Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Low-Molecular-Weight J-Aggregate Solid Red Emitter for Selective and Quantitative Detection of Cyanide.

A dimethylaniline (donor)-indanedione (acceptor) conjugate (sensor 1) with a very low molecular weight of 277 g mol-1 and intramolecular charge transfer (ICT) characteristics was synthesized. Sensor 1 shows weak ICT fluorescence in solution, but strong emission (Φ=16%) in the solid state owing to intramolecular and intermolecular C-H⋅⋅⋅O hydrogen bonds that inhibit the free rotation of the exocyclic C-C single bond. Compared to yellow emitter 1Y, which has a similar donor-acceptor structure, sensor 1 shows red fluorescence in the solid state owing to J-aggregate formation. The colorimetric and fluorometric responses of sensor 1 to cyanide in both solution and solid state are due to the nucleophilic addition of cyanide to the ß-conjugated carbon of the indanedione group, which prohibits ICT. Additionally, inexpensive portable paper-based test kits based on sensor 1 were easily prepared and could be used for fast and quantitative naked-eye cyanide detection in real time.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits.

AIM: To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. METHODS: Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. RESULTS: During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1ß (IL-1ß) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1ß expression. Ozurdex suppressed the expression of IL-1ß, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. CONCLUSION: The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1ß, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1ß inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

Deoxynivalenol triggers porcine intestinal tight junction disorder: Insights from mitochondrial dynamics and mitophagy.

Deoxynivalenol (DON) is universally detected trichothecene in most cereal commodities, which is considered as a major hazardous material for human and animal health. Intestine is the most vulnerable organ with higher concentration of DON than other organs, owing to the first defense barrier function to exogenous substances. However, the underling mechanisms about DON-induced intestinal toxicity remain poorly understood. Here, DON poisoning models of IPEC-J2 cells was established to explore adverse effect and the potential mechanism of DON-induced enterotoxicity. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Intestinal epithelial barrier injury was caused by DON with increasing LDH release, decreasing cell viability as well decreasing tight junction protein expressions (Occludin, N-Cad, ZO-1, Claudin-1 and Claudin-3). Moreover, DON caused mitochondrial dysfunction by opening mitochondrial permeability transition pore and eliminating mitochondrial membrane potential. DON exposure upregulated protein and mRNA expression of mitochondrial fission factors (Drp1, Fis1, MIEF1 and MFF) and mitophagy factors (PINK1, Parkin and LC3), downregulated mitochondrial fusion factors (Mfn1, Mfn2, except OPA1), resulting in mitochondrial dynamics imbalance and mitophagy. Overall, these findings suggested that DON induced tight junction dysfunction in IPEC-J2 cells was related to mitochondrial dynamics-mediated mitophagy.

Dynamic Assessment of Tissue and Plasma EGFR-Activating and T790M Mutations with Droplet Digital PCR Assays for Monitoring Response and Resistance in Non-Small Cell Lung Cancers Treated with EGFR-TKIs.

Assessing tumor EGFR mutation status is necessary for the proper management of patients with advanced non-small cell lung cancer (NSCLC). We evaluated the impact of dynamic analyses of the plasma and tissue EGFR mutation using ultra-sensitive droplet digital PCR (ddPCR) assays to manage NSCLC patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). Paired tumor tissues and plasma samples from 137 EGFR-mutated lung adenocarcinoma patients prior to the first-line EGFR-TKIs treatment (at baseline) and at disease progression were subjected to EGFR mutation analysis using ddPCR, together with the analyses of the clinicopathological characteristics and treatment outcomes. Patients with EGFR-activating mutations detected in baseline plasma were associated with bone metastasis (p = 0.002) and had shorter progression-free survival (12.9 vs. 17.7 months, p = 0.02) and overall survival (24.0 vs. 39.4 months, p = 0.02) compared to those without. Pre-treatment EGFR T790M mutation found in baseline tumor tissues of 28 patients (20.4%; 28/137) was significantly associated with brain metastasis (p = 0.005) and a shorter brain metastasis-free survival (p = 0.001). The presence of EGFR T790M mutations in baseline tumor tissues did not correlate with the emergence of acquired EGFR T790M mutations detected at progression. At disease progression, acquired EGFR T790M mutations were detected in 26.6% (21/79) of the plasma samples and 42.9% (15/35) of the rebiopsy tissues, with a concordance rate of 71.4% (25/35). The dynamic monitoring of tissue and plasma EGFR mutation status at baseline and progression using ddPCR has a clinical impact on the evaluation of EGFR-TKIs treatment efficacy and patient outcomes, as well as the emergence of resistance in NSCLC.

