Clinical Follow-up Study Research Articles

Comparison of two techniques in gingival recession treatment: A randomized one-year clinical follow-up study.

Gingival recession (GR) is highly prevalent in the general population and represents a significant concern for patients and clinicians. Various surgical techniques have been proposed to treat gingival recession. Well-designed trials with clinicianand patient-based parameters, evaluating the envelope connective tissue graft (E-CTG) and semilunar coronally advanced flap (SCAF) techniques are still needed. The aim of this trial was to compare the effectiveness of E-CTG and SCAF in the treatment of GR during a 1-year follow-up. A total of 42 patients with GR were treated with E-CTG (n = 20) or SCAF (n = 22). Clinician-based recordings of recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), keratinized tissue width (KTW), tissue thickness (TT), clinical attachment gain (CAG), root coverage (RC), keratinized tissue change (KTC), and wound healing index (WHI), as well as patient-based parameters of dentine hypersensitivity (DH), tissue appearance, patient expectations, and esthetics were collected at baseline (BL), 6 weeks (T 1 ), 6 months (T 2 ), and 1 year (T 3 ). After the treatment, E-CTG demonstrated better outcomes than SCAF in terms of CAG (50.70% vs. 33.33%), RC (85.60% vs. 35.60%) and KTC (1.70 ±1.49 mm vs. 0.36 ±0.96 mm) at T 3 . Similar findings were detected in terms of WHI, tissue appearance, patient expectations, and esthetics. Although inconvenient surgical experience was recorded, better results were obtained after E-CTG in terms of DH and meeting the RC expectations. Despite it being more difficult surgical experience and the risk of keloid formation, E-CTG was superior to SCAF in terms of RC percentage, reducing DH and obtaining satisfactory RC. However, it is still necessary to improve patient comfort in the case of E-CTG.

Transient modifications of the olfactory bulb on MR follow-up of COVID-19 patients with related olfactory dysfunction

Background: Olfactory dysfunction (OD) has been reported with a high prevalence on mild to moderate COVID-19 patients. Previous reports suggest that volume and signal intensity of olfactory bulbs (OB) have been reported as abnormal on acute phase of COVID-19 anosmia, but a prospective MRI and clinical follow-up study of COVID-19 patients presenting with OD was missing, aiming at understanding the modification of OB during patients'follow-up.Methods: A prospective multicenter study was conducted including 11 COVID-19 patients with OD. Patients underwent MRI and psychophysical olfactory assessments at baseline and 6-month post-COVID-19. T2 FLAIR-Signal intensity ratio (SIR) was measured between the average signal of the OB and the average signal of white matter. OB volumes and obstruction of olfactory clefts (OC) were evaluated at both evaluation times.Results: The psychophysical evaluations demonstrated a 6-month recovery in 10/11 patients (90.9%). The mean values of OB-SIR significantly decreased from baseline (1.66±0.24) to 6-month follow-up (1.35±0.27), reporting a mean variation of -17.82±15.20 % (p<0.001).The mean values of OB volumes significantly decreased from baseline (49.22±10.46 mm3) to 6-month follow-up (43.70±9.88 mm3), (p=0.006).Conclusion: Patients with demonstrated anosmia reported abnormalities in OB imaging that may be objectively evaluated with the measurement of SIR and OB volumes. SIR and OB volumes significantly normalized when patient recovered smell. This supports the underlying mechanism of a transient inflammation of the OB as a cause of Olfactory Dysfunction in COVID-19 patients.

Comparison between the rotary (Hyflex EDM®) and manual (k-file) technique for instrumentation of primary molars: a 12-month randomized clinical follow-up study.

Rotational instrumentation is an alternative for the clinical practice of pediatric dentists. However, there are few records in the literature on the clinical and radiographic aspects of treated teeth over time.Objectives:Compare instrumentation time and filling quality between manual (k-file) and rotary (Hyflex EDM®) files, and clinically and radiographically follow-up the treated teeth for 12 months. Moreover, the characteristics of glass ionomer restorations and their interference in the treatment prognosis over time were evaluated.Methodology:In total, 40 children with pulp involvement in primary molars received treatment with Hyflex EDM® or manual rotary files, performed by an operator. Clinical and radiographic aspects were observed at different times to determine the effectiveness of each technique.Results:The rotary system reduced instrumentation time when compared to the use of manual files (p≤0.05), but there was no difference in filling quality between the groups (p≥0.05). Moreover, both types of instrumentation were effective for 12 months (p≥0.05), and restoration retention influenced the emergence of periapical lesions (p≤0.05).Conclusion:Although rotary files reduce clinical time, the clinical and radiographic aspects of both techniques were similar over 12 months. Moreover, restoration retention has been shown to be related to treatment prognosis.

