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Background: Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs). Materials and Methods: Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6–12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov ). Results: More than 26% ( n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6–12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score ( p < 0.001, p < 0.001), the total UF symptom QOL score ( p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale ( p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up. Conclusion: UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs.

Abstract In-stent stenosis has a reported prevalence of 14% to 19% at 1-yr follow-up after carotid stenting and is associated with an increased risk of acute ischemic stroke. 1,2 Risk factors include female sex, diabetes, and dyslipidemia. Cutting balloon angioplasty is a safe and effective treatment modality for the treatment of carotid in-stent stenosis, and alternative treatment options include observation with medical management and placement of another stent. 3,4 The authors present the case of a 61-yr-old man with carotid in-stent restenosis and progressive worsening on serial imaging with ultrasound. The patient had a history of carotid stenting for symptomatic stenosis 6 mo prior and was maintained on aspirin and clopidogrel. In light of the progressive worsening, the in-stent stenosis was confirmed on computed tomography (CT) angiogram. The options were discussed with the patient and he consented for treatment with cutting balloon angioplasty. Final angiogram showed improvement of the luminal diameter with a residual stenosis of 15%. The patient tolerated the procedure well and was discharged home on postoperative day 1. Follow-up ultrasound demonstrated moderate improvement in peak systolic velocities, and the plan is to continue observation with a clinical follow-up and repeat carotid Dopplers at 3 mo.

Context.— It is unclear if preimplantation frozen section biopsy correlates with outcomes after deceased donor kidney transplantation. Objective.— To assess if chronic histologic changes on the preimplant frozen section correlates with graft loss and estimated glomerular filtration rate independently of kidney donor profile index (KDPI). Design.— Seven hundred three preimplantation biopsies were reviewed and a Banff sum score was calculated using glomerular sclerosis, interstitial fibrosis, vascular intimal thickening, and arteriolar hyalinosis. The posttransplant outcomes were compared for preimplantation biopsy Banff sum 0-1, 2-3, and 4-9. The cohort was also stratified by KDPI 85 or less versus more than 85. Results.— For the entire biopsy cohort, graft survival, estimated glomerular filtration rate at 1 year, and chronic changes on a 1-year posttransplant biopsy were superior in the group with preimplantation Banff sum 0-1. After stratifying by KDPI, the Banff sum no longer correlated with graft survival. In a univariate mode, using the Banff sum score as a continuous variable, a higher Banff sum score was significantly associated with graft failure (P = .03); however, after adjusting the KDPI, the Banff sum score no longer correlated with graft failure (P = .45). The 1-year estimated glomerular filtration rate and 1-year biopsy changes were superior in the group with Banff sum 0-1 only in the cohort with KDPI 85 or less. Conclusions.— In donor kidneys used for transplant, preimplantation biopsy chronic changes correlate with estimated glomerular filtration rate and biopsy findings at 1 year, but biopsies with mostly mild chronicity and Banff sum scores less than or equal to 5 did not impact graft survival beyond KDPI.

