Prospective Analysis Research Articles

3122: Outcomes in Locally Advanced Rectal Cancer: A Comparative Analysis of PROSPECT and Real-World Data

3122: Outcomes in Locally Advanced Rectal Cancer: A Comparative Analysis of PROSPECT and Real-World Data

Analysis of the Application Prospect of Biochar Production From Characteristic Solid Waste Biomass Resources in the Qinghai-Tibet Plateau

Analysis of the Application Prospect of Biochar Production From Characteristic Solid Waste Biomass Resources in the Qinghai-Tibet Plateau

Fatty Acid Intake and Polyunsaturated Fatty Acid Biomarkers and Risk of Total Knee or Hip Arthroplasty Among Older Women in the Women's Health Initiative.

The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

The Role of Multilevel Intercostal Nerve Block in Local Anesthetic Thoracoscopy.

Intercostal nerve block (ICNB) has long been used in thoracic surgery. Local anesthetic thoracoscopy (LAT) is performed under conscious sedation with local anesthesia at the port insertion site. This alone, however, does not anesthetize the parietal pleura from where biopsies are taken and patients can experience pain. To compare LAT with multilevel ICNB versus standard care to determine whether it reduces pain during and post-LAT, its effect on analgesia use, the hospital length of stay (LOS), and related complications. Prospective analysis of patients undergoing LAT between January and June 2021. In the ICNB group, levobupivacaine/xylocaine is administered at the angle of the rib immediately before LAT (up to 5 rib spaces). Visual Analog Score for pain (0 to 100mm) was measured at 1 and 2 hours post-LAT and daily including analgesia use. Twenty patients (10 ICNB vs. 10 standard care group). The mean age is 68 years with 70% males. Visual Analog Score for pain in the ICNB group reduced by 55mm at 1 and 2 hours post-LAT and 45mm at day 1 ( P <0.05) (minimal clinically important difference >16mm]. Median LOS was reduced by 50% in the ICNB group ( P <0.05). Paracetamol use reduced by 56% ( P <0.05). ICNB not only significantly reduces postprocedure pain but also reduces LOS.

Abstract 1167: Prospective analysis of pretreatment circulating CD4 memory T cell features associated with severe immunotherapy toxicity

Abstract Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, significantly improving outcomes. Nevertheless, too many melanoma patients undergoing ICI treatment experience severe and often debilitating immune-related adverse events (irAEs). In a retrospective melanoma cohort treated with ICIs, we previously found that elevated baseline levels of circulating CD4 effector memory T (TEM) cells were associated with the development of severe irAEs, irrespective of the affected organ system (Lozano et al., Nature Medicine, 2022). Here, we present data from an extended prospective validation cohort from 47 patients across two academic medical centers. Methods: Of 47 patients, 26 received combination anti-PD1/anti-CTLA4 ICIs, 3 combination anti-PD1/anti-LAG3 ICIs, 17 anti-PD1 ICI, and 1 anti-CTLA4 ICI. Peripheral blood mononuclear cells (PBMCs) were prepared from pretreatment (Cycle 1 Day 1) blood samples obtained from all patients. We performed mass cytometry (CyTOF) on PBMCs using a 38-marker panel to deeply profile immune subsets. We further leveraged bulk RNA-seq from 24 patients to (i) deconvolve CD4 memory T cell abundance using CIBERSORTx and (ii) determine T cell receptor (TCR) diversity using Shannon entropy following MiXCR clonotype assembly. irAEs were graded on a 5-point scale using the Common Terminology Criteria for Adverse Events v5. Results: After treatment initiation, 14 patients experienced severe irAEs (grade 3+) at a median of 12.1 weeks (range 4-54), including 4 with life-threatening (grade 4) irAEs. CyTOF revealed elevated circulating CD4 TEM cells in patients that developed severe irAEs (P&amp;lt;0.0001; AUC=0.87), including those treated with combination ICIs (P=0.0001; AUC=0.89). We further observed a continuous relationship between increasing CD4 TEM levels and irAE grade (P=3e-6, Jonckheere-Terpstra test). We then combined CD4 memory T cell abundance and TCR diversity derived from bulk RNA-seq on 24 of these patients using logistic regression (trained on data from Lozano et al.) to yield a composite model score. The pretreatment composite model score was strongly associated with severe irAE development (P=0.0009, AUC=0.88), and in a median split, identified patients with shorter time to severe irAE development (3 months vs. not reached; P=0.006; HR=10.5). Notably, composite model features and the overall score had no significant association with immunotherapy benefit. Conclusion: In this prospective study, both circulating CD4 TEM levels determined by CyTOF and a composite model score measured by RNA-seq were strongly associated with severe irAE development, independent of response status. These findings hold promise for future pretreatment risk stratification of ICI therapy. Citation Format: Abul Usmani, Noah Earland, Wubing Zhang, Peter K. Harris, Antonietta Bacchiocchi, Chloe M. Sachs, Aishwarya Nene, David Y. Chen, Mario Sznol, Ruth Halaban, Aaron M. Newman, Aadel A. Chaudhuri. Prospective analysis of pretreatment circulating CD4 memory T cell features associated with severe immunotherapy toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1167.

