Surrogate Marker Research Articles

Biomarkers of bone metabolism in [223Ra] RaCl2 therapy - association with extent of disease and prediction of overall survival

BackgroundThe alpha-emitting radionuclide therapy [223Ra]RaCl2 (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.MethodsProspective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.ResultsA total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7–16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1–4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1–2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3–5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1–13.9), P < 0.001).ConclusionBMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.Trial registrationClinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1.

Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs.

The identification of the activation of the mammalian target of rapamycin (mTOR) signalling pathway as a frequent molecular event in canine cutaneous papillomas (CPs) has provided the rational foundation to explore novel molecular-targeted therapies. Recent evidence indicates that metformin reduces the size of CPs in mice by inhibiting the mTOR signalling pathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter. The aim of the present study was to characterise the expression pattern of the metformin uptake transporter OCT3 in canine samples of CP that have shown activation of the mTOR signalling pathway in order to predict if this hyperplastic epidermal lesion is potentially sensitive to metformin. The expression of OCT3 was evaluated by immunohistochemical investigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluated for the mTOR activation marker pS6. OCT3 was highly expressed in the membrane and cytoplasm of the basal and suprabasal epidermal cells in all samples of canine CP. This OCT3 expression was localised at similar epidermal compartments to those observed for pS6. These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.

Prevalence of physiological and perceptual markers of low energy availability in male academy football players: a study protocol for a cross-sectional study

Low energy availability (LEA) is a core feature of the female athlete triad and relative energy deficiency in sport (REDs). LEA underpins multiple adverse health and performance outcomes in various...

Phenotypic Characterisation of Obstructive Sleep Apnoea in Acute Coronary Syndrome

Recent neutral randomised clinical trials have created clinical equipoise for treating obstructive sleep apnoea (OSA) for managing cardiovascular risk. The importance of defining the links between OSA and cardiovascular disease is needed with the aim of advancing the robustness of future clinical trials. We aimed to define the clinical correlates and characterise surrogate cardiovascular markers in patients with acute coronary syndrome (ACS) and OSA. Overall, 66 patients diagnosed with ACS were studied. Patients underwent an unattended polysomnogram after hospital discharge (median [interquartile range] 62 [37-132] days). The Epworth Sleepiness Scale, Berlin, and STOP-BANG questionnaires were administered. Surrogate measures of vascular structure and function, and cardiovascular autonomic function were conducted. Pulse wave amplitude drop was derived from the pulse oximetry signals of the overnight polysomnogram. OSA (apnoea-hypopnea index [AHI] ≥5) was diagnosed in 94% of patients. Moderate-to-severe OSA (AHI≥15) was observed in 68% of patients. Daytime sleepiness (Epworth Sleepiness Scale ≥10) was reported in 17% of patients. OSA screening questionnaires were inadequate to identify moderate-to-severe OSA, with an area under the receiver operating characteristic curve of approximately 0.64. Arterial stiffness (carotid-femoral pulse wave velocity, 6.1 [5.2-6.8] vs 7.4 [6.6-8.6] m/s, p=0.002) and carotid intima-media thickness (0.8 [0.7-1.0] vs 0.9 [0.8-1.0] mm, p=0.027) was elevated in patients with moderate-to-severe OSA. After adjusting for age, sex and body mass index, these relationships were not statistically significant. No relationships were observed in other surrogate cardiovascular markers. A high prevalence of OSA in a mostly non-sleepy population with ACS was identified, highlighting a gross underdiagnosis of OSA among cardiovascular patients. The limitations of OSA screening questionnaires highlight the need for new models of OSA screening as part of cardiovascular risk management. A range of inconsistent abnormalities were observed in measures of vascular structure and function, and these appear to be largely explained by confounding factors. Further research is required to elucidate biomarkers for the presence and impact of OSA in ACS patients.

Proteinuria as an Endpoint in Clinical Trials of Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis (FSGS) is a characteristic histopathological lesion that is indicative of underlying glomerular dysfunction. It is not a single disease entity but rather a heterogeneous disorder that is an important cause of nephrotic syndrome and kidney failure in children and adults. The aim of this Kidney Health Initiative project was to evaluate potential endpoints for clinical trials in FSGS. This paper focuses on the data supporting proteinuria as a surrogate endpoint. Available data support the use of complete remission of proteinuria in patients with heavy proteinuria as a surrogate endpoint for progression to kidney failure. While substantial treatment effects on proteinuria that are short of a complete remission may also predict the effect of a treatment on progression to kidney failure, further work is needed to determine how such an endpoint should be defined. Fortunately, efforts are underway to bring together patient-level data from randomized controlled trials, observational studies, and registries to address this issue.

