Retrospective Exploratory Analysis Research Articles

Real-World Outcomes of a Digital Behavioral Coaching Intervention to Improve Employee Health Status: Retrospective Observational Study.

Chronic noncommunicable diseases (NCDs) account for major disability and premature mortality worldwide, with low- and middle-income countries being disproportionately burdened. Given the negative impact of NCDs on employee performance and work productivity, there is a rising need for stakeholders to identify effective workplace solutions that can improve employee health outcomes. As the workplace becomes more dispersed post pandemic, digital behavioral coaching offers a scalable, personalized, and cost-effective method of managing chronic disease risk factors among employees. This study aimed to retrospectively evaluate the impact of a digital behavioral coaching program on year-to-year changes in employee health status in a cohort of Indonesian employees. This retrospective real-world exploratory analysis of secondary health data followed 774 employees of an Indonesian company who completed company-sponsored health screenings between 2021 and 2022 and were given access to Naluri (Naluri Hidup Sdn Bhd), a holistic digital therapeutics platform offering digital behavioral health coaching and self-help tools. Participants were retrospectively classified as those who received active coaching (n=177), passive coaching (n=108), and no coaching (n=489). Linear mixed-effects models were used to evaluate the year-to-year changes in health outcomes across the 3 employee groups, with post hoc analyses evaluating within-group differences between the 2 time points and between-group differences at follow-up. Significant time×group interaction effects were detected for body weight, BMI, hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic and diastolic blood pressure. Post hoc pairwise comparisons revealed significant improvements in hemoglobin A1c (mean difference [Mdiff]=-0.14, P=.008), high-density lipoprotein (Mdiff=+2.14, P<.001), and total cholesterol (Mdiff=-11.45, P<.001) for employees in the Active Coaching group between 2021 and 2022, with the other 2 groups reporting deteriorations in multiple health outcomes throughout the 2 time points. At follow-up, those who received active coaching between 2021 and 2022 reported significantly lower body weight (P<.001), BMI (P=.001), low-density lipoprotein (P=.045), and total cholesterol (P<.001) than the No Coaching group. This study demonstrates real-world outcomes and implications supporting the use of workplace digital behavioral coaching in improving employee health status. Given the rising burden of NCDs in the Southeast Asian region, our findings underscore the role that workplace digital health interventions can play in preventing and managing chronic disease risk factors.

Sleep Duration Alters Overfeeding-mediated Reduction in Insulin Sensitivity.

Weight gain and sleep restriction both reduce insulin sensitivity. However, it is not known if sleep duration alters glucose metabolism in response to overfeeding. To examine the effect of sleep duration on overfeeding-mediated alterations in carbohydrate metabolism and insulin sensitivity. Retrospective exploratory analysis of a longitudinal overfeeding study in healthy participants (n = 28, age: 26.9 ± 5.5 years, body mass index: 25.74 ± 2.45 kg/m2). After providing baseline study measures, participants were overfed 40% above weight maintenance calorie requirements for 8 weeks. Insulin sensitivity was determined by a 2-step hyperinsulinemic-euglycemic clamp. Baseline habitual sleep duration was estimated by accelerometry, and sleep groups were created based on median sleep duration (5.2 hours/night). Overfeeding led to an average body weight gain of 7.3 ± .4 kg. Habitual sleep duration did not alter overfeeding-mediated body weight gain, fat gain, and fat distribution (all P > .15). Compared to participants with more sleep, fasting insulin (P = .01) and homeostatic model assessment for insulin resistance (P = .02) increased while fasting glucose remained unchanged (P = .68) with overfeeding in participants with shorter sleep duration. Glucose infusion rate during high insulin dose was reduced with overfeeding in participants with short sleep duration but not in participants with more sleep (P < .01). Overfeeding mediated weight gain reduced liver, adipose, and whole-body insulin sensitivity prominently in individuals with short sleep duration but not in individuals with longer sleep duration. This suggests that promoting adequate sleep during short periods of overeating may prevent detrimental effects on glucose metabolism.

