Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

BACKGROUND: Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM: To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS: A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS: Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION: In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

Influence of physical exercise on negative emotions in college students: chain mediating role of sleep quality and self-rated health.

Background: Negative emotions in college students are a significant factor affecting mental health, with suicide behaviors caused by negative emotions showing an annual increasing trend. Existing studies suggest that physical exercise is essential to alleviate negative feelings, yet the intrinsic mechanisms by which it affects negative emotions have not been fully revealed. Objective: Negative emotions in college students represent a significant issue affecting mental health. This study investigates the relationship between physical exercise and negative emotions among college students, incorporating sleep quality and self-rated health (SRH) as mediators to analyze the pathway mechanism of how physical exercise affects students' negative emotions. Methods: A cross-sectional study design was utilized, employing online questionnaires for investigation. The scales included the Physical Activity Rating Scale-3 (PARS-3), the Depression Anxiety Stress Scales-21 (DASS-21), the Pittsburgh Sleep Quality Index (PSQI), and the 12-Item Short Form Health Survey (SF-12), resulting in the collection of 30,475 valid questionnaires, with a validity rate of 91%. Chain mediation tests and Bootstrap methods were applied for effect analysis. Results: The proportions of university students engaged in low, medium, and high levels of physical exercise were 77.6, 13.1, and 9.3%, respectively. The proportions of students experiencing "very severe" levels of stress, anxiety, and depression were 4.5, 10.9, and 3.6%, respectively. Physical exercise was significantly positively correlated with self-rated health (r = 0.194, p < 0.01), significantly negatively correlated with sleep quality (r = -0.035, p < 0.01), and significantly negatively correlated with stress, anxiety, and depression (r = -0.03, p < 0.01; r = -0.058, p < 0.01; r = -0.055, p < 0.01). Sleep quality was significantly negatively correlated with self-rated health (r = -0.242, p < 0.01). Mediation effect testing indicated that sleep quality and self-rated health partially mediated the relationship between physical exercise and negative emotions, with total effect, total direct effect, and total indirect effect values of -1.702, -0.426, and - 1.277, respectively. Conclusion: College students primarily engage in low-intensity physical activity. Sleep quality and self-rated health mediate the impact of physical exercise on students' negative emotions. A certain level of physical activity can directly affect students' emotional states and indirectly influence their negative emotions via sleep and self-rated health. Regular engagement in physical activities primarily positively impacts emotional states by enhancing mood stability and overall emotional resilience.

Genetic architecture of ecological divergence between Oryza rufipogon and Oryza nivara.

Ecological divergence due to habitat difference plays a prominent role in the formation of new species, but the genetic architecture during ecological speciation and the mechanism underlying phenotypic divergence remain less understood. Two wild ancestors of rice (Oryza rufipogon and Oryza nivara) are a progenitor-derivative species pair with ecological divergence and provide a unique system for studying ecological adaptation/speciation. Here, we constructed a high-resolution linkage map and conducted a quantitative trait locus (QTL) analysis of 19 phenotypic traits using an F2 population generated from a cross between the two Oryza species. We identified 113 QTLs associated with interspecific divergence of 16 quantitative traits, with effect sizes ranging from 1.61% to 34.1% in terms of the percentage of variation explained (PVE). The distribution of effect sizes of QTLs followed a negative exponential, suggesting that a few genes of large effect and many genes of small effect were responsible for the phenotypic divergence. We observed 18 clusters of QTLs (QTL hotspots) on 11 chromosomes, significantly more than that expected by chance, demonstrating the importance of coinheritance of loci/genes in ecological adaptation/speciation. Analysis of effect direction and v-test statistics revealed that interspecific differentiation of most traits was driven by divergent natural selection, supporting the argument that ecological adaptation/speciation would proceed rapidly under coordinated selection on multiple traits. Our findings provide new insights into the understanding of genetic architecture of ecological adaptation and speciation in plants and help effective manipulation of specific genes or gene cluster in rice breeding.

Underlying Mechanisms of the Hedgehog-Like Panicle and Filamentous Leaf Tissue Symptoms Caused by Sclerospora graminicola in Foxtail Millet.

