Changes in planta K nutrient content altered the interaction pattern between Nicotiana benthamiana and Alternaria longipes.

Potassium (K) fertilisation has frequently been shown to enhance plant resistance against pathogens, though the mechanisms remain elusive. This study investigates the interaction dynamics between Nicotiana benthamiana and the pathogen Alternaria longipes under different planta K levels. On the host side, adding K activated the expressions of three NLR (nucleotide-binding domain and leucine-rich repeat-containing proteins) resistance genes, including NbRPM1, NbR1B23 and NbNBS12. Silencing these NLRs attenuated resistance in high-K (HK, 40.8 g/kg) plant, whereas their overexpression strengthened resistance in low-K (LK, 23.9 g/kg) plant. Typically, these NLRs mainly strengthened plant resistance via promoting the expression of pathogenesis-related genes (PRs), ROS burst and synthesis of antifungal metabolites in HK plant. On the pathogen side, the expression of effectors HKCSP1, HKCSP2 and LKCSP were shown to be related to planta K content. A. longipes mainly expressed effectors HKCSP1 and HKCSP2 in HK plant to interfere host resistance. HKCSP1 physically interacted with NbRPM1 to promote the degradation of NbRPM1, then attenuated related resistance in HK N. benthamiana. Meanwhile, HKCSP2 directly interacted with NbPR5 to suppress resistance in HK plant. In LK plant, A. longipes mainly deployed LKCSP that interacted with NbR1B23 to interfere reduce resistance in N. benthamiana. Overall, our research insights that both pathogen and host mobilise distinct strategies to outcompete each other during interactions in different K nutrient environments.

CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Direct and indirect costs for patients with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are associated with substantial healthcare resource use and productivity loss. This retrospective cohort analysis used disability leave and medical claims data to measure direct and indirect healthcare costs associated with MPNs. The analysis included 173 patients with myelofibrosis (MF), 4477 with polycythemia vera (PV), 6061 with essential thrombocythemia (ET), and matched controls (n = 519, n = 13,431, and n = 18,183, respectively). Total healthcare costs were significantly higher for cases versus controls in each cohort (mean cost difference: MF, $67,456; PV, $10,970; ET, $22,279). Cases were more likely than controls to take disability leave and incurred higher disability-related costs. Among subgroups with thrombotic events, direct and indirect costs were higher for cases versus controls. Thrombotic events substantially increased direct costs and disability leave for patients with PV or ET compared with the full PV or ET cohorts. These findings demonstrate increased economic burden for patients with MPNs.

Mechanochemical C-H Arylation and Alkylation of Indoles Using 3 d Transition Metal and Zero-Valent Magnesium.

Although the 3 d transition-metal catalyzed C-H functionalization have been extensively employed to promote the formation of valuable carbon-carbon bonds, the persistent problems, including the use of sensitive Grignard reagents and the rigorous operations (solvent-drying, inert gas protection, metal pre-activation and RMgX addition rate control), still leave great room for further development of sustainable methodologies. Herein, we report a mechanochemical technology toward in-situ preparation of highly sensitive organomagnesium reagents, and thus building two general 3 d transition-metal catalytic platforms that enables regioselective arylation and alkylation of indoles with a wide variety of halides (including those containing post transformable functionalities and heteroaromatic rings). This mechanochemical strategy also brings unique reactivity and high step-economy in producing functionalized N-free indole products.

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL.

ABSTRACT: Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The prospective observational study of patients with polycythemia vera in US clinical practices (REVEAL) study collected prospective clinical data from 2510 patients with PV with a median follow-up of 44.7 months (range, 2-59 months) from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates), and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit level >45% (hazard ratio [HR], 1.84; 95% confidence interval [95% CI], 1.234-2.749; P = .0028) and WBCs >11 × 109/L (HR, 2.35; 95% CI, 1.598-3.465; P < .0001). Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC count >12 × 109/L was significantly associated with TE occurrence (HR, 1.95; 95% CI, 1.066-3.554; P = .0300). The results support incorporation of WBC count into PV risk stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial was registered at www.clinicaltrials.gov as #NCT02252159.

A straight-forward gene mining strategy to identify TaCIPK19 as a new regulator of drought tolerance in wheat.

