Retrospective Longitudinal Study Research Articles

Proteomics profiling and machine learning in nusinersen-treated patients with spinal muscular atrophy

AimThe availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need for reliable prognostic biomarkers to classify patients according to disease severity. We aim to identify cerebrospinal fluid (CSF) prognostic protein biomarkers in CSF samples of SMA patients collected at baseline (T0), and to describe proteomic profile changes and biological pathways influenced by nusinersen before the sixth nusinersen infusion (T302).MethodsIn this multicenter retrospective longitudinal study, we employed an untargeted liquid chromatography mass spectrometry (LC-MS)-based proteomic approach on CSF samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at T0 at T302. The Random Forest (RF) machine learning algorithm and pathway enrichment analysis were applied for analysis.ResultsThe RF algorithm, applied to the protein expression profile of naïve patients, revealed several proteins that could classify the different types of SMA according to their differential abundance at T0. Analysis of changes in proteomic profiles identified a total of 147 differentially expressed proteins after nusinersen treatment in SMA1, 135 in SMA2, and 289 in SMA3.Overall, nusinersen-induced changes on proteomic profile were consistent with i) common effects observed in allSMA types (i.e. regulation of axonogenesis), and ii) disease severity-specific changes, namely regulation of glucose metabolism in SMA1, of coagulation processes in SMA2, and of complement cascade in SMA3.ConclusionsThis untargeted LC-MS proteomic profiling in the CSF of SMA patients revealed differences in protein expression in naïve patients and showed nusinersen-related modulation in several biological processes after 10 months of treatment. Further confirmatory studies are needed to validate these results in larger number of patients and over abroader timeframe.

Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study

We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome inchildren (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7±2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p<0.001) and cardiac dysfunction was less common (17% vs. 68%, p<0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p<0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p=0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p=0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. The U.S. Food and Drug Administration.

Non-rapid eye movement sleep slow-wave activity features are associated with amyloid accumulation in older adults with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with an increased risk for cognitive impairment and dementia, which likely involves Alzheimer's disease pathology. Non-rapid eye movement slow-wave activity (SWA) has been implicated in amyloid clearance, but it has not been studied in the context of longitudinal amyloid accumulation in OSA. This longitudinal retrospective study aims to investigate the relationship between polysomnographic and electrophysiological SWA features and amyloid accumulation. From the Mayo Clinic Study of Aging cohort, we identified 71 participants ≥60 years old with OSA (mean baseline age = 72.9 ± 7.5 years, 60.6% male, 93% cognitively unimpaired) who had at least 2 consecutive Amyloid Pittsburgh Compound B (PiB)-PET scans and a polysomnographic study within 5 years of the baseline scan and before the second scan. Annualized PiB-PET accumulation [global ΔPiB(log)/year] was estimated by the difference between the second and first log-transformed global PiB-PET uptake estimations divided by the interval between scans (years). Sixty-four participants were included in SWA analysis. SWA was characterized by the mean relative spectral power density (%) in slow oscillation (SO: 0.5-0.9 Hz) and delta (1-3.9 Hz) frequency bands and by their downslopes (SO-slope and delta-slope, respectively) during the diagnostic portion of polysomnography. We fit linear regression models to test for associations among global ΔPiB(log)/year, SWA features (mean SO% and delta% or mean SO-slope and delta-slope), and OSA severity markers, after adjusting for age at baseline PiB-PET, APOE ɛ4 and baseline amyloid positivity. For 1 SD increase in SO% and SO-slope, global ΔPiB(log)/year increased by 0.0033 (95% CI: 0.0001; 0.0064, P = 0.042) and 0.0069 (95% CI: 0.0009; 0.0129, P = 0.026), which were comparable to 32% and 59% of the effect size associated with baseline amyloid positivity, respectively. Delta-slope was associated with a reduction in global ΔPiB(log)/year by -0.0082 (95% CI: -0.0143; -0.0021, P = 0.009). Sleep apnoea severity was not associated with amyloid accumulation. Regional associations were stronger in the pre-frontal region. Both slow-wave slopes had more significant and widespread regional associations. Annualized PiB-PET accumulation was positively associated with SO and SO-slope, which may reflect altered sleep homeostasis due to increased homeostatic pressure in the setting of unmet sleep needs, increased synaptic strength, and/or hyper-excitability in OSA. Delta-slope was inversely associated with PiB-PET accumulation, suggesting it may represent residual physiological activity. Further investigation of SWA dynamics in the presence of sleep disorders before and after treatment is necessary for understanding the relationship between amyloid accumulation and SWA physiology.

