Different Rates Of Progression Research Articles

Cerebrospinal Fluid Neurofilaments Light-Chain Differentiate Patients Affected by Alzheimer's Disease with Different Rate of Progression (RoP): A Preliminary Study.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia. One major challenge for clinicians is accurately assessing the rate of disease progression (RoP) early in the diagnostic process, which is crucial for patient management and clinical trial stratification. This study evaluated the role of cerebrospinal fluid biomarkers-Aβ42, t-Tau, pTau, Neurogranin (Ng), and Neurofilament light-chain (NF-L)-in predicting RoP at the time of AD diagnosis. We included 56 AD patients and monitored cognitive impairment using MMSE scores at diagnosis and during six-month follow-up visits. RoP scores were calculated based on these assessments. Our correlation analyses revealed significant associations between RoP and pTau, Aβ42/Ng ratio, and NF-L levels. When patients were stratified by median RoP values into low-to-moderate (L-M: <2) and upper-moderate (U-M: >2) groups, those in the U-M group had notably higher CSF NF-L levels compared to the L-M group. Logistic regression analysis further demonstrated that elevated CSF NF-L levels were predictive of a faster RoP. These findings highlight the potential of CSF NF-L as a prognostic biomarker for rapid disease progression in AD. By identifying patients at risk for accelerated cognitive decline, CSF NF-L could significantly enhance early intervention strategies and improve patient management in clinical settings.

Differences in Clinical Outcomes and Survival Among Primary, Secondary, and Concomitant Carcinoma In Situ of the Bladder.

Carcinoma in situ (CIS) is a flat, high-grade, and aggressive form of urothelial carcinoma with a high risk of progression to muscle-invasive disease and metastasis. This study aimed to investigate differences in clinical outcomes and survival among patients with primary, secondary, and concomitant CIS of the bladder. A total of 209 patients diagnosed with CIS between 2010 and 2022 in our department with a minimum follow-up of 12 months were retrospectively analyzed. Patients with muscle-invasive cancer at diagnosis, those with recurrence within one month after diagnosis, and those with primary malignant melanoma were excluded. The recurrence, progression, and cancer-specific mortality rates of patients receiving Bacillus Calmette-Guérin therapy for CIS were analyzed. A total of 96 patients with primary (n = 18), secondary (n = 29), and concomitant CIS (n = 49) were included in the analysis. The median follow-up was 52.2 months. Patients with secondary CIS had a significantly higher recurrence rate than those with concomitant CIS (58.6% vs. 32.7%, p = 0.016). However, no significant difference in progression rates was observed among the three groups. Furthermore, no significant association was observed between CIS subtypes and recurrence-free survival (RFS) (HR = 1.45, 95% CI 0.96-2.46, p = 0.16) or progression-free survival (PFS) (HR = 2.20, 95% CI 0.99-4.87, p = 0.054). Secondary CIS had a significantly higher recurrence rate than concomitant CIS. However, no statistically significant association was observed between CIS subtypes and RFS or PFS.

Investigating the timing and site of recurrence for ovarian clear cell carcinoma: Analysis of the JGOG/GCIG trial-JGOG 3017-A3

BackgroundThis study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery. MethodsYielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks. ResultsThe peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months. DiscussionThe incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important.

Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Acute Myeloid Leukemia and Other Blood Malignancies.

Blood cancers encompass a group of diseases affecting the blood, bone marrow, or lymphatic system, representing the fourth most commonly diagnosed cancer worldwide. Leukemias are characterized by the dysregulated proliferation of myeloid and lymphoid cells with different rates of progression (acute or chronic). Among the chronic forms, hairy cell leukemia (HCL) is a rare disease, and no drugs have been approved to date. However, acute myeloid leukemia (AML) is one of the most aggressive malignancies, with a low survival rate, especially in cases with FLT3-ITD mutations. Epigenetic modifications have emerged as promising strategies for the treatment of blood cancers. Epigenetic modulators, such as histone deacetylase (HDAC) inhibitors, are increasingly used for targeted cancer therapy. New hydroxamic acid derivatives, preferentially inhibiting HDAC6 (5a-q), were developed and their efficacy was investigated in different blood cancers, including multiple myeloma (MM), HCL, and AML, pointing out their pro-apoptotic effect as the mechanism of cell death. Among the inhibitors described, 5c, 5g, and 5h were able to rescue the hematopoietic phenotype in vivo using the FLT3-ITD zebrafish model of AML. 5c (leuxinostat) proved its efficacy in cells from FLT3-ITD AML patients, promoting marked acetylation of α-tubulin compared to histone H3, thereby confirming HDAC6 as a preferential target for this new class of hydroxamic acid derivatives at the tested doses.