Intramolecular C-H⋠⋠⋠O Hydrogen-Bonded Solid Emitter as Colorimetric and Fluorometric Cyanide-Selective Chemodosimeter.

An indole-indanedione-based small molecule, compound 1Me, comprising an intramolecular C-H⋅⋅⋅O hydrogen-bond (H-bond) and with an intramolecular charge transfer (ICT) characteristic was prepared for the colorimetric and fluorometric detection of CN- . Compound 1Me is virtually nonfluorescent in solution but emits a strong yellow fluorescence in the solid state because of the intramolecular C-H⋅⋅⋅O H-bond, which inhibits the free rotation of the exocyclic C-C single bond of 1Me. The nucleophilic addition of CN- to the ß-conjugated carbon of the indanedione group of 1Me, which breaks the intramolecular C-H⋅⋅⋅O H-bond and blocks ICT, causes the colorimetric and fluorometric responses of 1Me to CN- . Furthermore, inexpensive and portable paper-based test kits containing 1Me could be used to rapidly and conveniently sense CN- using the naked eye in real time. The results provide a new strategy for designing colorimetric and fluorometric cyanide-selective sensors based on an intramolecular C-H⋅⋅⋅O hydrogen bonded solid emitter.

Acute appendicitis after colorectal endoscopic mucosal resection: a case report.

Endoscopic mucosal resection (EMR) was originally described in 1973 and is currently a popular practice used in treating polyps, small adenomas, and early cancers. Although the safety of EMR has been proven in numerous studies, complications occur occasionally. We report a case in which the patient complained of severe upper abdominal pain and who was diagnosed with acute appendicitis after colorectal EMR. The patient recovered well after surgery. Cautious observation is necessary when resuming oral intake in patients who undergo colorectal EMR and who complain of postoperative abdominal pain. Observation is especially important for patients with a fecalith that may have originally existed in the appendix or in the colon near the appendix.

A Shigella species variant is causally linked to intractable functional constipation.

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

Real-world Evaluation of a Sample Pooling Strategy for Large-Scale Rapid COVID-19 Testing.

BACKGROUND: The worldwide outbreak of COVID-19 has become a public health crisis of unprecedented proportions. The fast spread of emerging variants increases the needs of rapid diagnostic and screening testing. Sample pooling efficiently expands the testing capacity under limited resources. OBJECTIVES: We evaluated the performance of sample pooling on the Point-of-Care (POC) Liat® and cobas® 6800 systems and provided real-world experiences for implementing these systems in large-scale screenings. METHODS: Positive nasopharyngeal (NP) specimens with Ct values < 25, 25∼30 or > 30 were tested individually and in pools to optimize the POC Liat® and cobas® 6800 systems, which were then implemented in community screenings. RESULTS: The 5-sample pooling strategy did not affect the positive detection rates on Liat® or cobas® 6800 in samples with Ct values <25 or 25∼30. However, in samples with low viral loads (Ct values >30), five-sample pooling has a higher positive detection rate on POC Liat® (20/20; 100%), compared to cobas® 6800 (9/20; 45%). Five-sample pooled on POC Liat® and two-sample pooled on cobas® 6800 appear to be appropriate for SARS-CoV-2 detection. By implementing the pooling strategies in two large-scale community screenings, 7,606 NP specimens was tested within 36 h; the average turn-around time was 4.8 h for cobas® 6800 and 1.3 h for POC Liat®. Eight positive specimens (0.11%; 8/7,606) were identified, with Ct values ranging from 18.85 to 37.68. CONCLUSION: The performance of sample pooling on POC Liat® was demonstrated to be an effective, accurate, and economical approach for large-scale community screenings for COVID-19.

