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Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI≥4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT≥45seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every10-second NCTincrease associated with a0.08-LFIincrease (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

OBJECTIVE To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2-dose SARS-CoV-2 messenger RNA (mRNA) vaccination. METHODS RMD patients (n = 1,377) who received 2-dose SARS-CoV-2 mRNA vaccination between December 16, 2020 and April 15, 2021 completed questionnaires detailing local and systemic reactions experienced within 7 days of each vaccine dose (dose 1 and dose 2), and 1 month after dose 2, detailing any flares of RMD. Associations between demographic/clinical characteristics and flares requiring treatment were evaluated using modified Poisson regression. RESULTS Among the patients, 11% reported flares requiring treatment; there were no reports of severe flares. Flares were associated with prior SARS-CoV-2 infection (incidence rate ratio [IRR] 2.09, P = 0.02), flares in the 6 months preceding vaccination (IRR 2.36, P

BACKGROUND: While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. METHODS: US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. RESULTS: Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. CONCLUSIONS: HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n=1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI≥4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate

Supplemental Digital Content is available in the text., Background. We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials. Methods. US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression. Results. We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44–69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P

Prior studies have demonstrated a decreased humoral response in solid organ transplant recipients (SOTRs) to SARS-CoV-2 mRNA vaccination (17% antibody response after dose 1, 54% after dose 2) as compared to the general population (100%). However, these studies were dominated by kidney transplant recipients, and included only a small percentage of liver transplant (LT) recipients (19.6%).(1-4) Since LT recipients often receive milder induction and maintenance immunosuppression, they may have a more robust humoral response. To investigate this, we studied SARS-CoV-2 antibody development in a cohort of LT recipients who completed a two-dose mRNA vaccine series of either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech).

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = 0.84 0.890.93 ), LDLTs were 49% fewer (IRR = 0.37 0.510.72 ), and DDLTs were 9% fewer (IRR = 0.85 0.910.97 ). In May, new listings were 21% fewer (IRR = 0.74 0.790.84 ), LDLTs were 42% fewer (IRR = 0.39 0.580.85 ) and DDLTs were 13% more (IRR = 1.07 1.151.23 ). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = 1.09 1.592.32 ) and 34% fewer DDLTs (IRR = 0.50 0.660.86 ). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.

Mycophenolate is the mainstay of treatment for many organ and life-threatening manifestations of rheumatic and musculoskeletal diseases (RMD). In contrast to most patients with RMD, those taking mycophenolate have an attenuated humoral response to SARS-CoV-2 mRNA vaccination.1 2 The American College of Rheumatology recently recommended withholding mycophenolate for 1 week after vaccination to enhance immunogenicity in this vulnerable population.3 Thus, we sought to analyse the impact of withholding perivaccination mycophenolate in 24 patients with RMD. We leveraged our observational prospective cohort of patients with RMD without prior COVID-19 who underwent SARS-CoV-2 vaccination between 17 December 2020 and 13 May 2021.2 Information on demographics, diagnoses, immunosuppressive regimens and management of perivaccination immunosuppression was collected via electronic questionnaire. One month following vaccination, venipuncture samples were obtained and tested on the semiquantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay which tests for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein; a consistent correlate of neutralising antibody.4 We compared the percentage of participants with detectable anti-RBD antibody in the group that withheld mycophenolate (n=24) to the group that continued mycophenolate (n=171) using Fisher’s exact test (online supplemental table 1). Crude and adjusted logistic regression analyses were performed to assess associations between antibody response and the primary variable of withholding mycophenolate, as well as after adjusting for clinical characteristics (age, sex, race, vaccine type (mRNA vs adenovirus vector), use of rituximab and glucocorticoids). Wilcoxon rank-sum test was used to compare anti-RBD titers of the …

A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.

