Low-risk Disease Research Articles

Transvitreal Retinochoroidal Biopsies of Primary Uveal Melanoma Reveal an Association of Low HLA Class I and High NK Cell Abundance in Low-Risk Disease.

Immune cells in primary uveal melanoma (PUM) have mostly been studied in enucleated tissue, thereby precluding material from thinner, low-risk PUM tumors for research purposes. Here, we investigated the feasibility of using tumor tissue acquired by transvitreal retinochoroidal (TVRC) tumor biopsies to study the tumor immune microenvironment and relation to genetic risk class. Collected tumor biopsies of 41 patients were tested for genetic aberrations to determine high-risk (n = 19), medium-risk (n = 12), and low-risk (n = 9) tumors and were digested for flow cytometry analysis of immune cell and tumor markers. In addition, 13 patient-matched enucleated tumors were stained using multiplex immunohistochemistry. Tumor biopsies showed a high variability in the degree of immune infiltration. The tumor-specific lymphocyte infiltration pattern correlated well with the infiltration pattern in patient-matched enucleations. High-risk tumors tended to have a higher abundance of CD8 T cells, which expressed activation markers CD39, CD69, and PD-1, with reduced CD127 expression. In general, low-risk tumors exhibited decreased human leukocyte antigen (HLA) class I expression, coinciding with a higher abundance of natural killer (NK) cells (P = 0.0049), indicating a different lymphocyte infiltration pattern between low-, medium- and high-risk tumors. TVRC biopsies are a suitable and valuable source of PUM tissue for research purposes. An abundance of CD8 T cells was found in high-risk PUM tumors. Further, medium- and low-risk PUM tumors are characterized by decreased HLA class I expression with a concomitant increase in NK cell infiltration as compared to high-risk PUM tumors, correlating with decreased risk of disease recurrence.

Management of Adverse Effects in Testosterone Replacement Therapy.

This narrative review aims to provide the most updated knowledge regarding the treatment of adverse effects secondary to testosterone replacement therapy (TRT), such as gynecomastia, cardiovascular and hematologic risks, prostate health risk, and liver dysfunction risks. An extensive literature review was conducted, incorporating guidelines from the American Urological Association and the Endocrine Society. The studies determined common adverse effects and their most common methods of management. TRT improves the quality of life, sexual function, and mood in hypogonadal men. Possible adverse effects associated with TRT include increased estrogen levels and gynecomastia, which are usually managed with aromatase inhibitors and tamoxifen. Cardiovascular risks from TRT include hypertension and erythrocytosis, which mandate periodic hematocrit and blood pressure monitoring; therapeutic phlebotomy is indicated if the hematocrit exceeds 52%. No significant concern regarding prostate cancer has been observed in the closely monitored patient. However, TRT should not be administered to individuals with active evidence of untreated prostate cancer, except under rare circumstances such as active surveillance for very low-risk disease. Older oral forms of TRT can affect liver function; therefore, transdermal, newer oral forms and injectables are generally favored in men with a history of liver disease. Monitoring and management of adverse effects are critical to maximize benefit and minimize the risks of TRT. Ongoing research will further elucidate the safety of TRT while advancing evidence-based practices in managing its associated adverse effects. Effective patient education and counseling are also essential to improve compliance and treatment outcomes.

Real-World Data on Lymphoma in Adolescents and Young Adults (AYA)-Report From the Lymphoma and Related Diseases Registry (LaRDR).

Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15-39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options. We performed a retrospective review of patients aged 18-60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18-39 years) and older adults (OAs) (aged 40-60). AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs. The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40-60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes. The authors have confirmed clinical trial registration is not needed for this submission.

Accelerometer-measured physical activity timing with incident dementia.

Moderate to vigorous physical activity (MVPA) is linked to lower dementia risk, though the optimal timing remains unclear. Using accelerometer-measured MVPA data from 90,329 dementia-free UK Biobank participants with at least 2 years of follow-up, we assessed associations between MVPA patterns (morning, afternoon, evening, mixed, inactive) and dementia risk via multivariable-adjusted Cox proportional hazards models. Compared to the inactive group, participants with a tendency of morning MVPA had a lower risk of all-cause dementia (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.90) and Alzheimer's disease (AD) risk (HR: 0.44, 95% CI: 0.22-0.86). No association of the other time point with all-cause dementia was observed. Additionally, the incidence of vascular dementia (VD) did not exhibit a significant relationship among all timing groups. Morning MVPA was associated with a lower risk of all-cause dementia and AD, while MVPA at any time point showed no association with VD. Few studies have examined accelerometer-measured moderate to vigorous physical activity (MVPA) timing with incident dementia. Participants with a tendency of morning MVPA had a lower risk of all-cause dementia and Alzheimer's disease. No significant association was found between all MVPA timing and vascular dementia (VD) risk. Findings suggest timing-specific physical activityinterventions for dementia prevention.

