Search

Recombinant zoster vaccine has been recommended by the US Advisory Committee on Immunization Practices (ACIP) for the prevention of herpes zoster (HZ) in immunocompetent adults aged at least 50 years since 2018. In January 2022, this was extended to immunodeficient/immunosuppressed adults aged at least 19 years. Key study objectives were to assess specialists' knowledge of the ACIP HZ vaccination recommendations, their attitudes toward HZ vaccination, and HZ vaccination practices/barriers. This cross-sectional, web-based survey (conducted in March 2022) included US dermatologists, gastroenterologists, infectious disease specialists, oncologists, and rheumatologists who treat patients with psoriasis, inflammatory bowel disease, human immunodeficiency syndrome, solid tumors/hematological malignancies, and rheumatoid arthritis, respectively. Although most of the 613 specialists correctly identified the ACIP HZ vaccination recommendations for adults aged at least 50 years (84%) and immunodeficient/immunosuppressed adults aged at least 19 years (67%), only 29% knew that recombinant zoster vaccine is recommended for individuals who have previously received zoster vaccine live, and only 18% knew all current ACIP recommendations. For patients with the diseases listed, 84% of specialists thought that HZ is a serious risk, 75% that HZ vaccination is extremely/very important, and 69% were extremely/very likely to recommend HZ vaccination. Only 36% administer vaccines themselves, mainly because patients receive vaccinations from others. Barriers to vaccination included more urgent/acute issues, insufficient time, and lack of patient motivation/willingness. Full knowledge of the ACIP HZ vaccination recommendations among the surveyed specialists was low. There may be a need to educate specialists to improve adherence to these recommendations. [ABSTRACT FROM AUTHOR]

Background Hospital- onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. Methods We conducted a cross- sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non- commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1--3 were collectively considered 'potentially preventable' and 4--6 'potentially not preventable'. Results Among 1789 HOB events with noncommensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non- commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non- commensal HOB events, events attributed to intravascular catheter- related infection, indwelling urinary catheter- related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and Discussion Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB- related quality metric. [ABSTRACT FROM AUTHOR]

Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA's goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 17 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations. [ABSTRACT FROM AUTHOR]

Total shoulder arthroplasty (TSA) is increasingly recognized as a therapeutic solution for various shoulder disorders. However, the correlation between preoperative determinants of health and postoperative TSA revisions remains underexplored. These correlations are scientifically important as they may be used to design higher-level clinical studies to confirm if they are in-fact predictive of revision. As such, this investigation aims to identify possible health and demographic disparities between primary TSA and revision TSA cohorts. Data for this research was sourced from the American College of Surgeons National Surgical Quality Improvement Program database from 2013 to 2021. Patients were classified based on Current Procedural Terminology (CPT) codes into 2 groups: primary TSA (CPT: 23472) and revision TSA (CPT: 23473 or 23474). Nineteen demographic and preoperative variables were compared between the cohorts using multivariate logistic regression. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were calculated and graphically displayed. To account for multiple exploratory comparisons, Bonferroni correction was utilized with an adjusted significance threshold of 0.0026. TSA revision patients were more likely to arrive from a nursing home (OR 1.87, 95% CI [1.50, 2.32], P <.001), have diabetes (OR 1.09, 95% CI [1.05, 1.14], P <.001), be diagnosed with Systemic inflammatory response syndrome prior to surgery (1.38, 95% CI [1.13, 1.69], P =.002) and less likely to have independent functional status prior to surgery (OR 0.69, 95% CI [0.63, 0.76], P <.001). Moreover, those in the revision group were predominantly younger, male, receiving immunosuppressive therapy, exhibited baseline dyspnea, and had elevated American Society of Anesthesiologists class. Notably, factors such as smoking, racial background, and hypertension showed no significant differences (P >.0026). Contrary to contemporary literature, our findings suggest that, when demographic factors are controlled for, smoking is not correlated with revisions in TSA when compared to primary TSA. Furthermore, patients undergoing primary TSA are more likely to be functionally independent than patients undergoing revision TSA. While at the same time, a patient's arrival at surgery from a nursing home gave the greatest likelihood of a revision. [ABSTRACT FROM AUTHOR]

Introduction: Avascular necrosis is a debilitating osseous complication in transplant recipients. Project Aim: This program evaluation sought to describe risk factors and adverse outcomes of avascular necrosis in kidney transplant recipients. Design: This was a retrospective evaluation of all recipients of kidneys and simultaneous pancreas and kidneys between 2001 and 2018 from a single center. Controls were selected based on the incidence density, sampling at a 1:3 ratio based on the post-transplant interval. Outcomes of interest were acute rejection, death-censored graft failure, and patient mortality. Results: A total of 88 kidney recipients had avascular necrosis and were compared with 257 controls. Most of the recipient's and donors' baseline characteristics were similar between the groups, except calcineurin inhibitor-based immunosuppression was more prevalent, and non-white donors were less prevalent in the control group. Looking for risk factors for avascular necrosis, calcineurin inhibitor-based immunosuppression was associated with a lower risk for avascular necrosis in the univariate analysis, but this was not found after adjustment of multiple variables. In multivariate analysis, avascular necrosis was associated with an increased risk for patient death (hazard ratio: 1.68; 95% confidence interval: 1.16-2.44; P =.008) but not for acute rejection or death censored graft failure. Conclusion: Although limited by small sample size, this evaluation found avascular necrosis to be associated with an increased risk of patient death. This finding may be useful for the provider taking care of the patients and discussing the various outcomes after the transplant. [ABSTRACT FROM AUTHOR]

