6-month Intervals Research Articles

The Efficacy and Safety of Sodium-Glucose Co-transporter2 (SGLT2) Inhibitors in Real-World Clinical Practice: Potential Cautionary Use in Elderly Patients with Type2 Diabetes (T2D).

Sodium-glucose co-transporter2 (SGLT2) inhibitors have shown safe and therapeutic efficacy in randomized controlled trials (RCT) to reduce adverse cardiorenal events in high-risk patients with type2 diabetes (T2D). In this study, we investigated the efficacy and safety of SGLT2 intervention in patients with T2D in a real-world clinical practice to confirm the validity of the RCT results. As a retrospective study, we evaluated medical records from 596 patients with T2D treated with SGLT2 inhibitors (dapagliflozin or empagliflozin) in addition to their prior drug regimen to improve glucose control between 2015 and 2019 in the Endocrinology Department at Chungbuk National University Hospital. No control arm was evaluated to compare the effects of adding SGLT inhibitors to the pre-existing regimen. The primary objective was the measurement of glycated hemoglobin (HbA1c) from each individual patient over a 36-month period at 6-month intervals. The secondary parameters were the measurement of fasting plasma glucose (FPG) and body weight (Bwt) changes, as well as the monitoring of adverse events (AEs) and determining the reasons for drug discontinuation. HbA1c levels were reduced at each of the time points throughout the 36-month period and were significantly reduced by 12.5% (P < 0.01) from time0 (8.8 ± 1.3%) to 36months (7.7 ± 1.0%). FPG levels [from basal (180 ± 60mg/dL) to 36months (138 ± 38mg/dL)] and Bwt [from basal (74 ± 15kg) to 36months (72 ± 15kg)] were also significantly reduced (P < 0.01) for both measurements in the SGLT2 inhibitor add-on group. Similar to HbA1c profile, the FPG and Bwt were measured at a consistently lower level at 6months until the end of the study. The most common AEs were hypoglycemia (n = 57), genitourinary infection (GUI) (n = 31), and polyuria (n = 28). In the elderly population (≥ 75years old), AEs (31%) were generally more prevalent (P < 0.001) than those (21%) in the adult (< 75years old) patients. Over the study period, 211 (35%) patients either dropped or completely discontinued the use of the SGLT2 inhibitor, and the elderly patients tended to have a higher discontinuation rate (52%; P = 0.005) than the adults (33%). In this study, we demonstrated that SGLT2 inhibitors are an effective and durable hypoglycemic agent to control blood glucose levels with reduced maintenance of Bwt, but their use in the elderly (≥ 75years old) patients with T2D may warrant some additional caution due to increased probability of AEs and discontinuation of drug use.

A Prospective Study of the Diagnostic Performance of Photon-Counting CT Compared With MRI in the Characterization of Renal Masses.

The aim of this study was to assess the interreader reliability and per-RCC sensitivity of high-resolution photon-counting computed tomography (PCCT) in the detection and characterization of renal masses in comparison to MRI. This prospective study included 24 adult patients (mean age, 52 ± 14 years; 14 females) who underwent PCCT (using an investigational whole-body CT scanner) and abdominal MRI within a 3-month time interval and underwent surgical resection (partial or radical nephrectomy) with histopathology (n = 70 lesions). Of the 24 patients, 17 had a germline mutation and the remainder were sporadic cases. Two radiologists (R1 and R2) assessed the PCCT and corresponding MRI studies with a 3-week washout period between reviews. Readers recorded the number of lesions in each patient and graded each targeted lesion's characteristic features, dimensions, and location. Data were analyzed using a 2-sample t test, Fisher exact test, and weighted kappa. In patients with von Hippel-Lindau mutation, R1 identified a similar number of lesions suspicious for neoplasm on both modalities (51 vs 50, P = 0.94), whereas R2 identified more suspicious lesions on PCCT scans as compared with MRI studies (80 vs 56, P = 0.12). R1 and R2 characterized more lesions as predominantly solid in MRIs (R1: 58/70 in MRI vs 52/70 in PCCT, P < 0.001; R2: 60/70 in MRI vs 55/70 in PCCT, P < 0.001). R1 and R2 performed similarly in detecting neoplastic lesions on PCCT and MRI studies (R1: 94% vs 90%, P = 0.5; R2: 73% vs 79%, P = 0.13). The interreader reliability and per-RCC sensitivity of PCCT scans acquired on an investigational whole-body PCCT were comparable to MRI scans in detecting and characterizing renal masses. PCCT scans have comparable performance to MRI studies while allowing for improved characterization of the internal composition of lesions due to material decomposition analysis. Future generations of this imaging modality may reveal additional advantages of PCCT over MRI.