Cord blood metabolite profiles and childhood cardio-metabolic outcomes in a population-based cohort.

Adverse exposures in utero might cause adaptations of cardiovascular and metabolic organ development, predisposing individuals to an adverse cardio-metabolic risk profile from childhood onwards. We hypothesized that adaptations in metabolic pathways underlie these associations and examined associations of metabolite profiles at birth with childhood cardio-metabolic risk factors. The study included 763 mother-child pairs participating in an ongoing population-based prospective cohort study with an overall low disease risk. Cord blood serum concentrations of amino acids (AA), non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines (Carn) were obtained using a liquid chromatography coupled with tandem mass-spectrometry. We measured android/gynoid fat mass ratio, blood pressure, insulin, and lipid concentrations at the children's age of 5.9 (0.3) and 9.8 (0.9) years. We did not observe associations of cord blood metabolites with systolic or diastolic blood pressure, insulin, triglycerides and android/gynoid fat mass ratio at both ages and cardio-metabolic risk clustering at age 10 years. Five short- and medium-chain Carn.a metabolites were positively associated with cardio-metabolic risk clustering at age 6 but did not survive more stringent confounder adjustment. No consistent associations between cord blood metabolites and cardiovascular risk factors at school age were observed.

Hypofractionated image-guided radiotherapy with 70 Gy in 28 fractions for prostate cancer confined to the pelvis: a single institute experience in Taiwan

BackgroundThe incidence of prostate cancer is increasing in Asian countries. Although moderately hypofractionated radiotherapy is not inferior to conventional fractionated radiation according to the updated guidelines, data regarding its efficacy and safety in Taiwan are currently lacking. The aim of this study was to investigate the outcomes of prostate cancer patients treated with hypofractionated image-guided radiotherapy at a single institution in Taiwan.MethodsWe retrospectively included patients with prostate cancer across all risk groups who were treated with hypofractionated image-guided radiotherapy 70 Gy (Gy) in 28 fractions (at 2.5 Gy/fraction) between 2007 and 2022. We analyzed treatment efficacy by assessing overall survival, prostate cancer-specific survival, event-free survival, biochemical failure, locoregional recurrence, and distant metastasis. The safety of the treatment was evaluated through acute and late gastrointestinal (GI) and genitourinary (GU) toxicity grading based on the Radiation Therapy Oncology Group criteria. Event-free survival, overall survival, prostate cancer-specific survival, biochemical failure, locoregional recurrence, and distant metastasis were evaluated using the Kaplan–Meier method.ResultsWe identified 150 consecutive men with prostate cancer: 12.7% were at low risk, 32.7% were at intermediate risk, 44.6% were at high risk, and 10% had N1 disease. The median follow-up time was 68.9 months (range: 2.3–172 months). The 5-year overall survival rate was 91.7% for the entire cohort, with rates of 100%, 94.3%, 93.3% and 71.1% for the low-risk, intermediate-risk, high-risk, and N1-disease groups, respectively (p < 0.001). The 5-year event-free survival rate for all patients was 75.8%. Among the risk groups, the 5-year event-free survival rates were 100%, 86.3%, 68.3% and 52.5% for the low-risk, intermediate-risk, high-risk, and N1 disease groups, respectively (p < 0.001). Grade ≥ 2 late GI toxicity was rare (0.7%), and grade ≥ 2 late GU toxicity was observed in 9.3% of the patients.ConclusionsHypofractionated image-guided radiotherapy, delivering 70 Gy at 2.5 Gy per fraction, is both effective and safe for Taiwanese patients with prostate cancer across all risk groups, consistent with findings from existing large randomized trials. Therefore, as a solution to enhance patient convenience, hypofractionated radiotherapy is a reasonable option for the definitive treatment of prostate cancer.Trial registrationNot applicable.