Dermatophytoses are fungal infections of the skin, hair, and nails that affect approximately 25% of the global population. Occlusive clothing, living in a hot humid environment, poor hygiene, proximity to animals, and crowded living conditions are important risk factors. Dermatophyte infections are named for the anatomic area they infect, and include tinea corporis, cruris, capitis, barbae, faciei, pedis, and manuum. Tinea incognito describes steroid-modified tinea. In some patients, especially those who are immunosuppressed or who have a history of corticosteroid use, dermatophyte infections may spread to involve extensive skin areas, and, in rare cases, may extend to the dermis and hair follicle. Over the past decade, dermatophytoses cases not responding to standard of care therapy have been increasingly reported. These cases are especially prevalent in the Indian subcontinent, and Trichophyton indotineae has been identified as the causative species, generating concern regarding resistance to available antifungal therapies. Antifungal-resistant dermatophyte infections have been recently recognized in the United States. Antifungal resistance is now a global health concern. When feasible, mycological confirmation before starting treatment is considered best practice. To curb antifungal-resistant infections, it is necessary for physicians to maintain a high index of suspicion for resistant dermatophyte infections coupled with antifungal stewardship efforts. Furthermore, by forging partnerships with federal agencies, state and local public health agencies, professional societies, and academic institutions, dermatologists can lead efforts to prevent the spread of antifungal-resistant dermatophytes. [ABSTRACT FROM AUTHOR]

Introduction: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. Objectives: This report describes the dental status of a cohort of patients within the Chronic Graft‐versus‐Host Disease Consortium and treatment rendered prior to transplant. Methods: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana‐Farber: n = 241). Both centers have institutional‐based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. Results: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). Conclusions: Retrospective analysis of pre‐AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care. [ABSTRACT FROM AUTHOR]

Burkholderia cenocepacia (B cenocepacia) is a gram-negative bacteria associated with significant morbidity and mortality following lung transplantation. Most US transplant programs consider B cenocepacia colonization to be an absolute contraindication to transplantation. This article argues that, if clinicians have good clinical reasons to expect poor outcomes for patients with B cenocepacia, then offering transplantation anyway is an abrogation of clinicians’ fiduciary duties. This article also discusses other fiduciary obligations transplant programs might have to patients with B cenocepacia, such as referring to another transplant center, considering novel treatment options, and investigating how the infection’s virulence factors stratify that patient’s risk for poor transplant outcomes. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), stands as the fourth leading cause of cancer-related deaths in the United States, marked by challenging treatment and dismal prognoses. As immunotherapy emerges as a promising avenue for mitigating PDAC's malignant progression, a comprehensive understanding of the tumor's immunosuppressive characteristics becomes imperative. This paper systematically delves into the intricate immunosuppressive network within PDAC, spotlighting the significant crosstalk between immunosuppressive cells and factors in the hypoxic acidic pancreatic tumor microenvironment. By elucidating these mechanisms, we aim to provide insights into potential immunotherapy strategies and treatment targets, laying the groundwork for future studies on PDAC immunosuppression. Recognizing the profound impact of immunosuppression on PDAC invasion and metastasis, this discussion aims to catalyze the development of more effective and targeted immunotherapies for PDAC patients. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia treatment centres (HTCs) and healthcare providers (HCPs) will need to adapt to a new treatment paradigm with the emergence of adeno‐associated virus (AAV)‐based gene therapy for the treatment of haemophilia in adults. Aim: This review examines the upcoming patient and institutional journeys, along with practical aspects of preparedness for clinical delivery of gene therapy by HTCs. Methods: Based on our clinical experience and examination of published literature, we explored the parallel journeys for patients and treatment centres to navigate before, during, and after administration of gene therapy. Results: The patient journey includes: information gathering; decision making; comprehensive patient assessment; preparation for the infusion itself; short‐ and long‐term monitoring; lifestyle modifications; and the possible need for immunosuppressive treatment. Informed decision‐making may require patient education with extensive discussions and an understanding that not all people with haemophilia will choose or be eligible for gene therapy, although eligibility criteria continue to evolve. The institutional journey includes: consideration of biosafety procedures; planning for product procurement, handling, storage, and administration; development of detailed protocols and guidance documents; contingency planning for immunosuppressive and haemostatic management; consideration of clinical capabilities and staff training needs; coordination of efforts by the full multidisciplinary team; and collaboration between referring, dosing, and follow‐up treatment centres. Documented protocols and guidance documents are pivotal for this complex therapy to ensure safe handling, optimal delivery, and post‐infusion management and follow‐up. Conclusion: Successful implementation of this new treatment modality will require communication and collaboration among multiple stakeholders. [ABSTRACT FROM AUTHOR]

