Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The tumor immune microenvironment in cancer treatment response and resistance is of increasing interest. This retrospective study characterized and investigated programmed death-ligand 1 (PD-L1), PD-L2, and the immune gene expression signature and their association with clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC). PATIENTS AND METHODS: PD-L1 and PD-L2 expression on tumor and immune-infiltrating cells (positivity defined as combined positive score or immunohistochemistry proportion score >1) and T-cell-inflamed gene expression profile (TcellinfGEP) were evaluated in patients with LA HNSCC treated in South Korea from 2000 to 2015. Correlations among the three biomarkers and their associations with overall survival and recurrence-free survival were assessed. RESULTS: Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high TcellinfGEP (≤-0.162) status were observed in 83.6%, 85.4%, and 73.2% of patients, respectively; 4.1% were posttreatment samples. Correlation between PD-L1 and PD-L2 scores was moderate (rSpearman = 0.50), and each biomarker was slightly less correlated with TcellinfGEP (0.41-0.45). PD-L1 expression and high TcellinfGEP status were associated with human papillomavirus positivity. Higher levels of all biomarkers were observed in oral cavity and oropharyngeal cancers compared with other HNSCC sites. In a multivariable analysis that simultaneously adjusted for all three biomarkers, only high TcellinfGEP was significantly associated with longer overall survival (adjusted hazard ratio, 0.57; 95% confidence interval 0.33-0.98) and recurrence-free survival (adjusted hazard ratio, 0.41; 95% confidence interval 0.23-0.74). CONCLUSION: High TcellinfGEP status, but not PD-L1 or PD-L2 expression, was independently associated with longer survival in patients with LA HNSCC. Results may have implications for evaluating therapies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) in HNSCC.

HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9+ macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7+ HLA-EHIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Optimal Hydrofluoric Acid Etching Duration and Impact of Silane/Adhesive on Profilometric Properties and Bonding to Lithium Disilicate Glass Ceramics.

OBJECTIVES: This study aimed to assess the surface roughness, surface free energy (SFE), and shear bond strength (SBS) on a lithium disilicate glass-ceramic surface following varying etching protocols (time variation) and application of silane either with or without adhesive material. METHODS AND MATERIALS: Lithium disilicate glassceramic (LDGC) computer-aided design and computer-aided manufacture (CAD/CAM) blocks were cut using a slow-speed cutting mechanism. CAD/CAM blocks were then evaluated for surface roughness, 6 groups (n=20); SFE,12 groups (n=5); and SBS, 10 groups (n=10). The cut CAD/CAM blocks were randomly allocated to 28 groups. Groups were based on the following: 30 or 90 seconds of etching with 9% hydrofluoric acid (HF); application or absence of silane coupling agent (Sil); and application or absence of adhesive (Adh).The control group (Cont) had untreated surfaces. Unetched surfaces were surveyed with only silane (Sil), only adhesive (Adh), or silane+adhesive (SilAdh). Further etched groups were HF30 with HF for 30 seconds, HF30-Sil, HF30-Adh, and HF30-SilAdh. Alternative 90-second etching times produced similar groups: HF90, HF90-Sil, HF90-Adh, and HF90-SilAdh. A digital profilometer was used to assess the surface roughness of specimens, and two readings were recorded. Sessile drop analysis was used to examine SFE specimens, and the OWRK model was modified to measure liquid surface tension. A universal testing machine (UltraTester, Ultradent Products, Inc, South Jordan, UT, USA) was utilized for the SBS test, with the crosshead speed set at 0.5 mm/min until failure. Representative treated specimens from each group were submitted to surface morphological evaluation and chemical analysis using scanning electron microscopy/energy dispersive x-ray spectroscopy (SEM/EDXS) (n=3). After data collection, evaluation using one- or two-way analysis of variance and the post-hoc Tukey test (α=5%) was conducted. RESULTS: A longer etching time of 90 seconds produced a rougher surface. After the 90-second etching process, SFE displayed the greatest values; nevertheless, the use of silane did not affect SFE. For every group examined, the application of silane followed by adhesive resulted in an increase in SBS and more stable bonding over time. SEM/EDXS showed that etching times did affect the amount of cerium on the surface and altered surface morphology. CONCLUSIONS: Higher and more consistent bond strengths have been observed with longer etching periods. Silane and adhesive application on the ceramic surface showed stronger and enhanced bond strength, specifically when longer etching times were employed.

