Prospective Observational Cohort Study Research Articles

Prospective observational cohort study of the change of the marginal bone crest in relation to the prosthetic abutment height and the peri-implant vertical mucosal thickness at implants positioned subcrestally.

To evaluate the influence on peri-implant crestal bone loss exerted by the vertical mucosal thickness and the abutment height over 12 months after placement of the restoration on subcrestal implants with change of platform, using a restoration abutment platform smaller than the implant platform. A total of 99 implants were rehabilitated in the maxillary and mandibular posterior regions. A total of 22 implants were rehabilitated in the maxilla and 77 implants in the mandible, using digitally designed customized abutments with Atlantis weborder software, from the commercial house Dentsply Sirona (Dentsply Sirona S.A., Barcelona, Spain), version 4.6.5, adapting the height to the vertical thickness of the mucosa. Clinical and radiographic monitoring begins during the surgical procedure of placement of the implant and ends 12 months afterwards. Crestal bone loss was evaluated through the Carestream® CS8100 3D radiographic equipment. In all cases, the greatest loss of marginal bone occurred between the day of surgery (Tx) and placement of the rehabilitation (To). The average bone loss between both times was greater when the abutment height and vertical mucosal thickness did not exceed 3 mm. Subsequently, bone loss slowed and stabilized at 12 months. The minimum abutment height and the vertical mucosal thickness are factors to take into account when minimizing peri-implant marginal bone loss, the abutment height having the greatest importance according to the clinical data obtained.

Measuring pain or discomfort during routine nursing care in lightly sedated mechanically ventilated intensive care patients: A prospective preliminary cohort study

BackgroundPain is routinely measured on mechanically ventilated ICU patients. However, the tools used are not designed to discriminate between pain and non-pain discomfort, a distinction with therapeutic implications. ObjectivesTo evaluate whether clinical measurement tools can discern both pain and non-pain discomfort. MethodsA prospective observational cohort study was conducted in a General ICU at a tertiary Medical Center in Israel. The Behavior Pain Scale (BPS) and Visual Analog Scale (VAS) of Discomfort were simultaneously assessed by a researcher and bedside nurse on thirteen lightly sedated patients during 71 routine nursing interventions in lightly sedated, mechanically ventilated, adult patients. Patients were asked whether they were in pain due to these interventions. ResultsStatistically significant increases from baseline during interventions were observed [median change: 1.00 (-1–5), 1.5(-4–8.5), p < 0.001] as measured by BPS and VAS Discomfort Scale, respectively. BPS scores ranged between 4 and 6 when the majority (53 %) of the patients replied that they had no pain but were interpreted by the clinicians as discomfort. Endotracheal suctioning caused the greatest increase in BPS and VAS, with no statistically significant differences in BPS and VAS Discomfort Scale scores whether patients reported or did not report pain. A BPS>6 had a higher sensitivity and specificity to reported pain (accuracy of 76 %) compared to a BPS of 4–6. ConclusionsStandard assessments are sensitive to pain caused by routine nursing care interventions. However, this study presents evidence that among lightly sedated ICU patients, moderate BPS scores could also measure non-pain discomfort. ICU nurses should be aware that signs of unpleasantness measured by a pain scale could reflect non-pain discomfort.

CAUSES OF CHRONIC PAIN UNRELATED TO SURGICAL TRAUMA AFTER GROIN HERNIA REPAIR: A PROSPECTIVE COHORT STUDY

Abstract Background Chronic inguinal pain (CIP) can be caused by several factors including musculoskeletal or neurological pathologies as well as by surgical trauma following groin hernia repair. The principal aim of this prospective cohort observational study was to find the incidence and causes of CIP unrelated to surgical trauma 12 months after inguinal hernia repair. Method During sixteen months patients consulting a hernia center for groin-related symptoms were included in the study. Patients were physically evaluated by surgeons and filled out an Inguinal Pain Questionnaire and a Numerical Rating Scale pain-questionnaire. For patients undergoing groin hernia repair, postoperative questionnaires similar to the pre-operative ones were sent out at 12 months. Patients scoring pain on postoperative questionnaires were reevaluated by phone consultation and physical examination. Results 289 patients (78.1%) of 370 repaired patients filled in the postoperative questionnaires. 62 (21.4%) patients scored pain, of these patients 5 (1.7%, 5/289) answered incorrectly in the pain questionnaires and 14 (4.8%, 14/289) had non-surgical trauma causes of pain: 5 musculoskeletal, 4 neurological and 3 other medical pathologies. Conclusion This cohort study found CIP unrelated to surgical trauma in 4.8 % of patients undergoing a groin hernia repair. Most causes of pain unrelated to surgical trauma were musculoskeletal and neurological pathologies. Nearly a third of patients scoring groin pain on pain-questionnaires did not have chronic post-operative pain (CPSP), therefore incidence of CPSP should not be based solely on pain questionnaires. Clinical assessment of patients with pain is necessary to excluded CIP unrelated to surgical trauma.