Efficacy of Ranibizumab in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion

Objective: Branch retinal vein occlusion (BRVO), a major cause of vision loss, is a significant ocular health concern. The frequency of macular edema due to BRVO is a critical area of study because of its profound impact on patient quality of life. This study investigated the effectiveness of ranibizumab, a monoclonal antibody fragment and VEGF inhibitor, in the treatment of macular edema in patients with BRVO. Material and Methods: Twelve patients (12 eyes) diagnosed with macular edema secondary to BRVO were included in this study. Patients were selected on the basis of specific visual acuity and macular thickness criteria, excluding those with other ocular conditions or systemic diseases. 0.05 milligrams of ranibizumab was administered intravitreally to each patient. Ophthalmological assessments were conducted both before and after the injection and at 1, 2, 3, and 6-month intervals following medication administration. Results: The average follow-up duration was 5.5±1.16 months (ranging from 2 to 6 months). The average central macular thickness before the injection was 542.66±191.44 µm, which decreased to 320.50±101.44 µm at 1-month post-injection, 283.66±125.01 µm at 2 months, 299.40±91.52 µm at 3 months, and 260.90±144.97 µm at 6 months. The reduction in central macular thickness at all time points was statistically significant (p&lt;0.01). The mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter score was 55.83±23.91 before the injection and improved to 71.25±17.07 at 1 month, 74.33±15.97 at 2 months, 66.7±21.60 at 3 months, and 71.2±17.38 at 6 months post-injection. The increase in visual acuity at 1, 2, 3, and 6 months after the injection was statistically significant compared to the pre-injection ETDRS letter scores (p&lt;0.05). An improvement of two or more lines in visual acuity was observed in 58.3% of cases at 1 month, 58.3% at 2 months, 50% at 3 months, and 80% at 6 months (one line equivalent to five letters). Conclusion: Intravitreal Ranibizumab injections have been found to be effective and reliable in the early stages of treating macular edema due to branch retinal vein occlusion.

Model-Informed Clinical Development of 6-Monthly Injection of Paliperidone Palmitate in Patients with Schizophrenia: Dosing Strategies Guided by Population Pharmacokinetic Modeling and Simulation (Part II).

Paliperidone palmitate 6-month (PP6M) intramuscular (IM) injection is the longest-acting treatment available for patients with schizophrenia. A population pharmacokinetic (popPK) modeling and simulation approach was deployed to inform dosing strategies for PP6M. The extensive analysis database included 15,932 paliperidone samples from 700 patients receiving gluteal paliperidone palmitate 3-month (PP3M) or PP6M injections in the double-blind phase of a phase-3 noninferiority study (NCT03345342). Exposure parameters for paliperidone appeared to increase dose-proportionally within each dosing schedule (PP3M/PP6M). The range of paliperidone exposures after IM administration of PP6M overlaps with that of corresponding doses of oral paliperidone extended release, PP 1-month (PP1M), and PP3M. Model-based simulations were performed to investigate paliperidone exposures in different PP6M dosing scenarios and relevant subpopulations. A dosing window of ≤ 2 weeks earlier and ≤ 3 weeks later than the target 6-month interval for maintenance treatment with PP6M dosing maintains paliperidone exposures at levels that are not expected to substantially impact its safety and efficacy. For missed-dose scenarios, tailored re-initiation regimens are proposed that should be applied before resuming PP6M maintenance dosing. Regarding subpopulations, PP6M 700 mg eq. is the highest dose recommended in mild renal-impairment patients; the paliperidone pharmacokinetics after PP6M administration is not affected by sex, body mass index, or age in a clinically meaningful way. Paliperidone concentration-time profiles after PP6M and PP3M dosing were adequately described by the popPK model. Model-based simulation results provide guidance for clinicians on initiating PP6M therapy, transitioning between paliperidone formulations, the dosing windows to use for maintenance dosing, and managing missed PP6M doses.

Automated Analysis of Split Kidney Function from CT Scans Using Deep Learning and Delta Radiomics.

