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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Its prevalence in cancer patients undergoing treatment with radiation or chemotherapeutic agents has been on the rise. The most common offending agents are alkylating agents and anthracyclines causing various types of arrhythmias, including AF. We report a case of a 62-year-old male who was diagnosed with stage IV pleomorphic rhabdomyosarcoma and was started on chemotherapy with a mesna-ifosfamide and doxorubicin (MAI) regimen. He developed AF with a rapid ventricular rate soon after his second cycle of treatment, which got better with the initiation of beta-blocker therapy. Since low blood counts, including low platelet levels, are expected in patients with chemotherapy, the continual use of anticoagulation therapy varies on a case-to-case basis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hassan et al.)

Background: Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome., Methods: We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs)., Results: Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy., Conclusions: Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown., Methods: In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed., Results: Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly., Conclusion: This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Staal, Cortenbach, Gorris, van der Woude, Srinivas, Heijmen, Geuzebroek, Grewal, Hebeda, de Vries, DeRuiter and van Kimmenade.)

Competing Interests: Conflict of interestThe authors declare no competing interests.

Background: Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine., Objective: This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals., Materials and Methods: Bicuspid aortic valve (BAV; n = 36), TAV ( n = 23), and MFS ( n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression., Results: The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima ( p < 0.0005), a lower expression of contractile VSMCs ( p < 0.05), more elastic fiber thinning ( p < 0.001), lack of inflammation ( p < 0.001), and a decreased progerin expression ( p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration ( p < 0.0001), VSMC nuclei loss ( p < 0.0001), apoptosis of the vessel wall ( p < 0.03), and elastic fiber fragmentation and disorganization ( p < 0.001), as compared to the MFS and dilated TAV., Conclusion: This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grewal, Dolmaci, Jansen, Klautz, Driessen and Poelmann.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Type A aortic dissections (TAAD) are devastating aortic complications. Patients with Marfan syndrome, a bicuspid aortic valve or a thoracic aortic aneurysm have an increased risk to develop a TAAD. These predisposing conditions are characterized by a histologically thin intimal layer and hardly any atherosclerosis. Little is known about the susceptibility for atherosclerosis in patients with a type A aortic dissection., Objective: We aim to systematically describe atherosclerotic lesions in TAAD patients., Materials and Methods: A total of 51 patients with a TAAD (mean age 62.5 ± 10.8 years, 49% females) and 17 control patients (mean age 63 ± 5.5 years, 53% females) were included in this study. Cardiovascular risk factors were assessed clinically. All sections were stained with Movat pentachrome and hematoxylin eosin. Plaque morphology was classified according to the modified AHA classification scheme proposed by Virmani et al., Results: In the TAAD group thirty-seven percent were overweight (BMI > 25). Diabetes and peripheral arterial disease were not present in any of the patients. Fifty-nine percent of the patients had a history of hypertension. The intima in TAAD patients was significantly thinner as compared to the control group (mean thickness 143 ± 126.5 μm versus 193 ± 132 μm, p < 0.023). Seven TAAD patients had a normal intima without any form of adaptive or pathological thickening. Twenty-three TAAD patients demonstrated adaptive intimal thickening. Fourteen had an intimal xanthoma, also known as fatty streaks. A minority of 7 TAAD patients had progressive atherosclerotic lesions, 4 of which demonstrated pathological intimal thickening, 3 patients showed early fibroatheroma, late fibroatheroma and thin cap fibroatheroma. In the control group the majority of the patients exhibited progressive atherosclerotic lesions: three pathologic intimal thickening, two early fibroatheroma, six late fibroatheroma, one healed rupture and two fibrotic calcified plaque., Discussion: This study shows that TAAD patients hardly exhibit any form of progressive atherosclerosis. The majority of TAAD patients showcase non-progressive intimal lesions, whereas the control group mostly demonstrated progressive intimal atherosclerotic lesions. Findings are independent of age, sex, or the presence of (a history of) hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer M-JG declared a shared affiliation with the authors NG, OD, JL, and RP to the handling editor at the time of review., (Copyright © 2023 Grewal, Dolmaci, Jansen, Klautz, Driessen, Lindeman and Poelmann.)

Lyme's carditis and neuroborreliosis are common manifestation of disseminated Lyme disease. However, third-degree atrioventricular blocks with Lyme's carditis requiring permanent pacemaker with neuroborreliosis and Lyme's disease-associated immunodeficiency are uncommon. Here we present a case of 64-year-old female presenting with neurological symptoms and electrocardiogram changes suggestive of complete heart block with no improvement in the degree of heart block with intravenous antibiotics, requiring permanent pacemaker implantation and course complicated by fungemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients., Methods: BAV (n=41) and tricuspid aortic valve (TAV) (n=18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompassing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracellular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells., Results: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis (P<.001). The medial layer is significantly thicker (P<.001) with more mucoid extracellular matrix accumulation (P<.001). All other medial pathologic features were more prominent in the TAV (P<.001). The media has significantly less differentiated vascular smooth muscle cells (P<.001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV (P<.0001)., Conclusions: The BAV ascending aorta without dilatation is characterized by a differentiation defect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt pathologic features., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal aneurysm patients. It has been hypothesized that associated risk relates to loss of aortic compliance. If this hypothesis is correct, observations for abdominal aneurysms would also apply to thoracic aortic aneurysms. The objective of this study is to test whether thoracic aneurysms are also associated with an increased cardiovascular risk burden. Methods: Patients who underwent aortic valve or root surgery were included in the study (n = 239). Cardiovascular risk factors were studied and atherosclerosis was scored based on the preoperative coronary angiographies. Multivariate analyses were performed, controlling for cardiovascular risk factors and aortic valve morphology. Comparisons were made with the age- and gender-matched general population and non-aneurysm patients as control groups. A thoracic aortic aneurysm was defined as an aortic aneurysm of ≥45 mm. Results: Thoracic aortic aneurysm was not associated with an increased coronary atherosclerotic burden (p = 0.548). Comparison with the general population revealed a significantly higher prevalence of hypertension (61.4% vs. 32.2%, p < 0.001) and a lower prevalence of diabetes (1.4% vs. 13.1%, p = 0.001) in the thoracic aneurysm group. Conclusions: The extreme cardiovascular risk associated with abdominal aortic aneurysms is location-specific and not explained by loss of aortic compliance. Thoracic aortic aneurysm, in contrast to abdominal, is not part of the atherosclerotic disease spectrum and, therefore, cardiovascular risk management does not need to be implemented in treatment guidelines of isolated thoracic aneurysms. Hypertension should be treated.