Multidimensional frailty in elderly emergency department patients: unveiling the prevalence and significance of social frailty.

This study aimed to assess the prevalence and factors of physical, psychological, and social frailty among older adults in the emergency department, comparing these data with community population to understand emergency setting manifestations. Conducted at the Emergency Department of National Taiwan University BioMedical Park Hospital, this prospective observational cohort study enrolled older adult patients over a three-month period. Frailty assessments included the Study of Osteoporotic Fractures scale for physical frailty, the Tilburg Frailty Indicator for psychological frailty, and the Makizako Social Frailty Index for social frailty. Data analysis involved a multivariable logistic model to determine the risk factors associated with each frailty type. Out of 991 older adult individuals seeking medical care, 207 participated in the study. The study found high prevalence rates of frailty: 46.38% for physical, 41.06% for psychological, and 48.79% for social frailty. Risk factors for frailty included older age and a history of falls. Interestingly, the prevalence of social frailty was notably higher than physical and psychological frailty. Gender and polypharmacy showed no significant association with any frailty type. This research reveals high physical, psychological, and social frailty among older ED patients, especially noting social frailty's prevalence. It highlights the importance for emergency care to adopt holistic care strategies that address older adults' multifaceted health challenges, suggesting a paradigm shift in current healthcare practices to better cater to the multifaceted needs of this vulnerable population.

Assessment of disease pattern and drug utilization among neurology intensive care unit patients in a developing country: an observational analysis

ABSTRACT Objective This study aimed to assess the disease pattern and drug utilization among admitted patients in a tertiary-care hospital’s neuro ICU. Methods A prospective observational cohort study was conducted between August 2022 and January 2023. Patients of any age and gender admitted to the neuro ICU were included, but those who declined to participate were excluded. Demographics, clinical, and medication details were consistently gathered and maintained until discharge. The World Health Organisation (WHO)/International Network of Rational Use of Drugs (INRUD) prescribing indicators and the Anatomical Therapeutic Chemical (ATC) classification/Defined Daily Dose (DDD) system were used to evaluate drug use. Results A total of 516 patients were included, predominantly male (65.1%), with an average age of 54.6 ± 15.07 years. The most common diagnosis was stroke (72.3%), followed by seizure disorders (6.6%), and central nervous system infections (5.4%). Patients received an average of 7.8 medications, 32.3% prescribed by generic name, 16.0% antibiotics, 74.1% injection, and 100% essential drugs. A (28.5%), C (19.2%), N (17.3%), J (19.2%), B (13.5%), and R (2.3%) were commonly prescribed ATC classes of medications. Number of DDDs was maximum for pantoprazole, and furosemide. Based on discharged status, 41.0% were discharged on request, 24.8% against medical advice, 23.8% routine, and 10.2% mortality during hospitalization. Conclusion Our study reveals a high prevalence of hemorrhagic stroke, especially among men, diverging from global ischemic stroke trends. Irregular hypertension treatment is the primary cause, exacerbated by low healthcare knowledge in rural areas, where patients often discharge themselves due to socioeconomic reasons. Urgent public awareness campaigns and further research are needed to address this elevated hemorrhagic stroke incidence.

Management and Outcomes of Pulmonary Artery Hypertension and Eisenmenger Syndrome During Pregnancy: A Prospective Observational Cohort Study

(BJOG. 2023;130(10):1258–1268) Pregnancies complicated by pulmonary arterial hypertension (PAH) and Eisenmenger syndrome often result in severe maternal and fetal morbidity and mortality. Clinicians often counsel women with these conditions to avoid pregnancy or terminate a pregnancy. Multidisciplinary specialty centers, however, have seen good outcomes in these high-risk women and their babies.

Immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV in the Netherlands.

We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH). Prospective observational cohort study. PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those < 45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1:2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses, and cytokine responses up to 180 days post-vaccination. Forty PWH received mRNA-1273.214 (N = 35) or BNT162b2 (N = 5) following mRNA-based (N = 29) or vector-based (N = 11) primary vaccination. PWH were predominantly male (87% vs 26% of non-PWH) and median 57 years (interquartile range [IQR] 53-59). Their median CD4+ T-cell count was 775 (IQR 511-965) and the plasma HIV-RNA load was < 50 copies/mL in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH (4.48, 95% confidence interval [CI] 3.24-6.19) and non-PWH (4.07, 95% CI 3.42-4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. IFN-γ, IL-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH. A bivalent BA.1 booster vaccine was immunogenic in well-treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities

BackgroundCardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes.MethodsThis is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied.ResultsMean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed.ConclusionYoung adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D.Trial Registration: ISRCTN91419926.