The purpose of this article is to study topical issues of the emergence, formation and manifestation of the international componentin the activities of local self-government bodies of Ukraine.It has been proved that the international legal component of local self-government is based on multilateral and multi-level coope -ration of the member states of the international community, acquiring phenomenological properties, because: A) relies on the possibi -lities of the phenomenon of globalization, which manifests itself in it in all three of its currently defined forms – economic, politicaland legal; B) uses the powerful spatially unifying potential of legal globalization as a powerful systemic and complex megatrend thatencompasses not only peoples and states, but also unites them around common strategic, tactical, and what is especially important –existential and everyday patterns of organization and implementation of the international, state, regional, local (collective), group andindividual life – through their coordination, integration and unification, convergence (rapprochement of the legal systems of states),their adaptation, approximation, and the like; C) determines and contextualizes new forms of interstate and international cooperationaimed at: deeper interaction of its subjects; is a powerful factor that is permanent in time; and multivariate in forms; poly-level andpoly-object development, which is accompanied by new and still unknown phenomena and trends – that is, we can talk about qualitative-paradigmatic and discursive civilizational changes, accompanied and manifested by the emergence of corresponding patterns ofdeep interaction, and significantly affecting the path of existence and further development peoples and states.It is argued that under the international component in its content, it is necessary to understand such aspects of the activities oflocal self-government bodies that are actually not connected in their emergence with the issues of “internal”, intrastate activities of thesepublic authorities, although in a broad teleological sense, it is this “international component “is aimed at facilitating and improving theactivities of such bodies within the national state through the acquisition of foreign experience, participation in international commercialand foreign economic activity, the formation of a local system of international cooperation.It is argued that the definition of a number of provisions (factors) of methodological properties that demonstrate the principles ofthe international and international legal potential of local self-government, its bodies and subjects (historical, psychological, collaboration,intersubjective, functional-active, ideological, public-state factors).

Clinical decision-making in kidney transplant (KT) during the coronavirus disease 2019 (COVID-19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid_sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID-19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions.

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.

Stakeholders have expressed concerns regarding decreased deceased donor kidney transplant (DDKT) rates for pediatric candidates under the Kidney Allocation System (KAS). To better understand what might be driving this, we studied Scientific Registry of Transplant Recipients kidney offer data for 3642 pediatric (age

Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown.Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97).Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Background Immunocompromised patients were excluded from the trials of SARS-CoV-2 vaccines. Boyarsky et al recently reported that, only 17% of transplant recipients who received a single dose of SARS-CoV-2 vaccine developed detectable anti-spike antibody (compared to 100% of the nonimmunocompromised subjects in the pivotal trials) and after 2 doses response increased to 54% in transplant recipients.1,2. Methods Retrospective chart review of 14 patients who were diagnosed with COVID-19 despite completion of vaccination series. Results Fourteen SOT recipients were diagnosed with COVID-19 a median of 23.5 days from completion of vaccination. One patient died, 2 remain hospitalized and 11 are recovered at home. Fifty percent of patients infected required hospitalization for treatment of disease. Conclusions With this report of 14 patients who developed COVID-19 infection after completion of vaccination, we believe there is sufficient evidence to issue warnings that immunoincompetent populations should continue to practice strict COVID-19 precautions postvaccination. Transplant centers should reinforce that guidance given to the general population may not be applicable to the transplant population. A centralized transplant registry of fully vaccinated solid organ transplant patients who develop COVID-19 infections is vital. Further studies are critically needed to optimize COVID-19 vaccination protocols in transplant recipients.