Incidence of heparin resistance and heparin failure in patients receiving extracorporeal membrane oxygenation: an exploratory retrospective analysis

BackgroundUnfractionated heparin (UFH) is used in most centers for extracorporeal membrane oxygenation (ECMO) anticoagulation. When standard doses do not achieve desired target values, heparin resistance is reported, most commonly defined as doses of UFH > 35 000 IU/d. ObjectivesTo study the incidence of heparin resistance and its association with thromboembolic complications in patients requiring ECMO support. MethodsIn this observational cohort study, we included adults who received venovenous, venoarterial ECMO and extracorporeal carbon dioxide removal between January 2010 and May 2022. Main risk factor was heparin resistance (UFH, > 35 000 IU/d or > 20 IU/kg/h); the outcome was thromboembolism. Multivariable Poisson regression was used to estimate the effects of heparin resistance, adjusted for several clinical variables on the thromboembolism rate per 100 ECMO patient-days. ResultsOf the 197 patients included, 33 (16.8%) required UFH > 35 000 IU/d and 14 (7.1%) required UFH > 20 IU/kg/h. Thromboembolic complications occurred at a rate of 5.89/100 ECMO d. Heparin resistance was not associated with thromboembolic events (incidence rate ratio [IRR], 0.93; 95% CI, 0.14-5.82), whereas COVID-19 (IRR, 2.33; 95% CI, 1.4-3.96; P < .001) and ECMO type (venoarterial ECMO: IRR, 2.29; 95% CI, 1.34-3.92; P = .002; extracorporeal carbon dioxide removal: IRR, 2.89; 95% CI, 1.46-5.59; P = .002; reference venovenous ECMO) were significantly associated with the risk of thromboembolic events. ConclusionA significant proportion of patients fulfilled the common definition of heparin resistance. However, this did not influence the occurrence of thromboembolic events.

The prognostic value of the Merkel cell polyomavirus serum antibody test: A dual institutional observational study.

Merkel cell carcinoma (MCC) is an aggressive cancer with often poor outcomes. Limited biomarkers exist for predicting clinical outcomes. The Merkel cell polyomavirus (MCPyV) serum antibody test (AMERK) has shown potential for indicating better recurrence-free survival in a single-institution study. The study aimed to evaluate the link between initial AMERK serostatus and survival. Secondary objectives included examining the relationship between initial AMERK titer levels and tumor burden. A retrospective cohort study across two institutions analyzed patients tested with AMERK within 90 days of MCC diagnosis. Regression models assessed the association of survival outcomes with serostatus, considering various factors. The relationship between AMERK titer and tumor burden indicators was evaluated using ANOVA. Significance testing was exploratory, without a fixed significance level. Of 261 MCC patients tested, 49.4% were initially seropositive (titer ≥75). Multivariable analysis showed that seropositivity improved recurrence, event-free, overall, and MCC-specific survival rates. Strong associations were found between initial AMERK titer and clinical, tumor, and nodal stages, tumor size, and disease extent. Notably, improved survival with seropositivity was observed only in patients with localized disease at initial presentation. Circulating antibodies to MCPyV oncoproteins, as indicated by the AMERK test, are linked with better survival in MCC patients with localized disease at presentation. This could enhance patient risk profiling and treatment personalization. The study's retrospective nature and exploratory analysis are key limitations. Merkel cell carcinoma (MCC) is a potentially aggressive skin cancer, and tools to predict patient outcomes are limited. A blood test called anti-Merkel cell panel (AMERK), which checks for specific antibodies related to this cancer, might give us some clues. In this study, we looked at 261 MCC patients who took the AMERK test within 90 days of diagnosis. We found that patients with an initial positive AMERK result tended to have better outcomes, especially if their cancer was in the early stages. However, it is important to note that this study has limitations, including using retrospective data and exploratory analyses.

