Clinical Group Study Research Articles

Application of Risk-Based Cancer Screening in Patients With Dermatomyositis.

This cohort study investigates the performance of the International Myositis Assessment and Clinical Studies Group cancer screening recommendations in a community setting.

High-intensity resistance training improves quality of life, muscle endurance and strength in patients with myositis: a randomised controlled trial

Myositis is associated with reduced quality of life, which is accompanied by significant impairments in muscle endurance and strength, altogether representing cardinal traits in patients with myositis. This randomised controlled trial aimed to investigate the effect of high-intensity resistance training on quality of life in patients with myositis. Thirty-two patients with established, stable myositis were randomised to 16 weeks of high-intensity resistance training (intervention group) or 16 weeks of usual care (control group). Primary outcome was quality of life assessed as the change in the physical component summary score (PCS) of the Short Form-36 health questionnaire from baseline to post-intervention. Secondary outcomes included functional capacity measures, such as functional index 3, and International Myositis Assessment and Clinical Studies Group (IMACS) disease activity and damage core set measures, including manual muscle testing 8 (MMT8). The primary outcome PCS showed an improvement in favour of high-intensity resistance training with a between-group difference of 5.33 (95% CI 0.61; 10.05) (p = 0.03). Additionally, functional index 3 showed a between-group difference indicating greater gains with high-intensity resistance training 11.49 (95% CI 3.37; 19.60) (p = 0.04), along with a between-group improvement in MMT8 1.30 (95% CI 0.09; 2.51) (p = 0.04). High-intensity resistance training for 16 weeks effectively improved quality of life in patients with myositis. Clinical measures of muscle endurance and muscle strength were also found to improve with high-intensity resistance training, while patients stayed in disease remission. Consequently, progressively adjusted high-intensity resistance training is feasible and causes no aggravation of the disease, while benefitting patients with myositis.Clinical trial registration: Clinicaltrials.gov ID: NCT04486261—https://clinicaltrials.gov/study/NCT04486261.

Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk.

Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition.

Muscle biopsy practices in the evaluation of idiopathic inflammatory myopathies: An international survey of expert clinicians

BackgroundMuscle biopsy is an important test in the evaluation of individuals with suspected myopathy, including those with suspected idiopathic inflammatory myopathy (IIM). Various approaches, including open surgical biopsy, needle biopsy and conchotome forceps, have been reported. However the real-world utilisation of these approaches remains unclear. There are no established guidelines for the use of muscle biopsy, or selection of biopsy technique, in investigating IIM and international practices are not well-documented. This study describes current approaches to muscle biopsy amongst clinicians with expertise in IIM. MethodsA survey regarding muscle biopsy practices was disseminated among members of the International Myositis Assessment and Clinical Studies (IMACS) group. Data were analysed using descriptive statistics. ResultsOne-hundred and sixteen clinicians completed the survey, primarily rheumatologists. Open surgical biopsy was the most commonly employed technique (74.5 %), followed by needle (11.3 %) and conchotome (9.4 %) approaches. Clinical examination was the most common method of muscle selection, with 85.2 % of respondents reporting they ‘always or almost always’ relied on it. MRI and electromyography were also frequently utilised for muscle selection (51.9 %, 45.4 % respectively). There was variability in the perceived utility of muscle biopsy in certain clinical contexts, such as presence of myositis specific antibodies or cutaneous manifestations of dermatomyositis. While respondents generally reported low complication rates following muscle biopsy, non-diagnostic histopathology was commonly reported, regardless of procedural approach. ConclusionClinicians managing IIM report muscle biopsy to be well tolerated however, non-diagnostic results are common. Substantial heterogeneity regarding perceived indications for biopsy, procedural approaches, and muscle selection strategies were observed within this expert group. Future research is needed to establish best practice and determine the role of muscle biopsy in the context of continued advancements in serological profiling of IIM.

Clinical and Functional Effects of Rehabilitation of Patients after COVID-19 Infection.

