Dana R Jorgensen (Dana Jorgensen Murdock)

BackgroundThe relationship between underlying type 2 inflammation and immune response to COVID-19 is unclear.ObjectiveAssessing relationships between allergic conditions and COVID-19 susceptibility and outcomes.MethodsIn the Optum® database, adult patients with and without major allergic conditions (asthma, atopic dermatitis [AD], allergic rhinitis [AR], food allergy, anaphylaxis, eosinophilic esophagitis [EoE]) and patients with and without severe asthma/AD were identified. Adjusted incidence rate ratios (aIRR) for COVID-19 were compared among patients with vs without allergic conditions or severe asthma/AD vs non-severe asthma/AD during 4/1/2020–12/31/2020. Among patients with COVID-19, adjusted hazard ratios (aHR) of 30-day COVID-19-related hospitalization/all-cause mortality were estimated for the same comparisons during 4/1/2020–3/31/2022.ResultsPatients with (N = 1,273,231 …

Introduction/Aims: Global studies of epidemiology of myasthenia gravis (MG) have pointed to increasing prevalence of this rare autoimmune disorder affecting the neuromuscular synapse; however, no new data for the USA were available for decades. We aimed to estimate the incidence rate and prevalence of MG in a large-scale insured US population. Methods: We conducted a population-based retrospective cohort study to estimate the annual incidence and prevalence of MG cases in the USA during 2017. Using a previously validated algorithm, we identified cases of MG in two Truven Health MarketScan databases, which during 2017 included a sample of approximately 20 million commercially insured and Medicare recipients, plus 10 million Medicaid recipients. We report crude incidence and prevalence and calculated age- and sex-standardized estimates for the USA based on the 2017 American Community Survey. We estimated the number of adult cases during 2021 by extrapolating from the stratified estimates to the population size from the 2021 American Community Survey.Results: From the US commercially/Medicare-insured cohort, we calculated an age- and sex-standardized incidence of 68.5 new cases per million person-years with an adjusted prevalence of 316.4 per million. Within the Medicaid-insured population, similar yet slightly lower numbers emerged: the adjusted incidence was 49.7 new cases per million person-years, and the adjusted prevalence rate was 203.7 cases per million. Given our results, we were able to estimate that there were approximately 82,715 US adults living with MG in 2021 (or an estimated 320.2 …

Background Acute antibody mediated rejection is increasingly identified in liver allografts as a unique form of alloimmune injury associated with donor specific antibodies (DSA). This manifests pathologically as microvascular injury and C4d uptake. Despite the liver allograft's relative resistance to alloimmune injury, liver allografts are not impervious to cellular and antibody‐mediated rejection. Methods In this blinded control study, we evaluated CD163 immunohistochemistry and applied the Banff 2016 criteria for diagnosis of acute AMR on a group of indication allograft liver biopsies from DSA positive patients and compared them to indication biopsies from DSA negative controls. Results Most DSA positive patients were females (75%, p = .027), and underwent transplantation for HCV infection. Significant histopathological predictors of serum DSA positivity were Banff H‐score (p = .01), moderate to severe …

Although cholesterol has been hypothesized to promote cancer development through several potential pathways, its role in the risk of developing hormonally driven cancer is controversial. This literature review summarizes evidence from the highest quality studies to examine the consistency and strength of the relationship between serum cholesterol parameters and incidence of hormonally driven cancer. Articles were identified using EMBASE. Longitudinal observational studies published between January 2000 and December 2020 were considered for inclusion. The endpoint of interest was incident prostate, ovary, breast, endometrium, and uterine cancers. In total, 2732 reports were identified and screened; 41 studies were included in the review. No associations were found for ovarian cancer. Most endometrial cancer studies were null. The majority (76.9%) of studies reported no association between …

IntroductionWe aimed to describe our procedure for vascular reconstruction and back table bench preparation for the right lobe live donor allograft. Live donor liver transplantation (LDLT) remains an important option for the expansion of the donor pool. The procedure has been widely used, and its success is dependent on a technically perfect operation with appropriate inflow and outflow of the allograft. Adequate preparation of the right lobe (RL) allograft prior to implantation remains a vital part of the procedure.MethodsOur technique of back table vascular reconstruction of the RL allograft has been performed using a hepatic vein patch venoplasty, inferior hepatic vein inclusion, portal vein reconstruction, and segment V and VIII reconstruction for all of our LDLTs.ResultsBetween March 2009 and January 2020, 321 consecutive adult LDLTs were performed and underwent back table reconstruction with the …

BackgroundSarcopenia is defined as age-related low muscle mass and function, and can also describe the loss of muscle mass in certain medical conditions, such as sarcopenic obesity. Sarcopenic obesity describes loss of muscle and function in obese individuals; however, as sarcopenia is an age-related condition and obesity can occur in any age group, a more accurate term is obesity with low lean muscle mass (OLLMM). Given limited data on OLLMM (particularly in those aged < 65 years), the purpose of this study was to estimate the prevalence of OLLMM in adults aged ≥ 20 years in the USA.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 and 1999–2006 were used. OLLMM was defined as an appendicular lean mass, adjusted for body mass index (BMI), cut-off point < 0.789 for males and < 0.512 for females, measured by dual-energy X-ray absorptiometry …