Longitudinal observation of distal tibial degeneration in varus ankle osteoarthritis using plain radiograph

BackgroundThis study aimed to explore the natural history of distal tibial deformity in varus ankle osteoarthritis and to identify risk factors for its progression. MethodsThis retrospective longitudinal observational study included 97 ankles with moderate to severe varus ankle osteoarthritis, monitored for > 2 years. Radiographic assessments were conducted on weightbearing plain radiographs at the initial and final visit. ResultsSignificant tibial anterior surface angle reduction (p = 0.008), talus center medial migration (p = 0.038), and tibial lateral surface angle increase (p = 0.034) occurred. Multiple logistic analysis revealed an association between progression and coronal talar tilt angle at the first visit (odds ratio 1.17, p = 0.015) ConclusionThe progression of radiographic distal tibial deformity in varus ankle osteoarthritis was clarified, identifying the coronal talar tilt angle as a risk factor. Level of EvidenceLevel IV, retrospective longitudinal observation study

O60 SURVIVAL DISPARITIES AMONG INDIGENOUS GROUPS WITH HTN LINKED TO THEIR POPULATION CONCENTRATION

Background and objective: The indigenous groups are considered minority populations, primarily residing in rural areas. Cardiovascular disease stands as the leading cause of mortality, affecting native populations as well. This study aims to compare the overall survival (OS) rates among patients diagnosed with hypertension (HTN) in four Colombian departments where the population concentration of indigenous groups is over 10% compared to departments where it is less than 1%. Methods: Longitudinal retrospective cohort study. Population: Indigenous adults diagnosed with HTN from July 1st, 2014, to June 30 th, 2015, from the National Registry of Chronic Kidney Disease (NRCKD). The follow-up period was until July 30, 2023. We grouped indigenous communities according to their population concentration calculated by the Observatory of the Colombian Presidential Program for Human Rights. The probability of global survival from the date of diagnosis was estimated using Kaplan-Meier analysis. An unadjusted Royston Parmar flexible regression model was fitted. Right-censoring was defined as abandonment or completion of follow-up without death occurring. Results: 67,353 indigenous prevalent cases were identified from July 1st, 2022 to June 30th, 2023, representing an HTN prevalence of 2.76%. Among them, 48.90% are in Cauca, Nariño, La Guajira, and Córdoba. Natives of Nariño registered a higher proportion of GFR stages 3 and 4, calculated using the CKD-EPI formula, compared to departments with a concentration of less than 1% (48.30% and 3.15% vs. 8.08% and 0.45% respectively). 2.600 cases were included in the survival analysis. Natives residents from Nariño and Cauca had the highest risk of all-cause mortality (HR = 7.66; 95% CI 3.33 – 17.59 and HR = 7.36; 95% CI 3.26 – 16.61) compared to groups living in departments with &lt;1% concentration. Conclusions: In the Colombian health system, the hazard of all-cause mortality is higher for indigenous individuals with HTN living in Nariño and Cauca compared to those living in departments with less than 1% of the indigenous population.