There is increasing focus on applying deep learning methods to electrocardiograms (ECGs), with recent studies showing that neural networks (NNs) can predict future heart failure or atrial fibrillation from the ECG alone. However, large numbers of ECGs are needed to train NNs, and many ECGs are currently only in paper format, which are not suitable for NN training. We developed a fully-automated online ECG digitisation tool to convert scanned paper ECGs into digital signals. Using automated horizontal and vertical anchor point detection, the algorithm automatically segments the ECG image into separate images for the 12 leads and a dynamical morphological algorithm is then applied to extract the signal of interest. We then validated the performance of the algorithm on 515 digital ECGs, of which 45 were printed, scanned and redigitised. The automated digitisation tool achieved 99.0% correlation between the digitised signals and the ground truth ECG (n = 515 standard 3-by-4 ECGs) after excluding ECGs with overlap of lead signals. Without exclusion, the performance of average correlation was from 90 to 97% across the leads on all 3-by-4 ECGs. There was a 97% correlation for 12-by-1 and 3-by-1 ECG formats after excluding ECGs with overlap of lead signals. Without exclusion, the average correlation of some leads in 12-by-1 ECGs was 60-70% and the average correlation of 3-by-1 ECGs achieved 80-90%. ECGs that were printed, scanned, and redigitised, our tool achieved 96% correlation with the original signals. We have developed and validated a fully-automated, user-friendly, online ECG digitisation tool. Unlike other available tools, this does not require any manual segmentation of ECG signals. Our tool can facilitate the rapid and automated digitisation of large repositories of paper ECGs to allow them to be used for deep learning projects., (© 2022. The Author(s).)

Background: Rituximab and tacrolimus are therapies reserved for patients with frequently relapsing or steroid-dependent nephrotic syndrome who have failed conventional steroid-sparing agents. Given their toxicities, demonstrating non-inferiority of rituximab to tacrolimus may enable choice between these medications., Methods: This investigator-initiated, single-center, open-label, pilot randomized controlled trial examined the non-inferiority of two doses of intravenous (IV) rituximab given one-week apart to oral therapy with tacrolimus (1:1 allocation), in maintaining sustained remission over 12 months follow-up, in patients with difficult-to-treat steroid-sensitive nephrotic syndrome, defined as frequently relapsing or steroid-dependent disease that had failed ≥ 2 steroid-sparing strategies. Secondary outcomes included frequency of relapses, proportion with frequent relapses, time to relapse and frequent relapses, and adverse events (CTRI/2018/11/016342)., Results: Baseline characteristics were comparable for 41 patients randomized to receive rituximab (n = 21) or tacrolimus (n = 20). While 55% of patients in each limb were in sustained remission at 1 year, non-inferiority of rituximab to tacrolimus was not demonstrated (mean difference 0%; 95% CI - 30.8%, 30.8%; non-inferiority limit - 20%; P = 0.50). Frequent relapses were more common in patients administered rituximab compared to tacrolimus (risk difference 30%, 95% CI 7.0, 53.0, P = 0.023). Both groups showed similar reductions in relapse rates and prednisolone use. Common adverse events were infusion-related with rituximab and gastrointestinal symptoms with tacrolimus., Conclusions: Therapy with rituximab was not shown to be non-inferior to 12-months treatment with tacrolimus in maintaining remission in patients with difficult-to-treat steroid-sensitive nephrotic syndrome. Frequent relapses were more common with rituximab. While effective, both agents require close monitoring for adverse events. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

The efficacy of continuous glucose monitors (CGM) to improve glycaemic control in individuals on intensive insulin therapy (basal and prandial) has been well established in several studies; however, there is limited evidence on its usage and efficacy in patients with type 2 diabetes (T2D) who are on non-insulin therapies. Lifestyle modifications and glucose monitoring are essential components of the management of T2D. We report a case that demonstrates the impact of CGM use as an effective tool for patient education and motivation to implement and adhere to lifestyle modifications in improving glycaemic control in a patient with long-standing poorly controlled T2D who was on oral glucose-lowering medications. CGM use is associated with high level of patient satisfaction which can improve quality of life and has the potential to reduce long-term complications related to poor glycaemic control. These observations emphasise the need to broaden the use of CGM in this patient population., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Extracorporeal circulation (ECC) in cardiac surgery is performed under systemic heparinization. Adequacy of heparin therapy and anticoagulation during ECC is assessed by activated clotting time (ACT), although there are concerns regarding the reliability of this measure. The ACT can be affected by factors other than heparin anticoagulation. A novel factor that should be considered is the influence of a COVID-19 infection. More than half of the hospitalized COVID-19 patients develop coagulation abnormalities with dysregulated coagulation test results. Patients recently recovered from COVID-19 may still demonstrate some forms of coagulation disorder affecting the ACT. This case describes an inaccurate point-of-care ACT testing in a patient with previous COVID-19 infection undergoing cardiac surgery with ECC and the alternative coagulation testing performed., Case Presentation: A 77-years-old Caucasian male presented with symptomatic severe mitral valve regurgitation for which he underwent surgery. Medical history revealed a COVID-19 infection one month before surgery. Pre-operative hematological lab results were normal and baseline ACT during surgery was 100 s. To achieve an adequate ACT of > 400 s, multiple doses of heparin were needed and after administration of a triple dose (75,000 IE heparin in total) this adequate ACT was achieved. In the meanwhile we measured anti-Xa level and APTT, which were at adequate levels when ACT was still < 400 s., Discussion: This case emphasizes the need of alternative methods for monitoring heparin therapy in case ACT does not respond adequately. Another point to highlight in this case is the poorly correlated relation between ACT and APTT and anti-Xa in light of the recent COVID-19 infection. Although studies have shown that COVID-19 infection can cause coagulopathy and altered hemostatic parameters, ACT has never been investigated in COVID-19 patient. Understanding the correlation between ACT, APTT and anti-Xa in COVID-19 patients is mandatory., (© 2022. The Author(s).)