Epirubicin and Non-Muscle Invasive Bladder Cancer Treatment: A Systematic Review.

(1) Background: Intravesical chemotherapy is the standard of care in intermediate-risk non-muscleinvasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost, and practice patterns. Epirubicin (EPI), one of these agents, has been used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability are still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: This study aimed to systematically review the efficacy and safety profile of Epirubicin (EPI) in the management of non-muscle invasive bladder cancer (NMIBC) compared to other adjuvant therapies. A systematic search of the PUBMED, Web of Science, clinicaltrials.gov, and Google Scholar databases was conducted on 31 December 2023, using relevant terms related to EPI, bladder cancer, and NMIBC. The inclusion criteria targeted studies that evaluated patients treated with EPI following the transurethral resection of bladder tumors (TURBT) for NMIBC and compared oncological outcomes such as recurrence and progression with other adjuvant therapies, including Mitomycin C (MMC), Gemcitabine (GEM), and Bacillus Calmette-Guérin (BCG). Additionally, studies investigating the safety profile of EPI administered intravesically at room temperature and under hyperthermia, as well as oncological outcomes associated with hyperthermic intravesical EPI administration, were included. (3) Results: Eleven studies reported adverse events after adjuvant intravesical instillations with EPI; the most frequently reported adverse events included cystitis (34%), dysuria, pollakiuria, hematuria, bladder irritation/spasms, fever, nausea and vomiting, and generalized skin rash (2.3%). Nine studies compared EPI to BCG in terms of recurrence and progression rates; BCG instillations showed a lower recurrence rate compared to EPI, with limited or non-significant differences in progression rates. Two studies found no significant differences between EPI and MMC regarding progression and recurrence rates. One study showed statistically significant lower recurrence and progression rates with GEM in high-risk NMIBC patients. Another study found no significant differences between EPI and GEM regarding recurrence and progression. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are interesting newcomers.

Differential Rates of Toxicity Between Chloroquine and Hydroxychloroquine

Purpose: To describe two cases of patients with systemic lupus erythematosus (SLE) who manifested differential rates of retinal toxicity progression on hydroxychloroquine (HCQ) and chloroquine (CQ), respectively. Methods: Retrospective case reports. Results: Case 1 is a 41-year-old woman with SLE and history of renal involvement, who had been managed on HCQ for 14 years and gradually progressed to moderate retinal toxicity over several years. Case 2 is a 59-year-old woman with SLE and history of renal involvement, who had been managed on quinacrine for 20 years followed by chloroquine for 5 years and initially presented without any evidence of retinal toxicity. One year later, she manifested moderate retinal toxicity. Both cases were screened regularly. In case 1, the diagnosis was missed and toxicity progressed predictably and slowly while on HQ. In case 2, there was no salient pathology on OCT or HVF testing at initial presentation. One year later, there was moderate toxicity. Conclusion: Given the dramatically different rate of progression of retinal toxicity in these two patients, these cases highlight potential gaps in our understanding of retinal toxicity and provide rationale to potentially study rates of retinal toxicity progression in patients on CQ or quinacrine.

Comparing the migration behavior and survival of Atlantic salmon (Salmo salar) and brown trout (Salmo trutta) smolts.