Background/Objectives: The most common post-acute consequences of SARS-CoV-2 include lung dysfunction, the impairment of cognitive functions and mental health, as well as the impairment of the musculoskeletal system in the form of fatigue and muscle weakness. Post-COVID-19 patients often experience impaired balance and reduced physical capacity. It is important to implement a rehabilitation program that eliminates the side effects of COVID-19 and allows for significant improvement in the patient's functionality. The aim of our study was to assess patient functionality after a 6-week rehabilitation program on balance, foot pressure distribution, and physical capacity in post-COVID-19 patients. Methods: The clinical study group consisted of 53 people 3 months after COVID-19 infection, confirmed by a positive PCR test. Exclusion from the study included people with comorbidities that impaired balance and gait. The patients underwent a posturographic assessment-Romberg test, a baropodometric assessment-static and dynamic, and a performance assessment-a 6 min walk test determining shortness of breath on the mMRC scale, blood pressure, heart rate, and saturation. Patients participated in rehabilitation until the sixth week, after which they were assessed again. Comparisons were made using IBM SPSS Statistics 27.0 software using the Wilcoxon pairwise order test, at a significance level of p < 0.05. Results: The result of the postural control assessment showed an improvement in the ability to maintain the centre of gravity in terms of the foot support area-statistical decreases were observed in the ellipse area, from 745.28 mm2 to 453.52 mm2 (p = 0.009), as well as maximum (from 3133.5 gr/cm2 to 2994.2 gr/cm2; p = 0.065) and average load on the left foot (from 1010.1 gr/cm2 to 969.38 gr/cm2; p = 0.028). In the 6 min walk test before and after exercise, the heart rate decreased after the therapy (shortness of breath on the mMRC scale also decreased from 79.12 to 74.95). This means that patients achieved better physical fitness and efficiency. Conclusions: Rehabilitation significantly improved balance, as measured by a decrease in ellipse area during the Romberg test.

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK

ObjectivesTo validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)’s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy.MethodsTwelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them.ResultsIn total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases).ConclusionsA decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.

E059 Identifying the associations between anxiety/depression and disease activity in idiopathic inflammatory myopathy

Abstract Background/Aims Idiopathic inflammatory myopathy (IIM) is characterised by myositis, which can impact activities of daily living. The 2022 BSR IIM management guideline recommends assessing/managing factors associated with poor mental wellbeing and quality of life. Research into anxiety and depression associated with IIM is limited. This study aims to investigate associations between anxiety/depression and IIM disease activity. Methods The MYOPROSP study recruited UK adults with verified IIM throughout a 36 month period between 2016 and 2020. Patient questionnaires were collected at three, six, and 12 months. Participants completed the EQ-5D-5L questionnaire, which includes a question relating to anxiety and depression with five possible responses: “I am (not/slightly/moderately/severely/extremely) anxious or depressed”. The cohort was divided by response to the EQ-5D-5L anxiety/depression question at the time of recruitment. Disease activity was assessed using International Myositis Assessment &amp; Clinical Studies Group (IMACS) Disease Activity Core Set Measures (see Table 1) and summarised across each EQ-5D-5L anxiety/depression group. The EQ-5D-5L visual analogue scale (VAS) relating to “overall health” (higher values correspond to better health) this value was summarised across each EQ-5D-5L anxiety/depression group. Only participants with complete data at recruitment were included in analysis. One-way ANOVA was performed to determine statistical significance (p &amp;lt; 0.05) of each IMACS Disease Activity Core Set Measure and EQ-5D-5L VAS across anxiety/depression groups. Results Complete data on 35 participants (71% female) was collected. All participants reported to have no, slight, or moderate anxiety/depression (i.e. no participant reported severe or extreme anxiety/depression) (Table 1). The “not anxious/depressed” group demonstrated higher EQ-5D VAS values (reflecting better perceived health), shorter disease duration, and higher CK levels, compared to groups with “slight” and “moderate” anxiety/depression. All other investigated variables did not consistently vary across anxiety/depression groups. One-way ANOVA identified that only disease duration and EQ-5D VAS were significantly associated with EQ-5D-5L anxiety/depression group. Conclusion Anxiety and depression are associated with longer disease duration and poorer overall health in adults with IIM. These findings suggest that anxiety/depression in adults with IIM may be due to sustained muscle damage and resulting impacts upon activities of daily living and quality of life, rather than disease activity. Disclosure N.Z. Aziz: None. A. Oldroyd: None. F. Bozan: None. X. Lyu: None. J.A. Lamb: None. P. Gordon: None. D.A. Isenberg: None. N. McHugh: None. H. Gunawardena: None. P. Kiely: None. P.M. Machado: Consultancies; PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. J. Miller: None. S. Tansley: None. A. Bharadwaj: None. R. Laxminarayan: None. N. Jordan: None. C. Yee: None. D. Makkuni: None. J. Taylor: None. P.C. Lanyon: Consultancies; PCL has received consultancy fees from Pfizer. Grants/research support; PCL has received research grants, speaker fees and conference attendance support from CSL Vifor. V.H. Ong: None. A. Prabu: None. M. Akil: None. K.M. Douglas: None. E. Stathopoulou: None. M. Regan: None. H. Chinoy: None.