Abstract PO5-02-08: Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort

Abstract 【Background】 Lipid metabolism is one of the most conspicuous metabolic changes in malignant tumors. Previous studies confirmed that higher levels of “adverse lipids” might lead to poor outcomes and lipid-lowering drugs could act as a protective role in improving the prognosis of breast cancer patients. Nevertheless, few studies have clarified the impact of serum lipid levels and their changes on the tumor prognosis. Particularly for breast cancer patients treated with neoadjuvant chemotherapy, little has been studied whether their lipid levels or changes during neoadjuvant chemotherapy can serve as a valid prognostic factor. 【Methods】This study enrolled patients who received surgical treatment after neoadjuvant chemotherapy in Renji Hospital from March 2016 to December 2020. Patients were included if they were female aged 18 years or older; had pathologically confirmed unilateral invasive breast cancer; had tumor of at least 2cm in size without distant metastasis (T1-4, N0-3, M0); and underwent radical surgery for breast cancer successfully after neoadjuvant chemotherapy. We retrospectively gathered the baseline clinicopathological information and lipid metabolism-related biomarkers from electronic medical records. The study endpoints were disease free survival (DFS), overall survival (OS), relapse free survival (RFS), distance recurrence free survival (DRFS), and local recurrence free survival (LRFS). The prognostic value of each lipid levels and their variation levels were systematically evaluated and the importance of lipid biomarkers were ranked by Random Forest. 【Results】 The baseline clinicopathological information and lipid metabolism biomarkers were available from 200 eligible patients. As of the last follow-up in March 2023, 11 patients died, 24 experienced DFS events and 20 underwent RFS events. It showed no significant correlations of lipid levels before (baseline) and after (preoperative) neoadjuvant chemotherapy with any survival outcome. However, we found that the relative increase of low-density lipoprotein (LDL) led to poorer DFS (P=0.003), RFS (P=0.01), DRFS (P=0.01), and LRFS (P=0.0039), meanwhile the relative increase of total cholesterol (TC) and non-high-density lipoprotein (NHDL) during neoadjuvant period was significantly related to the worse prognosis (TC, DFS P=0.0084; NHDL, DFS P=0.031, RFS P=0.009) as well. After adjusted by multiple factors, the adverse impacts of increasing TC (DFS P=0.005; RFS P=0.026), LDL (DFS P=0.004; RFS P=0.006) and NHDL (DFS P=0.032; RFS P=0.014) on DFS or RFS were still maintained. The results of Random Forest revealed that LDL changes and Body Mass Index (BMI) ranked higher in terms of predicting survival outcomes. Based on these data, BMI &amp;gt;25.4 kg/m2 or LDL elevation &amp;gt;0.54 mmol/L were defined as High-risk Lipid Metabolism (HLM), while BMI ≤ 25.4 kg/m2 and LDL elevation ≤ 0.54 mmol/L were regarded as Low-risk Lipid Metabolism (LLM). Compared to LLM, HLM had a worse OS (P=0.026), DFS (P=0.0011) and RFS (P=0.0011). 【Conclusion】Our study demonstrated that the relative elevation of LDL, TC and NHDL levels during neoadjuvant chemotherapy is an independent prognostic risk factor for breast cancer patients. It was also the first time to propose the concept of high-risk lipid metabolism (HLM). 【keywords】Breast cancer, Lipid metabolism, Low-density lipoprotein (LDL), Body Mass Index (BMI), Prognosis. Citation Format: Xinru Chen, Wenjin Yin, Yingying Zhao, Jinsong Lu. Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-08.

Evaluation of Total Parenteral Nutrition in the Autologous Transplantation Setting in Patients with AML: A Retrospective Exploratory Analysis

Malnutrition remains a clinical challenge in AML patients undergoing autologous hematopoietic stem cell transplantation (ASCT), leading to physical deconditioning and prolonged hospitalization. Prospective data are mainly lacking to identify those patients who may particularly benefit from parenteral nutrition in this setting. This observational, non-randomized, retrospective, exploratory cohort study assessed the nutritional development in patients following high-dose chemotherapy (HDCT) with ASCT and explored their survival outcomes. The study included all consecutive AML patients who underwent HDCT with ASCT at a single academic center between January 2000 and January 2019. Patients were divided into two primary cohorts: those who received TPN following high-dose chemotherapy and ASCT and those who did not. We identified 126 patients with AML in first complete remission undergoing ASCT consolidation, including 75 patients receiving TPN after HDCT and ASCT and 51 patients without TPN. Neither group differed in gender, age, or subgroups of AML. The nutritional condition at first diagnosis and after induction chemotherapy was equal in both groups, as were median weight changes throughout the induction chemotherapy cycles. Finally, progression-free and overall survival rates were comparable in both groups. Our data suggest that the need to provide TPN for an average of 11 days following HDCT with ASCT for consolidation of first remission in AML patients does not affect the clinical outcome of these patients.

