Function, cognition, and quality of life among older adults with lung cancer who live alone: A prospective cohort study.

INTRODUCTION: Among older adults without cancer, living alone is associated with poor health outcomes. However, among older adults with non-small cell lung cancer (NSCLC) who live alone, data on function, cognition, and quality of life (QOL) during systemic treatment remain limited. MATERIALS AND METHODS: We enrolled adults aged ≥65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen with non-curative intent. Patients completed geriatric assessments including instrumental activities of daily living (IADL), Montreal Cognitive Assessment, and QOL pretreatment and at 1, 2, 4, and 6 months, or until treatment discontinuation, whichever occurred earlier. We categorized change in IADL, cognition, and QOL as stable/improved, declined with recovery, or declined without recovery using clinically meaningful definitions of change. We used multinomial logistic regression to compare change between patients who lived alone versus with others. RESULTS: Among 149 patients, median age was 73; 21% lived alone. Pretreatment IADL, cognition, and QOL scores were similar between older adults who lived alone versus with others. During NSCLC treatment, older adults who lived alone had similar trajectories of function (52% functional decline vs 38%), cognition (43% cognitive decline vs 50%), and QOL (45% QOL decline vs 44%) compared with those who lived with others. In unadjusted analyses, patients who lived alone were more likely to develop functional decline with recovery (reference category: stable/improved function) than those who lived with others (relative risk ratio 4.07, 95% CI 1.14-14.6, p = 0.03). However, this association was not observed after adjusting for age, race, prior NSCLC treatment, current treatment group, and pretreatment geriatric assessment differences. There were no differences in cognitive or QOL trajectories in unadjusted or adjusted analyses. DISCUSSION: Approximately half of older adults with advanced NSCLC who lived alone were able to maintain their function, cognition, and QOL during NSCLC treatment, which was similar to older adults who lived with others. Many older adults with advanced NSCLC who live alone can receive systemic treatment with individualized supportive care.

Telemedicine-based serious illness conversations, healthcare utilization, and end of life care among patients with advanced lung cancer.

PURPOSE: Little is known about serious illness conversations (SIC) conducted during telemedicine visits and their impact on end-of-life (EOL) outcomes for patients with advanced cancer. PATIENTS AND METHODS: We conducted a retrospective analysis telemedicine visits for patients with metastatic lung cancer conducted during the first surge of the COVID-19 pandemic (October 3, 2020-October 6, 2020). We used natural language processing (NLP) to characterize documentation of SIC domains (ie, goals of care [GOC], limitation of life-sustaining treatment [LLST], prognostic awareness [PA], palliative care [PC], and hospice). We used unadjusted logistic regression to evaluate factors associated with SIC documentation and the relationship between SIC documentation and EOL outcomes. RESULTS: The study included 634 telemedicine visits across 360 patients. Documentation of at least one SIC domain was present in 188 (29.7%) visits with GOC and PA being the most discussed domains. Family presence (odds ratio [OR], 1.66; P = .004), progressive or newly diagnosed disease (OR, 5.42; P < .000), age ≥ 70 (OR, 1.80; P = .009), and male sex (OR, 2.23; P < .000) were associated with a greater likelihood of discussing ≥ 1 SIC domain. Of the 61 patients who died within 12 months of the study period, having ≥ 1 SIC domain discussed was associated with a lower likelihood of hospitalization in the last 30 days of life (OR, 0.27; P = .020). CONCLUSION: In this study of telehealth visits, we identified important factors associated with an increased likelihood of having documentation of an SIC and demonstrated that SIC documentation correlated with lower likelihood of hospitalization at EOL.

Metabolic profiling of psoriasis vulgaris and palmoplantar pustulosis.