Cardiopulmonary Resuscitation Without Aortic Valve Compression Increases the Chances of Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest: A Prospective Observational Cohort Study.

Following current cardiopulmonary resuscitation (CPR) guidelines, which recommend chest compressions at "the center of the chest," ~50% of patients experiencing out-of-hospital cardiac arrest (OHCA) undergo aortic valve (AV) compression, obstructing blood flow. We used resuscitative transesophageal echocardiography (TEE) to elucidate the impact of uncompressed vs. compressed AV on outcomes of adult patients experiencing OHCA. Prospective observational cohort study. Single center. This study included adult OHCA patients undergoing resuscitative TEE in the emergency department. Patients were categorized into AV uncompressed or AV compressed groups based on TEE findings. None. The primary outcome was sustained return of spontaneous circulation (ROSC). The secondary outcomes included end-tidal co2 (Etco2) during CPR, any ROSC, survival to ICU and hospital discharge, post-resuscitation withdrawal, and favorable neurologic outcomes at discharge. Additional analyses on intra-arrest arterial blood pressure (ABP) were also conducted. The sample size was pre-estimated at 37 patients/group. From October 2020 to January 2023, 76 patients were enrolled, 39 and 37 in the AV uncompressed and AV compressed groups, respectively. Intergroup baseline characteristics were similar. Compared with the AV compressed group, the AV uncompressed group had a higher probability of sustained ROSC (53.8% vs. 24.3%; adjusted odds ratio [aOR], 4.72; p = 0.010), any ROSC (56.4% vs. 32.4%; aOR, 3.30; p = 0.033), and survival to ICU (33.3% vs. 8.1%; aOR, 6.74; p = 0.010), and recorded higher initial diastolic ABP (33.4 vs. 11.5 mm Hg; p = 0.002) and a larger proportion achieving diastolic ABP greater than 20 mm Hg during CPR (93.8% vs. 33.3%; p < 0.001). The Etco2, post-resuscitation withdrawal, and survival to discharge revealed no significant intergroup differences. No patients were discharged with favorable neurologic outcomes. Uncompressed AV seemed critical for sustained ROSC across all subgroups. Absence of AV compression during OHCA resuscitation is associated with an increased chance of ROSC and survival to ICU. However, its effect on long-term outcomes remains unclear.

The association of fecal incontinence, constipation, and pelvic pain with the course of lower urinary tract symptoms in community-dwelling men and women.

Fecal incontinence, constipation, and pelvic pain are common pelvic floor symptoms (PFS), and frequently coexist with lower urinary tract symptoms (LUTS). However, their association with the longitudinal trajectory of LUTS have not been well described. Our objective was to investigate the association between PFS and the course of LUTS in community-dwelling men and women. Men and women aged ≥16 years were invited to participate in a prospective observational cohort study. At baseline, and after 12 and 24 months, participants filled in the International Consultation on Incontinence Modular Questionnaire (ICIQ-MLUTS and ICIQ-FLUTS) for men and women respectively, the Wexner incontinence and constipation scale, and a questionnaire on pelvic pain. Generalized estimating equations were used to examine the association between change scores in defecation problems and pelvic pain, and LUTS change scores. A total of 694 men and 997 women gave informed consent, with 417 men and 566 women included in the analysis. The mean age was 63.2 ± 12.7 years for men and 58.6 ± 14.8 years for women. The study showed minor changes in LUTS scores over the 0-12 and 12-24-month periods. Generalized estimating equations revealed positive associations between changes in constipation and fecal incontinence and LUTS changes in both sexes. For instance, a one-point increase in Wexner constipation score was associated with 0.376 (0.165, 0.587) points higher LUTS change in men and 0.223 (0.109, 0.336) points in women during the 0-12-month follow-up. However, associations between changes in pain and LUTS scores varied across sexes and time periods. We observed minor changes in LUTS over time and weak associations between PFS and LUTS that sometimes differed between males and females, emphasizing the need for sex-specific considerations. These insights can provide valuable guidance for the development of targeted prevention trials, ultimately aiming to enhance overall pelvic health and patient well-being.