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with autoimmune disease,1 2 and immunosuppressed status has been associated with an increased risk of COVID-19 infection despite vaccination.3 Recent studies have demonstrated enhanced humoral response to third-dose SARS-CoV-2 vaccination in immunosuppressed transplant patients,4 5 but the immunogenicity of booster vaccination in other immunosuppressed populations is unknown. Thus, we sought to describe the humoral response in patients with autoimmune disease who received a booster SARS-CoV-2 vaccine. Using our prospective cohort of patients with autoimmune disease,5 we included patients who reported receipt of a single booster dose of SARS-CoV-2 mRNA or adenovirus vector vaccine between 10 April and 11 June 2021. We observed serial anti-spike antibody responses among these participants. A total of 18 participants received a booster SARS-CoV-2 vaccine dose (table 1). Most (13/18) were women with median (IQR) age of 55 (44–63) years. The most common autoimmune diagnoses included myositis (n=6) and inflammatory arthritis (n=3). Most (14/18) were on antimetabolite therapy; mycophenolate was the most commonly reported immunosuppressive therapy (n=8), with a median (IQR) daily dose of 3000 mg (2500–3000 mg). Participants completed initial vaccination with either Pfizer (n=8), Moderna (n=6) or Johnson & Johnson/Janssen (J&J) Ad26.COV2.S (n=4). View this table: Table 1 Vaccines administered, autoimmune diagnoses, immunosuppression and peri-vaccination management with longitudinal anti-spike antibody responses Anti-spike antibodies, evaluated via Roche Elecsys anti-RBD pan-Ig were negative in 10 participants (anti-RBD

This study of SARS-CoV-2 mRNA vaccination in 14 persons with HIV (PWH) demonstrated uniformly high anti-SARS-CoV-2 receptor binding domain (RBD) antibody titres after two doses, despite varied titres after a single dose. The majority of vaccine reactions were mild and no adverse events occurred.

Study question To investigate the therapeutic efficacy of follitropin alpha biosimilar therapy in nonselected patients undergoing IVF. Summary answer This large retrospective study demonstrated similar therapeutic efficacy for follitropin alpha biosimilar therapy in women who underwent ovarian stimulation (OS) using different protocols. What is known already Based on data from the last meta-analyses (Budani et al., 2020), follitropin alpha biosimilars showed similar efficacy and safety in randomized controlled trials aimed at proving the therapeutic equivalence in terms of oocytes retrieved in women undergoing OS. In most cases, normogonadotrophic patients were enrolled in such studies without any endocrine or ovarian disturbances. The absence of real-world data can be compensated by additional post-marketing studies aimed at investigating the efficacy of biosimilars in different OS protocols using antagonists and agonists of GnRH and OS with mixed gonadotropins. Study design, size, duration A retrospective, observational, anonymized cohort study conducted at 35 IVF clinics in Russia, named “FOLLITROPIN”, compared the efficacy of OS in 2020. The OS protocols analysed where follitropin alpha biosimilar (Primapur®) was applied for at least 5 days. All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins. No inclusion or exclusion criteria were applied. Overall, 5484 OS protocols were analysed. Participants/materials, setting, methods The efficacy of 5484 OS protocols was calculated, and two subgroups were extracted: (1) mixed gonadotropin OS protocols (N = 2625) vs monotherapy with Primapur® (N = 2859); (2) GnRH antagonist OS (N = 2183) vs GnRH agonist (N = 676) using only Primapur®. Demographic and clinical characteristics: (1) Age 34.9±4.8 vs 32.9±4.7 (p Main results and the role of chance The total efficacy of OS with Primapur®: oocytes retrieved: 9.5±7.2, MII: 6.8±6.6, 2PN: 6.1±5.8, clinical pregnancy per ET (PR) 6 weeks after ET: 38.4%. Subgroup 1 analysis: oocytes retrieved: 8.6±6.8 vs 10.3±7.4 (p Limitations, reasons for caution The real-world patient data analysed in this study were representative, showing the ability of follitropin biosimilars to develop both folliculogenesis and clinical pregnancy in a nonselected population. Additional comparative studies are needed to confirm the efficacy of the biosimilars in patients with classified types of infertility causes, including unexplained infertility. Wider implications of the findings: In this study, we demonstrated the therapeutic efficacy of biosimilars in terms of oocyte yield and clinical pregnancy development in women undergoing different OS protocols. Further large-scale studies with known hormonal levels before and during OS, as well as the micro- and macronutrient status of both parents, are needed. Trial registration number None

Purpose of review We report the current state of HIV+ to HIV+ kidney transplantation in the United States and remaining challenges in implementing this practice nationally. Recent findings The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV+ to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false positive HOPE donors resulting in more than 120 transplants. Summary The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV+ donors into HIV+ recipients. Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV+ to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact.