Acute aortic dissection is a rare, but potentially life-threatening and time-critical condition that is frequently misdiagnosed. Therefore, its prompt and proper diagnosis is vital to increase a patient's chance of survival and to prevent grievous complications. Raising awareness and educating the general population and healthcare professionals about an aortic dissection is mandatory, for early diagnosis and improving the chances of survival., (Copyright © 2021 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Objective: We aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease., Methods: A total of 131 patients referred for aortic valve replacement were grouped by valve dysfunction (aortic stenosis vs aortic regurgitation) and valve morphology (bicuspid vs tricuspid). On the basis of magnetic resonance imaging, aortic tissue from outer and inner curvature was collected for gene expression and histologic analysis. To identify differences in aortic remodeling, age- and sex-adjusted data for inflammation (CCL2, VCAM1, inflammation and atherosclerosis) and medial degeneration (COL1A1, ELN, fibrosis, elastin fragmentation, and cystic medial necrosis) were compared., Results: First, we compared all patients with aortic regurgitation (n = 64) and patients with aortic stenosis (n = 67). In patients with aortic regurgitation, COL1A1 expression and all histologic markers were significantly increased. With respect to aortic diameter, all subsequent analyses were refined by considering only individuals with aortic diameter 40 mm or greater. Second, patients with bicuspid aortic valve were compared, resulting in a similar aortic diameter. Although patients with aortic regurgitation were younger, no differences were found in gene expression or histologic level. Third, valve morphology was compared in patients with aortic regurgitation. Although aortic diameter was similar, patients with regurgitant bicuspid aortic valve were younger than patients with regurgitant tricuspid aortic valve. Inflammatory markers were similar, whereas markers for medial degeneration were increased in patients with regurgitant tricuspid aortic valve., Conclusions: Our results indicate that the proximal aorta in patients with aortic regurgitation showed an increased inflammation and medial degeneration compared with patients with aortic stenosis. Refining both groups by valve morphology, in patients with bicuspid aortic valve, no difference except age was detected between aortic regurgitation and aortic stenosis. In patients with aortic regurgitation, tricuspid aortic valve revealed increased markers for medial degeneration but no differences regarding inflammatory markers., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background : The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left ventricular cavity. Mixing of blood in crocodilians cannot occur at the ventricular level as in other reptiles but instead takes place at the aortic root level by a shunt, the foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods : Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris were studied histologically. Results and Conclusions : The outflow tract septation complex can be divided into two components. The aorto-pulmonary septum divides the pulmonary trunk from both aortas, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.

Objective: Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the older age of TAV patients and/or accumulation of atherosclerotic risk factors or that the BAV phenotype is atheroprotective. Therefore, we compared the atherosclerotic disease burden of BAV and TAV patients, with that of the general (age-matched) population., Methods: The prevalence of coronary artery disease (CAD) and CAD risk factors in BAV and TAV patients who underwent aortic valve surgery were compared with the Dutch general practitioners registry data. BAV (n=454) and TAV (n=1101) patients were divided into four groups: BAV with aortic valve stenosis (BAV-AoS), BAV with aortic valve regurgitation (BAV-AR), TAV with AoS (TAV-AoS) and TAV with AR (TAV-AR). The atherosclerotic disease burden of each group was compared with that of the corresponding age cohort for the general population., Results: CAD risk factors hypertension and hypercholesterolaemia were more prevalent in the surgery groups than the age-matched general population (all p<0.001). All BAVs (BAV-AoS and BAV-AR) and TAV-AR had a similar incidence of CAD history as compared to the age-matched general populations (p=0.689, p=0.325 and p=0.617 respectively), whereas TAV-AoS had a higher incidence (21.6% versus 14.9% in the age-matched general population, p<0.001)., Conclusions: Stenotic TAV disease is part of the atherosclerotic disease spectrum, while regurgitant TAV and all BAVs are not. Although the prevalence of cardiovascular risk factors is higher in all BAV patients, the prevalence of CAD is similar to the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The law often calls on the concept of public interest for assistance. Privacy law makes use of this concept in several ways, including to justify consent waivers for secondary research on health information. Because the law sees information privacy as a means for individuals to control their personal information, consent can only be set aside in special circumstances. Ballantyne and Schaefer argue that only public interest, and only a broad conception of public interest, can do the special 'normative justificatory work' to override consent requirements. Other, similar-sounding concepts, such as public benefit, public good and social value, also provide useful services. But none more so than public interest. In fact, they argue, public interest is the superior concept precisely because it can capture those concepts as well as a range of other interests. Our response focuses on this claim. We argue their strategy is not as promising as it might first seem. Ballantyne and Schaefer construe the important role that public interest plays in this context as their endpoint. They claim that unless the concept is open and content-rich, it will lose some of its importance. But by refusing to place limits around it, their inquiry leads us back to a catch-all concept that lacks clear focus or meaning. In reply, we argue that, for practically minded theorists, a narrow conception of public interest is more useful. Further, the narrowing of public interest in this context can be achieved by first analysing it in its legal, rather than ethical, sense., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: First-time dental treatment for children is often sought due to carious, malformed, fractured, and discolored teeth. The strip crown represents a highly esthetic and popular option for the restoration of primary anterior teeth. However, there are limited data on the clinical success of these crowns based on the extent of surface area used for adhesion., Aims Settings and Design: This in vivo study aimed to assess the clinical, radiographic, and photographic performance of 66 composite strip crown restorations on primary anterior teeth for up to 15 months and compare the outcome based on the extent and surface area of tooth structure available., Materials and Methods: The amount of surface area available in each group after removal of affected enamel was evaluated through 3D scanning of study casts and digital measurements. The teeth were thus grouped into three categories: group I with crown structure involvement up to the incisal one-third, group II with involvement up to the middle of the middle third, and group III with involvement up to the cervical one-third., Statistical Analysis Used: Kruskal-Wallis H test and Mann-Whitney U test were used for computation of mean scores for intra- and intergroup comparison, respectively. Scoring was done as per FDI clinical criteria on a scale of 1 to 5., Results: Group III showed the highest mean scores at different time intervals and also the highest failure rate (52.38%), followed by group II (12%) and group I (5%). The overall retention rate observed for the strip crowns was 77.28% at the end of 15 months., Conclusion: Strip crowns should be considered for teeth that offer a minimum of half to two-thirds of the healthy tooth structure remaining. Further, longitudinal studies are required to add to the results of the final outcome of these restorations., Key Messages: A critical surface area value of <50 mm 2 or less than half of the available sound tooth structure was found to be detrimental to the retention rate of these crowns in this study. It could therefore be suggested to consider strip crowns for teeth that offer a minimum of half to two-thirds of healthy tooth structure remaining., How to Cite This Article: Grewal N, Jha S, Kaur N. Clinical and Radiographic Success of Resin-bonded Strip Crowns in Primary Incisors with Varying Extents of Sound Tooth Structure Available for Bonding. Int J Clin Pediatr Dent 2021;14(4):454-461., Competing Interests: Source of support: ICMR PG thesis grant (No. 3/2/September-2016/PG-Thesis-HRD/20) Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly associates with coronary artery disease (CAD) with common pathophysiological factors. Yet, it remains unclear whether AoS in patients with BAV is also associated with CAD. This study investigated the association between the aortic valve morphological features and the extent of CAD. Methods and Results A single-center study was performed, including all patients who underwent an aortic valve replacement attributable to AoS between 2006 and 2019. Coronary sclerosis was graded on preoperative coronary angiographies using the coronary artery greater even than scoring method, which divides the coronaries in 28 segments and scores nonobstructive (20%-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Multivariate analyses were performed, controlling for age, sex, and CAD risk factors. A total of 1296 patients (931 TAV and 365 BAV) were included, resulting in 548 matched patients. Patients with TAV exhibited more CAD risk factors (odds ratio [OR], 2.66; 95% CI, 1.79-3.96; P <0.001). Patients with BAV had lower coronary artery greater even than 20 (1.61±2.35 versus 3.60±2.79) and coronary artery greater even than 50 (1.24±2.43 versus 3.37±3.49) scores ( P <0.001), even after correcting for CAD risk factors ( P <0.001). Patients with TAV more often needed concomitant coronary revascularization (OR, 3.50; 95% CI, 2.42-5.06; P <0.001). Conclusions Patients with BAV who are undergoing surgery for AoS carry a lower cardiovascular risk profile, correlating with less coronary sclerosis and a lower incidence of concomitant coronary revascularization compared with patients with TAV.