Objectives Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus resistance protein A (MxA) expression among sarcoidosis patients. Methods We reviewed the Mayo Clinic database (May 1980–December 2020) to identify sarcoidosis patients with myopathic symptoms and pathological evidence of myopathy. Results Among 5885 sarcoidosis patients, 21 had symptomatic myopathy. Eight carried a diagnosis of sarcoidosis 5.5 years (median) prior to myopathy onset. Eleven patients had ScM. The remaining had non-sarcoid myopathies (five IBM, one immune-mediated necrotizing myopathy, one non-specific myositis, two non-specific myopathy and one steroid myopathy). Estimated frequency of IBM is 85 per 100 000 sarcoidosis patients. The following features were associated with non-sarcoid myopathies (P  < 0.05): (i) predominant finger flexor and quadriceps weakness, (ii) modified Rankin scale (mRS) >2 at time of diagnosis, (iii) creatine kinase >500 U/l, and (iv) absence of intramuscular granulomas. Sarcoplasmic MxA expression was observed in scattered myofibres in three patients, two of whom were tested for DM-specific autoantibodies and were negative. Immunosuppressive therapy led to improvement in mRS ≥1 in 5/10 ScM, none of the five IBM, and 3/3 remaining patients with non-sarcoid myopathies. Discussion Symptomatic myopathy occurred in 0.36% of sarcoidosis. IBM was the second most common cause of myopathies after ScM. Frequency of IBM in sarcoidosis is higher than in the general population. Recognition of features suggestive of alternative aetiologies can guide proper treatment. Our findings of abnormal MxA expression warrant a larger study. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types. Methods: This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and posttransplant malignancy. Results: A total of 5,591 patients, 6,142 transplanted organs, and 517 posttransplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia. Conclusion: Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to life-long immunosuppression, organ transplant recipients are prone to skin cancer development. We evaluated the association of cumulative UV burden with skin aging and skin cancer in two groups of transplant patients with and without skin cancer, who were matched for gender, age, type of organ transplanted, post-transplantation period, and immunosuppressive therapy. Individuals with actinic keratoses had a 7.5-fold risk for skin cancer development, and those with green or blue eyes a 4.1- or 3.6-fold risk, respectively; carriers of particular MC1R genotypes associated with a diminished function had a 1.9-fold increased risk. The extent of skin aging was only connected with a higher number of tumors, but not with the development of skin cancer per se. The risk of keratinocyte cancer is determined by intrinsic and extrinsic factors, which also influence skin aging. Few studies have linked skin aging and UV exposure with the incidence of non-melanoma skin cancer (NMSC). We evaluated signs of actinic skin damage and aging, individual UV burden, and melanocortin-1 receptor (MC1R) variants. A total of 194 organ transplant recipients (OTR) who suffered from NMSC were compared to 194 tumor-free controls matched for gender, age, type of transplanted organ, post-transplantation (TX) period, and immunosuppressive therapy. Compared with the cases, the controls scored higher in all skin aging scores and there were no differences in UV burden except for intentional whole-body UV exposure for specific UV scenarios and periods of life in favor of cases. The number of NMSCs correlated with all types of skin aging scores, the extent of intentional sun exposure, older age, longer post-TX period, shorter interval from TX to first NMSC, and specific MC1R risk groups. Multivariable models revealed a 7.5-fold risk of developing NMSC in individuals with actinic keratosis; 4.1- or 3.6-fold in those with green or blue eyes, respectively; and a 1.9-fold increased risk in the MC1R medium- + high-risk group. In the absence of skin aging contributing to NMSC development, certain MC1R risk types may identify OTR at risk for high tumor burden. [ABSTRACT FROM AUTHOR]

Cancer continues to be a substantial health concern and a leading cause of death in the United States and around the world. Therefore, it is important to continue to explore the potential of novel therapeutic targets and combinatorial therapies. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that associates with DNAX activation protein (DAP) 12 and DAP10 to propagate signals within the cell. TREM2 has primarily been recognized for its expression on cells in the monocyte-macrophage lineage, with the majority of work focusing on microglial function in Alzheimer's Disease. However, expansion of TREM2 research into the field of cancer has revealed that epithelial tumor cells as well as intratumoral macrophages and myeloid regulatory cells also express TREM2. In this review, we discuss evidence that TREM2 contributes to tumor suppressing or oncogenic activity when expressed by epithelial tumor cells. In addition, we discuss the immunosuppressive role of TREM2-expressing intratumoral macrophages, and the therapeutic potential of targeting TREM2 in combination with immune checkpoint therapy. Overall, the literature reveals TREM2 could be considered a novel therapeutic target for certain types of cancer. [ABSTRACT FROM AUTHOR]

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54-66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02-1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34-1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02-1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08-1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management., (© 2024. The Author(s).)

