Determining patient preferences for the medical management of osteoporosis using conjoint analysis.

We used conjoint analysis-a method that assesses complex decision making-to quantify patients' choices when selecting an osteoporosis therapy. While 60% of people prioritized medication efficacy when deciding among treatments, the remaining 40% highly valued factors other than efficacy, suggesting the need for personalized shared decision-making tools. INTRODUCTION: In this study, we aimed to examine patient decision-making surrounding osteoporosis medications using conjoint analysis. METHODS: We enrolled osteoporosis patients at an academic medical center to complete an online conjoint exercise which calculated each patient's relative importance score of 6 osteoporosis medication attributes (higher = greater relative importance in decision-making). We used latent class analysis to identify distinct segments of patients with similar choice patterns and then used logistic regression to determine if demographics and osteoporosis disease features were associated with latent class assignment. RESULTS: Overall, 304 participants completed the survey. The rank order of medication attributes by importance score was the following: efficacy at preventing hip fractures (accounted for 31.0% of decision making), mode of administration (17.5%); risk of serious side effects (16.6%); dose frequency (13.9%); efficacy at preventing spine fractures (12.5%); risk of non-serious side effects (8.4%). We found that 60.9% of the cohort prioritized medication efficacy as their top factor when selecting among the therapies. Being a college graduate, having stronger beliefs on the necessity of using medications for osteoporosis, and never having used osteoporosis medicines were the only factors associated with prioritizing medication efficacy for fracture prevention over the other factors in the decision-making process. CONCLUSIONS: While about 60% of patients prioritized efficacy when selecting an osteoporosis therapy, the remaining 40% valued other factors more highly. Furthermore, individual patient characteristics and clinical factors did not reliably predict patient decision making, suggesting that development and implementation of shared decision-making tools is warranted.

Interactive Inflammatory Bowel Disease Biologics Decision Aid Does Not Improve Patient Outcomes Over Static Education: Results From a Randomized Trial.

INTRODUCTION: To support shared decision-making (SDM) between patients and providers surrounding biologic treatments, we created IBD&me ( ibdandme.org )-a freely available, unbranded, interactive decision aid. We performed a multicenter comparative effectiveness trial comparing the impact of IBD&me on SDM vs a biologics fact sheet developed by the Crohn's & Colitis Foundation. METHODS: We enrolled patients with inflammatory bowel disease (IBD) being seen at a clinic within IBD Qorus-a multicenter adult IBD learning health system-between March 5, 2019, and May 14, 2021. Eligible patients included those with recent IBD-related symptoms who reported that they wanted to discuss biologics with their provider during their upcoming visit. Patients were randomized 1:1 using stratified block randomization and received an e-mail 1 week before their visit inviting them to review either IBD&me or a fact sheet. The primary outcome was patient perception of SDM as measured by the 9-Item SDM Questionnaire (0-100 scale; higher = better); the Student t test was used to compare outcomes between arms. RESULTS: Overall, 152 patients were randomized (biologics fact sheet 75, IBD&me 77); most patients had Crohn's disease (66.4%) and were biologic-experienced (82.9%). No differences were seen between groups regarding SDM (fact sheet 72.6 ± 25.6, IBD&me 75.0 ± 20.8; P = .57). Most patients stated they would be likely to recommend the fact sheet (79.6%) or IBD&me (84.9%; P = .48) to another patient with IBD. DISCUSSION: No differences in outcomes were seen between IBD&me and the biologics fact sheet in this comparative effectiveness study; patients reported high satisfaction with both resources. Further study, particularly among biologic naïve patients, is needed to determine the utility of interactive components to IBD decision aids.

A Cultural Dance Program Improves Hypertension Control and Cardiovascular Disease Risk in Native Hawaiians: A Randomized Controlled Trial.