O61 HYPERTENSION IN COLOMBIA: ETHNIC GROUP COMPARISONS IN CHARACTERIZATION AND SURVIVAL

Background and objective: Research has shown that ethnic minorities may be disproportionately affected by arterial hypertension. The aim of this study is to compare the overall survival (OS) HTN patients within the Colombian health system, by their ethnic group. Methods: Design: Longitudinal retrospective cohort study. Population: Adults diagnosed with HTN from June 1, 2014, to July 30, 2015, from the National Registry of Chronic Kidney Disease (NRCKD). The follow-up period was until July 30, 2023. Analysis: The probability of global survival from the date of diagnosis was estimated using Kaplan-Meier analysis. An unadjusted Royston Parmar flexible regression model was fitted. Right-censoring was defined as abandonment or completion of follow-up without death occurring. Results: 5,634,812 cases were identified from june 1st 2022 to july 30th 2023, and 299,161 incident cases were included in the survival analysis. 95.29% had no ethnic group, 1.20% were indigenous, 3.47% were Afro-descendant and 0.03% were Gypsy (ROMA). ROMA group had a higher proportion of residents in Bogotá, D.C. compared to other groups (13.96% vs ∼3%). Afro-descendant group had a higher proportion of obesity (30.61% vs. 27.86%) and diagnosis of Chronic Kidney Disease (27.31% vs. 15.69%) compared to cases with no ethnic group, while ROMA group had a higher occurrence of DM cases (23.46% vs. 21.66%). 9 years OS was higher in ROMA group (OS = 0.85; CI 95% 0.71 – 0.93) compared to indigenous (OS = 0.83; CI 95% 0.81 – 0.84) and afro-descendants (OS = 0.83; CI 95% 0.83 – 0.84). The probability of all-cause mortality was approximately 20% higher among afro-descendants and indigenous people (HR = 1.20; 95% CI 1.14 – 1.25 and HR = 1.22; 95% CI 1.12 – 1.32, respectively) compared to the non-ethnic group. In contrast, the ROMA did not present differences (p = 0.712). Conclusions: In the Colombian health system, differences in OS among afro-descendant and indigenous groups are observed compared to non-ethnic population.

P034 THE INFLUENCE OF SOCIODEMOGRAPHICAL CHARACTERISTICS AND COMORBIDITIES ON SURVIVAL IN ADULTS WITH HTN IN COLOMBIA

Background and objective: Awareness of the impact of hypertension (HTN) on health enables the implementation of effective measures to control the disease. This study characterizes the survival of the Colombian adult population with hypertension. Methods: This longitudinal retrospective cohort study included adults diagnosed with HTN from July 1, 2013, to june 30, 2014, from the National Registry of Chronic Kidney Disease (NRCKD). The primary outcome was the time from diagnosis to all-cause mortality. The probability of from the date of diagnosis was estimated using Kaplan-Meier analysis. Log-rank test evaluated differences in survivor functions. Patients were followed from baseline until death, abandonment, or the end of follow-up on July 30, 2023. Results: Baseline characteristics: The analysis included 285,418 cases. The mean age at diagnosis was 59.17 ± 14.58 years. 61.25% were females, 67.13% were affiliated with third-payer insurance, and 28.81% resided in the Central region. At baseline, 36.77% of the study population had comorbidities, including diabetes mellitus (DM) or chronic kidney disease (CKD) or both. 36,110 all-cause deaths were recorded during the follow-up period. Survival analysis: The 10-year overall survival (OS) rate was 0.84 (95% CI 0.84–0.84). The unadjusted log-rank comparisons revealed a lower probability of survival for men compared to women (0.81 vs. 0.86, respectively) and for individuals with state insurance compared to those with third-party insurance (0.80 vs. 0.86, respectively). The survival rates were found to be lower in individuals with HTA, DM, and HTN at baseline (0.68) compared to those with HTN and CKD (0.78), HTN and DM (0.81), or only HTN (0.88) (p &lt; 0.001). Conclusions: The survival of individuals with HTN is influenced by a variety of sociodemographic characteristics and can be further complicated by the presence of other comorbidities, which can potentially amplify the negative effects on an individual's health. These findings may be useful for decision-makers to focus on the identification of patients with different characteristics of risk.