Background: Differential kidney function assessment is an important part of preoperative evaluation of various urological interventions. It is obtained through dedicated nuclear medical imaging and is not yet implemented through conventional Imaging. Objective: We assess if differential kidney function can be obtained through evaluation of contrast-enhanced computed tomography(CT) using a combination of deep learning and (2D and 3D) radiomic features. Methods: All patients who underwent kidney nuclear scanning at Mayo Clinic sites between 2018-2022 were collected. CT scans of the kidneys were obtained within a 3-month interval before or after the nuclear scans were extracted. Patients who underwent a urological or radiological intervention within this time frame were excluded. A segmentation model was used to segment both kidneys. 2D and 3D radiomics features were extracted and compared between the two kidneys to compute delta radiomics and assess its ability to predict differential kidney function. Performance was reported using receiver operating characteristics, sensitivity, and specificity. Results: Studies from Arizona & Rochester formed our internal dataset (n = 1,159). Studies from Florida were separately processed as an external test set to validate generalizability. We obtained 323 studies from our internal sites and 39 studies from external sites. The best results were obtained by a random forest model trained on 3D delta radiomics features. This model achieved an area under curve (AUC) of 0.85 and 0.81 on internal and external test sets, while specificity and sensitivity were 0.84,0.68 on the internal set, 0.70, and 0.65 on the external set. Conclusion: This proposed automated pipeline can derive important differential kidney function information from contrast-enhanced CT and reduce the need for dedicated nuclear scans for early-stage differential kidney functional assessment. Clinical Impact: We establish a machine learning methodology for assessing differential kidney function from routine CT without the need for expensive and radioactive nuclear medicine scans.

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial.

Glaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care. The HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. The study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6months. We hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. HIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression. The trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage.

Intensive glucose control and the clinical paradox of transient progression of diabetic retinopathy: Prioritising the relevance of eye screening intervals.

The paradoxical early worsening of diabetic retinopathy with optimisation of glycaemic control is well recognised. Patients with type 2 diabetes mellitus with R0M0 grading at eye screening with enhanced glycaemic control and progression of diabetic retinopathy may get missed with just biennial monitoring as per the changes to national diabetes eye screening programme guidelines. However, from the perspective of patients with type 1 diabetes mellitus being offered newer hybrid closed-loop systems for insulin delivery, very recent guidance allows for this recommendation of a 24-month screening interval to be adjusted. There is an override option within the screening software to enable an additional 12-month screen following the initiation of the closed-loop system. More frequent screening during pregnancy when glycaemic control is tightened, was established several years ago. Interestingly, no such guidance is currently available for patients being treated with GLP-1RA for T2DM, or in patients following bariatric surgery despite the well-recognised impact that has been observed. With newer incretin mimetic treatments in the horizon, this warrants a review and needs a re-appraisal.

Evaluation of Brainstem Auditory-Evoked Potentials in Infants with Iron Deficiency Anemia

Purpose: To evaluate and compare the brain functions of infants with and without Iron Deficiency anaemia (IDA) electrophysiologically with brainstem auditory potentials (BAEPs). Materials and Methods: BAEP tests were performed on 26 healthy infants and 26 infants with iron deficiency anaemia, aged 6-24 months, who were followed through the Paediatric Haematology Department at SDU Faculty of Medicine. Children were classified as anaemic if their haemoglobin (Hb) level fell below -2 standard deviations for their age. All patients diagnosed with iron deficiency anaemia received 5 mg/kg/day of divalent iron glycine sulphate complex in three doses daily for a duration of 12 weeks, to be taken on an empty stomach. Both group were orally administered Chloral hydrate at a dosage of 50mg/kg prior to the BAEP test to induce sedation. The BAEP was recorded at a sound intensity level of 90 decibels, with a frequency of 10 Hertz, and with click stimuli ranging from 1000 to 2000. The BAEP test was administered to the IDA group before and after treatment, as well as to the control group, with a 3-month interval between tests. Results: 14 (53.8%) of the IDA patients were males, and 16 (61.5%) of the control group were females. Patients with IDA had an average age of 14.4±3.09 months, while the control group patients have an average age of 11.2±4.04 months. Patients with iron deficiency anaemia had lower pre-treatment levels of Hb, Hct, MCV, MCH, MCHC, transferrin saturation percentage, and ferritin compared to the control group, whereas platelet and RDW values were greater (p˂0.001). The study compared the Brainstem Auditory Evoked Potential (BAEP) values of patients with Iron Deficiency Anaemia (IDA) before treatment with those of control patients. The results indicated that the III-V interval, showing nerve conduction time, was significantly prolonged in the pre-treatment BAEPs (p˂0.05). There was no significant difference in interpeak latencies between the control group and patients with iron deficiency anaemia (IDA) following therapy (p˂0.05). Significant differences were found in the I-III, III-V, and I-V interpeak latencies of individuals with iron deficiency anaemia before and after treatment (p

Development of working memory and inhibitory control in early childhood: Cross-sectional analysis by age intervals and gender in Ecuadorian preschoolers.