BACKGROUND: Native Hawaiians have higher hypertension (HTN) and cardiovascular disease (CVD) rates than non-Hispanic whites, calling for culturally responsive interventions to close this gap. PURPOSE: We tested the effects of a 6-month behavioral intervention, a cultural dance program based on hula (the customary dance of Hawai'i), for improving blood pressure (BP) and CVD risk among Native Hawaiians with uncontrolled HTN. METHODS: In a randomized controlled trial, we tested the effects of the hula-based intervention among 263 Native Hawaiians with uncontrolled HTN (systolic ≥ 140 or ≥ 130 mmHg if diabetes) and no CVD at enrollment. All participants received a brief culturally tailored heart health education before random assignment to the hula-based intervention (n = 131) or the education-only waitlist control (n = 132). Intervention received hula lessons and group-based activities for 6 months. Control received only 1-week education through 6 months. RESULTS: Intervention yielded greater reductions in systolic (-15.3 mmHg) and diastolic (-6.4 mmHg) BP than control (-11.8 and -2.6 mmHg, respectively) from baseline to 6 months (p < .05). At 6 months, 43% of intervention participants compared to 21% of controls achieved a HTN stage <130/80 mmHg (p < .001). The 10-year CVD risk reduction was two times greater for the intervention group than the control group based on the Framingham Risk Score calculator. All improvements for intervention participants were maintained at 12 months. CONCLUSIONS: This trial represents one of the few rigorously conducted examinations of an Indigenous practice leveraged for health promotion, with implications for other ethnic populations.

Disparities in Alzheimer Disease and Mild Cognitive Impairment Among Native Hawaiians and Pacific Islanders.

BACKGROUND: Previous studies of racial differences in Alzheimer disease (AD) presentation have not included Native Hawaiians and Pacific Islanders (NHPI). OBJECTIVE: To explore the presentation of AD and mild cognitive impairment (MCI) in NHPI. METHOD: We conducted a retrospective review of patient records from Hawaii with a diagnosis of unspecified AD or MCI from September 2000 to September 2019. Variables of interest included age at diagnosis, gender, race, marital status, insurance, comorbidities, and scores on the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). RESULTS: We reviewed the medical records of 598 patients, including 224 Asians, 202 Whites, 87 NHPI, and 85 Other. AD was more dominant than MCI across all of the groups, with the highest percentage in NHPI. Among the mean ages of diagnosis, NHPI were the youngest. Across all groups, a higher proportion of women than men had AD, with the highest female prevalence among NHPI. Hypertension, hyperlipidemia, and type II diabetes were highest among NHPI compared with the other groups. Of individuals with MMSE/MoCA scores, there were significant variations in scores by racial group. The mean MMSE/MoCA score was highest among Whites and lowest among NHPI. CONCLUSION: Compared with other racial groups, NHPI have a higher proportion of AD than MCI at diagnosis, are diagnosed at a younger age, have a higher female prevalence, have more comorbidities that may contribute to AD/MCI onset, and present with lower MMSE scores.

The Importance of Echocardiogram during the Second Week of Illness in Children with Kawasaki Disease.

OBJECTIVE: To determine the timing of peak coronary artery dilation and the characteristics of patients who present with new-onset coronary artery dilation during the acute phase of Kawasaki disease with an initial normal echocardiogram. STUDY DESIGN: This retrospective study analyzed 231 children hospitalized for Kawasaki disease in Hawai'i over a period of 7 years. Clinical and echocardiographic data were collected to calculate the timing of peak z score, and study subjects were compared based on the timing of coronary dilation. RESULTS: Peak coronary artery dilation was observed on average at 11.5 days from the onset of fever (median 8, IQR 7-13 days). Among study subjects with normal z scores in both coronary arteries during the initial encounter and echocardiogram (n = 164), 16 (10%) developed coronary artery dilation or aneurysm at the second echocardiogram, and 5 (3%) continued to have coronary artery dilation or aneurysm at the convalescent phase. CONCLUSIONS: A repeat echocardiogram during the second week of illness (day 7-14 from fever onset) in patients with normal initial echocardiogram could identify new-onset coronary artery dilation or aneurysm and could be useful in the timely adjustment of antithrombotic or anti-inflammatory therapies.

Prevalence of Selected Chronic Conditions Among Children, Adolescents, and Young Adults in Acute Care Settings in Hawai'i.