Computed tomography coronary angiography as an alternative to invasive coronary angiography in preoperative evaluation for mitral surgery.

The aim of this study was to assess the effectiveness of non-invasive coronary computed tomography angiography (CTA) as an alternative to traditional invasive coronary angiography (ICA) for preoperative evaluation of low risk patients with an indication for non-emergent mitral surgery and to assess any difference in adverse outcomes from this strategy. This was a retrospective cohort study from a single center with data collected from July 2014 - June 2020 for 1576 patients undergoing mitral valve surgery of all etiologies - excluding patients requiring coronary artery bypass surgery. We performed a 1:2 propensity score matching for patients evaluated with CT (n=345) to those evaluated with ICA (n=602). The primary outcome was a composite of major adverse events in the immediate postoperative period, including death, stroke, new onset renal failure, post-operative cardiac arrest, need for unplanned coronary artery bypass grafting or percutaneous coronary re-vascularization. The odds ratio was calculated for occurrence of major adverse events in the CT angiography group compared to the catheterization group. The mean age (standard deviation) was 55.62 years (11.54) for the CTA group and 58.22 years (10.11) for the ICA group. In the CTA group 334 (96.8%) and from the ICA group 582 (96.7%) patients underwent mitral valve repair. 13 (3.8%) patients in the CTA group experienced a major adverse event compared to 25 (4.2%) patients in the ICA group. Of these, there were no mortalities in the CTA group but one (0.2%) operative mortality in the ICA group. Four (1.2%) patients in the CTA group had a post-operative stroke compared to three (0.5%) patients in the ICA group. One (0.3%) patient in the CTA group required renal replacement therapy postoperatively compared to 11 (1.8%) in the ICA group. Percutaneous coronary intervention was required in one (0.3%) patient in CTA group and 2 (0.3%) patients in ICA group for a coronary complication of valve surgery despite non-obstructive coronary anatomy being confirmed in both groups pre-operatively. The odds ratio for having a major adverse event when worked up by CTA compared to ICA was 0.904 (0.443, 1.761). There were no increased odds of experiencing a major adverse event for low risk mitral valve patients undergoing preoperative coronary evaluation with CTA compared to ICA. This data has modified our practice pattern where we now offer coronary CTA to all elective patients who are low risk for coronary artery disease.

Multicenter Retrospective Analysis of Pediatric Differentiated Thyroid Carcinoma: Treatment Practices and Outcomes Prior to Pediatric American Thyroid Association Guidelines Implementation.

Differentiated thyroid carcinoma (DTC) is the most common pediatric thyroid malignancy, with papillary thyroid carcinoma (PTC) representing 90% of the cases. In 2015, the American Thyroid Association (ATA) developed management guidelines for pediatric DTC. Patients less than 21years of age diagnosed with DTC between 2000 and 2015 at Texas Children's Hospital, Seattle Children's Hospital, Children's Healthcare of Atlanta, Children's Hospital Colorado, and Nationwide Children's Hospital were retrospectively analyzed to evaluate treatment practices before the implementation of the ATA guidelines. We included 216 pediatric patients with DTC. A majority were female (76%) with a median age at diagnosis of 14.8years. Neck swelling (56%) and palpable nodules (49%) were common presenting symptoms. Diagnostic evaluations typically included thyroid ultrasound, with common features being microcalcifications (47.7%) and hypoechogenicity (39.0%). Fine-needle aspiration cytology confirmed diagnosis in 50.5%. The majority of patients underwent total thyroidectomy (78.7%) and lymph node dissection (75.5%). ATA risk stratification was low, intermediate, and high risk in 111 (51.4%), 29 (13.4%), and 76 patients (35.2%), respectively. Upfront radioactive iodine (RAI) was administered in 83%. At 1-year follow-up, 46% were disease-free (66% low risk, 59% intermediate risk, and 13% high risk). The 5-year progression-free survival for low, intermediate, and high risk were 86%, 53%, and 43%, respectively. The disease-related overall survival was 100%. Prior to the introduction of the ATA guidelines, a majority of patients underwent total thyroidectomy with lymph node dissection followed by RAI. Selective use of RAI for low-risk disease as recommended in the current guidelines may be appropriate.