Downy mildew caused by Sclerospora graminicola is a systemic infectious disease affecting foxtail millet production in Africa and Asia. S. graminicola-infected leaves could be decomposed to a state where only the veins remain, resulting in a filamentous leaf tissue symptom. The aim of the present study was to investigate how S. graminicola influences the formation of the filamentous leaf tissue symptoms in hosts at the morphological and molecular levels. We discovered that vegetative hyphae expanded rapidly, with high biomass accumulated at the early stages of S. graminicola infection. In addition, S. graminicola could affect spikelet morphological development at the panicle branch differentiation stage to the pistil and stamen differentiation stage by interfering with hormones and nutrient metabolism in the host, resulting in hedgehog-like panicle symptoms. S. graminicola could acquire high amounts of nutrients from host tissues through secretion of ß-glucosidase, endoglucanase, and pectic enzyme, and destroyed host mesophyll cells by mechanical pressure caused by rapid expansion of hyphae. At the later stages, S. graminicola could rapidly complete sexual reproduction through tryptophan, fatty acid, starch, and sucrose metabolism and subsequently produce numerous oospores. Oospore proliferation and development further damage host leaves via mechanical pressure, resulting in a large number of degraded and extinct mesophyll cells and, subsequently, malformed leaves with only veins left, that is, "filamentous leaf tissue." Our study revealed the S. graminicola expansion characteristics from its asexual to sexual development stages, and the potential mechanisms via which the destructive effects of S. graminicola on hosts occur at different growth stages.

Effect of Ursodeoxycholic Acid on Preventing SARS-CoV-2 Infection in Patients With Liver Transplantation: a multicenter retrospective cohort study.

BACKGROUND: Immunosuppressed recipients of liver transplantation (LT) are more likely to develop coronavirus disease 2019 (COVID-19) and may have an increased risk of developing worse outcomes. AIM: To assess the effect of ursodeoxycholic acid (UDCA) on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. DESIGN: Adult patients (aged ≥ 18 years) who underwent LT between January 1st, 2015, and December 31st, 2022, were included and categorized into two groups according to their use of UDCA. METHODS: The prevalence and severity of COVID-19 among transplantation patients between the UDCA and non-UDCA groups were estimated and compared. RESULTS: Among the 897 LT patients who met the inclusion criteria, infection rate of SARS-CoV-2 was 78.4%, and the rate of severe illness was 5.1% from January 2022 to January 2023 in China. In the multivariate analysis, only UDCA treatment (P = 0.006) was found to be a protective factor against SARS-CoV-2 infection. After propensity score matching, the SARS-CoV-2 infection rate in the UDCA group was lower than that in the non-UDCA group (74.1% vs. 84.6%, P = 0.002). This rate was further reduced to 62.1% (P = 0.002) when the oral administration dose was greater than 15 mg/kg/d. There was no difference in the rates of severe COVID-19 illness, ICU admission, or ventilation rate or length of hospital stay with or without UDCA treatment (all P > 0.05). CONCLUSIONS: The use of UDCA in LT patients significantly reduced the SARS-CoV-2 infection rate and showed a dose-dependent protective effect.

Genome and Transcriptome Analysis to Elucidate the Biocontrol Mechanism of Bacillus amyloliquefaciens XJ5 against Alternaria solani.

Early blight, caused by Alternaria solani, is an important disease affecting tomatoes. Biological control offers an environmentally friendly approach to controlling pathogens. Herein, we identified a B. amyloliquefaciens strain XJ5 and investigated its biocontrol mechanism against A. solani. A. solani growth was significantly inhibited by XJ5, with the inhibition rate of cell-free culture supernatants reaching 82.3%. Furthermore, XJ5 crude protein extracts inhibited conidia germination and altered the mycelial morphology of A. solani. To uncover the potential biocontrol mechanism of XJ5, we analyzed its genome sequence and transcriptome. The genome of XJ5 comprised a 4.16 Mb circular chromosome and two circular plasmids. A total of 13 biosynthetic gene clusters and 127 genes encoding hydrolases were identified, suggestive of the ability of XJ5 to secrete antagonistic secondary metabolites and hydrolases. Transcript analysis revealed 174 differentially expressed genes on exposing A. solani to XJ5 crude protein extracts. The expression of genes related to chitin and mannose synthesis was downregulated, indicating that XJ5 metabolites may impact chitin and mannose synthesis in A. solani. Overall, these findings enhance our understanding of the interactions between B. amyloliquefaciens and phytopathogens and pave the way for the agricultural application of this promising biocontrol agent.