Background/objectives: The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States., Methods: A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use., Results: In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy., Discussion: Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab., (© 2024. The Author(s).)

We analyzed administrative data to determine the 1-year incidence of invasive fungal infections (IFIs) in patients beginning small molecule kinase inhibitor (SMKI) therapy. The incidence of IFIs by small molecule kinase inhibitor ranged from 0.0% to 10.6%, with patients taking midostaurin having the highest incidence. An IFI developed in 38 of 1286 patients taking ibrutinib (3.0%). [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a rare condition in pediatric patients. Little is known about practice patterns and outcomes of pediatric transplant patients. The purpose of our study was to examine differences in patient characteristics, immunosuppression, and long-term graft outcomes between ANCA and non-ANCA vasculitis recipients. Methods: We used the Scientific Registry of Transplant Recipients to evaluate pediatric ANCA vasculitis recipients between the ages of 1 and 22 years old from 1991 to 2017 and compared them to non-ANCA vasculitis patients during the same time cohort in the USA. Results: A total of 26,431 transplant recipients were identified, of these, 337 with ANCA vasculitis. Mean 1-year eGFR was 62.46 and 64.92 ml/min/1.73 m2 (p = 0.002), and mean 5-year eGFR was 57.95 and 59.38 ml/min/1.73 m2 (p = 0.18) between the non-ANCA and ANCA groups, respectively. Five-year graft survival was similar in both groups (non-ANCA 75.5 vs. ANCA 78.6%; p = 0.19). Of those with graft loss within the ANCA group, only 0.6% was secondary to disease recurrence (p = 0.14). Conclusions: Kidney transplant is a safe treatment modality for children with ANCA-related kidney failure. ANCA patients have comparable graft survival when compared to the general transplant population with a low risk of recurrence. Thymoglobulin was used in a higher proportion within the ANCA group compared to the non-ANCA group. Tacrolimus, mycophenolate mofetil/mycophenolic acid, and steroids were the predominant maintenance immunosuppression used in both groups. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) is associated with tumor aggressiveness, drug resistance, and poor survival in non-small cell lung cancer (NSCLC) and other cancers. The identification of immune-checkpoint ligands (ICPLs) associated with NSCLCs that display a mesenchymal phenotype (mNSCLC) could help to define subgroups of patients who may benefit from treatment strategies using immunotherapy. We evaluated ICPL expression in silico in 130 NSCLC cell lines. In vitro , CRISPR/Cas9-mediated knockdown and lentiviral expression were used to assess the impact of ZEB1 expression on CD70. Gene expression profiles of lung cancer samples from the TCGA (n = 1018) and a dataset from MD Anderson Cancer Center (n = 275) were analyzed. Independent validation was performed by immunohistochemistry and targeted-RNA sequencing in 154 NSCLC whole sections, including a large cohort of pulmonary sarcomatoid carcinomas (SC, n = 55). We uncover that the expression of CD70, a regulatory ligand from the tumor necrosis factor ligand family, is enriched in mNSCLC in vitro models. Mechanistically, the EMT-inducer ZEB1 impacted CD70 expression and fostered increased activity of the CD70 promoter. CD70 overexpression was also evidenced in mNSCLC patient tumor samples and was particularly enriched in SC, a lung cancer subtype associated with poor prognosis. In these tumors, CD70 expression was associated with decreased CD3+ and CD8+ T-cell infiltration and increased T-cell exhaustion markers. Our results provide evidence on the pivotal roles of CD70 and ZEB1 in immune escape in mNSCLC, suggesting that EMT might promote cancer progression and metastasis by not only increasing cancer cell plasticity but also reprogramming the immune response in the local tumor microenvironment. • The EMT-inducer ZEB1 modulates the expression of CD70, a ligand from the TNF family. • CD70 expression is enriched in pulmonary sarcomatoid carcinomas (SC). • In SC, CD70 expression is associated with features of an immunosuppressive environment. [ABSTRACT FROM AUTHOR]

Background As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. Methods In a multicenter case-control analysis of US adults hospitalized March 11–May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. Results Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7–91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18–49 years (97.4%; 95% CI, 79.3–9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8–82.6) than without immunosuppression (91.3%; 95% CI, 85.6–94.8). Conclusion During March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. Method/Objective: This comprehensive review aims to discuss steroid‐related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. Results: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. Conclusion: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid‐inclusive maintenance immunosuppression in pediatric kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared with both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intrahost viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and 9 persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent coronavirus disease 2019 (COVID-19) demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study., Objective: We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment., Methods: A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups., Results: All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025., Conclusions: This study will quantify immunocompromised individuals' physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities., International Registered Report Identifier (irrid): RR1-10.2196/52643., (©Paul Williams, Timothy A Herring, Renata T C Yokota, Tiago Maia, Sudhir Venkatesan, James C Marcus, Gabriella Settergren, Sofie Arnetorp, Andrew Lloyd, Johan L Severens, James W Varni, Sharon Dixon, Lweendo Hamusankwa, Philip A Powell, Sylvia Taylor, John E Ware Jr, Marieke Krol. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.08.2024.)

