Healthy Population Research Articles

9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. BACKGROUND AND OBJECTIVE: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects > 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects > 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

9221 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects > 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. BACKGROUND AND OBJECTIVE: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects > 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024

Biological Reference Ranges for Healthy Indian Blood Donors: Experience of a Tertiary Care Center Vis-à-Vis International Literature.

Complete blood count is the most common, basic test requisitioned in hematology. The normal reference ranges of hematological parameters are required owing to variable socioeconomic, environmental, and genetic factors in populations. The current study determines the reference ranges of the healthy Indian donor population of a high socioeconomic group. The study was conducted in the Department of Transfusion Medicine at a tertiary care hospital in India and included 4098 individuals, aged 18-65 years coming for voluntary blood donation from July 2021 to October 2022. Blood samples were collected in K2EDTA, analyzed on the Sysmex XN-31 hematology analyzer, and using statistical tools, the normal reference ranges were calculated. The reference ranges for hemoglobin (HB) (137-185 g/L), WBC (5.1-1.7 × 109/L), platelet count (115.6-370.0 × 109/L) were noted. No statistically significant changes were observed in different age groups. There were gender-wise differences noted in nearly all parameters. The HB and hematocrit (HCT) range was slightly higher in other Indian and other Asian populations with comparable values with the Chinese, Korean populations, and Western populations; RBC parameters were overall comparable with minor differences; the WBC count was higher than the other Indian and Asian populations particularly the upper limit of lymphocyte and monocyte; and the range of platelet counts had a comparable upper limit with all populations and had the lowest lower value in males in our study, which was comparable to only the Chinese population. It is concluded that reference ranges of common parameters were calculated with minor changes noted in all hematological parameters on comparing with other Indian, Asian population, and Western data.

The relationship between prodromal symptom levels and affective temperament features and emotional dysregulation in patients diagnosed with bipolar disorder and their first-degree relatives: A controlled study

BackgroundThe frequency of developing psychiatric symptoms is higher in the first-degree relatives of bipolar patients compared to the healthy population. This study aims to determine the possible diagnosis of bipolarity by revealing the bipolar prodromal features, temperament changes, and emotional disregulation in the first-degree relatives of bipolar patients and their interrelationships. MethodsA total of 150 patients, including bipolar disorder patients, their first-degree relatives, and a healthy control group, aged 18–65 who met the study inclusion criteria, were included in the study. Sociodemographic data form, Bipolar Prodromal Symptom Scale (BPSS), Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A), and Difficulty in Emotion Regulation Scale (DERS) were administered to all participants. ResultsSignificant differences were found between the BPSS, TEMPS-A, and DERS total and subscale scores of the bipolar patient group, first-degree relatives, and healthy control group (p < 0.001). There were significant differences in BPSS frequency and severity subscale scores, TEMPS-A hyperthymic and cyclothymic subscale scores, and DERS strategy, goal-oriented, and awareness subscale scores between patients and their first-degree relatives (p < 0.001). Additionally, all scale scores of the patient relatives were significantly different from the healthy control group (p < 0.001). A significant relationship was found between the prodromal scores and temperament scores of the patient relatives, and between the temperament scores and DERS scores (p < 0.001). ConclusionIt has been observed that the severity and frequency of bipolar prodromal symptoms, temperament changes, and difficulty in mood regulation are higher in bipolar patients and their first-degree relatives compared to the healthy population. Differences were found in hyperthymic and cyclothymic temperament features and difficulty in mood regulation scores between bipolar patients and their first-degree relatives. Patient relatives showed significant changes in all parameters compared to the healthy group. The severity of bipolar prodromal symptoms in patient relatives was associated with cyclothymic and anxious temperament features, while the frequency of bipolar symptoms was associated with anxious temperament. Relationships were found between some temperament and mood regulation difficulty sub-scores. In light of these findings, evaluating clinical variables such as the frequency and severity of prodromal symptoms, temperament features, and difficulty in mood regulation in the first-degree relatives of bipolar patients may be an appropriate approach for diagnosing mood disorders.

A network analysis of affective and motivational individual differences and error monitoring in a non-clinical sample.