Drought stress is one of the most impactful abiotic stresses to global wheat production. Therefore, identifying key regulators such as the calcineurin B-like protein interacting protein kinase (CIPK) in the signaling cascades known to coordinate developmental cues and environmental stimuli represents a useful approach to improve drought tolerance. However, functional studies have been very limited partly due to the difficulties in prioritizing candidate genes from the large TaCIPK family. To address this issue, we demonstrate a straight-forward strategy by analyzing gene expression patterns in response to phytohormones or stresses and identified TaCIPK19 as a new regulator to improve drought tolerance. The effects of TaCIPK19 on drought tolerance were evaluated in both tobacco and wheat through transgenic approach. Ectopic expression of TaCIPK19 in tobacco greatly improves drought tolerance with enhanced ABA biosynthesis/signaling and ROS scavenging capacity. TaCIPK19 overexpression in wheat also confers the drought tolerance at both seedling and mature stages with enhanced ROS scavenging capacity. Additionally, potential CBL partners interacting with TaCIPK19 were investigated. Collectively, our finding exemplifies a straight-forward approach to facilitate reverse genetics related to abiotic stress improvement and demonstrates TaCIPK19 as a new candidate gene to improve ROS scavenging capacity and drought tolerance, which is useful for genetic improvement and breeding application in wheat.

Interference Effects of Commercial Persistent Luminescence Materials on Rice Germination and Seedling Growth.

Persistent luminescence materials (PLMs) are widely used across a multitude of fields due to their distinct optical properties. However, like other micron-sized materials such as microplastics, the production and recycling processes of PLMs can lead to their accumulation in soil and water, potentially posing detrimental effects on plant growth and development. In this study, we investigated the impact of commercially available blue PLM (bPLM), green PLM (gPLM), and red PLM (rPLM) on germination, seedling growth, and oxidative stress responses in rice. Our findings demonstrate that the morphology and size of PLMs do not significantly differ in their effects on rice growth. All three types of PLMs significantly inhibited root length and stem length, disrupted root cell structures, and decreased seedling biomass. Interestingly, gPLM and bPLM were found to stimulate the synthesis of osmolytes and chlorophyll in rice, while rPLM had the opposite effect. Changes in the antioxidant enzyme system in rice clearly indicated that the three types of PLMs induced reactive oxygen species (ROS) damage in rice. This study enhances our understanding of the potential environmental impacts of PLMs, offering valuable insights for the safe and responsible use of these materials in various applications.

Ruxolitinib for myelofibrosis in elderly non-transplant patients: healthcare resource utilization and costs.

AIM: This study evaluated real-world healthcare resource utilization (HCRU), direct costs, and overall survival (OS) of patients who were Medicare beneficiaries and were newly diagnosed with myelofibrosis (MF) who filled ≥1 prescription of ruxolitinib versus those who did not. PATIENTS AND METHODS: This was a study of the US Medicare fee-for-service database. Beneficiaries were aged ≥65 years with an MF diagnosis (index) between January 1, 2012 - December 31, 2017. Data were summarized descriptively. OS was estimated using Kaplan-Meier analysis. RESULTS: Patients with ≥1 prescription fill of ruxolitinib (n = 2,787) had lower mean rates (per patient per month [PPPM]) versus patients who did not fill a prescription for ruxolitinib (n = 7,262) for hospitalizations (0.16 vs 0.32), length of inpatient stay (0.16 vs 2.44 days), emergency department visits (0.10 vs 0.14), physician office visits (4.68 vs 6.25), skilled nursing facility stays (0.02 vs 0.12), home health/durable medical equipment services (0.32 vs 0.47), and hospice visits (0.30 vs 1.70). Monthly medical costs were numerically lower in patients who had ≥1 fill of ruxolitinib versus those who did not fill a prescription for ruxolitinib ($6,553 vs $12,929), largely driven by inpatient costs ($3,428 vs $6,689). Pharmacy costs were $10,065 and $987 in patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively; total PPPM all-cause healthcare costs were $16,618 and $13,916, respectively. The median OS was 37.5 and 18.7 months for the cohorts of patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively (hazard ratio = 0.63, 95% CI = 0.59 - 0.67). CONCLUSIONS: Ruxolitinib is associated with reduced HCRU and direct costs of medical care in addition to increased survival, suggesting it to be a cost-effective advance for patients with MF.

