Full Follow-up Research Articles

P0412 Predicting outcomes of disease in patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: a retrospective multicentric study

Abstract Background The impact of coexistent IBD and PSC on disease progression and prognosis is unclear. This study evaluates outcomes in patients with both conditions, using the novel PSC Risk Estimate Tool (PREsTO) for PSC prognosis. Methods A retrospective multicentric study identified IBD-PSC patients through a national survey. PREsTO was calculated to predict PSC-related liver decompensation, and IBD progression was tracked via composite outcome measures. Results Among 77 identified patients from six nationwide participating centres, 59 were included, predominantly with ulcerative colitis (77%) and pancolitis (89%). Median ages at diagnosis were 22.3 for IBD and 29.8 for PSC, with follow-ups of 12.0 and 6.9 years, respectively. PREsTO predicted a median 5-year risk of liver decompensation of 5.3% according to baseline characteristics. However, within this period only 1 patient experienced variceal bleeding; no other liver decompensation events were reported. Notably, over full follow-up, there were 20 additional events: jaundice (7), variceal bleeding (1), cholangitis (5), pruritus (7). One patient (1.7%) ultimately required liver transplant. For IBD, during follow-up, 10 patients (17%) were hospitalised for IBD-related reasons (1 bowel subocclusion, 9 flare-ups). Twelve patients (21%) required at least one course of corticosteroids, and 34% started advanced medical therapy, of whom 57% needed either dose optimisation or modification. Three patients underwent surgery due to refractory disease activity (1 colectomy, 2 proctocolectomies). Importantly, 39% of patients showed subclinical disease activity at the last follow-up, indicated by faecal calprotectin above 250µg/g. Conclusion PREsTO may overestimate liver decompensation risk in our IBD-PSC population, which may be due to a young population. However, the impact of PSC extends beyond portal hypertension complications. Nonetheless, the high prevalence of IBD subclinical inflammation in this group raises concerns about potential disease progression and increased cancer risk.

Time to neonatal mortality and its predictors among preterm neonates admitted to the neonatal intensive care unit in northern Ethiopia, 2023/2024: a retrospective cohort study

BackgroundA preterm neonate is defined by the World Health Organization as a child delivered before 37 weeks of gestation. In low- and middle-income countries, including Ethiopia, preterm-related complications are serious health problems due to increases in the mortality and morbidity of newborns and children under 5 years of age. The aim of this study was to assess the time to neonatal mortality and its predictors among preterm neonates admitted to the neonatal intensive care unit in northern Ethiopia, 2023/2024.MethodsAn institution-based retrospective cohort study was conducted among 495 randomly selected preterm neonates in six out of the fourteen general hospitals of Tigray, Ethiopia from October 2023 to June 2024. Epi Data version 4.6 and STATA version 14 were used for data entry and analysis, respectively. Descriptive statistics were carried out to determine the distribution. Kaplan-Meier analysis, life table, and log rank were computed. Cox proportional hazards models were fitted to identify independent predictors of preterm mortality.ResultsThe proportion of preterm neonatal mortality was 109 (22.7%). The overall median survival time was 21 (95% CI: 20, 28) days. Initiation of breast milk (AHR = 0.38 (95% CI: 0.24, 0.61)), respiratory distress syndrome (AHR = 1.9 (95% CI: 1.07,3.63)), perinatal asphyxia (AHR = 2.05 (95% CI: 1.05, 4.00)), receiving kangaroo mother care practice (AHR = 0.5 (95% CI: 0.34, 0.83)), and gestational age (AHR = 1.6 (95% CI 1.07, 2.59) were the predictors of time to death.ConclusionRespiratory distress syndrome, gestational age less than 32 weeks, and perinatal asphyxia at admission were found to be independent risk factors for preterm neonatal mortality. Breastfeeding and receiving kangaroo-mother care were independent preventive predictors of preterm neonatal mortality. It is better to give full emphasis and close follow-up to preterm neonates, especially during the early neonatal period.