Association between paediatric eye injuries, later aca-demic success and social performance

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;To investigate an association between eye injury and later academic and social performance.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;A retrospective longitudinal study of taking measurements multiple times was conducted including all severe eye injuries admitted during 2011-2017 at the main regional clinic to investigate changes in academic success and social inclusion before and after an injury. Parents/caregivers were surveyed asking questions on academic performance, and community/social involvement. In 2023 data on employment status were obtained. Kappa (ĸ) and non-parametric Wilcox-on signed-rank test for multiple comparisons were used. For association of employment status and post-injury visual acuity Fisher score was tested.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;The total sample for assessing social inclusion and academic success was 36 and 25 children, respectively. In the following academic year ĸ agreements decreased from 0.88 (p&amp;amp;lt;0.001) comparing pre-injury with a one-year post to 0.5106 (p&amp;amp;lt;.0001) in the second year and 0.4750 (p=0.003) in the third, suggesting a deteriorating trend. A comparison of academic success before injury to two and three years after injury showed the trend significantly worsening with time (p=0.005, and 0.003, respectively). No association between an eye injury and social inclusion, as well as between employment and final visual acuity was noticed.&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;Our findings suggest no association between social inclusion, employment, and eye trauma, while in later years academic success may be more impacted by the eye injury. Due to eye injury unpredictability in childhood age, both an informed and supportive climate environment at home and school is essential to minimize deleterious responses to eye trauma.&amp;lt;/p&amp;gt;

Social determinants of health and somatic growth in preterm infants and children with chronic lung disease.

Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with impaired lung function and increased morbidity in childhood. These children display heterogeneous somatic growth patterns which may ultimately impact their risk for later respiratory disease. We aim to understand the relationship between socioenvironmental exposures and growth in this population. A retrospective longitudinal cohort study was conducted using participants (n = 616) enrolled in the Johns Hopkins Outpatient BPD Registry. Growth measurements between 0 and 36 months of age were obtained. Somatic growth measurements, both corrected and uncorrected for gestational age, were converted to z-scores using Center for Disease Control and Prevention normative data. Using a participant's residential zip code, we utilized the 2019 Area Deprivation Index (ADI), the Childhood Opportunity Index (COI) 2.0, and neighborhood food insecurity data from the Maryland Food Bank. Linear regression analysis was performed employing individual socioenvironmental measures as independent variables and growth z-scores as dependent variables in univariate analysis. Univariate analysis was repeated adjusting for gestational age, BPD severity, and the presence of a gastrostomy tube (GT). Of the three measures analyzed, national COI (nCOI) showed a significant association with mean weight z-scores, mean ADI showed some association with mean weight z-scores, and the percentage of a community experiencing food insecurity showed no association with mean weight z-scores. After adjusting for gestational age, BPD severity, and presence of a GT, children living in areas of greater opportunity (higher nCOI values), had significantly lower weight z-scores at 12 months corrected and at 24 and 36 months uncorrected CONCLUSIONS: Our findings suggest that the COI 2.0, a multidimensional measure, captures more facets of an individual's social environment, as compared to the singular nature of a measure of food insecurity. There are several potential explanations for the phenomenon seen, and further understanding of this dynamic is crucial for designing effective interventions and policies to better address inequities in outcomes.

Body Mass Index Changes Among Adolescents and Young Adults Using the Etonogestrel Contraceptive Implant.