Prediction of early bladder outcomes after spinal cord injury: The HALT score.

Neurogenic bladder (NB) is a prevalent and debilitating consequence of spinal cord injury (SCI). Indeed, the accurate prognostication of early bladder outcomes is crucial for patient counseling, rehabilitation goal setting, and personalized intervention planning. A retrospective exploratory analysis was conducted on a cohort of consecutive SCI patients admitted to a rehabilitation facility in China from May 2016 to December 2022. Demographic, clinical, and electrophysiological data were collected within 40 days post-SCI, with bladder outcomes assessed at 3 months following SCI onset. The present study enrolled 202 SCI patients with a mean age of 40.3 ± 12.3 years. At 3 months post-SCI, 79 participants exhibited complete bladder emptying. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analyses identified the H-reflex of the soleus muscle, the American Spinal Injury Association Lower Extremity Motor Score (ASIA-LEMS), and the time from lesion to rehabilitation facility (TLRF) as significant independent predictors for bladder emptying. A scoring system named HALT was developed, yielding a strong discriminatory performance with an area under the receiver operating characteristics curve (aROC) of 0.878 (95% CI: 0.823-0.933). A simplified model utilizing only the H-reflex exhibited excellent discriminatory ability with an aROC of 0.824 (95% CI: 0.766-0.881). Both models demonstrated good calibration via the Hosmer-Lemeshow test and favorable clinical net benefits through decision curve analysis (DCA). In comparison to ASIA-LEMS, both the HALT score and H-reflex showed superior predictive accuracy for bladder outcome. Notably, in individuals with incomplete injuries, the HALT score (aROC = 0.973, 95% CI: 0.940-1.000) and the H-reflex (aROC = 0.888, 95% CI: 0.807-0.970) displayed enhanced performance. Two reliable models, the HALT score and the H-reflex, were developed to predict bladder outcomes as early as 3 months after SCI onset. Importantly, this study provides hitherto undocumented evidence regarding the predictive significance of the soleus H-reflex in relation to bladder outcomes in SCI patients.

A single-institution retrospective exploratory analysis on the effectiveness and safety of lenvatinib plus pembrolizumab for advanced endometrial cancer: insights from ProMisE molecular classification system.

The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear. This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital's ethics committee (approval number: MH2022-093). This study enrolled 20 patients, who underwent a median follow-up of 17.8months (95% confidence interval: 16.6-18.9). The best overall response rate was 60.0% (36.1-80.9), and the median progression-free survival was 11.6months (2.9-20.3). The median progression-free survival in the p53 abnormal group (n =9) was 3.4months (3.0-3.8); however, progression-free survival did not reach the median (P<0.001) in the mismatch repair-deficient/no specific molecular profile group (n=11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred. The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.

Clinical patterns and implications of prescription opioid use in a pediatric population for the management of urolithiasis in the emergency room.

Extrapolations from the adult population have suggested that opioids should be avoided in the management of pediatric urolithiasis, but the literature is sparse with regards to actual practice patterns and the downstream implications. We sought to investigate the rate of oral opioid administration for children presenting to the emergency room (ER) with urolithiasis and to identify associations between opioid administration and return visits and persistent opioid use. The TriNetX Research and Diamond Networks were used for retrospective exploratory and validation analyses, respectively. Patients <18 years presenting to the emergency room with urolithiasis were stratified by the receipt of oral opioids. Propensity score matching was performed in a 1:1 fashion. Incident cases of opioid administration and risk ratios (RRs) for a return ER visit within 14 days and the presence of an opioid prescription at 6 to 12 months were calculated. Of the 4672 patients in the exploratory cohort, 11.9% were prescribed oral opioids. Matching yielded a total of 1084 patients. Opioids at the index visit were associated with an increased risk of return visits (RR 1.51, 95% CI 1.04-2.20, P = 0.03) and persistent opioid use (RR 4.00, 95% CI 2.20-7.26, P < 0.001). The validation cohort included 6524 patients, of whom 5.7% were prescribed oral opioids. Matching yielded a total of 722 patients and demonstrated that opioids were associated with an increased risk of return visits (RR 1.50, 95% CI 1.04-2.16, P = 0.03) but not persistent opioid use (RR 1.70, 95% CI 0.79-3.67, P = 0.17). We find that the opioid administration rate for pediatric urolithiasis appears reassuringly low and that opioids are associated with a greater risk of return visits and persistent use.