Automated provision of clinical routine data for a complex clinical follow-up study: A data warehouse solution.

A deep integration of routine care and research remains challenging in many respects. We aimed to show the feasibility of an automated transformation and transfer process feeding deeply structured data with a high level of granularity collected for a clinical prospective cohort study from our hospital information system to the study's electronic data capture system, while accounting for study-specific data and visits. We developed a system integrating all necessary software and organizational processes then used in the study. The process and key system components are described together with descriptive statistics to show its feasibility in general and to identify individual challenges in particular. Data of 2051 patients enrolled between 2014 and 2020 was transferred. We were able to automate the transfer of approximately 11 million individual data values, representing 95% of all entered study data. These were recorded in n = 314 variables (28% of all variables), with some variables being used multiple times for follow-up visits. Our validation approach allowed for constant good data quality over the course of the study. In conclusion, the automated transfer of multi-dimensional routine medical data from HIS to study databases using specific study data and visit structures is complex, yet viable.

Clinical follow-up study of myelin oligodendrocyte glycoprotein antibody-associated disease in children

Objective: To summarize the clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare the differences in efficacy of different disease-modifying drugs. Methods: An ambispective cohort study was conducted in 42 children diagnosed with MOGAD at Department of Pediatrics, Peking University First Hospital from January 2012 to March 2021 and conducted long-term follow-up to analyze clinical phenotypes and compare the efficacy of different disease-modifying drugs such as rituximab, mycophenolate mofetil and azathioprine. Kruskal-Wallis H test was used to compare the annual relapse rate of disease-modifying drugs at different times, expanded disability status scale (EDSS) score at the last follow-up, and Wilcoxon rank test was used to compare the annual relapse rate before and after modified disease therapy. The Log-rank (Mantel-Cox) survival curve was used to compare the relapse rate of different disease-modifying drugs. Results: Of the 42 cases, 22 were male and 20 were female, with the age at disease onset of 5.96 (2.33-12.90) years. The disease duration was 4.46 (1.25-13.00) years at the last follow-up with 161 clinical acute attacks. Acute disseminated encephalomyelitis (ADEM) was the most common phenotype of first attack and all attacks during disease course ((60% (25/42) for first attack, 38% (61/161) for all attacks). The most common clinical syndrome was neuromyelitis optica spectrum disorders (NMOSD) (50%, 21/42). Of the 42 children, 5 (12%) showed encephalitis and 6 (14%) combined with anti-N-methyl-D-aspartate receptor (NMDAR) antibody overlap syndrome. The most commonly involved areas of brain magnetic resonance imaging (MRI) were subcortical white matter (71%, 88/124), cortex (26%, 32/124) and periventricular white matter (25%, 32/124). Spinal cord MRI was most frequently involved in cervical (70%, 16/23) and thoracic (61%, 14/23) medulla, and 43% (10/23) longitudinally extensive transeverse myelitis. Disease-modifying drugs were used in 34 patients. The annual relapse rate after treatment with rituximab, mycophenolate mofetil and azathioprine decreased (all P<0.05) and there was no statistically significant difference in the annual relapse proportion among the groups (P=0.307). Conclusions: The most common clinical attack of first and all of MOGAD in children is ADEM, and the most common clinical syndrome is NMOSD. Rituximab, mycophenolate mofetil and azathioprine can reduce the annual relapse rate, but it is not clear effect of which treatment is better.