Managerial aspects spects of digitalization of the transport and logistics ecosystem

A virtual organization is the newest form of business organizations, one of the forms of which are distributed companies with their own production facilities and transport and logistics resources, or using the services of production and logistics centers located on different continents and in different countries, forming project/matrix management structures, attracting specialists from different countries. The article discusses the advantages and risks of managing distributed organizations based on digital technologies. The authors characterize the fields of activity of distributed companies and assess the potential for their expansion. The trend towards digitalization of management processes determines the logic of transformation of the organizational structure model from a traditional hierarchical to an open, flexible one. It is shown that transportation and logistics functions are critically important in ensuring the activities of distributed organizations, within the framework of which the transfer of raw materials, materials in progress, finished products, goods between production centers, sales centers, intermediaries of various kinds, customers and end consumers is realized.The following research methods were used: scientific review, monitoring, situational, retrospective and prospective analysis, as well as critical assessment and formulation of author’s judgments and conclusions on the scientific basis of leading scientists and specialists in the field of economics, management, logistics, operational work management.

Heterozygous Pyrin (MEFV) E148Q allele carriers indicate a reduced glaucoma risk for Turkish population: a prospective clinical analysis

ABSTRACT Purpose The MEFV gene encodes pyrin, a protein linked to increased severity of symptoms in Familial Mediterranean Fever (FMF). We consider that inflammation due to MEFV variants would increase eye inflammation and damage aqueous humor regulation. The present study is the first analysis investigating a MEFV (E148Q) variant as a marker protecting from glaucoma. Methods In this prospective clinical analyze, we performed detailed gene sequencing focusing on 22 specific regions of the pyrin (MEFV) gene. The study involved two distinct groups: individuals diagnosed with glaucoma (n = 200) and control subjects without glaucoma (n = 100). Both groups were carefully selected to exclude individuals with symptoms or a previous diagnosis of Familial Mediterranean Fever (FMF). The diagnosis of glaucoma for each participant was rigorously established through comprehensive direct ophthalmic examinations. Results A significant odds ratio for protection against glaucoma was found in carriers of the subclinical E148Q allele (OR:2.22; 95%CI: 1.098–4.485). No significant differences were found for other variants. One mutant E148Q-allele could decrease the probability of glaucoma development by approximately 68,9%. We observed no differences in the genotype frequency between glaucoma and healthy for the other MEFV gene variants. Conclusion The pyrin variant of the MEFV gene resulting in a subclinical phenotype appears to reduce the incidence of glaucoma, and heterozygous pyrin (MEFV) E148Q allele carriers confer protection against glaucoma. It is important to consider the limitations arising from the relatively small number of studies conducted on this topic.