Working memory (WM) and inhibitory control (IC) play a crucial role in learning during early childhood. The literature suggests a non-linear developmental trajectory of executive functions (EFs) with varied results according to gender, usually attributed to environmental factors. However, there is insufficient and inconclusive data on whether this pattern is reproduced in the Latin American preschool population since most studies have been conducted in English-speaking, European, and Asian environments. Thus, objectively comparing children's executive performance across diverse international geographical contexts becomes challenging. This study aimed to conduct a cross-sectional analysis of the performance in WM and IC of 982 Ecuadorian preschoolers aged between 42 and 65 months (M = 53.71; SD = 5.714) and belonging to medium-high, medium, and low-medium socioeconomic strata. The participants consisted of 496 boys (M = 53.77; SD = 5.598) and 486 girls (M = 53.65; SD = 5.834), representing nine cities in Ecuador. To assess the effect of age and gender on performance in these two domains, the sample was divided into four 6-month age intervals. Two tests were administered to the participants, and a survey was conducted with 799 of their usual caregivers. Viewing the cross-sectional mean scores of the WM and IC tests as a temporal continuum reveals an upward trend in each age interval studied. Girls outperformed boys on the IC test, showing statistically significant differences in the earliest age interval. The gender differences in executive performance reported in the literature emphasize the need to explore the modulating effect of environmental variables on early childhood development. This information could offer valuable insights for adapting and optimizing cognitive and didactic strategies in early childhood tailored to the characteristics and needs of the preschool population.

Evaluation of Genetic and Non-genetic Factors Influencing Semen Production Potential in Sahiwal Bulls

Background: Understanding genetic and non-genetic factors that influence the quality and quantity of semen production plays a crucial role in determining the reproductive efficiency and genetic progress within the Sahiwal breed. The objective of this study was to assess the impact of genetic and non-genetic factors on the semen production potential of Sahiwal bulls. Methods: Semen ejaculate data, including volume (VOL), sperm concentration per milliliter (CONC), total sperm count per ejaculate (TS), initial motility (INIT) and post-thaw motility (PT), as well as semen quality traits such as hypo-osmotic swelling test (HOST) and acrosome integrity of frozen semen (AIFS), were obtained from 52 Sahiwal bulls. The data spanned from January 2011 to December 2018 and were collected at BAIF’s frozen semen station in Jind, Haryana, India. To ensure data reliability, observations beyond the mean±4 standard deviations (S.D.) were identified as outliers and subsequently excluded from the study. Two key factors, namely the season of semen collection (winter, summer and monsoon) and the age of bulls at collection (categorized into 12-month intervals ranging from less than 36 months to 156 months), were considered influential factors affecting semen characteristics. To investigate the correlation between bulls (genetic + permanent environmental correlation) and semen parameters, a repeatability animal model was employed, treating the bull as a random effect. The statistical analysis was conducted using WOMBAT software. Result: The findings revealed that the season of semen collection had a highly significant effect (P less than 0.01) on VOL, CONC, TS and PT. However, INIT, HOST and AIFS were not influenced (P greater than 0.05) by the season of collection. Furthermore, age at semen collection significantly affected all semen characteristics. VOL and TS exhibited an increasing trend until 72 to 84 months, followed by a decline until 96 to 108 months.

Effectiveness of School-based Substance abuse Prevention Programme (SSPP) on awareness, attitude, peer pressure, and life skills among adolescents in selected public schools of Pokhara, Nepal–A cluster randomized trial protocol

ObjectiveEarly substance use has been linked to various adverse outcomes and escalates quickly during adolescence. Delaying the onset of substance use among adolescents is a primary public priority as it is associated with severe effects. The objective of the study is to develop and determine the effectiveness of a School-based Substance Abuse Prevention Programme (SSPP) on awareness, attitude, peer pressure, and life skills towards preventing substance abuse among adolescents. MethodPhase I of the study is a qualitative approach, where a focus group discussion (FGD) will be conducted among different stakeholders to explore their perceptions regarding the prevention of substance use among adolescents. The anticipated sample size is 38. Thematic analysis will be done by using ATLAS.ti software. The inputs given by the stakeholders will be incorporated in developing the intervention (SSPP). Phase II is a cluster randomized controlled trial. A minimum of 210 adolescents (105 each in the intervention and control groups) between the age group of 13 to 15 years from 8th and 9th grade will be recruited for the study. In this study, the school will be the cluster and will be randomly assigned either to an intervention or control arm. The data will be collected at pre, post, 3-month, and 6-month intervals. The ethical approval was obtained from the Nepal Health Research Council Committee, Nepal (NHRC 276/2023). The trial was also registered under the Clinical Trial Registry of USA-Clinical Trials.gov (CTRI 06004726/2023/08/22/). Descriptive and inferential statistics will be used to analyze the data. Expected resultsImplementation of the SSPP module will improve the awareness, attitude, peer pressure, and life skills of adolescents toward preventing substance use behavior. Overall, the study aims to achieve Sustainable Development Goal (SDG) 3.5- ‘Good Health and Well-being; strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.’ ConclusionThe present study protocol will help to develop a unique training module (SSPP) focused on preventing substance use behaviour among adolescents in Nepal.

