Multivariable Mendelian randomization with incomplete measurements on the exposure variables in the Hispanic Community Health Study/Study of Latinos.

Multivariable Mendelian randomization allows simultaneous estimation of direct causal effects of multiple exposure variables on an outcome. When the exposure variables of interest are quantitative omic features, obtaining complete data can be economically and technically challenging: the measurement cost is high, and the measurement devices may have inherent detection limits. In this paper, we propose a valid and efficient method to handle unmeasured and undetectable values of the exposure variables in a one-sample multivariable Mendelian randomization analysis with individual-level data. We estimate the direct causal effects with maximum likelihood estimation and develop an expectation-maximization algorithm to compute the estimators. We show the advantages of the proposed method through simulation studies and provide an application to the Hispanic Community Health Study/Study of Latinos, which has a large amount of unmeasured exposure data.

Percutaneous nucleoplasty and intradiscal electrothermal therapy in the management of lumbar discogenic pain: A retrospective comparative study.

Percutaneous lumbar nucleoplasty (PLN) and intradiscal electrothermal therapy (IDET) are effective treatment options for discogenic low back pain (D-LBP). We evaluated the effectiveness of PLN and IDET and the positive predictive factors associated with intradiscal procedures. We reviewed the medical records of 205 patients who underwent IDET or PLN in patients with D-LBP followed by positive provocation discography. A successful outcome was defined as ≥ 50% pain relief on the numerical rating scale (NRS) pain score at the 6-month follow-up visit. The relationship between the outcome of the intradiscal procedure and clinical variables was investigated using multivariate analyses. Of the 142 patients (89 with PLN and 53 with IDET), 86 (60.5%) experienced a successful outcome, which was more substantial in PLN (n = 61, 68.5%) than in IDET (n = 25, 47.2%; P = .010). The high-grade Modified Dallas Discogram Scale in provocation discography and a procedure at the L3/L4 spinal level were independent positive predictors of successful outcomes (P = .023 and .010, respectively). Coexisting psychiatric disorders, such as depression and anxiety, were negative predictors of successful treatment (P = .007). No serious complications related to the intradiscal procedures were reported during the 6-month follow-up period. PLN and IDET might be effective for managing low back pain (LBP) from internal disc disruption (IDD). The high-grade Modified Dallas Discogram, a procedure at the L3/4 spinal level, and the absence of neuropsychiatric disorders could be positive factors for the successful outcome of the intradiscal procedure.

LifeCourse Socioeconomic Position and Ideal Cardiovascular Health in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults. METHODS AND RESULTS: We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association "Life's Essential 8," we built a score of ideal CVH at baseline and the 6-year follow-up. Linear mixed-effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (ß for high school versus high school versus

Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

The pros and cons of ultrasound-guided procedures in pain medicine.

The application of ultrasound (US) in pain medicine has been a rapidly growing field since the 2000s. Musculoskeletal injections, peripheral nerve blocks, and neuraxial injections under US guidance have been acknowledged for managing chronic pain. Although many studies on US-guided pain procedures have been published, there needs to be a classification system to evaluate which image device, the US or fluoroscopy, is clinically and technically better in various pain interventions. Therefore, this narrative review introduces the classification system for the US-guided pain procedures according to their clinical and technical outcomes and designates US-guided pain procedures into one of the four categories by reviewing previous prospective randomized comparative trials.

Synthesis and evaluation of antibody-drug conjugates with high drug-to-antibody ratio using dimaleimide-DM1 as a linker- payload.

The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through monoclonal antibodies (mAbs) and a high ratio of drug to antibody (DAR). The achievements of Kadcyla® (T-DM1) and Enhertu® (T-Dxd) have demonstrated that HER2-targeting antibodies, such as trastuzumab, have shown to be competitive in terms of efficacy and price for development. Furthermore, with the arrival of T-Dxd and Trodelvy®, high-DAR (7-8) ADCs, which differ from the moderate DAR (3-4) ADCs that were formerly regarded as conventional, are being acknowledged for their worth. Following this trend of drug development, we endeavored to develop a high-DAR ADC using a straightforward approach involving the utilization of DM1, a highly potent substance, in combination with the widely recognized trastuzumab. To achieve a high DAR, DM1 was conjugated to reduced cysteine through the simple design and synthesis of various dimaleimide linkers with differing lengths. Using LC and MS analysis, we have demonstrated that our synthesis methodology is uncomplicated and efficacious, yielding trastuzumab-based ADCs that exhibit a remarkable degree of uniformity. These ADCs have been experimentally substantiated to exert an inhibitory effect on cancer cells in vitro, thus affirming their value as noteworthy additions to the realm of ADCs.

