Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury.

Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.

NRF2 is a spatiotemporal metabolic hub essential for the polyfunctionality of Th2 cells.

Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.

Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1.

Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis that inhibits T cell receptor (TCR)-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation remain unclear. Here, we demonstrate that LXR is a crucial negative regulator of follicular helper T (Tfh) cells in vivo. Both mixed bone marrow chimera and antigen-specific T cell adoptive cotransfer studies show a specific increase in Tfh cells among LXRß-deficient CD4+ T cell population in response to immunization and lymphocytic choriomeningitis mammarenavirus (LCMV) infection. Mechanistically, LXRß-deficient Tfh cells express augmented levels of T cell factor 1 (TCF-1) but comparable levels of Bcl6, CXCR5, and PD-1 in comparison with those of LXRß-sufficient Tfh cells. Loss of LXRß confers inactivation of GSK3ß induced by either AKT/Extracellular signal-regulated kinase (ERK) activation or Wnt/ß-catenin pathway, leading to elevated TCF-1 expression in CD4+ T cells. Conversely, ligation of LXR represses TCF-1 expression and Tfh cell differentiation in both murine and human CD4+ T cells. LXR agonist significantly diminishes Tfh cells and the levels of antigen-specific IgG upon immunization. These findings unveil a cell-intrinsic regulatory function of LXR in Tfh cell differentiation via the GSK3ß-TCF1 pathway, which may serve as a promising target for pharmacological intervention in Tfh-mediated diseases.

A molecular beacon design for a colorimetric loop-mediated isothermal amplification assay.

In this study, a molecular beacon (MB) was designed for colorimetric loop-mediated isothermal amplification (cLAMP). The length of complementary bases on the MB, guanine and cytosine content (GC content), and hybridization sites of complementary bases were investigated as key factors affecting the design of the MB. We designed MBs consisting of 10, 15, and 20 complementary bases located at both ends of the HRPzyme. In the case of the long dumbbell DNA structure amplified from the hlyA gene of Listeria monocytogenes, possessing a flat region (F1c-B1) of 61 base pairs (bp), an MB was designed to intercalate into the flat region between the F1c and B1 regions of the LAMP amplicons. In the case of the short dumbbell DNA structure amplified from the bcfD gene of Salmonella species possessing a flat region (F1c-B1) length of 6 bp, another MB was designed to intercalate into the LoopF or LoopB regions of the LAMP amplicons. The results revealed that the hybridization site of the MB on the LAMP amplicons was not crucial in designing the MB, but the GC content was an important factor. The highest hybridization efficiencies for LAMP amplicons were obtained from hlyA gene-specific and bcfD gene-specific MBs containing 20- and 15-base complementary sequences, respectively, which exhibited the highest GC content. Therefore, designing MBs with a high GC content is an effective solution to overcome the low hybridization efficiency of cLAMP assays. The results obtained can be used as primary data for designing MBs to improve cLAMP accessibility.

Human glioblastoma arises from subventricular zone cells with low-level driver mutations.

Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months1,2. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates3-5. However, there is a lack of direct genetic evidence from human patients with GBM4,6-10. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.

Characteristics and outcomes of patients with do-not-resuscitate and physician orders for life-sustaining treatment in a medical intensive care unit: a retrospective cohort study.

BACKGROUND: In the intensive care unit (ICU), we may encounter patients who have completed a Do-Not-Resuscitate (DNR) or a Physician Orders to Stop Life-Sustaining Treatment (POLST) document. However, the characteristics of ICU patients who choose DNR/POLST are not well understood. METHODS: We retrospectively analyzed the electronic medical records of 577 patients admitted to a medical ICU from October 2019 to November 2020, focusing on the characteristics of patients according to whether they completed DNR/POLST documents. Patients were categorized into DNR/POLST group and no DNR/POLST group according to whether they completed DNR/POLST documents, and logistic regression analysis was used to evaluate factors influencing DNR/POLST document completion. RESULTS: A total of 577 patients were admitted to the ICU. Of these, 211 patients (36.6%) had DNR or POLST records. DNR and/or POLST were completed prior to ICU admission in 48 (22.7%) patients. The DNR/POLST group was older (72.9 ± 13.5 vs. 67.6 ± 13.8 years, p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (26.1 ± 9.2 vs. 20.3 ± 7.7, p < 0.001) and clinical frailty scale (5.1 ± 1.4 vs. 4.4 ± 1.4, p < 0.001) than the other groups. Solid tumors, hematologic malignancies, and chronic lung disease were the most common comorbidities in the DNR/POLST groups. The DNR/POLST group had higher ICU and in-hospital mortality and more invasive treatments (arterial line, central line, renal replacement therapy, invasive mechanical ventilation) than the other groups. Body mass index, APAHCE II score, hematologic malignancy, DNR/POLST were factors associated with in-hospital mortality. CONCLUSIONS: Among ICU patients, 36.6% had DNR or POLST orders and received more invasive treatments. This is contrary to the common belief that DNR/POLST patients would receive less invasive treatment and underscores the need to better understand and include end-of-life care as an important ongoing aspect of patient care, along with communication with patients and families.