What do we really know about vital pulp therapy?

Retrospective cohort study using STROBE cohort reporting guidelines. Patients from Mehr Dental Clinic in Tehran, Iran, who received different types of vital pulp therapy (VPT) by a single endodontist, due to carious pulpal exposure, between April 2011 and October 2022. These were: Full Pulpotomy (FP), Miniature Pulpotomy (MP) and Direct Pulp Capping (DPC). Data were accessed via the dental clinic's electronic database. Patients were deemed eligible if they had pulpal exposure due to caries, but not trauma. Pre-operative, immediate post-operative and at least one follow-up radiograph at a minimum 3-month interval were required. Demographic, diagnostic, and procedural data as well as informed consent were also required. Teeth with probing depths greater than 4 mm or pulpal necrosis were excluded. Patient, tooth and treatment factors were statistically analysed for an outcome of success or failure using a Cox proportional hazards model. Kaplan/Meier curves were used to establish the mean survival times. The Log-rank test was used to compare survival across the three treatment groups. The Omnibus test of model and the -2 log likelihood ratio (-2LL) were used to assess sensitivity and model fitness. Statistical analyses were determined using the IBM SPSS Statistics for Windows Version 21.0, with P value set at <0.05. 1257 VPTs from 1149 patients had complete data and were used in the analysis. 802 cases were excluded due to no follow up radiograph. The VPT cases were divided into FP (n = 272), MP (n = 217) and DPC (n = 768). The average follow up was 42.21 months, with an overall 116-month survival rate of 99.1% and success rate of 91.6%. FP had a mean survival time of 99.43 months; for MP it was 104.26 months; for DPC it was 102.27 months. There were no significant differences between these groups (P = 0.363). There were statistically significant correlations between symptomatic Irreversible Periodontitis (IP), radiographic signs of Apical Periodontitis (AP), restoration type, restoration surfaces and the outcome of VPT. This is one of the largest cohort studies of its kind, with over 1250 cases of various VPT techniques in 10 years. There was deviation from gold standard practice, with lack of rubber dam. A lack of haemostasis after 2 min could be construed as bacterially infected pulpal tissue and require further resection of pulp. Yet, these approaches still resulted in successful outcomes. Another interesting finding was that symptomatic IP with associated AP was treated with VPT, with a 78% success rate. Considering this study and other emerging evidence in the literature, application of VPT as an alternative to conventional Root Canal Treatment could be adopted in general practice, depending on the skills and knowledge of the practitioner and patient preferences.

Persistent increased severity of cannabis use disorder symptoms in adolescents compared to adults: a one-year longitudinal study.

Adolescence is a developmental period characterised by increased vulnerability to cannabis use disorder (CUD). However, previous investigations of this vulnerability have relied on cross-sectional comparisons and lack a detailed assessment of cannabis quantity, a potentially important confounding factor. Here, we aimed to investigate the one-year course of CUD in adolescents compared to adults who currently use cannabis, adjusting for a comprehensive measure of cannabis quantity. Data are from a one-year observational longitudinal study (CannTeen) of adolescents and adults who currently used cannabis regularly with five waves of assessment at 3-monthly intervals, based in London, UK. Participants were n = 70 adults (26-29, 45.7% female), who did not regularly use cannabis when they were under age 18, and n = 76 adolescents (16-17, 50.0% female). The exposure was adolescent (compared to adult) frequent cannabis use. The primary outcome was CUD symptoms measured using the cannabis use disorder identification test revised (CUDIT-R) at five time points. Models were adjusted for cannabis quantity using mean weekly standard THC units (one unit = 5mg THC). Other covariates included gender, and whether each session occurred before or during the COVID-19 pandemic. In models adjusted for pre-registered covariates, adolescents scored 3.7 points higher on the CUDIT-R compared to the adult group across the 5 assessment waves (3.66 95% CIs 1.99, 5.34). There was also evidence of a linear reduction in symptoms over time in both groups (-0.47, 95%CIs -0.67, -0.27). Adolescents had persistently increased CUD symptoms compared to adults across the 12-month period. This association was robust after adjusting for the quantity of cannabis consumed and other covariates.

Peripheral blood quantitation of CD26 positive leukemic stem cells as a predictor of tyrosine kinase inhibitor response in chronic myeloid leukemia.

Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML-LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML-CP. This was a prospective, observational, non-interventional single center study including newly diagnosed adult (>18 yrs) CML-CP patients. Absolute CD26 + CML-LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3-month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale. A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML-LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/μL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/μL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months. Absolute CML-LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/μL is highly predictive of achieving MMR at 12 months.

Comparison of virtual reality and computed tomography in the preoperative planning of complex tibial plateau fractures

IntroductionPreoperative planning is a critical step in the success of any complex surgery. The pur-pose of this study is to evaluate the advantage of VR glasses in surgical planning of complex tibial plateau fractures compared to CT planning.Materials and methodsFive orthopedic surgeons performed preoperative planning for 30 fractures using either conventional CT slices or VR visualization with a VR headset. Planning was performed in a randomized order with a 3-month interval between planning sessions. A standardized questionnaire assessed planned operative time, planning time, fracture classification and understanding, and surgeons’ subjective confidence in surgical planning.ResultsThe mean planned operative time of 156 (SD 47) minutes was significantly lower (p < 0.001) in the VR group than in the CT group (172 min; SD 44). The mean planning time in the VR group was 3.48 min (SD 2.4), 17% longer than in the CT group (2.98 min, SD 1.9; p = 0.027). Relevant parameters influencing planning time were surgeon experience (-0.61 min) and estimated complexity of fracture treatment (+ 0.65 min).ConclusionThe use of virtual reality for surgical planning of complex tibial plateau fractures resulted in significantly shorter planned operative time, while planning time was longer compared to CT planning. After VR planning, more surgeons felt (very) well prepared for surgery.

Abstract PO4-15-09: Unraveling the influence of progesterone receptor status on endocrine therapy sensitivity: insight from epigenetic and fragmentomics ctDNA profiling in estrogen receptor positive, HER2 negative metastatic breast cancer (MBC)

Abstract Background: In patients (pts) with estrogen receptor (ER) positive (pos), HER2 negative (neg) MBC, the absence of progesterone receptor (PR) expression is generally associated with a poorer endocrine therapy (ET) response and an unfavorable prognosis. However, real-time molecular changes during ET according to PR status are still not fully understood. The aim of this study was to examine the prognostic impact of PR and its association with the methylation levels of ESR1 promoters A (promA) and B (promB) at different timepoints in pts with ERpos HER2neg MBC who received first-line ET. Methods: Pts were enrolled in the prospective multicenter MAGNETIC.1 trial (CRO-2018-56) between January 2018 and January 2023. As first-line ET, pts received either fulvestrant or AIs with or without CDK4/6 inhibitors (CDK4/6i) as first-line ET. ctDNA samples were collected at baseline (T0) and at 3-month intervals (T3 and T6) and analyzed through methylation-specific (MS) droplet digital PCR (ddPCR), ddPCR fragmentomics and next generation sequencing (NGS). Clinico-pathological differences across the PR expression spectrum were analyzed using Fisher’s exact test. Matched pairs variations across timepoints (T0, T3, T6) of ACTBfragments distribution and ESR1 promA and promB were tested through Wilcoxon signed rank test. Results: Out of the 111 enrolled pts, 28 had PRneg MBC, of which 20 had an invasive ductal carcinoma (IDC) histotype, and 10 were diagnosed as de novo disease. Bone was the most common metastatic site both in the PRpos and PRneg subgroups (75% vs 73%), most pts received ET+CDK4/6i (96% vs 95%). ESR1 and PIK3CA mutations were respectively detected in 8% and 6%, and in 23% and 25% pts respectively for PRpos and PRneg. The prognostic impact of PR status was evident for both PFS (median 38 mos and 14 mos respectively for PRpos and PRneg, P = 0.0048) and OS (median not reached and median 33 mos respectively for PRpos and PRneg, P= 0.001). A significant increase in promB was observed at T3 vs T0 and at T6 vs T3 in the PRpos subgroup (respectively P=0.0158 and P&amp;lt; 0.001) but not in the PRneg. When comparing T6 to T0, no significant differences were observed regardless of PR status. At T3, significant decreases were observed in both the PRpos and PRneg populations for ACTBshort (P &amp;lt; 0.001 and P=0.03, respectively), ACTBmedium (P=0.0049 and P= 0.035, respectively) and ACTBlong(P&amp;lt; 0.001 and P&amp;lt; 0.001, respectively), compared to T0. In the comparison of T6 to T3, a significant variation in ACTBshort levels was observed in both subgroups (P&amp;lt; 0.001 for PRpos and P=0.012 for PRneg). while a significant reduction in ACTBmedium levels was observed only in the PRpos population when comparing T6 to T0 (P&amp;lt; 0.001). Conclusions: PRneg status was confirmed as an unfavorable prognostic factor with respect to PRpos both for PFS and OS, potentially due to different ET sensitivity. Epigenetic ctDNA profiling revealed different dynamics of ESR1 promB between PR-positive and PR-negative MBC, suggesting a distinct role of ESR1 in the onset of ET resistance within the two subgroups. Citation Format: Lorenzo Foffano, Elisabetta Molteni, Arianna Dri, Alessandra Franzoni, Linda Cucciniello, Lucia Da Ros, Silvia Buriolla, Silvia Bolzonello, Claudia Noto, Stefania Russo, Simon Spazzapan, Elena Nascimbeni, Brenno Pastò, Giada Targato, Serena Della Rossa, Marta Bonotto, Alessandro Marco Minisini, Giuseppe Damante, Barbara Belletti, Lorenzo Gerratana, Fabio Puglisi. Unraveling the influence of progesterone receptor status on endocrine therapy sensitivity: insight from epigenetic and fragmentomics ctDNA profiling in estrogen receptor positive, HER2 negative metastatic breast cancer (MBC) [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 PO4-15-09.