Life cycle thinking for the assessment of waste and circular economy policy: status and perspectives from the EU example

Life cycle thinking methods such as life cycle assessment (LCA) and costing (LCC) were originally developed to assess the performance of products and services (business-making decisions). However, they are increasingly deployed to support policy-making along the entire policy cycle, including via impact assessment (IA) of different policy options. These applications are associated with a number of challenges, mainly related to the dynamic and prospective nature of policy IA, typically forward-looking into 10–20 years ahead. This requires the application of prospective scenario analyses to develop the baseline scenario, reflecting the ‘do nothing’ into the future (business-as-usual), and the alternative scenarios, reflecting the consequences incurred by the implementation of the policy options under study. Such prospective and broadened boundary nature of policy IA challenges traditional LCA/LCC practices mostly based on retrospective, static scenarios and datasets. The present study provides an overview of recent IA studies supporting waste policy to show the state-of-the-art and the main challenges associated with the application of life cycle methods in IA, focusing on the most recent EU waste and circular economy policies. Moreover, since specific and transparent guidance on how to implement consistently these methods in policy IA is lacking, the study provides an initial guidance for application of life cycle thinking in IA drawing upon the knowledge obtained conducting waste policy IA studies. Key challenges in the field are still to be addressed, and might inspire further research to improve the application of life cycle thinking to policy assessment.

Quantitative Characterization of Respiratory Patterns on Dynamic Higher Temporal Resolution MRI to Stratify Postacute Covid-19 Patients by Cardiopulmonary Symptom Burden.

Postacute Covid-19 patients commonly present with respiratory symptoms; however, a noninvasive imaging method for quantitative characterization of respiratory patterns is lacking. To evaluate if quantitative characterization of respiratory pattern on free-breathing higher temporal resolution MRI stratifies patients by cardiopulmonary symptom burden. Prospective analysis of retrospectively acquired data. A total of 37 postacute Covid-19 patients (25 male; median [interquartile range (IQR)] age: 58 [42-64] years; median [IQR] days from acute infection: 335 [186-449]). 0.55 T/two-dimensional coronal true fast imaging with steady-state free precession (trueFISP) at higher temporal resolution. Patients were stratified into three groups based on presence of no (N = 11), 1 (N = 14), or ≥2 (N = 14) cardiopulmonary symptoms, assessed using a standardized symptom inventory within 1 month of MRI. An automated lung postprocessing workflow segmented each lung in each trueFISP image (temporal resolution 0.2 seconds) and respiratory curves were generated. Quantitative parameters were derived including tidal lung area, rates of inspiration and expiration, lung area coefficient of variability (CV), and respiratory incoherence (departure from sinusoidal pattern) were. Pulmonary function tests were recorded if within 1 month of MRI. Qualitative assessment of respiratory pattern and lung opacity was performed by three independent readers with 6, 9, and 23 years of experience. Analysis of variance to assess differences in demographic, clinical, and quantitative MRI parameters among groups; univariable analysis and multinomial logistic regression modeling to determine features predictive of patient symptom status; Akaike information criterion to compare the quality of regression models; Cohen and Fleiss kappa (κ) to quantify inter-reader reliability. Two-sided 5% significance level was used. Tidal area and lung area CV were significantly higher in patients with two or more symptoms than in those with one or no symptoms (area: 15.4 cm2 vs. 12.9 cm2 vs. 12.8 cm2 ; CV: 0.072, 0.067, and 0.058). Respiratory incoherence was significantly higher in patients with two or more symptoms than in those with one or no symptoms (0.05 vs. 0.043 vs. 0.033). There were no significant differences in patient age (P = 0.19), sex (P = 0.88), lung opacity severity (P = 0.48), or pulmonary function tests (P = 0.35-0.97) among groups. Qualitative reader assessment did not distinguish between groups and showed slight inter-reader agreement (κ = 0.05-0.11). Quantitative respiratory pattern measures derived from dynamic higher-temporal resolution MRI have potential to stratify patients by symptom burden in a postacute Covid-19 cohort. 3 TECHNICAL EFFICACY: Stage 3.