Evaluating antimicrobial utilization in 20 Korean long-term care hospitals: a call to action for antimicrobial stewardship.

BACKGROUND: Evaluation of hospital-specific antimicrobial use is necessary for successful national antimicrobial stewardship. This study aimed to identify antimicrobial use in long-term care hospitals (LCHs) in Korea. METHODS: A multi-centre retrospective study was conducted to evaluate the prescription patterns and appropriateness of antimicrobials in 20 LCHs in Korea. The medical record data of hospitalized patients who were newly prescribed antimicrobials at each hospital were collected manually between 10th July and 31st October 2023 to evaluate the appropriateness of antimicrobial use. RESULTS: The prevalence of antimicrobial prescriptions was 8.9% (365/4086) and 10.3% (402/3892) on 12th July 2023 and 18th October 2023, respectively. In total, 885 antimicrobials were prescribed to 740 patients. Among the antimicrobials, third- or fourth-generation cephalosporins (31.9%) represented the most prescribed antimicrobial class. A large majority of antimicrobials (96.6%, 855/885) were prescribed for the treatment of infectious diseases; however, only 37.7% (322/855) of antimicrobials were prescribed appropriately for infections. The route of administration, dosage and prescribed antimicrobial were appropriate in 99.6% (852/855), 56.1% (480/855) and 62.0% (530/855) of cases, respectively. In total, 35.2% (252/715) of patients were prescribed antimicrobials appropriately. The diagnosis of infectious disease was appropriate for 52.9% (472/892) of cases. Of the five, 15 and 10 antimicrobials used for surgical site infection prophylaxis, medical prophylaxis and other purposes, respectively, none were used appropriately. CONCLUSION: The proportion of antimicrobials used appropriately is low in Korean LCHs. These data highlight the importance of establishing antimicrobial stewardship in LCHs.

Effects of fermented milk intake and physical activity on the suppression of age-related decline in physical fitness among the elderly.

Physical deterioration in the elderly can lead to disability and mortality. Although the intake of fermented milk has been recently attracting attention as a proposed measure to prevent physical weakness, studies and findings are limited. Here, we investigated the effect of intake of fermented milk products on suppression of age-related decline in physical fitness through a long-term epidemiological study of community-dwelling elderly people who are capable of independent living. A retrospective analysis was conducted on 581 elderly people aged 65-92 years from the Nakanojo Study, with the addition of a 5-year prospective analysis on 240 elderlies. Subjects were arbitrarily grouped on the basis of questionnaire estimates of fermented milk products intake (<3 or ≥3 days/week) and pedometer/accelerometer-determined patterns of physical activity (<7,000 or ≥7,000 steps/day). After adjustment for potential confounders, the retrospective study showed that the group consuming fermented milk products ≥3 days/week showed significantly faster walking speeds than the <3 days/week group. The group taking ≥7,000 steps/day had a significantly faster walking speed than the group taking <7,000 steps/day. Those who did both walked the fastest, indicating an additive effect. Adding protein or energy intake as a covariate to the potential confounders found a correlation between the intake of fermented milk products and walking speed, suggesting that the effect of fermented milk products consumption is independent of nutritional intake status, due to the beneficial properties of bacteria included in fermented milk. The 5-year prospective study confirmed a clear relationship between the frequency of consumption of fermented milk products and the suppression of preferred walking speed decline. Our findings suggest that habitual intake of fermented milk contributes to the suppression of walking speed decline in elderly people.

Socioeconomic Status, Lifestyle, and DNA Methylation Age Among Racially and Ethnically Diverse Adults: NIMHD Social Epigenomics Program.