Abstract GS03-01: Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112

Abstract BACKGROUND. Advanced diagnostics such as magnetic resonance imaging (MRI) and gene-expression profiles are potentially useful to guide treatment in patients with ductal carcinoma in situ (DCIS). To evaluate these tests, we performed a prospective single arm multicenter study. We have previously reported the impact of MRI on surgical management of DCIS patients, and the effect of a 12-gene DCIS Score (DS) on radiotherapy (RT) use after wide local excision (WLE). We now report a pre-planned analysis of ipsilateral breast events (IBE) at 5-years. METHODS. Adult women with a core needle biopsy diagnosis of DCIS and eligible for WLE based on conventional imaging were registered following consent. All registered patients underwent breast MRI. Those still eligible, and willing, to receive WLE after appropriate follow-up biopsies underwent resection to free margins. DCIS sections were submitted to Exact Sciences for DS. Those with a low DS (&amp;lt; 39) were advised to omit RT; those with intermediate/high (inter/hi) DS (≥39) were advised to receive RT. All participants were monitored at 6-month intervals for any breast cancer event, and for survival. An IBE was defined as the first DCIS or invasive recurrence in the ipsilateral breast following the final WLE. Participants without IBE were censored by date of last contact or date of death for those who died. Follow-up was truncated at 5 years from WLE. Using data available as of 07-06-2023, Kaplan-Meier (K-M) curves were constructed to estimate the time-to-event distributions for subjects who received RT and for those who did not. The 5-year IBE rates and 95% confidence intervals (CIs) were estimated from K-M curves for all subjects with a DS (analogue of Intention to Treat [ITT] analysis), and for the subset who were compliant with their DS-based RT recommendation (Per Protocol analysis). The analyses were repeated for subgroups based on age at DCIS diagnosis (&amp;lt; 50 vs. ≥ 50). RESULTS. Of 339 women evaluable for the previously reported primary analysis (PMID 30653209), 171 (50.4%) underwent WLE with free surgical margins and had DS available for RT recommendations (ITT population). Of these, 7/82 low DS patients underwent RT, and 5/89 inter/hi DS patients declined RT; thus, the adherence to DS-based RT recommendations was 93%. At a median of 5 years of follow-up from final WLE, the ITT population experienced a total of eight IBE events (4.8%, 95% CI 2.4, 9.4) with 5-year IBE rates that were similar for participants with a low DS and for those with a inter/hi DS: 5.1% (95% CI: 1.9, 12.9) and 4.5% (95% CI 1.7, 11.7), respectively. Stratification by age did not alter these results: among women aged &amp;lt; 50 years (n=33), the IBE rate was 6.7% (95% CI 1.0, 38.7) for low DS and 5.6% (95% CI 0.8, 33.4) for inter/hi DS. Among women aged ≥ 50 years (n=138), the IBE rate was 4.7% (95% CI 1.5, 13.8) for low DS and 4.3% (95% CI 1.4, 12.7) for inter/hi DS. In the per-protocol analysis (N=159 adherent to RT recommendations), IBE rates were also similar for participants who had a low DS and no RT [5.5% (95% CI 2.1, 14.1)] and for those with inter/hi DS who received RT [4.8% (95% CI: 1.8% to 12.3%)]. Again, there was no discernible influence by age as categorized above. CONCLUSION. We report the first prospective data on use of DCIS Score for RT decisions, and 5-year IBE rates. We find that DS-based recommendations are followed by &amp;gt;90% of patients. Although the sample size is limited, the data are reassuring in that the IBE rate is similar between the low DS group treated with WLE alone and the inter/hi DS group treated with WLE and radiation, whereas prior studies have shown a marked difference in IBE rates by DS with excision alone. Therefore, this prospective trial provides strong evidence to support the omission of RT after surgery in DCIS patients with low DS, and its use in patients with intermediate/high DS. Citation Format: Seema Khan, Justin Romanoff, Constantine Gatsonis, Habib Rahbar, Ruth Carlos, Sunil Badve, Jean Wright, Constance Lehman, Worta McCaskill-Stevens, Ralph Corsetti, Derrick Spell, Kenneth Blankstein, Linda Han, Jennifer Sabol, John Bumberry, Ilana Gareen, Bradley Snyder, Lynne Wagner, Kathy Miller, Joseph Sparano, Christopher Comstock. Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112 [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 GS03-01.

THE PHYSICAL AND MENTAL HEALTH BENEFITS OF PARTICIPATING IN A LUNGS IN ACTION COMMUNITY EXERCISE MAINTENANCE PROGRAM FOLLOWING REHABILITATION

INTRODUCTION AND AIM Lungs in Action (LIA), a signature program of Lung Foundation Australia (LFA) is a community exercise program for people with chronic lung and cardiac conditions. Facilitated by Exercise Physiologists, Physiotherapists and Fitness Instructors, LIA supports patients to maintain the benefits achieved in pulmonary or cardiac rehabilitation. This research aimed to determine the holistic health benefits of participation in LIA through a national participant evaluation, concurrently with functional outcome measures over a 3-month period. METHODS A convenience sample of LIA participants completed an online health questionnaire (Qualtrics) that incorporated the EQ-5D-5L Health Questionnaire, demographics and structured health and wellbeing questions at baseline. A follow-up health questionnaire was undertaken 3-months post baseline. Concurrently, LIA Instructors conducted functional assessments of muscular strength (30sec Sit to Stand (30STS)), mobility, and balance (Timed Up and Go (TUG)) at baseline and 3-months post, to assess if physiological adaptations were evident. RESULTS 108 LIA participants (60±8 years; F=72) consented to complete the baseline questionnaire with n=61 (60±7 years; F=41) completing the 3-month post questionnaire. There were significant improvements in EQ-5D-5L anxiety domain (MD±SD; 0.18±0.22; p=0.04) and overall health rating (EQ-VAS) (MD±SD; 5.62±2.72; p=0.02). 74 participants (60±7 years; F=52) who attended an average of 11±6 classes over the 3-month interval, completed functional testing at both timepoints. There was a significant decrease in time to complete the TUG (MD±SD; -0.81±1.41 sec; p&amp;lt;0.0001) and increase in repetitions for the 30sSTS (MD±SD; 1.68±2.76 reps; p&amp;lt;0.0001). CONCLUSION Results indicate an increase in functional capacity, overall health, and a decrease in anxiety over the 3-month period. These benefits may relate to improved independence and activities of daily living.

Comparison of growth patterns in the first year of life between term small for gestational age and appropriate for gestational age South Indian infants

BackgroundEarly life growth trajectories of Indian small for gestational age (SGA) infants are sparse. This study aimed to compare longitudinal growth in appropriate for gestational age (AGA) and SGA infants...

Psychological maltreatment by teachers and peer victimization in Chinese youth: Depression and aggression as mediators

BackgroundPsychological maltreatment by teachers and peer victimization are significant public health issues among youth. However, few studies have verified transactional associations between psychological maltreatment by teachers and peer victimization at the within-person level and the mediating roles of depression and aggression have yet to be fully evaluated. ObjectiveThis study examined the transactional associations between psychological maltreatment by teachers and peer victimization from middle childhood to early adolescence, separating within- and between-person variation. The study also examined whether youth's depression and aggression mediated the associations. Participants and settingA total of 4945 Chinese youth (Mage = 9.92 years, SD = 0.73 53 % boys) completed a packet of measures on five occasions at 6-month intervals from May of 2017 to May of 2019. MethodsRandom Intercept Cross-Lagged Panel Models (RI-CLPMs) were used to distinguish between- and within-person effects. ResultsThe results indicated that: (a) Psychological maltreatment by teachers predicted peer victimization, and vice versa; (b) Depression (but not aggression) mediated the associations from peer victimization to psychological maltreatment by teachers. ConclusionsThe findings supported bidirectional spillover effects between adverse teacher-student and peer interactions and demonstrated at the within-person level that such effects were transmitted indirectly via youth's depression.