Background: More women of childbearing age are surviving after heart transplantation (HT), many of whom have a desire to become pregnant. Limited data exist evaluating patients' perspectives, receipt of counseling, and knowledge surrounding contraception, pregnancy, breastfeeding, and medication safety after HT., Methods: We conducted a voluntary, confidential, web-based cross-sectional survey of women who were childbearing age (defined as 18-45 years) at the time of HT. Transplants occurred between January 2005 and January 2020. Surveys were conducted across 6 high-volume HT centers in the United States., Results: There were 64 responses from women who were of childbearing age at the time of HT. Twenty-five women (39.1%) were pregnant before HT, and 6 (9.4%) women reported at least 1 pregnancy post-transplant. Fifty-three percent (n=34) reported they did not receive enough information on post-HT pregnancy before listing for HT, and 26% (n=16) did not discuss their ability to become pregnant with their care team before proceeding with HT. Following HT, 44% (n=28) still felt that they had not received enough information regarding pregnancy. The majority of women (n=49, 77%) had discussed contraception to prevent unplanned pregnancy with their transplant team. Twenty percent (n=13) reported that pregnancy was never safe after transplantation based on the information they had received from their transplant providers., Conclusions: Many women feel they are not receiving adequate counseling with regard to posttransplant reproductive health. This survey highlights an opportunity to improve both provider education and patient communication to better support women with HT desiring posttransplant pregnancy., Competing Interests: None.

Background: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of CDI among kidney transplant (KT) recipients., Methods: Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression., Results: A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without., Conclusions: We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Published by Elsevier Inc.)

Background: We studied the association of induction immunosuppression and pediatric deceased‐donor kidney recipient and graft survival. Methods: We utilized the SRTR to evaluate all primary pediatric deceased‐donor kidney transplants from January 1st, 2000, through December 2018. We included only recipients who were maintained on tacrolimus and mycophenolate. Recipients were grouped by induction type: alemtuzumab n = 320, r‐ATG n = 2091 and IL‐2RA n = 2165. Recipient and allograft survival, and their predictors, were examined. Models were adjusted for age, sex, ethnicity, HLA‐antigen mismatches, transplant year, steroid maintenance, pre‐emptive transplantation and payor type, with the transplant center included as a random effect. Results: Rejection rates at 6 months (alemtuzumab 8.6% vs r‐ATG 7.8% vs IL2‐RA 9.2%; P =.30) and 12 months (alemtuzumab 17.2% vs r‐ATG 15.7% vs IL2‐RA 16.5%; P =.70) were not significantly different between induction groups. In the multivariable models, compared to IL‐2RA neither alemtuzumab nor r‐ATG was associated with improved recipient [alemtuzumab (HR 1.06, P =.88); r‐ATG (HR 1.03, P =.84)] or graft survival [alemtuzumab (HR 1.18, P =.32); r‐ATG (HR 1.10, P =.21)]. Conclusion: In this large cohort of standard immunological risk primary pediatric deceased‐donor kidney recipients on tacrolimus and mycophenolate maintenance, depletional induction regimens were not associated with better rejection rates, recipient, or graft survival compared to IL‐2RA induction. Racial, payor type, and sex‐related outcome disparities were significant in this group independent of the induction choice. [ABSTRACT FROM AUTHOR]

Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer mortality in the United States, with non-small cell lung cancer (NSCLC) accounting for around 85% of cases. Of particular concern is the poor responsiveness of this malignancy to therapy, resulting in a very low 5-year survival rate (17.4%) and a prominent tendency to progress to metastatic disease. A number of very recent studies, both pre-clinical and clinical, have implicated the neutrophil in both the pathogenesis and unsatisfactory response to therapy of NSCLC. In this context, movement of neutrophils into the tumor microenvironment (TME) is a common feature of NSCLC. Indeed neutrophils are the dominant type of immune cell in the NSCLC TME, creating a highly immunosuppressive milieu that is not only conducive to tumor growth and spread, but also represents a significant obstacle to the success of anti-tumor therapy, especially novel immunotherapies. The clinically relevant adverse impact of a neutrophil predominance both systemically and in the TME of patients with NSCLC is underscored by the negative prognostic value of both a persistent neutrophilia and, in particular, a high (≥5) neutrophil:lymphocyte ratio. On a more positive note, however, recognition of the involvement of the neutrophil in both the pathophysiology of NSCLC and treatment failure has enabled identification of neutrophil-targeted strategies that have the potential to serve as adjuncts to standard anti-cancer therapies, including immunotherapy. These strategies together with a consideration of the immunosuppressive, pro-tumorigenic properties of the neutrophil represent the major thrusts of this review. [ABSTRACT FROM AUTHOR]