Psoriasis is a chronic inflammatory skin disorder with various subtypes, including psoriasis vulgaris (PV) and palmoplantar pustulosis (PPP). Metabolomics studies have provided insights into psoriasis pathogenesis. However, research on metabolomic alterations in PV and PPP patients is limited. We aimed to explore and compare the metabolic profiles of patients with PV and PPP to those of healthy volunteers (HVs). A single-centre retrospective cohort was constructed, comprising Korean patients with psoriasis and HVs matched by age and sex. Clinical information including demographics, disease severity, and comorbidities were collected. Plasma samples were subjected to targeted metabolic analysis using an Absolute IDQ®p180 kit, which quantified 188 metabolites, including amino acids and carnitines. Statistical significance was assessed using an independent t-test and chi-square test, with p-values adjusted by the Benjamini-Hochberg procedure. Pathway analyses were employed to gain a comprehensive understanding of the metabolite profile. This study included 93 patients (73 PV and 20 PPP) and an equal number of HVs. PV patients showed increased levels of sarcosine, serotonin, propionylcarnitine, proline, aspartic acid, tyrosine, taurine, spermine and ornithine, but exhibited a decreased level of acetylcarnitine than matched HVs. Notably, sarcosine levels were significantly elevated in PPP patients. Furthermore, the sarcosine/glycine ratio was significantly higher in both PV and PPP patients than in HVs. Pathway analysis showed significant increases in metabolites involved in amino acid metabolism and the urea cycle in PV patients. In conclusion, this study demonstrated distinct metabolic profiles in PV and PPP patients compared to HVs, suggesting sarcosine as a potential biomarker for psoriasis.

One-year post-acute COVID-19 syndrome and mortality in South Korea: a nationwide matched cohort study using claims data.

Background: Current understanding of post-COVID-19 syndrome in South Korea is primarily based on survey studies or research targeting specific patient groups, such as those hospitalized. Moreover, the majority of relevant studies have been conducted in European and North American populations, which may limit their applicability to the South Korean context. To address this gap, our study explores the one-year outcomes of COVID-19, focusing on the potential post-acute syndrome and all-cause mortality in South Korea. Methods: This retrospective cohort study used nationwide claims data in South Korea, including adults aged >18 with records between January 20, 2020, and February 25, 2021. Patients were classified into COVID-19 and non-COVID-19 groups and matched 1:1 based on propensity scores. Primary outcomes were 12-month post-acute COVID-19 syndrome and all-cause mortality. Results: The study involved 34,802 matched patients. The COVID-19 group had significantly elevated risks of coagulopathies (OR = 2.70 [2.24, 3.28]; p < 0.001), chronic lower respiratory diseases (OR = 1.96 [1.80, 2.14]; p < 0.001), symptoms of the circulatory and respiratory systems (OR = 1.91 [1.80, 2.04]; p < 0.001), mood disorders (OR = 1.67 [1.51, 1.86]; p < 0.001), cardiac diseases (OR = 1.39 [1.21, 1.59]; p < 0.001), and symptoms of cognition, perception, emotional state, and behavior (OR = 1.15 [1.04, 1.27]; p = 0.005). All-cause mortality was higher in the COVID-19 group during the 6 months (OR = 1.34 [1.06, 1.69]; p = 0.015), but gradually decreased, reaching an OR of 0.996 ([0.83, 1.19]; p = 0.964) at 1 year. Conclusion: In South Korea, the 12-month post-acute COVID-19 syndrome includes coagulopathies, respiratory issues, mood disorders, and cardiac diseases. The risk of all-cause mortality post-COVID-19 is heightened for up to 6 months, then significantly decreases and resolves within a year.

Nano-revolution in hepatocellular carcinoma: A multidisciplinary odyssey - Are we there yet?

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense potential of nanotechnology, particularly ligand-receptor mediated nanotherapy, in revolutionizing the treatment landscape of HCC. Despite advancements in multidisciplinary treatment, HCC remains a significant global health challenge. Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites, targeting specific receptors overexpressed in HCC cells, thereby enhancing efficacy and minimizing side effects. Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine, bypassing traditional hurdles encountered in chemotherapy. Examples include targeting glypican-3, asialoglycoprotein, transferrin receptor or folic acid receptors, capitalizing on their over-expression in tumor cells. The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy. However, challenges including immune responses, reproducibility in nanoparticle synthesis, and production scalability remain. Future directions involve refining targeting strategies, improving drug release mechanisms, and streamlining production processes to enable personalized and multifunctional nanotherapies. Overall, the integration of nanotherapy in HCC treatment holds immense promise, but continued partnership and effort are needed in offering hope for more effective, precise, and accessible clinical care in the management of HCC.