Evaluation of thoracic sympathetic ganglion block as a predictor for response to ketamine infusion therapy and spinal cord stimulation in patients with chronic upper extremity pain.

OBJECTIVE: To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). DESIGN: Retrospective. SETTING: Tertiary hospital single-center. SUBJECTS: Patients who underwent TSGB receiving KIT or SCS within a 3-year window. METHODS: Positive TSGB outcomes were defined as ≥2 0-10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2-4 weeks post-KIT and ≥4 NRS score reduction at 2-4 weeks post-SCS implantation, respectively. RESULTS: Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n = 20) reported a ≥ 2 0-10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n = 14) KIT responders, significantly higher than that in 30.8% (n = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26-39.02). Among 32 patients who underwent SCS implantation, 68.8% (n = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. CONCLUSIONS: A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS.

Genetic Subtypes of Prediabetes, Healthy Lifestyle, and Risk of Type 2 Diabetes.

Prediabetes is a heterogenous metabolic state with various risks for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latino participants without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic White participants without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n = 3,677) and UKBB (n = 16,284) separately based on these pPRSs. Six clusters of individuals with prediabetes with distinctive patterns of pPRSs and corresponding metabolic traits were identified in the HCHS/SOL, five of which were confirmed in the UKBB. Although baseline glycemic traits were similar across clusters, individuals in cluster 5 and cluster 6 showed an elevated risk of T2D during follow-up compared with cluster 1 (risk ratios [RRs] 1.29 [95% CI 1.08, 1.53] and 1.34 [1.13, 1.60], respectively). Inverse associations between a healthy lifestyle score and risk of T2D were observed across different clusters, with a suggestively stronger association observed in cluster 5 compared with cluster 1. Among individuals with a healthy lifestyle, those in cluster 5 had a similar risk of T2D compared with those in cluster 1 (RR 1.03 [0.91, 1.18]). This study identified genetic subtypes of prediabetes that differed in risk of progression to T2D and in benefits from a healthy lifestyle.

Metabolic and inflammatory perturbation of diabetes associated gut dysbiosis in people living with and without HIV infection.

BACKGROUND: Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. METHODS: We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women's Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria-diabetes associations are explained by altered metabolites and proteins. RESULTS: Seven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera-diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV. CONCLUSION: Among individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera-diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection.

Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice.

Background: : Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: : The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: : HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: : APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

Prognostic indicators of corneal ulcer clinical outcomes at a tertiary care center in the Bronx, New York.

PURPOSE: Corneal ulcers frequently result in ocular morbidity and may lead to permanent visual impairment if severe or untreated. This study aims to evaluate the association of patient factors and ocular exam findings on clinical outcomes for patients diagnosed with a corneal ulcer at a tertiary care center in the Bronx, New York. METHODS: A retrospective chart review was conducted on all ambulatory and admitted patients diagnosed with a corneal ulcer (identified using ICD-10 code H16.0) at Montefiore Medical Center, Bronx, NY between 2016-2022. Patient demographics, presence of known risk factors, characteristics of subsequent clinical course, and microbiological studies were noted. Clinical outcomes following treatment were longitudinally evaluated and categorized based upon the following criteria: 1) 'No Surgical Intervention': No severe complications or surgery required after presentation, 2) 'Surgical Intervention': Decline in BCVA with surgery required for a severe complication. RESULTS: The search criteria identified 205 patients (205 eyes) with the diagnosis of a corneal ulcer. Mean age was 55.3 ± 21.1 years (mean ± SD). Mean ulcer area at presentation was 7 ± 10.5 mm2. Mean LogMAR at presentation was 1.2 ± 1, and following treatment, improved to 1.0 ± 1. 'Surgical Intervention' outcome was associated with advanced age (p = 0.005), presence of ocular surface disease (p = 0.008), central location of ulcer (p = 0.014), greater ulcer area at presentation (p = 0.003), worse visual acuity at presentation (p < 0.001), and isolation of fungi (p = 0.004). CONCLUSION: Identification of risk factors associated with a poor clinical prognosis can guide treatment and inform expectations for patients diagnosed with a corneal ulcer. Our study highlights the importance of timely diagnosis, work-up, and initiation of appropriate management, particularly in vulnerable populations where access to specialty care is logistically challenging.

Effect of Air Pollutants on Allergic Inflammation in Structural Cells of the Nasal Mucosa.