Vaccination in adults remains one of the most important means of preventing disease in vulnerable populations. Certain vaccines, such as influenza, tetanus/diphtheria/pertussis, and the new COVID-19 vaccine are recommended for all adults, while others are recommended in subsets of adults depending on age, comorbidities, and certain risk factors. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer. [ABSTRACT FROM AUTHOR]

Pediatric transplant recipients are on multiple prescription and non‐prescription drugs. Many patients also use dietary, nutritional, and herbal supplements. This manuscript researched formulations of immunosuppressive drugs currently available and presents information on generic immunosuppressive drugs, commonly used non‐prescription medications, dietary supplements, and herbal supplements. Immunosuppressive drugs are available in various formulations. Not all formulations are interchangeable. A number of FDA‐approved generic formulations are available commercially in the United States. Generally generic formulations produce similar blood concentration vs time profiles compared to brand name products in adults and are considered to be bioequivalent. NSAID should be avoided in transplant patients due to potential drug interactions and increased risk associated with NSAID use; and appropriate doses of acetaminophen should be used for treatment of pain. Over‐the‐counter medications, such as guaifenesin and dextromethorphan, antihistamine medications, including diphenhydramine, loratadine, cetirizine, and fexofenadine, can be safely used in pediatric solid organ transplant population. Many safe and effective over‐the‐counter options exist for stool softening and as laxative. Diarrhea can lead to an increase in calcineurin inhibitor levels. Food can alter the absorption of immunosuppressive drugs. Several herbal products can alter immune status of the patients or alter the blood concentration of immunosuppressive drugs or may produce renal or hepatic toxicities and should be avoided in pediatric transplant recipients. It is important to educate pediatric transplant recipients and their families about not only immunosuppressive drug therapy but also about non‐prescription drugs, dietary, and herbal supplement use. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID‐19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID‐19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS‐CoV‐2 infection monitored by both RT‐PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti‐SARS‐CoV‐2 antibodies. [ABSTRACT FROM AUTHOR]

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1‐year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under‐ and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long‐term outcomes during the next era of immunosuppression, which will move from universal protocols to patient‐specific optimization. [ABSTRACT FROM AUTHOR]

This study aimed to model the financial impact of caplacizumab with therapeutic plasma exchange (TPE) + immunosuppression for patients experiencing an acute acquired thrombotic thrombocytopenic purpura (aTTP) episode versus TPE + immunosuppression, from a US hospital's perspective. We developed an economic model to estimate the impact of caplacizumab on a US hospital's budget. Cost offsets from caplacizumab utilization targeted inpatient general ward days, intensive care unit (ICU) days, and TPE utilization. Costs and event probabilities were estimated from primary data analyses of the phase 3 HERCULES trial and peer-reviewed literature or other public sources. Plan reimbursement was obtained from 2019 Medicare Fee Schedules and adjusted to represent reimbursement from different US payers. Cost of ICU and general ward utilization were estimated from Medicare Provider Analysis and Review data analyses capturing hospital discharges. The model results indicate that caplacizumab leads to hospitalization cost savings of over $8,000 ($23,148 versus $14,904) along with TPE cost savings of over $14,000 ($37,150 versus $23,033) per patient. When the cost of caplacizumab and plan reimbursement are incorporated into the results, the per-patient cost of TPE + immunosuppression is $23,120 versus $70,068 for caplacizumab with TPE + immunosuppression, an incremental cost of $46,948. The model was robust to several scenario analyses; however, when limited to Medicare fee-for-service (FFS), the incremental cost of caplacizumab per patient was reduced to $4,852 due to add-on payments. Caplacizumab with TPE + immunosuppression is associated with an increase in costs; however, the increase is nominal among payers who provide an add-on payment consistent with that of Medicare FFS. [ABSTRACT FROM AUTHOR]