Association between patient activation and delayed discharge in elective laparoscopic cholecystectomy: A prospective cohort analysis

BackgroundImproving patient activation may be an effective way to reduce healthcare costs and improve patient outcomes after surgery. ObjectiveTo determine whether preoperative patient activation is associated with delayed discharge (i.e., length of stay >24 h) after elective laparoscopic cholecystectomy. Postoperative symptoms, unscheduled access to healthcare facilities within seven days of surgery, unplanned hospital readmissions, and postoperative complications were analyzed as secondary outcomes. DesignThis cohort study was a secondary analysis of the DeDiLaCo study (Delayed Discharge after day-surgery Laparoscopic Cholecystectomy) collecting data of patients undergoing elective laparoscopic cholecystectomy during 2021 in Italy. Data was analyzed from June 2022 to April 2023. Setting90 Italian surgical centers participating in the study. Participants4708 adult patients with an instrumental diagnosis of gallbladder disease and undergoing laparoscopic cholecystectomy. Patient activation was assessed using the Italian translation of Patient Activation Measure in the preoperative setting. ResultsOf 4532 cases analyzed the median (IQR) Patient Activation Measure score was 80.3 (71.2–92.3). Participants were on average 55.5 years of age and 58.1 % were female. Two groups based on the activation level were created: 270 (6 %) had low activation, and 4262 had high activation. The low activation level was associated with the likelihood of delayed discharge (odds ratio [OR] 1.47, 95 % CI, 1.11–1.95; P = .008), higher symptom burden (OR 1.99, 95 % CI 1.49–2.66, P < .0001), and unplanned healthcare utilization within seven days after hospital discharge (OR 1.85, 95 % CI, 1.29–2.63; P = .001). There was no difference between the high and low activation groups in the incidence of postoperative complications (OR 1.28, 95 % CI, 0.95–1.73; P = .10) and hospital readmission after discharge (OR 0.95, 95 % CI, 0.30–3.05; P = .93). ConclusionsOur results suggest that patients with low activation have 1.47 times the risk of delayed discharge compared with patients with higher activation, almost twice the risk of the onset of postoperative symptoms, and 1.85 times the risk of unscheduled use of hospital services. Screening for patient activation in the preoperative setting could not only identify patients not suitable for early discharge, but more importantly, help physicians and nurses develop tailored interventions.

Safety and cost effectiveness of immediate sequential bilateral cataracts surgery

A clinical decision report using: Rush SW, Gerald AE, Smith JC, Rush AJ, Rush RB. Prospective analysis of outcomes and economic factors of same-day bilateral cataract surgery in the United States. Journal of Cataract and Refractive Surgery. 2015;41(4):732-739. https://doi.org/10.1016/j.jcrs.2014.07.034 for a patient with bilateral cataracts.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

Creating more comparable cohorts in observational palliative care studies: A proposed framework to improve applicability and replicability of research

Background: Palliative care is characterised by heterogeneous patient and caregiver populations who are provided care in different health systems and a research base including a large proportion of observational, mostly retrospective studies. The inherent diversity of palliative care populations and the often inadequate study descriptions challenge the application of new knowledge into practice and reproducibility for confirmatory studies. Being able to define systematically study populations would significantly increase their generalisability and effective translation into practice. Proposal: Based on an informal consensus process by active palliative care researchers challenged by this problem and a review of the current evidence, we propose an approach to creating more comparable cohorts in observational (non-randomised) palliative care studies that relies on defining the study population in relation to a fixed, well-defined event from which analyses are built (‘anchoring’). In addition to providing a detailed and complete description of the study population, anchoring is the critical step in creating more comparable cohorts in observational palliative care studies. Anchoring can be done with respect to a single or multiple data points, and can support both prospective and retrospective data collection and analysis. Discussion: Anchoring the cohort to reproducible data points will help create more comparable cohorts in palliative care whilst mitigating its inherent heterogeneity. This, in turn, will help optimise the generalisability, applicability and reproducibility of observational palliative care studies to strengthen the evidence base and improve practice.