OBJECTIVES: Air pollution is an increasing global concern, and its effect on allergic inflammation has attracted the attention of many researchers. Particulate matter (PM) is a major component of ambient air pollution, and heavy metals are the primary toxic constituents of PM. As previous studies on the impact of air pollutants on allergic inflammation did not adequately mimic real-world atmospheric exposure, we developed an experimental model to investigate the effects of aerosolized air pollutants on nasal epithelial cells and fibroblasts. METHODS: We collected particulate matter 2.5 (PM2.5) samples from ambient 24-hour air samples obtained in Seoul from August 2020 to August 2022, and then conducted component analysis for metallic constituents. Primary nasal epithelial cells and nasal fibroblasts, obtained and cultured from the turbinate tissues of human participants, were treated with PM2.5. The associations of heavy metals identified from the component analysis with cytokine expression were investigated. A three-dimensional (3D)-hybrid culture model, consisting of co-culture of an air-liquid interface and nasal fibroblast spheroids, was constructed to observe the impact of aerosolized air pollutants. RESULTS: Among the heavy metals, Si was the predominant component of PM2.5, and Zn showed the highest correlation with the concentration of PM2.5 in Seoul. PM2.5, Zn, and Si increased the production of epithelial cell-derived cytokines, and PM2.5 and Zn exhibited similar trends with one another. Exposure of the 3D-hybrid model to aerosolized PM2.5 and Zn resulted in elevated periostin, alpha-smooth muscle actin, and fibronectin expression in fibroblast spheroids, and those without an epithelial barrier exhibited a similar increase in periostin expression. CONCLUSION: Ambient air pollutants in the form of aerosols increase the expression of allergic inflammatory cytokines in both nasal epithelial cells and fibroblasts. Regulations on air pollution will help reduce the global burden of allergic diseases in the future.

Association of HIV and HCV Infection With Carotid Artery Plaque Echomorphology in the MACS/WIHS Combined Cohort Study.

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.

Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States.

Background :   Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI). Methods: Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves. Results: MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011). Conclusion: In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes.

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for example, enriched Bifidobacterium and reduced Prevotella) and circulating metabolites (for example, increased indolepropionate and reduced branched-chain amino acid metabolites). Many of these metabolites are related to the identified milk-associated bacteria and partially mediate the association between milk intake and T2D in LNP individuals. Our study demonstrates a protective association between milk intake and T2D among LNP individuals and a potential involvement of gut microbiota and blood metabolites in this association.

Assessing an Exposure Keratopathy Prevention Strategy in Mechanically Ventilated Patients: A Retrospective Study.

OBJECTIVE: Patients who are intubated and sedated are at risk for developing exposure keratopathy, which can lead to permanent vision loss. This retrospective study assesses the incidence of exposure keratopathy (EK) in intensive care unit (ICU) patients before and after implementation of an EK Prevention Order Set. METHODS: At one tertiary care hospital (Bronx, NY), an "Exposure Keratopathy Prevention Order Set" was implemented to ameliorate this risk which included the application of white petrolatum-mineral oil lubricating ointment every 6 hours in both eyes. This retrospective chart review study analyzed the incidence of EK diagnosis before and after implementation of this EK Prevention Order Set. Patients who were on mechanical ventilation at the time of ophthalmology consult request between January 1, 2021, and December 31, 2021, were included. Ophthalmology consult notes of patients with EK diagnosis were reviewed for details regarding the consult request, examination findings, diagnosis, and treatment plan. RESULTS: There were 247 and 361 ventilated ICU patients before and after the order set, respectively. The number of ophthalmology consults decreased slightly after the order set from 15 of 247 to 20 of 361 ventilated patients. In addition, the rate of EK among ventilated patients decreased from 4.5% (11 of 247 patients over 151 days) to 2.2% (8 of 361 patients over 212 days; P =0.154) with a risk ratio of 0.50 (95% CI 0.20-1.22). CONCLUSION: The number of patients diagnosed with EK trended down after implementation of the EK Prevention Order Set.

Mendelian randomization with incomplete measurements on the exposure in the Hispanic Community Health Study/Study of Latinos.