Phylogenetic position and genetic features of HIV-1 in CNS

Background. Due to the wide coverage with antiretroviral therapy, the life expectancy of HIV infected people has significantly increased. Against the background of a decrease in mortality from HIV infection, HIV-associated neurocognitive disorders, which develop even during effective treatment, are of high importance. The overall prevalence of this pathology among HIV-infected people reaches 42.6%.&#x0D; The objective of the study was to research the genetic features and phylogenetic position of HIV-1 persisting in the central nervous system.&#x0D; Materials and methods. The clinical study group consisted of 38 patients with severe neurocognitive disorders against the background of HIV infection in stage 4B. The viral load of HIV-1 in blood plasma and cerebrospinal fluid (CSF) was measured using the "AmpliSens HIV Monitor-FRT" reagents kit. Sanger sequencing was performed using the AmpliSens HIV-Resist-Seq assay kit on an Applied Biosystems 3500 analyzer. Phylogenetic analysis of the pol gene fragments of HIV-1 strains (the site encoding the viral protease and part of the reverse transcriptase) was carried out using maximum likelihood method with the GTR+G nucleotide substitution model. Comparisons of the tertiary structure of viral proteins were performed according to three-dimensional models of the protease and p51 and p66 reverse transcriptase subunits obtained by homologous reconstruction using the SWISS-MODEL tools.&#x0D; Results. The viral load in the sample of patients with severe CNS lesions in blood plasma was 6.27 times higher than in CSF and amounted to 4.67 and 3.87 lg copies/ml respectively by median (p = 0,004).&#x0D; Phylogenetic analysis with the use of all available HIV-1 genomes from GenBank, which differed from the studied ones by less than 5% showed close genetic relations of viruses circulating in Chelyabinsk region, apart from strains circulating in Russian Federation, with viruses circulating in neighboring countries, in most abundance — from Ukraine and Kyrgyzstan, slightly less — from Belarus, Tajikistan, Kazakhstan and Armenia and also with strains from certain foreign countries: Poland and Germany. Phylogenetic analysis of 38 HIV-1 genomes revealed significant genetic distances between HIV isolates from blood plasma and CSF in 5 patients, 4 of whom were PWID, which may indicate an event of superinfection.&#x0D; The amount of independent amino acid substitutions in protease in isolates from blood plasma ranged from 1 to 3, in isolates from CSF — from 1 to 2. An amount of such substitutions in a fragment of reverse transcriptase in isolates from blood plasma ranged from 1 to 6, while in isolates from CSF, it ranged from 1 to 7. HIV isolates from blood plasma and CSF from 5 patients had differences in the tertiary structure of HIV-1 reverse transcriptase p51 subunit in amino acid positions 16–20 and 210–235. Isolates from 3 other patients differed in the tertiary structure only in amino acid positons 210–235. Isolates from 3 patients differed in the structure of HIV-1 RT p66 subunit in a non-nucleoside reverse transcriptase inhibitor binding pocket (NNRTI) region. Fixed differences in the tertiary structure of p51 subunit required at minimum only 1 amino acid substitution to emerge. Alterations in the tertiary structure of p66 subunit required at least 3 amino acid substitutions.&#x0D; Conclusion. Microevolution of HIV-1 proceeds in parallel within the same patient, in different compartments, which is reflected in the accumulation of amino acid substitutions different from another compartment in the conserved pol gene. There is a weak correlation between the viral load level in plasma and in CSF. The genetic heterogeneity of HIV strains from patients of the Chelyabinsk region indicates a high frequency of reintroduction of HIV infection in the region from other countries. Differences in the tertiary structure of HIV-1 reverse transcriptase between blood plasma and CSF isolates are regularly fixed in certain domens, which also confirms the presence of parallel HIV microevolution during virus persistence in tissues separated by the blood-brain barrier which allows a better understanding of the fixation trends of individual amino acid substitutions during HIV-induced damage to central nervous system.