Navigating the orphan medicinal product designation: Evidence requirements for gene therapies in Europe

To provide insight into regulatory decision-making at the time of granting initial orphan designation by the Committee for Orphan Medicinal Products, we have conducted a retrospective analysis for viral vector-mediated gene therapies in rare non-oncological conditions with respect to the data provided to support the criteria to be met in successful applications. We found that a high proportion of non-clinical in vivo data was used for gene therapies, indicating earlier submissions of products which are at the stage of preclinical research and not in clinical development. Clinical data was submitted in only 13% of the applications, containing preliminary results derived from early-stage clinical trials in few patients. Mouse models were used in the majority of the submissions to generate meaningful non-clinical in vivo data highlighting their utility for proof-of-concept studies, and half of the applications containing non-clinical data generated results based solely on surrogate endpoints. The criterion of significant benefit was applicable in 54% of the submissions, which indicates that sponsors are focusing gene therapy development in areas of high unmet medical need, particularly where there are no authorized medicines available.

Shared Decision-Making Communication and Prognostic Misunderstanding in the ICU

Surrogate misunderstanding of patient survival prognosis in the intensive care unit (ICU) is associated with poor patient and surrogate outcomes. Shared decision-making (SDM) may reduce misunderstanding. To evaluate the association between SDM-aligned communication and prognostic misunderstanding. This retrospective cohort study was conducted at 13 medical and surgical ICUs at 5 hospitals in North Carolina, Pennsylvania, and Washington between December 2012 and January 2017. Participants were surrogates of adult patients receiving prolonged mechanical ventilation and ICU physicians. Analysis was performed May to November 2023. SDM-aligned communication during ICU family meetings, defined as the presence of high-quality serious illness communication behaviors aligned with SDM principles. The primary outcome was postmeeting surrogate prognostic misunderstanding, defined as the absolute difference between the physician's estimate of survival prognosis and the surrogate's perception of that estimate (range, 0-100 percentage points). The secondary outcome was postmeeting physician misunderstanding, defined as the absolute difference between a surrogate's estimate of survival prognosis and the physician's perception of that estimate (range, 0-100 percentage points). Prognostic misunderstanding of 20 percentage points or greater was considered clinically significant as in prior work. Of 137 surrogates, most were female (102 [74.5%]), and there were 22 (16.1%) Black surrogates, 107 (78.1%) White surrogates, and 8 surrogates (5.8%) with other race and ethnicity. Of 100 physicians, most were male (64 [64.0%]), with 11 (11.0%) Asian physicians, 4 (4.0%) Black physicians, and 75 (75.0%) White physicians. Median (IQR) surrogate prognostic misunderstanding declined significantly after family meetings (before: 22.0 [10.0 to 40.0] percentage points; after: 15.0 [5.0 to 34.0] percentage points; P = .002), but there was no significant change in median (IQR) physician prognostic misunderstanding (before: 12.0 [5.0 to 30.0] percentage points; after: 15.0 [5.0 to 29.0] percentage points; P = .99). In adjusted analyses, SDM-aligned communication was not associated with prognostic misunderstanding among surrogates or physicians (surrogates: β = -0.74; 95% CI, -1.81 to 0.32; P = .17; physicians: β = -0.51; 95% CI, -1.63 to 0.62; P = .38). In a prespecified subgroup analysis of 78 surrogates (56.9%) with clinically significant premeeting prognostic misunderstanding, SDM-aligned communication was associated with reduced surrogate postmeeting prognostic misunderstanding (β = -1.71; 95% CI, -3.09 to -0.34; P = .01). In this retrospective cohort study, SDM-aligned communication was not associated with changes in prognostic misunderstanding for all surrogates or physicians, but it was associated with reduced prognostic misunderstanding among surrogates with clinically significant misunderstanding at baseline.

The Association Between Hypoalbuminemia and Catheter-Related Infections in Hemodialysis Patients

Background: Catheter-related infections cause significant complications in patients with end-stage kidney disease (ESKD) undergoing hemodialysis (HD). Objectives: This study aimed to evaluate the association between serum albumin level and catheter-related infection in HD patients. Methods: This study included 210 HD patients with positive blood and catheter cultures and 210 without catheter infection. Mean albumin level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were also checked as surrogate disease markers and compared between the two groups. Results: Staphylococcus aureus (38.6% of cases) and Staphylococcus epidermidis (27.6% of cases) were the most frequently detected bacteria. Erythrocyte sedimentation rate and CRP were significantly higher in the target group (P = 0.002 and P = 0.001, respectively). Conclusions: In this investigation, hypoalbuminemia did not emerge as an independent risk factor for access-related infections. S. aureus and S. epidermidis were the predominant bacteria responsible for catheter-related infections in HD patients.

