Gender and Age Differences in the Evaluation and Clinical Outcomes of Patients with Palpitations.

BACKGROUND: Palpitations represent a common clinic complaint. OBJECTIVE: To explore gender and age differences in the evaluation and outcomes of patients with palpitations in outpatient settings. DESIGN/PARTICIPANTS: This is a retrospective observational study of 58,543 patients with no known structural cardiac disease or arrythmias presenting to primary care and cardiology clinics in an integrated health system in California with palpitations between January 2017 and December 2021. The primary and secondary endpoints were hospitalization for arrhythmia and all-cause mortality at 1 year. Multivariable logistic regression models evaluated the association between gender, age, and outcomes. RESULTS: Men and women were equally as likely to be started on beta-blockers (adjusted OR 0.96, 95% CI 0.90-1.02) and evaluated with electrocardiograms (adjusted OR 0.95, 95% CI 0.90-1.01) and cardiac monitors (adjusted OR 1.04, 95% CI 0.99-1.08). Patients who completed Holter or event monitors had a lower rate of hospitalization for cardiovascular disease at 1 year than those without (2.3% vs. 2.7%, p = 0.001). At 1 year, women had a lower risk of all-cause mortality (adjusted OR 0.47, 95% CI 0.35-0.64) and hospitalization for atrial fibrillation (adjusted OR 0.47, 95% CI 0.30-0.72) and arrhythmias (adjusted OR 0.73, 95% CI 0.58-0.91) compared to men. Among older women and men (≥ 80 years), there was no significant difference in 1-year all-cause mortality (adjusted OR 0.57, 95% CI 0.29-1.12), hospitalization for atrial fibrillation (adjusted OR 0.58, 95% CI 0.17-1.97), or arrhythmias (adjusted OR 1.15, 95% CI 0.12-11.07). CONCLUSIONS: There were no gender differences in referrals for cardiac monitoring or prescriptions for beta-blockers. Women had a better prognosis with a lower risk of hospitalization for arrhythmias and death at 1 year compared to men. However, 1-year risks for mortality and hospitalization for arrythmias among older women were comparable to those of older men, underscoring the importance of considering age and gender in managing patients with palpitations.

TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

Stress, COVID-19 related knowledge, attitude, and infection control performance of nurses at long-term care hospitals.

This study aimed to identify the stress level, knowledge, attitude, and infection control performance of nurses at long-term care hospitals (LTCHs) designated for infectious disease management and to investigate factors contributing to infection control performance. A total of 178 nurses who had worked for at least 1 month at seven LTCHs designated for infectious disease management and provided care for patients confirmed with COVID-19 were enrolled in the study. Data were collected from February to March 2022 using written and online self-report questionnaires. COVID-19 infection control performance was higher among married than among single participants (t = -3.71, p < 0.001), among those aged 40-49 versus 30-39 years (F = 4.10, p = 0.003), and those with 1-2, 3-4, or ≥5 sessions versus no prior education (F = 6.41, p < 0.001). COVID-19 infection control performance was negatively correlated with stress (r = 0.26, p < 0.001) and positively correlated with knowledge (r = 0.40, p < 0.001) and attitude toward COVID-19 (r = -0.36, p < 0.001). Stress (ß = -0.17, p = 0.012), knowledge of COVID-19 (ß = 0.28, p < 0.001), attitude toward COVID-19 (ß = 0.20, p = 0.004), and marital status (ß = 0.18, p = 0.009) were identified as predictors of COVID-19 infection control performance.

Neutrophil-lymphocyte ratio and carotid plaque burden in patients with essential thrombocythemia and polycythemia vera.