Characteristics of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; carriage in the pediatric population

Objective: to investigate the regional peculiarities of Streptococcus pneumoniae carriage in the pediatric population and characterize the dominant serotypes of the pathogen.&#x0D; Materials and methods. The clinical study group consisted of 509 healthy children attending preschool institutions. Examination of nasopharyngeal samples for the detection of S. pneumonae was carried out by classical bacteriological and molecular biological methods. The serotype was determined by real-time PCR. Genome-wide sequencing of the serogroups 15 and 11 isolates and bioinformatic analysis were performed.&#x0D; Results. The S. pneumoniae bacterial carriers in the group of healthy children was detected in 207 children (40.7%), while the frequency of detection of S. pneumoniae in urban children living in Kazan was significantly higher than in children living in rural area and amounted to 53.4 and 31.1%, respectively (p 0.05). Among children vaccinated with the 13-valent pneumococcal conjugate vaccine (PCV-13), S. pneumoniae carriers were not detected in 57.5% of cases. There were no significant differences in the degree of nasopharyngeal contamination depending on the vaccination status. Analysis of the serotype composition indicates the predominance of vaccine serotypes (57.7%), while the share of serotypes included in the PСV-13 vaccine accounts for only 24.7%, the share of non-vaccine serotypes was 32.1%, untyped — 10.2%. In unvaccinated children, vaccine serotypes that are part of the PCV-13 and 23-valent polysaccharide pneumococcal vaccine prevailed (PPSV-23): 6ABCD (21%), 11 AD (15%), 14 (13%). In vaccinated children, serotypes not included in the active vaccines dominated: 15AF (17.4%), 23A (19.2%), as well as 11AD (19.6%) (11А is included in PPSV-23). The 27 Kz isolate (serotype 15C) belonged to one of the most common sequence types ST1025. The 105_Kz isolate (serotype 11D) belonged to another common sequence type ST 62.&#x0D; Conclusion. In order to improve epidemiological surveillance of pneumococcal infection, it is necessary to introduce the monitoring of circulating clonal complexes of dominant S. pneumoniae serogroups and analyze the genetic determinants of antibiotic resistance and virulence depending on the sequence type.

Exploratory prospective, randomized phaseII study of neoadjuvant transcatheter arterial chemoembolization plus surgery versus surgery alone for large hepatocellular carcinoma (CSGO-HBP-005): Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group.

Neoadjuvant transcatheter arterial chemoembolization (TACE) for large tumors is controversial, especially in the minimally invasive surgery era. The aim of this study was to compare features between groups treated with neoadjuvant TACE followed by surgery (TACE+surgery) or upfront surgery for hepatocellular carcinoma >5cm. In this exploratory, multicenter, randomized phaseI study, the primary measure was 2-year disease-free survival (DFS). Secondary measures were resection rate, necrosis rate by TACE, 2-year overall survival, and site of recurrence. A total of 30 patients were randomly allocated to each arm. The two arms did not differ in patient characteristics. The median time to surgery from randomization was 48days for TACE+surgery and 29 for surgery only (p<0.001). Postoperative morbidities did not differ between arms. The 2-year DFS, overall survival, and resection rates were 56.7%, 80.0%, and 93.3%, respectively, in the TACE+surgery arm, and 56.1%, 89.9%, and 90.0% in the upfront surgery arm. Minimally invasive surgery was carried out in 35.7% in the TACE+surgery arm and in 29.6% in the upfront surgery arm. The median necrosis rate by TACE was 90.0%. In resected specimens, invasion to the hepatic vein was less with TACE+surgery (3.6% vs. 22.2%, p=0.0380). In cases of 100% necrosis with TACE, 2-year DFS was 100%. Site of recurrence did not differ between groups. Neoadjuvant TACE did not improve 2-year DFS, and neoadjuvant TACE allowed delay of surgical treatment without increased morbidity and cancer progress. UMIN: 000005241.

A Review of The Evidence for the Utility of Physical Activity Monitor Use in Patients with Idiopathic Inflammatory Myopathies.

Few proven therapies exist for patients with idiopathic inflammatory myopathies (IIM), partly due to the lack of reliable and valid outcome measures for assessing treatment responses. The current core set measures developed by the International Myositis Assessment and Clinical Studies group were developed to standardize assessments of disease activity and treatment effect. None of the current measures address functional improvement in muscle weakness. Therefore, supplemental measures for more objectively assessing physical activity levels and fatiguability in free-living settings are needed to assess disease activity more comprehensively. Validated physical activity monitors (PAMs) have the potential to serve as an objective functional outcome measure in clinical trials and observational studies. This review examines the current evidence for using body-worn PAMs in clinical settings with IIM patients. A practical overview of methods for PAM use in clinical patient populations (including measurement details and data processing) that focuses on IIM patients is also presented.