THE INTERPLAY AMONG IMMUNITY, INFLAMMATION, AND FRIED FRAILTY ON ALZHEIMER’S DISEASE

Abstract Unraveling shared mechanisms for both frailty and Alzheimer’s Disease (AD) including immunity and inflammation is crucial for understanding the link between these two complex multifactorial conditions. This study aimed to characterize the interplay among circulating immune cells, inflammatory biomarkers, and frailty phenotypes on AD onset in the Framingham Heart Study Offspring cohort. A sample of 519 participants (52% female, mean age 66 years), had extensive profiling of immune cells from peripheral blood mononuclear cells and inflammatory protein biomarkers (OLINK Proteomics) at Exam 7 and were dementia-free at the time of Fried frailty measurement (Exam 8). Data from 146 immune cells, 68 proteins, and 5 frailty phenotype components were integrated using sparse multiple Canonical Correlation Analysis (SmCCA) adjusted for relevant covariates. SmCCA seeks linear combinations of variables maximizing inter-correlated canonical scores for all three datasets, yielding signatures of immunity, inflammation, and frailty for each participant that screened variables contributing to the establishment of signatures and inter-datasets pathways. Full follow-up for up to 13.8 years (median 12.1 years) identified 24 incident AD cases. Cox proportional hazard models, accounting for covariates including age, sex, education, and APOE genotype, were employed to assess signatures as risk factors for AD incidence. The inflammation and immunity signatures were correlated (r2=0.32, p-value< 0.001). Both immunity and frailty signatures were significantly associated with AD incidence (immunity: HR=1.1, p-value=0.03; frailty: HR=3.14, p-value=0.02). This study disentangles potential pathways among immune cells and inflammatory biomarkers that contributed to associations with frailty and AD. We will extend to larger studies for replication.

Tea Consumption and Long-Term Mortality in Very Elderly Individuals With or Without Cardiovascular and Cerebrovascular Disease: Findings From a Sample of 19664 Chinese.

The association between tea consumption and mortality among very elderly individuals, with or without cardiovascular and cerebrovascular diseases (CCD), including stroke, remains unclear. This study hypothesised that a significant association exists. We analysed data from two waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), spanning 1998/2000 to 2018, with a maximum follow-up of 20 years. Cox proportional hazards models, adjusted for potential confounders, were used to examine the association between tea consumption and all-cause mortality among the oldest old ( ≥ 80 years) with or without CCD. Participants were categorised based on the frequency of tea consumption (rare, occasional or regular) at the time of the survey and around the age of 60. Due to violations of the proportional hazards assumption, Cox model results were reliable only for the first 8 years of follow-up. Among 19,664 elderly participants, frequent tea consumption was associated with a lower mortality risk during the initial 8 years (adjusted HR 0.93, 95% CI 0.89-0.97) compared to never or rare tea consumption. However, this association diminished over the full 20-year follow-up. The significant association was observed only in participants who also reported frequent tea consumption around the age of 60 (adjusted HR 0.91, 95% CI 0.85-0.95). No significant interaction was found between pre-existing CCD and the 8-year effect of tea consumption (P for interaction > 0.05). Among very elderly Chinese individuals, frequent tea consumption was associated with reduced mortality over the short term, particularly in those who maintained this habit throughout life. No significant interaction effect was observed between pre-existing CCD and the mortality benefits of tea consumption.

The learning curve for hood-sparing robotic-assisted radical prostatectomy: A single-surgeon experience.

This study aimed to assess the impact of anterior hood-sparing robot-assisted radical prostatectomy (RARP) with posterior-anterior reconstruction in a single-surgeon series by analysing oncological and functional continence outcomes. We carried out a cohort comparison study of a prospectively collected single-surgeon series. The surgeon was an 'in-training' fellowship trained surgeon in their first 2years of independent practice. There were three cohorts identified from electronic and scanned paper operation notes. The first cohort of standard anterior RARP (no hood sparing) included initial patients and any patient in the consecutive series who had completed 3month FU after RARP. The second cohort was hemi-hood-sparing RARP again within the consecutive database of patients and lastly full-hood-sparing RARP. Early continence was defined by patients reporting being 'dry' and with 0 pad or 1 confidence/security pad. Data was collected in an Excel spreadsheet, and SPSS was used to assess distribution with non-parametric data being analysed using a Mann Whitney U test and parametric data with an unpaired t-test. We identified 174 patients from March 2020 to February 2022 who were operated on. Full pathology and 6-week follow-up pad use data was available for all patients. At 12 months, some data for EPIC-26 was not available (lack of response/clinic non-attendance). The results demonstrate doubling in early continence to over 75% at 6-week follow-up with comparable positive margin rates. This difference was statistically significantly better in the dorsal venous complex RARP sparing group in comparison to standard RARP (p< 0.001). Anterior hood-sparing RARP with anterior reconstruction is a modification to the standard anterior RARP approach with a short learning curve which provides patients with better early and late continence without compromise to oncological outcomes.