To evaluate body mass index (BMI) over 36 months among adolescents and young adults using the etonogestrel implant compared with those using depot medroxyprogesterone acetate (DMPA) and a control group. We conducted a retrospective longitudinal cohort study of postmenarchal adolescents and young adults assigned female at birth. The etonogestrel implant and DMPA groups initiated etonogestrel or DMPA between January 1, 2010, and December 31, 2017. Adolescents and young adults in the control group were prescribed a weight-neutral contraceptive or no contraceptive during the same timeframe. The primary outcome of BMI over time was estimated and compared between study groups with inverse probability of treatment weighting linear mixed-effects modeling. Changes in BMI weight category (underweight or normal weight, overweight, obesity) at 12, 24, and 36 months were also explored. Among the 20,409 eligible patients, 860 initiated etonogestrel, 1,817 initiated DMPA, and 17,732 made up the control group. Compared with individuals in the control group, those in the etonogestrel group had a significantly higher mean BMI difference at 9 months (+0.5, P<.01); at 36 months, the mean BMI difference was +1.0 (P<.01). Compared with individuals in the control group, those in the DMPA group had higher mean BMI at 6 months (+0.3, P<.01); at 36 months, the mean BMI difference was +1.3 (P<.01). Regardless of weight changes, increases in BMI weight categories were rare in all groups. Adolescent and young adult patients who initiated the etonogestrel implant demonstrated BMI changes like those on DMPA and higher than control patients; however, these differences may not be clinically concerning. This study provides important information that can help in counseling adolescent and young adult patients about expectations when starting and using etonogestrel.

Audiological outcome of bimodal CI users over time and depending on different influencing factors

Hearing-impaired persons with asymmetric hearing loss and aunilateral indication for acochlear implant (CI) generally benefit from abimodal hearing solution. The influence of bimodal fitting on speech comprehension (SC) over time has not yet been sufficiently investigated. The present study examines the influence of bimodal fitting on SC in bimodally fitted CI users with postlingual deafness at least 36months after implantation and analyzes possible influencing factors. Included in this retrospective longitudinal study were 54bimodally fitted speech-competent CI users with at least 36months of CI experience. Audiometric data of these CI users at predefined timepoints were compared. The change in the results of the Freiburg monosyllabic test (FT) over 36months was significant (p < 5%) for the deafness group at <10years for both the 65 dB sound pressure level (SPL) and at 80 dB SPL and also significant for the deafness group ≥10years for 65 dB SPL. In the Oldenburg sentence test (OlSa) there was ahighly significant change (p < 0.1%) for S0, S0N0, and S0NCI configurations and avery significant change (p < 1%) for S0NHA (HA: hearing aid). Age at implantation as apossible influencing factor could not be confirmed in the FT. In contrast, the duration of deafness was anegative influencing factor for SC with CI in the FT, whereas alonger duration of deafness was associated with worse results in the FT. The degree of hearing loss in the ear fitted with an HA did not influence SC. The median bimodal benefit (here: difference in SC with bimodal fitting compared to unilateral HA fitting for FT at 65 dB SPL) was 10% over the total study period. For amedian of 79% of the test subjects, the bimodal benefit was found over the entire period of 36months. Over time, SC improves significantly with aCI for the bimodal test subjects. The investigated influencing factors (age, duration of deafness, and degree of hearing loss in the contralateral ear) support the indication for bimodal provision in accordance with the guideline in Germany for cochlear implantation-regardless of age, duration of deafness, and hearing ability of the contralateral ear.

Phosphatidylserine-Dependent Anti-prothrombin Antibodies as a Key Predictor for Systemic Lupus Erythematosus in Patients with Primary Antiphospholipid Syndrome: A retrospective longitudinal cohort study.

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder characterized by thrombosis and pregnancy morbidity. Although PAPS is distinct from systemic lupus erythematosus (SLE), the two conditions share clinical features and susceptibility genes. Progression from PAPS to SLE is well-recognized. However, risk factors for this transition are poorly understood. We aimed to identify predictors of progression to SLE in patients with PAPS. A longitudinal single-center study was conducted at Hokkaido University Hospital from 1990 to 2021. Baseline characteristics including clinical features, laboratory data, aPL profiles were compared between patients who progressed to SLE (SLE group) and those who did not (non-SLE group). Among 64 patients diagnosed with PAPS at baseline, nine (13.8%) progressed to SLE over a mean follow-up of 9 years (incidence rate, 1.61 per 100 person-years). At the diagnosis of PAPS, the SLE group had a higher prevalence of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-dsDNA antibodies compared to the non-SLE group. Other clinical findings, autoantibody profiles, and serum complement levels were similar between the two groups. Multivariate Cox analysis showed that IgG aPS/PT was significantly associated with SLE development (Hazard ratio: 10.3, 95% CI: 1.13-92.6, p=0.04). IgG aPS/PT may be a predictive factor for new-onset SLE in patients with PAPS, suggesting its utility in guiding risk stratification and monitoring strategies for these patients.

