterns, light blue crests (LBC), blue-whitish patchy areas on the metaplastic epithelia of the stomach, can predict SIM in BE under ME-NBI observation. METHODS: A total of 54 patients with BE underwent ME-NBI to identify IM pits (tubular and villous pits) and LBC. Biopsy samples were taken for histological evaluation of IM, immunohistochemical staining for CD10, MUC2 and MUC5AC antigen, transmission electron microscopy and real-time polymerase chain reaction (RT-PCR) analysis of CD10 mRNA expression. RESULTS: IM pit pattern with ME-NBI for the diagnosis of IM yielded acceptable sensitivity, specificity and accuracy at 92%, 77% and 83%, respectively. However, the sensitivity, specificity and accuracy of LBC with ME-NBI for IM were comparably high at 79%, 97% and 89%, respectively. Upon immunohistochemistry, all 19 metaplastic epithelia of LBC-positive BE showed immunoreactivity against anti-MUC2 antibody, whereas CD10 antigen was identified in 11 of the 19 LBC-positive BE. Brush borders were seen on IM epithelia using electron microscopy. On real-time PCR analysis, CD10 mRNA levels in the LBC-positive BE were higher compared to those in the LBC-negative BE. CONCLUSION: The appearance of LBC can be an accurate sign to predict SIM in BE and may be associated with high CD10 expression, possibly along with brush borders.

[A case of sacroiliitis complicated with ulcerative colitis which was treated with leukocytapheresis].

A 51-year-old woman was admitted to our hospital because of fever and pain in the right buttock. She had ulcerative colitis. She was given a diagnosis of sacroiliitis complicated with ulcerative colitis, based on a physical examination and magnetic resonance imaging (MRI) . Her sacroiliitis was successfully treated by leukocytapheresis (LCAP) . Sacroiliitis complicated with ulcerative colitis is rare in Japan, and its treatment and pathogenesis remain unclear. We report an unusual case of sacroiliitis complicated with ulcerative colitis, which was successfully treated by LCAP.

Effects of smoking cessation on gastric emptying in smokers.

BACKGROUND: Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. AIM: This study sought to determine how smoking cessation affects gastric emptying in smokers. METHODS: Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half-life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. RESULTS: Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. CONCLUSIONS: Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.

[A case of hepatic portal venous gas caused by transient type ischemic enteritis].

We report a case of hepatic portal venous gas (HPVG) caused by transient type ischemic enteritis. The patient was a 65-year-old woman, previously given a diagnosis of hypertension and diabetes mellitus. She was admitted to our hospital because of vomiting and epigastric pain. Abdominal computed tomography showed dilatation of the stomach and small intestine, with hepatic portal and superior mesenteric venous gas. Upper gastrointestinal endoscopy showed diffuse edematous and erosive change, and an extensive ulcer in the duodenum. There was no muscular defence, and physical and laboratory examinations did not indicate necrotic bowel. We diagnosed as HPVG caused by ischemic enteritis, and she responded to conservative treatment. We discuss a rare case of HPVG caused by transient type ischemic enteritis with references.

High dose immune globulin therapy ameliorates peripartum cardiomyopathy with elevated serum antibody titer to influenza virus: case report of two patients.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare complication characterized by heart failure that arises between the last month of pregnancy and the first 5 months after delivery. The etiology of this disorder has not been clarified due to its low incidence. We describe two patients with PPCM and elevated antibody titers to influenza virus in paired sera that were recovered by high doses of intravenous immune globulin. CASE REPORT: Case 1. One day before delivery by cesarean section, a 32-year-old woman developed PPCM that was immediately improved after the administration of a total cumulative dose of 1.7 g/kg immunoglobulin together with intra-aortic balloon pumping and percutaneous cardiopulmonary support. Antibody titers to influenza virus subtypes A and B were elevated in paired sera from this patient. Case 2. Four days postpartum, a 29-year-old woman developed PPCM and a total of 2.0 g/kg immunoglobulin recovered her cardiac function. The antibody titer to influenza virus subtype B was elevated in paired sera from this patient. Evidence of myocarditis was absent in endomyocardial specimens from both patients. CONCLUSIONS: These cases suggest that viral infection including influenza contributes to PPCM and that high doses of immunoglobulin constitute an effective treatment for this disorder.

Endoscopic submucosal dissection for colorectal epithelial neoplasms.