New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment.

A Novel Titanium Cranioplasty Technique of Marking the Coronal and Squamosoparietal Sutures in Three-Dimensional Titanium Mesh as Anatomical Positioning Markers to Increase the Surgical Accuracy and Reduce Postoperative Complications.

Objective: The objective of this research is to modify the titanium cranioplasty (Ti-CP) technique to increase the surgical accuracy and preliminarily verify the effectiveness and safety of this improvement. Methods: We developed a novel technique of marking the coronal and squamosoparietal sutures in three-dimensional (3D) titanium mesh as anatomical positioning markers and designed a prospective trial in patients with a unilateral frontotemporoparietal skull defect. Patients were randomly divided into two groups by the presence or absence of the anatomical positioning markers, and the therapeutic effects of these two groups were compared. Results: Forty-four patients were included in this study, including 28 (64%) males and 16 (36%) females. The mean age was 44.8 ± 15.2 years (range, 13-75 years). Overall postoperative complication rate of the intervention group (18%) was significantly (P = 0.03) lower than the control group (50%). Surgical accuracy of the intervention group (97.8%) was significantly (P < 0.001) higher than the control group (94%). Visual analog scale for cosmesis (VASC) of the intervention group (8.4) was significantly (P < 0.001) higher than the control group (7). The overall postoperative complication rate was 34%. Multivariate analyses showed that surgical accuracy <95.8% (OR = 19.20, 95% CI = 3.17-116.45, P = 0.001) was significantly associated with overall postoperative complications. Independent predictor of overall postoperative complications was surgical accuracy (OR = 0.57, 95% CI = 0.40-0.82, P = 0.002). Conclusions: This novel technique for repairing frontotemporoparietal skull defects increases surgical accuracy, improves cosmetic prognosis, and reduces postoperative complications. Therefore, it is a safe and effective improvement for Ti-CP.

NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling.

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-ß levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-ß in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.

Prognostic implications of predialysis patients' symptoms in peritoneal dialysis patients.

BACKGROUND: As kidney disease progresses, patients often experience a variety of symptoms. There are very few studies reporting spectrum of predialysis patients' symptoms in peritoneal dialysis (PD) patients. Furthermore, the clinical significance of predialysis patients' symptoms for PD patients' prognosis remains unknown. METHODS: In this retrospective cohort study, patients who started PD during 1 January 2006 to 31 January 2018 were included. Patients' predialysis symptoms and clinical parameters were obtained. Both the short- and long-term patients' outcome were investigated by Cox regression and Kaplan-Meier's survival analysis to identify the relationship between clinical symptoms and patients' mortality on PD. RESULTS: A total of 898 incident PD patients were included. The anorexia (58%) was the most common predialysis symptom in the present cohort, followed by insomnia (32.7%), fatigue (27.6%), syndromes of heart failure (27.6%), and nausea (20.5%). The only symptom significantly associated with both six-months and 12-months mortality on PD was nausea (HR 2.359, 95% CI 1.377-4.040, p=.002 and HR 1.791, 95% CI 1.176-2.729, p=.007, respectively). But in the long-term, anorexia (HR 1.392, 95% CI 1.070-1.811, p=.014) was the only symptom significantly associated with patient's all-cause mortality after adjusting for other confounding factors. CONCLUSIONS: Our study demonstrated that nausea and anorexia were the most important predialysis symptoms, which was associated with patients' short- and long-term mortality on PD treatment, respectively. The results indicated that predialysis evaluation and management of symptoms of nausea and anorexia may be a possible way to improve patients' outcome on PD.