A Systematic Review of Oxidative Stress Markers and Risk of Coronary Artery Calcification

Background: Early diagnosis of atherosclerosis, particularly in its subclinical phase, is crucial for reducing mortality and morbidity associated with cardiovascular diseases. This study aims to investigate the relationship between oxidative stress markers and coronary artery calcification (CAC), enhancing our understanding of the pathophysiology of CAC. Methods: In October 2022, we conducted a systematic search of the Web of Science, Scopus, PubMed, and Embase databases without language or time restrictions, screening a total of 557 records. We excluded studies involving animals, in vitro experiments, reviews, case reports, clinical trials, editorials, and clinical guidelines. Eligible human observational studies (cohort and cross-sectional) that examined the link between CAC and oxidative stress markers were included. The Newcastle-Ottawa Scale was employed to assess the quality of the included studies. Results: Our systematic review encompassed 40 studies, all of which included both male and female participants, predominantly using cross-sectional designs. Participants included individuals at low, intermediate, or high risk of coronary artery disease, patients with type 2 diabetes, those with existing cardiovascular disease, and asymptomatic individuals. The studies investigated various oxidative stress markers, including serum uric acid and 8-isoprostane, both of which showed strong correlations with CAC incidence and severity. Conclusion: Oxidative stress markers may positively correlate with CAC scores, indicating a potential avenue for identifying individuals at heightened risk. This review underscores the need for further studies to facilitate early diagnosis of cardiovascular complications and the establishment of novel pharmacological targets.

Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines.

Vitamin D offers numerous under-recognized health benefits beyond its well-known role in musculoskeletal health. It is vital for extra-renal tissues, prenatal health, brain function, immunity, pregnancy, cancer prevention, and cardiovascular health. Existing guidelines issued by governmental and health organizations are bone-centric and largely overlook the abovementioned extra-skeletal benefits and optimal thresholds for vitamin D. In addition, they rely on randomized controlled trials (RCTs), which seldom show benefits due to high baseline 25-hydroxyvitamin D [25(OH)D] concentrations, moderate supplementation doses, and flawed study designs. This review emphasizes the findings from prospective cohort studies showing that higher 25(OH)D concentrations reduce the risks of major diseases and mortality, including pregnancy and birth outcomes. Serum concentrations > 30 ng/mL (75 nmol/L) significantly lower disease and mortality risks compared to <20 ng/mL. With 25% of the U.S. population and 60% of Central Europeans having levels <20 ng/mL, concentrations should be raised above 30 ng/mL. This is achievable through daily supplementation with 2000 IU/day (50 mcg/day) of vitamin D3, which prevent diseases and deaths. Furthermore, a daily dose between 4000 and 6000 IU of vitamin D3 to achieve serum 25(OH)D levels between 40 and 70 ng/mL would provide greater protection against many adverse health outcomes. Future guidelines and recommendations should integrate the findings from observational prospective cohort studies and well-designed RCTs to improve public health and personalized care.

Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model.

Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.

Treatment Response Evaluation in Necrotizing Otitis Externa Using 18F-FDG-PET Imaging.

This study aims to identify 18F-FDG-PET imaging features for improving treatment response evaluation in patients with necrotizing otitis externa (NOE), aiding in the difficult differentiation between sterile inflammation and active infection. Retrospective cohort study. Tertiary hospital. Patients diagnosed with NOE between 2011 and 2022. NOE criteria included otalgia, otorrhea, granulation, and radiological features consistent with osteomyelitis. 18F-FDG-PET/computed tomography (CT) parameters were derived from manually delineated regions of interest and were evaluated on both pretreatment and end-of-treatment scans. Recurrent disease of NOE after end-of-treatment 18F-FDG-PET scans. This study comprised 20 NOE patients, including 5 (25%) experiencing recurrent disease after the end-of-treatment scan. The end-of-treatment 18F-FDG-PET parameters of maximal and peak standardized uptake value (SUVmax and SUVpeak) were significantly higher in recurrent cases (p = 0.025 and p = 0.025, respectively). Both parameters demonstrated good discrimination ability in predicting recurrence, with optimal cutoffs yielding 100% sensitivity and 67% specificity. Other parameters, including mean SUV and total lesion glycolysis (TLG), did not yield significant results, neither did the calculated difference in uptake between end-of-treatment and pretreatment scans. SUVpeak on 18F-FDG-PET was the preferred parameter for treatment response evaluation of NOE at the end-of-treatment scan. A high residual SUVpeak may adequately detect patients at risk for recurrent disease, which may necessitate prolonged treatment, while low SUVpeak is found in patients with low risk for recurrent disease permitting safe treatment cessation.

