Background/Aims: This study aimed to clarify the risk of progression in patients with non-dysplastic Barrett’s esophagus (NDBE) and patients with confirmed low-grade dysplasia (LGD) and indefinite for dysplasia (IND) after an expert pathologist review of patients with BE with suspected dysplasia in a prospective cohort. Methods: Patients with Barrett’s esophagus diagnosed with dysplasia at Ersta Hospital in Stockholm from 1998 to 2012 were included. The first dysplastic specimen in all patients was re-evaluated by two expert pathologists and classified as NDBE, LGD, IND, or cancer, including high-grade dysplasia. The incidence rates (IRs) and IR ratios were calculated with 95% confidence intervals. Results: Of 423 patients with Barrett’s esophagus with dysplasia, 266 (62.9%) were re-classified as NDBE, 83 (19.6%) had LGD, 71 (16.8%) had IND, and 3 (0.7%) patients had cancer. During the follow-up, 34 (8%) patients developed cancer, most of them within five years, while others progressed after up to 25 years of surveillance. IRs for cancer among patients with NDBE was 0.41%/year compared to 1.84%/year for LGD (p<0.001) and 1.43%/year for IND (p=0.008). Conclusions Long-term risk of progression to cancer did not differ between patients with confirmed LGD and IND. These findings suggest that patients with IND should undergo similar management as patients with LGD.

Background/Aims: This study aimed to clarify the risk of progression in patients with non-dysplastic Barrett’s esophagus (NDBE) and patients with confirmed low-grade dysplasia (LGD) and indefinite for dysplasia (IND) after an expert pathologist review of patients with BE with suspected dysplasia in a prospective cohort. Methods: Patients with Barrett’s esophagus diagnosed with dysplasia at Ersta Hospital in Stockholm from 1998 to 2012 were included. The first dysplastic specimen in all patients was re-evaluated by two expert pathologists and classified as NDBE, LGD, IND, or cancer, including high-grade dysplasia. The incidence rates (IRs) and IR ratios were calculated with 95% confidence intervals. Results: Of 423 patients with Barrett’s esophagus with dysplasia, 266 (62.9%) were re-classified as NDBE, 83 (19.6%) had LGD, 71 (16.8%) had IND, and 3 (0.7%) patients had cancer. During the follow-up, 34 (8%) patients developed cancer, most of them within five years, while others progressed after up to 25 years of surveillance. IRs for cancer among patients with NDBE was 0.41%/year compared to 1.84%/year for LGD (p<0.001) and 1.43%/year for IND (p=0.008). Conclusions Long-term risk of progression to cancer did not differ between patients with confirmed LGD and IND. These findings suggest that patients with IND should undergo similar management as patients with LGD.

Background/Aims: This study aimed to clarify the risk of progression in patients with non-dysplastic Barrett’s esophagus (NDBE) and patients with confirmed low-grade dysplasia (LGD) and indefinite for dysplasia (IND) after an expert pathologist review of patients with BE with suspected dysplasia in a prospective cohort. Methods: Patients with Barrett’s esophagus diagnosed with dysplasia at Ersta Hospital in Stockholm from 1998 to 2012 were included. The first dysplastic specimen in all patients was re-evaluated by two expert pathologists and classified as NDBE, LGD, IND, or cancer, including high-grade dysplasia. The incidence rates (IRs) and IR ratios were calculated with 95% confidence intervals. Results: Of 423 patients with Barrett’s esophagus with dysplasia, 266 (62.9%) were re-classified as NDBE, 83 (19.6%) had LGD, 71 (16.8%) had IND, and 3 (0.7%) patients had cancer. During the follow-up, 34 (8%) patients developed cancer, most of them within five years, while others progressed after up to 25 years of surveillance. IRs for cancer among patients with NDBE was 0.41%/year compared to 1.84%/year for LGD (p<0.001) and 1.43%/year for IND (p=0.008). Conclusions Long-term risk of progression to cancer did not differ between patients with confirmed LGD and IND. These findings suggest that patients with IND should undergo similar management as patients with LGD.

Problem: The Global Outbreak Alert and Response Network (GOARN) has responded to more than 100 outbreaks during the past 23 years. The coronavirus disease (COVID-19) pandemic presented unprecedented operational constraints that challenged GOARN’s core mission to rapidly deploy technical experts from its partners to support national in-country responses to public health emergencies. This paper describes the type and duration of GOARN deployments to and within the World Health Organization’s (WHO’s) Western Pacific Region during the COVID-19 pandemic. Context: Despite strict border closures and ever-changing vaccination and quarantine requirements, GOARN continued to deploy international technical assistance to strengthen COVID-19 response operations within the Region, as requested. Action: Data were analysed from the GOARN Knowledge Platform about deployments to and within the Region for responses to the COVID-19 pandemic between 1 January 2020 and 5 May 2023. Data were available about deployment duration, technical role requested, country or area, partner organization and deployed expert’s demographics. Feedback from postdeployment briefings with the experts was collected and thematically analysed to determine ongoing needs and gaps to help improve deployment operations. Outcome: There were 72 experts deployed on 89 missions through GOARN to 12 countries and areas in the Region, for a total of 4558 field days, to support the response to the COVID-19 pandemic. Discussion: The volume of requests for assistance from countries and areas in the Region to respond to the COVID-19 pandemic uncovered a deficit in human resources available for domestic response to outbreaks and the reliance on international assistance. Strengthening the in-country capacity of ready-to-respond public health emergency staff is critical to meet the needs for outbreak response. The ongoing demand for technical experts to support national responses means that these lessons may have immediate implications.