Can requests for real-world evidence by the French HTA body be planned? An exhaustive retrospective case-control study of medicinal products appraisals from 2016 to 2021.

In France, decisions for pricing and reimbursement for medicinal products are based on appraisals performed by the National authority for health (Haute Autorité de Santé (HAS)). During the appraisal process, additional real-world evidence can be requested as "Post-Registration Studies" (PRS) when there are uncertainties in evidence that could be resolved by additional data collection. To facilitate PRS planning, a retrospective exploratory analysis was conducted to identify the characteristics of medicinal products associated with a PRS request. This analysis encompassed all appraisals finalized between January 1, 2016 and December 31, 2021 and compared products for which the appraisal led to a PRS request with those that did not. Six hundred positive opinions for reimbursement were identified, with a PRS request present in 17 percent (n=103) of cases. The independent characteristics associated with a PRS request were a mild or moderate clinical benefit score, a major to moderate or minor clinical added value score, previous availability under an early access program, and certain therapeutic areas (neurology, pulmonology, and endocrinology). These findings suggest two different profiles of PRS requests: (i) products for which there is uncertainty in the size of the clinical benefit and (ii) innovative products for which a substantial benefit is expected but uncertainties persist. These results will assist health technology developers to better anticipate data generation to promptly address uncertainties identified by HAS. It may also help HAS and other assessment agencies to work together to improve postlaunch evidence generation according to the characteristics of the medicinal products.

Whole-body MRI with diffusion-weighted imaging as an adjunct to18 F-fluorodeoxyglucose positron emission tomography and CT in patients with suspected recurrent colorectal cancer.

The aim was to explore how findings of whole-body MRI including diffusion-weighted imaging (DW-MRI) compared to the routine diagnostic workup with CT and/or 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with suspected recurrent colorectal cancer (CRC). This was an exploratory retrospective analysis of 55 patients with a clinical suspicion of recurrent CRC who underwent DW-MRI following CT and/or FDG-PET/CT. Two readers in consensus interpreted all clinical imaging reports and converted each described lesion into a confidence score (1 = definitely benign to 5 = definitely malignant). DW-MRI findings were compared to the most recent previous CT or PET/CT. Any discrepant or additional DW-MRI findings were documented and compared with histology and/or clinical follow-up (if available). Whole-body MRI including diffusion-weighted imaging (DW-MRI) resulted in discrepant/additional findings in 26/55 (47%) cases; 23/37 (62%) compared to previous CT and 3/18 (17%) compared to previous PET/CT. These included 10 cases where DW-MRI converted previously inconclusive CT (n = 8) or PET/CT (n = 2) findings into a conclusive diagnosis, one where it contradicted a previous CT diagnosis of recurrence, five where DW-MRI diagnosed recurrent disease not previously reported on CT and 10 cases where DW-MRI detected additional lesions compared to CT (n = 9) or PET/CT (n = 1). Eighty-eight per cent of cases with discrepant/additional findings concerned patients with recurrent/metachronous peritoneal metastases. In total, DW-MRI resulted in 42 discrepant/additional lesions; the DW-MRI diagnosis was correct in 76% of these lesions and incorrect (false positive) in 7%. In the remaining 17%, no standard of reference was available. This explorative study suggests that DW-MRI may be of added value to patients with a clinical suspicion for recurrent CRC, in particular to identify patients with peritoneal metastases. DW-MRI mainly has potential as a 'problem-solver' in patients with inconclusive or negative findings on previous imaging (in particular CT) and to detect additional disease sites in patients already diagnosed with recurrent disease.