Myelofibrosis is a rare bone marrow cancer. People with this disease do not live as long as the general population. They have difficult symptoms, can tire easily, and may have a large spleen that can be uncomfortable. Ruxolitinib is a treatment for myelofibrosis that can improve symptoms and help patients live longer.This study asked how treating patients with ruxolitinib affected three things. (1) How often do they go to a healthcare provider? (2) How much do they spend on their healthcare? (3) How long do they live? The authors looked at Medicare records to answer these questions.The study found that treated patients visited hospitals, doctors' offices, and other services less often. When they did require hospital care, they stayed in the hospital for a shorter amount of time. As a result, treated patients spent about half as much on these services. However, patients treated with ruxolitinib spent more at the pharmacy. Finally, treated patients lived about twice as long as those who were never treated with ruxolitinib. These findings suggest that ruxolitinib is worthwhile for patients with myelofibrosis.

Impact of Chronic Graft-versus-Host Disease on Patient Employment, Income, and Informal Caregiver Burden: Findings From the Living With Chronic GVHD Patient Survey.

The development of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) results in impaired physical function and quality of life. However, limited data exist regarding the employment and financial impact on patients and caregivers. The objective of this study was to examine the impact of chronic GVHD on patient employment, disability leave, income, reliance on caregivers, and effects on caregiver employment. The Living With Chronic GVHD Patient Survey was a cross-sectional online survey administered from May to August 2020 in the United States to adult HSCT survivors diagnosed with chronic GVHD within the past 5 years. Data on respondent demographics and disease characteristics and the effects of chronic GVHD on employment, income, and need for caregiver assistance were collected. Respondents also were asked to report on the impact of their chronic GVHD on their caregivers' employment. All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. A total of 165 respondents completed the survey (median age, 57.0 years; 63.6% women; 83.0% white). The respondents had been experiencing chronic GVHD for a median of 4.5 years (range, .1 to 36.7 years), with a median of .5 years (range, 0 to 3.6 years) from the most recent transplantation to chronic GVHD diagnosis. Among those employed full- or part-time at the time of their most recent transplantation (n = 80), 61.3% reported taking disability leave, 58.8% worked reduced hours, 27.5% took a less demanding job, and 33.8% left a job because of chronic GVHD. Additionally, 71.3% believed they had lost income due to chronic GVHD. Among all respondents, 72.1% reported receiving regular caregiver assistance. Respondents commonly reported employment changes among unpaid caregivers; 34.5% reduced their working hours, and 16.6% left a job). HSCT survivors who develop chronic GVHD are vulnerable to employment changes and financial hardship. This analysis highlights the need for effective therapies and improved symptom management to reduce the multifaceted burden of chronic GVHD on patients and their caregivers and ultimately improve long-term HSCT outcomes.

C-4 Regioselective Alkylation of Pyridines Driven by Mechanochemically Activated Magnesium Metal.

Mechanochemically activated magnesium(0) metal as a highly active mediator driving direct C-4-H alkylation of pyridines with alkyl halides has been developed. Excellent regioselectivity and substrate scope, including those containing reducible functionalities, free amines, and alcohols, as well as biologically relevant molecules were achieved to access 4-alkylpyridine products. Preliminary mechanistic studies suggested a radical-radical coupling pathway.

Overexpression of CASC19 contributes to tumor progression and predicts poor prognosis after radical resection in hepatocellular carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated as functional molecules in hepatocellular carcinoma (HCC) progression. The present research aimed to investigate the levels of LncRNA cancer susceptibility candidate gene 19 (CASC19) in HCC tissues and cell lines and to explore its potential role in the diagnosis and prognosis of HCC. METHODS: HCC tissues and cell lines were collected to assess the levels of CASC19 by real-time quantitative reverse transcription PCR (RT-qPCR). The prognostic value of CASC19 was evaluated using the Kaplan-Meier method and Cox regression analysis. The functional role of CASC19 in regulating HCC cell proliferation, migration, and invasion was evaluated by Cell Counting Kit-8 (CCK-8) and Transwell analysis. The potential targeted miR-140-5p of CASC19 was confirmed by a dual-luciferase reporter assay. RESULTS: High CASC19 expression positively correlated with tumor size, differentiation, and TNM stage in HCC patients (P < 0.05). Patients with high CASC19 expression have a poorer survival prognosis and are prone to relapse compared to those with low CASC19. miR-140-5p, a target miRNA for CASC19, negatively correlated with CASC19 levels in tumor tissues. Reduced CASC19 levels attenuated cell proliferation, migration, and invasion, but this attenuation was reversed by suppression of miR-140-5p. CONCLUSION: Up-regulated CASC19 may serve as a biomarker for predicting poor prognosis in HCC patients. In vitro, overexpressed CASC19 promoted the progression of HCC, indicating that CASC19 may be a possible therapeutic target for the treatment of HCC.