Establishing diagnostic algorithms for SARS-CoV-2 nucleic acid testing in clinical practice.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Our laboratory initially used a two-step molecular assay, first reported by Corman et al, for SARS-CoV-2 identification (the Taiwan Center for Disease Control [T-CDC] method). As rapid and accurate diagnosis of COVID-19 is required to control the spread of this infectious disease, the current study evaluated three commercially available assays, including the TaqPath COVID-19 Combo kit, the cobas SARS-CoV-2 test, and the Rendu 2019-nCoV Assay kit, to establish diagnostic algorithms for clinical laboratories. METHODS: A total of 790 clinical specimens, including nasopharyngeal swabs, throat swabs, sputum, saliva, stool, endotracheal aspirate, and serum were obtained from patients who were suspected or already confirmed to have COVID-19 at the Taipei Veterans General Hospital from February to May 2020. These specimens were tested for SARS-CoV-2 using the different assays and the performance variance between the assays was analyzed. RESULTS: Of the assays we evaluated, the T-CDC method and the TaqPath COVID-19 Combo kit require lots of hands-on practical laboratory work, while the cobas SARS-CoV-2 test and the Rendu 2019-nCoV Assay kit are fully automated detection systems. The T-CDC method and the TaqPath COVID-19 Combo kit showed similar detection sensitivity; however, the T-CDC method frequently delivered false-positive signals for envelope (E) and/or RNA-dependent RNA polymerase (RdRP) gene detection, thus increasing the risk of reporting false-positive results. A manual test-based testing strategy combining the T-CDC method and the TaqPath COVID-19 Combo kit was developed, which demonstrated excellent concordance rates (>99%) with the cobas and Rendu automatic systems. There were a few cases showing discrepant results, which may be due to the varied detection sensitivities as well as targets among the different platforms. Moreover, the concordance rate between the cobas and Rendu assays was 100%. CONCLUSION: Based on our evaluation, two SARS-CoV-2 diagnostic algorithms, one focusing on the manual assays and the other on the automatic platforms, were proposed. Our results provide valuable information that allows clinical laboratories to implement optimal diagnostic strategies for SARS-CoV-2 testing based on their clinical needs, such as test volume, turn-around time, and staff/resource limitations.

High-throughput sequencing provides insights into oral microbiota dysbiosis in association with inflammatory bowel disease.

Although the prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, the etiology remains elusive. Investigating oral microbiota dysbiosis is essential to understanding IBD pathogenesis. Our study evaluated variations in salivary microbiota and identified potential associations with IBD. The saliva microbiota of 22 IBD patients and 8 healthy controls (HCs) was determined using 16S ribosomal RNA (rRNA) gene sequencing and analyzed using QIIME2. A distinct saliva microbiota dysbiosis in IBD, characterized by alterations in microbiota biodiversity and composition, was identified. Saccharibacteria (TM7), Absconditabacteria (SR1), Leptotrichia, Prevotella, Bulleidia, and Atopobium, some of which are oral biofilm-forming bacteria, were significantly increased. Moreover, levels of inflammatory cytokines associated with IBD were elevated and positively correlated with TM7 and SR1. Functional variations include down-regulation of genetic information processing, while up-regulation of carbohydrate metabolism and protein processing in the endoplasmic reticulum in IBD. Our data implicate salivary microbiota dysbiosis involving in IBD pathogenesis.

Can admission lipoprotein-associated phospholipase A2 predict the symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage?

BACKGROUND: Inflammation has been believed to be related to the development of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). A potential biomarker for vascular inflammation that is well recognized is the lipoprotein-associated phospholipase A2 (Lp-PLA2). However, whether Lp-PLA2 can predict the occurrence of symptomatic cerebral vasospasm (SCV) in aSAH patients is still unknown. Thus, this study aimed to assess the value of Lp-PLA2 for predicting SCV in patients with aSAH. METHODS: Between March 2017 and April 2018, we evaluated 128 consecutive aSAH patients who were admitted in the First Affiliated Hospital of Fujian Medical University. Their Lp-PLA2 level was obtained within 24 h of the initial bleeding. Factors might be related to SCV were analyzed. RESULTS: Compared to patients without SCV, those with SCV (9.4%, 12/128) had significantly higher Lp-PLA2 level. Multivariate logistic analysis revealed that worse modified Fisher grade (OR = 10.08, 95% CI = 2.04-49.86, P = 0.005) and higher Lp-PLA2 level (OR = 6.66, 95% CI = 1.33-3.30, P = 0.021) were significantly associated with SCV, even after adjustment for confounders. Based on the best threshold, Lp-PLA2 had a sensitivity of 83.3% and a specificity of 51.7% for predicting SCV, as shown by the receiver operating characteristic curve analysis. In the poor World Federation of Neurosurgical Societies grade patient sub-group, patients with Lp-PLA2 > 200 µg/L had significantly higher SCV rate than that of patients having Lp-PLA2 ≤ 200 µg/L. CONCLUSION: The admission Lp-PLA2 level might be a helpful predictor for SCV in aSAH.