Multiple domestications of Asian rice.

The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.

Molecular characterization of a novel ambiguivirus isolated from the phytopathogenic fungus Setosphaeria turcica.

In this study, a novel single-stranded RNA virus was isolated from the plant-pathogenic fungus Setosphaeria turcica strain TG2, and the virus was named "Setosphaeria turcica ambiguivirus 2" (StAV2). The complete nucleotide sequence of the StAV2 genome was determined using RT-PCR and RLM-RACE. The StAV2 genome comprises 3,000 nucleotides with a G+C content of 57.77%. StAV2 contains two in-frame open reading frames (ORFs) with the potential to produce an ORF1-ORF2 fusion protein via a stop codon readthrough mechanism. ORF1 encodes a hypothetical protein (HP) of unknown function. The ORF2-encoded protein shows a high degree of sequence similarity to the RNA-dependent RNA polymerases (RdRps) of ambiguiviruses. BLASTp searches showed that the StAV2 HP and RdRp share the highest amino acid sequence identity (46.38% and 69.23%, respectively) with the corresponding proteins of a virus identified as "Riboviria sp." isolated from a soil sample. Multiple sequence alignments and phylogenetic analysis based on the amino acid sequences of the RdRp revealed that StAV2 is a new member of the proposed family "Ambiguiviridae".

Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study.

BACKGROUND AND AIM: Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. METHODS: Insurance claims data (11/2016-6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). RESULTS: In all cohorts (mean age 51-53 years; 67-70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53-68% (p < .001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p < .001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p < .001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. CONCLUSION: Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation.

Benralizumab is a biologic approved as an add-on treatment for severe eosinophilic asthma. Previous real-world studies and clinical trials have shown that benralizumab can reduce the rate of asthma exacerbations and systemic corticosteroid use. However, there is little information on the economic value of benralizumab in real-world patient populations. This study showed that patients with severe asthma in the United States had lower rates of asthma exacerbations after starting treatment with benralizumab. The patients also had fewer asthma exacerbation-related hospitalizations, emergency department visits, and outpatient visits as well as lower medical costs related to asthma exacerbations compared with before the treatment. These benefits were observed in patients who had never taken and those who had been previously treated with biologic therapies, and for up to 24 months after starting benralizumab treatment. These results show that the clinical value of benralizumab translates into reduced medical utilization for patients with severe asthma.

Real-world effectiveness of omadacycline and impact of unapproved omadacycline prescription claims among adult outpatients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections.

BACKGROUND: Omadacycline is an amino-methylcycline antibiotic that is indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Like many new antibiotics, there are scant real-world effectiveness data for omadacycline. There is also a high potential that an omadacycline prescription is rejected or reversed, and it is not known whether patients who have an unapproved omadacycline claim are at higher risk for 30-day emergency department (ED)/inpatient (IP) visits. OBJECTIVE: To describe the real-world effectiveness of omadacycline and assess the impact of unapproved omadacycline claims among adult outpatients with CABP or ABSSSIs. METHODS: The study population included patients who received 1 or more omadacycline outpatient prescriptions from a large US claims database (October 2018 to September 2020) and had a diagnosis for CABP or ABSSSI. The approval status of omadacycline claims was determined. The proportion of all-cause 30-day ED/IP visits among patients with an approved vs unapproved claim was compared. RESULTS: 404 patients met the inclusion criteria (CABP: 97; ABSSSI: 307). Of the 404 patients, 146 (36%) had an unapproved claim (CABP: 28; ABSSSI: 118). Overall, the proportion of 30-day ED/IP visits (yes/no) for those with an unapproved and approved claim was 28% vs 17%, respectively (P < 0.05). The overall adjusted 30-day ED/IP visits incidence difference was 11% (95% CI = 2 - 19), corresponding to an adjusted number needed to treat of 9 (95% CI = 5 - 43). CONCLUSIONS: A high incidence (36%) of unapproved omadacydine claims was observed in this study. Patients with unapproved daims had an 11% higher incidence of 30-day all-cause ED/IP visits than patients with approved claims. DISCLOSURES This study was funded by Paratek Pharmaceuticals, Inc (King of Prussia, PA). Dr Lodise is a consultant to Paratek Pharmaceuticals, Inc, and has received consultancy payments. Drs Gunter, Sandor, and Berman are employees and shareholders of Paratek Pharmaceuticals, Inc. Dr Mu, Ms Gao, Ms Yang, and Ms Yim are employees of Analysis Group. Analysis Group has received payment from Paratek Pharmaceuticals, Inc, to conduct part of this study.