Trends in overall mortality among US veterans with primary myelofibrosis.

BACKGROUND: Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. METHODS: This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007-12/31/2010) and post-ruxolitinib approval (01/01/2015-09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 109/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. RESULTS: The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2-2.6] years vs not reached [3.4-not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37-0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. CONCLUSIONS: Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period.

Patient-reported symptom burden and impact on daily activities in chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) treatment for hematologic malignancies. There are limited patient-reported data concerning symptom burden and effects on activities of daily living (ADL). METHODS: The cross-sectional Living With Chronic GVHD Patient Survey was administered online in the United States (May-August 2020) to participants aged ≥18 years who underwent allogeneic HSCT, were diagnosed with chronic GVHD by a healthcare provider, and self-reported active chronic GVHD (within past 5 years). Information on patient demographics, disease characteristics, symptom burden, and ability to perform ADL was collected. Symptom burden was assessed using the validated Lee Symptom Scale (range from 0-100 with higher scores indicating greater burden). All data were summarized using descriptive statistics; no formal statistical comparisons were conducted. RESULTS: Out of 580 participants who entered the survey screener, 165 participants (28.4%) across 33 states fulfilled all study eligibility criteria, completed the entire survey, and were included (age: mean [SD], 53.7 (13.8) years; median [range], 57.0 [18-78] years; female, n = 105 [63.6%]; White, n = 137 [83.0%]). Respondents described their chronic GVHD severity primarily as moderate (n = 54 [32.7%]) or severe (n = 102 [61.8%]) at the time when symptoms were at their worst. One-third of respondents (33.9%) indicated that their chronic GVHD symptoms were at their worst for ≥1 year in duration. Mean (SD; range) Lee Symptom Scale score was 44.8 (19.4; 2-100); 44% of respondents considered "dry eye" the most burdensome symptom. Almost half of respondents (n = 73 [44.2%]) rated their overall quality of life (QoL) as poor. Participants reported a detrimental impact of symptoms on ADL, including basic activities (eg, eating, personal hygiene, dressing). CONCLUSIONS: Survey respondents self-reported high chronic GVHD symptom burden and felt that their symptoms severely interfered with physical function and ADL. Effective strategies to mitigate chronic GVHD symptoms are needed to improve QoL among HSCT survivors.

A Retrospective Chart Review of 809 Patients with Physician-Diagnosed Essential Thrombocythemia Receiving Cytoreductive Therapy in US Community Oncology Practices.

INTRODUCTION: This analysis reports demographic and clinical characteristics of patients with physician-diagnosed essential thrombocythemia (ET) receiving cytoreductive therapy in US community clinical practice. METHODS: Patient characteristics, medical history, diagnostic test results, signs/symptoms, treatment patterns, and physician practice settings were extracted from medical charts for patients with physician-diagnosed ET receiving cytoreductive therapy. RESULTS: Among 809 patients (51.1% female; 75.4% White; median age, 69 years) from 50 community practices, 64.5% had physician-reported diagnosis per World Health Organization criteria. Only 48.8% underwent diagnostic bone marrow biopsies; 87.5% had JAK2 mutation testing. Among those tested, 512/708 (72.3%), 57/213 (26.8%), and 37/213 (17.4%) had JAK2, CALR, and MPLmutations, respectively. Of physician-assigned risk assessments, 41.8% were misclassifications based on data-derived risk assessment. Most patients (93.3%) received first-line hydroxyurea (HU) cytoreductive therapy. Discontinuations were primarily for intolerance (35.4%) and resistance (23.8%). Of those who discontinued, 65.9% received no subsequent therapy and had higher ET symptom rates at last visit versus patients continuing HU (48.8% vs. 25.0%). CONCLUSION: This study shows notable gaps in ET diagnosis and management. Half of patients were diagnosed without bone marrow biopsy, many received incorrect risk assignment, and the majority who discontinued HU received no subsequent therapy despite continued need.

The ryanodine receptor mutational characteristics and its indication for cancer prognosis.