Where to start? The Irish Emergency Department Antimicrobial Discharge (EDAD) study: a multicentre, prospective cohort analysis.

To determine the percentage of patients across Ireland who are discharged from the Emergency Department (ED) with an antimicrobial prescription, the indication, classification of infections, and guideline compliance. To identify potential areas for antimicrobial stewardship (AMS) interventions in the ED. A multicentre, prospective cohort analysis study in EDs across eight hospitals in Ireland. At each site, patients aged 1 month and older who presented to the ED and were discharged directly from the ED were included. A random selection of records of patients discharged from the ED were reviewed until a minimum of 30 records with an infection diagnosis resulting in an antibiotic prescription were obtained per hospital. The number of patient discharges with no antibiotic prescriptions were included to calculate the denominator. The indication, infection classification and guideline compliance data were collected on the 30 prescriptions in the participating hospitals. A total of 2619 patient records were reviewed. Of these, 249 (9.5%) patients were discharged with antimicrobial prescriptions from the ED. Most (158; 63%) were classified as probable bacterial infection, 21 (8%) as probable viral, and 18 (7%) had no documented evidence of infection. Three indications accounted for 73% of antimicrobial prescriptions: skin/soft tissue infection; ear, nose and throat infection; and urinary tract infection. Overall guideline compliance was 64%. Several areas for AMS interventions to optimize antimicrobial prescribing in the ED were identified, including targeted local and national guideline reviews, delayed prescribing, improved point-of-care testing and prescriber and patient education.

Short-term patency of iliofemoral to tibial bypass with vascular allografts in a minority population: A retrospective analysis of a single center acute care facility.

The aim of this study was to examine the short-term patency rates and associated factors of open lower limb, iliofemoral to tibial bypass using cryopreserved saphenous vein (CSV) in a minority population at an acute care hospital in New York City. A retrospective analysis of patients undergoing infra-inguinal bypass from iliofemoral vessels to tibial arteries with CSV between March 2020-April 2022 at an acute care facility (Harlem Hospital Center, Harlem, New York) was performed. Data including patient demographics, comorbidities, type of operation, follow-up surveillance, and salvage procedures were collected. Results were presented in patency line graphs and a life table. Target limb revascularization (TLR) and amputation free survival (AFS) were also calculated. Eleven bypass procedures were included in the analysis. Patients were followed for a mean of 10.8months. Cumulative primary patency rates at 1, 6, and 12months were 72.7%, 54.5%, and 40.9%, respectively. TLR was 36.4% and the AFS was 66.67% at the mean 10.8-month follow-up. The patency rates of minority patients undergoing bypass with CSV were analyzed with creation of a life table and calculation of patency rates, TLR and AFS. The short-term primary patency rates and post-operative outcomes were found to be comparable to larger studies in non-minority cohorts. These results suggest that larger studies as well as prospective analyses and randomized controlled trials in this patient cohort and demographic are needed, as well as optimal selection of patients to determine true clinical implications.

Associations of diabesity with all-cause and cardiovascular disease mortality: Findings from the Mexico City Prospective Study.