(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens in TAAD patients. (2) Methods: Ascending aortic wall specimens ( n = 58, mean age 63 years) with TAAD were collected. Autopsy tissues ( n = 17, mean age 63 years) served as controls. All sections were studied histopathologically. (3) Results: Pathomorphology in TAAD showed predominantly moderate elastic fiber fragmentation/loss, elastic fiber thinning, elastic fiber degeneration, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration. The control group showed significantly fewer signs of those histopathological features (none-mild, p = 0.00). It was concluded that the dissection plane consistently coincides with the vasa vasorum network, and that TAAD associates with a significantly thinner intimal layer p = 0.005). (4) Conclusions: On the basis of the systematic evaluation and the consistent presence of diffuse, pre-existing medial defects, we hypothesize that TAAD relates to a developmental defect of the ascending aorta and is caused by a triple-hit mechanism that involves (I) an intimal tear; and (II) a diseased media, which allows (III) propagation of the tear towards the plane of the vasa vasorum where the dissection further progresses.

Aim and Objective: The aim and objective of this study was to review the literature to analyze the prevalence of developmental dental anomalies regarding shape in India., Background: Although there have been several studies investigating the prevalence of individual dental anomalies related to shape, only a few studies considered all subtypes and their distribution among genders, especially in India., Results: An electronic search was made in the PUBMED database to review prevalence-based data on developmental dental anomalies related to shape in India up to December 2018. A diverse range of results regarding prevalence of developmental dental anomalies related to shape were seen in these studies due to vast regional, cultural, and ethnic diversities and various environmental factors affecting the tooth development., Conclusion: There is a necessity to conduct more study on shape-related dental anomalies because there are very limited studies regarding prevalence of concrescence, dilacerations, and accessory root and various associated factors., Clinical Significance: Early diagnosis and timely management of these anomalies can prevent complications. The knowledge on identification and prevalence of dental anomalies helps the dental practitioners improve the treatment plan. The prevalence studies can be of utmost importance in the formulation of oral healthcare programs by using their data to analyze the intensity of dental anomalies., How to Cite This Article: Goswami M, Bhardwaj S, Grewal N. Prevalence of Shape-related Developmental Dental Anomalies in India: A Retrospective Study. Int J Clin Pediatr Dent 2020;13(4):407-411., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Background: This study assessed the direct, indirect and total effect of distal - political - risk indicators (affecting populations), and proximal risk indicators (affecting women) on the global prevalence of early childhood caries (ECC) in 3-5 year old children., Methods: Data on global ECC prevalence were obtained from a prior study. Data for distal risk indicators (voice and accountability; political stability/absence of terrorism; control of corruption) were obtained from the World Bank Governance indicators, 2016. Data for proximal risk indicators (women's opportunity for leadership; percentage of female legislators, top officials and managers; basic employability status of women; ability of women to afford time off work to care for newborns; gross national income (GNI) per capita for females) were derived from the Human Development Index, 2016. Associations between variables were assessed with path analysis., Results: Voice and accountability (β = - 0.60) and GNI per capita for females (β = - 0.33) were directly associated with a lower ECC prevalence. Political stability/absence of terrorism (β =0.40) and higher percentage of female legislators, senior officials and managers (β = 0.18) were directly associated with a higher ECC prevalence. Control of corruption (β = - 0.23) was indirectly associated with a lower ECC prevalence. Voice and accountability (β = 0.12) was indirectly associated with a higher ECC prevalence. Overall, voice and accountability (β = - 0.49), political stability/absence of terrorism (β = 0.34) and higher female GNI (β = - 0.33) had the greatest effects on ECC prevalence., Conclusion: Distal risk indicators may have a stronger impact on ECC prevalence than do proximal risk indicators.. Approaches to control ECC may need to include political reforms.

Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for future studies on aortopathy and related syndromes., Methods: Non-dilated TAV and BAV ascending aortic wall samples were collected, including 60 TAV (embryonic-70 years) and 32 BAV specimens (fetal-72 years, categorized in eight age groups., Results: In TAV, intimal development starts in the neonatal phase. After birth, the thickness of the medial layer increases significantly by increase of elastic lamellae up to and including the "young child" phase stabilizing afterwards. The BAV shows already prenatal intimal thickening becoming significantly thinner after birth subsequently stabilizing. In BAV, increase in elastic lamellae is seen between the young child and the adolescent phases, stabilizing afterwards., Conclusions: Vascular development in TAV is described in three phases: maturation, stabilization, and degeneration. For BAV, the development can be described in two phases: maturation (already prenatally) and degeneration. After birth, the development of the aorta is characterized by degeneration, leading to weakening of the ascending aortic wall and increasing the risk of aortopathy., Competing Interests: The authors declare no conflict of interest.