International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical StudiesGroup (IMACS)initiative.

Adult-onset idiopathic inflammatory myopathy (IIM) is associated with an increased cancer risk within the 3 years preceding and following IIM onset. Evidence- and consensus-based recommendations for IIM-associated cancer screening can potentially improve outcomes. This International Guideline for IIM-Associated Cancer Screening provides recommendations addressing IIM-associated cancer risk stratification, cancer screening modalities and screening frequency. The international Expert Group formed a total of 18 recommendations via a modified Delphi approach using a series of online surveys. First, the recommendations enable an individual patient's IIM-associated cancer risk to be stratified into standard, moderate or high risk according to the IIM subtype, autoantibody status and clinical features. Second, the recommendations outline a 'basic' screening panel (including chest radiography and preliminary laboratory tests) and an 'enhanced' screening panel (including CT and tumour markers). Third, the recommendations advise on the timing and frequency of screening via basic and enhanced panels, according to risk status. The recommendations also advise consideration of upper or lower gastrointestinal endoscopy, nasoendoscopy and 18F-FDG PET-CT scanning in specific patient populations. These recommendations are aimed at facilitating earlier IIM-associated cancer detection, especially in those who are at a high risk, thus potentially improving outcomes, including survival.

Diverse Research Teams and Underrepresented Groups in Clinical Studies

Several ophthalmic diseases disproportionately affect racial and ethnic minority patients, yet most clinical trials struggle to enroll cohorts that are demographically representative of disease burden; some barriers to recruitment include time and transportation, language and cultural differences, and fear and mistrust of research due to historical abuses. Incorporating diversity within the research team has been proposed as a method to increase trust and improve engagement among potential study participants. To examine how demographic factors of potential research participants and personnel may be associated with patient consent rates to participate in prospective ophthalmic clinical studies. This retrospective cohort study included patients from an urban, academic hospital who were approached for consent to participate in prospective ophthalmic clinical studies conducted between January 2015 and December 2021. Multivariable logistic regression assessing associations between patient and research personnel demographics and rates of affirmative consent to participate was used. In total, 1380 patients (mean [SD] age, 58.6 [14.9] years; 50.3% male) who were approached for consent to participate in 10 prospective ophthalmic clinical studies were included. Of prospective patients, 566 (43.5%) were Black; 327 (25.1%), Hispanic or Latino; 373 (28.6%), White; 36 (2.8%), other race and ethnicity; and 78 (5.8%) declined to answer. Black patients (odds ratio [OR], 0.32; 95% CI, 0.24-0.44; P < .001) and Hispanic or Latino patients (OR, 0.31; 95% CI, 0.20-0.47; P < .001) were less likely to consent compared with White patients. Patients with lower socioeconomic status were less likely to consent than patients with higher socioeconomic status (OR, 0.43; 95% CI, 0.33-0.53; P < .001). Concordance between patient and research staff race and ethnicity was associated with increased odds of affirmative consent (OR, 2.72; 95% CI, 1.99-3.73; P < .001). In this cohort study, patients from underrepresented racial and ethnic groups and those with lower socioeconomic status were less likely to participate in ophthalmic clinical studies. Concordance of race and ethnicity between patients and research staff was associated with improved participant enrollment. These findings underscore the importance of increasing diversity in clinical research teams to improve racial and ethnic representation in clinical studies.

VersKiK: Study protocol of an observational registry-based study on the current state of follow-up care and adherence to follow-up guidelines after cancer in childhood or adolescence