Telephone follow-up is one of the important ways to follow up patients. High-quality follow-up can benefit both doctors and patients. However, clinical research-related follow-up is often faced with problems such as time-consuming, laborious and poor patient compliance. The authors belong to a team that has been committed to the study of patient-reported outcomes for a long time. The team has carried out long-term follow-up of symptoms, daily function and postoperative complications of more than 1 000 patients after lung cancer surgery, and accumulated certain experience. In this paper, the experience of telephone follow-up was summarized and discussed with relevant literatures from the aspects of clarifying the purpose of clinical research follow-up, understanding the needs of patients in follow-up, and using follow-up skills.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. It is often reported to be worsened by psychological stress. Objective: To explore the role of psychological stress and related triggers in AD, and its connection to worsening of this disease, focusing on patients’ perspectives. Methods: In total, 28 patients with AD were included in focus groups. Topics regarding psychological stress and psychological triggers were discussed. Results: The hypothesis that psychological stress may have impact on eczema and its pruritus was supported by all of the patients. Distinguishing the worsening effect of psychological stress from effects of physiological triggers, such as infection, climate and allergic factors, was claimed to be difficult by many patients. Most of the patients thought that chronic stress affected the AD more when compared to acute stress. Family problems, financial problems, work overload, school exam periods, lack of structure at work, and unforeseen events were identified as important psychological triggers. Conventional treatment/therapy with topical corticosteroids and emollients, UV light treatment, were suggested as possible treatments, as well as psychological intervention and physical exercise. Conclusion Psychological stress is an important factor to consider in the management of patients with AD. In particular, chronic stress tends to worsen AD. The type of stress can possibly also affect the quality of the pruritus experienced by the patients. Unforeseen events and decision making were frequently mentioned as important triggers. Furthermore, physical exercise was reported to provide beneficial effects.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9), the third-generation genome editing tool, has been favored because of its high efficiency and clear system composition. In this technology, the introduced double-strand breaks (DSBs) are mainly repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathways. The high-fidelity HDR pathway is used for genome modification, which can introduce artificially controllable insertions, deletions, or substitutions carried by the donor templates. Although high-level knock-out can be easily achieved by NHEJ, accurate HDR-mediated knock-in remains a technical challenge. In most circumstances, although both alleles are broken by endonucleases, only one can be repaired by HDR, and the other one is usually recombined by NHEJ. For gene function studies or disease model establishment, biallelic editing to generate homozygous cell lines and homozygotes is needed to ensure consistent phenotypes. Thus, there is an urgent need for an efficient biallelic editing system. Here, we developed three pairs of integrated selection systems, where each of the two selection cassettes contained one drug-screening gene and one fluorescent marker. Flanked by homologous arms containing the mutated sequences, the selection cassettes were integrated into the target site, mediated by CRISPR/Cas9-induced HDR. Positively targeted cell clones were massively enriched by fluorescent microscopy after screening for drug resistance. We tested this novel method on the amyloid precursor protein (APP) and presenilin 1 (PSEN1) loci and demonstrated up to 82.0% biallelic editing efficiency after optimization. Our results indicate that this strategy can provide a new efficient approach for biallelic editing and lay a foundation for establishment of an easier and more efficient disease model.
Alleles ; CRISPR-Cas Systems ; DNA End-Joining Repair ; Gene Editing/methods* ; Recombinational DNA Repair

A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

Background/Aims: Many unanswered questions remain about the treatment of malignant hilar obstruction. We investigated endoscopic stenting for malignant biliary strictures, as reported in a nationwide registry. Methods: All endoscopic retrograde cholangiopancreatography (ERCP) procedures entered in the Swedish Registry of Gallstone Surgery and ERCP from January 2010 to December 2017 in which stenting was performed for malignant biliary stricture management were included in this study. Patency was estimated by determining the time to reintervention. Results: Endoscopic stenting was performed for malignant stricture management in 4623 ERCP procedures, of which 1364 (29.5%) were performed for hilar strictures. Of the hilar strictures, 320 (23.5%) were intrahepatic strictures (Bismuth–Corlette III–IV). Adverse events were more common after hilar stenting than after distal stenting (17.2% vs. 12.0%, p<0.0001). The 6-month reintervention rate was 73.4% after hilar stenting compared with 55.9% after distal stenting (p<0.0001). The 6-month reintervention rates for Bismuth–Corlette types I, II, IIIa, IIIb, and IV were 70.4%, 75.6%, 90.0%, 87.5%, and 85.7%, respectively. In multivariate analysis, the risk for reintervention was three times higher after hilar stenting than after distal stenting (hazard ratio 3.47, 95% confidence interval 2.01–6.00, p<0.001). Conclusions This study with a relatively large patient cohort undergoing endoscopic stenting confirms that stenting for malignant hilar obstruction has more adverse events and lower patency than stenting for distal malignant obstruction.