Importance: Variation in DNA methylation at specific loci estimates biological age, which is associated with morbidity, mortality, and social experiences. Aging estimates known as epigenetic clocks, including the Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), were trained on data predominately from individuals of European ancestry; however, limited research has explored DunedinPACE in underrepresented populations experiencing health disparities. Objective: To investigate associations of neighborhood and individual sociobehavioral factors with biological aging in a racially and ethnically diverse population. Design, Setting, and Participants: This cohort study, part of the Multiethnic Cohort study conducted from May 1993 to September 1996 to examine racial and ethnic disparities in chronic diseases, integrated biospecimen and self-reported data collected between April 2004 and November 2005 from healthy Hawaii residents aged 45 to 76 years. These participants self-identified as of Japanese American, Native Hawaiian, or White racial and ethnic background. Data were analyzed from January 2022 to May 2024. Main Outcomes and Measures: DNA methylation data were generated from monocytes enriched from cryopreserved lymphocytes and used to derive DunedinPACE scores from November 2017 to June 2021. Neighborhood social economic status (NSES) was estimated from 1990 US Census Bureau data to include factors such as educational level, occupation, and income. Individual-level factors analyzed included educational level, body mass index (BMI), physical activity (PA), and diet quality measured by the Healthy Eating Index (HEI). Linear regression analysis of DunedinPACE scores was used to examine their associations with NSES and sociobehavioral variables. Results: A total of 376 participants were included (113 [30.1%] Japanese American, 144 [38.3%] Native Hawaiian, and 119 [31.6%] White; 189 [50.3%] were female). Mean (SE) age was 57.81 (0.38) years. Overall, mean (SE) DunedinPACE scores were significantly higher among females than among males (1.28 [0.01] vs 1.25 [0.01]; P = .005); correlated negatively with NSES (R = -0.09; P = .08), HEI (R = -0.11; P = .03), and educational attainment (R = -0.15; P = .003) and positively with BMI (R = 0.31; P < .001); and varied by race and ethnicity. Native Hawaiian participants exhibited a higher mean (SE) DunedinPACE score (1.31 [0.01]) compared with Japanese American (1.25 [0.01]; P < .001) or White (1.22 [0.01]; P < .001) participants. Controlling for age, sex, HEI, BMI, and NSES, linear regression analyses revealed a negative association between educational level and DunedinPACE score among Japanese American (ß, -0.005 [95% CI, -0.013 to 0.002]; P = .03) and Native Hawaiian (ß, -0.003 [95% CI, -0.011 to 0.005]; P = .08) participants, yet this association was positive among White participants (ß, 0.007; 95% CI, -0.001 to 0.015; P = .09). Moderate to vigorous PA was associated with lower DunedinPACE scores only among Native Hawaiian participants (ß, -0.006; 95% CI, -0.011 to -0.001; P = .005), independent of NSES. Conclusions and Relevance: In this study of a racially and ethnically diverse sample of 376 adults, low NSES was associated with a higher rate of biological aging measured by DunedinPACE score, yet individual-level factors such as educational level and physical activity affected this association, which varied by race and ethnicity. These findings support sociobehavioral interventions in addressing health inequities.

The quality of antimicrobial prescribing in skin and soft tissue management in Australian hospitals: an analysis of the National Antimicrobial Prescribing Survey data.