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2.

BACKGROUND: Benralizumab is an mAb therapy for severe eosinophilic asthma. Real-world data on its clinical impact in various patient populations such as patients with varying eosinophil levels, previous biologic use, and extended follow-up in the United States are limited. OBJECTIVE: To determine the effectiveness of benralizumab in different asthmatic patient cohorts and its long-term clinical impact. METHODS: Patients with asthma treated with benralizumab from November 2017 to June 2019 with 2 or more exacerbations in the 12 months before benralizumab initiation (index) were included in this pre-post cohort study that used medical, laboratory, and pharmacy US insurance claims. Asthma exacerbation rates in the 12 months pre and post index were compared. Nonmutually exclusive patient cohorts were defined by blood eosinophil counts (<150, ≥150, 150-<300, <300, and ≥300 cells/µL), a switch from another biologic, or follow-up for 18 or 24 months post index. RESULTS: There were 429 patients in the eosinophil cohort, 349 in the biologic-experienced cohort, and 419 in the extended follow-up cohort. In all eosinophil cohort subgroups, the asthma exacerbation rate decreased from 3.10-3.55 per patient-year (PPY) pre index to 1.11-1.72 PPY post index (52%-64% decrease; P < .001). Similar decreases were observed in patients switching from omalizumab (3.25 to 1.25 PPY [62%]) or mepolizumab (3.81 to 1.78 PPY [53%]) to benralizumab and those followed up for 18 months (3.38 to 1.18 PPY [65%]) or 24 months (3.38 to 1.08 PPY [68%]) (all P < .001). In the extended follow-up cohort, 39% and 49% had no exacerbations in the 0 to 12 months and the 12 to 24 months post index, respectively. CONCLUSIONS: Benralizumab achieved significantly improved asthma control in real-world patients with different blood eosinophil counts, including eosinophil counts ranging from less than 150 to greater than or equal to 300 cells/µL, switching from other biologics, or treated for up to 24 months.

Real-World Modifications of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Hyperkalemia Initiating Sodium Zirconium Cyclosilicate Therapy: The OPTIMIZE I Study.

INTRODUCTION: Hyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK. METHODS: Adults (≥ 18 years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes. RESULTS: A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0 years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up = 8.1 months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p < 0.05) and fewer prior emergency department (ED) visits (0.78 [0.63-0.96]; p < 0.05). CONCLUSION: Consistent with clinical trial findings, nearly 80% of patients who initiated SZC for HK optimized their RAASi therapy. Patients may require long-term SZC therapy to encourage continuation of RAASi therapy especially after inpatient and ED visits.

Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in Nurses' Health Study II.

Few studies have assessed the association between endogenous steroid hormone levels and a subsequent diagnosis of endometriosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically confirmed endometriosis in a nested case-control study within Nurses' Health Study II. Between blood collection (1996-1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RRs) and 95% confidence intervals (CIs). Women with greater early follicular-phase total or free estradiol levels had a nonlinear increased risk of endometriosis (early follicular total estradiol: second quartile vs. first, RR = 2.23 (95% CI: 1.44, 3.47); third quartile, RR = 1.83 (95% CI: 1.16, 2.88); fourth quartile, RR = 1.68 (95% CI: 1.05, 2.68); early follicular free estradiol: second quartile vs. first, RR = 1.63 (95% CI: 1.05, 2.54); third quartile, RR = 2.02 (95% CI: 1.31, 3.12); fourth quartile, RR = 1.04 (95% CI: 0.66, 1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed, with a positive association among women in the top 2% of free testosterone levels. Levels of mid-luteal-phase total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects.