BACKGROUND AND AIMS: Chronic inflammation plays a critical role in the pathogenesis of myeloproliferative neoplasm (MPN), and inflammatory conditions are closely related to the development and exacerbation of atherosclerosis. This study aimed to compare carotid plaque burden and neutrophil-lymphocyte ratio (NLR) in the essential thrombocythemia (ET)/polycythemia vera (PV) and control groups. METHODS AND RESULTS: We retrospectively assessed carotid plaque burden and NLR in patients with ET/PV between January 2010 and September 2021 and propensity-score matched these patients to control subjects from the general population. All patients underwent carotid imaging using carotid ultrasonography for atherosclerosis screening. After 3:1 propensity-score matching, 140 patients in the control group were matched to 51 patients in ET/PV group. The mean NLR was significantly higher in the MPN group than in the control group (4.77 ± 3.96 vs. 1.93 ± 1.03, p < 0.001). The carotid plaque score was also higher in MPN group than in the control group (2.37 ± 1.47 vs. 1.94 ± 1.17, p = 0.038). CONCLUSION: Patients with PV/ET show a higher NLR and carotid plaque burden than the normal population. This reflected that PV/ET was a highly inflammatory and atherosclerotic condition expressing potentially increased cardiovascular risk.

A pilot study investigating the social contact patterns of Korean elderly.

OBJECTIVES: This pilot study describes the characteristics of social contact patterns of the elderly, a group at high-risk for contracting infections. DESIGN: A cross-sectional design was used. SAMPLE: Participants included 30 volunteers aged 65 years or older. MEASUREMENTS: Records of a contact diary were maintained for a period of 24-hr. RESULTS: Thirty participants recorded 340 contacts within the 24 hr period, with a mean of 11.3 people daily. Physical encounters accounted for 50.9% of contacts. Participants with an occupation had significantly higher contacts than those without (p=.013). Contact type differed by location and duration (p<.001). Contact locations included: home (11.5%), work (2.4%), elderly welfare facilities (32.9%), transport (1.2%), and other places (52.1%). Contact duration (p < .001) and frequency (p < .001) differed by location. Contact duration differed by frequency (p < .001). CONCLUSIONS: The elderly participate in frequent physical contact that increases their risk of infection, especially among those with an occupation in comparison to those without an occupation. Infection control nursing should focus on providing education to reduce the risk of infections during contact events. Social distancing should be applied to limited periods of infection transmission risk.

Factors affecting frontline Korean nurses' mental health during the COVID-19 pandemic.

AIM: To identify the factors affecting fear, anxiety and depressive symptoms among frontline nurses working with COVID-19 patients or are in charge of COVID-19 screening in Korea. BACKGROUND: Nurses are at a higher risk of COVID-19 infection because they are in closer, longer-duration contact with patients. These situations can negatively affect the mental health of nurses. METHODS: This study analysed data from COVID-19 module in the Korean Nurses' Health Study. Data from 906 participants were analysed. To identify the factors influencing mental health, descriptive statistics, Pearson's correlation and hierarchical multiple regression analyses were performed. RESULTS: Caring for patients who are COVID-19-positive increased levels of fear, anxiety and depressive symptoms of nurses. The hospital safety climate influenced mental well-being among nurses. CONCLUSION: Caring for patients with COVID-19 had a negative impact on fear, anxiety and depressive symptoms. However, the higher was the perceived hospital safety climate, the lower were the nurses' psychological symptoms. Further research on the mental health of nurses is warranted. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Institutions should manage human resources to enable periodic rotation of nurses' work and working periods related to COVID-19. In addition, hospital managers should provide sufficient personal protective equipment, related education, and safety climate.

Golden Bristlegrass-Like Hierarchical Graphene Nanofibers Entangled with N-Doped CNTs Containing CoSe2 Nanocrystals at Each Node as Anodes for High-Rate Sodium-Ion Batteries.

Golden bristlegrass-like unique nanostructures comprising reduced graphene oxide (rGO) matrixed nanofibers entangled with bamboo-like N-doped carbon nanotubes (CNTs) containing CoSe2 nanocrystals at each node (denoted as N-CNT/rGO/CoSe2 NF) are designed as anodes for high-rate sodium-ion batteries (SIBs). Bamboo-like N-doped CNTs (N-CNTs) are successfully generated on the rGO matrixed nanofiber surface, between rGO sheets and mesopores, and interconnected chemically with homogeneously distributed rGO sheets. The defects in the N-CNTs formed by a simple etching process allow the complete phase conversion of Co into CoSe2 through the efficient penetration of H2 Se gas inside the CNT walls. The N-CNTs bridge the vertical defects for electron transfer in the rGO sheet layers and increase the distance between the rGO sheets during cycles. The discharge capacity of N-CNT/rGO/CoSe2 NF after the 10 000th cycle at an extremely high current density of 10 A g-1 is 264 mA h g-1 , and the capacity retention measured at the 100th cycle is 89%. N-CNT/rGO/CoSe2 NF has final discharge capacities of 395, 363, 328, 304, 283, 263, 246, 223, 197, 171, and 151 mA h g-1 at current densities of 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 A g-1 , respectively.