BACKGROUND: Skin and soft tissue infections (SSTIs) are among the most common indications for antimicrobial prescribing in hospitals. Inappropriate antimicrobial use can lead to increased morbidity, unnecessary hospital re-admission and increased antimicrobial resistance. This study aimed to assess the quality of antimicrobial prescribing practices in SSTI management within Australian hospitals to provide guidance for future practice. METHODS: A retrospective analysis was conducted with data from the National Antimicrobial Prescribing Survey (NAPS). SSTI prescribing data from Hospital NAPS (2013-2022) and surgical site infection data from Surgical NAPS (2016-2022) datasets were analysed. Variables assessed included guideline compliance, appropriateness as per the structured NAPS algorithm, and reasons for inappropriateness. RESULTS: From the Hospital NAPS dataset, 40,535 antimicrobial prescriptions for SSTIs were analysed. The most common indication was cellulitis (34.1%, N=13,822), and the most prescribed antimicrobial was flucloxacillin (18.8%, N=7,638). SSTI indications had a lower rate of guideline compliance but a higher rate of appropriateness compared with all other indications for antimicrobial prescriptions (guideline compliance 66.3%, N=21,035 vs 67.4%, N=156,285; appropriateness 75.6%, N=30,639 vs 72.7%, N=209,383). The most common reason for inappropriateness was incorrect dose or frequency (29.3%, N=2367). From the Surgical NAPS dataset, 5674 prescriptions for surgical site infections were analysed. Of these, 68.2% (N=3867) were deemed to be appropriate. The most common reason for inappropriateness was incorrect dose or frequency (27.7%, N=350). CONCLUSIONS: As SSTIs are a common indication for prescribing an antimicrobial in Australian hospitals, identifying effective antimicrobial stewardship strategies to optimize antimicrobial use for SSTI management is recommended to improve patient outcomes.

Long-term association between physical activity and global functioning in patients with axial spondyloarthritis: results of a two-year prospective study.

OBJECTIVES: To assess the longitudinal association between physical activity and global functioning in patients with axial spondyloarthritis (axSpA), and to identify the subtype of physical activity that is longitudinally related to global functioning. METHOD: Physical activity was measured using Global Physical Activity Questionnaire. Global functioning was assessed using the Assessment of SpondyloArthritis international Society Health Index (ASAS HI). The amount and subtype (work, transport, and recreation) of physical activity, disease activity, and ASAS HI were assessed at baseline, and at 1 and 2 year follow-up. Physical activity levels were categorized as low, moderate, or high. The longitudinal association between physical activity and ASAS HI scores was analysed using a generalized estimating equation. RESULTS: The study evaluated 160 patients. Univariate analysis identified physical activity at moderate level and higher, Ankylosing Spondylitis Disease Activity Score (ASDAS), and syndesmophyte number as being longitudinally associated with ASAS HI over 2 years. Multivariate analysis identified physical activity at moderate level and higher as being longitudinally associated with ASAS HI. Physical activity above moderate levels was associated independently with good global functioning. In the analysis stratified by radiographic axSpA and non-radiographic axSpA, a positive association between physical activity and global functioning was observed in both groups. Only recreational activity, but not work- and transport-related activity, showed an independent longitudinal relationship with the ASAS HI score. CONCLUSIONS: Physical activity at moderate level and higher was associated independently with global functioning in axSpA. Therefore, patients should maintain physical activity above moderate levels to preserve global function.

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

Clinical characteristics and management of orbital apex syndrome: a 10-year multicentre experience.

BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study.

BACKGROUND: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. METHODS: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk. RESULTS: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10-1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03-1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. CONCLUSIONS: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. IMPACT: Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

Rapid response system for critically ill patients with haematological malignancies: A pre- and post-intervention study.

BACKGROUND: This study aimed to determine whether implementing a rapid response system (RRS) is associated with improved short-term outcomes in critically ill patients with haematological malignancies. METHODS: Our monocentric pre- versus post-intervention study was conducted between January 2012 and April 2020. RRS was activated at early signs of haemodynamic or respiratory failure. The primary outcome was the reduction in Sequential Organ Failure Assessment (SOFA) score on Day 3 after intensive care unit (ICU) admission. Secondary outcomes included time to ICU admission and mortality. RESULTS: A total of 209 patients with a median age of 59 years were enrolled (108 in the pre-intervention period and 101 in the post-intervention period). 22% of them had received an allogeneic transplant. The post-intervention period was associated with a shorter time to ICU admission (195 vs. 390 min, p < .001), a more frequent favourable trend in SOFA score (57% vs. 42%, adjusted odds ratio, 2.02, 95% confidence interval, 1.09 to 3.76), no significant changes in ICU (22% vs. 26%, p = .48) and 1-year (62% vs. 58%, p = .62) mortality rates. CONCLUSION: Detection of early organ failure and activation of an RRS was associated with faster ICU admission and lower SOFA scores on Day 3 of admission in critically ill patients with haematological malignancies.