Oral clinical courses of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection: A clinical follow up (a prospective prevalent cohort) study

IntroductionContemporary literature has revealed that SARS-CoV-2 causes acute sialadenitis and related symptoms, such as discomfort, pain, swelling, and secretory dysfunction in salivary glands. The secretory dysfunction is due to SARS-CoV-2 infection-induced xerostomia and other associated clinical courses such as sore tongue, mucosal ulcer, and gingivitis in the oral cavity. Furthermore, it has been reported that COVID-19 causes the development of other oral manifestations.PurposeThis cohort study was initiated to identify the possible oral clinical manifestations of patients with SARS-CoV-2 infection admitted at Eka General Hospital COVID-19 treatment center in Addis Ababa, Ethiopia.Materials and MethodsA prospective clinical follow-up (a prevalent cohort) study was conducted to identify the possible oral manifestations of SARS-CoV-2 infection among patients admitted at the Eka General Hospital COVID-19 treatment center. Patients were followed for an average period of 3.5 weeks.ResultsThe findings of this cohort prevalent study were adjusted around the main objectives of the research. A total of 55 patients (36 males and 19 females) fulfilling the inclusion criteria were included in the cohort. The age of the cohorts ranged from 8 to 90 years. The overall prevalence of oral clinical courses in patients with SARS-CoV-2 was 0.18 (n=10). Oral mucosal lesions, xerostomia, thickening of saliva yielded prevalence data of 0.5 (n=6), 0.42 (n=5), and 0.08 (n=1), respectively. The oral mucosal lesions prevalence finding was further refined into aphthous lesions 0.5 (n=3), candidiasis 0.17 (n=1), geographic tongue 0.17 (n=1), and localized gingivitis 0.17 (n=1).ConclusionThe findings of the study suggest the importance of initiating oral health care for patients with COVID-19. Therefore, multidisciplinary healthcare approaches to management should be promoted to assure optimal health outcomes. Accordingly, oral health care should be a substantial part of the multidisciplinary approach.

Abstract 12893: Early- and Delayed-Afterdepolarizations as Cellular Promoter of Ventricular Fibrillation in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) represents the main cause of sudden cardiac death (SCD) due to ventricular fibrillation in young adults. Recent data suggest that enhanced cellular automaticity as early- and delayed-afterdepolarizations (EADs and DADs) could represent a major trigger of arrhythmogenesis in HCM. Hypothesis: To deeper understand the cellular mechanisms of arrhythmogenesis and to establish an arrhythmic rysk stratification in HCM patients, we performed a translational and retrospective study in 61 HCM patients who underwent surgical interventricular-septum myectomy to relieve refractory obstruction-related symptoms, combining a clinical follow-up study with in vitro assessment of ventricular myocyte arrhythmogenicity. Methods: At the time of surgery, fresh ventricular tissue was collected and used to isolate single ventricular cardiomyocytes, which were then used to perform patch clamp experiments, to assess the occurrence of EADs and DADs. HCM patients were followed up for a median time of 8 years, monitoring the occurrence of non-sustained ventricular tachycardia (NSVT) or life-threatening arrhytmic events (LAE, including sustained VT and VF). Results: Our data show that EADs occurred in 36% of patients (22/61) and were correlated to a prolongation of action potential duration (due to larger I Nal and I CaL density), while DADs occurred in 27% of patients and were associated to an impairment of Ca 2+ handling. During follow up, NSVT events occurred in 19/62 patients, while LAE occurred in 4/62 patients (combined occurrence 37%). Moreover, patients with NSVT/LAE were more likely to show specific "pro-arrhythmic" ECG-patterns. The occurrence of NSVT/ LAE was strongly associated with the presence of DADs in cells but not with the presence of EADs. Interestingly, the occurrence of DADs in cells was also associated with the presence of "proarrhythmic" ECG-patterns. Conclusions: The presence of cellular triggers as DADs, related with changes of ion channels and intracellular calcium homeostasis, appear to be necessary for arrhythmia generation in HCM. Such pro-arrhythmic changes seem to be linked with specific alterations at ECG level, that might be used as clinical arrhythmia predictors in HCM patients.

The Influence of Lymph Node Count on Oncological Outcome of Radical Cystectomy in Chemotherapy Pre-Treated and Chemotherapy-Naïve Patients with Muscle Invasive Bladder Cancer.

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). The extent of PLND and number of removed lymph nodes (LNs) have been associated with improved staging and survival outcomes in several series of RC patients. Neoadjuvant chemotherapy (NAC) has become standard of care for cisplatin-eligible patients qualified to RC, yet few studies on PLND stratified cases according to the receipt of NAC. We aimed to address this issue and reevaluate the prognostic value of PLND nodal yields in series of patients who underwent RC on the verge of the NAC era. This single-center, retrospective, clinical follow-up study enrolled 439 consecutive patients, out of whom 83 received NAC. We analyzed survival outcome of RC according to the number of removed nodes between NAC and non-NAC subgroups. We found PLND thresholds of 10 and 15 LNs prognostically meaningful in our study cohort, and this association was particularly pronounced in the non-NAC subgroup. Higher numbers of LNs provided a 25% reduction in risk of all-cause mortality and correspondingly correlated with up to a 14% increase in 3-year overall survival. The receipt of NAC diminished the benefit of adequate PLND, as the number of retrieved LNs was not associated with survival in the NAC-RC cohort. Given the limitations of our study, additional research is needed to verify these findings.