Understanding the pharmacokinetic journey of Fc-fusion protein, rhIL-7-hyFc using complementary approach of two analytical methods, accelerator mass spectrometry and ELISA.

Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc's affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT.

A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real-World Data: A Retrospective Observational Study.

Background: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥7 days before RIC in 2012-2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed. Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03-0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25-1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses. Conclusion: Prephase steroid treatment for ≥7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

PURPOSE: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). MATERIALS AND METHODS: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. RESULTS: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). CONCLUSION: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Added to Dual or Triple Treatment in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: We evaluated the effectiveness and safety of sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on treatment in patients with type 2 diabetes mellitus (T2DM) in the real-world setting. METHODS: This single-center retrospective study used the clinical database of Seoul National University Hospital in South Korea. Patients who received metformin monotherapy or combination therapy with ≥ 1 other oral hypoglycemic medication and had a baseline glycosylated hemoglobin (HbA1c) between 7.0% and 10.5% were included. Propensity score matching was applied between patients treated with and without SGLT2 inhibitors (SGLT2i and non-SGLT2i groups, respectively). Changes in HbA1c from baseline to week 26 were compared between the SGLT2i and non-SGLT2i groups, and risk of adverse events (AE) were also assessed. RESULTS: A total of 1106 patients were included. At week 26, HbA1c was significantly more reduced by 0.35 percentage points in the SGLT2i group than in the non-SGLT2i group (95% CI 0.30-0.41, P < 0.001). Likewise, the proportion of patients achieving HbA1c < 7% was also significantly higher (51.9% vs. 37.6%, P < 0.05) in the SGLT2i group than in the non-SGLT2i group. The risk of adverse events in the SGLT2i group was mostly comparable with those in the non-SGLT2i group except for diseases of the liver, pain, hypertensive diseases, and metabolic disorders, which showed significantly higher odds in the SGLT2i group. CONCLUSIONS: SGLT2i add-on treatment is an effective and safe therapeutic option for patients with T2DM in the real-world practice setting.

Trends in medical care utilization in patients with cancer: An analysis of real-world data in a tertiary hospital in Korea, 2014-2019.

BACKGROUND: Rising costs of cancer treatments challenge even areas with universal health coverage. There's a need to assess current medical care utilization trends among patients with cancer to guide public health policy, resource allocation, and set informed healthcare goals. METHODS: We analyzed the latest trends in medical care utilization by cancer patients in four areas-drugs, radiation therapy (RT), surgery, and diagnostic procedures-using clinical databases extracted from electronic medical records of a tertiary hospital in Korea between 2014 and 2019. Compound adjusted growth rates (CAGR) were computed to capture the annual growth over the study period. RESULTS: A total of 74,285 cancer patients were identified, with 40.3% (29,962), 14.2% (10,577), 31.1% (23,066), and 92.6% (68,849) of patients having received at least one anticancer agent, RT, surgery, and diagnostic procedure, respectively, over the period. We observed a 1.7-fold increase in the use of targeted · immune-oncology agents (from 6.8% to 11.6%) and a 21-fold increase (from 3.0% in 2014 to 65.7%) in intensity-modulated RT (IMRT) use over the period. In contrast, we observed a continuous decrease in the proportion of patients who underwent surgical treatment from 12.2% in 2014 to 10.9% in 2019. This decrease was particularly noticeable in patients with colon cancer (from 28.5% to 24.2%) and liver cancer (from 4.1% to 2.9%). CONCLUSION: From 2014 to 2019, there was a significant rise in the use of targeted · immune-oncology agents and IMRT, alongside a decline in surgeries. While targeted · immune-oncology agents and IMRT may offer promising outcomes, their financial impact and potential for overuse necessitate careful oversight and long-term cost-effectiveness studies.

Clinical Characteristics Associated with Adherence and Persistence in Patients with Type 2 Diabetes Mellitus Treated with Dulaglutide.