#2143 Unveiling key factors on arteriovenous fistulas maturation—a prospective observational study

Abstract Background and Aims The incidence of patients starting haemodialysis is increasing. While Arteriovenous Fistula (AVF) stands as the preferred vascular access method, a significant proportion of AVFs experience primary failure, with rates ranging from 20% to 65%. Moreover, around 50% require reintervention due to delayed maturation, resulting in increased costs and patient morbidity. Understanding the factors involved and their influence on AVF development is paramount. This analysis aims to improve the preoperative decision-making process, advocating for a personalized patient approach, thereby increasing the likelihood of success. Method A prospective observational cohort study that included patients with chronic kidney disease either on dialysis or in the pre-dialysis stage. The study enrolled a total of 140 patients attending a multidisciplinary team appointment (including a vascular surgeon and a nephrologist) at a Tertiary Hospital Centre during the first semester of 2023, of whom 98 patients were included. Demographic characteristics, comorbidities, and vascular parameters observed through ultrasound underwent a comprehensive analysis. The newly formed fistulas were then thoroughly reassessed for maturation using both physical and ultrasound examinations. Results The cohort comprised 56.1% male, with a mean age of 71.06 ± 12.51 years. Among the newly formed fistulas, there were 35.7% (n = 35) radiocephalic fistulas, 46.9% (n = 46) brachiocephalic fistulas, and 17.3% (n = 17) brachiobasilic fistulas. Out of the total 98 AVFs, 59.2% (n = 58) AVFs were maturate and 11.22% (n = 11) AVFs had delayed maturation and were proposed for surgery or angiography procedure. Primary failure occurred in 29.6% (n = 29) AVF, with 42.9% (n = 15) occurring in the forearm, and 22.2% (n = 14) in the upper arm. The major cause of primary failure was thrombosis, accounting for 93.1% (n = 27) of cases. The analysis unveiled that the absence of immediate post-operative thrill, forearm AVFs and previous fistula failure were associated with a higher likelihood of AVF primary failure and non-maturation. Conversely, a larger vein diameter was linked with a reduced likelihood of AVF primary failure, with a Youden Index-derived cut-off of 4.25 mm, with 40.9% sensitivity and 86.2% specificity (p &amp;lt; 0.05). No other clinical or ultrasound factors exhibited a statistically significant impact. Conclusion This study sheds light on the challenges faced in AVF maturation due to a high incidence of primary fistula failure and a maturation rate that only slightly surpasses 50%. A larger vein diameter emerges as a significant predictor of AVF maturation. Although the cut-off point for vein diameter is frequently cited as 2 mm, this value often varies in the literature. This study underscores the importance of considering higher vein diameters, but, more importantly, it suggests that establishing a rigid and uniform cut-off for all centres may not be beneficial. It is crucial to recognize that the optimal vascular characteristics may vary based on the unique circumstances of each centre and the specific needs and features of each patient. The lack of association between demographic parameters and comorbidities with primary failure, juxtaposed with the evidence of more susceptible patients to consecutive primary failure, underscores the need for further studies to explore the unique individual circumstances that may account for this phenomenon.

#671 Perinatal factors, age of onset, early glycaemic control, sex and the development of microvascular complications in type 1 diabetes after 30 years

Abstract Background and Aims Long-term glycaemic control and duration of disease are both well-established risk factors for the development of complications in type 1 diabetes (T1D). The effect of perinatal factors, age at onset of T1D and early glycaemic control on development of diabetic complications have not been fully evaluated. The aim of this study was to investigate the long-term impact of such factors in childhood-onset type 1 diabetes. Method 90 subjects diagnosed with T1D between the ages of 0-14 years were included in this prospective observational cohort study in in a geographically defined area in northern Sweden. Baseline data for these subjects have previously been reported by Svensson M et al (Diabetes Care 2004). Outcome and follow-up data was obtained during approximately 30 years of follow-up from the Swedish National Diabetes Registry (NDR). Differences between groups were assessed using independent t-test and Chi-square test. Kaplan-Meier survival curves were used to illustrate time-to-diabetic nephropathy (DN) by sex and age at onset. Multivariable logistic regression analyses were performed to evaluate the influence of risk factors of interest on the development of DN, assessed as any degree of albuminuria without signs of other underlying conditions. Results Forty-one subjects (46%) developed any degree of DN during the follow-up period of mean 33 (range 19-40) years after T1D onset. Moreover, 80 subjects (89%) had any degree of retinopathy (RP) and among those, 18 (20%) had proliferative diabetic retinopathy (PDR), and 13 (4%) had both PDR and DN. Mean HbA1c during the first five and ten years after diagnosis was higher in subjects who developed DN or PDR compared to those who did not develop these complications; DN 58 ± 16 vs 51 ± 13 (p = 0.038) and 63 ± 16 vs 55 ± 11 mmol/mol (p = 0.007), respectively; PDR 60 ± 13 vs 53 ± 15 (p = 0.059) and 67 ± 10 vs 56 ± 14 mmol/mol (p = 0.002), respectively. Women had an increased risk of PDR compared to men (28% vs 11%, p = 0.045) and a near-significantly higher risk of DN (55% vs 36%, p = 0.087) (Table 1). Time to DN by sex and by age at onset are shown in Figure 1A and B. Women seemed to have a somewhat lower risk in the early years, but in the later years the risk was increased. A young age at onset of diabetes prolonged the time to development of DN but after twenty years of diabetes duration, no difference was seen. In a multivariate regression analysis, older age of gestation was negatively associated with (OR 95% CI 0.894-0.989, p = 0.017) and hyperglycaemia (higher HbA1c) during the first five years (OR 95% CI 1.004-1.078, p = 0.028) were positively and independently associated with development of DN (Fig. 1C). Conclusion Interestingly, longer gestational time at birth and, more well-known, poor early glycaemic control were associated with development of DN after 30 years of diabetes duration. However, there was no impact of age of onset or sex on the long-term risk for DN.