Cellular determinants of arrhythmic rysk in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiac disease, with a prevalence of 1/500 in the general population. The most devastating consequence of HCM is sudden cardiac death (SCD) due to ventricular fibrillation, particularly common in children and young adults (age &amp;lt;30 years). The positive correlation between the extent of late gadolinium enhancement (LGE, reflecting myocardial fibrosis) and the arrhythmic risk in HCM suggests that ventricular arrhythmias are held to originate from the fibrotic regions, by a mechanism of electrical re-entry. However, recent data suggest that enhanced cellular automaticity (i.e. early- or delayed-afterdepolarizations, EADs or DADs-), rather than macro-reentry, may be clinically relevant in promoting ventricular arrhythmias in patients. Purpose Aiming to better understand the cellular and molecular mechanisms of arrhythmogenesis in HCM and to establish a reliable arrhythmic risk stratification in patients, we performed a translational study in HCM patients who underwent surgical myectomy, by combining a clinical follow-up study with in vitro assessments of cellular arrhythmogenicity in ventricular cardiomyocytes. Methods We retrospectively studied 61 HCM patients who underwent surgical interventricular-septum myectomy to relieve refractory obstruction-related symptoms. At the time of surgery, fresh ventricular tissue was collected and used to isolate single ventricular cardiomyocytes (CMs), which were used for patch-clamp measurements to assess the occurrence of EADs and DADs. Patients were followed up for a median time of 8 years and the occurrence of non-sustained ventricular tachycardia (NSVT) or life-threatening arrhythmic events (LAE) was monitored. Moreover, data from ECG and contract cardiac magnetic-resonance studies were collected. Results EADs occurred in CMs from 36% of patients and were associated with prolonged action potential duration. DADs occurred in 24% of patients and were associated with abnormalities of CM intracellular Ca2+ handling. The occurrence of NSVT/ LAE in patients was strongly associated with the presence of DADs in cardiomyocytes but not with the presence of EADs. Patients with NSVT/LAE were more likely to show specific “pro-arrhythmic” pathological ECG-patterns. Among patients with LGE, the presence of DADs in cells behaved as a necessary pre-requisite for NSVT/LAE, as none of the patients with evidence of fibrosis who were negative for DADs had arrhythmic events. Conclusions The presence of pro-arrhythmic changes appears to be necessary for arrhythmia generation in HCM and seems to be related with specific alterations at ECG level, that might be used as clinical arrhythmia predictors in HCM patients. Fibrosis per se is not a major predictor of arrhythmias in HCM but may contribute to generate sustained arrhythmias in the presence of substantial cellular triggers (DADs). Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020. Grant number 777204 (silico FCM).

Tick-transmitted co-infections among erythema migrans patients in a general practice setting in Norway: a clinical and laboratory follow-up study

BackgroundErythema migrans (EM) is the most common manifestation of Lyme borreliosis. Here, we examined EM patients in Norwegian general practice to find the proportion exposed to tick-transmitted microorganisms other than Borrelia, and the impact of co-infection on the clinical manifestations and disease duration.MethodsSkin biopsies from 139/188 EM patients were analyzed using PCR for Neoehrlichia mikurensis, Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Follow-up sera from 135/188 patients were analyzed for spotted fever group (SFG) Rickettsia, A. phagocytophilum and Babesia microti antibodies, and tested with PCR if positive. Day 0 sera from patients with fever (8/188) or EM duration of ≥ 21 days (69/188) were analyzed, using PCR, for A. phagocytophilum, Rickettsia spp., Babesia spp. and N. mikurensis. Day 14 sera were tested for TBEV IgG.ResultsWe detected no microorganisms in the skin biopsies nor in the sera of patients with fever or prolonged EM duration. Serological signs of exposure against SFG Rickettsia and A. phagocytophilum were detected in 11/135 and 8/135, respectively. Three patients exhibited both SFG Rickettsia and A. phagocytophilum antibodies, albeit negative PCR. No antibodies were detected against B. microti. 2/187 had TBEV antibodies without prior immunization. There was no significant increase in clinical symptoms or disease duration in patients with possible co-infection.ConclusionsCo-infection with N. mikurensis, A. phagocytophilum, SFG Rickettsia, Babesia spp. and TBEV is uncommon in Norwegian EM patients. Despite detecting antibodies against SFG Rickettsia and A. phagocytophilum in some patients, no clinical implications could be demonstrated.