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients (n=736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR<20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; n=131) or DSA- (n=605). DSA+ group were more DR mismatched (p=0.02), more sensitized (cPRA ≥90%, p=0.002), less Caucasian (p=0.04), and had less pre-emptive (p=0.04) & more deceased donor transplants (p=0.03). DSA+ patients had similar eGFR (54.8 vs 53.8 mL/min/1.73m2, p=0.56), DCGS (91% vs 94%, p=0.30), and graft failure free survival (76% vs 82%, p=0.11). DSA timing and type did not impact survival. Among those with a protocol biopsy (n=515), DSA detected on 1st year screening was a predictor for graft failure on multivariate analysis (1.91, 95%CI 1.03–3.55, p=0.04). Overall, early DSA detection in stable patients was an independent risk factor for graft failure, though only among those who underwent a protocol biopsy.

ObjectiveTo assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with COVID-19 in the ambulatory setting, including patients diagnosed during the Delta-dominant period prior to Omicron emergence.DesignRetrospective cohort study.SettingKomodo Health closed claims database.Participants13 273 128 patients diagnosed with COVID-19 (December 2020 through September 2021) were treated with CAS+IMD or untreated but treatment eligible under the Emergency Use Authorization (EUA). Each treated patient was exact and propensity score matched without replacement to up to five untreated EUA-eligible patients.InterventionsCAS+IMD.Primary and secondary outcome measuresComposite endpoint of 30-day all-cause mortality or COVID-19-related hospitalisation. Kaplan-Meier estimators were used to calculate …

IntroductionData on real-world effectiveness of subcutaneous (SC) casirivimab and imdevimab (CAS+IMD) for the treatment of coronavirus disease 2019 (COVID-19) are limited. The objective of this study was to assess the effectiveness of SC CAS+IMD versus no antibody treatment among patients with COVID-19.MethodsThis retrospective cohort study linked Komodo Health and CDR Maguire Health and Medical data. Patients diagnosed with COVID-19 in ambulatory settings (August 1–October 30, 2021) treated with SC CAS+IMD were exact- and propensity score-matched to fewer than five untreated treatment-eligible patients and followed for the composite endpoint of 30-day all-cause mortality or COVID-19-related hospitalization. Kaplan–Meier estimators were used to calculate outcome risk overall and across subgroups. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR …

Letter to the Editor 309 standing test) in a quiet room at 24 C. After enough resting time (at least 10 min), the subjects were asked to lie in the supine position for 10 min. Then, they had to initiate and maintain an active standing position for another 10 min if tolerated. Blood pressure (BP) and HR were recorded every minute by an electric sphygmomanometer (Nico PS501, Parama-tech, Japan). Thereafter, the participants filled out a checklist assessing somatic symptoms that occurred during orthostatic testing (table 1). Baseline BP and HR were taken as average values of the last 5 min in the supine position. Change in HR (ΔHR) was expressed as the difference in HR after standing from baseline HR. Based on the results of orthostatic testing, they were diagnosed into 3 orthostatic intolerance subtypes: POTS, OH and neutrally-mediated syncope (NMS). OH was defined by a fall in BP of at least 20 mm Hg in systolic BP or 10 mm Hg in diastolic BP within 3 min in the upright position [13]. NMS was diagnosed as a sudden onset of fainting/near-fainting during standing [14]. Differences among the groups were assessed using a Pearson X 2 test for categorical variables or by Fisher’s exact probability test if appropriate, and 1-way analysis of variance for continuous variables. A random effects model was used to test the differences in HR among the groups after standing across every minute. This study was approved by the Kyushu University Institutional Review Board and all participants provided oral informed consent. POTS was found in 17% of the depressive disorder patients, 3% of the anxiety disorder patients, 6% of the somatoform disorder patients …

Therapeutic drug monitoring is routine for Tacrolimus, while levels are not routinely monitored for mycophenolic acid (MPA). This study investigated the effect of early post‐transplant pharmacokinetics (PK) of MPA and Tacrolimus along with the pharmacodynamics (PD) of MPA on biopsy‐proven acute rejection (BPAR) after renal transplantation. A prospective PK/PD study with limited sampling (three blood samples) was conducted in renal transplant recipients on week 1, around Day 6 (n = 42) and at the 3rd‐month biopsy on Day 90 (n = 23). The partial exposures (area under curve [AUC]0‐3.5 h) of both MPA and Tacrolimus obtained during the first week were more predictive of rejection (combined clinical and subclinical rejection) by Day 90 than their trough concentrations or Day 90 exposures. Patients with rejection had significantly worse renal function (eGFR) and a comparatively lower exposure to MPA during …