To quantify the wider impacts of increased graft survival on the size of the kidney transplant waitlist and health and economic outcomes. The analysis employed known steady-state solutions to a double-queueing system as well as simulations of this system. Baseline input parameters were sourced from the Organ Procurement and Transplant Network and the United States Renal Data System. Three increased graft survival scenarios were modeled: decreases in repeat transplant candidates joining the waitlist of 25%, 50%, and 100%. Under the three scenarios, we estimated that the US waitlist size would decrease from 91,822 to 85,461 (6.9% decrease), 80,073 (12.8% decrease), and 69,340 (24.4% decrease), respectively. Patient outcomes improved, with lifetime quality-adjusted life years (QALYs) for a 1-year cohort of transplant recipients increasing by 10,010, 16,888, and 43,345 over the three scenarios. Discounted lifetime costs for the cohort in the new steady state were lower by $1.6 billion, $2.3 billion, and $9.0 billion for each scenario, respectively. Spillover impacts (i.e. benefits that accrued beyond the patients who directly experienced increased graft survival) accounted for 58–65% of the QALY gains and ranged from cost increases of 3.3% to decreases of 5.5%. The model is a simplification of reality and does not account for the full degree of patient heterogeneity occurring in the real world. Health economic outcomes are extrapolated based on the assumption that the median patient is representative of the overall population. Increasing graft survival reduces demand from repeat transplants candidates, allowing additional candidates to receive transplants. These spillover impacts decrease waitlist size and shorten wait times, leading to improvements in graft and patient survival as well as quality-of-life. Cost-effectiveness analyses of treatments that increase kidney graft survival should incorporate spillover benefits that accrue beyond the direct recipient of an intervention. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review reflects on the impact of the COVID-19 pandemic on the field of rheumatology, emphasizing resulting insights related to the risks of viral infections in immunosuppressed patients, vaccine immunogenicity in immunocompromised patients, and immune dysregulation in the setting of viral infection., Recent Findings: During the pandemic, global patient registries provided real-time insights into the risk factors associated with severe COVID-19 outcomes in rheumatology patients. Updated evidence-based recommendations from the American College of Rheumatology (ACR) guided rheumatology practice during a time of considerable uncertainty. Studies on COVID-19 vaccines in immunocompromised populations enhanced our understanding of specific immunosuppressive therapies on vaccine efficacy. The immune dysregulation seen in severe COVID-19 underscored a role for immunomodulation in this and other severe infections. Furthermore, novel post-infectious conditions, namely multisystem inflammatory syndrome in children (MIS-C) and Long COVID, reshaped our understanding of post-viral syndromes and revealed novel pathological mechanisms. Lessons from the COVID-19 pandemic demonstrate the power of collaborative research. The scientific revelations from this dreadful time will, nonetheless, benefit the practice of rheumatology for years to come., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Examine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk., Materials and Methods: We queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Criteria for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month periods prior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, <30 days, 30 days - 1 year, 1 to 2 years, and >2+ years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models., Results: We identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively)., Conclusion: In this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis., Competing Interests: Disclosure All authors whose names are listed on this manuscript certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Background: Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC.Methods: This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29 months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing.Results: A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05).Conclusions: In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC. [ABSTRACT FROM AUTHOR]

Background: Poor sleep behavior appears to have adverse effects on health by metabolic disruption and immunity suppression. Sleep disturbance is strongly associated with diabetes, cardiovascular diseases, and some cancers. This study aimed to evaluate the association between sleep duration and periodontal disease in a national US population study in a National Health and Nutrition Examination Survey (NHANES).Methods: The data were collected from individuals aged ≥30 years and included 3,624 participants in the United States NHANES 2013 to 2014. A weighted multivariable logistic regression modeling quantified the association between sleep and severe periodontal disease. We tested for diabetes as an effect modifier, adjusting for potential confounders such as smoking status, sex, age, education level, and dental visit.Results: Individuals who sleep >7 hours/night with no trouble sleeping are 40% less likely to have severe periodontal disease (odds ratio [OR] = 0.6, P < 0.05), adjusting for age, sex, smoking status, FPL, education level, and dental visit. Additionally, diabetes was a significant positive effect modifier of the relationship between sleep and severe periodontal disease (OR = 4.8, P < 0.05).Conclusions: Findings of this cross-sectional representative study of an adult US population revealed a statistically significant association between sleep duration and severe periodontitis. In this study, individuals who slept >7 hours/night were less likely to exhibit severe periodontal disease. It also seems that this relationship was stronger among individuals with diabetes compared with individuals without diabetes. [ABSTRACT FROM AUTHOR]

Background Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults. Methods We identified adults hospitalized with laboratory-confirmed influenza during 2011–2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors. Results Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P <.001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20–1.76). Intensive care was more likely among IC patients 65–79 years (aOR, 1.25; 95% CI, 1.06–1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06–1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI,.83–.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05–1.36). Conclusions Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults. [ABSTRACT FROM AUTHOR]