Traumatic vertebra and endplate fractures promote adjacent disc degeneration: evidence from a clinical MR follow-up study.

The integrity of endplate is important for maintaining the health of adjacent disc and trabeculae. Yet, pathological impacts of traumatic vertebra and endplate fractures were less studied using clinical approaches. This study aims to investigate their effects on the development of adjacent disc degeneration, segmental kyphosis, Modic changes (MCs), and high-intensity zones (HIZs). Magnetic resonance (MR) images of patients with acute traumatic vertebral compression fractures (T11-L5) were studied. On MR images, endplate fractures were evaluated as present or absent. Disc signal, height, bulging area, sagittal Cobb angle, MCs, and HIZs were measured on baseline and follow-up MR images to study the changes of the disc in relation to vertebra fractures and endplate fractures. Ninety-seven patients were followed up for 15.4 ± 14.0months. There were 123 fractured vertebrae, including 79 (64.2%) with endplate fractures and 44 (35.8%) without. Both the adjacent and control discs decreased in signal and height over time (p < 0.001), and the disc adjacent to vertebral fractures had greater signal and height loss than the control disc (p < 0.05). In the presence of endplate fractures, the adjacent discs had greater signal decrease in follow-up (p < 0.05), as compared to those without endplate fractures. Sagittal Cobb angle significantly increased in segments with endplate fractures (p < 0.05). Vertebra fractures were associated with new occurrence of MCs in the fractured vertebra (p < 0.001) but not HIZs in the adjacent disc. Traumatic vertebral fractures were associated with accelerated adjacent disc degeneration, which appears to be further promoted by concomitant endplate fractures. Endplate fractures were associated with progression of segmental kyphosis.

Prevalence of iatrogenic atrial septal defects (iASD) after mitral valve (MV) transcatheter edge-to-edge repair (TEER) in the long-term follow-up

ObjectivesTo investigate prevalence of iatrogenic atrial septal defects (iASDs) after mitral valve (MV) transcatheter edge-to-edge repair (TEER) with the MitraClip in the long-term follow-up.BackgroundMV TEER requires transseptal puncture using a...

Percutaneous arteriovenous fistula creation with the 4F WavelinQ EndoAVF System

BackgroundPercutaneous devices for creation of native arteriovenous fistulae offer an alternative to traditional open surgical techniques. The 4F WavelinQ EndoAVF System was developed as a lower profile alternative to facilitate access through smaller vessels and minimize access site complications; The current report is the original first experience of this device, assessing outcome in 120 patients followed for 6 months. MethodsThe use of the 4F WavelinQ system in three studies, EASE (32 patients), EASE-2 (24 patients), and the EU postmarket clinical follow-up study (64 patients) was aggregated and analyzed. Patients were followed with duplex ultrasound at discharge and follow-up visits at 1, 3, and 6 months. Primary, assisted primary, and secondary patency rates were evaluated as Kaplan-Meier estimates and standard errors. Time to maturity and time to successful cannulation were defined as the mean ± standard deviation days from the procedure in patients enrolled on dialysis. ResultsProcedural success was achieved in 116 patients (96.7%). Primary, assisted-primary, and secondary 6-month patency rates were 71.9% ± 4.5%, 80.7% ± 4.1%, and 87.8% ± 3.3%, respectively. Time to maturity averaged 41 ± 17 days. Time to successful cannulation averaged 68 ± 51 days. Device-related serious adverse events were reported in 3 of 120 patients (2.5%) and procedure-related serious adverse events occurred in 7 of 120 patients (5.8%). Arterial or venous access complications were not reported in any of the patients. Access circuit reinterventions were performed in 23 patients (19.2%), split between those performed for EndoAVF maturation (13/120 [10.8%]) and maintenance (11/120 [9.2%]). ConclusionsPercutaneous creation of native dialysis fistulae with the 4F WavelinQ EndoAVF System is safe and effective, with favorable durability and a low rate of serious complications and reinterventions through 6-month follow-up. Use of the 4F device allows for percutaneous fistula creation between the radial artery and radial vein or the ulnar artery and ulnar vein. These findings suggest that the 4F device is a useful percutaneous alternative to open surgical AVF or endovascular AVF with larger bore devices.