Many organisms rely on migrations between habitats to maximize lifetime fitness, but these migrations can be risky due to a suite of factors. In anadromous salmonids, the smolt migration from fresh water to sea is a critical life stage, during which smolts can experience high mortality from multiple sources. This study investigated the migratory behavior and survival of Atlantic salmon (Salmo salar) and anadromous brown trout (Salmo trutta) smolts during their seaward migration using acoustic telemetry between March and May 2021. Due to the extinction of wild salmon in the River Gudenaa after the construction of the Tange hydropower plant, this study used hatchery-reared salmon originating from a nearby Danish river. A total of 75 hatchery-reared salmon smolts, 75 hatchery-reared trout smolts, and 75 wild trout smolts were tagged with acoustic transmitters and released into River Gudenaa, Denmark. The downstream movements of tagged fish were monitored using acoustic receivers deployed in the river and fjord. Hatchery-reared trout initiated migration first, followed by hatchery-reared salmon, with wild trout being the last to migrate. There was no difference in riverine progression rates among the three smolt groups, but noticeable differences emerged once in the fjord: trout (wild and hatchery) slowed down, whereas hatchery-reared salmon maintained their speed. Riverine migration was predominantly nocturnal for all smolts; however, daytime migration increased at the fjord arrays. Day-of-year significantly influenced diurnal patterns in the river and fjord, where daytime migration increased later in the year. Hatchery-reared salmon and wild trout had reasonably good overall survival from river to sea entry (≥66%), whereas hatchery-reared trout had poor survival (c.26%). The fjord was the major bottleneck for survival of hatchery-reared trout. We found no strong evidence for differences in progression rate or diurnal patterns between wild and hatchery-reared trout to explain the lower survival. This study demonstrates that salmon and trout differ in their life-history strategy already in the post-smolt phase, and that stocking is a sub-optimal strategy to aid wild populations.

Different timing for abdominal paracentesis catheter placement and drainage in severe acute pancreatitis complicated by intra-abdominal fluid accumulation.

Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis (SAP). However, there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter placement and drainage. To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumulation. Using a retrospective approach, 184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement: group A (catheter placement within 2 d of symptom onset, n = 89), group B (catheter placement between days 3 and 5 after symptom onset, n = 55), and group C (catheter placement between days 6 and 7 after symptom onset, n = 40). The differences in progression rate, mortality rate, and the number of cases with organ dysfunction were compared among the three groups. The progression rate of group A was significantly lower than those in groups B and groups C (2.25% vs 21.82% and 32.50%, P < 0.05). Further, the proportion of patients with at least one organ dysfunction in group A was significantly lower than those in groups B and groups C (41.57% vs 70.91% and 75.00%, P < 0.05). The mortality rates in group A, group B, and group C were similar (P > 0.05). At postoperative day 3, the levels of C-reactive protein (55.41 ± 19.32 mg/L vs 82.25 ± 20.41 mg/L and 88.65 ± 19.14 mg/L, P < 0.05), procalcitonin (1.36 ± 0.51 ng/mL vs 3.20 ± 0.97 ng/mL and 3.41 ± 0.98 ng/mL, P < 0.05), tumor necrosis factor-alpha (15.12 ± 6.63 pg/L vs 22.26 ± 9.96 pg/L and 23.39 ± 9.12 pg/L, P < 0.05), interleukin-6 (332.14 ± 90.16 ng/L vs 412.20 ± 88.50 ng/L and 420.08 ± 87.65ng/L, P < 0.05), interleukin-8 (415.54 ± 68.43 ng/L vs 505.80 ± 66.90 ng/L and 510.43 ± 68.23ng/L, P < 0.05) and serum amyloid A (270.06 ± 78.49 mg/L vs 344.41 ± 81.96 mg/L and 350.60 ± 80.42 mg/L, P < 0.05) were significantly lower in group A compared to those in groups B and group C. The length of hospital stay in group A was significantly lower than those in groups B and group C (24.50 ± 4.16 d vs 35.54 ± 6.62 d and 38.89 ± 7.10 d, P < 0.05). The hospitalization expenses in group A were also significantly lower than those in groups B and groups C [2.70 (1.20, 3.55) ten-thousand-yuan vs 5.50 (2.98, 7.12) ten-thousand-yuan and 6.00 (3.10, 8.05) ten-thousand-yuan, P < 0.05). The incidence of complications in group A was markedly lower than that in group C (5.62% vs 25.00%, P < 0.05), and similar to group B (P > 0.05). Percutaneous catheter drainage for the treatment of SAP complicated by intra-abdominal fluid accumulation is most effective when performed within 2 d of onset.

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

IntroductionGenetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. MethodsA cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. ResultsThe allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). ConclusionThis study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Validating Trend-Based End Points for Neuroprotection Trials in Glaucoma.