New clinicopathological concept of endometrial carcinoma with integration of histological features and molecular profiles.

The dual-stratified pathway of endometrial carcinomas (ECs) has long been dominant. However, in 2013, The Cancer Genome Atlas (TCGA) defined four EC subgroups with distinctive prognoses. Inspired by TCGA, in 2018, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) provided four pragmatic molecular classifiers to apply surrogate immunohistochemical markers to TCGA subgroup categorization. These trends prompted the revision of 2020 WHO Classification of Female Genital Tumors, 5th edition (2020 WHO classification), in which four molecular subtypes are recognized: POLE-ultramutated; mismatch repair-deficient; p53-mutant; and no specific molecular profile. In the 2020 WHO classification, the diagnostic algorithm is characterized by prioritizing POLEmut over other molecular abnormalities. Following the 2020 WHO classification, Federation of International Gynecology and Obstetrics (FIGO) proposed a new staging system in 2023. The updated system focuses on diagnostic parameters, such as histological type and grade, lymphovascular space invasion, and molecular alterations. These new histomolecular diagnostic concepts of ECs are being accordingly introduced into the routine pathology practice. For the first time, the 2020 WHO classification includes mesonephric-like adenocarcinoma (MLA) as a novel histological entity, mimicking the conventional mesonephric adenocarcinoma, but is considered of Müllerian ductal origin.

Performance of eGFR Slope as a Surrogate End Point for Clinical Kidney Events in a Nonglomerular Mechanism of Acute eGFR Change

Performance of eGFR Slope as a Surrogate End Point for Clinical Kidney Events in a Nonglomerular Mechanism of Acute eGFR Change

Impact of delays in neoadjuvant chemotherapy initiation on pathologic complete response among patients with HER2-positive or triple negative breast cancer.

102 Background: Pathologic complete response (pCR) is used as a surrogate endpoint for overall survival (OS) in high-risk early-stage breast cancer (BC). pCR rates vary according to BC molecular subtype and have the highest association with OS in triple negative BC (TNBC) and HER2-positive (HER2+) BC. In these subgroups, neoadjuvant chemotherapy (NACT) is often the standard of care. We evaluated the association of delays in NACT initiation (NACTI) with pCR. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis cT2+ or lymph node positive HER2+ or TNBC between 1/1/2010 – 12/31/2020, who were treated with NACT within 180 days of BC diagnosis. Time to chemotherapy (TTC) was recorded in days. Patients were categorized by receptor status. We used AJCC 7 th and 8 th edition T and N staging to define pCR (pT0 or pTis and pN0 or pN0I-). Delay was defined as TTC &gt; 60 days. Multivariable logistic regression, adjusted for demographic, socioeconomic and tumor characteristics, was used to calculate odds of pCR associated with delays. A sensitivity analysis defining delay &gt;30 and &gt;90 days was also conducted. Results: We identified 105,352 eligible patients, 73% were White, 19% were Black, 3% were Asian, and 4% were Other/Unknown. Median age at diagnosis was 52 years (range 18-90), median TTC was 32 days (range 0-180). There were 56,868 patients with HER2+ BC and 48,484 with TNBC; 9% of patients were delayed &gt; 60 days in each group. Among all HER2+ patients, 39.1% achieved a pCR: 35.0% with delay compared to 39.5% without delay. Among TNBC patients, 30% achieved a pCR: 25% with delay compared to 31% without delay (p &lt; 0.0001 for all). In multivariable analysis, patients with HER2+ disease (OR 0.85, 95%CI 0.79-0.92) and TNBC (OR 0.80, 95%CI 0.73-0.87) were less likely to achieve pCR if delayed &gt; 60 days. In a sensitivity analysis, delay &gt; 30 days was associated with lower likelihood of achieving pCR for all and delay &gt; 90 days was associated with lower likelihood for TNBC (Table). Conclusions: Delays in NACTI &gt;60 days among patients with HER2+ and TNBC BC was an independent predictor of not achieving pCR. Given the known association between socioeconomic factors and delays to initiation of treatment, interventions aimed at reducing delays may reduce disparities in BC outcomes. Future studies to identify causes of delays and the downstream impact are needed to ultimately develop interventions that mitigate these effects among patients with HER2+ or TNBC, where pCR rates are associated with OS. Association of pCR in patients who experience NACTI delay using multivariable logistic regression* n(complete case) = 77,690. Subgroup &gt;30-day Delay in NACTIOR (95% CI) &gt;60-day Delay in NACTIOR (95% CI) &gt;90-day Delay in NACTIOR (95% CI) HER2+n =41,672 0.91 (0.87-0.95) 0.85 (0.79-0.92) 0.93 (0.80-1.07) TNBCn = 36,018 0.87 (0.83-0.92) 0.80 (0.73-0.87) 0.78 (0.65-0.92) *Adjusted for demographic, socioeconomic and tumor characteristics.