Adherence of denosumab treatment for low bone mineral density in Japanese people living with HIV: a retrospective observational study

BackgroundLong-term care issues, specifically metabolic bone disorders, are a concern for people living with human immunodeficiency virus (PLWH) who undergo life-long antiretroviral therapy (ART). Previous clinical trials with denosumab, an anti-RANKL antibody inhibitor, have revealed its effectiveness in increasing bone mineral density (BMD) in patients with osteoporosis. However, there are limited data on adherence and effectiveness of denosumab treatment for osteoporosis in PLWH. Hence, this study aimed to investigate the adherence and effectiveness of denosumab treatment for osteoporosis in Japanese PLWH.MethodsThis study is a retrospective exploratory analysis of 29 Japanese PLWH who initiated denosumab treatment for osteoporosis, between 2013 and 2021. The study included patients who received at least one dose of denosumab every 6 months. Adherence and persistence were defined as receiving two consecutive injections of denosumab 6 months ± 4 weeks apart and 6 months + 8 weeks apart, respectively. The primary outcome measure of the study was the adherence of denosumab treatment for 24 months. The secondary outcome measures included treatment persistence and BMD. The period after January 2020 was defined as the coronavirus disease 2019 (COVID-19) pandemic period, and its impact on adherence was investigated.ResultsThe treatment adherence rates at 12 and 24 months were 89.7% and 60.7%, respectively. By contrast, the treatment persistence at 12 and 24 months was 100% and 85.7%, respectively. More patients in the group who initiated denosumab treatment after the COVID-19 pandemic reached non-adherence than in the group who initiated denosumab treatment before the pandemic. BMD at the lumbar spine and femoral neck significantly increased compared to that at baseline, with median percentage changes of 8.7% (p < 0.001) and 3.5% (p = 0.001), respectively.ConclusionsThe results showed that patients in the study had a high rate of non-adherence but a lower rate of non-persistence. Additionally, PLWH on ongoing ART experienced increased BMD with denosumab treatment. This study provides an opportunity to improve future strategies for denosumab treatment in the Japanese PLWH.

An Exploratory Retrospective Data Analysis Comparing the Outcomes of Selective Laser Trabeculoplasty and Argon Laser Trabeculoplasty in Patients with Open-Angle Glaucoma or Ocular Hypertension in Vienna, Austria, from the Year 2012 to 2022.

Background and Objectives: The aim of the present study was to compare the short-term outcomes of selective laser trabeculoplasty (SLT) with argon laser trabeculoplasty (ALT) in patients with glaucoma in a real-world setting. Materials and Methods: The present study was conducted as a retrospective case-control study. The main outcome was the change in intraocular pressure (IOP) three months after laser surgery. In addition, the number of substances used for lowering of IOP and adverse events (AEs) were assessed. Results: Charts from 25 patients were included in the present study, of which 12 had received ALT and 13 SLT. In both groups, IOP significantly decreased from baseline values 6 weeks and 3 months after laser treatment (p < 0.01 vs. baseline at each timepoint for both groups). While after 6 weeks, no difference between groups was found, after 3 months, the decrease in IOP was significantly more pronounced in the SLT group (-26 ± 21% in the ALT group vs. -41 ± 14% in the SLT group, p = 0.018 between groups, ANOVA). Three months after laser treatment, the number of IOP-lowering substances used by each patient had decreased with no difference between groups (ALT: from 2.7 ± 0.8 to 2.3 ± 0.9 substances; SLT: from 1.8 ± 1.2 to 1.3 ± 1.1 substances, p = 0.386). Only a few AEs were observed. Two patients in the ALT and one patient in the SLT group required trabeculectomy within 1 year after laser treatment due to IOP decompensation. Conclusions: In the present study, SLT was at least as effective as ALT with fewer AEs and a similar reduction in concomitant IOP-lowering medication.

A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC. Many studies have demonstrated that cytokines and growth factors packaged into extracellular vesicles (EVs) have an essential role in tumor progression and drug resistance. In this study, we examined the role of serum-derived EV-associated cytokines as prognostic biomarkers for long-term outcomes in patients who underwent anthracycline-taxane-based NAC. We isolated extracellular vesicles from the serum of 190 TNBC patients who underwent NAC between 2015 and 2018 at Samsung Medical Center. EV-associated cytokine concentrations were measured with ProcartaPlex Immune Monitoring 65-plex panels. The prognostic value of EV-associated cytokines was studied. We found that patients with high EV_APRIL, EV_CXCL13, and EV_VEGF-A levels had shorter overall survival (OS). We further evaluated the role of these selected biomarkers as prognostic factors in patients with residual disease (RD) after NAC. Even in patients with RD, high levels of EV_APRIL, EV_CXCL13, and EV_VEGF-A were correlated with poor OS. In all subgroup analyses, EV_CXCL13 overexpression was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that a high level of EV_CXCL13 was an independent predictor of poor OS. Correlation analysis between biomarker levels in EVs and serum showed that EV_VEGF-A positively correlated with soluble VEGF-A but not CXCL13. An elevated level of soluble VEGF-A was also associated with poor OS. These findings suggest that EV_APRIL, EV_CXCL13, and EV_VEGF-A may be useful in identifying TNBC patients at risk of poor survival outcomes after NAC.

Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique.

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis (Mtb) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size (n = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB.

Modification of Respiratory Drive and Lung Stress by Level of Support Pressure and ECMO Sweep Gas Flow in Patients With Severe COVID-19–Associated Acute Respiratory Distress Syndrome: an Exploratory Retrospective Analysis

Patients with severe acute respiratory distress syndrome (ARDS) often exhibit an unusually strong respiratory drive, which predisposes them to effort-induced lung injury. Careful titration of support pressure via the ventilator and carbon dioxide removal via extracorporeal membrane oxygenation (ECMO) may attenuate respiratory drive and lung stress. A retrospective cohort study. At a single center, a university hospital. Ten patients with severe COVID-19-associated ARDS (CARDS) on venovenous ECMO therapy. Assessment of the effect of titrated support pressure and titrated ECMO sweep gas flow on respiratory drive and lung stress in spontaneously breathing patients during ECMO therapy. Airway occlusion pressure (P0.1) and the total swing of the transpulmonary pressure were determined as surrogate parameters of respiratory drive and lung stress. Ventilator-mediated elevation of support pressure decreased P0.1 but increased transpulmonary driving pressure, airway pressure, tidal volume, and end-inspiratory transpulmonary occlusion pressure. The increase in ECMO sweep gas flow lowered P0.1, transpulmonary pressures, tidal volume, and respiratory frequency linearly. In patients with CARDS on pressure support ventilation, even moderate support pressure may lead to overassistance during assisted ventilation, which is only reflected by advanced monitoring of respiratory mechanics. Modifying carbon dioxide removal via the extracorporeal system profoundly affects respiratory effort and mechanics. Spontaneously breathing patients with CARDS may benefit from consequent carbon dioxide removal.

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients.

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.

Comparison between Sugammadex and Neostigmine after Video-Assisted Thoracoscopic Surgery-Thymectomy in Patients with Myasthenia Gravis: A Single-Center Retrospective Exploratory Analysis.

This single-center retrospective exploratory analysis evaluated the effects of sugammadex compared with neostigmine on postoperative recovery in patients with myasthenia gravis (MG) who underwent video-assisted thoracoscopic surgery (VATS)-thymectomy. This retrospective study included 180 patients with MG, aged >18 years, who received sugammadex (sugammadex group, n = 83) or neostigmine-glycopyrrolate (neostigmine group, n = 88) after VATS-thymectomy between November 2007 and December 2020. Inverse probability of treatment weighting (IPTW) adjustment was performed to balance the baseline characteristics between the two groups. The primary outcome was the length of postoperative hospital stay, and the secondary outcomes were the incidence of postoperative mortality and complications, as well as the postoperative extubation and reintubation rates, in the operating room after VATS-thymectomy; the outcomes were compared between the two groups. After IPTW adjustment, the sugammadex group showed a significantly shorter median postoperative hospital stay than the neostigmine group (4 (2, 4) vs. 5 (3, 6) days, respectively; p = 0.003). There were no significant differences between the two groups in the incidences of postoperative complications (including postoperative myasthenic crisis, nerve palsy, atelectasis, and pleural effusion). Patients with MG following VATS-thymectomy who received sugammadex showed a significantly shorter postoperative hospital stay than those who received neostigmine.