INTRODUCTION: Chronic disease prevalence among young people is understudied generally and specifically for Native Hawaiian, Filipino, and Pacific Islander youth who are at high risk for these conditions. We determined the statewide prevalence of chronic diseases in acute care for those aged 5 to 29 years, including Native Hawaiians, Filipinos, and Pacific Islanders. METHODS: We used Hawai'i statewide inpatient and emergency department (ED) data across all payers from 2015-2016 to determine the presence of at least 1 of 5 chronic conditions (ie, asthma, hypertension, chronic kidney disease, diabetes, stroke) from 13,514 inpatient stays by 9,467 unique individuals and 228,548 ED visits by 127,854 individuals. RESULTS: Twenty-eight percent of youth who were hospitalized and 12% with an ED visit had at least 1 chronic condition. Medicaid covered more than half of these visits. When comparing patients with and without a chronic condition, race/ethnicity, age group, and payer varied significantly in both inpatient and ED settings. Patients with a chronic condition were disproportionately Native Hawaiian, Filipino, and Pacific Islander; 32.3% of those with an inpatient chronic condition and 34.9% of those with an ED chronic condition were Native Hawaiian. Prevalence of chronic conditions among racial/ethnic groups varied significantly by age. CONCLUSION: Chronic diseases, including those more often seen in adulthood, are prevalent in young people in acute care settings in Hawai'i, with notable disparities. These findings can help justify, guide, and support programs that are needed to address these changing epidemiological trends, which may be of particular interest for Medicaid.

Customizing Physiologic Alarms in the Emergency Department: A Regression Discontinuity, Quality Improvement Study.

INTRODUCTION: Clinical alarms promote patient safety by alerting clinicians when there is an indication or change in a condition requiring a response. An excessive volume of alarm fires, however, contributes to sensory overload and desensitization, referred to as alarm fatigue, which has significant implications when alarms are missed. This evidence-based, practice project aimed to implement and evaluate a program that reduces the number of clinically nonactionable, physiologic alarms in an emergency department. Although alarm fatigue is an important negative consequence, the focus of this project is not on alarm fatigue but on measures to reduce the volume of clinically nonactionable alarms that lead to alarm fatigue. The Iowa Model was used as a conceptual framework. METHODS: This project involved adjusting default alarm settings and implementing an education plan on the safe use of alarms. The sample population included all patients on physiologic monitors at an emergency department. Retrospective data were collected, and regression discontinuity design was applied to compare the rate of alarm fires triggered by the physiologic monitor between pre- and postimplementation of an alarm protocol. RESULTS: A significant change in the rate of alarm fires occurred with an estimated reduction of 14.96 (P = 0.003). There were no reports of adverse outcomes such as a delay in responding to a change in patient condition or delay leading to cardiopulmonary arrest. DISCUSSION: A reduction in nonactionable, physiologic alarms was attained after implementing multimodal strategies inclusive of adjusting default settings, staff education on managing alarms, and emphasis on staff accountability.

Examining the validity of a predictive model for vaginal birth after cesarean.

Background The Maternal-Fetal Medicine Units (MFMU) vaginal birth after cesarean (VBAC) calculator, while accurate for candidates with high predicted success rates, is not as accurate for poor candidates. This study examines the calculator's validity in an understudied multiracial cohort with a high proportion of poor candidates. Methods This retrospective study examined women with one or two prior cesarean deliveries who attempted VBAC at a single institution. Subjects were placed into quartiles based on MFMU-predicted success rates. For each quartile, actual and predicted success rates were compared. The calculated area under the receiver operating characteristic curve (AUC) was compared to the original AUC. Results The study included 1604 women. Actual and predicted VBAC rates were similar in the lowest and highest quartile groups, 18.2% vs. 21.2% (n = 11, P > 0.99) and 87.1% vs. 88.5% (n = 1090, P = 0.14), respectively. In the 51-75% predicted success rate group, the actual VBAC rate was higher than the predicted rate, 69.9% vs. 65.5% (n = 394) but not statistically significant (P = 0.07). In the 25-50% predicted success rate group, the actual VBAC rate was significantly higher than the predicted rate 55.1% vs. 39.6% (n = 109, P = 0.002). The actual AUC was lower than the MFMU model, 0.72 [95% confidence interval (CI) 0.69-0.75] vs. 0.77 (95% CI 0.76-0.78) (P < 0.001). Conclusion The MFMU VBAC calculator's predicted success rates were comparable to actual success rates for candidates with predicted success rates >75%. As predicted success rates declined, the calculator was increasingly inaccurate and underestimated the success rate. Caution should be taken when using the MFMU VBAC calculator for poor candidates.

