Therkildsenbladt5939

7% vs 2.9%; p<0.001). Median (IQR) % improvement in GERD-HRQL was significantly higher in the EFTP group at 6 (81.4 (60.9-100.0) versus 8.0 (2.2-21.6); p<0.001) and 12 (92.3 (84.4-100.0) versus 9.1 (4.8-36.0); p<0.001) months. In the EFTP group, 62.8% patients were off-PPI at 12 months compared with 11.4% in the sham group (p<0.001). pH-metry parameters partially improved at 3 months, (n=70; total reflux episodes in EFTP arm and non-acid reflux episodes for EFTP vs sham) but not at 12 months (n=27); endoscopic oesophagitis was seen in 0% in the treatment (n=18) and 5 (29.4%) in the control group (n=17) at 12 months. PF-543 in vivo No major procedure-related adverse events were encountered in either group.

EFTP using a novel device is safe and effective in improving quality of life in patients with PPI dependent mostly non-erosive reflux disease at short and long terms; objective parameters showed a limited response rate.

NCT03322553.

NCT03322553.

COVID-19 has resulted in the death of over 1 million people to date. Following government-implemented regulations, there has been concern over the apparent decline in emergency department (ED) attendances and the resultant health legacy. Therefore, we aimed to characterise the attendances to an Irish tertiary hospital ED following the implementation of these regulations during the COVID-19 pandemic.

This retrospective observational study investigated all attendances to the Cork University Hospital ED from 15 February to 11 April in 2020 and 2017-2019. Attendances were stratified into four periods Before COVID (BC) (15 February to 5 March), After COVID (AC) (6 March to 12 March), Educational Closure (EC) (13 March to 27 March) and Stay Home (SH) (28 March to 11 April), as per government regulations. link2 Triage presentations of abdominal pain, shortness of breath, chest pain, headache and trauma were examined. Data were analysed by independent t-tests and χ

analysis.

There were 8261 attendances to the ED innment-imposed restrictions and perceived risk of attending an ED during a pandemic may contribute to reduced attendances. Public confidence in EDs is necessary to reduce collateral damage caused by failure to seek medical attention during a pandemic; adequate infrastructure to allow social distancing and isolation capacity in EDs is a necessity.

We compared the uptake of telemedicine for diabetes care across multiple demographic groups during the coronavirus disease 2019 pandemic to understand the impact of telemedicine adoption on access to care.

The study analyzed demographic information of patients with type 1 diabetes seen between 1 January 2018 and 30 June 2020 at a single center. We compared the odds of completing a visit via telemedicine across multiple demographic characteristics.

Among 28,977 patient visits, the odds of completing a visit via telemedicine were lower among non-English-speaking (1.7% vs. 2.7%; adjusted odds ratio [aOR] 0.45, 95% CI 0.26-0.79) and Medicaid-insured (32.0% vs. link3 35.9%; aOR 0.83, 95% CI 0.72-0.95) pediatric patients. No clinically significant differences were observed for other demographic factors.

Rapid transition to telemedicine did not significantly impact access to diabetes care for most demographic groups. However, disparities in access to care for historically marginalized groups merit close attention to ensure that use of telemedicine does not exacerbate these inequities.

Rapid transition to telemedicine did not significantly impact access to diabetes care for most demographic groups. However, disparities in access to care for historically marginalized groups merit close attention to ensure that use of telemedicine does not exacerbate these inequities.The glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.

The neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1-positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear.

A total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened. Glomerular immunohistochemistry staining for NELL-1 was performed in 43 patients with PLA2R- and THSD7A-negative membranous nephropathy, 31 patients with PLA2R-positive membranous nephropathy, and two patients with PLA2R and THSD7A double positivity. The NELL-1 antibody was also detected in the sera of patients with NELL-1-positive membranous nephropathy by western blot. Clinical and pathologic features were comparable between patients with isolated NELL-1-positive, isolated PLA2R/THSD7A-positive, and triple antigen-negative membous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.

About one third of patients who were PLA2R and THSD7A negative were NELL-1 positive in Chinese patients with primary membranous nephropathy. NELL-1-positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.

Immune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs.

This is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR.

We included a total of 169 patients 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR.

ETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.

ETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.

Current guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care.

Retrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge.

Thirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15-25) in the rapid-taper group compared withd over 3 weeks.

Anti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but is effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor β (CD122) augment CD8

antitumor T cells known to improve αPD-L1 efficacy. We hypothesized that the tumor microenvironment, including local immune cells in primary versus metastatic BC, differentially affects immunotherapy responses and that IL-2c effects could differ from, and thus complement αPD-L1.

We studied mechanisms of IL-2c and αPD-L1 efficacy using PD-L1

mouse BC cell lines MB49 and MBT-2 in orthotopic (bladder) and metastatic (lung) sites.

IL-2c reduced orthotopic tumor burden and extended survival in MB49 and MBT-2 BC models, similar to αPD-L1. Using antibody-mediated cell depletions and genetically T cell-deficient mice, we unexpectedly found that CD8

T cells were not necessary for IL-2c efficacy against tumors in bladder, whereas γδ T cells, not reported to contribute tancers. These studies also provide insights into γδ T cell contributions to immunotherapy in bladder and engagement of adaptive immunity by IL-2c plus αPD-L1 to treat refractory lung metastases.

Mechanistic insights into differential IL-2c and αPD-L1 treatment and tissue-dependent effects could help develop rational combination treatment strategies to improve treatment efficacy in distinct cancers. These studies also provide insights into γδ T cell contributions to immunotherapy in bladder and engagement of adaptive immunity by IL-2c plus αPD-L1 to treat refractory lung metastases.

We present a radiomics-based model for predicting response to pembrolizumab in patients with advanced rare cancers.

The study included 57 patients with advanced rare cancers who were enrolled in our phase II clinical trial of pembrolizumab. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST). Patients were categorized as 20 "controlled disease" (stable disease, partial response, or complete response) or 37 progressive disease). We used 3D-slicer to segment target lesions on standard-of-care, pretreatment contrast enhanced CT scans. We extracted 610 features (10 histogram-based features and 600 second-order texture features) from each volume of interest. Least absolute shrinkage and selection operator logistic regression was used to detect the most discriminatory features. Selected features were used to create a classification model, using XGBoost, for the prediction of tumor response to pembrolizumab. Leave-one-out cross-validation was performed to assess model performance.