To investigate the joint associations of diabetes and obesity with all-cause and cardiovascular disease (CVD) mortality in the Mexico City Prospective Study. In total, 154 128 participants (67.2% women) were included in this prospective analysis. Diabetes was self-reported, while body mass index was used to calculate obesity. Using diabetes and obesity classifications, six groups were created: (a) normal (no diabetes and normal weight); (b) normal weight and diabetes; (c) overweight but not diabetes (overweight); (d) overweight and diabetes (prediabesity); (e) obesity but not diabetes (obesity); and (f) obesity and diabetes (diabesity). Associations between these categories and outcomes were investigated using Cox proportional hazard models adjusted for confounder factors. During 18.3 years of follow-up, 27 197 (17.6%) participants died (28.5% because of CV causes). In the maximally adjusted model, participants those with the highest risk {hazard ratio (HR): 2.37 [95% confidence interval (CI): 2.24-2.51]}, followed by those with diabesity [HR: 2.04 (95% CI: 1.94-2.15)]. Similar trends of associations were observed for CVD mortality. The highest CV mortality risk was observed in individuals with diabesity [HR: 1.80 (95% CI: 1.63-1.99)], followed by normal weight and diabetic individuals [HR: 1.78 (95% CI: 1.60-1.98)]. This large prospective study identified that diabetes was the main driver of all-cause and CVD mortality in all the categories studied, with diabesity being the riskiest. Given the high prevalence of both conditions in Mexico, our results reinforce the importance of initiating prevention strategies from an early age.

What Is the Correlation between Coronal Plane Alignment Measured on Pre- and Postoperative Weight-bearing Radiographs and Intraoperative Navigation When Stress Is Applied to the Knee?

This study examines the correlation between the weight-bearing (WB) long leg radiograph (LLR)-derived hip-knee-ankle angle (HKAA) and intraoperative supine computer-assisted surgery (CAS)-derived HKAA measurements at the beginning and end of total knee arthroplasty (TKA). The primary aim of the study was to determine if WB alignment could be mimicked or inferred based on intraoperative alignment findings. We conducted a prospective analysis from a cohort of 129 TKAs undergoing a CAS TKA at a single center by a single surgeon. The HKAA was recorded using the CAS navigation system immediately postregistration of navigation data and after implantation of the prosthesis. The intraoperative HKAA was recorded in both the supine "resting" position of the knee and also while the knee was manipulated in an effort to replicate the patient's WB alignment. These measurements were compared with the HKAA recorded on pre- and postoperative WB LLRs. There was a strong correlation between the preoperative WB LLR HKAA and the intraoperative preimplant CAS-derived stressed HKAA (R = 0.946). However, there was no correlation between the postoperative WB LLR HKAA and the postimplant insertion HKAA as measured intraoperatively via CAS for either a "resting" or "stressed" position of the operated knee (R = 0.165 and R = 0.041, respectively). Thus, the interpretation of intraoperative alignment data is potentially problematic. Despite technological advances in the development and utilization of computer navigation and robotics in arthroplasty to help obtain the optimal alignment, it would seem apparent from our study that this alignment does not correlate to upright stance postoperatively. Surgeons should apply caution to the strength of assumptions they place on intraoperative coronal plane alignment findings.

Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative

Abstract Background: Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings. Further, few studies examined associations by ovarian cancer histotypes or were able to disentangle the influence of infertility vs. fertility treatment. Differences across studies could also have been influenced by different study populations (e.g., population-based vs. clinical population/registry of in-vitro fertilization [IVF]) and lack of consistent statistical control for important confounding factors including nulliparity, number of pregnancies, and age at first pregnancy. Finally, prior prospective studies have had limited follow-up, thus not capturing cancers that occur after menopause and which may have different risk factor profiles. Our objective was to determine the association between history of infertility and risk of postmenopausal ovarian cancer in a population that had not received treatment with IVF. Methods: We utilized the Women’s Health Initiative (n=114,761) with over 25 years of follow-up. At study baseline participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of incident ovarian cancer comparing participants with a history of infertility to parous participants without infertility. Logistic regression models were used to calculate odds ratios (OR) for prevalent ovarian cancer at study baseline. Results: Approximately 16% of participants reported a history of infertility. 1,376 participants reported prevalent ovarian cancer at study baseline and 852 cases of ovarian cancer were diagnosed during study follow-up. In the prospective analyses, no statistically significant association was observed between infertility and risk of ovarian cancer overall (HR=1.16; 95% CI=0.98-1.37), by histotype, or with any specific infertility diagnoses. When prevalent ovarian cancer was examined, those reporting a history of infertility had a greater odds of ovarian cancer diagnosis (1.34; 95% CI=1.13-1.58) at WHI cohort baseline. This association was present for most infertility diagnoses with the strongest associations for hormonal/ovulatory (OR=1.97;95% CI=1.24-3.12), tubal/uterine factor (OR=1.63; 95% CI=1.15-2.31), and male factor (OR=1.71; 95% CI=1.19-2.47) infertility. Conclusions: We observed no significant association between infertility history and incident ovarian cancer in our population of postmenopausal participants. An association between infertility and ovarian cancer was present when prevalent ovarian cancer cases were examined, consistent with prior analyses that show stronger associations between ovarian cancer risk factors and ovarian cancer among younger women. Citation Format: Holly Harris, Kimberly Lind, Cynthia Thomson, Nazmus Saquib, Aladdin Shadyab, Peter Schnatz, Rogelio Robles-Morales, Lihong Qi, Howard Strickler, Denise Roe, Leslie Farland. History of infertility and risk of ovarian cancer in the women’s health initiative [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A042.