Aims: This study is aimed at identifying clinical characteristics associated with adherence and persistence in patients with type 2 diabetes mellitus (T2DM) treated with dulaglutide. Materials and Methods: This retrospective observational cohort study used the Common Data Model at Seoul National University Hospital, Seoul, South Korea. Eligible subjects were followed for one year. Multivariate logistic and linear regressions were used to identify the factors associated with categorical (i.e., adherence status and continuation status) and continuous (i.e., proportion of days covered, or PDC, and treatment duration) outcome measures, respectively. Subgroup analysis was conducted involving patients at high cardiovascular disease (CVD) risk (i.e., having ≥2 identifiable risk factors). Results: A total of 236 patients were included. Increase in age and estimated glomerular filtration rate significantly increased the likelihood of adherence and treatment continuation. In contrast, baseline obesity and baseline use of sulfonylurea and insulin significantly reduced the likelihood of continuing dulaglutide. Similarly, increase in age, switching dulaglutide dose, and baseline neuropathy significantly increased PDC and treatment duration. None of the adherence or persistence outcome measures were significantly different between patients at high CVD risk and their matched controls. Baseline hypertension and the higher baseline LDL-C level significantly increased the likelihood of adherence in patients at high CVD risk. Conclusion: Clinical characteristics of dulaglutide users that could have affected their adherence and persistence were identified. Physicians treating T2DM patients with dulaglutide can refer to those clinical characteristics identified in this study to optimize the adherence and persistence to dulaglutide.

Automatic Extraction of Comprehensive Drug Safety Information from Adverse Drug Event Narratives in the Korea Adverse Event Reporting System Using Natural Language Processing Techniques.

INTRODUCTION: Concerns have been raised over the quality of drug safety information, particularly data completeness, collected through spontaneous reporting systems (SRS), although regulatory agencies routinely use SRS data to guide their pharmacovigilance programs. We expected that collecting additional drug safety information from adverse event (ADE) narratives and incorporating it into the SRS database would improve data completeness. OBJECTIVE: The aims of this study were to define the extraction of comprehensive drug safety information from ADE narratives reported through the Korea Adverse Event Reporting System (KAERS) as natural language processing (NLP) tasks and to provide baseline models for the defined tasks. METHODS: This study used ADE narratives and structured drug safety information from individual case safety reports (ICSRs) reported through KAERS between 1 January 2015 and 31 December 2019. We developed the annotation guideline for the extraction of comprehensive drug safety information from ADE narratives based on the International Conference on Harmonisation (ICH) E2B(R3) guideline and manually annotated 3723 ADE narratives. Then, we developed a domain-specific Korean Bidirectional Encoder Representations from Transformers (KAERS-BERT) model using 1.2 million ADE narratives in KAERS and provided baseline models for the task we defined. In addition, we performed an ablation experiment to investigate whether named entity recognition (NER) models were improved when a training dataset contained more diverse ADE narratives. RESULTS: We defined 21 types of word entities, six types of entity labels, and 49 types of relations to formulate the extraction of comprehensive drug safety information as NLP tasks. We obtained a total of 86,750 entities, 81,828 entity labels, and 45,107 relations from manually annotated ADE narratives. The KAERS-BERT model achieved F1-scores of 83.81 and 76.62% on the NER and sentence extraction tasks, respectively, while outperforming other baseline models on all the NLP tasks we defined except the sentence extraction task. Finally, utilizing the NER model for extracting drug safety information from ADE narratives resulted in an average increase of 3.24% in data completeness for KAERS structured data fields. CONCLUSIONS: We formulated the extraction of comprehensive drug safety information from ADE narratives as NLP tasks and developed the annotated corpus and strong baseline models for the tasks. The annotated corpus and models for extracting comprehensive drug safety information can improve the data quality of an SRS database.

Multifocal Pyloric Gland Adenoma of the Esophagus Treated by Circumferential Endoscopic Submucosal Dissection.

Pyloric gland adenoma is a rare neoplasm of the gastrointestinal tract typically observed in the stomach with a substantial malignant potential warranting its resection. While isolated esophageal pyloric gland adenoma has been reported, there is no literature on the encounter of diffuse, multifocal esophageal pyloric gland adenoma or its management. We present a unique case of multifocal pyloric gland adenoma of the esophagus treated by circumferential endoscopic submucosal dissection. We demonstrate endoscopic submucosal dissection to be a feasible management option.