Defense Automated Neurobehavioral Assessment Accurately Measures Cognition in Patients Undergoing Electroconvulsive Therapy for Major Depressive Disorder.

OBJECTIVES: The Defense Automated Neurobehavioral Assessment (DANA) is an electronic cognitive test battery. The present study compares DANA to the standard Mini-Mental State Examination (MMSE) in subjects undergoing electroconvulsive therapy for the treatment of major depressive disorder. METHODS: Seventeen inpatient subjects in the Johns Hopkins Hospital Department of Psychiatry were administered longitudinal paired DANA and MMSE tests (7.6 ± 4.1 per patient) from January 10, 2014 to September 26, 2014. Regression analyses were conducted (with or without MMSE scores of 30) to study the impact of the MMSE upper limit, and within-subject regression analyses were conducted to compare MMSE and DANA scores over time. RESULTS: Statistically significant relationships were measured between DANA and MMSE scores. Relationships strengthened when MMSE scores of 30 were omitted from analyses, demonstrating a ceiling effect of the MMSE. Within-subject analyses revealed relationships between MMSE and DANA scores over the duration of the inpatient stay. CONCLUSIONS: Defense Automated Neurobehavioral Assessment is an electronic, mobile, repeatable, sensitive, and valid method of measuring cognition over time in depressed patients undergoing electroconvulsive therapy treatment. Automation of the DANA allows for more frequent cognitive testing in a busy clinical setting and enhances cognitive assessment sensitivity with a timed component to each test.

Impact of a Fast Pass on Emergency Department Wait Times for Oncology Patients with Febrile Neutropenia.

This pilot study examined differences in wait times for oncology patients who presented to the emergency department, with or without a Fast Pass, for febrile neutropenia (FN). Inadequate circulating neutrophils create a health risk for FN patients. An increased number of patients are receiving chemotherapy in an outpatient setting and may experience delays when seeking treatment in the emergency department. These delays in treatment may be due to overcrowding, patients who require life-saving medical interventions, and inconsistencies in recognizing febrile neutropenia, where fever may be the only presenting sign. The purpose of this study was to measure the impact on wait times, increasing possible risk of bacterial or viral exposure in the emergency department waiting room, for patients with a potential diagnosis of FN who presented their "Fast Pass" from the hospital cancer center's program upon arrival. Electronic medical records were reviewed over a period of 21 months, comparing wait times in the ED for oncology patients with potential FN before and after implementation of the Fast Pass program at an urban medical center in Hawai'i. Of the 1300 oncology patient chart reviews conducted, 6 patients met the study-defined inclusion criteria pre-Fast Pass and 10 met the study-defined inclusion criteria post-Fast Pass. Influence of the use of a Fast Pass on patient wait times was tested using a multivariate regression adjusted for ED patient volume. There were no differences in overall wait times pre- and post-Fast Pass.

Medications that Regulate Gastrointestinal Transit Influence Inpatient Blood Glucose.

Objective: A multitude of factors affect a hospitalized individual's blood glucose (BG), making BG difficult to predict and manage. Beyond medications well established to alter BG, such as beta-blockers, there are likely many medications with undiscovered effects on BG variability. Identification of these medications and the strength and timing of these relationships has potential to improve glycemic management and patient safety. Materials and Methods: EHR data from 103,871 inpatient encounters over 8 years within a large, urban health system was used to extract over 500 medications, laboratory measurements, and clinical predictors of BG. Feature selection was performed using an optimized Lasso model with repeated 5-fold cross-validation on the 80% training set, followed by a linear mixed regression model to evaluate statistical significance. Significant medication predictors were then evaluated for novelty against a comprehensive adverse drug event database. Results: We found 29 statistically significant features associated with BG; 24 were medications including 10 medications not previously documented to alter BG. The remaining five factors were Black/African American race, history of type 2 diabetes mellitus, prior BG (mean and last) and creatinine. Discussion: The unexpected medications, including several agents involved in gastrointestinal motility, found to affect BG were supported by available studies. This study may bring to light medications to use with caution in individuals with hyper- or hypoglycemia. Further investigation of these potential candidates is needed to enhance clinical utility of these findings. Conclusion: This study uniquely identifies medications involved in gastrointestinal transit to be predictors of BG that may not well established and recognized in clinical practice.