In this study of 12 people with HIV (PWH) who received the first dose of SARS-CoV-2 mRNA vaccination, anti-SARS-CoV-2 receptor-binding domain antibodies were detectable in all participants; lower antibody levels were seen in those with lower CD4(+) counts, and vaccine reactions were generally mild.

During the COVID‐19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case‐by‐case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high‐risk transplantations. For induction, 26.5% were less likely to give T‐cell depletion and 14.8% were more likely to give non‐depleting agents. These practices varied by program‐level factors more so than the COVID‐19 burden. In patients with mild, moderate and severe COVID‐19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti‐metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID‐19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti‐metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high‐risk transplants and increased maintenance steroids. The long‐term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.

BACKGROUND & AIMS: Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology. METHODS: Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; ‘frail’ = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness). RESULTS: Of 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in ‘other’ (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and ‘other’ (OR 1.58, 95% CI 1. 06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and ‘other’ (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term). CONCLUSIONS: Frailty is more common in patients with ALD, NAFLD and ‘other’ aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.

SARS-CoV-2 mRNA vaccination elicited high immunogenicity in immunocompetent people in the original vaccine trials,1 2 though recent studies have shown blunted immunogenicity in patients with rheumatic and musculoskeletal diseases (RMDs) after a single dose and case reports of non-response after two doses.3 4 We previously detailed antibody response in patients with RMD following the first dose of SARS-CoV-2 mRNA vaccination and herein report response and factors associated with response to two-dose vaccination in a larger cohort. As previously reported,3 patients aged ≥18 years old with RMD were recruited to participate in this prospective, observational cohort via social media outreach to national RMD organisations between 12 July 2020 and 16 March 2021. Demographics, diagnoses and therapeutic regimens were collected via participant report through the Research Electronic Data Capture tool. One month after dose 2 (D2), participants underwent SARS-CoV-2 antibody testing on the semiquantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures total antibody (IgM and IgG) to the SARS-CoV-2 S receptor-binding domain (RBD) protein,5 the target of the mRNA vaccines. Results range from 250 U/mL with a positive response defined as >0.79 U/mL. Associations were evaluated using Fisher’s exact and Wilcoxon rank-sum tests. Participants provided informed consent. We studied 404 participants who received two doses of the SARS-CoV-2 mRNA vaccine (online supplemental table 1). The median (IQR) age was 44 (36–57), 96% were female, 9% were non-white, …

Recently, model for end-stage liver disease (MELD)-based liver allocation in the United States has been questioned based on concerns that waitlist mortality for a given biologic MELD (bMELD), calculated using laboratory values alone, might be higher at certain centers in certain locations across the country. Therefore, we aimed to quantify the center-level variation in bMELD-predicted mortality risk. Using Scientific Registry of Transplant Recipients (SRTR) data from January 2015 to December 2019, we modeled mortality risk in 33 260 adult, first-time waitlisted candidates from 120 centers using multilevel Poisson regression, adjusting for sex, and time-varying age and bMELD. We calculated a "MELD correction factor" using each center's random intercept and bMELD coefficient. A MELD correction factor of +1 means that center's candidates have a higher-than-average bMELD-predicted mortality risk equivalent to 1 bMELD point. We found that the "MELD correction factor" median (IQR) was 0.03 (-0.47, 0.52), indicating almost no center-level variation. The number of centers with "MELD correction factors" within ±0.5 points, and between ±0.5-± 1, ±1.0-±1.5, and ±1.5-±2.0 points was 62, 41, 13, and 4, respectively. No centers had waitlisted candidates with a higher-than-average bMELD-predicted mortality risk beyond ±2 bMELD points. Given that bMELD similarly predicts waitlist mortality at centers across the country, our results support continued MELD-based prioritization of waitlisted candidates irrespective of center.