Improved postoperative care for renal transplant recipients has advanced both duration and overall quality of life. However, degenerative spinal pathology is increasingly prevalent after transplant. Outcomes following spinal fusion among the renal transplant population in the United States are rarely addressed. The Healthcare Cost and Utilization Project National Inpatient Sample database was employed. Cases in years 2008–2014 for patients ≥18 years old receiving spinal fusion, exploration/decompression, and/or spinal revision/re-fusion surgeries were included. Cases were divided into kidney transplant recipients (KTR) and non–kidney transplant recipients. Complications, demographics, and socioeconomic outcomes were compared between cohorts. Of 579,726 patients who met inclusion criteria, 685 (0.1%) were KTRs. The KTR population was older and included more men compared with the non–kidney transplant recipient population (60.1 years vs. 56.6 years, P < 0.001; 58% male vs. 45.5% male, P < 0.001). KTRs experienced higher total complication rates (29.8% vs. 18.9%, P < 0.001). Prevalence of acute posthemorrhagic anemia and need for transfusion was markedly higher for KTRs (15.8% vs. 9.1%, P < 0.001; 13.6% vs. 6.2%, P < 0.001). Multivariate analysis revealed longer length of stay (median 1.23 days, interquartile range 0.94–1.53, P < 0.001), lower routine discharge (odds ratio = 0.57, 95% confidence interval 0.48–0.69, P < 0.001), and higher discharge to alternative care facilities (odds ratio = 1.91, 95% confidence interval 1.57–2.33, P < 0.001) for KTRs. The inpatient course for KTRs undergoing spinal operations was significantly costlier ($87,445 vs. $71,589, P < 0.001). History of renal transplant was associated with increased inpatient medical and socioeconomic complications following spinal fusion. Physicians and patients must understand and respect the potentially increased perioperative challenges facing KTRs. [ABSTRACT FROM AUTHOR]

Background People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods We studied 102 777 PLWH during 1996–2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5–51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5–6.6). Conclusions Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk. [ABSTRACT FROM AUTHOR]

Background Cryptococcosis is increasingly recognized in people without human immunodeficiency virus (HIV). Methods A multicenter, prospective cohort study was performed in 25 US centers. Consenting patients were prospectively followed for ≤2 years. Neurological morbidities were assessed with longitudinal event depiction and functional scores (Montreal Cognitive Assessment [MoCA]). Risks of death were analyzed using Cox regression. Results One hundred forty-five subjects were enrolled. Most were male (95; 65.5%) and had immunosuppression (120; 82.8%), including solid organ transplant (SOT; 33.8%), autoimmunity (15.9%), and hematologic malignancies (11.7%). Disease involved the central nervous system (CNS) in 71 subjects (49%). Fever was uncommon, documented in 40 (27.8%) subjects, and absence was associated with diagnostic delay (mean: 48.2 vs 16.5 days; P =.007). Abnormal MoCA scores (<26) were predictive of CNS disease; low scores (<22) were associated with poor long-term cognition. Longitudinal event depiction demonstrated frequent complications in people with CNS disease; 25 subjects (35.2%) required >1 lumbar puncture and 8 (11.3%) required ventriculostomies. In multivariable models, older age (>60 years) was associated with higher risks of death (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.05–4.38; P =.036), and lower risks were noted with underlying hematologic malignancy (HR, 0.29; 95% CI, 0.09–0.98; P =.05) and prior SOT (HR, 0.153; 95% CI, 0.05–0.44; P =.001). Conclusions Despite aggressive antifungal therapies, outcomes of CNS cryptococcosis in people without HIV are characterized by substantial long-term neurological sequelae. Studies are needed to understand mechanism(s) of cognitive decline and to enable better treatment algorithms. [ABSTRACT FROM AUTHOR]

Background Existing data on the clinical features and outcomes of immunocompromised children with influenza are limited. Methods Data from the 2011–2012 through 2014–2015 influenza seasons were collected as part of the Centers for Disease Control and Prevention (CDC) Influenza Hospitalization Surveillance Network (FluSurv-NET). We compared clinical features and outcomes between immunocompromised and nonimmunocompromised children (<18 years old) hospitalized with laboratory-confirmed community-acquired influenza. Immunocompromised children were defined as those for whom ≥1 of the following applies: human immunodeficiency virus/acquired immunodeficiency syndrome, cancer, stem cell or solid organ transplantation, nonsteroidal immunosuppressive therapy, immunoglobulin deficiency, complement deficiency, asplenia, and/or another rare condition. The primary outcomes were intensive care admission, duration of hospitalization, and in-hospital death. Results Among 5262 hospitalized children, 242 (4.6%) were immunocompromised; receipt of nonsteroidal immunosuppressive therapy (60%), cancer (39%), and solid organ transplantation (14%) were most common. Immunocompromised children were older than the nonimmunocompromised children (median, 8.8 vs 2.8 years, respectively; P <.001), more likely to have another comorbidity (58% vs 49%, respectively; P =.007), and more likely to have received an influenza vaccination (58% vs 39%, respectively; P <.001) and early antiviral treatment (35% vs 27%, respectively; P =.013). In multivariable analyses, immunocompromised children were less likely to receive intensive care (adjusted odds ratio [95% confidence interval], 0.31 [0.20–0.49]) and had a slightly longer duration of hospitalization (adjusted hazard ratio of hospital discharge [95% confidence interval], 0.89 [0.80–0.99]). Death was uncommon in both groups. Conclusions Immunocompromised children hospitalized with influenza received intensive care less frequently but had a longer hospitalization duration than nonimmunocompromised children. Vaccination and early antiviral use could be improved substantially. Data are needed to determine whether immunocompromised children are more commonly admitted with milder influenza severity than are nonimmunocompromised children. [ABSTRACT FROM AUTHOR]