A prospective cohort study: promising results with minimally invasive plate osteosynthesis of anterior bridge plating in adult humeral shaft fractures.

Adult humeral shaft fractures have traditionally been managed conservatively, but surgical intervention is considered for displaced fractures or when conservative treatment is unlikely to be successful. The optimal surgical approach remains controversial, with open reduction and internal fixation (ORIF) using plates and screws considered the gold standard. However, concerns about soft tissue damage have led to the development of less invasive techniques, such as anterior bridge plating using minimally invasive plate osteosynthesis (MIPO). This study aimed to evaluate the outcomes of MIPO for humeral shaft fractures. A prospective cohort study included 43 patients who underwent anterior bridge plating with MIPO for closed, displaced humeral shaft fractures. Forty patients had full follow-up (functional and radiological) and three patients were lost to follow-up. Fractures were classified using the AO classification system. Surgical technique involved incision, reduction, and fixation with locking compression plates. Follow-up assessments were conducted at various intervals, and functional outcomes were evaluated. Fracture union was achieved in 38 of 40 patients (95%). Two patients required secondary bone grafts for non-union. The mean time to union was between 12 and 16 weeks. Excellent shoulder function was observed in 82.5% of patients, and excellent elbow function in 77.5%. The range of motion on the operated side differed statistically significantly from the nonoperated side but was not clinically significant. MIPO with anterior bridge plating is a viable option for the surgical management of humeral shaft fractures. It offers good fracture healing rates and satisfactory functional outcomes and avoids extensive soft tissue dissection associated with ORIF. Level of evidence: II.

Caregiver Impressions of Bracing and Its Association With Unsuccessful Outcomes Throughout the Ponseti Treatment.

Clubfoot is a common congenital foot deformity, occurring in about 1 in 1000 live births. The Ponseti method consists of weeks of manipulation and serial casting, followed by years of orthotic wear. Recurrent or relapse deformity following the Ponseti method remains a challenging problem for many patients. Many studies have attributed relapse to noncompliance with the treatment plan, particularly during the maintenance phase. Many patient risk factors have been studied and attributed to recurrent deformity, but less emphasis has been placed on aspects of the treatment method from the caregiver's perspective. From 2010 to 2014, 127 patients between 1 and 354 days old who had been diagnosed with clubfoot were recruited for the parent study. At the initial visit, and each subsequent follow-up, the primary caregiver was given a questionnaire that included 21 binary belief questions exploring his or her experience with the Ponseti method. Univariate analyses were performed to find any relationship with caregiver responses and either clinical recurrence of the deformity or overall failure of treatment. Of the recruited patients, 126 were enrolled in the parent study and 100 were able to complete the full 3-year follow-up. Patient demographics and characteristics (sex, race, family history of clubfoot, laterality, and severity of deformity) were similar. Statistical analysis of the questionnaire responses found that choosing "yes" for either "I don't feel the braces are necessary" or "I am not comfortable with applying and removing the braces" was associated with significantly increased risk of overall failure. Gathering insight from the caregiver's perspective can help identify barriers to treatment not recognized by the provider. Lack of comfortability with the orthosis and lack of understanding are associated with increased risk of overall failure. A better understanding of the caregiver's perspective on barriers to treatment could help guide the Ponseti method provider's educational efforts. Level III.

Comparison of optimized surface ablation and combined customized plus optimized surface ablation in myopic eyes

Background Proscan treats errors of refraction without affecting asphericity, while customized treatment treats correction with high-order aberration (HOA). Recently, Zyoptix HD has been used in the treatment of preoperative HOA and lower-order aberrations without inducing spherical aberrations. Aim To compare the visual outcomes and HOAs after optimized surface ablation versus Zyoptix HD surface ablation for myopia. Patients and methods A prospective comparative clinically controlled study was conducted on patients who have myopia, 40 eyes of 20 patients divided into two groups. Group I: 20 eyes underwent optimized surface ablation. Group II: 20 eyes underwent customized plus optimized surface ablation. The selection of treatment was according to root mean square and spherical aberration corneal topography. All participants were examined by a slit lamp just after the operation, on the first, third, seventh postoperative day, weekly for 1 month, then biweekly for 3 months. The patients had full follow-up by best corrected visual acuity, slit lamp, Orbscan IIZ, and wavefront aberrometry using Zywave after 3 months of procedure. Results The comparison between preoperative uncorrected visual acuity and 3 months postoperative uncorrected visual acuity improved significantly in both groups but better in group II. The comparison between preoperative and 3 months postoperative root mean square in group I increased significantly, and in group II improved significantly, which is better in group II. Conclusion Zyoptix HD is superior to optimized surface ablation in the correction of low-order and high-order eye aberrations, correcting myopia and visual acuity.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Switching to a 100% remote follow-up of implantable cardiac electronic devices: Organizational model and results of a single center experience.