Background: Loss-of-function variants in RAD51C are associated with familial ovarian cancer, but its role in hereditary breast cancer remains unclear. The aim of this study was to couple breast tumor sequencing with case-control data to clarify the contribution of RAD51C to hereditary breast cancer., Methods: RAD51C was sequenced in 3080 breast cancer index cases that were negative in BRCA1/2 clinical tests and 4840 population-matched cancer-free controls. Pedigree and pathology data were analyzed. Nine breast cancers and one ovarian cancer from RAD51C variant carriers were sequenced to identify biallelic inactivation of RAD51C, copy number variation, mutational signatures, and the spectrum of somatic mutations in breast cancer driver genes. The promoter of RAD51C was analyzed for DNA methylation., Results: A statistically significant excess of loss-of-function variants was identified in 3080 cases (0.4%) compared with 2 among 4840 controls (0.04%; odds ratio = 8.67, 95% confidence interval = 1.89 to 80.52, P< .001), with more than half of the carriers having no personal or family history of ovarian cancer. In addition, the association was highly statistically significant among cases with estrogen-negative (P <. 001) or triple-negative cancer (P < .001), but not in estrogen-positive cases. Tumor sequencing from carriers confirmed bi-allelic inactivation in all the triple-negative cases and was associated with high homologous recombination deficiency scores and mutational signature 3 indicating homologous recombination repair deficiency., Conclusions: This study provides evidence that germline loss-of-function variants of RAD51C are associated with hereditary breast cancer, particularly triple-negative type. RAD51C-null breast cancers possess similar genomic and clinical features to BRCA1-null cancers and may also be vulnerable to DNA double-strand break inducing chemotherapies and poly ADP-ribose polymerase inhibitors., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to address the role of hemodynamic influences on the development of aortopathy in BAV patients., Patient and Methods: BAV (n=36) and tricuspid aortic valve (TAV) patients (n=17) undergoing aortic valve replacement underwent preoperative flow magnetic resonance imaging (MRI) assessment to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, paired ascending aortic wall samples [i.e., area of maximal jet impact (jet sample) and the opposite aortic wall (nonjet sample)] were collected during surgery. To study and describe the effects of jet stream on the complete vascular wall, a pathology score was developed based on the recently published aortic consensus paper statement on surgical pathology of the aorta using routine histologic stainings (resorcin fuchsin, hematoxylin-eosin, and Movat) and immunohistochemistry (alpha smooth muscle actin, smooth muscle 22 alpha, platelet endothelial cell adhesion molecule)., Results: Comparing the jet and nonjet samples in both BAV and TAV, regions of maximal jet impact did not show any difference in the pathology score in the adventitia and the middle and outer media. In the jet samples, the inner media however showed loss of actin expression in both BAV (P<.0001) and the TAV (P=.0074), and the intimal thickness was significantly enlarged in both patient groups (BAV P=.0005, TAV P=.0041), which was not accompanied by loss of elastic lamellae or vascular smooth muscle cell nuclei., Conclusions: In our study population, we could not demonstrate a potential distinct role for hemodynamics in the development of aortopathy in BAV patients even if corrected for aortic diameter, raphe position, or whether the valve is stenotic or regurgitant. The intimal layer and inner media however showed alterations in all jet specimens., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Equity is fundamental to public health practice. However, limited work has evaluated public health units, as employers, in ensuring equitable workplaces. Public health units must examine their policies for promoting equity, diversity, and inclusiveness. We suggest strategies that these organizations may adopt to establish a diverse workforce, including programs of responsibility, broader advertisement of employment opportunities, and standardized application processes. These practices are site dependent and are more effective when supported by senior management. By considering these strategies, institutions of public health can improve equity, diversity, and inclusion in their workplaces while addressing health equity in the communities they serve., Competing Interests: The article, in whole or in part, has not been published, nor is it being considered for publication elsewhere. There is no real or perceived conflict of interest. There was no financial support for this project.

Background: Complete pulpectomy and elimination of wide range of microorganisms from infected primary root canals is not possible through conventional endodontic procedures. Thus, lesion sterilization and tissue repair (LSTR) therapy employing 3Mix tri-antibiotic paste have been used as an alternative endodontic modality for infected primary teeth., Aim: This study aims to evaluate the root resorption rate of endodontically treated mandibular primary molars with conventional endodontic treatment or LSTR therapy and to compare it with their healthy contralateral teeth., Materials and Methods: Fifty carious first and second primary mandibular molars from 25 healthy children aged 7-10 years were treated with two different endodontic procedures using LSTR Therapy and conventional endodontic treatment. The resorption rate of these teeth with healthy contralateral teeth was compared clinically and radiographically at 3, 6, 12 and 36 months using Chi-square test., Results: At 12 months, clinically, there was no difference in the outcomes of both groups but radiographically, statistically significant difference (P < 0.001) in root resorption between treated teeth and their controls in both the groups was observed. At 36 months, interradicular bone resorption around the crown of succedaneous teeth and their delayed eruption was noted in LSTR group., Conclusions: LSTR therapy could be a viable treatment modality for infected/nonvital primary molars with poor prognosis and intended to be maintained for shorter duration in the oral cavity as natural space maintainers., Competing Interests: There are no conflicts of interest

Background: Oral intake for traumatic brain injury (TBI) patients is often not an option because of facial trauma, swallowing dysfunctions, altered consciousness, etc. These patients often require percutaneous endoscopic gastrostomy (PEG) placement for nutrition support. To date, there is lack of studies examining the relationship between the timing of PEG placement and patient outcome in the TBI group., Methods: We conducted a population-based study in a retrospective cohort of TBI patients undergoing PEG, using the national inpatient sample for years 2011 to 2013., Results: A total of 96,625 patients were identified for TBI and 3343 of those patients received PEG. TBI patients who undergo an early or late PEG placement had a higher rate of in-hospital mortality, when compared with patients with a standard timing of PEG placement. Late PEG was preferably placed in patients with higher Charlson index and trauma-related comorbidities, and these patients had a higher incidence of complications, that is, sepsis, urinary tract infection, acute respiratory distress syndrome/pneumonia, and deep vein thrombosis/pulmonary embolism. When stratified by mortality-risk groups, early PEG was associated with higher rates of in-hospital mortality while standard PEG was associated with best mortality outcomes in low-mortality-risk group and moderate-mortality-risk group., Conclusions: The results of this study suggest that if a PEG placement is indicated for a TBI patient, a standard (7 to 14 d) timing may be associated with better patient outcomes. However, secondary to limitations associated with the use of administrative databases, further prospective studies are needed to establish clear guidelines regarding the optimal timing of placing PEG in TBI patients.