Multicenter Clinical Trial to Validate Efficacy of Sundt Carotid Shunt

Shunting during carotid endarterectomy (CEA) preserves intraoperative cerebral perfusion. Our Food and Drug Administration–directed post market clinical follow-up study evaluated the safety and efficacy of the Sundt carotid shunt (Integra LifeSciences, Plainsboro Township, NJ).

Delta neutrophil index: in search of an early indicator of sepsis.

Sepsis is a significant cause of morbidity and mortality worldwide. Current clinical practice, however, lacks reliable diagnostic indicators for it and its prognosis. The present study aimed to investigate the efficacy of delta neutrophil index (DNI), which reflects the proportion of circulating immature granulocytes, in predicting infections and sepsis. A prospective non-interventional single-center clinical follow-up study was performed in a Bulgarian ICU between January 1, 2017 and May 31, 2018. We analyzed adult patients: 45 patients met the sepsis criteria, as defined in SEPSIS-3, whereas 37 were infected patients fulfilling no criteria of sepsis. Logistic regression and Roc-curve analysis were used to evaluate the severity and prognostic value of DNI as a prediction marker in critically ill septic patients. The results have shown that at DNI values of 1.4 there is 73% sensitivity and 87% specificity (AUC 0.764, 95% CI 0.650-0.878, p=0.0001) to assume the presence of sepsis. Additionally, DNI was significantly associated with the severity of the condition of patients, the organ dysfunction and the IL-8 marker. DNI may serve as a useful marker for early diagnosis of sepsis and could support decision making process regarding its treatment at an early stage of a disease development.

Multicenter Clinical Trial to Validate Efficacy of Sundt Carotid Shunt

Shunting during carotid endarterectomy (CEA) preserves intraoperative cerebral perfusion. The Food and Drug Administration–directed post-market clinical follow-up study evaluated the safety and efficacy of the Sundt (Integra LifeSciences, Billerica, Mass) carotid shunt.

Comment on Laratta et al. Marital Stability and Quality of Couple Relationships after Acquired Brain Injury: A Two-Year Follow-Up Clinical Study. Healthcare 2021, 9, 283.

We read with great interest the recent article by Laratta et al. [...].

Cardiovascular Risk Factor Progression in Adolescents and Young Adults With Type 2 Diabetes

Background: Onset of type 2 diabetes (T2D) in youth confers a high risk of early adverse cardiovascular outcomes. We describe the cumulative incidence of hypertension, LDL-cholesterol dyslipidemia, hypertriglyceridemia, and prevalence of smoking over time, and examine the relationships with body mass index and measures of glycemia, insulin sensitivity, and beta-cell function in an adolescent cohort with T2D enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods: Longitudinal data from the TODAY clinical trial and TODAY2 observational follow-up study were used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors using time-to-event models and generalized estimating equation models. Findings: Data were available on 677 participants. Mean age at baseline was 14±2 years and mean follow-up 10·2±4·5 years. The 14-year cumulative incidence of hypertension, LDL-C dyslipidemia, and hypertriglyceridemia was 59%, 33%, and 37% respectively, and the average prevalence of reported smoking was 23%. Male sex, non-Hispanic white race/ethnicity, obesity, poor glycemic control, lower insulin sensitivity, and reduced beta-cell function were significantly associated with an unfavorable cardiovascular risk profile. After an average of 10·2 years of follow-up, 54% of the cohort had ≥2 cardiovascular risk factors in addition to T2D. Interpretation: Cardiovascular risk factor incidence and prevalence was high over a decade of follow-up in young adults with youth-onset T2D. Addressing glucose control and insulin sensitivity, as well as medical management of cardiovascular risk factors will be critical in youth with T2D for prevention of cardiovascular morbidity and mortality. Trial Registration: Clinicaltrials.gov NCT00081328. Funding: United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease. Declaration of Interest: None of the authors reported a conflict of interest. Ethical Approval: The TODAY and TODAY2 studies were approved by institutional review boards at all 15 centers and all participants and guardians provided written informed assent and/or consent as appropriate for age.