3039 Background: Patients with multiple organ metastases have poorer prognoses than those with a single organ metastasis, are frequently associated with drug resistance, and have higher tumor burden. Engorged (≥50um) Cancer Associated Macrophage-Like Cells (CAMLs) are a circulating stromal cell subtype detected in the blood of patients with solid tumors at high risk for recurrence or progression. While numerous studies have shown that ≥50um CAMLs predict poor clinical outcomes, meta-analysis of these studies have also suggested that hyper engorged CAMLs ≥100um (heCAMLs) may be associated with multifocal metastatic disease and even worse outcomes. In this prospective study, we evaluated the presence of heCAMLs in patients with metastatic disease and demonstrated a strong relationship with multi organ spread, which also correlated with shorter Progression Free Survival (PFS) and Overall Survival (OS). Methods: We prospectively recruited 151 patients with metastatic (m) mbreast (n = 58), mlung (n = 34), mprostate (n = 39), and mrenal (n = 20) cancers. Peripheral blood was collected prior to the induction of new treatment for metastatic cancer. Cells were isolated following standard CellSieve techniques, then imaged and measured in ZenBlue. Multi organ metastasis was defined as spread to ≥2 distant organ sites, or any spread to the brain. Single factor ANOVA was conducted to compare heCAML presence in multi organ metastatic patients versus patients with single organ site metastasis. Univariate and multivariate analysis was run to evaluate for PFS and OS against heCAMLs, and all known clinical parameters. Results: 150 viable samples (excluding 1 failed sample) were obtained. Multi organ metastases were present in 55% (n = 83/150) of patients. heCAMLs were found in 59% (n = 49/83) of the multi organ metastatic population, but only in 16% (n = 11/67) of the single site metastatic cohort (p < 0.001). heCAML presence appeared to differentiate multi organ vs single organ metastases in mbreast (85% vs. 52%, p = 0.006), mlung (71% vs. 26%, p = 0.025), mprostate (75% vs. 37%, p = 0.029), and mRCC (88% vs. 36%, p = 0.025). Further, in all n = 150 patients, heCAML presence predicted a significantly shorter median PFS of 4.5 versus 7.2 months, 24 month PFS (HR = 1.67, 95%CI = 1.13-2.45, p = 0.013), and significantly shorter median OS of 13.1 versus 20.4 months, 24 month OS (HR = 2.05, 95%CI = 1.24-3.39, p = 0.008). Conclusions: We examined a non-invasive prognostic blood based assay to determine its relationship to multi organ metastatic spread as well as its prognostic value in several solid cancers. These results showed patients with heCAMLs had higher rates of multi organ metastases, and appear to predict for shorter PFS and OS. Studies of larger cohorts are needed for prospective validation of these initial findings.

ABSTRACT Human babesiosis in the United States is caused predominantly by Babesia microti , a tick-transmitted blood parasite. Improved testing methods for the detection of infection with this parasite are needed, since asymptomatic B. microti infection represents a potential threat to the blood supply in areas where B. microti is endemic. We performed immunoscreening of an expression library of genomic DNA from a human isolate of B. microti (strain MN1). Among 17 unique immunoreactive clones, we identified 9 which represent a related family of genes with little sequence homology to other known sequences but with an architecture resembling that of several surface proteins of Plasmodium . Within this family, a tandem array of a degenerate six-amino-acid repeat (SEAGGP, SEAGWP, SGTGWP, SGTVGP) was found in various lengths between relatively well conserved segments at the N and C termini. In order to examine within-clone variation, we developed a PCR protocol for direct recovery of a specific bmn1-6 homologue directly from 30 human blood isolates, 4 corresponding hamster isolates, and 5 geographically corresponding Peromyscus leucopus (white-footed mouse) isolates. Isolates from the hamsters had the same sequences as those found in the corresponding human blood, suggesting that genetic variation of bmn1-6 does not occur during passage. However, clones from different patients were often substantially different from each other with regard to the number and location of the degenerate repeats within the bmn1-6 homologue. Moreover, we found that strains that were closely related geographically were also closely related at the sequence level; nine patients, all from Nantucket Island, Mass., harbored clones that were indistinguishable from each other but that were distinct from those found in other northeastern or upper midwestern strains. We conclude that considerable genetic and antigenic diversity exists among isolates of B. microti from the United States and that geographic clustering of subtypes may exist. The nature of the bmn1-6 gene family suggests a mechanism of antigenic variation in B. microti that may occur by recombination, differential expression, or a combination of both mechanisms.