The purpose of this study was to evaluate the power of trend-based visual field (VF) progression end points against long-term development of event-based end points accepted by the US Food and Drug Administration (FDA). One eye from 3352 patients with ≥10 24-2 VFs (median = 11 years) follow-up were analyzed. Two FDA-compatible criteria were applied to these series to label "true-progressed" eyes: ≥5 locations changing from baseline by more than 7 dB (FDA-7) or by more than the expected test-retest variability (GPA-like) in 2 consecutive tests. Observed rates of progression (RoP) were used to simulate trial-like series (2 years) randomly assigned (1000 times) to a "placebo" or a "treatment" arm. We simulated neuroprotective "treatment" effects by changing the proportion of "true progressed" eyes in the two arms. Two trend-based methods for mean deviation (MD) were assessed: (1) linear mixed model (LMM), testing average difference in RoP between the two arms, and (2) time-to-progression (TTP), calculated by linear regression as time needed for MD to decline by predefined cutoffs from baseline. Power curves with 95% confidence intervals were calculated for trend and event-based methods on the simulated series. The FDA-7 and GPA-like progression was achieved by 45% and 55% of the eyes in the clinical database. LMM and TTP had similar power, significantly superior to the event-based methods, none of which reached 80% power. All methods had a 5% false-positive rate. The trend-based methods can efficiently detect treatment effects defined by long-term FDA-compatible progression. The assessment of the power of trend-based methods to detect clinically relevant progression end points.

An exploration of the factors affecting the likelihood of young people in England progressing into higher education

ObjectivesThis research sought to identify the extent to which the likelihood of young people in England progressing into Higher Education (HE) is affected by their gender, ethnicity, socioeconomic background, area of residence, school attainment and the intersection of these characteristics.&#x0D; MethodsData from the Department for Education’s National Pupil Database concerning the entire cohort of young people in English state schools who turned 16 between September 2014 and August 2015 was accessed. Data concerned pupils’ attainment, personal characteristics and postcode of residence. This data was matched with records from the Higher Education Statistics Agency to identify whether pupils had progressed to HE by the age of 19. Raw differences in progression rates by pupil characteristic were established and binary logistic regression was used to explore how individual factors influenced the likelihood of progression once attainment and other characteristics were controlled for.&#x0D; ResultsFemales were more likely than males to progress to HE, however this could be explained predominantly by their higher average attainment in school examinations. Pupils in receipt of free school meals were substantially less likely to progress to HE, though this trend reversed once attainment was controlled for.&#x0D; Pupils residing in London were considerably more likely to progress to HE than pupils in all other regions of England, though this can be explained almost entirely by the higher average attainment of pupils in London as well as average demographic differences between London and other English regions.&#x0D; There are large disparities in progression to HE by pupil ethnicity and these disparities persist even once prior attainment and other characteristics are controlled for.&#x0D; ConclusionThe results overall suggest that some disparities in access to HE (such as by gender and FSM status) might be eliminated if corresponding disparities in school attainment were eliminated. The relationship between attainment disparities and HE progression disparities is less straightforward with respect to other characteristics such as pupil ethnicity.

Rethinking National Competitiveness for Europe 2050: The Case of EU Countries

The EU climate policy affects the competitiveness of both the European Union (EU) as a whole and individual member states, leading countries to search for new knowledge to increase their national competitiveness. However, there has been little empirical research about the implementation of green competitive strategies in the common European space from different countries’ perspectives. Using the Porter Hypothesis and system theory, this paper explores national competitive strategies that align with climate neutrality in the EU. We used index construction, clusterization, principal components analysis and trajectories change analysis to analyze data from the 24 EU countries from a 10-year period (2012–2021). The main findings reveal three green competitiveness profiles and five green competitiveness progress strategies in the EU. We found that EU countries have different strategies and conditions in terms of their transition towards climate neutrality and competitiveness, which ultimately lead to different rates of progress. Our results provide an initial basis for the development of nation-specific policies to achieve green competitiveness.