Seroprevalence of COVID-19 in Taiwan revealed by testing anti-SARS-CoV-2 serological antibodies on 14,765 hospital patients.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 25 million cases with over 0•85 million deaths, as of September 2, 2020. Taiwan has been successful in countering the COVID-19 outbreak, however, the potential risk for asymptomatic infections and the prevalence rates remain unknown. We aimed to estimate the seroprevalence of COVID-19 in Taiwan via serologically testing hospital patients with neither symptoms indicative of nor positive nucleic acid test for SARS-CoV-2 infection. METHODS: Residual specimens from laboratory blood tests for outpatient and emergency department patients visiting a medical centre in Taipei, Taiwan, within one week in May and another in July, 2020, were collected. We used Elecsys Anti-SARS-CoV-2 Assay to screen and further validated cases with high cutoff index by a confirmatory ELISA assay. We also analysed antibody responses against SARS-CoV-2 along disease progression in four nucleic acid test confirmed COVID-19 patients. FINDINGS: Blood samples from a total of 14,765 patients were tested. The unweighted seroprevalence of anti-SARS-CoV-2 antibodies was 0•07% [95% CI, 0•04%-0•13%]; after weighting with the population demographics of Taiwan, the estimated overall seroprevalence was 0•05% [95% CI, 0•02%-0•10%]. Furthermore, based on data of the four COVID-19 cases, the seroconversion dates for IgM were as early as 9 days and that for IgG 11 days after symptoms onset. INTERPRETATION: We screened the anti-SARS-CoV-2 antibodies in a small-scale population-based study and observed an approximately 0•05% seroprevalence of COVID-19, indicating that the current containment protocols emphasising mask wearing, hand washing, social distancing and mandatory quarantine for all incomers are effective in Taiwan. FUNDING: Taipei Veterans General Hospital, Taipei, Taiwan.

The clinicopathologic features and prognosis of esophageal neuroendocrine carcinomas: a single-center study of 53 resection cases.

BACKGROUND: Esophageal neuroendocrine carcinomas (NECs) are exceedingly rare and poorly understood. The aims of the retrospective study were to delineate the clinicopathologic features and prognosis of patients with the disease. METHODS: We performed a retrospective study containing 53 patients of esophageal NECs in our center from 2002 through 2018. Patients were assigned to the pure esophageal NECs group and the esophageal NECs mixed with squamous carcinoma and/or esophageal adenocarcinoma (MiNECs) group. Demographic, clinical, pathologic and prognostic factors were recorded and analyzed. RESULTS: Of the 53 patients, elderly male patients were predominant. Dysphagia was the most common symptom (45/53, 84.9%). Most tumors were centered in the middle esophagus (36/53,67.9%).Ulcerated appearance was frequently seen in the pure NECs (56.8%), and the tumors in the MiNECs group mostly represented elevated types (57.9%). Synaptophysin (38/45, 84.4%), chromogranin A (21/38, 55.3%) and CD56(23/27, 85.2%) have been proven to be positive markers for NECs. Most patients (46/53, 86.8%) received surgery combined with chemotherapy. Though the pathologic stages were alike (P = 0.129), the median survival time was 3.53 years for the pure NECs group and 7 years for the MiNECs group. In multivariate analysis, pathologic stage (RR = 1.938, P = 0.045) and age (RR = 2.410, P = 0.028) were independent prognostic factors for patients with MiNECs. The prognosis of patients with pure NECs was independent from any factors. CONCLUSIONS: Careful endoscopic examination could help distinguish pure NECs from MiNECs. NECs were aggressive, but a relative better prognosis for patients with MiNECs. Surgery should be performed if applicable, and chemotherapy might be helpful.