During the SARS-CoV-2 COVID-19 pandemic, the global health system needed to review important processes involved in daily routines such as outpatient activities within the hospital, including follow-up visits of implantable cardiac electronic devices (CIEDs) carried out in office. The aim of this study is to describe our 3.5 years of real-world experience of a full remote CIED follow-up, evaluate the success rate of remote transmissions, and verify the adopted organizational model. From April 2020 to November 2023, all patients with an activated and well-functioning remote monitoring (RM) system and automatic algorithms, like autocapture and autosensing, underwent exclusive RM follow-up. Unscheduled in-office visits were only prompted by remote yellow or red alerts. Patients were divided into two groups, based on available technology: Manual Transmission System (MTS) and Automatic Transmission System (ATS). The ATS group, in addition to ensuring a daily transmission of any yellow or red alerts, was checked at least every 15 days to ensure a valid connection. An automatic transmission was scheduled once a year, irrespective of alerts occurred. The MTS group provided a manual transmission every 6 months. One thousand nine hundred thirty-seven consecutive patients were included in the study. By the end of November 2023, a total of 1409 patients (1192 in the ATS and 217 in the MTS group) were still actively followed by our remote clinic (384 expired, 137 dismissed, 7 transferred). The overall success rate of transmissions with the adopted organizational model was 96.6% in the ATS group (connection index) and 87% in the MTS group. Conventional in-hospital follow-up visits decreased by 44%. Total clinic working time, resulting from the sum of the time spent during in-hospital and remote follow-up, after an initial increase, was progressively reduced to the actual -25%. Mortality rate for any cause was 7.5% per year in remote follow-up patients and 8.3% (p=NS) in in-office patients. In the ATS group, no device malfunctions were notified to our remote clinic, before we had already realized it through appropriate alerts. The available technology makes moving to a 100% remote clinic possible, without overwhelming clinic workflow, safely. Adopting an appropriate organizational model, it is possible to maintain high transmission success rates. The automatic transmissions allow a more frequent control of patients with CIED.

Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma

Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. First-line P+A or I+N. HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P < .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P < .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.

Organoids for Functional Precision Medicine in Advanced Pancreatic Cancer

Patient-derived organoids (PDOs) are promising tumor avatars that could enable exvivo drug tests to personalize patients' treatments in the frame of functional precision oncology. However, clinical evidence remains scarce. This study aims to evaluate whether PDOs can be implemented in clinical practice to benefit patients with advanced refractory pancreatic ductal adenocarcinoma (PDAC). During 2021 to 2022, 87 patients were prospectively enrolled in an institutional review board-approved protocol. Inclusion criteria were histologically confirmed PDAC with the tumor site accessible. A panel of 25 approved antitumor therapies (chemogram) was tested and compared to patient responses to assess PDO predictive values and map the drug sensitivity landscape in PDAC. Fifty-four PDOs were generated from 87 pretreated patients (take-on rate, 62%). The main PDO mutations were KRAS (96%), TP53 (88%), and CDKN2A/B (22%), with a 91% concordance rate with their tumor of origin. The mean turnaround time to chemogram was 6.8 weeks. In 91% of cases, ≥1 hit was identified (gemcitabine (n= 20 of 54), docetaxel (n= 18 of 54), and vinorelbine (n= 17 of 54), with a median of 3 hits/patient (range, 0-12). Our cohort included 34 evaluable patients with full clinical follow-up. We report a chemogram sensitivity of 83.3% and specificity of 92.9%. The overall response rate and progression-free survival were higher when patients received a hit treatment as compared to patients who received a nonhit drug (as part of routine management). Finally, we leveraged our PDO collection as a platform for drug validation and combo identification. We tested anti-KRASG12D (MRTX1133), alone or combined, and identified a specific synergy with anti-EGFR therapies in KRASG12D variants. We report the largest prospective study aiming at implementing PDO-based functional precision oncology and identify very robust predictive values in this clinical setting. In a clinically relevant turnaround time, we identify putative hits for 91% of patients, providing unexpected potential survival benefits in this very aggressive indication. Although this remains to be confirmed in interventional precision oncology trials, PDO collection already provides powerful opportunities for drugs and combinatorial treatment development.

Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n=443) had a mean age of 68.8±11.2years, 77% male (usual care cohort: n=315, mean age of 66.2±14.5years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P=0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P=0.077). These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.

Evaluation of a Population-Based Targeted Screening Approach for Skin Cancer with Long-Time Follow-Up in Austria including Potential Effects on Melanoma Mortality.

whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.

Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis.

The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease (IBD). In early onset IBD, it may differ but the evidence is sparse. We aimed to investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis. A register-based study included all Danish patients with early onset of IBD (≤18 years) between 1980 and 2021 and 50 matched references without IBD for each case. We examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis in Cox regression models. In total, 6822 patients with IBD were identified, and 337 728 matched references. The median age at the time of IBD diagnosis or index date for the matched references was 16 years (25-75 percentile: 13-18 years), and the median age at the time of an outcome or at the end of follow-up was 28.1 years (25-75 percentile: 21.5-37.0 years). According to the cumulative incidence plots psoriatic arthritis, and spondyloarthritis was diagnosed approximately 10 years after the IBD onset, and the remaining outcomes later. The adjusted hazard ratio after full follow-up was 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis, 5.21 (95% CI, 4.17-6.50) for spondyloarthritis, 2.77 (95% CI, 1.92-4.00) for celiac disease, 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis, 1.69 (95% CI, 1.23-2.32) and 1.64 (95% CI, 1.21-2.21) for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16 (95% CI, 0.97-1.40). The risk estimates were significantly increased for all outcomes at the end of follow-up, except for thyroid disease, but according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.

Natural course of partially embolized carotid-cavernous fistulas.

To present the first study analyzing the clinical and radiological course of carotid-cavernous fistulas (CCFs) following incomplete embolization. The study compares magnetic resonance angiography (MRA) to plain angiography (digital subtraction angiography [DSA]) and investigates the long-term ophthalmological impact of residual fistula. Fistulas classified as partially embolized after the last endovascular treatment were prospectively followed with DSA, MRA, and ophthalmological examination. Both direct and indirect CCFs were included. Twenty-one CCFs were included in the study. Nine (43%) fistulas were direct and 12 (57%) were indirect. A favorable clinical outcome of modified Rankin scale ≤2 was recorded in 19 (90%) patients at the last follow-up. Postinterventional ophthalmologic examinations in 16 patients revealed no negative effects of residual fistulas; five remaining patients refused to undergo further examination. Spontaneous thrombosis and complete occlusion of the CCF were demonstrated in 90% of patients, with a mean time to occlusion of 5.7±4.7months. Fourteen (66%) patients completed the full imaging follow-up (MRA and DSA). In 21% of these cases, discrepancy between the two imaging modalities was observed-MRA failed to detect persistent fistulas identified by DSA. The goal of CCF treatment is safe and complete embolization. However, if adequate flow reduction is achieved, both direct and indirect CCFs tend to spontaneously thrombose. Residual flow does not result in ophthalmological deterioration until the fistula is completely closed. MRA may not be sufficiently sensitive to detect residues of fistulas including cortical venous drainage. Therefore, complete CCF closure should be confirmed through DSA.

Prospective assessment of functional and clinical results of surgical patellar stabilization in rural and urban populations. Equal chance to success?

Patella dislocation represents 3.3% of all knee injuries often leading to persistent instability. Medial patello-femoral ligament(MPFL) reconstruction is the standard method of treatment in the patellar instability. Rehabilitation after MPFL-R is a long and demanding procedure. The hypothesis presented reflects the idea that despite relatively good access to hospital care and surgical options, the post-operative rehabilitation care system is still inferior in rural areas versus the one offered in major cities and towns. Between January 2015 - January 2018, 47 patients met the study inclusion criteria, diagnosed and operated on due to patellar instability. 8 patients were lost for full follow-up. Finally, 39 patients were included, divided into two groups - group A (19 from cities), group B (20 from rural area). Prospective KOOS and Kujala scales assessments were conducted: preoperative, 6 and 12 months after surgery. Knee isokinetic muscle strength was measured at 3 stages; prior to surgery, 6 and 12 months after reconstruction. All patients showed significant improvement measured in the KOOS and Kujala scales after the procedure, compared to the pre-operational results. Despite equal clinical improvement, patients from Group A(city) achieved better functional outcomes as presented in the results of knee extensor functional tests using a Biodex dynamometer. Rehabilitation after MPFL reconstruction improves muscle strength and clinical outcome. Patients from rural areas had inferior functional results in comparison to the patients from major cities, even 12 months after surgical patella stabilization. Despite the development of roads and transport according to the EU cohesion policy, there are still differences in rehabilitation results between rural and city areas.

Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups.

It is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups. Cognitively unimpaired individuals from the Amsterdam Dementia Cohort and the SCIENCe project with available AD biomarkers, obtained from CSF, PET scans, and plasma at baseline, were followed over time (4.5 ± 3.1 years, range 0.6-18.9 years). Based on common inclusion criteria for clinical trials, we defined groups (amyloid, phosphorylated tau [p-tau], APOE ε4). Linear mixed models, adjusted for age, sex, and education, were used to estimate change over time in neuropsychological tests, a functional outcome, and 2 cognitive composite measures. Standardized regression coefficients of time in years (βtime) were reported as outcome of interest. We analyzed change over time with full follow-up, as well as with follow-up limited to 1.5 and 3 years. We included 387 individuals (aged 61.7 ± 8.6 years; 44% female) in the following (partly overlapping) biomarker groups: APOE ε4 carriers (n = 212), amyloid-positive individuals (n = 109), amyloid-positive APOE ε4 carriers (n = 66), CSF p-tau-positive individuals (n = 127), plasma p-tau-positive individuals (n = 71), and amyloid and CSF p-tau-positive individuals (n = 50), or in a control group (normal biomarkers; n = 65). An executive functioning task showed most decline in all biomarker groups (βtime range -0.30 to -0.71), followed by delayed word list recognition (βtime range -0.18 to -0.50). Functional decline (βtime range -0.17 to -0.63) was observed in all, except the CSF and plasma tau-positive groups. Both composites showed comparable amounts of change (βtime range -0.12 to -0.62) in all groups, except plasma p-tau-positive individuals. When limiting original follow-up duration, many effects disappeared or even flipped direction. In conclusion, functional, composite, and neuropsychological outcome measures across all cognitive domains detect changes over time in various biomarker-defined groups, with changes being most evident among individuals with more AD pathology. AD prevention trials should use sufficiently long follow-up duration and/or more sensitive outcome measures to optimally capture subtle cognitive changes over time.

Long-term patient-reported outcomes from monarchE: Abemaciclib plus endocrine therapy as adjuvant therapy for HR+, HER2-, node-positive, high-risk, early breast cancer

In monarchE, abemaciclib demonstrated a sustained benefit in invasive disease-free survival and a tolerable safety profile at 42-months median follow-up. With no expected disease-related symptoms, therapies in the adjuvant setting should preserve quality of life (QoL). With all patients off abemaciclib, we report updated patient-reported outcomes (PROs) for the full 2-year treatment period and follow-up. Patients completed PROs including FACT-B, FACT-ES, and FACIT-Fatigue at baseline, 3, 6, 12, 18, and 24 months during treatment, and 1, 6, and 12 months after treatment discontinuation. Mixed effects repeated measures model estimated changes from baseline within and between arms for QoL scales and individual items. Meaningful changes were prespecified and no statistical testing was performed. Frequencies of responses to items associated with relevant adverse events and treatment bother were summarized. At baseline, completion rates for PRO instruments were >96 %. Mean changes from baseline for all QoL scales were numerically similar within and between arms (ie, less than prespecified thresholds). The same was observed for all individual items, except diarrhea. Within abemaciclib arm, meaningful differences for diarrhea were observed at 3 and 6 months (mean increases of 1.19 and 1.03 points on 5-point scale, respectively). During treatment, most patients in both arms (69-78 %) reported being bothered "a little bit" or "not at all" by side effects. Overall, patterns for fatigue were similar between arms. During post-treatment follow-up, PROs in both arms were similar to baseline. PRO findings confirm a tolerable and reversible toxicity profile for abemaciclib. QoL was preserved with the addition of adjuvant abemaciclib to endocrine therapy, supporting its use in patients with HR+, HER2-, high-risk early breast cancer.

Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis and Extended Clinical Follow-up.

To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease. We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors. Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathologic downstaging (HR = 4.7; P = 0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR = 3.4; P = 0.0005) and after RC (HR = 17.8; P = 0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Basal/Squamous (Ba/Sq) subtype and enrichment of epithelial-to-mesenchymal transition and cell cycle-associated gene sets. ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than 5 years follow-up and outperforms pathologic downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.