#6786 ADTKD DUE TO MUC-1 GENE MUTATION: A MAJOR DIAGNOSTIC CHALLENGE, NOT IDENTIFIED BY EXOME SEQUENCING

Abstract Background and Aims Autosomal dominant tubulointerstitial renal disease (ADTKD) is a rare cause of end-stage renal disease (ESKD) in adulthood. In addition to its rarity, ADTKD is probably underdiagnosed due to the very non-specific and heterogeneous clinical-laboratory-histopathological-instrumental picture and because of the diagnostic need to use specific methods of genetic investigation in order to highlight the mutations within the VNTR sequences of the MUC1 gene, not recognized by the most common exome sequencing. Mutations in the MUC1 gene, together with those in the UMOD gene, are the main mutations implicated in the pathogenesis of ADTKD. Method We analyzed the clinical, laboratory and histopathological characteristics of four families followed by our center with suspected diagnosis of ADTKD and detection of mutation of the MUC1 gene. Results Our data (Table 1) revealed a marked phenotypic variability, even within members of the same family (Fig. 1), and in particular as regards the age of disease onset and the different rate of progression towards ESKD (range 16 – 88 years). From a laboratory point of view, in 10 out of 13 patients the sediment was negative, and only in 3 patients proteinuria &amp;gt;1 g/24h was highlighted. In 6/13 the onset occurred at the age of less than 35 years and among these, 4 of them presented ESKD early. In the few cases in which renal biopsy was performed (4/17), representing 0.4% of all biopsies in our centre, the most frequent finding was the presence of tubular atrophy and interstitial fibrosis (3/4), with cystic ectasia of the tubular lumen at the cortical-medullary level in half of the cases. Among the 10 patients subjected to genetic analysis, only in one case the mutation was highlighted by exome sequencing. Conclusion The large phenotypic variability, in particular of age at achievement of ESKD, suggests that other factors (modifier or environmental genes) could also affect disease progression. Common gene sequencing methods (e.g. exome sequencing, Sanger) have proved unable, in most cases, to identify mutations within the VNTR sequences of the MUC1 gene.

Five-Year Visual Field Outcomes of the HORIZON Trial

To compare visual field (VF) progression between glaucoma patients receiving cataract surgery alone (CS) or with a Hydrus microstent (CS-HMS). Post hoc analysis of VF data from the HORIZON multicenter randomized controlled trial. A total of 556 patients with glaucoma and cataract were randomized 2:1 to either CS-HMS (369) or CS (187) and followed up for 5 years. VF was performed at 6 months and then every year after surgery. We analyzed data for all participants with at least 3 reliable VFs (false positives < 15%). Average between-group difference in rate of progression (RoP) was tested using a Bayesian mixed model and a 2-sided Bayesian P value <.05 (main outcome). A multivariable model measured the effect of intraocular pressure (IOP). A survival analysis compared the probability of global VF sensitivity dropping by predefined cutoffs (2.5, 3.5, 4.5, and 5.5 dB) from baseline. Data from 352 eyes in the CS-HMS arm and 165 in the CS arm were analyzed (2966 VFs). The mean RoP was -0.26 dB/y (95% credible interval -0.36, -0.16) for CS-HMS and -0.49 dB/y (95% credible interval -0.63, -0.34) for CS. This difference was significant (P=.0138). The difference in IOP only explained 17% of the effect (P < .0001). Five-year survival analysis showed an increased probability of VF worsening by 5.5 dB (P=.0170), indicating a greater proportion of fast progressors in the CS arm. CS-HMS has a significant effect on VF preservation in glaucoma patients compared with CS alone, reducing the proportion of fast progressors.

Ultrasound Simulation for Training Trainees when the Luxury Becomes Essential: Opinion and Evidence Obtained during the Latvian Research Council Project Implementation.

Simulation as a proxy tool for conditional clinical training became a powerful technique for introducing trainees to the ultrasound imaging world, allowing them to become a trained sonographer taking into consideration different rates of progress in completing a specific task against the time and ensuring the long-lasting maintenance of the obtained practical skills. Adding a costly, but effective high-fidelity simulator to the residency program justified the expense, demonstrating efficiency of training for improving the clinical performance and confidence of trainees. A pilot study in Riga Maternity Hospital within the framework of the study "Role of metabolome, biomarkers and ultrasound parameters in successful labor induction" (Fundamental and Applied Research Programme lzp-2021/1-0300) was performed between March 1st 2022 and 31st April 2022. A virtual-reality simulator (ScanTrainer, MedaphorTM, Cardiff, UK) was used with the teaching module for assessment of the uterine cervix. Five trainees in obstetrics and two young specialists included in the study. None of them had Fetal Medicine Foundation certificate of competence in the assessment of the uterine cervical lenght before. The time used on the simulator, the number of simulations and a mean confidence in cervical length assessment before and after simulation were recorded. The study on assesment of uterine cervical lenght demonstrated statistically significant increase in confidence (p=0.008) and statistically significant decrease in time needed to complete correctly the same tasks for the trainees (p=0.008) that shows a positive learning curve over the time of training on ScanTrainer, Medaphor. The simple task allows to become a certified specialist in uterine cervical assessment in the short period of time. That support the productiveness of the simulation-based education. The training program should be updated taking into consideration simulation curriculum.