#1858 Delirium among patients admitted to a Nephrology ward-risk factors and association with short-term outcomes: an observational prospective cohort study

Abstract Background and Aims To date, delirium is considered one of the most frequent neuropsychiatric acute syndromes among hospitalized populations. In general medicine, the risk factors for delirium are well-established but there are limited data concerning the incidence and predictors of delirium in nephrological patients. The aims of the study were (i) to assess the prevalence and the risk factors for delirium in hospitalized patients with acute kidney injury (AKI) and chronic kidney disease (CKD), and (ii) to evaluate the effect of delirium on in-hospital mortality. Method A cohort of 942 patients admitted to the Nephrology Department of a tertiary-care Hospital from January 2023 to December 2023 were enrolled in a prospective observational study. Delirium was diagnosed by a psychiatrist during the hospitalization. The endpoint was defined as hospital death or hospital discharge. Relevant sociodemographic, nephrological- and medical-related clusters were assessed with logistic uni- and multivariable regression methods to evaluate their association with delirium and in-hospital mortality. A two-tailed value &amp;lt;0.05 was considered significant. Results In the studied group, mean age was 62.85 years, 519 (55.09%) patients being males. The prevalence of delirium was 5.41% (51/942 patients). The delirious patients were older (mean 70.04 vs. 62.44 years; P&amp;lt;0.001) and with a longer duration of hospitalization (13.12 ± 7.90 days vs. 10.76 ± 8.92 days; P=0.007). Univariable regression analysis showed that delirium was associated with age (r=0.117, P&amp;lt;0.001), alcohol abuse (r=0.144, P&amp;lt;0.001), history of stroke (r=0.184, P&amp;lt;0.001), vascular dementia (r=0.125, P&amp;lt;0.001), dehydration (r=0.175, P&amp;lt;0.001), sepsis (r=0.144, P&amp;lt;0.001), and acute kidney injury (AKI) stage 2 and 3 (r=0.155, P&amp;lt;0.001). In multivariable regression analysis, the independent predictors of delirium were: age (adjusted odds ratio (OR) 1.029, 95% confidence interval (CI): 1.002–1.056, P=0.034), alcohol abuse (OR=4.728, 95% CI: 1.968-11.359, P=0.001), history of stroke (OR=3.493, 95% CI: 1.849-6.598, P&amp;lt;0.001), and AKI stage 2 and 3 (OR=2.175, 95% CI: 1.152-4.105, P=0.017). Chronic kidney disease was not associated with a higher risk of delirium (OR=0.583, 95% CI: 0.308-1.110, P=0.097). Delirium was associated with increased in-hospital mortality (47.05% vs. no-delirium 14.36%, P&amp;lt;0.001) and was an independent predictor of in-hospital mortality (OR=3.074, 95% CI: 1.630-5.797, P=0.001). Conclusion In this study conducted on patients hospitalized in a nephrology ward age, alcohol abuse, history of stroke, and AKI stage 2 and 3 were independent risk factors for delirium. Delirium significantly increased in-hospital mortality. The findings of the study emphasize the strong connectivity between AKI and acute brain dysfunction.