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn's disease.

BACKGROUND: Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence (POR) of Crohn's disease (CD). However, its prognostic value is uncertain, in part, due to difficulties studying it non-invasively. AIM: To evaluate the prognostic value of pre-operative radiographic mesenteric parameters for early endoscopic POR (ePOR). METHODS: We conducted a retrospective cohort study of CD subjects ≥ 12 years who underwent ileocecal or small bowel resection between 1/1/2007 to 12/31/2021 with computerized tomography abdomen/pelvis ≤ 6 months pre-operatively and underwent ileocolonoscopy ≤ 15 months post-operatively. Visceral adipose tissue (VAT) volume (cm3), ratio of VAT:subcutaneous adipose tissue (SAT) volume, VAT radiodensity, and ratio of VAT:SAT radiodensity were generated semiautomatically. Mesenteric lymphadenopathy (LAD, largest lymph node > 10 mm) and severe vasa recta (VR) engorgement (diameter of the VR supplying diseased bowel ≥ 2 × VR supplying healthy bowel) were derived manually. The primary outcome was early ePOR (Rutgeert's score ≥ i2 on first endoscopy ≤ 15 months post-operatively) and the secondary outcome was ePOR severity (Rutgeert's score i0-4). Regression analyses were performed adjusting for demographic and disease-related characteristics to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: Of the 139 subjects included, 45% of subjects developed early ePOR (n = 63). VAT radiodensity (aOR 0.59, 95%CI: 0.38-0.90) and VAT:SAT radiodensity (aOR 8.54, 95%CI: 1.48-49.28) were associated with early ePOR, whereas, VAT volume (aOR 1.23, 95%CI: 0.78-1.95), VAT:SAT volume (aOR 0.80, 95%CI: 0.53-1.20), severe VR engorgement (aOR 1.53, 95%CI: 0.64-3.66), and mesenteric LAD (aOR 1.59, 95%CI: 0.67-3.79) were not. Similar results were observed for severity of ePOR. CONCLUSION: VAT radiodensity is potentially a novel non-invasive prognostic imaging marker to help risk stratify CD patients for POR.

Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92 · 3% of patients received the primer vaccine, 70 · 8% received one monovalent booster, but only 30 · 1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR = 0 · 61, p = 0 · 024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed.

Predictors of Multi-Vessel Identification, Outcome, and Optimal Surgical Timing for Microvascular Decompression in Hemifacial Spasm.

OBJECTIVES AND BACKGROUND: Hemifacial spasm (HFS) is a disabling condition that imposes significant burden upon patients. Microvascular decompression (MVD) surgery is the most effective and long-lasting treatment for HFS, but outcomes following this surgery may vary based on a variety of clinical and operative factors. A more thorough understanding of the variables that impact patient outcome after MVD surgery is needed. METHODS: A systematic review and meta-analysis of Medline, Embase, and Central was conducted (n = 2108 screened; n = 86 included) with the goal of determining the impact of the following variables on outcome: duration of disease, geographic location, intraoperative use of an endoscope, and intraoperative finding of single versus multi-vessel neurovascular compression. RESULTS: Most cases of hemifacial spasm occur on the left side (53.9%, p < 0.001) and are more common in women than men (66.5% versus 33.5%, p < 0.0001). The offending vessel frequencies were: 40.8% anterior inferior cerebellar artery [AICA], 24.9% posterior inferior cerebellar artery [PICA], 17.2% multiple vessels, and 4.7% vertebral artery [VA]. Multiple vessel combinations involved: 26.5% PICA + AICA, 24.6% PICA + VA, 23.1% AICA + VA, and 4.7% AICA + PICA + VA. Relative to the Americas, AICA was less frequent in Europe (p = 0.005), while PICA more frequent in Europe (p = 0.009) and Asia (p < 0.0001). With endoscope assistance, frequency of multiple vessels identified was 31.7% (versus 14.7% with non-endoscopic, p = 0.005), and 27.4% for AICA (43.5% with non-endoscopic, p = 0.003). Spasm improvement was 94.1% near discharge and 96.0% at maximum follow-up. Complications occurred in 16.5% of cases, with spasm recurrence in 2.4%. Greatest frequency of spasm improvement (p < 0.0001) and lowest spasm recurrence rates (p = 0.0005) were reported in series from Asia. For every additional month of pre-operative spasm, the effect size of post-operative improvement decreased (p = 0.04). With every subsequent postoperative month, the effect size of spasm improvement increased (p = 0.0497). The frequency of spasm improvement was significantly higher in series published after 2005 (94.4% versus 97.4%, p = 0.005). CONCLUSION: Clinical outcomes following MVD for HFS have improved since 2005. Consideration should be given to earlier operation (shorter disease duration) and use of an endoscope may increase detection of multiple offending vessels. Further studies are needed to understand regional differences in culprit vessel incidence and surgical outcomes in the Americas, Europe, and Asia.