The real-world effectiveness of allergy immunotherapy (REACT)-study was an observational, retrospective database study that mirrored the scientific rigor of randomised controlled trials (RCTs) to provide robust and complementary long-term real-world evidence in AIT. 1 While most RCTs in AIT have demonstrated shorterterm efficacy on symptoms and use of symptom-relieving medication for allergic rhinitis (AR), 2 the REACT-study used routinely collected health care data to assess the long-term effectiveness in a large, unselected, patient population treated with AIT in clinical practice, ie without exclusion of patients with certain comorbidities or low adherence. 3It is an identified limitation of the REACT-study, that only prescription data were captured in the database since patients could also get symptom-reliving medications for AR as over-the-counter (OTC) drugs. As discussed in the REACT publication 3 and …

Background High kidney‐donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. Methods We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I‐KDPI ≤ 25% (n = 151), Group II‐KDPI 26–50% (n = 182), Group III‐KDPI 51–75% (n = 176), and Group IV‐KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5‐years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the …

DANA J. MURDOCK, NING WU, DAVID J. GLASS, JOSEPH S. GRIMSBY, ROBERTO A. CALLE, STEPHEN DONAHUE, MARK SLEEMAN, ROBERT J. SANCHEZ; 1200-P: The Prevalence of Obesity-Associated Loss of Lean Muscle Mass. Diabetes 1 June 2022; 71 (Supplement_1): 1200–P. https://doi. org/10.2337/db22-1200-P

This study aimed to investigate whether magnetic resonance imaging‐derived proton density fat fraction (MRI‐PDFF) can be a viable noninvasive alternative to liver biopsy for the quantification of living liver donor steatosis. Hepatic steatosis for 143 donors was graded by MRI‐PDFF. Study endpoints included liver volume regeneration in donors, recipient outcomes including length of hospital stay, deaths, primary non‐function (PNF), early allograft dysfunction (EAD), and small for size syndrome (SFSS). Correlation between MRI‐PDFF determined donor steatosis and endpoints were analyzed. Donors had lower steatosis grade than non‐donors. Donor remnant liver regenerated to an average of 82% of pre‐donation volume by 101 ± 24 days with no complications. There was no correlation between percent liver regeneration and steatosis severity. Among recipients, 4 underwent redo‐transplantation and 6 died …

Background and aimsLiver transplantation is the most effective treatment for end-stage liver disease (ESLD). Whether moderately macrosteatotic livers (30%-60%) represent a risk for worsened graft function is controversial. The uncertainty, in large part, is owing to the heterogeneous steatosis grading. Our aim was to determine the short- and long-term outcomes of moderately macrosteatotic allografts that were graded according to a standardized institutional protocol.MethodsWe performed a retrospective analysis of transplants performed between 1994 and 2014. All patients with allografts biopsied pretransplantation were included. Relevant donor and recipient variable were recorded. Moderately macrosteatotic livers were compared with mildly macrosteatotic and nonsteatotic livers. Primary outcomes of interest were patient survival at 90 days, 1 year, and 5 years. Cox regression analyses were carried out to …

Aim The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1‐year post 1‐transplant surveillance kidney allograft biopsy. Methods Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups. Results DCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD versus 19% in DBD, P = .0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43 …

The prevalence of portal vein thrombosis (PVT), renal dysfunction (RD), and simultaneous PVT/RD in liver transplantation (LT) is poorly understood. We analyzed the prevalence of PVT, RD, simultaneous PVT/RD, and the outcomes of adult recipients of LT for nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) between 2006 and 2016 in the United States. We found that the prevalence of PVT (7.2% → 11.3%), RD (33.8% → 39.2%), and simultaneous PVT/RD (2.4% → 4.5%) has increased significantly over the study period (all P‐values <0.05). NAFLD patients had a higher proportion of PVT (14.8% vs. 9.2%), RD (45.0% vs. 42.1%), and simultaneous PVT/RD (6.5% vs. 3.9%; all P‐values <0.05). 90‐day mortality was 3.8%, 6.3%, 6.8%, and 9.8% for PVT(−)/RD(−), PVT(−)/RD(+), PVT(+)/RD(−), and PVT(+)/RD(+) recipients, respectively (P < 0.01). 5‐year survival was 82.1%, 75.5%, 74.8%, and …

For assessing human leukocyte antigen compatibility in deceased donor kidney transplantation, virtual crossmatch is used as an alternative to physical crossmatch and has potential to reduce cold ischemia time. The 2014 United States kidney allocation system prioritized highly sensitized candidates but led to increased shipping of kidneys. Using data from the Scientific Registry of Transplant Recipients, we evaluated changes in virtual crossmatch use with the new allocation policy and the impact of virtual crossmatch use on cold ischemia time and transplant outcomes. This was a retrospective cohort study of adult deceased donor kidney recipients in the United States (2011-2018) transplanted with either 9,632 virtual or 71,839 physical crossmatches. Before allocation change, only 9% of transplants were performed relying on a virtual crossmatch. After the 2014 allocation change, this increased by 2.4%/year so …

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.