#1917 SGLT2-Inhibition in patients with Alport syndrome – an international, retrospective and in parts prospective observational large cohort study

Abstract Background and Aims Large-scale trials showed positive outcomes of SGLT2-inhibitors (SGLT2i) in elderly patients with CKD. Patients with Alport syndrome, a type IV collagen disease, develop CKD early in life. Whether the use of SGLT2i is safe and effective in patients with the type IV collagen disease Alport syndrome (and thus a different pathogenesis) has not yet been investigated specifically besides case reports. Method For the first time, this observational, multicenter, international study (NCT02378805) assessed 112 patients with AS from nine countries and 21 trial sites after start of SGLT2i at early stages of their chronic kidney disease (CKD). The study's primary endpoint was change of albuminuria in albumin/g creatinine after start of therapy with SGLT2i. Results Compared to the large randomized trials investigating the effect of SGLT2i in CKD, the adult patients in this trial were much younger (38 ± 14 years; n = 101), had a better eGFR (63 ± 35 ml/min/1.73m2; n = 98) and had a higher albuminuria (1699 ± 1472 mg/g creatinine; n = 51). At a mean time on SGLT2i-therapy of 6 ± 1 months, albuminuria decreased significantly (1727 ± 1564 vs. 1203 ± 1165 mg/g creatinine; n = 33; p = 0.01). Compared to baseline, at the first three follow-up visits after initiation of SGLT2i-therapy, a significant reduction of albuminuria &amp;gt;30% was observed. Mean loss of eGFR was 9 ± 12 ml/min/1.73 m² almost one year after initiation of SGLT2i-therapy (n = 35). At a mean follow up of 12 ± 2 month after initiation of SGLT2i-therapy, serum-albumin increased significantly from 3.7 ± 0.7 to 4.0 ± 0.4 g/dL (n = 18; p = 0.019). At a total of 68 patient-years at risk, adverse events occurred in 11/85 patients (13%). Two very serious adverse events (acute necrotizing pancreatitis and Fournier's gangrene) occurred. Conclusion This study demonstrated that SGLT2i, when added to RASi, have the potential to reduce the rate of albuminuria in adult patients with Alport Syndrome. The study will be continued to provide valuable data on the long-term course of CKD under SGLT2i-therapy in AS to investigate if the promising reduction of albuminuria results in a clinical relevant delay in renal failure. This observational study successfully formed the scientific basis for the current randomized controlled trial with SGLT2i in children and young adults with AS Double Protect Alport.

#804 The nonlinear association between body mass index and chronic kidney disease: a prospective cohort study and Mendelian randomization analysis

Abstract Background and Aims Previous studies mainly focused on linear association between body mass index (BMI) and the risk of chronic kidney disease (CKD). In the current research, we conducted a prospective cohort observational study and Mendelian Randomization analysis to explore whether non-linear relationship exists between BMI and CKD. Method In the prospective cohort study, 495,465 participants from the UK biobank were included. The Cox proportional hazards model with fractional polynomial transformation was used to estimate the hazard ratio of BMI for incident CKD. In addition, nonlinear Mendelian Randomization analysis was performed using the fractional polynomial method to verify the causality of the association. Results In the observational analysis, a J-shaped association was observed between BMI and the risk of CKD. The risk of CKD was lowest when the BMI was around 18-20 kg/m2, and the hazard of developing CKD increased in participants with lower or higher BMI (Fig. 1). When assessing the causal relationship, in Mendelian Randomization analysis, despite that a nonlinear relationship still held true (P-value for non-linearity = 0.008), the odds ratio for CKD monotonically rised with increasing BMI (Fig. 2). Conclusion The J-shape association between BMI and CKD revealed by the observational cohort study was not supported by the Mendelian Randomization, which indicated a monotonically causal relationship that the risk of CKD rised with increasing BMI.