The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity.

PURPOSE: Tetracyclines have activity against matrix metalloproteinases (MMP). Oral medications with effects on the ocular surface are of interest in patients where repeated topical dosing is limited. The aim of this study was to characterize the concentration of minocycline in the tears of normal horses after oral administration and to determine if this level directly inhibits MMP activity. METHODS: Five healthy adult ponies were administered oral minocycline (Wedgewood Pharmacy; Swedesboro, NJ) at 4 mg/kg every 12 h for 5 days. Tears were collected at T = 2, 26, 50, 56, 74, 80, and 98 h. Tear minocycline concentrations were analyzed using high performance liquid chromatography. The inhibition of recombinant human MMP-2 and MMP-9 by minocycline was investigated using fluorescence resonance energy transfer. RESULTS: Minocycline was present in the tears of each pony at every measurement but with interpony variability. A mean concentration of 11.8 µg/mL was present 2 h after administration of the first dose. Minocycline did not directly inhibit MMP-2 or MMP-9 function at a concentration achieved in the pony tear film. CONCLUSIONS: Minocycline was present in the tears of all ponies at each sampling point following oral administration. One pony of the five had consistently lower levels of minocycline secretion (P ≤ 0.05). The concentration secreted in the tears did not directly inhibit MMP-2 or MMP-9 when tested in vitro. The inconsistencies in the tear concentration and the inhibition activity suggest topical application may be necessary to attain direct inhibition of MMP with minocycline.

Effects of hazard perception training (HPT) on nursing students' risk sensitivity to patient safety and developing safety control confidence.

PURPOSE: This study identifies the effects of hazard perception training (HPT) on nursing students' risk sensitivities and safety control confidence. METHODS: The study uses a nonequivalent control group pre-and post-test design. The participants were 107 senior nursing students, 52 in the experimental group, and 55 in the control group. The experimental group was shown 5 hospital situation pictures to determine hazard sensitivity. Students' risk sensitivity scores and safety control confidence were measured pre-HPT and post-HPT. RESULTS: The experimental group showed significantly higher (on) total risk sensitivity score (t=12.47, p<0.001) and themes, such as fall down (t=19.33, p<0.001), preoperative time out (t=3.18, p<0.001), invasive treatment (t=12.40, p<0.001), and medication (t=10.98, p<0.001). However, the difference for telephone orders was insignificant between the experimental and control groups (t=-0.17, p=0.864). In addition, difference of mean scores for safety control confidence was insignificant between the experimental and the control groups (t=1.10, p=0.275). CONCLUSION: Nursing education should incorporate hazard perception training more often, and educators need to develop education programs to improve nursing students' safety control confidence. Further, a Hazard Perception Training (HPT) that incorporates various kinds of educational methods for students majoring in healthcare fields is needed.

A Case of Multiple Cardiovascular and Tracheal Anomalies Presented with Wolff-Parkinson-White Syndrome in a Middle-aged Adult.

Congenital cardiovascular anomalies, such as dextrocardia, persistent left superior vena cava (SVC), and pulmonary artery (PA) sling, are rare disorders. These congenital anomalies can occur alone, or coincide with other congenital malformations. In the majority of cases, congenital anomalies are detected early in life by certain signs and symptoms. A 56-year-old man with no previous medical history was admitted due to recurrent wide QRS complex tachycardia with hemodynamic collapse. A chest radiograph showed dextrocardia. After synchronized cardioversion, an electrocardiogram revealed Wolff-Parkinson-White (WPW) syndrome. Persistent left SVC, PA sling, and right tracheal bronchus were also detected by a chest computed tomography (CT) scan. He was diagnosed with paroxysmal supraventricular tachycardia (PSVT) associated with WPW syndrome, and underwent radiofrequency ablation. We reported the first case of situs solitus dextrocardia coexisting with persistent left SVC, PA sling and right tracheal bronchus presented with WPW and PSVT in a middle-aged adult. In patients with a cardiovascular anomaly, clinicians should consider thorough evaluation of possibly combined cardiovascular and airway malformations and cardiac dysrhythmia.

Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis.

The protective antigen component of Bacillus anthracis toxins can interact with at least three distinct proteins on the host cell surface, capillary morphogenesis gene 2 (CMG2), tumor endothelial marker 8, and ß1-integrin, and, with the assistance of other host proteins, enters targeted cells by receptor-mediated endocytosis. Using an antisense-based phenotypic screen, we discovered the role of calpains in this process. We show that functions of a ubiquitous Ca(2+)-dependent cysteine protease, calpain-2, and of the calpain substrate talin-1 are exploited for association of anthrax toxin and its principal receptor, CMG2, with higher-order actin filaments and consequently for toxin entry into host cells. Down-regulated expression of calpain-2 or talin-1, or pharmacological interference with calpain action, did not affect toxin binding but reduced endocytosis and increased the survival of cells exposed to anthrax lethal toxin. Adventitious expression of wild-type talin-1 promoted toxin endocytosis and lethality, whereas expression of a talin-1 mutant (L432G) that is insensitive to calpain cleavage did not. Disruption of talin-1, which links integrin-containing focal adhesion complexes to the actin cytoskeleton, facilitated association of toxin bound to its principal cell-surface receptor, CMG2, with higher-order actin filaments undergoing dynamic disassembly and reassembly during endocytosis. Our results reveal a mechanism by which a bacterial toxin uses constitutively occurring calpain-mediated cytoskeletal rearrangement for internalization.

Acute invasive small-bowel Anisakiasis: clinical and CT findings in 19 patients.

PURPOSE: To evaluate the clinical and CT findings in patients with small-bowel Anisakiasis. MATERIALS AND METHODS: Nineteen patients with small-bowel Anisakiasis and who underwent abdominal CT between 2005 and 2012 were enrolled in our study. All of these patients were diagnosed using either a serologic test for Anisakiasis (n = 18) or by pathology (n = 1). Their medical records were reviewed in order to determine the clinical findings. CT images were retrospectively reviewed by two radiologists to evaluate the characteristics of the involved bowel wall and the ancillary findings. RESULTS: All patients had presented with the acute onset of severe abdominal pain as well as a history of having recently eaten raw fish. The mean time interval from eating the fish to the onset of abdominal pain was 1.7 days. Eighteen patients were treated conservatively and experienced resolution of their symptoms within seven days of hospitalization. One patient underwent surgical exploration for presumed small-bowel ischemia. The sites of involvement included the ileum (16/19, 84%) and jejunum (3/19, 16%). All patients had circumferential bowel-wall thickening (mean, 0.8 cm) with an intermediate length of involved bowel (mean, 7.9 cm). Small-bowel obstruction occurred in 16 patients (84%). The target sign was present in 17 patients (89%), ascites, particularly in the perilesional area, in 16 patients (84%), and mesenteric edema in 15 patients (79%). CONCLUSION: Small-bowel Anisakiasis should be considered in the differential diagnosis of acute abdomen in order to avoid unnecessary surgery when patients present with abdominal pain after having recently eaten raw fish, concentric bowel-wall thickening with the target sign in the ileum, perilesional ascites, as well as bowel obstruction seen on CT.

Infection Control Experiences and Educational Needs of Geriatric Care Workers in Long-Term Care Facilities: A Pilot Study.