Error monitoring, which plays a crucial role in shaping adaptive behavior, is influenced by a complex interplay of affective and motivational factors. Understanding these associations often proves challenging due to the intricate nature of these variables. With the aim of addressing previous inconsistencies and methodological gaps, in this study, we utilized network analysis to investigate the relationship between affective and motivational individual differences and error monitoring. We employed six Gaussian Graphical Models on a non-clinical population ($N$ = 236) to examine the conditional dependence between the amplitude of response-related potentials (error-related negativity; correct-related negativity) and 29 self-report measures related to anxiety, depression, obsessive thoughts, compulsive behavior, and motivation while adjusting for covariates: age, handedness, and latency of error-related negativity and correct-related negativity. We then validated our results on an independent sample of 107 participants. Our findings revealed unique associations between error-related negativity amplitudes and specific traits. Notably, more pronounced error-related negativity amplitudes were associated with increased rumination and obsessing, and decreased reward sensitivity. Importantly, in our non-clinical sample, error-related negativity was not directly associated with trait anxiety. These results underscore the nuanced effects of affective and motivational traits on error processing in healthy population.

Functional connectivity across the lifespan: a cross-sectional analysis of changes.

In the era of functional brain networks, our understanding of how they evolve across life in a healthy population remains limited. Here, we investigate functional connectivity across the human lifespan using magnetoencephalography in a cohort of 792 healthy individuals, categorized into young (13 to 30 yr), middle (31 to 54 yr), and late adulthood (55 to 80 yr). Employing corrected imaginary phase-locking value, we map the evolving landscapes of connectivity within delta, theta, alpha, beta, and gamma classical frequency bands among brain areas. Our findings reveal significant shifts in functional connectivity patterns across all frequency bands, with certain networks exhibiting increased connectivity and others decreased, dependent on the frequency band and specific age groups, showcasing the dynamic reorganization of neural networks as age increases. This detailed exploration provides, to our knowledge, the first all-encompassing view of how electrophysiological functional connectivity evolves at different life stages, offering new insights into the brain's adaptability and the intricate interplay of cognitive aging and network connectivity. This work not only contributes to the body of knowledge on cognitive aging and neurological health but also emphasizes the need for further research to develop targeted interventions for maintaining cognitive function in the aging population.

Bone loss after bariatric surgery is observed mainly in the hip trabecular compartment and after hypoabsorptive techniques

We evaluated the impact of bariatric surgery on bone mineral density (BMD) and microarchitecture over one year using dual-energy X-ray absorptiometry (DXA), the trabecular bone score (TBS), and 3D-DXA to assess changes after different surgical techniques. This prospective, single-center study of 153 patients with severe obesity contrasts the effects on bone health of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and duodenal switch/single anastomosis duodeno-ileostomy with sleeve gastrectomy (DS/SADIS). To our knowledge, this is the first study to evaluate patients undergoing DS/SADIS and to incorporate 3D-DXA analysis in the assessment of bone loss.Patients were 81 % female with a mean age of 50 ± 9 years. Fifty-four per cent underwent SG; 16 %, RYGB; and 30 %, DS/SADIS. Our findings revealed a significant decrease in areal BMD at the LS (−3.49 ± 5.44 %), FN (−5.24 ± 5.86 %), and TH (−8.06 ± 5.14 %) one year after bariatric surgery. Bone microarchitecture at the LS assessed by TBS was degraded in 30 % of patients. Proximal femur 3D-DXA analysis showed that surgery-induced bone loss predominantly affects the trabecular compartment (Trabecular volumetric (v) BMD: −8.00 ± 6.57 %) rather than the cortical compartment (Cortical vBMD: −1.37 ± 2.79 %).These results suggest hypoabsorptive and mixed techniques (DS/SADIS and RYGB) were associated with greater BMD loss and deterioration of microarchitecture than restrictive techniques (SG).The primary determinants of bone density and impairment of microarchitecture were the extent of weight loss and the type of surgical procedure. Despite overall bone loss, Z-score assessments indicated that post-surgical bone status remained within or above the average ranges compared to a healthy population, except for TH following DS/SADIS.In conclusion, our research shows differences in the impact of bariatric surgery techniques on bone density and microarchitecture, emphasizing the need for careful postoperative monitoring of bone health, particularly in patients undergoing hypoabsorptive and mixed procedures.