CT-based Hounsfield unit values reflect the degree of steatohepatitis in patients with low-grade fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard. METHODS: Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard. RESULTS: The AUROC for diagnosing mild hepatic steatosis was 0.810 (p < 0.001) for the HSI, 0.732 (p < 0.001) for liver HU value, 0.802 (p < 0.001) for the difference between liver and spleen HU value (L-S HU value) and 0.813 (p < 0.001) for the FLI. Liver HU and L-S HU values were negatively correlated with the percentage of hepatic steatosis and NAFLD activity score (NAS) and significantly different between steatosis grades and between NAS grades. The L-S HU value was demonstrated the good performance for grading the severity of hepatic steatosis and the degree of intrahepatic inflammation. CONCLUSIONS: The HU values on CT are feasible for stratifying hepatic fat content and evaluating the degree of intrahepatic inflammation, and the HSI and the FLI demonstrated good performance with high sensitivity and specificity in diagnosing mild hepatic steatosis.

Rapid detection of Shiga-toxin-producing Escherichia coli O157:H7 based on a colorimetric loop-mediated isothermal amplification (cLAMP) assay using a molecular beacon paired with HRPzyme.

Contamination by Escherichia coli O157:H7 is considered a threat in the livestock and food industries. Therefore, it is necessary to develop methods for the convenient and rapid detection of Shiga-toxin-producing E. coli O157:H7. This study aimed to develop a colorimetric loop-mediated isothermal amplification (cLAMP) assay using a molecular beacon to rapidly detect E. coli O157:H7. Primers and a molecular beacon were designed for targeting the Shiga-toxin-producing virulence genes (stx1 and stx2) as molecular markers. Additionally, Bst polymerase concentration and amplification conditions for bacterial detection were optimized. The sensitivity and specificity of the assay were also investigated and validated on artificially tainted (100-104 CFU/g) Korean beef samples. The cLAMP assay could detect 1 × 101 CFU/g at 65 °C for both genes, and the assay was confirmed to be specific for E. coli O157:H7. The cLAMP takes about an hour and does not require expensive devices (e.g., thermal cycler and detector). Hence, the cLAMP assay proposed herein can be used in the meat industry as a fast and simple way to detect E. coli O157:H7.

Recent trends in radiotherapy use for major cancers in Korea.

BACKGROUND: Although the trend in radiotherapy in all cancer patients has been studied, changes in radiotherapy modalities for specific cancer types have not been reported. This study aimed to analyze radiotherapy patterns for major cancers in Korea in recent years. MATERIALS AND METHODS: We collected data from claims and reimbursement records of the Health and Insurance Review and Assessment Service from 2017 to 2020, according to initial diagnostic codes. The radiotherapy modalities for major cancers, such as lung, stomach, colorectal, breast and liver cancer, were analyzed. The radiotherapy modalities consisted of two-dimensional radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, proton radiotherapy and stereotactic body radiotherapy. RESULTS: Overall, from 2017 to 2020, the use of two-dimensional radiotherapy and three-dimensional conformal radiotherapy decreased, and intensity-modulated radiotherapy increased. In 2017, three-dimensional conformal radiotherapy accounted for approximately half of the radiotherapy in patients for lung and colorectal cancer, which was replaced by intensity-modulated radiotherapy in 2020. In 2020, stereotactic body radiotherapy also accounted for a large proportion of radiotherapy used in liver cancer cases. Intensity-modulated radiotherapy was most used, followed by three-dimensional conformal radiotherapy and two-dimensional radiotherapy for breast cancer in 2020. Among major cancers, radiotherapy utilization for breast cancer is the highest. Compared with other cancers, the number of patients receiving radiotherapy for stomach cancer was low. CONCLUSION: The number of patients receiving radiotherapy for major cancers has increased. The use of advanced forms of radiotherapy, such as intensity-modulated radiotherapy, is rapidly increasing for major cancers. The rate of radiotherapy utilization was higher in major cancer patients than in all cancer patients.