BACKGROUND: In the post-COVID-19 condition, infection control education is important for geriatric care workers who care for the elderly and are vulnerable to emerging infectious diseases. This study was conducted to enhance the insight into the experiences of geriatric care workers in managing novel infectious diseases (COVID-19) and to identify the newly required educational requirements necessary to effectively implement infectious disease control. METHODS: This is a qualitative and pilot study using focus group interviews. Data from 10 participants were collected using a focus group interview. The data were analyzed using Qualitative content analysis. RESULTS: The findings showed that geriatric healthcare workers experienced difficulties following infection control protocols and emotional distress related to visitor restrictions and had an increased workload. The participants requested further education regarding general knowledge of infectious diseases to decrease their fears of infection and reported that visual and practical teaching methods were preferable. CONCLUSIONS: Further attention is needed regarding the education of infection control to strengthen infection prevention in long-term care facilities vulnerable to the spread of emerging infectious diseases.

Educational Outcomes and Perception Changes in Medical Students After Visiting a Blood Donation Center.

Educating primary care physicians about blood donation and transfusion is critical. The Division of Hematology and Oncology at Soonchunhyang University Seoul Hospital in Korea introduced an on-site educational program termed the Blood Donation Center Visiting Program in the clerkship education for final-year medical students. We evaluated the educational outcomes and changes in perception among medical students after the Blood Donation Center Visiting Program based on a survey. The program was implemented from 2021 to 2023. As part of the program, students visited a blood donation center each week, one group at a time. They gained practical knowledge about the blood donation process, and some students actively participated in blood donation. After the program, 287 students were eligible for an online survey of the program, of whom 203 participated in the survey. Among the 203 students, 126 (62.1%) donated blood during their visit to the blood donation center as part of the program, and 88.7% of the students reported an increase (from 71.4% to 90.1%) in their knowledge and willingness to donate blood. The on-site educational Blood Donation Center Visiting Program appears to have generated positive changes in perceptions among students and enhanced their knowledge about blood donation.

Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin.

To kill macrophages, the lethal factor component of Bacillus anthracis toxin binds to a carrier protein (PA), which then interacts with the CMG2 receptor protein on the cell surface and is endocytosed into the cytoplasm. CMG2, as well as TEM8, a second PA receptor not present on macrophages, contain a von Willebrand A domain that is crucial for toxin binding. Here we report that integrin beta1, another cell surface von Willebrand A domain protein, can mediate and potentiate anthrax toxin endocytosis. By using microarray-based analysis to globally correlate gene expression profiles with toxin sensitivity, we associated toxin effects with the integrin-activating proteins osteopontin and CD44. Further study showed that PA binds to alpha4beta1- and alpha5beta1-integrin complexes, leading to their conjoint endocytosis, and also interacts-weakly relative to CMG2 but comparably to TEM8--with purified alpha5beta1 complex in vitro. Monoclonal antibody directed against beta1-integrin or its alpha integrin partners reduced PA/integrin endocytosis and anthrax toxin lethality, and hyaluronic acid--which interferes with CD44-mediated integrin activation--had similar effects. Remarkably, whereas deficiency of CMG2 protected macrophages from rapid killing by large toxin doses (>50 ng/mL), by 24 h the toxin-treated cells were dead. Such late killing of CMG2-deficient cells by high dose toxin as well as the late death observed during exposure of CMG2-producing macrophages to low-dose toxin (<1 ng/mL), was dependent on integrin function. Effects of inactivating both CMG2 and integrin were synergistic. Collectively, our findings argue strongly that beta1-integrin can both potentiate CMG2-mediated endocytosis and serve independently as a low-affinity PA receptor.

Development and Application of an Educational-Training Programme for Infection Control Practitioners in Long-Term Care Hospitals.

Elderly persons are at risk of infection due to underlying diseases and weak immune systems. All elderly persons do not require hospitalization in LTCHs, even if have chronic illness or weakened immune systems, but they require care in long-term care hospitals (LTCHs) that have well-trained infection control practitioners (ICPs). This study aimed to develop an educational-training programme for ICPs working in LTCHs using the Developing A Curriculum (DACUM) method. Based on the results of the literature review and the DACUM committee workshop, 12 duties and 51 tasks of ICPs were identified. A total of 209 ICPs participated in the survey, rating 12 duties and 51 tasks on a 5-point scale in terms of frequency, importance, and difficulty. An educational-training programme consisting of five modules was developed, focusing on tasks higher than the mean for each of frequency (2.71 ± 0.64), importance (3.90 ± 0.05), and difficulty (3.67 ± 0.44). Twenty nine ICPs participated in a pilot educational-training programme. The mean programme satisfaction level was 93.23 (standard deviation: ±3.79 points) out of 100 points. The average total knowledge and skill scores were significantly higher after the programme (26.13 ± 1.09, 24.91 ± 2.46, respectively) than before the programme (18.89 ± 2.39, 13.98 ± 3.56, respectively) (p < 0.001, p < 0.001, respectively). This programme will improve the knowledge and skills of ICPs, and thereby contribute to the reduction in healthcare-associated infections in LTCHs.