Ca2+ signaling is altered substantially in many cancers. The ryanodine receptors (RYRs) are among the key ion channels in Ca2+ signaling. This study aimed to establish the mutational profile of RYR in cancers and investigate the correlation between RYR alterations and cancer phenotypes. The somatic mutation and clinical data of 11,000 cancer patients across 33 cancer types was downloaded from The Cancer Genome Atlas (TCGA) database. Subsequent data processing was performed with corresponding packages of the R software. Mutational profile was analyzed and its correlation with tumor mutational burden (TMB), patient prognosis, age and smoking status was analyzed and compared. All three RYR isoforms exhibited random mutational distribution without hotspot mutations when all cancers were analyzed together. The number of mutations in RYR2 (2388 mutations) far overweight that of RYR1 (1439 mutations) and RYR3 (1573 mutations). Linear correlation was observed between cumulative TMB and cumulative number of mutations for all RYR isoforms. Patients with RYR mutations exhibited significantly higher TMB than those without RYR mutations for most cancer types. Strong correlation was also revealed in the average number of mutations per person between pairs of RYR isoforms. No stratification of patient overall survival (OS) by mutational status was found for all three RYR isoforms when all cancers were analyzed together, however, significant stratification of OS by RYR mutations was revealed in several individual cancers, most strikingly in LUAD (P = 0.0067, RYR1), BLCA (P = 0.00071, RYR2), LUSC (P = 0.036, RYR2) and KIRC (P = 0.0042, RYR3). Furthermore, RYR mutations were correlated with higher age, higher smoking history grading and higher number of pack years. Characteristic mutation profile of RYRs in cancers has been revealed for the first time. RYR mutations were correlated with TMB, age, smoking status and capable of stratifying the prognosis of patients in several cancer types.

Disease progression, treatments, hospitalization, and clinical outcomes in acute GVHD: a multicenter chart review.

Acute graft-versus-host disease (GVHD) remains a barrier to successful allogeneic hematopoietic cell transplantation (HCT) outcomes. This multicenter, retrospective chart review describes disease progression, treatment patterns, hospitalizations, and clinical outcomes among 475 patients (≥12 years old) who developed grades II-IV acute GVHD after their first HCT (January 2014-June 2016). Median (interquartile range) age at HCT was 55 (44-63) years. From the date of acute GVHD diagnosis, 190 patients (40.0%) experienced progression to more severe disease and/or developed new organ involvement. Among 431 patients with grades II-IV acute GVHD at diagnosis, 73.1% received first-line systemic corticosteroids. During follow-up (median 524 days since acute GVHD diagnosis), 23.4% of patients had an increase in steroid dose and 44.4% were unable to taper below 10 mg/day. Over half of patients (54.9%) required ≥1 hospital readmission within 100 days post-HCT (≥2 readmissions in 22.3%); mean inpatient length of stay upon readmission was 27.5 days. Approximately half of patients (52.8%) died during follow-up; 1-year overall mortality from date of acute GVHD diagnosis and nonrelapse mortality rates were 35.2% and 25.5%, respectively. Overall, patients who developed acute GVHD following HCT had poor clinical outcomes, highlighting the unmet need for early and effective treatment strategies.

Disease progression, hospital readmissions, and clinical outcomes for patients with steroid-refractory acute graft-versus-host disease: A multicenter, retrospective study.

Acute graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). This analysis of 168 patients (mean age, 54.8 years) from a multicenter, retrospective chart review describes the clinical course, treatment patterns, hospitalizations, and clinical outcomes of patients aged ≥12 years who developed grades II-IV acute GVHD after their first allogeneic HCT (January 1, 2014, to June 30, 2016) and were refractory to or dependent on corticosteroids. Between diagnosis and maximum grade (median, 6.0 days), 53.6% of patients had new organ involvement, particularly lower gastrointestinal tract acute GVHD, or an increase in acute GVHD grade. Eighty-nine patients (53.0%) received additional systemic GVHD therapy (after systemic corticosteroids) within a median of 21.0 days. Hospital readmission(s) was required for 56.5% of patients within 100 days post-HCT (mean inpatient length of readmission stay, 49.5 days); 24.4% had ≥2 readmissions within 100 days post-HCT. From the date of acute GVHD diagnosis, 70.2% of patients died at a median (interquartile range) of 117.5 (49-258) days. In summary, steroid-refractory and steroid-dependent acute GVHD is associated with a rapidly worsening clinical course that leads to high readmission and mortality rates, emphasizing the need for effective and tolerable therapies.