EP.12G.01 PFS as a Surrogate Endpoint for OS in Real-World Patients with ROS1+ advNSCLC in the United States

EP.12G.01 PFS as a Surrogate Endpoint for OS in Real-World Patients with ROS1+ advNSCLC in the United States

Prediction of central Augmentation Index in healthy adults.

Central Augmentation Index (AIx) is a surrogate marker of large artery stiffness that may provide valuable insight to cardiovascular health. The aim of this study was to evaluate the relationship between AIx and components of physical fitness. One hundred eighty-five healthy men and women (aged 20-79 years) underwent non-invasive assessment of arterial wave reflection to determine AIx, which was corrected to a heart rate of 75 beats per minute (AI×75). Body composition was evaluated using dual energy X-ray absorptiometry (DXA) and aerobic capacity (VO<inf>2max</inf>) was derived from expired gas analysis during a symptom limited exercise test on a treadmill. A multiple linear regression revealed age and VO<inf>2max</inf> as significant predictors of AI×75 [AI×75=32.055 + (0.252×age) - (0.722×VO<inf>2max</inf>)]. Upon removal of VO<inf>2max</inf> from regression analysis, resting heart rate (RHR) and % body fat (BF%) were revealed to be significant predictors of AI×75: AI×75=-61.316 + (0.481×age) + (0.565×BF%) + (0.56×RHR). Our findings demonstrate that central Augmentation Index can be reliably predicted in healthy adults who undergo a maximal exercise or body composition assessment. These prediction equations may be applied in non-medical settings to assist in creating comprehensive health and fitness profiles for healthy clientele.

A-139 B2 involvement as a surrogate marker for a rapid and sustained response to treatment with mogamulizumab in mycosis fungoides and Sézary syndrome

A-139 B2 involvement as a surrogate marker for a rapid and sustained response to treatment with mogamulizumab in mycosis fungoides and Sézary syndrome

Associations of non-insulin-based insulin resistance indices with presence and extent of multi-territorial atherosclerosis: A cross-sectional study

BackgroundNon-insulin-based insulin resistance (IR) indices, simple and reliable surrogates for IR calculated without insulin level, have been reported to be associated with cardiovascular and cerebrovascular diseases. MethodsParticipants without diabetes from the cross-sectional baseline survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study. Non-insulin-based IR indices, including triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR) index, were calculated and stratified into quartiles. Intracranial, extracranial, coronary, subclavian, aorta, renal, ilio-femoral, and peripheral arteries were also assessed at baseline. ResultsOf 2759 included participants, the average age was 60.9 ( ± 6.6) years, and 1460 (52.9 %) were female. Compared with the first quartile of TyG index, the fourth quartile of TyG index was associated with an increased presence and extent of atherosclerotic plaques (OR, 3.51; 95 %CI,1.30–1.87; cOR, 2.22; 95 %CI,1.76–2.79) and presence and extent of atherosclerotic stenosis (OR, 1.60; 95 %CI,1.24–2.06; cOR, 1.66; 95 %CI,1.30–2.12). Such associations were also observed for the relationship of TyG-BMI index, TG/HDL-C ratio, and METS-IR index with the presence and extent of atherosclerotic plaques and stenosis. Addition of 4 non-insulin-based IR indices to the basic model with traditional risk factors improved the predictive performance of the presence of atherosclerotic plaque and stenosis. ConclusionsElevated non-insulin-based IR indices levels were associated with an increased risk of presence and extent of atherosclerotic plaques and stenosis in non-diabetic, older individuals in the PRECISE study. Further, these IR surrogate markers have certain predictive performance to assess the risk of multi-territorial atherosclerosis.