#2201 Assessment of long-term cardiovascular comorbidities in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Background and Aims ANCA associated vasculitis (AAV) is closely correlated to elevated cardiovascular disease (CVD) rates, positioning it a one of the leading causes of death among these patients. The impact of AAV on the risk of CVD has not been described in large prospective cohorts with a long-term follow up. The aim of our study was to evaluate the occurrence of cardiovascular events, encompassing major adverse cardiovascular events (MACE), to delineate associated risk factors, and to draw comparisons with other cohorts of patients diagnosed with CKD. Method We included 848 patients with a diagnosis of AAV who participated in 7 EUVAS RCTs (NORAM, CYCAZAREM, CYCLOPS, MEPEX, IMPROVE, RITUXVAS, and MYCYC), recruited from 74 centers in 17 European countries. The three-point MACE outcome was defined as acute myocardial infarction (AMI), stroke, or death from cardiovascular event. We used multivariate logistic regression analysis to assess the risk factors of MACE. Patients from our cohort were compared to the patients from the Chronic Renal Insufficiency Cohort (CRIC), which is a multicenter, prospective observational cohort study of participants with CKD. Results During the median follow up of 8 years (range 0-24.5, IQR: 2.9-13.6), 100 (11.8%) patients developed diabetes, 98 (13.4%) coronary heart disease (CHD), 90 (12.1%) hypertension, 70 (9.6%) deep vein thrombosis (DVT), 43 patients (5.9%) had a stroke and 28 (3.8%) an AMI. The number of MACE during FU was 144 (17%). MACE was more frequent among patients older than 65 years (n = 62 (43.1%); p-value: 0.013). CVD was the primary cause of death in 43 patients (14%). During the first 5 years after randomization, there was a significant increase in the number of cardiovascular events compared to the period 6 years- end of follow up (CHD: n = 55 vs n = 23, p ≤ 0.001; DVT: n = 55 vs n = 29; p &amp;lt; 0.001; stroke: n = 35 vs n = 24, p-value &amp;lt; 0.001). The prognostic factors for MACE in our cohort were hemodialysis dependency during RCT, age, male sex, previous history of CHD and stroke, and occurrence of diabetes during follow up. Within the subset of patients who underwent kidney biopsy, those in the crescentic class (n = 16) followed by the mixed class (n = 15) exhibited a significant higher incidence of MACE (p = 0.02). When compared to the cohort of patients with CKD from the CRIC study, the risk for CHD was higher (13.4% (95% CI: 11.16-16.11) vs 5.4% (95% CI 4.5-6.5); respectively; RR: 2.49 (95% CI 1.91-3.24); p-value&amp;lt;0.01). Additionally, there was a higher risk for stroke (5.6% (95% CI 4.2-7.4) vs 2.8% (95% CI 2.2- 3.7); RR 1.97 (95% CI: 1.33- 2.91) p-value: 0.0006). Conclusion Patients with AAV had an increased risk of stroke and CHD compared to patients with CKD from other etiologies. During the first years after diagnosis, there is an increased risk for CVD occurrence. The prognostic factors for MACE in our cohort were hemodialysis dependency, age, male sex, previous story of CHD and stroke, and diabetes during follow up. Patients with AAV should be considered at high cardiovascular risk; therefore, the therapeutic approach should include the management of traditional cardiovascular risk factors and lifestyle modification. Efforts should be made to meet strict therapeutic targets and to implement early CVD detection programs.

#635 Effect of multi-biomarker panels based on urinary N-terminal osteopontin on prediction of diabetic kidney disease in patients with diabetes mellitus

Abstract Background and Aims Diabetic kidney disease (DKD), occurs in 20–40% of patients with diabetes mellitus (DM), is the leading cause of end-stage renal disease (ESRD). DKD is a clinical diagnosis mainly based on the persistent albuminuria and reduced estimated glomerular filtration rate (eGFR) [1]. However, increased UACR and reduced eGFR are the final consequences due to DKD, novel biomarkers are critical for predicting DKD development. Osteopontin (OPN) is a profibrotic adhesion phosphoprotein that participates in cell chemotaxis, adhesion, migration, and proliferation, as well as extracellular matrix (ECM) hyperplasia. Hyperglycemia could enhance OPN gene expression through the activation of the renin-angiotensin system (RAS), mTOR pathway, NF-κB, and TGF-β pathway and then cause podocyte injury and ECM hyperplasia. Therefore, OPN upregulation is not only the result of various pathophysiological processes in DKD, but also results in kidney injury. Osteopontin (OPN) could predict incident DKD in DM patients [2], N-terminal OPN (ntOPN) has a stronger profibrotic adhesion effect than full-length OPN. This study aims to reveal the clinical benefit of ntOPN as a potential marker to identify DM patients at high risk of DKD, and establish ntOPN-based diagnostic and forecast models for renal outcomes in DM patients. Method We performed a cross-sectional study of 316 adults with Type 1 DM≥ 5 years or Type 2 DM, then followed by a prospective observational cohort study of 143 adult DM patients without renal involvement at baseline and follow-up for at least one year. During the follow-up period, the primary endpoint was “DKD occurrence”, defined as the presence of one of the following conditions in DM patients [3]: (1) repeat UACR ≥30 mg/g at least 2 of 3 measurements within 3 to 6 months; (2) eGFR &amp;lt;60 mL/min/1.73 m2 for more than three months; (3) renal pathological findings were consistent with DKD. The secondary endpoint was “DKD progression”, which included: (1) eGFR sustained decreased by at least 25%; (2) development of ESRD, and/or need for renal replacement therapy; (3) death from the renal cause. Logistic regression analysis was performed to analyze the relationship between parameters and the events of DKD occurrence and progression. Receiver operator characteristic (ROC) analysis was used to assess the predictive ability of established models for clinical endpoints. Results The median value of urinary ntOPN (UntOPN) was 44.15 ng/ml in the cross-sectional cohort, DKD prevalence was significantly higher in the high UntOPN group than in the low UntOPN group. The ROC curves of UntOPN, urinary neutrophil gelatinase-associated lipocalin (UNGAL), and their combination indicated that both combination and ntOPN alone perform better than UNGAL for DKD diagnosis (Fig. 1A). In the prospective cohort, UntOPN was an independent risk factor and further improved the predictive ability for DKD occurrence and DKD progression than UNGAL (Figs. 1B and 1C). Based on the parameters detected as risk factors for DKD occurrence and progression, we set up a series of multi-biomarker panels for DKD prediction using UntOPN, UNGAL, serum cystatin C, serum creatinine (Scr), UACR, and TCH/HDL-C ratio. Compared with the model of Scr + UACR, the area under ROC curve (AUC) of the six-biomarker model was higher, and also ranked the highest among the six ROC curves in predicting 1-year risk of DKD occurrence and DKD progression (Figs. 1B and 1C). Conclusion Our results showed that urinary ntOPN is associated with DKD development, and elevated urinary ntOPN is an independent predictor for DKD occurrence and progression. Compared with the traditional biomarkers of Scr + UACR, our multi-biomarker models based on urinary ntOPN performed better in predicting DKD development, which could provide more accurate tools for DKD risk prediction, thereby improving the renal prognosis in DM patients.