Physician Payment Incentives and Active Surveillance in Low-Risk Prostate Cancer

Active surveillance in men with less aggressive prostate cancer is inconsistently used despite clinical guidelines. Renumeration generally favors treatment over conservative management and may contribute to the variable adoption of active surveillance, which suggests that value-based payment incentives may promote guideline-concordant care. To describe the adoption of active surveillance in low-risk prostate cancer, following the initiation of a novel payment incentive sponsored by a commercial payer to support its use. This cohort study included men with prostate cancer diagnosed between 2015 to 2021 with data registered with the Michigan Urological Surgery Improvement Collaborative (MUSIC), a statewide quality-improvement collaborative of practicing urologists. Eligible participants were men with newly diagnosed low-risk or low-volume, favorable intermediate-risk prostate cancer who were eligible for active surveillance. Data were analyzed from January 2015 through December 2021. Health insurance payment incentive established between June 9, 2017, and September 30, 2018, to encourage active surveillance adoption within MUSIC. Upon meeting the target (ie, at least 72% of men with low-risk disease consider or initiate surveillance), the insurer would provide enhanced reimbursement on claims covered by preferred provider organization plans independent of diagnosis. Active surveillance adoption relative to the preincentive period among men with low-risk prostate cancer. Secondary analyses examined practices by baseline surveillance use and proportion of patients with eligible insurance plans, as well as patients with favorable intermediate-risk disease. We identified 15 273 patients (median [IQR] age, 65 [59-70] years), of whom 10 457 (68.5%) had low-risk disease. The percentage of these men electing for surveillance increased, from 54.4% in 2015 (729 of 1340 men) to 84.1% in 2021 (1089 of 1295 men). Relative to the preincentive period, the payment incentive was not associated with increased surveillance use among patients with low-risk disease (odds ratio [OR], 0.96; 95% CI, 0.75-1.24) during its application. Secondary analyses similarly did not demonstrate an association between the payment incentive and active surveillance adoption. A payment incentive was not associated with increased active surveillance adoption in men with low-risk prostate cancer relative to the preincentive period. Value-based reimbursement incentives may require tailored implementation that considers existing reimbursement policy and practice characteristics to improve prostate cancer care quality.

Gestational trophoblastic neoplasm: Patient outcomes and clinical pearls from a multidisciplinary referral center.

To describe clinical outcomes and pearls for patients with gestational trophoblastic neoplasm (GTN). Patients with GTN treated at a referral center from 1/2006 to 12/2022 were included. Clinical characteristics, World Health Organization risk score (low-risk 0-6, high-risk ≥7), and treatments/outcomes were evaluated using summary statistics, stratified by initial treatment at a referral center versus locally. Histologies included complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), choriocarcinoma (CCA), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). Of 189 patients with GTN, 125 were treated initially at a referral center and 64 locally. Median age at diagnosis was 34years (range, 17-70). Most patients were White (n=132, 70%); 80 patients had CHM, 26 PHM, 52 CCA, 11 PSTT, 19 ETT, and 1 ETT/CCA. For low-risk GTN, first-line treatment was primarily methotrexate, although some were cured with repeat dilation and curettage. For high-risk disease, first-line therapy consisted of multiagent chemotherapy regimens at a referral center (n=18/18) compared to 7 of 15 patients with high-risk GTN treated with methotrexate at local institutions. Patients with low-risk and high-risk disease who received initial care at a tertiary referral institution had cure rates of 100% (n=87/87) and 89% (n=16/18), respectively, while patients with initial care locally had cure rates of 87% (n=33/37) and 47% (n=7/15), respectively. GTN is a rare gynecologic malignancy with high cure rates, particularly in low-risk disease. Treatment consolidation at a tertiary referral institution is critical for improved outcomes, particularly in those with high-risk disease or PSTT/ETT.

Local excision for T1 rectal cancer: A population-based study of practice patterns and oncological outcomes.

Local excision (LE) for T1 rectal cancer may be recommended in those with low-risk disease, while resection is typically recommended in those with a high risk of luminal recurrence or lymph node metastasis. The aim of this work was to compare survival between resection and LE. This was a population-based retrospective cohort study set in the Canadian province of Ontario. Patients were individuals with T1Nx rectal cancer between 2010 and 2014 and demographics, disease characteristics, treatments and outcomes were determined using linked administrative databases. This study does not include clinical information regarding individual patient treatment decisions. The main outcome measure was overall survival (OS). A total of 719 patients were identified, including 359 with upfront resection, 113 with LE and immediate resection (<90 days) and 247 with LE with definitive intent. The majority of LEs were performed via colonoscopy. Piecemeal excision (42% vs. 49%, p = 0.28) and positive margin (50% vs. 77%, p < 0.01) rates were high in both LE groups, with the highest rate in those with immediate resection. The prevalence of poor differentiation (<5%, p = 0.70) and lymphovascular invasion (LVI) (14%, p = 0.80) was similar across groups. In those with LE with definitive intent, 21% ultimately underwent resection (median 150 days, interquartile range 114-181 days) and 4% received radiation. There was no difference in 5-year OS between groups (resection83.2% vs. LE and immediate resection82.3% vs. definitive LE 83.3%; p = 0.33). Adjusted analyses demonstrated no association between approach and survival [definitive intent LE hazard ratio (HR) 0.97 (95% CI 0.70-1.35), LE and immediate resection HR 0.97 (95% CI 0.60-1.45), upfront resection HR 1 (Ref); p = 0.98]. Differentiation, piecemeal excisions and LVI were not associated with OS in the LE groups. There were no observed differences in survival between those who underwent resection, LE and immediate resection and definitive intent LE. Although, these are observational data, they call into question the reflexive decision to offer radical resection for those with suspected T1 rectal cancer.

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial.

The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy. Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival. Other variables included age, race, performance status, body mass index, stage, histologic type and grade, diagnostic procedure, lymphovascular space invasion before surgery and on final pathology, lymph node status, residual disease, and lesions >2 cm on final pathology. A total of 338 patients underwent simple hysterectomy. Of those, 281 (83%) were performed by minimally invasive surgery and 57 (17%) by open surgery. With a median follow-up of 4.5 years, a total of 12 (4.3%) recurrences were observed in 281 patients having simple hysterectomy by minimally invasive surgery versus 3 in 57 (5.3%) having open surgery (p = .73 from Fisher exact test). Although not randomized, the 2 groups were comparable except for histology and residual disease in the hysterectomy specimen. Patients with minimally invasive surgery had more adenocarcinoma and less adenosquamous compared to open surgery (35.9% versus 22.9% and 3.6% versus 14%, respectively; p = .005). Significantly fewer patients treated by minimally invasive surgery had residual disease in the hysterectomy specimen compared to open surgery (43.1 versus 57.9%; p = .04). No statistically significant difference between minimally invasive and open surgery in pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, or overall survival was found. Our data indicate no statistical evidence that minimally invasive surgery is associated with poorer clinical outcomes for patients meeting the SHAPE criteria who underwent simple hysterectomy. Because the surgical approach was not a randomization factor, a large prospective trial is needed to confirm our results before a routine simple hysterectomy by minimally invasive surgery can be recommended.

Posterior Dynamic/Semi-Rigid Stabilization as an Effective Treatment for Cervical Spinal Stenosis.

To investigate the short- term results of dynamic/semi-rigid stabilization in patients with cervical spinal stenosis and compare them with patients for which decompression and pos-terior cervical fusion was performed. 28 patients were included in this study. Group 1 was the semi-rigid group (four male, ten female), group 2 was the fusion group (nine male, five female). We compared the clinical status of the patients pre-operatively, first and twelfth month post-operatively using the Visual Analog Scale (VAS) and Neck Disability Index (NDI). Also radiologically, the pre-operative and on the postoperative first and twelfth month, cervical sagittal vertical axis (cSVA), cervical lordosis (C0-2) (C2-7) and T1 slope were measured. Our results showed that there was a significant improvement on the VAS and NDI score after semi-rigid and fusion surgery (p < 0.001). Also the cervical lordosis was obtained in both groups (p=0.033). Although, no significant differences was found between both groups regarding the change of variables over time between post-operative first and twelfth month. Although, posterior dynamic stabilization has been previously used in thoracic and lumbar pathologies before, there is no crucial evidence about their effects in cervical stenosis. This study states, that semi-rigid instrumentation is as effective in clinical and radiologic out-comes as posterior fusion surgery in periods of one year. Also, the lower risk of adjacent-segment disease and pseudoarthrosis and preservation of cervical sagittal alignment are the main advantages of the new method.

POLYPHENOLS IN PLANT-BASED FOODS: IMPLICATIONS FOR HEALTH, ANTIOXYDANTACTIVITY, COMPOSITION FACTORS, AND PROCESSING APPROCHES: A SYSTEMATIC REVIEW

Polyphenols are bioactive compounds found in plants, with diverse health benefits and antioxidant properties. They have anti-inflammatory, anti-carcinogenic, antidiabetic, antiviral activity and heart-protective effects. Research links polyphenol rich foods to a lower risk of chronic diseases like cardiovascular issues, cancer, and neurodegenerative disorders. For instance, resveratrol in grapes and red wine shows promise in protecting against age-related diseases, and polyphenols like quercetin and epigallocatechin gallate (EGCG) provide significant antioxidant and anti inflammatory benefits. These bioactive compounds play a crucial role in reducing oxidative stress and mitigating the risk of chronic diseases, though the antioxidant capacity varies among different types of polyphenols. However, the main problem lies in the variability and optimization of polyphenol content and bioavailability, which are influenced by genetic, environmental, and agronomic factors. Plant species, maturity, climate, soil conditions, and agricultural practices all affect polyphenol composition.

ASSOCIATION BETWEEN DIET AND RETINAL IMAGING MARKER IN THE PREVENT DEMENTIA STUDY

Abstract Eating a healthy diet is associated with a lower risk of neurodegenerative diseases, such as Alzheimer’s disease (AD). Identifying associations between diet and AD biomarkers is key to understanding and identifying critical periods for interventions. The retina provides a unique, non-invasive, window into brain health. This study explored cross-sectional and longitudinal associations between diet and retinal imaging markers in the PREVENT Dementia cohort (UK/Ireland). We calculated a Mediterranean diet (MedDiet) adherence score (Pyramid) for each participant and tested for associations with measures of retinal vessel morphology (CRAE Hubbard Zone C (HZC) and artery tortuosity) using generalised additive models due to abnormally distributed residuals. Additionally, we tested for associations with dietary intake of manganese. All analyses were completed cross-sectionally and then longitudinally in the participants with follow-up data (data collection ongoing). In a preliminary study, we included 86 participants, mean age 50.87 (5.63) years, majority female (57%), with 31 APOEe4 carriers (36%). Participants had a moderate mean Pyramid score (8.16 (SD = 1.40)), which was comparable to scores in other UK cohorts, and a dietary intake of 4.77 mg (SD = 3.05) manganese. There was evidence of an association between higher dietary manganese intake and lower CRAE HZC density in the right eye. There was no evidence of associations between the Pyramid score in either eye or dietary manganese in the left eye, and no signs of longitudinal associations (n=47). Further research is needed to explore any these analyses in a larger sample, and expand with other variables.

The relationship between radiographic disc calcification score and FGF4L2 genotype in dachshunds.

The relationship between radiographic disc calcification score and FGF4L2 genotype has been reported in only a small number of dachshunds. A genotype with either 0 or 1 FGF4L2 copy will be associated with a lower number of calcified discs (lower K-n) compared with a genotype with 2 FGF4L2 copies. Dachshunds registered with the Norwegian or Finnish Kennel Clubs for which both K-n and FGF4L2 genotype are known (n = 407). Retrospective study (2012-2024). The frequency and percentage of dachshunds within each K-n group (K0, K1/2, K3/4, K5+) by FGF4L2 genotype (FGF4L2/FGF4L2, N/FGF4L2, N/N) were reported. The K-n distribution differences among genotypes were analyzed by the Cochran-Mantel-Haenszel test in SAS 9.4. Significance was defined as P < .05. A difference in K-n distribution was found between dachshunds that have 0 or 2 FGF4L2 copies. However, no difference was found in the K-n distribution between dachshunds that have 1 or 2 FGF4L2 copies. Most dachshunds with 1 FGF4L2 copy have radiographic disc calcification scores that are associated with substantially lower risk of symptomatic disc disease. Radiographic disc calcification scores are similar in dachshunds with 0 and 1 FGF4L2 copies. Given the high allele frequency of FGF4L2, breeding to produce progeny with 1 FGF4L2 copy is expected to be a more achievable short-term goal for dachshund spinal health breeding programs than breeding for 0 copies. It is recommended that both K-n and FGF4L2 genotype status be considered when choosing dachshund breeding stock.