Delirium Prevention and Management in Frail Surgical Patients.

Delirium, an acute, fluctuating impairment in cognition and awareness, is one of the most common causes of postoperative brain dysfunction. It is associated with increased hospital length of stay, health care costs, and mortality. There is no FDA-approved treatment of delirium, and management relies on symptomatic control. Several preventative techniques have been proposed, including the choice of anesthetic agent, preoperative testing, and intraoperative monitoring. Frailty, a state of increased vulnerability to adverse events, is an independent and potentially modifiable risk factor for the development of delirium. Diligent preoperative screening techniques and implementation of prevention strategies could help improve outcomes in high-risk patients.

Implementing Preoperative Penicillin Allergy Testing in Surgical Patients.

Penicillin allergy is the most reported immunoglobulin E (IgE)-mediated reaction. About 10% of the general population and 20% of hospitalized patients have a history of penicillin allergy. Unconfirmed penicillin allergy with subsequent administration of second-line antibiotics has been associated with increased morbidity. However, when penicillin allergy testing is performed, the incidence of IgE-mediated reactions is extremely low; in fact, the negative predictive value of penicillin allergy testing exceeds 99%. This article aims to briefly describe implementing safe penicillin allergy testing as a routine test during the preoperative evaluation of surgical patients.

Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer.

PURPOSE: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures. METHODS: In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis. RESULTS: In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures (P = .04). CONCLUSION: Combining a computer prognosis model with care coaches increased ACP documentation.

A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions.

Interleukin-7 (IL-7) is an essential cytokine for T-cell homeostatic proliferation and maintenance. Clinical studies have shown the potential benefits of IL-7 therapy in various diseases associated with lymphopenia. However, the kinetics of the T-cell response to a single administration of IL-7 in humans have not been fully elucidated. Here, we investigated the effects of Fc-fused long-acting recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa) on lymphocytes in healthy adults after a single subcutaneous or intramuscular administration. Administration of hIL-7-hyFc increased the CD8+ and CD4+ T-cell numbers up to 2.5-fold, with corresponding upregulation of Ki-67 and Bcl-2 expression, peaking at day 3 or 7. Regulatory T cells (Tregs) did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The T-cell receptor repertoire diversity of naive CD8+ and CD4+ T cells was increased by hIL-7-hyFc, whereas the memory T-cell subsets did not differ between day 56 and day 0. Transcriptomic analysis revealed that hIL-7-hyFc induced robust T-cell expansion without changes in gene expression profiles associated with T-cell functions or genes related to T-cell exhaustion, senescence, and anergy. The effector functions of antigen-specific CD8+ T cells were preserved after hIL-7-hyFc administration. Our results suggest that hIL-7-hyFc administration induced a sustained increase in the numbers of CD8+ and CD4+ T cells, but not Tregs, without qualitative changes. These results support the potential of hIL-7-hyFc as a treatment for patients with compromised T-cell immunity or as a vaccine adjuvant.

Factors affecting the changes in antihypertensive medications in patients with hypertension.

As frequent changes in anti-hypertensive (HTN) medications may reduce adherence to the treatments, identifying modifiable factors leading to changes in anti-HTN medications can help clinicians optimize treatment strategies for individual patients. We performed this study to explore the pattern of anti-HTN medications and to identify factors that are associated with the changes in anti-HTN medications. To this end, we used a clinical database of Seoul National University Hospital, extracted, transformed, and loaded by the observational medical outcomes partnership common data model. Demographic and all recorded clinical diagnoses, medications, and procedures data of eligible subjects were collected. Of 636 subjects who were eligible for this study, 297 subjects with a record of ≥1 anti-HTN medication changes and other 297 subjects without a record of medication change were selected for the study population. High diastolic blood pressure (adjusted odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.001-1.040, p = 0.040), arrhythmia (adjusted OR: 10.01, 95% CI: 1.86-185.57, p = 0.030), and angina pectoris with antianginal agents (adjusted OR: 4.85, CI: 1.05-23.89, p = 0.046) were associated with the changes in anti-HTN medications, indicating that any patients with these covariates require additional attention to reduce the likelihood of changing anti-HTN medications.