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan, Korea.

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.

Older adult communication types and emotional well-being outcomes during COVID-19 pandemic.

BACKGROUND: The rationale for the present study is a result of the COVID-19 pandemic, as there are fewer opportunities available for older adults to engage in face-to-face interaction and social activities, which may result in changes in the communication methods with their social contacts. The purpose of this study was to explore the relationship between methods of social connectedness and emotional well-being outcomes among older adults at the start of the pandemic. METHODS: Two thousand five hundred and fifty-eight older adults Medicare beneficiaries (65 + years of age) in the National Health and Aging Trends Study at wave 10 (June 2020 to January 2021) were selected for cross-sectional analysis. Participants were measured on brief questionnaires regarding forms of communication with family and friends before and during the pandemic. Emotional well-being outcomes were measured on single items of sadness/depressed and loneliness; as well as a 6-item Likert scale of anxiety during the pandemic. Paired sample t-tests were utilized to examine the forms of communication between before and during pandemic. Hierarchical regressions were conducted to assess the relationship between forms of communication and emotional well-being outcomes. RESULTS: We found that there were overall decreases in communication frequency during pandemic. Findings from regression analyses indicated information communication technology (ICT) are associated with negative emotional well-being outcomes, whereas in-person social contact are associated with lower levels of negative affect. CONCLUSION: These findings suggest utilizing higher levels of ICT has negative implications for older adults' emotional well-being, contrasting with the positive implication of in-person contacts. These findings highlight the role of ICT in emotional well-being among older adults during pandemic.

Psychometric properties of the readiness for return to work scale in occupational rehabilitation in South Korea.

BACKGROUND: This study validated the Korean version of the Readiness to Return to Work (RRTW) scale, as an assessment measure, following a musculoskeletal, work-related injury and as a measure of following return to work. METHODS: The participants of this study were workers with experience in rehabilitation programs at the Workers' Compensation and Welfare Service (KCOMWEL) Hospital in Korea. Factor analyses were employed to ensure the validity and reliability of the RRTW scale in claimants who were in treatment without working (the not-working group) or who had already returned to work (the working group). To test structural validity, we analyzed exploratory factor analysis (EFA) respectively for the not working group (exploratory factor analysis (EFA) (n = 200), confirmatory factor analysis (CFA) (n = 109), and the working group (n = 123). To verify concurrent validity (multidimensional and assignment approach), the variables that were identified as relevant variables in previous studies were analyzed. RESULTS: The not working group EFA, as shown in the original scale, had four dimensions, and one item was deleted: (1) Precontemplation (PC), (2) Contemplation (C), (3) Prepared for Action-Self-evaluative (PAS), and (4) Prepared for Action-Behavioral (PAB). The CFA revealed that a good model fit and reliability were suitable. Regarding the working group of EFA, it appeared in two dimensions as in the original scale, one item was modified from the UM scale to the PM scale, and the reliability was appropriate. Concurrent validity was satisfied based on the correlation between the RRTW factor and related variables. CONCLUSIONS: RRTW in the Korean version of the instrument was similar to those reported for the original scale, indicating that it may be used in research and clinical settings.

Feasibility and acceptability of the community-based program: Plan Ahead.

OBJECTIVES: In this article, we assess the feasibility and acceptability and the effect of the Plan Ahead for community dwelling older adults. In addition, we investigated the effects of the program. In addition, we aimed to examine whether the completion of the specific Future Care Planning depended on the participants' competence level. METHODS: In this single group feasibility study, trained facilitators delivered the program to a sample of 234 community-residing older adults. Participants completed both pre, post assessments about the acceptability of the program and their completion of the recommended future care planning activities. RESULTS: Based on participant's report on the usefulness and satisfaction of the program after the completion of the program, we found that participants reported high levels of acceptance of the program. Participation rates also confirmed the feasibility of the program. In terms of effects of program implementation, statistically significant changes were noted for several outcomes, such as resource building and FCP activities. In particular, we found that these gains were particularly robust for participants in the low competence group. CONCLUSION: Pilot program results suggest the feasibility of a short community program enhancing proactive planning for future care needs among older adults residing in their community.