Validation of histopathological chronicity scores in native kidney biopsies using light microscopy and digital morphometry for predicting renal outcome

Quantitative assessment of chronicity changes in native kidney biopsies offer valuable insights in to disease prognosis, despite the strength of qualitative information. Yet, standardization and reproducibility remain challenging. The present study aims to assess and compare the prognostic utility and reproducibility of two chronicity scoring systems based on light microscopy and whole slide imaging with morphometry and also to evaluate the prognostic utility of structural measurements: cortical non-sclerotic glomerular (NSG) density and NSG area/volume. We designed a retrospective longitudinal study involving 101 adult and paediatric patients who underwent native kidney biopsies. Chronicity scoring was performed using two semi-quantitative methods: Method 1 (method proposed in PMID: 28314581) and Method 2 (method proposed in PMID: 32516862), under light microscopy as well as on whole-slide scanned images, and assessed for prognostic utility. Kidney-Failure-Risk-Equation (KFRE) was employed in combination with chronicity-scoring-methods and assessed for predictive capability. Interobserver reproducibility for the two chronicity methods was studied among three renal pathologists. Structural measurements were performed on whole-slide- scanned-images. Both the chronicity scoring methods significantly predicted decline in estimated glomerular filtration rate (eGFR) and persistent need for renal replacement therapy in follow-up. Method 1 combined with KFRE, outperformed Method 2 in predicting renal survival. Method 2 however showed higher interobserver reproducibility. Combined KFRE plus histopathological scoring methods showed better predictive accuracy. The study validates the precision of chronicity scoring using whole slide scanned images. The morphometric structural measurements showed significant correlations with follow-up eGFR, thereby providing supplementary prognostic information.

Accuracy of MSBase criteria to diagnose secondary progressive multiple sclerosis in large German real-world patient cohort

Background and ObjectivesAccurate diagnosis of secondary progression in multiple sclerosis (MS) remains a challenge since standardized criteria are missing. In 2016, the MSBase registry presented an algorithm that enabled the diagnosis of secondary progressive multiple sclerosis (SPMS) more than three years earlier compared to diagnosis by neurologists. This work aimed to test whether this approach is equally effective in a real-world cohort of MS patients. MethodsThis longitudinal retrospective study analyzed clinical data of outpatients with MS recorded until October 2020 in the NeuroTransData registry, a Germany-wide network of 153 certified neurologists. Patient data had been captured in time during clinical visits employing a defined standardized clinical data set in the webbased NeuroTransData patient management platform DESTINY®. The time between the diagnosis of relapsing-remitting multiple sclerosis (RRMS) to SPMS onset was compared with one determined using MSBase criteria (MSBC). Group 1 consisted of patients diagnosed with SPMS during the observation period, whereas group 2 included RRMS patients who did not convert to SPMS during the observation period. ResultsOf 21,281 patients with MS included in our registry, 194 and 9506 patients were allocated to groups 1 and 2, respectively. 10.3% of patients with RRMS were diagnosed with SPMS simultaneously, whereas 60.8% were diagnosed with SPMS at least 3 months earlier by treating neurologists compared to the MSBC. In group 1, the MSBC showed a low sensitivity of 32.0% and an accuracy of 61.4% but a high specificity of 89.6%. In group 2, the MSBC identified 7.8% of patients with SPMS at some point during the observation time. Moreover, test-retest variability remains a challenge since 29.4% of patients diagnosed with SPMS by treating physicians did not fulfil the MSBC at a later point in time. DiscussionThese results are inconsistent with earlier SPMS diagnosis using the MSBC compared to clinical diagnosis by treating physicians. Therefore, there remains a need for an operational, structured, and validated approach to SPMS diagnosis.