Background: Current practice guidelines emphasize the use of physical activity as the first-line treatment of knee osteoarthritis; however, up to 90% of people with osteoarthritis are inactive., Objective: We aimed to assess the efficacy of a technology-enabled counseling intervention for improving physical activity in people with either a physician-confirmed diagnosis of knee osteoarthritis or having passed two validated criteria for early osteoarthritis., Methods: We conducted a proof-of-concept randomized controlled trial. The immediate group received a brief education session by a physical therapist, a Fitbit Flex, and four biweekly phone calls for activity counseling. The delayed group received the same intervention 2 months later. Participants were assessed at baseline (T0) and at the end of 2 months (T1), 4 months (T2), and 6 months (T3). Outcomes included (1) mean time on moderate-to-vigorous physical activity (MVPA ≥3 metabolic equivalents [METs], primary outcome), (2) mean time on MVPA ≥4 METs, (3) mean daily steps, (4) mean time on sedentary activities, (5) Knee Injury and Osteoarthritis Outcome Score (KOOS), and (6) Partners in Health scale. Mixed-effects repeated measures analysis of variance was used to assess five planned contrasts of changes in outcome measures over measurement periods. The five contrasts were (1) immediate T1-T0 vs delayed T1-T0, (2) delayed T2-T1 vs delayed T1-T0, (3) mean of contrast 1 and contrast 2, (4) immediate T1-T0 vs delayed T2-T1, and (5) mean of immediate T2-T1 and delayed T3-T2. The first three contrasts estimate the between-group effects. The latter two contrasts estimate the effect of the 2-month intervention delay on outcomes., Results: We recruited 61 participants (immediate: n=30; delayed: n=31). Both groups were similar in age (immediate: mean 61.3, SD 9.4 years; delayed: mean 62.1, SD 8.5 years) and body mass index (immediate: mean 29.2, SD 5.5 kg/m 2 ; delayed: mean 29.2, SD 4.8 kg/m 2 ). Contrast analyses revealed significant between-group effects in MVPA ≥3 METs (contrast 1 coefficient: 26.6, 95% CI 4.0-49.1, P=.02; contrast 3 coefficient: 26.0, 95% CI 3.1-49.0, P=.03), daily steps (contrast 1 coefficient: 1699.2, 95% CI 349.0-3049.4, P=.02; contrast 2 coefficient: 1601.8, 95% CI 38.7-3164.9, P=.045; contrast 3 coefficient: 1650.5, 95% CI 332.3-2968.7; P=.02), KOOS activity of daily living subscale (contrast 1 coefficient: 6.9, 95% CI 0.1-13.7, P=.047; contrast 3 coefficient: 7.2, 95% CI 0.8-13.6, P=.03), and KOOS quality of life subscale (contrast 1 coefficient: 7.4, 95% CI 0.0-14.7, P=.049; contrast 3 coefficient: 7.3, 95% CI 0.1-14.6, P=.048). We found no significant effect in any outcome measures due to the 2-month delay of the intervention., Conclusions: Our counseling program improved MVPA ≥3 METs, daily steps, activity of daily living, and quality of life in people with knee osteoarthritis. These findings are important because an active lifestyle is an important component of successful self-management., Trial Registration: ClinicalTrials.gov NCT02315664; https://clinicaltrials.gov/ct2/show/NCT02315664 (Archived by WebCite at http://www.webcitation.org/6ynSgUyUC)., (©Linda C Li, Eric C Sayre, Hui Xie, Ryan S Falck, John R Best, Teresa Liu-Ambrose, Navi Grewal, Alison M Hoens, Greg Noonan, Lynne M Feehan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.04.2018.)

Background: Organic amine fluorides and nano-hydroxyapatite dentifrices have shown remineralization potential in various studies. However, there is a lack of direct comparison between amine fluoride and nano-hydroxyapatite with conventional inorganic fluorides as sodium monofluorophosphate., Aim: The aim of the study is to evaluate remineralizing efficacy of the three dentifrices on both primary and permanent enamel surfaces., Methods: Enamel sections were obtained from 40 sound molars - 20 primary and 20 permanent molars. Five enamel slabs were prepared from these extracted molars stored in artificial saliva, wherein one slab acted as control, second as demineralized (negative control), and other three slabs were brushed with sodium monofluorophosphate, amine fluoride, and nano-hydroxyapatite dentifrices, respectively, twice daily for 21 days. Scanning electron microscopy- Energy dispersive spectroscopy (SEM-EDS) analysis for surface morphology and calcium and phosphorus content and Vickers surface microhardness (SMH) values were evaluated at baseline, after demineralization, and postapplication of the experimental agents., Results: Highly significant changes in calcium phosphorus ratio and SMH values were seen in enamel slabs treated with nano-hydroxyapatite and amine fluoride dentifrice as compared to sodium monofluorophosphate in both primary and permanent teeth. Surface morphology of enamel slabs treated with amine fluoride most closely resembled natural enamel morphology, while sodium monofluorophosphate-treated surfaces showed globular pattern of remineralization. Deposition of a separate highly mineralized layer over existing surface was seen in nano-hydroxyapatite-treated surfaces., Conclusions: Nano-hydroxyapatite exhibited highest remineralization potential in terms of mineral gain followed by amine fluoride and sodium monofluorophosphate dentifrice., Competing Interests: There are no conflicts of interest

Dentine Dysplasia is a rare genetic condition. The treatment options and dilemmas associated with the condition remain undiscovered so far. This article highlights the variations in traits and challenges faced in the treatment of the cases., Competing Interests: There are no conflicts of interest

Background: Patients with Marfan (MFS) syndrome and patients with a bicuspid aortic valve (BAV) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common as well as distinct pathways of clinical relevance, we compared the histopathological substrates of aortic pathology., Patient and Methods: Ascending aortic wall specimen were divided in five groups: BAV (n=36) and TAV (n=23) without and with dilation and non-dilated MFS (n=8). We performed routine histology to study aortic wall features based on the aortic consensus statement. Immunohistological markers for vascular smooth muscle cell (VSMC) maturation, and expression of fibrillin-1 were additionally investigated for the underlying pathogenesis., Results: On basis of the routine histology the aorta in MFS was similar to the aorta in dilated TAVs (overall medial degeneration, elastic fiber fragmentation, loss and disorganization, , and VSMC nuclei loss). The other markers aided in clustering the MFS and BAV patients with a significantly lower fibrillin-1 expression as compared to the TAVs (p<0.05), a lower level of differentiated VSMC markers (p<0.05) and elastic fiber thinning., Conclusions: Pathogenesis of aortopathy in MFS overlaps with mechanisms seen in BAV and TAV, leading to a so called double hit hypothesis for aortic complications in MFS. The ascending aortic wall in MFS is immature with undifferentiated VSMCs and low levels of fibrillin-1. The immature media becomes even more vulnerable for aortopathy due to other degenerative features which develop probably as a direct consequence of the fibrillin-1 mutation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Being physically active is an essential component of successful self-management for people with inflammatory arthritis; however, the vast majority of patients are inactive. This study aims to determine whether a technology-enabled counselling intervention can improve physical activity participation and patient outcomes., Methods: The Effectiveness of Online Physical Activity Monitoring in Inflammatory Arthritis (OPAM-IA) project is a community-based randomized controlled trial with a delayed control design. We will recruit 130 people with rheumatoid arthritis or systemic lupus erythematosus, who can be physically active without health professional supervision. Randomization will be stratified by diagnosis. In Weeks 1-8, participants in the Immediate Group will: 1) receive education and counselling by a physical therapist (PT), 2) use a Fitbit and a new web-based application, FitViz, to track and obtain feedback about their physical activity, 3) receive 4 biweekly follow-up calls from the PT. Those in the Delayed Group will receive the same program in Week 10. We will interview a sample of participants about their experiences with the intervention. Participants will be assessed at baseline, and Weeks 9, 18 and 27. The primary outcome measure is time spent in moderate/vigorous physical activity in bouts of ≥ 10 min, measured with a portable multi-sensor device in the free-living environment. Secondary outcomes include step count, time in sedentary behaviour, pain, fatigue, mood, self-management capacity, and habitual behaviour., Discussion: A limitation of this study is that participants, who also administer the outcome measures, will not be blinded. Nonetheless, by customizing existing self-monitoring technologies in a patient-centred manner, individuals can be coached to engage in an active lifestyle and monitor their performance. The results will determine if this intervention improves physical activity participation. The qualitative interviews will also provide insight into a paradigm to integrate this program to support self-management., Trial Registration: Date of last update in ClinicalTrials.gov: September 18, 2015. ClinicalTrials.gov Identifier: NCT02554474., Competing Interests: Dr. Linda Li is supported by the Harold Robinson/Arthritis Society Chair in Arthritic Diseases award, the Canada Research Chair Program, and the Michael Smith Foundation for Health Research (MSFHR) Scholar Award. Dr. Hui Xie is supported by the Maureen and Milan Ilich / Merck Chair in Statistics for Arthritis and Musculoskeletal Diseases award. Dr. Antonio Aviña-Zubeita is supported the BC Lupus Association Scholar Award and the MSFHR Scholar Award. Dr. Diane Gromala is supported by the Canada Research Chair Program.The research protocol has been approved by the University of British Columbia Clinical Research Ethics Board (H15–01843), and published in ClinicalTials.gov (NCT02554474). Written consent will be obtained from all participants.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Owing to the innate noise in the biological data sources, a single source or a single measure do not suffice for an effective disease gene prioritization. So, the integration of multiple data sources or aggregation of multiple measures is the need of the hour. The aggregation operators combine multiple related data values to a single value such that the combined value has the effect of all the individual values. In this paper, an attempt has been made for applying the fuzzy aggregation on the network-based disease gene prioritization and investigate its effect under noise conditions. This study has been conducted for a set of 15 blood disorders by fusing four different network measures, computed from the protein interaction network, using a selected set of aggregation operators and ranking the genes on the basis of the aggregated value. The aggregation operator-based rankings have been compared with the "Random walk with restart" gene prioritization method. The impact of noise has also been investigated by adding varying proportions of noise to the seed set. The results reveal that for all the selected blood disorders, the Mean of Maximal operator has relatively outperformed the other aggregation operators for noisy as well as non-noisy data.