A-106 Determination of Urinary NGAL Reference Intervals from Specimens of Healthy Adult and Pediatric Individuals

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is a 25kDa protein implicated in multiple biological processes, including attenuation of apoptosis and differentiation of renal tubule epithelial cells and nephrons. NGAL is also produced and secreted by injured kidney tubule epithelial cells. As such, NGAL can serve as an early urinary biomarker for acute kidney injury (AKI). This multi-site, cross-sectional study aimed to establish reference intervals for urinary NGAL (uNGAL) in healthy pediatric and adult populations using a particle-enhanced turbidimetric assay. Methods Apparently healthy individuals, aged ≥ 3 months, were eligible for this study. Subjects with an active urinary tract infection (UTI) on the day of sample collection, acute kidney injury (AKI) or a history of AKI, stage 4 or 5 chronic kidney disease (CKD), known congenital anomalies of the kidney and urinary tract, known urothelial, urological, or kidney malignancies were excluded from the study. Subjects with uncorrected congenital heart disease, having undergone solid organ or bone marrow transplantation, receiving renal replacement therapy, and having undergone surgery (urologic, nephrectomy, or correction of congenital heart disease) were also excluded. A total of 688 subjects were screened, 677 were eligible, and 629 (91.4%) were considered evaluable per the protocol. The 59 excluded subjects were ineligible due to missing/incorrect information in the informed consent form, or not evaluable due to meeting exclusion criteria, mostly a positive UTI test. Urine samples were tested for NGAL on a Roche cobas® c501 analyzer in single determinations. Results Tables 1 and 2 describe the NGAL summary statistics and central 95% reference intervals by age and gender. Conclusions These data demonstrate the normal urine NGAL values in an apparently healthy pediatric and adult populations.

A-002 Analytical Validation of the Zybio High Sensitivity Cardiac Troponin I CLIA Assay

Abstract Background High-sensitivity cardiac troponin (hs-cTn) plays a pivotal role in the early diagnosis of Acute Coronary Syndrome (ACS). With technological advancements, the sensitivity of troponin assays has significantly improved. The International Federation of Clinical Chemistry (IFCC) criteria for hs-cTn assays include a total imprecision (Coefficient of Variation, CV) ≤10% at the gender-specific 99th percentile value and detectable levels in ≥50% of a healthy population. This study aims to evaluate the performance of Zybio's hs-cTnI assay against these high-sensitivity standards Methods This study involved 1661 individuals undergoing routine health checks at Chongqing Medical University Third Hospital. Exclusion criteria included recent medication use, abnormal NT-proBNP levels, significant cardiac silhouette changes in chest X-rays, age &amp;lt;20, incomplete data, pregnancy, or history of severe chronic diseases. Participants were classified into apparent healthy and healthy groups based on blood pressure, lipid profiles, and electrocardiogram results. Laboratory examinations included hs-cTn and NT-ProBNP concentrations using Zybio's chemiluminescence instrument EXI2400 and associated reagent kits, with other parameters measured using standard biochemical and high-performance liquid chromatography methods. Results Of the 1247 participants (556 males, 691 females) included in the final analysis, 1157 showed detectable hs-cTnI levels above the limit of detection (LOD), yielding an overall detection rate of 92.78%. Detection rates were 93.71% in males and 92.04% in females. The total imprecision (CV) of hs-cTnI at gender-specific 99th percentile values over 20 days was below 10%, meeting the high-sensitivity criteria. This finding was consistent across lower and higher concentration ranges. Conclusions The Zybio hs-cTnI assay demonstrated a high detection rate in a healthy population, with 92.78% detectability overall, 93.71% in males, and 92.04% in females. The assay met the high-sensitivity criteria of IFCC, with a total imprecision (CV) of less than 10% at the gender-specific 99th percentile levels. These results validate the utility of Zybio's hs-cTnI assay for clinical application in the early diagnosis of ACS.