Circulating Nucleated Red Blood Cells: An Updated Reference Interval.

Nucleated red blood cells (nRBCs) are not identified in the peripheral blood in healthy individuals beyond the neonatal period. Their presence in children and adults is traditionally considered pathologic. Contemporary hematology analyzers measure nRBCs at very low levels compared to traditional manual morphometric methods. The original launch of the Sysmex XN analyzer in this study's clinical laboratory verified the previously used nRBC reference interval of 0.00 to 0.01 × 106/μL. However, nRBC results from apparently healthy patients were flagged as abnormal (high), subsequently causing patient anxiety and increased subspecialty referrals. To determine whether current reference intervals (RIs) for nRBCs were clinically relevant. We performed a prospective analysis of 405 300 specimens from nonhospitalized individuals who received a complete blood count. Applying inclusion/exclusion criteria produced a total specimen pool of 66 498. Of the 66 498 samples with otherwise normal complete blood count results from healthy, nonhospitalized individuals, 338 showed results outside the previously established RI; 336 of 66 498 (0.5%) had nRBC results greater than 0.01 × 106/μL. Two samples had nRBC values greater than 0.10 ×106/μL. Based on statistical analysis of our results, we concluded that the upper limit of the RI could be updated from 0.01 × 106/μL to 0.10 × 106/μL. Increasing the upper limit of normal for the nRBC RI should decrease patient consternation from an abnormal laboratory value and significantly decrease costs through reducing unnecessary follow up care, and without causing patient harm.

Sentinel lymph node biopsy for melanoma in the older population: A prospective analysis of outcomes.

The use of sentinel lymph node biopsy (SLNB) in the older population, defined as those over 70 years old, has been debated since the adoption of SLNBinto routine practice. Interestingly, there remains a paucity of evidence, especially regarding the rates of SLNB positivity, complications, and subsequent adjuvant therapy in those with node positivity. Data on patient's comorbidities, positivity rates, complication rates, and subsequent adjuvant treatments were collected prospectively from 998 patients (644 patients < 70 and 354 patients ≥ 70 years old) between 2016 and 2022. Patients aged ≥ 70 were found to have a higher prevalence of comorbidities, including hypertension, diabetes and hyperlipidaemia. The mean Breslow thickness was 2.2 and 2.5 in the under and over 70 groups respectively (p = 0.03). The mean mitotic rate was found to be 3.3 in the under 70 s and 4.1 in the over 70 s (p = 0.02). Despite these results, no significant differences were observed in the positivity rates of sentinel lymph node biopsies or in the treatment options selected for positive results. The under 70 s were more likely to experience loss of sensation (p < 0.01), but no difference was found in the total number of complications between the two groups. Although patients aged 70 and above had a greater incidence of comorbidities, the study revealed that they had lower complications rates and there was no significant variation in the SLNB positivity rate or chosen treatment options between the two age groups. This study supports the move to physiological rather than chronological age assessments in SLNB of the elderly.