Objective: The National Inpatient Sample (NIS) from years 2010 through 2012 was utilized to determine the incidence, predictive risk factors, and outcomes of heparin-induced thrombocytopenia (HIT) in patients undergoing vascular surgery., Design: Retrospective population-based study., Setting: Data from the National Inpatient Sample (NIS) (2011 through 2013) using specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes corresponding with vascular surgery., Participants: 425,379 hospital admissions in patients which underwent vascular surgery. Among these, 1,290 (0.31%) were diagnosed with HIT, and 17,765 (4.18%) were diagnosed with secondary thrombocytopenia., Measurements and Results: The incidence of HIT is 0.3% in the vascular surgery population. The highest incidence is observed in thoraco-subclavian and vein reconstruction procedures. This study indicated that liver disease, endocarditis, chronic renal failure, congestive heart failure, atrial fibrillation, obesity, and female sex are associated with a higher incidence of HIT in this population. In vascular surgery patients, HIT can increase mortality by 3-fold and lead to severe complications such as acute renal failure, venous embolism, pulmonary embolism, and respiratory failure., Conclusion: The incidence of HIT in the vascular surgery population is similar to previously reported incidence in cardiac surgery patients. In the vascular surgery population, mortality increases 3-fold in patients with HIT versus those without any thrombocytopenia. Understanding the associated risk factors and complications will allow clinicians to make informed decisions and anticipate HIT and associated complications in certain high-risk populations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The transversus abdominis plane (TAP) block is a relatively straightforward regional technique used for postoperative analgesia in patients undergoing abdominal surgeries. Various adjuvants have been used in past to prolong the duration of action of analgesia in peripheral nerve blocks. Several studies investigating the analgesic efficacy of dexamethasone added to local anesthetic agents, such as bupivacaine, have shown promising results. However, there are few studies comparing the efficacy of dexamethasone with ropivacaine., Objectives: To determine if the addition of dexamethasone 8 mg to ropivacaine 0.2% in a TAP block would prolong the analgesic effect when compared with ropivacaine 0.2% alone after inguinal hernia repair and spermatocelectomy., Study Design: A randomized, double blinded, placebo-controlled, prospective study., Setting: Teaching hospital., Methods: A total of 82 patients undergoing inguinal hernia repair or spermatocelectomy were enrolled in the study, of which 41 patients received TAP block with ropivacaine with saline, and the other 41 received ropivacaine with dexamethasone immediately following surgery. Both the proceduralist (resident) and the patient were blinded to the solution used. Visual analog pain scores (0 - 10) were obtained pre-block and immediately post block. Our primary endpoint was visual analog pain score at 12 hours, with 24 and 48-hour pain scores as the secondary endpoints., Results: The averaged pre-block pain score was 7.6 ± 1.7 in the saline group and 7.7 ± 2.2 in the dexamethasone group. There was an improvement in the pain scores from the baseline, at 12 hours after the administration of the block in both the groups. Although the dexamethasone group had a greater change in pain score (-3.2) than the saline group (-2.2), the difference between the 2 groups was not statistically significant (0.08). We did not observe significant differences in change from baseline at 24 hours and 48 hours between the 2 groups (P value = 0.74 and 0.44, respectively)., Limitations: We did not assess the total dose of analgesics used during the surgery with the assumption that the effect of intraoperative analgesics should wear off by the time we collect the 12-hour pain score. We did not control for the expertise of the provider that performed the block, as some of the providers may have been junior residents with limited experience and expertise in the area. Additionally, we were unable to include postoperative opioid consumption due to concerns of inconsistencies during patient reporting and data quality., Conclusions: In conclusion, we could not show a statistically significant prolongation of analgesia for TAP blocks with ropivacaine when dexamethasone was added, though there was a one point drop in pain score at 12 hours post block when dexamethasone was added to the block solution. This decrease in pain scores at 12 hours may still be beneficial to patient satisfaction given the low side effect profile of dexamethasone. As ropivacaine has a lower pH than other local anesthetic agents, further well designed studies are needed to investigate the combination of this drug with more alkaline drugs like corticosteroids., Key Words: Regional anesthesia, transversus abdominis plane, dexamethasone, ropivacaine.