Protocol to evaluate human thermoregulation before and after thermal stress

Problem and motivationThe human body dissipates 60 % of its heat by emitting infrared radiation, it can be studied using Infrared Thermography (IRT). IRT images serve as thermal maps of the body, useful in medical applications to investigate the physiopathological of diseases that present symptoms such as swelling, pain, infection, rash, and increased local skin temperature. AimTo design a protocol to capture IRT images before and after physical activity. The protocol collects skin temperature data of the entire body, in the frontal (anterior and posterior) and sagittal (right and left) planes. MethodologyThe protocol was designed considering clinical, environmental, and technical factors and ensuring its reproducibility in both healthy and pathological populations. Thermographic images were acquired both at rest and after thermal stress (modified Bruce test). In addition, questionnaires were prepared to collect and store information on demographic data, core temperature, environmental conditions, pain perception, and level of physical activity. ResultsThe protocol combines the acquisition of IRT images with the application of the modified Bruce protocol on a treadmill as a thermal stress generator. Further impactThis protocol offers a valuable tool for studying the thermoregulatory capacity of the human body in the presence of different medical conditions.

A-082 Establishment of Infant Free T4 Reference Interval Through Indirect Methods

Abstract Background Children require reference intervals distinct from adults and, based on their unique developing physiology, several intervals are often required to accurately reflect the distribution of expected results in a healthy pediatric population. The establishment of pediatric reference intervals has proven challenging. While consenting adults volunteer to contribute their biological material towards the development of a reference interval, well children usually do not have the occasion to get blood drawn and the smaller the child, the more significant the impact of phlebotomy. For these reasons, scientists have sought out other methods for determining pediatric reference intervals. As an alternative, indirect statistical methods may be applied to large data sets of laboratory test results to ascertain a reference interval. The Multi-Modal Decomposition (MMD) is an iterative indirect method that decomposes a mixture of multiple normal distributions into separate components using the expectation-maximization (EM) algorithm The objective of the current study, was to apply MMD to ascertain reference intervals for free T4 in infants. Methods The study population included infants ranging in age from 1 day to 60 days who had specimens submitted for free T4 testing involving equilibrium dialysis followed by LC-MS/MS in a commercial reference laboratory (Quest Diagnostics Nichols Institute, San Juan Capistrano, CA). MMD was performed on 25,271 de-identified free T4 results to establish the reference intervals that were validated by comparison against free T4 values obtained on 238 de-identified specimens submitted for acylcarnitine testing, the specimen were analyzed for TSH and only the in-range specimens were include for Free T4 reference interval analysis. Results MMD analysis demonstrated distinct reference intervals for the following ages: 0 to 6 days (1.8 - 6.1 ng/dL), 7 days to &amp;lt;2 weeks (1 - 4.4 ng/dL), 2 to &amp;lt;3 weeks (0.8 - 3.5 ng/dL), 3 to &amp;lt;4 weeks (0.8 - 3 ng/dL), and 4 to &amp;lt;8 weeks (0.7 - 2.8 ng/dL). The data did not support the use of separate intervals for male and female children. Conclusions MMD analysis demonstrated distinct reference intervals for the following ages: 0 to 6 days (1.8 - 6.1 ng/dL), 7 days to &amp;lt;2 weeks (1 - 4.4 ng/dL), 2 to &amp;lt;3 weeks (0.8 - 3.5 ng/dL), 3 to &amp;lt;4 weeks (0.8 - 3 ng/dL), and 4 to &amp;lt;8 weeks (0.7 - 2.8 ng/dL). The data did not support the use of separate intervals for male and female children.