Development of a Tool to Measure Compliance with Infection Prevention Activities Against Emerging Respiratory Infectious Diseases among Nurses Working in Acute Care and Geriatric Hospitals.

BACKGROUND: This study developed a preliminary instrument to measure nurses' infection prevention compliance against emerging respiratory infectious diseases and to verify the reliability and validity of the developed instrument. METHOD: The participants were 199 nurses working at a university hospital with more than 800 beds and two long-term care hospitals. Data were collected in May 2022. RESULTS: The final version of the developed instrument consisted of six factors and 34 items, with an explanatory power of 61.68%. The six factors were equipment and environment management and education, hand hygiene and respiratory etiquette, infection risk assessment and flow management, protection of employees in contact with infected patients, ward access management of patients with infectious diseases, and wearing and removing personal protective equipment. We verified the convergent and discriminant validities of these factors. The instrument's internal consistency was adequate (Cronbach's α=0.82), and the Cronbach's α of each factor ranged from 0.71 to 0.91. CONCLUSION: This instrument can be utilized to determine the level of nurses' compliance with infection prevention activity against emerging respiratory infectious diseases and will contribute to measuring the effectiveness of future programs promoting infection-preventive activities.

The Optimal Tumor Mutational Burden Cutoff Value as a Novel Marker for Predicting the Efficacy of Programmed Cell Death-1 Checkpoint Inhibitors in Advanced Gastric Cancer.

PURPOSE: The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. MATERIALS AND METHODS: Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. RESULTS: A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). CONCLUSIONS: The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

Effects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial).

Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction from established lifestyle interventions. Using data from the original DASH (Dietary Approaches to Stop Hypertension) trial, we determined the effects of adopting the DASH diet on 10-year ASCVD risk compared with adopting a control or a fruits and vegetables (F/V) diet. The DASH trial included 459 adults aged 22 to 75 years without CVD and not taking antihypertensive or diabetes mellitus medications, who were randomized to controlled feeding of a control diet, an F/V diet, or the DASH diet for 8 weeks. We determined 10-year ASCVD risk with the American College of Cardiology/American Heart Association Pooled Cohort Equation based on blood pressure and lipids measured before and after the 8-week intervention. Compared with the control diet, the DASH and F/V diets changed 10-year ASCVD risk by -10.3% (95% confidence interval [CI] -14.4 to -5.9) and -9.9% (95% CI -14.0 to -5.5) respectively; these effects were more pronounced in women and Black adults. There was no difference between the DASH and F/V diets (-0.4%, 95% CI -6.9 to 6.5). ASCVD reductions attributable to the difference in systolic blood pressure alone were -14.6% (-17.3 to -11.7) with the DASH diet and -7.9% (-10.9 to -4.8) with the F/V diet, a net relative advantage of 7.2% greater relative reduction from DASH compared with F/V. This was offset by the effects on high-density lipoprotein of the DASH diet, which increased 10-year ASCVD by 8.8% (5.5 to 12.3) compared with the more neutral effect of the F/V diet of -1.9% (-5.0 to 1.2). In conclusion, compared with a typical American diet, the DASH and F/V diets reduced 10-year ASCVD risk scores by about 10% over 8 weeks. These findings are informative for counseling patients on both choices of diet and expectations for 10-year ASCVD risk reduction.

The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation.

Background: With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC. Objectives: There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations. Design: Retrospective observational study. Methods: We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression. Results: A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3-8.0] and 3.8 (IQR: 3.0-4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS. Conclusion: Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.