Abstract Background The increasing incidence and prevalence of inflammatory bowel disease (IBD), has fuelled the need for innovative models of care. We aimed to compare effectiveness of e-health interventions (virtual clinics, telephone consultation, remote monitoring or any web-based health platform) with standard care in management of IBD. Our primary outcomes were to assess the difference in disease activity and percentage of patients in clinical remission at the end of follow up. Our secondary outcomes were to investigate differences in quality of life (QoL), IBD-knowledge & rate ratios (RR) for endoscopic procedures, total healthcare encounters, corticosteroid use, and IBD related hospitalisation or surgery. Methods We searched Medline, Embase, PubMed, CINAHL, PsychInfo, Clinical trials registry and Cochrane databases for randomised controlled trials (RCT) published in the English language until November 2020, comparing e-health interventions to standard care for patients with IBD. Pooled estimates of dichotomous outcomes were calculated using the odds ratio (OR) and 95% confidence interval (CI) using the Mantel-Haenszel statistical method. For continuous data, the standardised mean difference (SMD) and 95% CI were calculated using the inverse variance statistical method. Event data were analysed and expressed as RR with 95% CI using the inverse variance statistical method. Random effects model was used. Results Nine studies involving 1841 participants (991 e-health group and 850 controls) were identified. There was no statistically significant difference between the mean disease activity scores for UC (SMD 0.22, 95% CI: -0.04–0.48) and CD (SMD 0.02, 95% CI: -0.18–0.22) in the e-health and standard care groups and no statistically significant difference in the percentage of patients in clinical remission at the end of follow up between both groups (OR -1.05, 95% CI: 0.76–1.45). Higher QoL (SMD 0.19, 95% CI: 0.05–0.34) and IBD knowledge (SMD 0.25, 95% CI: 0.12–0.37) scores were noted in the e-health group compared to standard care. There were no statistically significant differences noted in the RR for endoscopic procedures (RR 1.01, 95% CI: 0.81–1.26), total healthcare encounters (RR 1.03, 95% CI: 0.93–1.15;), IBD related, corticosteroid use (RR 0.99, 95% CI: 0.51–1.92), and IBD related hospitalisation (RR 0.81, 95% CI: 0.53–1.25) or surgery (RR 0.87, 95% CI: 0.49–1.55) between both groups. Conclusion E-health interventions are comparable with standard care for impact on disease activity, remission, endoscopy utilisation, total healthcare encounters, corticosteroid use, and IBD related hospitalisation or surgery. QoL and IBD related knowledge were higher in the e-health compared to the standard care group.

AbstractPhosphoglucomutase 1 (PGM1) catalyzes the interconversion of glucose‐6‐phosphate to glucose‐1‐phosphate and is a key enzyme of glycolysis, glycogenesis, and glycogenolysis. PGM1 deficiency (OMIM: 614921) was initially defined as a glycogen storage disorder (type XIV), and later re‐classified as a PGM1‐congenital disorder of glycosylation (PGM1‐CDG). Serum transferrin (Tf) glycan isoform analysis by liquid chromatography‐mass spectrometry (LC‐MS) is used as a primary diagnostic screen tool, and reveals a very unique CDG profile described as a mixture of CDG‐type I and CDG‐type II patterns. Oral d‐galactose supplementation shows significant clinical and metabolic improvements, which are indicated by the Tf glycan isoform normalization over time in patients with PGM1‐CDG. Thus, there is a need for biomarkers to guide d‐galactose dosage in patients in order to maintain effective and safe drug levels. Here, we present a simplified algorithm called PGM1‐CDG Treatment Monitoring Index (PGM1‐TMI) for assessing the response of PGM1‐CDG patients to d‐galactose supplementation. For our single‐center cohort of 16 PGM1‐CDG patients, the Tf glycan profile analysis provided the biochemical diagnosis in all of them. In addition, the PGM1‐TMI was reduced in PGM1‐CDG patients under d‐galactose supplementation as compared with their corresponding values before treatment, indicating that glycosylation proceeds towards normalization. PGM1‐TMI allows tracking Tf glycan isoform normalization over time when the patients are on d‐galactose supplementation.

A 78-year-old man with an implantable cardioverter-defibrillator (ICD) presented with chills and malaise. His history was significant for heart failure with reduced ejection fraction and complete heart block. He had undergone permanent pacemaker placement that was later upgraded to an ICD 5 years before his presentation. Physical examination revealed an open wound with surrounding erythema overlying the device site. Blood cultures obtained on admission were negative. Transesophageal echocardiogram did not show valve or lead vegetations. He underwent a prolonged extraction procedure. Postoperatively, he developed septic shock and cultures from the device, and repeat peripheral blood cultures grew Staphylococcus simulans and Staphylococcus epidermidis. He was treated with intravenous vancomycin but had refractory hypotension, leading to multiorgan failure. He later expired after being transitioned to comfort care. The patient may have acquired S. simulans by feeding cows on a nearby farm, and the prolonged extraction procedure may have precipitated the bacteraemia.

AbstractCSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow‐up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.