A-126 The Role of Lysozyme and Other Inflammatory Markers in Understanding GI Microbiome Changes

Abstract Background The role of GI microbiome in gut health, intestinal permeability, and the development of inflammation has been well-established however, few clinical studies assess microbiome (i.e. PCR) and biochemical markers from the same stool collection. Doctor’s Data Inc. (DDI) has been performing a GI microbiome test in conjunction with other stool biochemical markers for the past 3 years, with over 7000 patient samples analyzed. The aim of this study was to analyze GA-map® Probe results for possible correlations with elevated values for fecal calprotectin, lactoferrin, and lysozyme. Methods Microbiome characterization The microbiome analysis test used in this study identifies 48 targeted analytes across six phyla using the GA-map® Dysbiosis test (Genetic Analysis AS, Oslo). The test algorithm has been trained and validated using 48 bacterial markers signal intensity obtained from 668 adults, including healthy subjects, patients with IBS and IBD. GA-map® Dysbiosis Analyzer software calculates the degree of dysbiosis (DI) of a given sample, assigning a DI ranging from 1 to 5. DI greater than 2 indicates that the microbiota is deviant from a healthy reference population (“dysbiotic”), while a score of 2 or lower is reported as “normobiotic”. Biochemical marker characterization Each stool sample was analyzed for a suite of biochemical markers - in particular calprotectin, lactoferrin and lysozyme - with the concentration determined using commercially available ELISA kits (ALPCO, Techlab). Results Using clinical cut-offs of 100.0 ug/g (calprotectin) and 7.3 ug/g (lactoferrin) the patient data was sorted into cohorts indicating disease state of “Normal”, “Intermediate” and “IBD Likely”, and further differentiated using the lysozyme result. The biochemical marker results were correlated against DI score for each stool sample (Figure 1). Conclusions DI score increases as biochemical inflammatory markers increase, with lysozyme as the key differentiating factor between patient cohorts.

An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction

A discrete mathematical model based on ordinary differential equations and the associated continuous model formed by a partial differential equation, which simulate the generational and temporal evolution of a stem cell population, are proposed. The model parameters are the maximum proliferation potential and the rates of mitosis, death events and telomerase activity. The mean proliferation potential at each point in time is suggested as an indicator of population aging. The model is applied on hematopoietic stem cells (HSCs), with different telomerase activity rates, in a range of variation of maximum proliferation potential in healthy individuals, to study the temporal evolution of aging. HSCs express telomerase, however not at levels that are sufficient for maintaining constant telomere length with aging [1,2]. Women with primary ovarian insufficiency (POI) are known to have low telomerase activity in granulosa cells and peripheral blood mononuclear cells [3]. Extrapolating this to hematopoietic stem cells, the mathematical model shows the differences in proliferation potential of the cell populations when telomerase expression is activated using sexual steroids, though the endogenous promoter or with gene therapy using exogenous, stronger promoters within the adeno-associated virus. In the first case, proliferation potential of cells from POI condition increases, but when adeno-associated viruses are used, the proliferation potential reaches the levels of healthy cell populations.

A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing

Abstract Background Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases. Methods The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success. Results The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%. Conclusions Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.

Fat Oxidation With Cottonseed Oil Compared To Olive Oil In A Healthy Population

Fat Oxidation With Cottonseed Oil Compared To Olive Oil In A Healthy Population

Epidemiology of complications after non-compulsory planned hardware-removal after limbs fracture

IntroductionRemoval of hardware (HR) following a fracture is a frequent question from patients. The incidence of this kind of intervention remains very variable depending on the healthcare systems and its interest is debated in view of the benefits and associated risks that remain poorly defined. Mandatory preoperative information cannot be given optimally in this context. ObjectiveTo determine the rate of complications (major and minor) after non-compulsory planned hardware-removal following a limb fracture. HypothesisThe rate of major complications was greater than 1%. MethodsA 10-year retrospective single-center study included 1990 patients who had undergone routine HR. Analysis of medical records, with a minimum of one year of follow-up, allowed us to collect: patient data, the type and anatomical location of the osteosynthesis material, as well as the occurrence of a postoperative complication, categorized as a major complication (resulting in either a new surgical procedure, re-hospitalization, or lasting functional impairment) or a minor complication. ResultsOverall, 4.1% (79/1990) of patients experienced postoperative complications, including 1.56% (31/1990) major complications and 21 surgical revisions (1.06%). The time to onset of complications was 9.1 +/- 8.4 days. The most common complications were deep infections and impaired skin healing with superficial infection (55/79, 69.6%). Locations "around the knee" and "around the ankle" were at higher risk of complications (p < 0.01). Smoking was identified as a significant risk factor for complications, particularly deep infection (p = 0.004, OR = 8.7 [1.98; 38.11]). DiscussionNon-mandatory routine RH has a significant complication rate even in a healthy population. Preoperative information of the patient and the assessment of the benefit/risk balance are essential in this indication. This study also raises the question of mandatory smoking cessation preoperatively. Level of evidenceIV; retrospective study.