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. METHODS: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. RESULTS: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). CONCLUSION: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Colorimetric detection of norovirus by helicase-dependent amplification method based on specific primers integrated with HRPzyme.

Noroviruses (NoVs) are the most common causes of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and significant causes of foodborne illness. In the USA, approximately 21 million illnesses attributable to NoVs have annually occurred. Therefore, there is a great demand to develop a rapid, low-cost, and accurate detection method for NoVs. This study first reported colorimetric helicase-dependent amplification (HDA) methods based on specific primers integrated with HRPzyme for the rapid and sensitive detection of NoV GI and GII. The colorimetric HDA methods exhibited a detection limit of 10 copies mL-1 of each NoV GI and GII and were confirmed to be specific to each NoV GI and GII. The period required to complete the HDA method was 2 h, including a step of RNA extraction and cDNA synthesis without expensive instruments such as a thermal cycler and detector. The cutoff value of the method for the oyster artificially inoculated with a known amount of NoV was all 102 copies g-1 for NoV GI and GII. Therefore, the HDA method developed in this study can be useful tool for the on-site detection of NoVs in food samples.

Seroprevalence of Helicobacter pylori in human immunodeficiency virus-infected patients in a tertiary care hospital in Busan, South Korea.

INTRODUCTION: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated. METHODS: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies. RESULTS: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/µL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/µL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99). CONCLUSIONS: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years.

Volumetric Splenomegaly in Patients With Polycythemia Vera.

BACKGROUND: Non-palpable splenomegaly in patients with polycythemia vera (PV) has seldom been addressed. In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)-matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria. METHODS: Patients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient's age and BSA. Then the degree of splenomegaly was classified as no splenomegaly, borderline volumetric splenomegaly, overt volumetric splenomegaly, or palpable splenomegaly. RESULTS: Of the 87 PV patients enrolled, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021). CONCLUSION: The degree of splenomegaly, including volumetric splenomegaly, based on age- and BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of diagnosis and taken into consideration when predicting the prognosis of patients with PV.

The role of goal and meaning in life for older adults facing interpersonal stress.

Interpersonal stressful events (ISE) have been shown to be potent predictors of major depressive symptoms among older adults. This study examines the relationships between recent ISE and depressive symptoms in late life and explores whether having coping cognitive resource (e.g. finding meaning and goal in life) can buffer the effects of ISE on depressive symptoms for older adults. We utilized a sample of residents in Florida retirement communities (N = 588) who participated in a long-term-panel study using yearly assessments for six years. Additionally, we modeled within-person differences in ISE and depressive symptoms simultaneously with multilevel modeling. Then, we tested the moderating effect of coping resource (i.e. meaning in life and goal in life) in the association between ISE and depressive symptoms. We found that the mean level of ISE is associated with higher depressive symptoms and lower life satisfaction. In addition, higher levels of within-person meaning and goal buffered the negative effect of ISE on depressive symptoms for older adults. Similarly, within-person meaning and goal also attenuated the negative effect of ISE on life satisfaction.

Characteristics and outcomes of patients screened by rapid response team who transferred to the intensive care unit.

BACKGROUND: The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. METHODS: We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. RESULTS: A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. CONCLUSIONS: Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Caregiving Outcomes of Sub/Urban and Rural Caregivers: The Powerful Tools for Caregivers Program.

OBJECTIVES: The research aimed to investigate the effectiveness of the Powerful Tools for Caregivers (PTC) program for rural caregivers. METHODS: A total of 160 caregivers participated in the program. Exploratory factor analysis was performed to identify latent caregiving outcomes. Paired samples t-tests were conducted to investigate changes in caregiving outcomes before and after the program. To examine geographical differences in the caregiving outcomes, independent samples t-tests were performed. Qualitative responses of the participants were also analyzed. RESULTS: Self-care and positive coping strategies were identified as latent caregiving outcomes. When comparing these two outcome scores before and after the program, the scores significantly improved. The changes in the caregiving outcomes of rural caregivers were greater than those of sub/urban caregivers. Although rural and sub/urban caregivers qualitatively reported similar themes, there were geographical differences in the percentages of caregivers reporting each theme. CONCLUSIONS: The PTC program was effective in improving self-care and positive coping strategies, but the effect of the program was more pronounced in rural areas. Our findings suggest that interventions focusing on self-care and positive coping strategies may beneficially impact rural caregivers. CLINICAL IMPLICATIONS: The PTC program appears promising to improve self-care strategies and enhance self-efficacy of rural caregivers.