Normative data for the lateralization task in the assessment of intranasal trigeminal function

To provide normative data for the lateralization task in the assessment of intranasal trigeminal function, as well as to investigate potential effects of age, sex and olfactory function. The lateralization task using eucalyptus as target stimulus was performed to assess intranasal trigeminal function. Data were collected from: 360 healthy adult participants (mean age 37.5±17.4) for the 40-trial version; 284 participants (mean age 32.6±14.1) for the 20-trial version; and 418 participants (mean age 42.6±15.6) for the 10-trial version. The "Sniffin' Sticks" test was used to measure olfactory function. The mean scores were 35.46±4.50 for the 40-trial version, 15.64±3.65 for the 20-trial version, and 8.14±2.16 for the 10-trial version. In the reference group aged 18-25 years, the 10th percentiles were 33 for the 40-trial version, 11 for the 20-trial version, and 6 for the 10-trial version. Significant effects of age and odor discrimination score were observed on lateralization performance. We provide reference scores for the lateralization task, in large sample of healthy participants. Among the three examined tasks (40, 20 and 10), the 40-trial task yielded the most reliable information. For the 40-trial version, scores equal or higher to 33 points indicate a normal lateralization ability, whereas scores between 27 and 32 may warrant further assessment. Scores below 27 possibly point towards a decreased trigeminal function. The lateralization task serves as surrogate marker of intranasal trigeminal functions and further studies with pathological cases are needed to explore its clinical usefulness.

A Statistical Model for Inference of Recent and Incident HIV Infection Using Surveillance Data on Individuals Newly Diagnosed With HIV Infection in Scotland

Background: To inform global ambitions to end AIDS, evaluation of progress toward HIV incidence reduction requires robust methods to measure incidence. Although HIV diagnosis date in routine HIV/AIDS surveillance systems are often used as a surrogate marker for incidence, it can be misleading if acquisition of transmission occurred years before testing. Other information present in data such as antibody testing dates, avidity testing result, and CD4 counts can assist, but the degree of missing data is often prohibitive. Methods: We constructed a Bayesian statistical model to estimate the annual proportion of first ever HIV diagnoses in Scotland (period 2015–2019) that represent recent HIV infection (ie, occurring within the previous 3–4 months) and incident HIV infection (ie, infection within the previous 12 months), by synthesizing avidity testing results and surveillance data on the interval since last negative HIV test. Results: Over the 5-year analysis period, the model-estimated proportion of incident infection was 43.9% (95% CI: 40.9 to 47.0), and the proportion of recent HIV infection was 21.6% (95% CI: 19.1 to 24.1). Among the mode of HIV acquisition categories, the highest proportion of recent infection was estimated for people who inject drugs: 27.4% (95% CI: 20.4 to 34.4). Conclusions: The Bayesian approach is appropriate for the high prevalence of missing data that can occur in routine surveillance data sets. The proposed model will aid countries in improving their understanding of the number of people who have recently acquired their infection, which is needed to progress toward the goal of HIV transmission elimination.

Sex differences in the correlation between lipids related to cardiovascular risk factors and small dense LDL particles in patients with type 2 diabetes.

Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2. The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence. An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001). The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk.

Elevated osmol gaps in patients with alcoholic ketoacidosis.

The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 27. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

Association of Short Sleep Duration and Obstructive Sleep Apnea with Central Obesity: A Retrospective Study Utilizing Anthropometric Measures.

Central obesity, as measured by examination instruments, has been shown to be associated with both OSA and short sleep duration. However, objective measurement tools like CT, MRI, and DXA are expensive, cause radiation exposure, and have limited availability, especially in resource-limited settings. Thus, this study aimed to demonstrate the relevance of Body Mass Index (BMI) and Waist-to-Height Ratio (WHtR) as surrogate indicators of visceral obesity in the assessment of OSA and short sleep duration. We also intend to evaluate whether WHtR, in combination with BMI, can be a suitable surrogate marker for visceral adiposity. We recruited 333 adults with complete polysomnographic (PSG) records retrospectively. Logistic regression helped to assess the association of BMI and WHtR as surrogates for central adiposity with OSA and short sleep duration. Moreover, ROC curve analysis was conducted to evaluate the predictive ability of BMI and WHtR. Following the relevant adjustments, logistic regression analysis results showed that the combination of WHtR and BMI acting as central obesity surrogates was significantly associated with OSA and short sleep duration (p<0.05). According to univariate regression analysis, sleep latency and wakeaftersleeponset were independent predictors of the risk of central obesity in patients with short sleep duration and OSA. Additionally, ROC curve analysis demonstrated that the combination of BMI and WHtR provided a better assessment of central adiposity in patients with OSA and short sleep duration, compared to each measure alone. BMI and WHtR are significantly associated with OSA and short sleep duration, and might serve as a potential surrogate marker for central obesity. Sleep latency and wakeaftersleeponset can independently predict the risk of central obesity in patients with short sleep time and OSA. Thus, larger prospective studies are needed to verify our findings.