Healthcare Resource Utilization and Costs of Steroid-Associated Complications in Patients With Graft-Versus-Host Disease.

Acute and chronic graft-versus-host disease (aGVHD/cGVHD) are serious conditions occurring after allogeneic hematopoietic cell transplantation (HCT). Steroids are the most common first-line therapy; however, they are frequently associated with numerous morbid complications. To describe the healthcare resource utilization (HCRU) and costs of steroid-related complications in patients receiving systemic steroids for GVHD. This retrospective study used medical and pharmacy claims from the Optum Research database. Eligible patients were diagnosed with GVHD (aGVHD, cGVHD, or both) after HCT and were treated with systemic steroids between July 1, 2010, and August 31, 2019. The index date was the date of the first claim for systemic steroids after GVHD diagnosis. The baseline period was the 6 months before the index date, and the follow-up period was 2 years after the index date. Outcome variables included HCRU and costs associated with steroid complications, grouped into 4 categories: bone/muscle, gastrointestinal, infection, and metabolic/endocrine. A multivariate analysis was used to assess the cost ratio associated with the presence of each steroid complication; the linear model was adjusted for baseline patient characteristics and types of steroid conditions identified during follow-up. Another multivariate analysis assessed the hazard ratio for hospitalization associated with each steroid complication using a Cox proportional hazards regression model adjusted for the time-varying presence of each complication category. A total of 689 patients were studied (median age, 55 years; male, 60%); 22% had aGVHD only, 21% had cGVHD only, and 39% had both types of GVHD. After 2 years of follow-up, 97% had at least 1 steroid-associated complication. The most common complication category was infection (79.5%), followed by metabolic/endocrine (32.4%), gastrointestinal (29.2%), and bone/muscle conditions (19.7%). About two thirds (66%) of patients with any steroid complication had ≥1 hospitalization requiring a median (interquartile range [IQR]) of 20 (8-43) hospital days. Patients with an infection experienced the highest hospitalization rate (72%) and thus the highest associated costs. The total mean (median [IQR]) healthcare cost potentially related to steroid complications was $164,787 ($50,834 [$8865-$182,693]), and the largest expense was hospitalization (mean [median {IQR}], $140,637 [$26,782 {$0-$141,398}]). Of the different steroid complications, infections were associated with the highest cost (mean [median {IQR}], $167,473 [$57,680 {$16,261-$178,698}]). In addition, a significantly higher total adjusted cost was associated with the presence of an infection, gastrointestinal complication, or bone/muscle complication in patients with GVHD versus the absence of each complication (all P < .001). Complications occurring after steroid treatment for GVHD may add substantially to the HCRU and costs associated with GVHD management. Infections in particular required inpatient care and were associated with the highest economic burden.

Thrombotic events and mortality risk in patients with newly diagnosed polycythemia vera or essential thrombocythemia.

Patients with polycythemia vera (PV) and essential thrombocythemia (ET) have increased thrombotic risk. This retrospective, real-world analysis of Medicare patients (age ≥ 65 years) newly diagnosed with high-risk PV or intermediate-/high-risk ET compared mortality risk among those with versus without thrombotic events during the study period. Patients diagnosed with PV or ET with ≥ 1 inpatient or ≥ 2 outpatient claims (January 1, 2010-December 31, 2017; index was date of first qualifying claim) were included. The study included 50,405 Medicare beneficiaries with PV and 124,569 with ET. During follow-up (median [range]: PV, 34.5 [0-97.3] months; ET, 25.5 [0-97.4] months), 14,334 patients (28.4%) with PV and 30,478 (24.5%) with ET experienced thrombotic events (most commonly ischemic stroke [PV, 46.0%; ET, 42.5%]. Mortality risk was increased for patients with versus without post-index thrombosis for both PV (adjusted hazard ratio [aHR; 95% CI], 18.6 [16.1-21.6]; P < 0.001) and ET (aHR [95% CI], 25.2 [23.1-27.5]; P < 0.001). Median survival was shorter for patients who experienced a thrombotic event ≤ 1 year post-index versus those who did not (PV, 5.1 years vs not reached; ET, 3.7 vs 6.7 years; both P < 0.001). These findings highlight the importance of thrombosis risk mitigation in PV and ET management.