BackgroundThis article describes the study design of the quantitative part of the VersKiK study, The primary objectives of this study are to examine the occurrence of late effects in survivors of childhood or adolescent cancer (module 1), investigate health-related vulnerabilities and medical service utilization within this survivor group (modules 1 and 3), and assess the alignment between documented follow-up care for cardiological and audiological late effects with guideline recommendations, along with evaluating the extent of adherence among paediatric cancer survivors (module 3). MethodsThis is a non-interventional retrospective observational cohort study. It is based on stochastically linked insurance claims data from approximately 150,000 statutory insured persons with information concerning around 25,000–30,000 cancer survivors recorded in the German Childhood Cancer Register (GCCR). To explore adherence to selected follow-up guidelines, intention to treat treatment data from clinical study groups for particular diagnostic entities will be additionally included. DiscussionThe growing group of survivors after cancer in childhood and adolescence is representing a special population with an increasing demand for life-long healthcare services through relative high probability of late effects. Currently, there is a limited evidence in Germany on utilization of corresponding medical services and adherence to follow-up guidelines. With this study design, we are aiming to address these gaps and, consequently, suggest improvements to existing follow-up guidelines and follow-up care provision in Germany.

Advances in Precision Medicine Approaches for Type 2 Diabetes Management: A Comprehensive Review

Projections indicate that, approximately 700 million people will be living with diabetes by 2050, a figure that has doubled in the previous twenty years. The rising cost of type 2 diabetes care might be reduced and existing treatment gaps could be closed with the help of precision medicine. Taking into consideration each individual unique genetic, environmental, and behavioral characteristic, precision medicine is a new approach to treatment. The primary goal of precision medication is to accurately foresee how a patient will respond to treatment. It may be used as a prophylactic strategy for the whole population because of how broadly it applies. Medication, weight reduction, regular exercise, and a nutritious diet all work together to prevent type 2 diabetes. Optimizing metabolic control is one way in which this kind of diabetes therapy has a probability to reduce death rates and improve standard of life. Inadequate funding for translational health research, incompatible data formats, a lack of system interoperability, a lack of decision-making support systems, and a lack of IT infrastructure support are just some of the obstacles to the widespread utilization of precision medicine technologies in clinical practice. Forecast translation of scientific results into practical applications may be aided by the creation of a worldwide clinical studies group dedicated to raising public understanding and appreciation of the great advantages of precision medicine in treating diabetes.

The Effect of Topical Application of Hyaluronic Acid on the Stability of Immediate Loaded Dental Implants in the Posterior Maxilla: Clinical and Animal Study.

Objective: To assess the effect of topically applied hyaluronic acid (HA) on the stability of immediately loaded implants in the posterior maxilla. Materials and Methods: For the clinical study, a total of 20 implants were placed in 14 patients seeking the replacement of missing single or multiple posterior maxillary teeth. The patients were randomly divided into two groups. In the clinical control group (CC group), 10 implants were placed and immediately loaded, while in the clinical study group (CS group), 10 implants were coated with HA immediately before placement and immediately loaded. All patients had implant stability clinically evaluated at implant placement time (T0) and 1 (T1), 3 (T3), and 6 (T6) months after loading. Peri-implant pocket depth and modified sulcus bleeding index were evaluated clinically at 6 months in all patients. Bone density was evaluated radiographically after 3 months. All the clinical and radiographic data were subjected to statistical analysis. For the animal study, a total of 12 implants were placed in the tibiae of six rabbits. For each rabbit, 1 implant without any applied HA was placed in the left tibia (AC group), and 1 implant coated with HA was placed in the right tibia (AS group). The rabbits were euthanized at 21 and 45 days after implant insertion. Results: There were no significant statistical differences between the two groups regarding implant stability, peri-implant pocket depth, modified sulcus bleeding index, or bone density from the palatal and apical aspects. However, there was a significant statistical difference in the bone density from the buccal aspect in favor of the study group. The animal study showed that the newly formed bone in the right tibiae showed improved quantity and quality of bone, as it had denser bone trabeculae and smaller marrow spaces compared to the left tibiae. Conclusion: In the clinical study, the application of hyaluronic acid had a superior effect on the buccal bone density around immediately loaded implants. In the animal study, hyaluronic acid had a synergistic effect on the quality and quantity of bone formation around dental implants.

Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy.

This open-label, 24-week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM). Ten patients ≥7 years of age with moderate disease activity were enrolled in a 24-week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)-regulated gene score was performed on whole-blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay. Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P=0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P=0.01). Six patients had down-trending IFN-regulated gene scores and galectin-9 expression at week 24. Decreases in IFN-regulated gene scores and in levels of interferon-γ-inducible protein 10kDa, galectin-9, and interleukin-2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment-emergent adverse events were observed. This open-label study demonstrated that abatacept may be beneficial for patients with treatment-refractory juvenile DM.