Impact on hospitalizations of long-term versus short-term therapy with sodium zirconium cyclosilicate during routine outpatient care of patients with hyperkalemia: the recognize I study.

BACKGROUND: Hyperkalemia is associated with increased healthcare resource utilization (HRU). This study evaluated the impact of sodium zirconium cyclosilicate (SZC) use on HRU in outpatients with hyperkalemia. RESEARCH DESIGN AND METHODS: A retrospective noncomparative study using claims data from the HealthVerity warehouse, which included outpatients in the United States who initiated SZC between January and December 2019 (index date) with ≥6 months' continuous coverage before (baseline) and after (follow-up) the index date (total coverage of 12 months). The study aimed to describe HRU with long-term and short-term SZC (defined as >90 and ≤90 days' supply, respectively, during 180 days' follow-up) and identify characteristics associated with long-term versus short-term therapy. RESULTS: Of 1153 patients, 748 (64.9%) received short-term and 405 (35.1%) received long-term therapy. During follow-up, lower proportions of patients on long-term versus short-term therapy had hyperkalemia-related hospitalizations (10.1% vs 15.1%; P < 0.05) and all-cause hospitalizations (22.5% vs 29.3%; P < 0.05). Hyperkalemia-related and all-cause hospitalization proportions were 33.0% and 23.3% lower, respectively. Predictors of long-term therapy included stage 3 chronic kidney disease. CONCLUSIONS: Approximately one-third of patients with hyperkalemia received long-term SZC therapy. Hyperkalemia-related and all-cause hospitalization proportions were lower with long-term therapy, although further confirmatory studies are needed.

The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1-84): A retrospective cohort study.

OBJECTIVE: This study assessed the risk of developing chronic kidney disease (CKD) and decline in estimated glomerular filtration rate (eGFR) over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) compared with a historical control cohort of patients not treated with rhPTH(1-84). DESIGN: Retrospective cohort study of patients with chronic hypoparathyroidism treated with rhPTH(1-84) derived from the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309) and HEXT (NCT01199614, and its continuation study NCT02910466) clinical trials and a historical control cohort who did not receive PTH selected from an electronic medical record database. PATIENTS: One hundred and eighteen patients treated with rhPTH(1-84) and 497 patient controls. MEASUREMENTS: Incident CKD was defined as ≥2 eGFR measurements <60 ml/min/1.73 m2 ≥3 months apart during the study and a sustained eGFR decline of ≥30% from baseline. RESULTS: Over the 5-year period, Kaplan-Meier analyses showed that rhPTH(1-84)-treated patients had a significantly lower risk of developing CKD (log-rank p = .002) and a lower risk for a sustained eGFR decline ≥30% from baseline (log-rank p < .001) compared with patients in the control cohort. In adjusted analyses, patients in the rhPTH(1-84)-treated cohort had a 53% lower risk of developing CKD (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and a 65% lower risk for sustained eGFR decline ≥30% from baseline (HR, 0.35; 95% CI, 0.13-0.89) compared with controls. CONCLUSIONS: Patients with chronic hypoparathyroidism treated with rhPTH(1-84) in long-term clinical trials had a significantly lower risk of developing CKD compared with patients in a historical control cohort not treated with rhPTH(1-84).

Association of Calcium and Phosphate Levels with Incident Chronic Kidney Disease in Patients with Hypoparathyroidism: A Retrospective Case-Control Study.