PURPOSE: Endoscopic submucosal dissection permits removal of colorectal epithelial neoplasms en bloc, but long-term clinical outcomes remain unknown. METHODS: Endoscopic submucosal dissection was performed in 282 patients having 296 colorectal tumors that fulfilled the inclusion criteria, which included lesions greater than 20 mm in size for which en bloc resection would be difficult with endoscopic mucosal resection, lesions with fibrotic scar due to previous endoscopic treatment or biopsies, locally residual lesions after endoscopic resection, or invasive carcinoma with slight submucosal penetration. En bloc or piecemeal resection, complete (en bloc with tumor-free lateral/basal margins) or incomplete resection, and complications were assessed, and factors related to each were analyzed using logistic regression. Patients with early colon cancer received endoscopic follow-up and metastatic surveys for a median of 34 months. RESULTS: En bloc resection was achieved in 89.2% (264/296) and 234 lesions (79.1%) were deemed to have undergone complete resection. A right-side colonic location was the significant contributor to incomplete resection. Perforation was seen in 24 cases (8.1%) in association with tumor size and the presence of fibrosis. There was 1 case of locally recurrent tumor with incomplete resection, whereas neither recurrence nor residual disease was observed in the complete resection group. Neither cancer-related nor cancer-unrelated death was observed. CONCLUSIONS: Precise assessment of curability with successful en bloc resection may reduce tumor recurrence after endoscopic submucosal dissection. The prognosis of early colorectal cancer in patients treated by endoscopic submucosal dissection is likely to be excellent, although further longer follow-up studies are warranted.

Endoscopic snare papillectomy with biliary and pancreatic stent placement for tumors of the major duodenal papilla.

BACKGROUND: This study aimed to evaluate the feasibility, safety, and follow-up results of endoscopic papilletomy (ESP) with pancreatic and biliary duct stent placement for ampullary tumors. The therapeutic approach to benign ampullary tumors remains unsettled. The ESP procedure is a curative treatment option for benign papillary tumors, but ESP raises concerns about a relatively high risk for procedure-related complications such as pancreatitis. A pancreatic stent may protect against complications. METHODS: Between September 2000 and June 2008, 36 patients with ampullary tumors confined to the mucosa and no intraductal tumor growth underwent ESP. The preprocedural diagnostic tools included endoscopic ultrasound, transpapillary intraductal ultrasound, and endoscopic retrograde cholangiopancreatography. Pancreatic and biliary stent placement was attempted if feasible. Endoscopic follow-up evaluation was conducted periodically as surveillance for recurrence. RESULTS: En bloc ESP was achieved for 94% of lesions with a median size of 14 mm. There were 26 adenomas including 4 high-grade intraepithelial neoplasias (HGINs), 5 carcinomas in adenoma, and 3 intramucosal cancers. Complete resections with tumor-free lateral and basal margins was achieved for 81% of the cases. During the median follow-up period of 14 months, there was one recurrent adenoma, which was successfully eradicated by a repeat ESP. A pancreatic stent was placed in 35 cases and a biliary stent in 29 cases. Mild acute pancreatitis and bleeding, managed endoscopically, occurred in 3 cases each (8%). CONCLUSION: The ESP procedure can be feasible for benign ampullary adenoma, HGIN, and noninvasive cancer without intraductal tumor growth. Prophylactic stent placement in the pancreatic and bile ducts may reduce procedure-related complications.

A new thin endoscopic method of transanal drainage tube insertion for acute colonic obstruction due to colorectal cancer.

AIM: Insertion of a transanal drainage tube is effective in the management of obstructing colorectal cancer. We devised a new method of inserting the transanal drainage tube safely and quickly using a thin endoscope. METHODS: Sixteen patients (seven men and nine women) with obstructive left-sided colorectal cancer were treated by inserting a transanal drainage tube using a thin endoscope. We inserted a transanal drainage tube for 32 patients (21 men and 11 women) with left-sided colorectal cancer using the conventional method. RESULTS: Drainage tube placement by the conventional method was successful in 29 (90.6%) of 32 patients, while via the new method, it was successful in all 16 patients without major complications. Moreover, median insertion time was significantly shortened (34 minutes for the new method compared with 42 minutes for the conventional method). CONCLUSION: Management of acute colorectal obstruction by transanal drainage tube insertion using the thin endoscope was effective and safe.

Magnified endoscopic observation using narrow-band imaging of periampullary adenoma in a patient with familial adenomatous polyposis.

BACKGROUND: Adenoma of the major papilla carries a relatively high risk of malignant transformation to carcinoma, the leading cause of death in patients with familiar adenomatous polyposis (FAP) after colectomy. CASE REPORT: A 35-year-old man had undergone prophylactic colectomy for FAP 3 years earlier. On the forward-viewing and side-viewing endoscopy done for surveillance, the overlying mucosa of the major papilla showed even granularity. On magnifying duodenoscopy using a narrow-band system (NBI), which uses modified optical filters and yields clear images of fine surface structures on the mucosal layer, a compact formation of round pits was seen in the affected ampulla. The microvascular architecture on NBI magnification showed no abnormalities, such as dilated, tortuous or network-like vessels, suggestive of malignancy. On endoscopic retrograde pancreaticocholangiography there was no intraductal growth, and endoscopic ultrasonography showed confinement to the mucosal layer. The ampullary lesion was completely resected using endoscopic snare papillectomy. Histopathological examination of the removed specimen showed tubular adenoma without malignant foci. The patient's post-treatment course was uneventful and without complications, and no local recurrence was noted on repeat endoscopy. CONCLUSIONS: Thus, endoscopic surveillance and removal of ampullary adenomas appear to be justified.