Mendelian randomization has been widely used to assess the causal effect of a heritable exposure variable on an outcome of interest, using genetic variants as instrumental variables. In practice, data on the exposure variable can be incomplete due to high cost of measurement and technical limits of detection. In this paper, we propose a valid and efficient method to handle both unmeasured and undetectable values of the exposure variable in one-sample Mendelian randomization analysis with individual-level data. We estimate the causal effect of the exposure variable on the outcome using maximum likelihood estimation and develop an expectation maximization algorithm for the computation of the estimator. Simulation studies show that the proposed method performs well in making inference on the causal effect. We apply our method to the Hispanic Community Health Study/Study of Latinos, a community-based prospective cohort study, and estimate the causal effect of several metabolites on phenotypes of interest.

Clinical characteristics of local allergic rhinitis sensitized to house dust mites in Asia.

PURPOSE: Local allergic rhinitis (LAR) is characterized by a localized nasal allergic response without evidence of systemic atopy. LAR is an underdiagnosed entity and is a diagnostic and therapeutic challenge for clinicians. This study aimed to investigate the prevalence and clinical characteristics of patients with LAR to house dust mites (LAR-HDM) in Korea. METHODS: We performed a retrospective chart review of 336 adult patients with rhinitis symptoms who visited the Rhinologic Clinic at Korea University Guro Hospital from October 2019 to April 2021. Using results of the skin prick test, serologic test, and nasal provocation test, patients were classified as allergic rhinitis (AR) to HDM (AR-HDM), AR to other allergens, non-allergic rhinitis (NAR), or LAR-HDM. We excluded patients with AR to other allergens and compared the clinical characteristics of the remaining three groups. Patient demographic data were reviewed, and patients' nasal symptoms, olfactory function, serum total IgE, and severity of accompanying rhinosinusitis were evaluated. RESULTS: In total, 336 patients were examined. AR-HDM was diagnosed in 138 (41.1%) patients, AR to other allergens in 36 (10.7%) patients, NAR in 21 (42.0%) patients, and LAR-HDM in 21 (6.3%) patients. The mean age of patients with LAR-HDM was significantly higher than that of patients with AR-HDM. There were no significant differences in sex, smoking history, asthma, and family history of allergic diseases between the groups. Compared to NAR patients, there were significantly more patients with LAR-HDM who had persistent nasal symptoms. The frequency of nasal itching and sneezing was significantly higher in the LAR-HDM group than in the NAR group. The olfactory function score in the LAR-HDM group was significantly worse than that in the AR-HDM group, and the Lund-Mackay score was significantly higher in the LAR-HDM group than in the other groups. CONCLUSION: Clinical history and nasal symptoms are very similar in LAR-HDM and AR-HDM. Clinicians should take more care to differentiate them. LAR-HDM should also be considered in patients with persistent and severe nasal symptoms without systemic atopy.

Risk Factors for Sudden Cardiac Arrest Among Hispanic or Latino Adults in Southern California: Ventura PRESTO and HCHS/SOL.

Background Out-of-hospital sudden cardiac arrest (SCA) is a leading cause of mortality, making prevention of SCA a public health priority. No studies have evaluated predictors of SCA risk among Hispanic or Latino individuals in the United States. Methods and Results In this case-control study, adult SCA cases ages 18-85 (n=1,468) were ascertained in the ongoing Ventura Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) study (2015-2021) in Ventura County, California. Control subjects were selected from 3033 Hispanic or Latino participants who completed Visit 2 examinations (2014-2017) at the San Diego site of the HCHS/SOL (Hispanic Community Health Survey/Study of Latinos). We used logistic regression to evaluate the association of clinical factors with SCA. Among Hispanic or Latino SCA cases (n=295) and frequency-matched HCHS/SOL controls (n=590) (70.2% men with mean age 63.4 and 61.2 years, respectively), the following clinical variables were associated with SCA in models adjusted for age, sex, and other clinical variables: chronic kidney disease (odds ratio [OR], 7.3 [95% CI, 3.8-14.3]), heavy drinking (OR, 4.5 [95% CI, 2.3-9.0]), stroke (OR, 3.1 [95% CI, 1.2-8.0]), atrial fibrillation (OR, 3.7 [95% CI, 1.7-7.9]), coronary artery disease (OR, 2.9 [95% CI, 1.5-5.9]), heart failure (OR, 2.5 [95% CI, 1.2-5.1]), and diabetes (OR, 1.5 [95% CI, 1.0-2.3]). Conclusions In this first population-based study, to our knowledge, of SCA risk predictors among Hispanic or Latino adults, chronic kidney disease was the strongest risk factor for SCA, and established cardiovascular disease was also important. Early identification and management of chronic kidney disease may reduce SCA risk among Hispanic or Latino individuals, in addition to prevention and treatment of cardiovascular disease.