Assessment of post-COVID-19 vaccination neutralizing antibodies in kidney transplant and hemodialysis patients versus the general population

Background Patients receiving hemodialysis (HD) and kidney transplant recipients are immunocompromised populations prioritized for coronavirus disease 2019 (COVID-19) vaccination, however, there were few clinical trials with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine responses. Compared with controls, individuals with chronic kidney disease and those on immunosuppressants have lower antibody titers and rates of seroconversion after vaccination. There is a lack of data on their humoral response to COVID-19 immunization. To study the effect of different types of available COVID-19 vaccines in Egypt (AstraZeneca, Sinopharm, Pfizer/BioNTech, and Sputnik) on neutralizing antibodies against COVID-19 in HD and kidney transplantation patients compared with the healthy population. Patients and methods A total of 84 participants; 28 HD patients, 28 kidney transplant recipients, and 28 healthy medical staff members were recruited to test the serological reaction. Six months following the second dose of the COVID-19 vaccine, we evaluated antibody titers against SARS-CoV-2 by Elecsys Anti-SARS-CoV-2 S (Roch) and collected data from the patients, including their comorbidities and the length of time since their kidney transplant. Results All the study groups were comparable as regards age, sex, and BMI, however, hemoglobin was significantly higher in the control group. Antibody response to vaccination was strongest in the control group (100%), followed by HD patients (85%), with transplant recipients showing a significantly weaker response (60%). The Pfizer vaccine generated higher neutralizing antibody levels compared with other vaccines in this study. Yet, the difference was not statistically significant. Additionally, no significant difference in response between the different vaccine types. the transplant group displayed significantly lower levels compared with the control group (P&lt;0.001) and a trend towards lower levels compared with the dialysis group (P=0.06). Conclusion Our study found that all tested vaccines generated comparable levels of neutralizing antibodies in healthy individuals and those with chronic kidney disease (dialysis patients). While 85% of dialysis patients achieved seroconversion (positive antibody test) similar to the healthy control group, only 60% of kidney transplant recipients did. the duration post-transplant may be associated with higher rate of seroconversion. the transplant group displayed lower levels of antibodies compared with the control and the dialysis group which suggests a weaker immune response in transplant patients.

Impact of BMI on fertility in an otherwise healthy population: a systematic review and meta-analysis.

An increased body mass index (BMI) can lead to subfertility; however, current literature fails to exclude the effect of other confounding medical conditions, raising questions regarding the direct link between increased BMI and fertility outcomes. To conduct a systematic review and meta-analysis to elucidate the effects of increased BMI on fertility outcomes in females with no other comorbidities. A comprehensive search was conducted using EMBASE, MEDLINE and the Cochrane library from January 2000 until July 2023. Two authors independently conducted data extraction and assessed study quality. Odds ratio (OR) (dichotomous data), standardised mean difference (SMD) (continuous data) and 95% CIs were calculated. Nine eligible studies were identified: one natural conception and eight assisted reproductive technology (ART). Aggregated data revealed women with BMI ≥25 were less likely to attain clinical pregnancy (OR 0.76, 95% CIs 0.62 to 0.93, p=0.007), with BMI ≥30 associated with a further decreased likelihood of clinical pregnancy (OR 0.61, 95% CIs 0.39 to 0.98, p=0.04). Women with raised BMI required longer duration of stimulation (SMD=0.08, 95% CIs 0.00 to 0.16, p=0.04) and obtained reduced oocytes (SMD=-0.11, 95% CIs -0.18 to -0.04, p=0.002). These data demonstrate an adverse impact of being overweight/obese on ART outcomes in women with no other diagnosed medical comorbidities and highlight the distinct lack of data concerning the effects of isolated obesity on natural conception. Infertility represents an enormous burden for couples and society; it is essential to identify and tackle modifiable risk factors to improve chances of conception. CRD42022293631.