Comparison of nasotracheal versus orotracheal intubation for sedation, assisted spontaneous breathing, mobilization, and outcome in critically ill patients: an exploratory retrospective analysis

Nasotracheal intubation (NTI) may be used for long term ventilation in critically ill patients. Although tracheostomy is often favored, NTI may exhibit potential benefits. Compared to orotracheal intubation (OTI), patients receiving NTI may require less sedation and thus be more alert and with less episodes of depression of respiratory drive. We aimed to study the association of NTI versus OTI with sedation, assisted breathing, mobilization, and outcome in an exploratory analysis. Retrospective data on patients intubated in the intensive care unit (ICU) and ventilated for > 48 h were retrieved from electronic records for up to ten days after intubation. Outcome measures were a Richmond Agitation and Sedation Scale (RASS) of 0 or − 1, sedatives, vasopressors, assisted breathing, mobilization on the ICU mobility scale (ICU-MS), and outcome. From January 2018 to December 2020, 988 patients received OTI and 221 NTI. On day 1–3, a RASS of 0 or − 1 was attained in OTI for 4.0 ± 6.1 h/d versus 9.4 ± 8.4 h/d in NTI, p < 0.001. Propofol, sufentanil, and norepinephrine were required less frequently in NTI and doses were lower. The NTI group showed a higher proportion of spontaneous breathing from day 1 to 7 (day 1–6: p < 0.001, day 7: p = 0.002). ICU-MS scores were higher in the NTI group (d1–d9: p < 0.001, d10: p = 0.012). OTI was an independent predictor for mortality (odds ratio 1.602, 95% confidence interval 1.132–2.268, p = 0.008). No difference in the rate of tracheostomy was found. NTI was associated with less sedation, more spontaneous breathing, and a higher degree of mobilization during physiotherapy. OTI was identified as an independent predictor for mortality. Due to these findings a new prospective evaluation of NTI versus OTI should be conducted to study risks and benefits in current critical care medicine.

(036) Characterizing flibanserin’s safety profile among postmenopausal women with HSDD: An Exploratory Analysis

Abstract Introduction Flibanserin is approved in the United States (US) for premenopausal women and in Canada for pre and naturally postmenopausal women, ≤60 years of age, to treat acquired, generalized hypoactive sexual desire disorder (HSDD). Clinical trials suggest that flibanserin's safety profile is similar among pre-and postmenopausal women. During a Phase 3 postmenopausal study, the most frequently reported adverse events (AEs) were dizziness (10%), somnolence (9%), nausea (8%), and headache (6%). This study explores postmarketing AEs received from postmenopausal women and their clinicians during flibanserin treatment. Objective The primary objective of this safety study is to further characterize flibanserin's safety profile among postmenopausal women with HSDD treated in a clinical setting. Methods This study is a retrospective exploratory analysis of AEs captured in a global safety database (August 15, 2015, to May 12, 2022). The database was queried for US reports of AEs in postmenopausal women using the Medical Dictionary for Regulatory Activities Search Strategy Version 21.1. Preferred Term (PT) “Product use in unapproved indication.” This PT was selected as postmenopausal use is an unapproved indication in the US. Reports were filtered to identify and exclude non-postmenopausal unapproved usages, such as use in males and premenopausal women with non-HSDD conditions. All reports stating postmenopausal use are included in this analysis. If reproductive status was not specified, age was used as an indicator. If age was unknown, the report was excluded. The age range used in this study was 51-75 years. Adverse events were categorized using PTs, and descriptive statistics were used to summarize the results. Dispensing data from a sample of 30,000 scripts filled over the past year at one pharmacy were used to estimate the percentage of flibanserin prescriptions filled by women ages &amp;gt;50 years. No incidence data were calculated as AE reporting is voluntary and true exposure is unknown. Results We identified 195 unique reports of postmenopausal use with at least one AE during the study period. There were 656 reported AEs, 16 (2.4%) were serious, and no fatalities. Adverse events occurring in ≥5 postmenopausal women excluding events not related to a body system are summarized in the Figure. Approximately 18% of scripts filled over the past year at one pharmacy were for women ages &amp;gt;50 years. It is important to acknowledge that this pharmacy’s findings may not represent all pharmacies. Conclusions The postmarketing safety profile of flibanserin among postmenopausal women is similar to that observed with premenopausal women and during clinical trials. Excluding PTs not related to a body system such as unapproved use and drug ineffective, the most frequently reported postmarketing AEs included dizziness, nausea, and insomnia. No safety signals specific to postmenopausal women have been identified to date. Although informative, the lack of information on medical history, concomitant medications, and other potential interacting products limit the ability to make inferences on causality in most reported cases. Disclosure Yes, this is sponsored by industry/sponsor: Sprout Pharmaceuticals, Inc Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout Pharmaceuticals, Inc.