Long-term effects of COVID-19 pandemic on physical activity and eating behaviour of the Italian population: a longitudinal study.

Restrictive measures due to the Covid-19 pandemic strongly impacted lifestyle and daily behaviour. The purpose of this longitudinal retrospective study was to investigate short-term and long-term effects of Covid-19 pandemic on physical activity and eating habits of the Italian population investigating three time periods: pre-, during- and post-lockdown. A sample of 2773 adults recruited through social media provided data by an online survey administered from July to October 2023. Participants completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Mediterranean Diet Adherence Screener (MEDAS) and provided information about eating habits, socio-demographic and anthropometric characteristics. There was a significant increase (p < 0.001) in mean BMI from pre-pandemic period (24.53 ± 5.34 Kg/m2) to post-pandemic period (25.22 ± 6.0 Kg/m2). Physical Activity significantly decreased during the pandemic period compared to the pre-pandemic period (χ² = 271.97; p < 0.001; φ = 0.31) with an increase in inactive subjects from 25.7% to 52.8%. In the post pandemic period, there was an increase in the level of Physical Activity compared to the pandemic period (χ² = 413.61; p < 0.001; φ = 0.39) with a reduction of inactive subjects from 52.8% to 25.6%. Adherence to Mediterranean Diet score significantly (p < 0.001) increase from pre-pandemic (7.18 ± 1.58) to during-pandemic (7.29 ± 1.69) and post-pandemic (7.75 ± 1.63) periods with significant differences emerged in the consumption of single MEDAS items during the pandemic period by different BMI classes. Consumption of seasonal fruit and vegetables, water intake, the preparation/consumption of traditional or local dishes and the time dedicated for dinner and lunch significant increase (p < 0.001) during pandemic. The Covid-19 pandemic changed people's lifestyles, but in different ways for Physical Activity and diet. During the pandemic there was a negative effect for PA that decreased while the time spent sitting increased. This seems to be a temporary effect as, after the end of the phase of mandatory restrictions, it returns to the original level. The lockdown period improved the quality of the Italian population's eating habits, with an increase in adherence to the Mediterranean diet even after the end of the pandemic showing a rediscovery of traditional dishes, increase in consumption of seasonal products, greater preference for local products and more time spent preparing meals.

DiffErential attainment and Factors AssoCiated with Training applications and Outcomes (DE FACTO) study: Trauma & Orthopaedic surgery in the UK.

The aims of this study were to describe the demographic, socioeconomic, and educational factors associated with core surgical trainees (CSTs) who apply to and receive offers for higher surgical training (ST3) posts in Trauma & Orthopaedics (T&O). Data collected by the UK Medical Education Database (UKMED) between 1 January 2014 and 31 December 2019 were used in this retrospective longitudinal cohort study comprising 1,960 CSTs eligible for ST3. The primary outcome measures were whether CSTs applied for a T&O ST3 post and if they were subsequently offered a post. A directed acyclic graph was used for detecting confounders and adjusting logistic regression models to calculate odds ratios (ORs), which assessed the association between the primary outcomes and relevant exposures of interest, including: age, sex, ethnicity, parental socioeconomic status (SES), domiciliary status, category of medical school, Situational Judgement Test (SJT) scores at medical school, and success in postgraduate examinations. This study followed STROBE guidelines. Compared to the overall cohort of CSTs, females were significantly less likely to apply to T&O (OR 0.37, 95% CI 0.30 to 0.46; n = 155/720 female vs n = 535/1,240 male; p < 0.001). CSTs who were not UK-domiciled prior to university were nearly twice as likely to apply to T&O (OR 1.99, 95% CI 1.39 to 2.85; n = 50/205 vs not UK-domiciled vs n = 585/1,580 UK-domiciled; p < 0.001). Age, ethnicity, SES, and medical school category were not associated with applying to T&O. Applicants who identified as 'black and minority ethnic' (BME) were significantly less likely to be offered a T&O ST3 post (OR 0.70, 95% CI 0.51 to 0.97; n = 165/265 BME vs n = 265/385 white; p = 0.034). Differences in age, sex, SES, medical school category, and SJT scores were not significantly associated with being offered a T&O ST3 post. There is an evident disparity in sex between T&O applicants and an ethnic disparity between those who receive offers on their first attempt. Further high-quality, prospective research in the post-COVID-19 pandemic period is needed to improve equality, diversity, and inclusion in T&O training.