Pneumatosis intestinalis in ulcerative colitis.

BACKGROUND: UC patients are considered to be at risk for pneumatosis intestinalis (PI). CASE REPORT: A 50-year-old man who had been treated with prednisolone for left-sided ulcerative colitis (UC) underwent follow-up colonoscopy. In addition to active colitis in the left colon, some cystic lesions were found in the unaffected ascending colon. Endoscopic ultrasonography and computed tomography confirmed the presence of intramural air, consistent with PI. Since corticosteroid use might contribute to the development of PI, the patient was successfully treated with leukocytapheresis. At the last follow-up colonoscopy the UC was still in remission and the pneumatic cysts were resolving. CONCLUSIONS: It is important to determine the clinical significance of PI in each patient to ensure appropriate therapy.

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Endoscopic submucosal dissection of a minute intramucosal adenocarcinoma in Barrett's esophagus.

A 73-year-old man with short segmental Barrett's esophagus underwent esophagoscopy, and a slightly depressed, discolored lesion was found on the anterior wall of the lower esophagus. Under a provisional diagnosis of differentiated adenocarcinoma without local lymph node metastasis, endoscopic submucosal dissection (ESD) was carried out. En bloc resection with tumor-free lateral/basal margins was accomplished without complication. The resected area was 12 x 15 mm in size, whereas the neoplastic lesion was 4 x 4 mm. Histopathological examination confirmed intramucosal well-differentiated tubular adenocarcinoma without angiolymphatic invasion adjacent to the muscularis mucosae. Repeated esophagoscopy 6 months after ESD showed neither locally recurrent nor metachronous lesions. Considering that Barrett's esophagus is a precancerous condition, one may recommend eradication of both the neoplastic and non-neoplastic lesion with using ESD.

Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn's disease in the Japanese population.

OBJECTIVE: An association between susceptibility to inflammatory bowel disease (IBD) and polymorphisms of both the tyrosine kinase 2 gene (TYK2) and the signal transducer and activator of transcription 3 gene (STAT3) was examined in a Japanese population in order to identify the genetic determinants of IBD. METHODS: The study subjects comprised 112 patients with ulcerative colitis, 83 patients with Crohn's disease (CD), and 200 healthy control subjects. Seven tag single-nucleotide polymorphisms (SNPs) in TYK2 and STAT3 were detected by PCR-restriction fragment length polymorphism. RESULTS: The frequencies of a C allele and its homozygous C/C genotype at rs2293152 SNP in STAT3 in CD patients were significantly higher than those in control subjects (P = 0.007 and P = 0.001, respectively). Furthermore, out of four haplotypes composed of the two tag SNPs (rs280519 and rs2304256) in TYK2, the frequencies of a Hap 1 haplotype and its homozygous Hap 1/Hap1 diplotype were significantly higher in CD patients in comparison to those in control subjects (P = 0.023 and P = 0.024, respectively). In addition, the presence of both the C/C genotype at rs2293152 SNP in STAT3 and the Hap 1/Hap 1 diplotype of TYK2 independently contributes to the pathogenesis of CD and significantly increases the odds ratio to 7.486 for CD (P = 0.0008). CONCLUSION: TYK2 and STAT3 are genetic determinants of CD in the Japanese population. This combination polymorphism may be useful as a new genetic biomarker for the identification of high-risk individuals susceptible to CD.

Factors related to the curability of early gastric cancer with endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) yields substantially high rates for curative resection of early gastric cancer (EGC). It is suggested that larger, ulcerative, or upper EGCs may prevent successful ESD. A detailed analysis of factors associated with the curability of ESD was performed. METHODS: Endoscopic submucosal dissection was performed for patients with EGC that fulfilled the expanded criteria, which specified mucosal cancer without ulcer findings irrespective of tumor size, mucosal cancer with ulcers 3 cm in diameter or smaller, and minute submucosal invasive cancer 3 cm or smaller. Resectability (en bloc or by piecemeal resection), curability (curative or non-curative), and complications were assessed, and logistic regression analysis was used to analyze the related factors. RESULTS: Ulcerative EGCs showed a significantly higher risk associated with ESD on multivariate analysis. When the risk factors (tumor size, location, and ulcer findings) were combined, the larger EGCs (>30 mm) located in the upper third or ulcerative tumors located in the upper and middle portion of the stomach were at significantly higher risk of non-curative resection. Such lesions also were associated with increased risk of procedure-related perforation. CONCLUSIONS: When risk factors including positive ulcer findings and larger size and upper location of tumors are combined, ESD should be performed more carefully.