Background: Percutaneous endoscopic gastrostomy (PEG) is a frequently performed invasive procedure that has been associated with high short-term mortality. Its use of special interest in traumatic brain injury (TBI) patients as nutrition support constitutes important issues in intensive care of this group. We used a national database to determine the incidence of, and factors associated with, in-hospital mortality among TBI patients undergoing PEG., Methods: We conducted a retrospective study using the US nationwide inpatient sample to analyze data from all hospitalizations in 2008 with International Classification of Diseases, Ninth Revision, diagnostic and procedure codes identifying patients with TBI and hemorrhagic stroke who received PEG. Bivariate and multivariate logistic regression analyses were performed using demographic and clinical variables to identify predictors of in-hospital mortality in this patient population. Patients who did not undergo PEG were used as control., Results: In-hospital mortality after PEG was 6% (95% CI, 0.05-0.76%) among the TBI population with 0.2% occurring in the first 7 days and 2% occurring in the first 14 days. These patients had a higher incidence of other trauma-related comorbidities and were classified as high-risk stratification based on SRRi score compared to the non-PEG group. Factors strongly predictive of in-hospital mortality were age >51 years, not receiving a PEG, and having a high comorbidity burden of >2., Conclusion: Understanding the rate of mortality associated with PEG in this patient population and identifying factors that increase and decrease the risk of death will improve patient selection for those most likely to benefit from this procedure.

Background: Enamel remineralization potential of variety of products has been established, but there is a lack of evidence of comparison of remineralization potential of natural versus synthetic products., Aim: The aim of this study was to compare the enamel remineralization potential of saliva, cheese, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-based synthetic agent, and fluoride toothpaste., Design: In situ study was carried out on sixty individuals who wore an intraoral appliance containing demineralized enamel slabs for each agent. One out of six slabs was kept as a control so as to record the baseline values (neither subjected to demineralization nor remineralization). Experimental agents were applied on the designated enamel slabs on day 1, 4, 7, and 10 with a crossover wash out period of 7 days. Quantitative values of mineral content of slab were measured using energy dispersive X-ray and qualitative changes in surface topography of slab were seen under scanning electron microscope at ×20K magnification., Results: Highly significant changes from baseline values were seen in calcium and phosphorus content of slabs treated with cheese and CPP-ACP-based agent whereas levels of fluoride were significantly higher in enamel slabs treated with fluoride-containing toothpaste., Conclusion: Cheese is an organic, economical, and user-friendly option over prescribed synthetic agents. A synergistic effect of fluoride-containing toothpaste with intake of cheese could be a good enamel remineralization protocol.

Background: Considering the biological concerns of calcium hydroxide (CH) as a pulpotomy agent, an alternative silicate based dentin substitute i.e. Biodentine (Ca 3 SiO 5 ) was evaluated clinically and radiographically., Aims: To evaluate the effectiveness of dentin substitute (Biodentine) in regenerative pulpotomy of vital primary teeth that would giv a biological base to its use in forming reactive dentin bridge and overcoming the drawbacks of calcium hydroxide., Material and Methods: Randomised clinical trial on 40 bilateral carious primary molars in 20 participant children (aged 5-10 years) was carried out by same operator using Ca 3 SiO 5 (group-1) and CH (group-2) as vital pulpotomy agents. Blinded clinical and radiographic outcomes were observed at 3, 6 and 12 months interval., Results: Clinical outcomes of both protocols were analysed using Pearson's chi-square test applied at P < 0.05. Descriptive statistics were expressed as mean increase in dentin bridge formation in mms from two reference points in standardized radiographs using paired ' t '- test at baseline and 12 months and found to be statistically significant ( P < 0.05) in group-1 when compared with group-2., Conclusion: Group-1 revealed statistically favourable regenerative potential along with clinical success compared to group 2 thereby sharing both indications and mode of action with CH, but without its drawbacks of physical and clinical properties., Competing Interests: There are no conflicts of interest.

Background: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database., Methods: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www.genecards.org). The results of our search were entered into the Pathway Interaction Database from the National Cancer Institute (PID-NCI) (http://pid.nci.nih.gov), to generate a biomolecule interaction map., Results: The results of our query yielded 690 genes for HCC, 98 genes for CC and 50 genes for HCC-CC. Genes depicted in this analysis demonstrate the role of hormonal regulation, embryonic development, cell surface adhesion, cytokeratin stability, mucin production, metalloproteinase regulation, Ras signaling, metabolism and apoptosis. Examples of previously described markers included hepatocyte growth factor (HGF), mesenchymal epithelial transition (MET) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Novel markers included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), GPC3, choline kinase alpha (CHKA), prostaglandin-endoperoxide synthase 2 (PTGS2), telomerase reverse transcriptase (TERT), myeloid cell leukemia 1 (MCL1) and N-acetyltransferase 2 (NAT2)., Conclusions: GeneCards is a useful research tool in the genetic analysis of low frequency malignancies. Utilizing this tool we identified several biomarkers are methods for diagnosing HCC-CC. Finally, utilizing these methods, HCC-CC was found to be predominantly a subtype of CC.

Background: The objective of this meta-analysis to evaluate safety and efficacy of transradial vs the transfemoral approach for primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients., Methods: Randomized controlled trials that compared the transfemoral vs the transradial approach in STEMI patients who underwent PCI were searched in PubMed, Embase, CENTRAL, Cumulative Index to Nursing and Allied Health Literature, and clinicaltrials.gov. Random effect models were used to pool effect sizes., Results: Sixteen trials, comprising data from 9726 patients, were included in the meta-analysis. All-cause mortality (risk ratio [RR], 0.68; 95% confidence interval [CI], 0.54-0.85; relative risk reduction [RRR], 32.8%; I(2) = 0), major bleeding (RR 0.56; 95% CI, 0.42-0.74; RRR, 48.1%; I(2) = 0), access site bleeding (RR, 0.38; 95% CI, 0.29-0.50; RRR, 63.9%; I(2) = 0), major adverse cardiovascular events (RR, 0.80; 95% CI, 0.68-0.94; RRR, 19.3%; I(2) = 0), and length of hospital stay (standardized mean difference, -0.38 days; 95% CI, -0.46 to -0.31 days) were significantly lower with the transradial compared with the transfemoral approach. The greatest reduction in major bleeding was found in the subgroup with trials recruiting only primary PCI participants compared with varying proportions of rescue PCIs. Glycoprotein IIb/IIIa inhibitor use and cross-over rates did not have a significant association with outcome measures in the subgroup analysis. Incidence of stroke was numerically greater with the transradial approach but did not achieve statistical significance (RR, 1.22; 95% CI, 0.56-2.66; I(2) = 0). Overall statistical heterogeneity (I(2)) was very low except for length of hospital stay., Conclusions: The transradial approach for PCI in STEMI patients significantly reduced all-cause mortality, major and access site bleeding, major adverse cardiovascular events, and length of hospital stay. Difference in stroke incidence was not statistically significant with the transradial vs the transfemoral approach., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients.