Large Cohort Research Articles

Artificial neural networks analysis predicts long-term fistula function in hemodialysis patients following percutaneous transluminal angioplasty

Kidney failure is particularly common in the United States, where it affects over 700,000 individuals. It is typically treated through repeated sessions of hemodialysis to filter and clean the blood. Hemodialysis requires vascular access, in about 70% of cases through an arteriovenous fistula (AVF) surgically created by connecting an artery and vein. AVF take 6 weeks or more to mature. Mature fistulae often require intervention, most often percutaneous transluminal angioplasty (PTA), also known as fistulaplasty, to maintain the patency of the fistula. PTA is also the first-line intervention to restore blood flow and prolong the use of an AVF, and many patients undergo the procedure multiple times. Although PTA is important for AVF maturation and maintenance, research into predictive models of AVF function following PTA has been limited. Therefore, in this paper we hypothesize that based on patient-specific information collected during PTA, a predictive model can be created to help improve treatment planning. We test a set of rich, multimodal data from 28 patients that includes medical history, AVF blood flow, and interventional angiographic imaging (specifically excluding any post-PTA measurements) and build deep hybrid neural networks. A hybrid model combining a 3D convolutional neural network with a multi-layer perceptron to classify AVF was established. We found using this model that we were able to identify the association between different factors and evaluate whether the PTA procedure can maintain primary patency for more than 3 months. The testing accuracy achieved was 0.75 with a weighted F1-score of 0.75, and AUROC of 0.75. These results indicate that evaluating multimodal clinical data using artificial neural networks can predict the outcome of PTA. These initial findings suggest that the hybrid model combining clinical data, imaging and hemodynamic analysis can be useful to treatment planning for hemodialysis. Further study based on a large cohort is needed to refine the accuracy and model efficiency.

Genetically predicted systemic inflammation and the risk of atrial fibrillation: A bidirectional two-sample Mendelian randomization study

BackgroundSystemic inflammation has been proposed to be associated with the incidence of atrial fibrillation (AF), but whether it is a cause or a consequence of AF remains uncertain. We sought to explore the causal associations between systemic inflammation and AF using bidirectional Mendelian randomization (MR) analysis. MethodsIndependent genetic variants strongly associated with AF were selected as instrumental variables from the largest genome-wide association study (GWAS) with up to 1,030,836 individuals. Regarding inflammation traits, genetic associations with 41 inflammatory cytokines and 5 inflammatory biomarkers were obtained from their corresponding GWASs databases. Effect estimates were primarily evaluated using the inverse-variance weighted (IVW) method, supplemented by sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO methods. ResultsIn our initial MR analyses, we observed suggestive associations of genetically predicted interleukin-17 (IL-17), interleukin-2 receptor subunit alpha (IL-2rα), and procalcitonin (PCT) with AF. One standard deviation (SD) increase in IL-17, IL-2rα, and PCT caused an increase in AF risk by 6.3 % (OR 1.063, 95 %CI 1.011–––1.118, p = 0.018), 4.9 % (OR 1.049, 95 %CI 1.007–––1.094, p = 0.023) and 3.4 % (OR 1.034, 95 %CI 1.005–––1.064, p = 0.022), respectively. Furthermore, our reverse MR analyses indicated that genetically predicted AF contributed to a suggestive increase in the levels of macrophage inflammatory protein-1β (MIP1β) (β 0.055, 95 %CI 0.006 to 0.103, p = 0.028), while a decrease in the levels of fibrinogen (Fbg) (β −0.091, 95 %CI −0.140 to −0.041, p < 0.001), which remained significant after multiple test correction. ConclusionsOur MR study identified several inflammatory biomarkers with suggestive causal associations regarding the upstream and downstream regulation of AF occurrence, offering new insights for therapeutic exploitation of AF. Further research is required to validate the underlying link between systemic inflammation and AF in larger cohorts.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort

BackgroundThere is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). MethodsThis retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. ResultsOf 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). ConclusionIn NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

High Plasma Levels of IsoDGR Fibronectin Levels Are Associated With More Plaque Macrophages in a Large Cohort of Carotid Endarterectomy Patients

High Plasma Levels of IsoDGR Fibronectin Levels Are Associated With More Plaque Macrophages in a Large Cohort of Carotid Endarterectomy Patients

RFC1 Repeat Distribution in the Cypriot Population: Study of a Large Cohort of Patients With Undiagnosed Ataxia and Non-Disease Controls.

The intronic biallelic AAGGG expansion in the replication factor C subunit 1 (RFC1) gene was recently associated with a phenotype combining cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, as well as with late-onset ataxia. Following this discovery, studies in multiple populations extended the phenotypic and genotypic spectrum of this locus. Multiple benign and additional pathogenic configurations are currently known. Our main objectives were to study the prevalence of the pathogenic AAGGG expansion in the Cypriot population, to further characterize the RFC1 repeat locus allele distribution, and to search for possible novel repeat configurations. Cypriot undiagnosed patients, in the majority presenting at least with cerebellar ataxia and non-neurologic disease controls, were included in this study. A combination of conventional methods was used, including standard PCR flanking the repeat region, repeat-primed PCR, long-range PCR, and Sanger sequencing. Bioinformatics analysis of already available in-house short-read whole-genome sequencing data was also performed. A large group of undiagnosed patients (n = 194), mainly presenting with pure ataxia or with ataxia accompanied by neuropathy or additional symptoms, as well as a group of non-disease controls (n = 100), were investigated in the current study. Our findings include the diagnosis of 10 patients homozygous for the pathogenic AAGGG expansion and a high percentage of heterozygous AAGGG carriers in both groups. The benign AAAAGn, AAAGGn, and AAGAGn configurations were also identified in our cohorts. We also report and discuss the identification of 2 recently reported novel and possibly benign repeat configurations, AAAGGGn and AAGACn, thus confirming their existence in another distinct population, and we highlight an increased frequency of the AAAGGGn in the patient group, including a single case of homozygosity. Our findings indicate the existence of genetic heterogeneity regarding the RFC1 repeat configurations and that the AAGGG pathogenic expansion is a frequent cause of ataxia in the Cypriot population.

Outdoor walking, genetic predisposition, and the risk of incident osteoporosis among older adults: A prospective large population-based cohort study.

The available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis. 24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms. 4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3months. Those who walked outside for > 30 but ≤ 60min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72-0.95) for incident osteoporosis, whereas those who walked outside for > 60min per day had an HR of 0.60 (95% CI: 0.39-0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk. A significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

Association of optimism and social support with health-related quality of life among Australian women cancer survivors - A cohort study.

Large-scale studies investigating health-related quality of life (HRQL) in cancer survivors are limited. This study aims to investigate HRQL and its relation to optimism and social support among Australian women following a cancer diagnosis. Data were from the Australian Longitudinal Study on Women's Health, a large cohort study (n=14,715; born 1946-51), with 1428 incident cancer cases ascertained 1996-2017 via linkage to the Australian Cancer Database. HRQL was measured using the Short Form-36 (median 1.7 years post-cancer-diagnosis). Multivariable linear regression was performed on each HRQL domain, separately for all cancers combined, major cancer sites, and cancer-free peers. Higher optimism and social support were significantly associated with better HRQL across various domains in women with and without a cancer diagnosis (p<0.05). Mean HRQL scores across all domains for all cancer sites were significantly higher among optimistic versus not optimistic women with cancer (p<0.05). Adjusting for sociodemographic and other health conditions, lower optimism was associated with reduced scores across all domains, with greater reductions in mental health (adjusted mean difference (AMD)=-11.54, p<0.01) followed by general health (AMD=-11.08, p<0.01). Social support was less consistently related to HRQL scores, and following adjustment was only significantly associated with social functioning (AMD=-7.22, p<0.01) and mental health (AMD=-6.34, p<0.01). Our findings highlight a strong connection between optimism, social support, and HRQL among cancer survivors. Providing psychosocial support and addressing behavioral and socioeconomic factors and other health conditions associated with optimism and social support may improve HRQL.

Patterns of Care Following a Positive Fecal Blood Test for Colorectal Cancer: A Mixed Methods Study.

Multilevel barriers to colonoscopy after a positive fecal blood test for colorectal cancer (CRC) are well-documented. A less-explored barrier to appropriate follow-up is repeat fecal testing after a positive test. We investigated this phenomenon using mixed methods. This sequential mixed methods study included quantitative data from a large cohort of patients 50-89years from four healthcare systems with a positive fecal test 2010-2018 and qualitative data from interviews with physicians and patients. Logistic regression was used to evaluate whether repeat testing was associated with failure to complete subsequent colonoscopy and to identify factors associated with repeat testing. Interviews were coded and analyzed to explore reasons for repeat testing. A total of 316,443 patients had a positive fecal test. Within 1year, 76.3% received a colonoscopy without repeat fecal testing, 3% repeated testing and then received a colonoscopy, 4.4% repeated testing without colonoscopy, and 16.3% did nothing. Among repeat testers (7.4% of total cohort, N = 23,312), 59% did not receive a colonoscopy within 1year. In adjusted models, those with an initial positive test followed by a negative second test were significantly less likely to receive colonoscopy than those with two successive positive tests (OR 0.37, 95% CI 0.35-0.40). Older age (65-75 vs. 50-64years: OR 1.37, 95% CI 1.33-1.41) and higher comorbidity score (≥ 4 vs. 0: OR 1.75, 95% CI 1.67-1.83) were significantly associated with repeat testing compared to those who received colonoscopy without repeat tests. Qualitative interview data revealed reasons underlying repeat testing, including colonoscopy avoidance, bargaining, and disbelief of positive results. Among patients in this cohort, 7.4% repeated fecal testing after an initial positive test. Of those, over half did not go on to receive a colonoscopy within 1year. Efforts to improve CRC screening must address repeat fecal testing after a positive test as a barrier to completing colonoscopy.

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400μ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417μ and 430μ in the No-VMIA and VMIA groups respectively) and improved to approximately 300μ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108μ and 79μ, p= 0.04). There was a mean of 7 injections after 12 months. Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

A commentary on "Local resection for solid pseudopapillary neoplasms of the pancreas shows improved postoperative gastrointestinal function and reduced mental stress: a multiquestionnaire survey from a large cohort".

A commentary on "Local resection for solid pseudopapillary neoplasms of the pancreas shows improved postoperative gastrointestinal function and reduced mental stress: a multiquestionnaire survey from a large cohort".

Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease

BackgroundInsulin resistance (IR) is the cornerstone of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), pathophysiologically being the key link between MASLD, metabolic disorders, and cardiovascular (CV) diseases. There are no prospective studies comparing the predictive values of different markers of insulin resistance (IR) in identifying the presence of MASLD and the associated risk of cardiovascular events (CVEs).MethodsPost hoc analysis of the prospective Plinio Study, involving dysmetabolic patients evaluated for the presence of MASLD. The IR markers considered were Homeostatic Model Assessment for IR (HOMA-IR), Triglycerides-Glycemia (TyG) index, Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). Receiver operative characteristic (ROC) analyses were performed to find the optimal cut-offs of each IR marker for detecting MASLD and predicting CVEs in MASLD patients. Logistic and Cox multivariable regression analyses were performed, after dichotomizing the IR markers based on the optimal cut-offs, to assess the factors independently associated with MASLD and the risk of CVEs.ResultsThe study included 772 patients (age 55.6 ± 12.1 years, 39.4% women), of whom 82.8% had MASLD. VAI (Area Under the Curve [AUC] 0.731), TyG Index (AUC 0.723), and TG/HDL-C ratio (AUC: 0.721) predicted MASLD but was greater with HOMA-IR (AUC: 0.792) and LAP (AUC: 0.787). After a median follow-up of 48.7 (25.4–75.8) months, 53 MASLD patients experienced CVEs (1.8%/year). TyG index (AUC: 0.630), LAP (AUC: 0.626), TG/HDL-C (AUC: 0.614), and VAI (AUC: 0.590) demonstrated comparable, modest predictive values in assessing the CVEs risk in MASLD patients.ConclusionIn dysmetabolic patients HOMA-IR and LAP showed the best accuracy in detecting MASLD. The possible use of lipid-based IR markers in stratifying the CV risk in patients with MASLD needs further validation in larger cohorts.

Optimizing abemaciclib-induced diarrhea management in patients with breast cancer: a pragmatic 2-group study using a postbiotic microbiota stabilizer.

Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it. We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer. The prospective population (Postbio group) received postbiotic during the first cycle of abemaciclib, while the retrospective one received standard care (Standard group). Diarrhea grading was defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. During the first cycle, diarrhea occurred in 78.9% of patients in the Standard cohort and 97.1% in the Postbio one, with most cases being G1-G2. Severe (G3) diarrhea was significantly less frequent in the Postbio group (0%) compared to the Standard one (7.9%; P = .029). Over the entire study period, while the grading difference was not statistically significant, G3 events were less frequent in the Postbio population (5.9%) than the Standard one (15.4%). Moreover, Postbio patients required fewer dose reductions due to diarrhea compared to the Standard group (P = .002). Notably, in the Postbio population, G1 and G2 events had short median durations (3 and 1 days, respectively) and, for the 2 patients experiencing G3 events during the second abemaciclib cycle (off postbiotic), diarrhea lasted only 1 day. Our study demonstrates the effect of PostbiotiX-Restore in mitigating abemaciclib-induced diarrhea, resulting in reduced severity, fewer dose reductions, and shorter duration. Further exploration and validation in larger cohorts are needed.

Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020.

Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting. Data were collected at the Aachen aphasia ward in Germany between 2003 and 2020. Immediate treatment responses across different language domains were assessed with the Aachen Aphasia Test (AAT) using single-case psychometrics, conducted before and after 6-7 weeks of intensive SLT (10 h per week, median (IQR) dosage = 68 (61-76)). We adjusted for spontaneous recovery in subacute patients. Differential treatment effects between subgroups of chronicity and predictors of therapy response were investigated. A total of 448 PWA were included (29% female, median (IQR) age = 54 (46-62) years, median (IQR) time post-onset = 11 (6-20) months) with 12% in the early subacute, 15% in the late subacute and 74% in the chronic phase of aphasia. The immediate responder rate was 59%. Significant improvements in all AAT subtests und subscales were observed hinting at broad effectiveness across language domains. The degree of therapy-induced improvement did not differ between the chronicity groups. Time post-onset, dosage of therapy and aphasia severity at the beginning of treatment were predictors of immediate treatment response. Intensive therapy protocols for aphasia after stroke are yielding substantial responder rates in a routine clinical setting including a wide range of patients.

Imputation provides an opportunity to study filaggrin (FLG) null mutations in large population cohorts that lack bespoke genotyping

Background Null mutations within the filaggrin (FLG) gene are established genetic risk factors for atopic dermatitis. Studies of FLG have typically used sequencing or bespoke genotyping. Large-scale population cohorts with genome-wide imputed data offer powerful genetic analysis opportunities, but bespoke FLG genotyping is often not feasible in such studies. Therefore, we aimed to determine the quality of selected FLG null genotype data extracted from genome-wide imputed sources, focussing on UK population data. Methods We compared the allele frequencies of three FLG null mutations that could be detected by imputation (p.Arg501Ter, p.Arg2447Ter and p.Ser3247Ter; commonly referred to as R501X, R2447X and S3247X respectively) in directly genotyped and genome-wide imputed data in the ALSPAC cohort. Logistic regression analysis was used to test the association of atopic dermatitis with imputed and genotyped FLG null mutations in ALSPAC and UK Biobank to investigate the usefulness of imputed FLG data. Results The three FLG null mutations appear to be well imputed in datasets that use the Haplotype Reference Consortium (HRC) for imputation (0.3% discordance compared with directly genotyped data). However, a greater proportion of null alleles failed imputation compared to wild-type alleles. Despite the calling of FLG mutations in imputed data being imperfect, they are still strongly associated with atopic dermatitis (p-values between 7x10-10 and 5x10-75 in UK Biobank). Conclusions HRC imputed data appears to be adequate for UK population-based genetic analysis of selected FLG null mutations (p.Arg501Ter, p.Arg2447Ter and p.Ser3247Ter).

Biochemical Control in Cushing's syndrome: Outcomes of the treatment in a large single center cohort.

Normalization of hypercortisolism is essential to reduce morbidity and mortality in patients with Cushing's syndrome (CS). The aim of this analysis was to assess biochemical control rates in patients with Cushing's disease (CD), ectopic Cushing's syndrome (ECS) and adrenal Cushing's syndrome (ACS). Patients with confirmed CS (n= 296) treated in a single tertiary care center were retrospectively analysed (185 CD, 27 ECS, 84 uni- and bilateral ACS). Firstline treatment led to biochemical control in 82% of the patients. Time to biochemical control (median, IQR) was longer in CD (11.0 weeks, 5.6-29.8; p< 0.05) than in ACS (7.7 weeks, 4.1-17.1) and ECS (5.6 weeks, 4.1-23.3). Disease persistence or recurrence after first-line therapy was observed more often in CD (24% and 18%; p< 0.05) than in ECS (15% and 15%) and ACS (6% and 4%). Total time in hypercortisolism since diagnosis was significantly shorter in patients with CD diagnosed since 2013, after specialized patient care was implemented, compared to patients diagnosed before 2013 (13.5 weeks, vs. 26.1 weeks; p< 0.0070). Control of hypercortisolism at last follow up (76 months, 38-163) was achieved in 94% of patients with ACS, 100% of patients with ECS and 92% of patients with CD. Biochemical control can be achieved in most patients with different subtypes of CS within a reasonable time frame. Control of hypercortisolism has improved over time.

Assessing Patterns of CGM use and Metrics of Glycemic Control in T1D and T2D Patients in the Veterans Healthcare System: Integrating CGM Device Data with EHR Data.

To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for type 1 and type 2 diabetes patients in the Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. This observational study used Dexcom CGM device data linked with EHR (from 2015-2020) for a large national cohort of diabetes patients. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged three weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 hours over nearly three years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both type 1 and type 2 patients within the Veterans Affairs Healthcare System and is similar across major race/ethnicity and age groups.

High incidence of medial meniscus root/radial tears and extrusion in 253 patients with subchondral insufficiency fractures of the knee.

The demographic and radiological risk factors of subchondral insufficiency fractures of the knee (SIFK) continue to be a subject of debate. The purpose of this study was to associate patient-specific factors with SIFK in a large cohort of patients. Inclusion criteria consisted of patients with SIFK as verified on magnetic resonance imaging (MRI). All radiographs and MRIs were reviewed to assess characteristics such as meniscus tear presence and type, subchondral oedema presence and location, location of SIFK, mechanical limb alignment, osteoarthritis as assessed by Kellgren-Lawrence grade and ligamentous injury. A total of 253 patients (253 knees) were included, with 171 being female. The average body mass index (BMI) was 32.1 ± 7.0 kg/m2. SIFK was more common in patients with medial meniscus tears (77.1%, 195/253) rather than tears of the lateral meniscus (14.6%, 37/253) (p < 0.001). Medial meniscus root and radial tears of the posterior horn were present in 71.1% (180/253) of patients. Ninety-one percent (164/180) of medial meniscus posterior root and radial tears had an extrusion ≥3.0 mm. Eighty-one percent (119/147) of patients with SIFK on the medial femoral condyle and 86.8% (105/121) of patients with SIFK on the medial tibial plateau had a medial meniscus tear. Varus knees had a significantly increased rate of SIFK on the medial femoral condyle in comparison to valgus knees (p = 0.016). In this large cohort of patients with SIFK, there was a high association with medial meniscus root and radial tears of the posterior horn, meniscus extrusion ≥3.0 mm as well as higher age, female gender and higher BMI. Additionally, there was a particularly strong association of medial compartment SIFK with medial meniscus tears. As SIFK is frequently undiagnosed, identifying patient-specific demographic and radiological risk factors will help achieve a prompt diagnosis. Level IV.

Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.

P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting. This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD. There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients. We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.

The Estimated Fick Method Systematically Over-Estimates Cardiac Index Compared to Thermodilution in Children.

Cardiac index (CI) may be derived from the Fick method, using measured or estimated oxygen consumption (VO2), or from thermodilution. In children, LaFarge VO2 estimates correlate poorly with measured VO2 values. In a large adult cohort, there was only modest correlation between estimated Fick CI (eFick CI) and thermodilution CI (TDCI).We evaluated the extent of agreement between eFick CI using LaFarge estimates of VO2 and TDCI in a pediatric cohort. A retrospective, single-center chart review of patients 3-18years of age who underwent cardiac catheterization with documented eFick CI and TDCI from 2004 to 2020 included 201 catheterizations from 161 unique patients. The mean patient age at catheterization was 12.2y (SD 4.4y). The most frequent diagnosis was cardiomyopathy, followed by congenital heart disease and pulmonary hypertension. TDCI and eFick CI differed by > 20% in 49% of catheterizations. eFick CI systematically exceeded TDCI by a mean percentage difference of 24% (SD 31%). Higher mean CI ((eFick CI + TDCI)/2) and older age were predictive of greater percent difference between eFick CI and TDCI. For each increase in mean CI by 1.0 L/min/m2, the expected percent difference in CI increased by 9.9% (p < 0.001). In pediatric patients undergoing cardiac catheterization, eFick CI with LaFarge VO2 systematically exceeds TDCI. The difference between methods is frequently > 20%, which may have clinically significant implications. Discrepancies between eFick CI and TDCI increase at higher mean CI.

Proteomic features of soft tissue tumours in adolescents and young adults.

Adolescents and young adult (AYA) patients with soft tissue tumours including sarcomas are an underserved group with disparities in treatment outcomes. To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of soft tissue tumours across 10 histological subtypes (AYA n = 66, OA n = 243), and also analysed publicly available functional genomic data from soft tissue tumour cell lines (AYA n = 5, OA n = 8). Biological hallmarks analysis demonstrates that OA tumours are significantly enriched in MYC targets compared to AYA tumours. By comparing the patient-level proteomic data with functional genomic profiles from sarcoma cell lines, we show that the mRNA splicing pathway is an intrinsic vulnerability in cell lines from OA patients and that components of the spliceosome complex are independent prognostic factors for metastasis free survival in AYA patients. Our study highlights the importance of performing age-specific molecular profiling studies to identify risk stratification tools and targeted agents tailored for the clinical management of AYA patients.