Abstract 435: A novel image analysis assay for determining programmed death-ligand 1 (22C3) in non-small cell lung cancer that accounts for tissue and alveolar macrophages

Abstract The Dako PD-L1 (22C3) antibody is used in immunohistochemistry (IHC) to measure tumor programmed death-ligand 1 (PD-L1) levels, serving as a common companion diagnostic to the check point inhibitor drug pembrolizumab in non-small cell lung cancer (NSCLC). Yet for the practicing pathologist, interpretation of the PD-L1 (22C3) IHC assay is cumbersome and time-consuming resulting in poor intra- and inter-pathologist precision. We have developed a clinically validated PD-L1 (22C3) image analysis (IA) assay that was previously shown to perform equivalently to manual pathologist scoring, require less labor, and produce standardized and reproducible results with greater precision than manual scoring across repeated assessment. However, there is growing literature on the significance of macrophage PD-L1 positivity for predicting treatment response, highlighting the need to differentiate PD-L1 positivity in tumor cells versus macrophages. This need is further underscored by the tendency of manual and digital reads to confuse alveolar macrophages as tumor cells. In this study, we have applied a novel machine learning solution for tissue and alveolar macrophage detection to our PD-L1 (22C3) IA assay to improve its digital scoring accuracy in NSCLC as well as generate additional complementary data on the presence and PD-L1 positivity status of tissue and alveolar macrophages. 24 whole tissue NSCLC samples were purchased and IHC stained for PD-L1. Stained slides were scanned at 20X magnification and analyzed using Flagship's IA solutions that separate tumor and stromal compartments, identify tissue and alveolar macrophages, and quantify PD-L1 expression. Resulting image markups of cell detection and PD-L1 expression were reviewed by an MD pathologist for acceptance. PD-L1 staining was evaluated by digital IA and manual pathology in the sample's tumor compartment for Tumor Proportion Score (TPS). Applying the tissue and alveolar macrophage solution to the PD-L1 (22C3) assay successfully removed macrophages from the digital TPS assessment and generated additional data on tissue and alveolar macrophages (% present, % PD-L1 positive) without significantly impacting the integrity of the IA assay (i.e., the correlation between the digital and manual TPS remained high). This preliminary data demonstrates the robust performance of the clinically validated PD-L1 (22C3) IA assay, even when accounting for tissue and alveolar macrophages. Ongoing experiments include testing the macrophage algorithm on a larger sample of NSCLC tissues to determine the correlation and treatment cut-off concordance between digital and manual scoring obtained by three pathologists. A follow-up clinical validation study of the sensitivity, specificity, accuracy, and precision of this updated PD-L1 (22C3) IA assay is also pending. Citation Format: Roberto Gianani, Will Paces, Elliott Ergon, Vitria Adisetiyo, Charles Caldwell. A novel image analysis assay for determining programmed death-ligand 1 (22C3) in non-small cell lung cancer that accounts for tissue and alveolar macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 435.

Clinical follow-up study of 166 cases of children with hypertension.

BackgroundChildhood hypertension is a challenge for pediatricians to discover and diagnose. We sought to analyze its clinical characteristics and related risk factors in patients at a single center.MethodsFrom 2009 to 2019, 166 children with hypertension were retrospectively analyzed, and their clinical manifestations and relevant laboratory data were collected for statistical analysis.ResultsA total of 120 males and 46 females were included in this study. Males were more common than females (P=0.012), and 86.7% were from rural areas. Hypertension appeared in all age groups, but most of them were puberty (52.4%). Most primary hypertension cases (57/91) had no obvious clinical symptoms, and BMI (OR 1.085, 95% CI: 1.004–1.173, P=0.038) and a family history of hypertension (OR 5.605, 95% CI: 2.229–14.092, P<0.001) were the risk factors. In the 75 secondary hypertension cases, renal hypertension (62.7%) was the main cause and headache and dizziness were the most common symptoms, and the serum urea is a risk factor (OR 1.524, 95% CI: 1.037–2.239, P=0.032).ConclusionsBMI and a family history of hypertension were associated with primary hypertension. The serum urea was related to secondary hypertension. Emphasis on family history, strengthening family health management and education and publicity of hypertension, were important for diagnosis and detection of children with hypertension.