Research priorities relating to the delivery of cardiovascular prevention and rehabilitation programmes: results of a modified Delphi process

ObjectiveThe purpose of this British Association for Cardiovascular Prevention and Rehabilitation (BACPR) research priority setting project (PSP) was to identify a top 10 list of priority research questions for cardiovascular...

Rituximab in myositis: where are we now? A survey of current usage.

Dear Editor, In a retrospective analysis 7 years ago, it was estimated that ∼78% of patients with inflammatory myositis were considered to have improved with rituximab (RTX) [1]. The International Myositis Assessment & Clinical Studies (IMACS) group felt it was timely to undertake a prospective study of the use of RTX in myositis. Members of the group were invited to send information about RTX-treated patients from July 2021 during the following year. After lengthy discussions, a simple proforma was produced and sent to the IMACS members on four occasions during the year. The key aims of the study were to: assess the current use of B cell depletion in patients with myositis; obtain background information about which particular patients are being treated in this way; and ascertain if B cell depletion continues to be effective in myositis. Fifty myositis patients from nine referring centres were distinguished in two groups based on the time of first RTX infusion (29 had been prescribed it before July 2021, designated previous users, and 21 were new starters). The patients’ demographic features, characteristics of myositis and treatment response are summarized in Table 1. The median time from the diagnosis until the first RTX infusion was 21.5 months (interquartile range = 65). Most were females (74%), of Caucasian origin (56%) and had a diagnosis of anti-synthetase syndrome (56%). Three out of 50 patients were myositis-specific antibody (MSA) negative. The most common immunosuppressive agent used with RTX was CS (84%), followed by MMF (36%), MTX (10%), AZA (8%), CSA (8%) and CYC (2%). RTX was preferred as a first line drug with steroids in five patients (two were reported to have responded well). Effectiveness was assessed by the treating physician on the basis of clinical observation, reduction in the creatine kinase and capacity to reduce steroids. Based on these components, RTX was reported to be effective in 43 patients (86%), and no benefit was seen in 7 patients (14%). Treatment response was found to be similar in both groups (89.7% vs 81%, P = 0.434). Of note, no statistically significant difference was seen in RTX effectiveness among types of myositis (anti-synthetase syndrome vs others), MSAs and genders. Steroid taper was successfully achieved in 78.7% of patients. Adverse events were noted in seven patients; all were infectious complications with requirement for hospitalization in three cases. Three minor side effects including two infusion reactions and one nausea were reported during the entire follow-up.

A plain language summary of daratumumab plus lenalidomide/bortezomib/dexamethasone in transplant-eligible Black patients with newly diagnosed multiple myeloma in the GRIFFIN study.

This is a summary of a publication about Black participants of the GRIFFIN clinical study that was published in Blood Cancer Journal in April 2022. The GRIFFIN clinical study looked at the treatment combination of daratumumab plus a standard therapy for multiple myeloma (called RVd therapy, which stands for lenalidomide, bortezomib, and dexamethasone) in adult patients who had not been treated before for multiple myeloma and so were considered to have newly diagnosed multiply myeloma. Multiple myeloma is a blood cancer of plasma cells. Based on the participants' age, medical history, and indicators of good general health, the participants in the GRIFFIN study were also eligible to receive autologous stem cell transplant as part of their therapy. This summary describes results for the Black participants of the GRIFFIN clinical study who received daratumumab plus RVd therapy (called D-RVd) to see if D-RVd therapy is better than RVd therapy at reducing the amount of multiple myeloma cancer cells in a patient's body. Due to racial disparities leading to historically low representation of minority groups in clinical studies, optimal treatments are not defined for Black patients with newly diagnosed multiple myeloma. Since previously published results from the overall population in the GRIFFIN study indicated that D-RVd therapy was better than RVd therapy, the researchers wanted to determine if this was also the case among Black participants. Out of 207 participants in the GRIFFIN study, 15% (32 participants) were Black and 78% (161 participants) were White. In both Black and White participants, D-RVd therapy reduced the amount of myeloma cancer cells more than RVd therapy. Additionally, D-RVd and RVd therapy had similar safety results for Black and White participants. This analysis of GRIFFIN by race shows that Black people benefit from the daratumumab-containing D-RVd therapy as much as White people. Additionally, D-RVd therapy had similar safety results to RVd therapy for both Black and White people. Clinical Trial Registration: NCT02874742 (ClinicalTrials.gov).