Association of food insecurity with health, access to care, affordability of care, financial burden of care, and financial hardships among US adults during the COVID-19 pandemic.

OBJECTIVES: To examine the associations between food insecurity and health, access to care, affordability of care, financial burden of care, and financial hardships among US adults during the COVID-19 pandemic and examine whether the associations were less pronounced among adults with safety nets. STUDY DESIGN: We conducted a retrospective longitudinal cohort study using the 2020-2021 Medical Expenditure Panel Survey. METHODS: Linear probability models were used to assess the associations between food insecurity in one year and the outcomes of interest in the following year while adjusting for baseline characteristics. We performed the analyses for the entire population and then conducted stratified analyses for adults with and without Supplemental Nutrition Assistance Program (SNAP) benefits or Medicaid coverage. RESULTS: Compared with food-secure adults, food-insecure adults were 9.1 percentage points less likely to report life satisfaction and 9.9, 10.2, and 13.2 percentage points more likely to experience delays in getting medical care, postpone or forgo medical care because of cost, and struggle with paying medical bills. Food-insecure adults were 30.4, 27.2, and 23.5 percentage points more likely to face challenges in affording necessities, paying utility bills, and meeting rent or mortgage payments on time than food-secure adults. Notably, the strengths of these associations were attenuated among adults with SNAP benefits or Medicaid coverage. CONCLUSIONS: Food insecurity was associated with poor health, limited access to and affordability of care, and a greater financial burden of care among US adults during the pandemic. Nevertheless, safety net programs can play a critical role in alleviating adverse consequences.

The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea.

OBJECTIVES: There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with vancomycin-resistant enterococci (VRE) because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). METHODS: This retrospective quasi-experimental study was conducted at a tertiary-care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the haematology unit before (phase 1) and after (phase 2) the policy change. RESULTS: At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval (CI): -0.053 to 0.023, P=0.45 and 0.000, 95% CI: -0.002 to 0.002, P=0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the haematology unit (-0.285, 95% CI: -0.618 to 0.048, P=0.09 and -0.018, 95% CI: -0.036 to 0.000, P = 0.054, respectively) did not change significantly across the two phases. CONCLUSIONS: Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the haematology unit. Horizontal intervention for multi-drug-resistant organisms, including measures such as enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

DNP-Authored Articles in Peer-Reviewed Journals 2011-2021.

BACKGROUND: With an increasing number of doctor of nursing practice (DNP) graduates, the volume of peer-reviewed journal publications among DNP-prepared nurses is rising. PURPOSE: The primary aim of this study was to quantify, analyze, and categorize DNP-authored peer-reviewed journal publications. METHODS: A descriptive research design was used to analyze DNP-authored peer-reviewed journal publications in the WorldCat, EBSCO Discovery Service, and PubMed databases from 2011 through 2021. RESULTS: The 3839 journal publications included at least one DNP-prepared nurse author. There were 2495 (65%) publications with a DNP first author, 921 (24%) with a DNP solo author, and 2918 (76%) included publication collaboration. The majority of publications were practice- (40%), nursing- (17%), and education-focused (15%). Science translation in evidence-based practice and quality improvement publications accounted for 24%. CONCLUSIONS: This study demonstrates the proliferation of DNP-authored peer-reviewed journal publications, which may indicate an increase in the number of nursing care quality initiatives occurring in the clinical setting.

Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Different tumor growth pattern of clinically nonfunctioning pituitary neuroendocrine tumor according to sex and age: a longitudinal study.

PURPOSE: Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. METHODS: In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66 months. RESULTS: The median age of the patients was 53.0 years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51 years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50 years showed significantly lower annual tumor volume change than those aged > 50 years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50 years (0.01 vs. 0.15 cm3/year, P < 0.001). CONCLUSIONS: Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50 years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.

Effectiveness of next-generation sequencing for patients with advanced non-small-cell lung cancer: a population-based registry study.

BACKGROUND: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. MATERIALS AND METHODS: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. RESULTS: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). CONCLUSIONS: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.