Youth versus adult-onset type 2 diabetic kidney disease: Insights into currently known structural differences and the potential underlying mechanisms.

Type 2 diabetes (T2D) is a global health pandemic with significant humanitarian, economic, and societal implications, particularly for youth and young adults who are experiencing an exponential rise in incident disease. Youth-onset T2D has a more aggressive phenotype than adult-onset T2D, and this translates to important differences in rates of progression of diabetic kidney disease (DKD). We hypothesize that youth-onset DKD due to T2D may exhibit morphometric, metabolic, and molecular characteristics that are distinct from adult-onset T2D and develop secondary to inherent differences in renal energy expenditure and substrate metabolism, resulting in a central metabolic imbalance. Kidney structural changes that are evident at the onset of puberty also serve to exacerbate the organ's baseline high rates of energy expenditure. Additionally, the physiologic state of insulin resistance seen during puberty increases the risk for kidney disease and is exacerbated by both concurrent diabetes and obesity. A metabolic mismatch in renal energetics may represent a novel target for pharmacologic intervention, both for prevention and treatment of DKD. Further investigation into the underlying molecular mechanisms resulting in DKD in youth-onset T2D using metabolomics and RNA sequencing of kidney tissue obtained at biopsy is necessary to expand our understanding of early DKD and potential targets for therapeutic intervention. Furthermore, large-scale clinical trials evaluating the duration of kidney protective effects of pharmacologic interventions that target a metabolic mismatch in kidney energy expenditure are needed to help mitigate the risk of DKD in youth-onset T2D.

Two-Year Visual Field Outcomes of the Treatment of Advanced Glaucoma Study (TAGS)

to compare visual field (VF) progression between the 2 arms of the Treatment of Advanced Glaucoma Study (TAGS). Post hoc analysis of VF data from a 2-arm, multicenter, randomized controlled clinical trial. A total of 453 patients with newly diagnosed advanced open-angle glaucoma in at least 1 eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (n=227) or medication in their index eye (n=226) and followed-up for 2 years with 2 24-2 VF tests at baseline, 4, 12, and 24 months. Data were analyzed for participants with a reliable VF (false positive rate < 15%) at baseline and at least 2 other time points. Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5, and 2 dB) was compared using survival analysis. This study analyzed 211 eyes in the trabeculectomy first arm and 203 eyes in the medication first arm. The average RoP (estimate [95% credible intervals]) was -0.59 [-0.88, -0.31] dB/year in the medication first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy first arm. The difference was not significant (Bayesian P-value=.353). More eyes progressed in the medication first arm, but this difference was not significant. There was no significant difference in the average RoP at 2 years.

Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis. We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12 months and 24 months were compared with survival. Overall, 565 patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A). There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral (MR) and tricuspid regurgitation (TR) at 12- and 24-month assessments was associated with worse prognosis (change at 12 months: MR, hazard ratio 1.43 [95% confidence interval 1.14-1.80], p=0.002; TR, hazard ratio 1.38 [95% confidence interval 1.10-1.75], p=0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors. In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors.

Long-term antiretroviral therapy mitigates mortality and morbidity independent of HIV tropism: 18 years follow-up in a women's cohort.