Demographic recruitment bias of adults in United States randomized clinical trials by disease categories between 2008 to 2019: a systematic review and meta-analysis.

To promote health equity within the United States (US), randomized clinical trials should strive for unbiased representation. Thus, there is impetus to identify demographic disparities overall and by disease category in US clinical trial recruitment, by trial phase, level of masking, and multi-center status, relative to national demographics. A systematic review and meta-analysis were conducted using MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov, between 01/01/2008 to 12/30/2019. Clinical trials (N = 5,388) were identified based on the following inclusion criteria: study type, location, phase, and participant age. Each clinical trial was independently screened by two researchers. Data was pooled using a random-effects model. Median proportions for gender, race, and ethnicity of each trial were compared to the 2010 US Census proportions, matched by age. A second analysis was performed comparing gender, race, and ethnicity proportions by trial phase, multi-institutional status, quality, masking, and study start year. 2977 trials met inclusion criteria (participants, n = 607,181) for data extraction. 36% of trials reported ethnicity and 53% reported race. Three trials (0.10%) included transgender participants (n = 5). Compared with 2010 US Census data, females (48.3%, 95% CI 47.2-49.3, p < 0.0001), Hispanics (11.6%, 95% CI 10.8-12.4, p < 0.0001), American Indians and Alaskan Natives (AIAN, 0.19%, 95% CI 0.15-0.23, p < 0.0001), Asians (1.27%, 95% CI 1.13-1.42, p < 0.0001), Whites (77.6%, 95% CI 76.4-78.8, p < 0.0001), and multiracial participants (0.25%, 95% CI 0.21-0.31, p < 0.0001) were under-represented, while Native Hawaiians and Pacific Islanders (0.76%, 95% CI 0.71-0.82, p < 0.0001) and Blacks (17.0%, 95% CI 15.9-18.1, p < 0.0001) were over-represented. Inequitable representation was mirrored in analysis by phase, institutional status, quality assessment, and level of masking. Between 2008 to 2019 representation improved for only females and Hispanics. Analysis stratified by 44 disease categories (i.e., psychiatric, obstetric, neurological, etc.) exhibited significant yet varied disparities, with Asians, AIAN, and multiracial individuals the most under-represented. These results demonstrate disparities in US randomized clinical trial recruitment between 2008 to 2019, with the reporting of demographic data and representation of most minorities not having improved over time.

Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma.

C-C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice.

Dietary Composition, Angiographic Coronary Disease, and Cardiovascular Outcomes in the WISE Study (Women's Ischemia Syndrome Evaluation).

BACKGROUND: Studies relating diet to angiographic coronary artery disease (CAD) and subsequent major adverse cardiac events (MACE) in women are limited. Information on diet was collected in the Women's Ischemia Syndrome Evaluation (WISE), a prospective cohort study of symptomatic women referred for coronary angiography to evaluate suspected ischemic heart disease. METHODS: A consecutive subgroup (n = 201 of 936) of enrolled women completed the modified Block food frequency questionnaire (FFQ). Data on outcomes were collected and adjudicated after 8-year follow-up. A set of logistic regression models were fitted for non-obstructive versus obstructive coronary stenosis (<50% versus ≥50%). Cox proportional hazard regression models were fitted for outcomes, with each dietary composition variable adjusted for the degree of coronary stenosis. RESULTS: At baseline, the subgroup cohort was 58 ± 12 years old with a body mass index (BMI) of 30 ± 7 kg/m2. An increased proportion of calories consumed from protein was associated with higher levels of baseline obstructive coronary stenosis. Those individuals who ate a higher amount of protein, carotene, and servings of vegetables and meat, however, were each associated with lower subsequent adverse outcomes, respectively. CONCLUSIONS: Among women undergoing coronary angiography for suspected CAD, a higher percentage of protein intake was associated with higher baseline stenosis severity; however, the amount of protein intake, vegetable, meat, and carotene intake, was conversely associated with subsequent lower adverse cardiovascular outcome risk.

Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T-cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92·3% of patients received the primer vaccine, 70·8% received one monovalent booster, but only 30·1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR=0·61, P=0·024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed. Highlights: COVID-19 booster vaccinations increase antibody levels and maintain T-cell responses against SARS-CoV-2 in patients receiving various anti-cancer therapiesBooster vaccinations reduced all-cause mortality in patientsA significant proportion of patients remain unboosted and strategies are needed to encourage patients to be up-to-date with vaccinations.

Pituitary Incidentalomas in the United States: A National Database Estimate.

OBJECTIVE: Increasing use of imaging is associated with increasing diagnoses of pituitary incidentalomas (PIs), which often do not require surgical or medical treatment. In this study, we evaluate U.S. incidence, epidemiology, and trends of pituitary adenomas (PAs) and PIs from 2004 to 2018. METHODS: A total of 50,220 PAs were selected from the SEER (Surveillance Epidemiology and End Results) 2020 submission. PIs that do not initially require surgical or medical treatment were filtered from PAs if they were best diagnostically confirmed by radiography, not indicated as prolactinomas in physician reports, not recommended surgery initially, and reported a correct tumor size. Age-adjusted incidence rates, patient demographics, tumor characteristics, trends over time, and differences between PAs and PIs were explored. RESULTS: Between 2004 and 2018, the incidence rates of PAs and PIs were 4.28 ± 0.04 and 1.53 ± 0.02 per 100,000 population, respectively. When observing changes from 2004 to 2018, a nearly 3-fold increase from 0.73 ± 0.05 to 2.00 ± 0.09 per 100,000 was observed for PIs. The proportion of PIs significantly increased from 24.91% of all PA diagnoses in 2004 to 42.07% in 2018 (P < 0.001). When comparing non-PI PAs with PIs, PIs were more commonly diagnosed in females (64.72% vs. 54.27%; P < 0.001) with microadenomas (61.68% vs. 13.37%; P < 0.001). CONCLUSIONS: Reports of increasing PAs in the United States are likely caused by an increase in diagnosing PIs. This result parallels findings from other countries. This national PI estimate may serve as a point of comparison for future studies investigating imaging and PI rates at individual institutions.

Can lacrimal punctum size link to the severity of dry eye disease?

To investigate if larger punctum size links to the severity of dry eye disease (DED) and perhaps, punctum size inspection can be adopted to become one of the DED evaluations for practitioners. The records of 200 eyes of 114 patients that had temporary collagen punctum plugs due to severe DED (Level 2 to Level 4) from January 1, 2017, to July 31, 2018, were reviewed for the size of the plugs. Lacrimal punctum size of those eyes was approximated according to the size of vertical canalicular soft collagen plug (from 0.3 to 0.5 mm diameter, Oasis, Lacrimedics, Glendora, CA, USA). The dry eye severity grading from the International Dry Eye WorkShop was used to grade the level of the severity of DED. Those eyes classified as Level 2 and above were considered as severe due to the presentation of moderate-to-diffuse corneal staining and symptomatic. To assess if there is a correlation between punctum size and the severity of DED, the Spearman's rank correlation coefficient was calculated. Of the 200 Level 2 and above eyes, 131 (66%) eyes had a large punctum (≥0.5 mm). Punctum size larger than 0.4 mm was 95%. The estimated Spearman's ρ was 0.16. This indicates a statistical significant positive correlation (P = 0.02) between larger punctum size and higher level of DED. The larger size of lacrimal punctum may link to the severity of DED. Punctum inspection may be adopted to become one parameter for DED evaluation for practitioners.