The immune response to SARS-CoV-2 messenger RNA (mRNA) vaccines in patients with rheumatic and musculoskeletal diseases (RMD) is undefined because these individuals were largely excluded from phase I–III studies. To better understand the immune response to vaccination in this patient population, we studied the antibody response in patients with RMD who completed the first dose of SARS-CoV-2 mRNA vaccination. Participants with RMD across the USA were recruited to participate in this prospective cohort via social media. Those with prior SARS-CoV-2 were excluded. We collected demographics, RMD diagnoses and immunomodulatory regimens and tested for SARS-CoV-2 antibodies at baseline and prior to the second vaccine dose. Antibody testing was conducted on the semiquantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA) which tests for antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.1 We evaluated the association between demographic/clinical characteristics and positive antibody response using Fisher’s exact test and Wilcoxon rank-sum test. We studied 123 participants who received their first SARS-CoV-2 vaccination dose between 8 January 2021 and 12 February 2021; 52% underwent BNT162b2, and 48% underwent mRNA-1273 (table 1). The most common reported RMD diagnoses were inflammatory arthritis (28%), systemic lupus erythematosus (SLE) (20%), Sjogren’s syndrome (13%) and overlap connective tissue diseases(29%). Whereas …

Background and aims Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality. Approach and results Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79. Conclusions LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

In immunocompetent populations, the Janssen/Johnson & Johnson (J&J) SARS-CoV-2 vaccine induces antibody, CD4+ and CD8+ T cell responses and offers protection against severe and symptomatic SARS-CoV-2 infection.1 2 This vaccine is an adenovirus serotype 26 (Ad26) vector expressing a stabilised SARS-CoV-2 spike (S) (Ad26.COV2.S), a platform without prior approval for use in the general population, or for patients with rheumatic and musculoskeletal diseases (RMD).3 Patients on immunosuppressive therapy were excluded from the clinical trials1 2 and early data have suggested that the J&J vaccine results in lower humoral immunity than mRNA vaccination in immunosuppressed transplant patients.4 Given the attenuated immunogenicity to mRNA-based SARS-CoV-2 vaccines in certain patients with RMD,5 we studied the anti-spike antibody response to J&J SARS-CoV-2 vaccination in patients with RMD and compared them to recipients of the mRNA series. We used our prospective cohort of patients with RMD who underwent SARS-CoV-2 vaccination between December 2020 and May 2021.5 We collected information on demographics, rheumatic diagnoses and immunosuppressive medications. One month following completion of vaccine series (J&J or mRNA), serologic testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which tests for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 S protein, was completed. We compared the percentage of participants with detectable anti-RBD antibody in the J&J group (n=45) to the mRNA group (n=994) using Fisher’s exact test (online supplemental table 1). We compared the two …

BACKGROUND: Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective. METHODS: Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States. RESULTS: Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/µL. Median CD4 pre-COVID-19 was 298 cells/µL, declining to

Mobile devices, climate science, and autonomous vehicles all require advanced microwave antennas for imaging, radar, and wireless communications. We propose a waveguide-fed metasurface antenna architecture that enables electronic beamsteering from a lightweight circuit board with varactor-tuned elements. Our approach uses a unique feed structure and layout that enables spatial sampling at the Nyquist limit of half a wavelength. We detail the design of this Nyquist metasurface antenna and experimentally demonstrate electronic beamsteering in two directions. Nyquist metasurface antennas can realize high performance without costly and power hungry phase shifters, making them a compelling technology for future antenna hardware.

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.