CXCR4 (X4)-tropic HIV-1 was found previously to herald CD4 + cell depletion and disease progression in individuals who were antiretroviral-naive or took combination antiretroviral therapy (cART) for less than 5 years. We updated this finding by investigating whether the deleterious effect of X4-tropic strains is mitigated by long-term cART. We examined morbidity and mortality in relation to HIV-1 tropism and cART in 529 participants followed up to 18 years in the Women's Interagency HIV Study; 91% were women of color. Plasma-derived HIV-1 tropism was determined genotypically. We categorized participants according to the number of visits reported on cART after initiation. Group 1: three or less visits, 74% of these participants reporting no cART; group 2: at least four visits and less than 70% of visits on cART; group 3: at least 70% of visits on cART. AIDS mortality rates for participants in each group with X4 virus compared with those with R5 virus exclusively were, respectively: 62 vs. 40% ( P = 0.0088); 23% vs. 22% [nonsignificant (NS)]; 7% vs. 14% (NS). Kaplan-Meier curves showed accelerated progression to AIDS death or AIDS-defining illness in participants with three or less cART visits and X4 viruses ( P = 0.0028) but no difference in progression rates stratified by tropism in other groups. Logistic regression found that HIV-1 suppression for at least 10 semiannual visits (≥5 years total) mitigated X4 tropism's deleterious effect on mortality, controlling for maximal viral load, and CD4 + nadir. Long-term cART markedly mitigated the deleterious effect of X4 viruses on AIDS morbidity and mortality. Mitigation was correlated with duration of viral suppression, supporting HIV-1 suppression as a crucial goal.

P886: AFRICAN AMERICAN PATIENTS WITH SMOLDERING MULTIPLE MYELOMA MAY HAVE A LOWER RISK OF PROGRESSION COMPARED TO WHITE PATIENTS

Background: The incidence of multiple myeloma (MM) and its precursor stages is two to threefold higher in African Americans (AAs) compared to whites when adjusted for socioeconomic status, age, and sex. However, there is limited information on whether racial background affects the risk of progression from smoldering MM (SMM) to MM. Aims: To assess the effect of race on the progression from SMM to MM. Methods: Patients with SMM presenting to Memorial Sloan Kettering Cancer Center between the years 2000 and 2019 and who identified as either AA or white were included in this retrospective study. Baseline patient and disease characteristics were collected at the time of diagnosis including laboratory, imaging, and pathology reports. Differences in distributions of continuous and discrete characteristics were assessed by Kruskal-Wallis and chi-square tests. Time to progression (TTP) was assessed using the Kaplan-Meier method with log-rank test for comparisons. Univariate and multivariate Cox proportional hazard models were used to estimate effects of risk factors on TTP with hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 576 patients were included (70 were AA, 12%). Median follow-up time was 3 years in AAs and 4 years in whites. Differences in baseline characteristics between AAs and whites included median age (60 years in AAs [IQR 51-67] vs 64 years in whites [IQR 56-72], p = 0.01), median hemoglobin level (12.3g/dL in AA [IQR 11.8-13] vs 12.8g/dL in whites [IQR 11.8-13.9], p = 0.02), and immunoparesis including 1 or 2 uninvolved immunoglobulins (31% and 10% in AAs vs 56% and 27% in whites, p = 0.002). There was no difference in bone marrow plasma cell percentage (BMPC), M-spike, free light chain ratio, or Mayo-2018 SMM risk score. AA race was associated with a significantly decreased risk of progression in the univariate model (HR 0.57, CI 0.34-0.94). In the multivariate model adjusting for age, sex, and variables associated with an increased risk of progression in the univariate model (BMPC, M-spike, free light chain ratio, immunoparesis and low albumin), AA race remained associated with a decreased risk of progression (HR 0.39, CI 0.16-0.95). Overall, AA patients with SMM had a significantly (p = 0.027) longer median TTP (9.7 vs 6.2 years), and a lower 2-year (12.6% vs 20.1%) and 5-year (34% vs 44.6%) progression rate than whites. Because AA patients were younger at diagnosis, we stratified patients by age group, < 65 vs ≥65 years. In patients < 65 years, there was no difference in progression rate. In patients aged ≥65 years, AA patients continued to have a longer TTP than whites (9.8 vs 5.2 years, p = 0.02). Image:Summary/Conclusion: In our retrospective single institution experience, AA patients with SMM had a lower risk of progression to MM compared to whites. Both groups had similar Mayo-2018 risk scores, however, AA patients had a lower degree of immunoparesis at baseline. Future studies are needed to better understand if these differences are explained by differences in disease biology including genomic mechanisms, immune microenvironment, and systemic immune response.