#2852 Iron status and incident diabetes in kidney transplant recipients

Abstract Background and Aims Kidney transplant recipients (KTR) are prone to develop post-transplant diabetes (PTD). Iron plays a role in glucose homeostasis and patients with iron overload have a high prevalence of diabetes. Since iron overload can also occur in KTR, we investigated whether levels of ferritin are associated with incident PTD in KTR. Method This is a prospective observational cohort study of adult KTR ≥1 year after transplantation of the Transplantlines Insulin Resistance and Inflammation Biobank and Cohort study. Cox regression analyses were applied to study the association of serum ferritin with incident PTD (fasting plasma glucose ≥126 mg/dL, or nonfasting plasma glucose ≥200 mg/dL combined with diabetes symptoms, or use of glucose-lowering medication). Models were adjusted for age, sex, body mass index, C-reactive protein (CRP), diabetes risk factors, transplantation factors, and immunosuppressive drugs. To explore potential clinical cut-offs of ferritin levels from which the risk of PTD might increase, categories of ferritin (&amp;lt;100, 100-300, 300-500, and &amp;gt;500 µg/L) were used in subsequent analysis. Results We included 399 KTR (age 51 [IQR, 41-59 years], 54% males, and at a median of 6.1 [3.0-12.1] years after transplantation) without diabetes at baseline. During a median follow-up of 9.7 [7.6-10.3] years, 45 KTR (11%) developed PTD. In multivariable Cox regression analyses, serum ferritin levels were significantly associated with incident PTD independent of adjustment for potential confounders (Table 1, hazard ratio (HR) per 50 µg/L, 1.12; 95% CI 1.05-1.18; P = 0.0002). Furthermore, in analysis with ferritin categories, we identified that KTR with ferritin &amp;gt;500 µg/L (n = 38) had a significantly higher chance of PTD compared to KTR with ferritin between 100-300 µg /L (Fig. 1, HR, 3.66; 95% CI 1.37-9.77; P = 0.01). KTR with ferritin levels &amp;lt;100 and between 300-500 µg/L had a similar risk of PTD compared to KTR with ferritin levels between 100-300 µg/L. Conclusion Ferritin levels are associated with PTD in KTR, independent of other known diabetes risk factors, including inflammation. KTR with ferritin levels above 500 µg/L appear particularly prone to develop PTD. Further investigation should determine the underlying mechanisms and consequences of these findings with respect to target goals of ferritin levels after kidney transplantation.

D-dimer and fibrinogen indicate ischemic risk in patients with atrial fibrillation after percutaneous coronary intervention

BackgroundThis study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).MethodsIn this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1–3 after PCI. Dilute Russell’s viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-β2-Glycoprotein 1 (aβ2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis.Results158 patients were enrolled between May 2020 and May 2021 on day 1–3 after PCI. The median age was 78 years (interquartile range [IQR] 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39–5.49], p = 0.579), nor bleeding (HR 1.07 [0.30–3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09–23.41], p = 0.038) and major bleeding (HR 7.04 [1.58–31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60–0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70–0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11–11.96], p = 0.033).ConclusionBiomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.

Comparison of clinical outcomes in hospitalized patients with COVID-19 or non-COVID-19 community-acquired pneumonia in a prospective observational cohort study.

Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70]). Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.