Many deceased-donor and living-donor kidney transplants (KTs) rely on commercial airlines for transport. However, the coronavirus-19 pandemic has drastically impacted the commercial airline industry. To understand potential pandemic-related disruptions in the transportation network of kidneys across the United States, we used national flight data to compare scheduled flights during the pandemic vs 1-year earlier, focusing on Organ Procurement Organization (OPO) pairs between which kidneys historically most likely traveled by direct flight (High Volume by direct Air transport OPO Pairs, HVA-OPs). Across the United States, there were 39% fewer flights in April 2020 vs April 2019. Specific to the kidney transportation network, there were 65.1% fewer flights between HVA-OPs, with considerable OPO-level variation (interquartile range [IQR] 54.7%-75.3%; range 0%-100%). This translated to a drop in median number of flights between HVA-OPs from 112 flights/wk in April 2019 to 34 in April 2020 (P

In March 2020, coronavirus disease 2019 (COVID-19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living-donor and deceased-donor kidney transplants (LDKT/DDKT) March 15-April 30, 2020 to expected events calculated from preepidemic data January 2016-February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P&nbsp

Background The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. Methods To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. Results We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. Conclusions These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

COVID‐19 is a novel, rapidly changing pandemic: consequently, evidence‐based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center‐level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID‐19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID‐19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID‐19. Shortage of COVID‐19 tests was reported by 42.5%. Respondents reported a total of 148 COVID‐19 recipients from 10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center‐level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence‐based practices.

INTRODUCTION AND OBJECTIVE:The etiology of kidney stones is multi-factorial, with observed geographic and seasonal differences affecting the rate of stone formation. Multiple studies have reported ...

Nephron-sparing surgery has emerged as the treatment of choice for small renal masses. However, its role in larger tumors remains controversial. In this study, we compare the outcomes of laparoscopic partial nephrectomy (LPN) vs those of laparoscopic radical nephrectomy (LRN) for T2 renal tumors.Thirteen patients who had LPN and 16 patients who had LRN for T2 renal tumors were retrospectively analyzed for preoperative factors (age, gender, comorbidities, hemoglobin, and creatinine levels and estimated glomerular filtration rate [eGFR]), operative and perioperative characteristics (tumor characteristics, operative time [OT], warm ischemia time [WIT], estimated blood loss [EBL], length of stay [LOS], and postoperative complications), histopathologic results, and follow-up data (eGFR and recurrences).Tumor size was comparable between groups; however, tumors in the LRN group were more endophytic, central, and closer to the collecting system. There were no cases of positive surgical margins. Median OT was 160 minutes vs 230 minutes (p = 0.0029) and EBL was 25 mL vs 100 mL ([p = 0.0027], LRN vs LPN). Median WIT in the LPN group was 27 minutes, with three zero ischemias. Minor postoperative complications (≤Clavien-Dindo III) were noted in 6.25% and 23% (LRN vs LPN). Median LOS was 4.56 and 5.77 days (LRN vs LPN), respectively. Mean postsurgery eGFR was significantly lower for the LRN group (54.5 cc/[min ·1.73 mWe show that LPN is technically feasible for T2 tumors, with acceptable intra- and perioperative outcomes. Furthermore, our results show a significant advantage in preservation of renal function for LPN without compromising oncologic results. Taken together, we believe that LPN should be considered for larger tumors based on technical feasibility rather than only tumor size.

Subject of Research. One of the ways of automatic text analysis is the construction of subordination trees, in which the words of a sentence are connected with each other by semantic-syntactic links. The field of research is Russian-language texts, which have a general political, artistic and highly specialized character. Special attention is paid to the cases when the words are connected being far from each other at a considerable distance. Method. The subordination trees were built with the help of semantic-syntactical parser.Then the calculation of the distribution of links of different types by lengths was performed. The appearance frequencies of nonlocal links are studied. Main Results. It is shown that the fraction of non-local connections depending on the type can reach up to tens of percent. This is especially important for links coming from predicate nodes (subject, adverbial, etc.), as well as for anaphoric ones. It is noted that publicly available semantic classifiers and thesaurus have limited applicability for solving the problem of correct linking of remoted words in a sentence. Practical Relevance. It is shown that when solving the problem of extracting information that is ontological or scenario-based, as well as coreference, the long syntactic links that form the non-local semantic context cannot be neglected. The conclusion is drawn that the analysis of n-grams only is insufficient for the adequate selection of information from the text that is ontological or scenario. In this regard, there is a need to compile micro-dictionaries, focused on certain syntactic structures