Epicardial and liver fat implications in albuminuria: a retrospective study

BackgroundAlbuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status.MethodsA retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome.ResultsAfter a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]).ConclusionsIdentification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.

Variability in Disease Severity Among Cystic Fibrosis Patients carrying Residual Function Variants: Data from the European Cystic Fibrosis Society Patient Registry

BackgroundCystic Fibrosis (CF) variants that exhibit residual function (RF) of the CF transmembrane conductance regulator (CFTR) are considered to have a milder disease, however, the spectrum of CF phenotype within the different RF variants has not been extensively investigated.AimTo characterise the spectrum of CF disease severity in people with CF (pwCF) carrying different RF variants, using the European CF Society Patient Registry (ECFSPR) data.MethodsA retrospective cross-sectional and longitudinal cohort study included data from the ECFSPR during 2008–2016. Demographic and clinical characteristics of pwCF carrying different RF variants were compared to pwCF homozygous for F508del. Among RF, a distinction was made between pwCF carrying class IV or class V variants and pwCF carrying specific RF variants.ResultsOut of 56 701 pwCF in the ECFSPR, 6192 carried RF variants and 22 766 were homozygous for F508del. Class IV/F508del variants were associated with a milder course compared to class V/F508del, both were milder than pwCF homozygous for F508del. FEV1pp declined already in childhood in all groups. For adults, the hazard ratio of death for class V/F508delversusClass IV/F508del was 2.14 (0.99–4.63, p=0.052). PwCF carrying 3849+10kbC&gt;T/F508del and pwCF carrying R334W/F508del had age-specific FEV1pp and chronic bacterial colonisation similar to pwCF homozygous for F508del.ConclusionThere is a wide spectrum of disease severity between the different RF variants, while some such as 3849+10kbC&gt;T have a a severe disease, which is similar to pwCF homozygous for F508del.

Retrospective Longitudinal Observational Study on the Long-Term Effects of Sodium-Glucose Cotransporter-2 Inhibitors on the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetic Japanese Patients.

Background/Objectives: The health burden of metabolic dysfunction-associated fatty liver disease (MASLD) has been increasing lately. Cardiovascular disease (CVD) is the main cause of death in MASLD patients; therefore, the treatments for MASLD should improve both CV risk factors such as obesity, diabetes, and dyslipidemia, in addition to an improvement in liver function. The evidence on the long-term effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on the progression of MASLD in Asian populations is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at our institute. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between 1 April 2014 and 31 March 2018. We collected the data on metabolic parameters, including laboratory data and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. Three-year SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein cholesterol, triglyceride, and non-high-density lipoprotein cholesterol (non-HDL-C). Such favorable changes in serum lipids were remarkable in patients with statins. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Risk factors for prolonged length of hospital stay following elective hip replacement surgery: a retrospective longitudinal observational study

ObjectivesOur aim was to identify which patients are likely to stay in hospital longer following total hip replacement surgery.DesignLongitudinal, observational study used routinely collected data.SettingData were collected from an NHS...