Objective: Reasons for the increased incidence of chronic kidney disease (CKD) in patients with chronic hypoparathyroidism are poorly understood. This study evaluated associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product and the odds of CKD development in patients with chronic hypoparathyroidism. Design: A retrospective nested case-control study of adult patients with chronic hypoparathyroidism who had ≥1 prescription for calcitriol who developed CKD and matched controls who did not develop CKD were selected from the IBM® Explorys electronic medical record database. Patients. The study included a cohort of 300 patients for the albumin-corrected serum calcium analysis and 80 patients for the serum phosphate and calcium-phosphate product analyses. Measurements. We examined associations between albumin-corrected serum calcium, serum phosphate and calcium-phosphate product levels, and the risk of devloping CKD (defined as ≥2 outpatient estimated glomerular filtration values <60 mL/min/1.73 m2 occuring ≥3 months apart or ≥1 diagnostic code for CKD stages 3-5). Results: Individuals who had ≥67% of albumin-corrected serum calcium measurements outside, above, or below the study-defined range (2.00-2.25 mmol/L [8.0-9.0 mg/dL]) had 3.5-, 2.9-, and 2.7-fold higher odds of developing CKD (adjusted odds ratios [95% CI]: 3.46 [1.82-6.56], 2.85 [1.30-6.28], and 2.68 [1.16-6.15]), respectively, compared with patients who had <33% of albumin-corrected calcium measurements in those ranges. There was no association between developing CKD and having any serum phosphate measurements or any calcium-phosphate product measurements above normal population ranges. Conclusion: In adult patients with chronic hypoparathyroidism, a higher proportion of albumin-corrected calcium measurements outside of the 2.00-2.25 mmol/L (8.0-9.0 mg/dL) range was associated with higher odds of developing CKD.

Five-Year Estimated Glomerular Filtration Rate in Adults with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study.

INTRODUCTION: Chronic hypoparathyroidism is associated with higher risk of developing chronic kidney disease compared with the general population. This study evaluated changes in estimated glomerular filtration rate (eGFR) over a 5-year period in adult patients with chronic hypoparathyroidism treated with recombinant parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients who did not receive rhPTH(1-84). METHODS: This retrospective cohort study included patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309), and HEXT (NCT01199614 and continuation study NCT02910466) clinical trials. A historical control cohort who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials was selected from the IBM® Explorys electronic medical record database (January 2007-August 2019). Outcomes of interest were the annual rate of change in eGFR from baseline (i.e., eGFR slope) and the predicted eGFR change from baseline at years 1 through 5. RESULTS: The study comprised 72 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 176 control patients who did not receive rhPTH(1-84). Over 5 years, eGFR remained stable in the rhPTH(1-84) cohort, whereas eGFR declined at a rate of 1.67 mL/min/1.73 m2 per year in the control cohort (P < 0.001 for eGFR slope in the control cohort). At 5 years, predicted eGFR in the rhPTH(1-84) cohort increased from baseline by 1.21 mL/min/1.73 m2, whereas eGFR in the control cohort declined by 10.36 mL/min/1.73 m2, after adjusting for baseline variables. The difference in eGFR slopes between the cohorts over 5 years was 1.37 mL/min/1.73 m2 per year (95% CI 0.62-2.13; P < 0.001). CONCLUSION: Long-term treatment with rhPTH(1-84) was associated with stable eGFR compared with eGFR decline in the controls not treated with rhPTH(1-84). Preservation of renal function conferred by rhPTH(1-84) may benefit patients with chronic hypoparathyroidism by reducing risk of long-term renal complications.

Utilization of elderly donors in liver transplantation for patients with hepatocellular carcinoma: A national retrospective cohort study of China.

BACKGROUND: Profound organ shortages worldwide have led to the increased utilization of marginal organs from older individuals. However, the effectiveness of liver transplantation (LT) with organs from elderly donors for patients with hepatocellular carcinoma (HCC) remains controversial. The objective of the current study was to assess the overall survival (OS) and disease-free survival (DFS) of patients with HCC following LT using grafts from deceased donors over 60 years old. MATERIAL AND METHODS: Patients with HCC who underwent LT between 2015 and 2018 were identified in the China Liver Transplant Registry database. The overall survival and disease-free survival of older liver donors (OLDs) were compared with those of younger liver donors (YLDs) after propensity score matching. RESULTS: From January 2015 to December 2018, a total of 4971 HCC patients were enrolled in the study according to the screening criteria. The absolute and relative utilization of liver grafts from elderly patients over 60 years for HCC patients increased every year, from 65 (9.3%) in 2015 to 268 (14.5%) in 2018. Disease-free survival (DFS) was significantly lower in HCC patients with elderly donors (both P < 0.05) after propensity score matching. The OLD group had worse DFS than YLD group if patients had tumors beyond the Milan criteria (P < 0.05). CONCLUSIONS: The use of older donors for LT has been growing quickly in the last few years in China. Grafts from older donors can be safely used in HCC recipients with similar OS and comparable perioperative complications. However, further investigation into whether older donor has an impact on recurrence is warranted, especially among those with tumors beyond the Milan criteria.

Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study.

INTRODUCTION: Patients with chronic hypoparathyroidism are at increased risk of cardiovascular disease. This study evaluated the risk of developing cardiovascular conditions over a period of 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients not treated with rhPTH(1-84). METHODS: This retrospective cohort study comprised patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), and RACE (NCT01297309) clinical trials, and controls selected from the IBM® Explorys electronic medical record database (January 2007-August 2019) who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials. Cardiovascular outcomes were the first diagnosis of cerebrovascular, coronary artery, peripheral vascular disease, or heart failure during the study period. RESULTS: We evaluated 113 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 618 control patients who did not receive rhPTH(1-84). Over the 5-year follow-up period, 3.5% of patients (n = 4) in the rhPTH(1-84) cohort had a cardiovascular event compared with 16.3% (n = 101) in the control cohort. Kaplan-Meier analysis demonstrated that patients in the rhPTH(1-84) cohort had lower risk of experiencing a cardiovascular event compared with patients in the control cohort (P = 0.005). Multivariable analyses adjusted for baseline variables showed that patients in the rhPTH(1-84) cohort had 75% lower risk for a cardiovascular event compared with patients in the control cohort (adjusted hazard ratio, 0.25 [95% CI 0.08-0.81]; P = 0.020). CONCLUSION: Long-term treatment with rhPTH(1-84) was associated with a lower risk of incident cardiovascular conditions compared with conventional therapy in patients with chronic hypoparathyroidism. Previous studies demonstrated that mineral homeostasis was maintained with lower use of calcium and active vitamin D when rhPTH(1-84) was added to conventional therapy. Future studies are needed to understand whether improved regulation of mineral homeostasis conferred by rhPTH(1-84) may provide long-term cardiovascular benefits to patients with chronic hypoparathyroidism.

The Economic Burden of Eosinophilic Gastritis and Eosinophilic Enteritis in the United States.

INTRODUCTION: Eosinophilic gastritis and eosinophilic enteritis (EoG/EoN) are associated with a substantial clinical burden. However, limited information is available regarding the economic burden of EoG/EoN. This study was conducted to compare healthcare resource use (HRU) and costs among patients with EoG/EoN versus without EoG/EoN in the USA. METHODS: Administrative claims data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits Databases (2009-2019) was used to identify two cohorts of patients. Patients without EoG/EoN were matched 3:1 to patients with EoG/EoN on sex, year of birth, and healthcare plan type. Study measures included demographic characteristics, select comorbidities, all-cause HRU, and costs. Comparisons were made over a 1-year period following EoG/EoN diagnosis for patients with EoG/EoN and an eligible date for patients without EoG/EoN. RESULTS: A total of 2219 patients with EoG/EoN and 6657 patients without EoG/EoN were analyzed. Significantly higher proportions of patients with EoG/EoN versus without EoG/EoN had comorbid conditions. Rates of all-cause HRU were significantly higher among patients with EoG/EoN versus patients without EoG/EoN (adjusted rate ratio [95% confidence interval]: inpatient visits, 6.26 [5.26, 7.46]; outpatient visits, 1.17 [1.16, 1.19]; emergency department visits, 2.11 [1.98, 2.25]; all p < 0.001). Patients with EoG/EoN incurred significantly higher costs versus patients without EoG/EoN (adjusted mean cost difference $31,180; p < 0.001). Cost differences were largely due to outpatient (adjusted mean cost difference $14,018; p < 0.001) and inpatient (adjusted mean cost difference $11,224; p < 0.001) costs. CONCLUSION: The economic burden associated with EoG/EoN is substantial, with patients with EoG/EoN having a higher rate of HRU and incurring $31,180 more than patients without EoG/EoN on average. Most of the cost difference was attributable to outpatient and inpatient costs. Cost-saving strategies to lower the burden of illness in this patient population are needed.