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Asian Journal of Surgery Jun 2024
PubMed: 38942627
DOI: 10.1016/j.asjsur.2024.06.029 -
RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278 -
Korean Journal of Radiology Jul 2024Since the emergence of the first photon-counting computed tomography (PCCT) system in late 2021, its advantages and a wide range of applications in all fields of... (Review)
Review
Since the emergence of the first photon-counting computed tomography (PCCT) system in late 2021, its advantages and a wide range of applications in all fields of radiology have been demonstrated. Compared to standard energy-integrating detector-CT, PCCT allows for superior geometric dose efficiency in every examination. While this aspect by itself is groundbreaking, the advantages do not stop there. PCCT facilitates an unprecedented combination of ultra-high-resolution imaging without dose penalty or field-of-view restrictions, detector-based elimination of electronic noise, and ubiquitous multi-energy spectral information. Considering the high demands of orthopedic imaging for the visualization of minuscule details while simultaneously covering large portions of skeletal and soft tissue anatomy, no subspecialty may benefit more from this novel detector technology than musculoskeletal radiology. Deeply rooted in experimental and clinical research, this review article aims to provide an introduction to the cosmos of PCCT, explain its technical basics, and highlight the most promising applications for patient care, while also mentioning current limitations that need to be overcome.
Topics: Humans; Tomography, X-Ray Computed; Photons; Musculoskeletal Diseases; Musculoskeletal System; Radiation Dosage
PubMed: 38942460
DOI: 10.3348/kjr.2024.0096 -
Journal of Clinical Epidemiology Jun 2024Frailty is a dynamic health state that changes over time. Our hypothesis was that there are identifiable subgroups of the older population that have specific patterns of...
OBJECTIVE
Frailty is a dynamic health state that changes over time. Our hypothesis was that there are identifiable subgroups of the older population that have specific patterns of deterioration. The objective of this study was to evaluate the application of joint latent class model (JLCM) in identifying trajectories of frailty progression over time and their group-specific risk of death in older people.
STUDY DESIGN AND SETTING
The primary care records of UK patients, aged over 65 as of January 1 2010, included in the CPRD: GOLD and AURUM databases, were analysed and linked to mortality data. Electronic frailty index (eFI) scores were calculated at baseline and annually in subsequent years (2010-2013). JLCM was used to divide the population into clusters with different trajectories and associated mortality hazard ratios (HR). The model was built in GOLD and validated in AURUM.
RESULTS
Five trajectory clusters were identified and characterised based on baseline and speed of progression: low-slow, low-moderate, low-rapid, high-slow and high-rapid. The high-rapid cluster had the highest average starting eFI score; 7.9, while low-rapid cluster had the steepest rate of eFI progression; 1.7. Taking the low-slow cluster as reference, low-rapid and high-rapid had the highest HRs: 3.73 (95%CI 3.71 to 3.76) and 3.63 (3.57 to 3.69), respectively. Good validation was found in the AURUM population.
CONCLUSION
Our research found that there are vulnerable subgroups of the older population who are currently frail or have rapid frailty progression. Such groups may be targeted for greater healthcare monitoring.
PubMed: 38942178
DOI: 10.1016/j.jclinepi.2024.111442 -
The Lancet. Rheumatology Jun 2024Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial...
Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial.
BACKGROUND
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis.
METHODS
This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18-75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658).
FINDINGS
From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five).
INTERPRETATION
Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated.
FUNDING
Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.
PubMed: 38942047
DOI: 10.1016/S2665-9913(24)00099-7 -
Stem Cell Research Jun 2024Marfan Syndrome, a connective tissue disorder caused by Fibrillin-1 (FBN1) gene mutations, induces disease in the ocular, musculoskeletal, and cardiovascular systems and...
Marfan Syndrome, a connective tissue disorder caused by Fibrillin-1 (FBN1) gene mutations, induces disease in the ocular, musculoskeletal, and cardiovascular systems and increases aortic vulnerability to rupture associated with high mortality rates. We describe an induced pluripotent stem cell line (HFD1) generated from patient-derived human dermal fibroblasts harboring a heterozygous c.3338-2A>C intronic splice acceptor site variant preceding Exon 28 of FBN1. The clonal line, which produces abnormal FBN1 splice variants, has a normal karyotype, expresses appropriate stemness markers, and maintains trilineage differentiation potential. This line represents a valuable resource for studying how abnormal splicing variants contribute to Marfan Syndrome.
PubMed: 38941881
DOI: 10.1016/j.scr.2024.103475 -
International Journal of Surgery Case... Jun 2024Adamantinomas are rare, low-grade, malignant skeletal tumors accounting for only 0.33-0.48 % of primary malignant bone tumors.
INTRODUCTION AND IMPORTANCE
Adamantinomas are rare, low-grade, malignant skeletal tumors accounting for only 0.33-0.48 % of primary malignant bone tumors.
CASE PRESENTATION
An 11-year-old boy with adamantinoma of the ulna was treated with en bloc resection, kryptonite bone cement, and plate fixation. The surgery resulted in marked pain relief and good functional recovery. No evidence of recurrence was observed for 5 years postoperatively, and the Musculoskeletal Tumor Society score was 93.
CLINICAL DISCUSSION
This case of an 11-year-old previously treated for an aneurysmal bone cyst (ABC) illustrates the complexity of diagnosing adamantinoma, especially in atypical locations like the ulna. The successful use of en bloc resection and synthetic bone graft highlights the importance of accurate diagnosis and advanced surgical methods in achieving favorable outcomes in pediatric orthopedic oncology.
CONCLUSION
Ulnar adamantinomas are rare and can be difficult to diagnose. The successful treatment of this tumor, as described in this case report, can help guide the management of similar cases in the future.
PubMed: 38941733
DOI: 10.1016/j.ijscr.2024.109935 -
PloS One 2024Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal,...
BACKGROUND
Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal, cardiovascular and respiratory complications.
PURPOSE
This study aimed to identify the symptom responses and disease burden of long COVID in individuals with spinal cord injury.
METHODS
This case-control study was conducted on patients with SCI residing at a specialised rehabilitation centre in Bangladesh. Forty patients with SCI with and without long COVID symptoms (LCS) were enrolled in this study at a 1:1 ratio according to WHO criteria.
RESULT
Twelve LCS were observed in patients with SCI, including fatigue, musculoskeletal pain, memory loss, headache, respiratory problems, anxiety, depression, insomnia, problem in ADL problem in work, palpitation, and weakness. The predictors of developing long COVID include increasing age (p<0.002), increasing BMI (p<0.03), and longer duration of spinal cord injury (p<0.004). A significant difference (p<0.01) in overall years of healthy life lost due to disability (YLD) for non-long COVID cases was 2.04±0.596 compared to long COVID (LC) cases 1.22±2.09 was observed.
CONCLUSION
Bangladeshi patients of SCI presented 12 long COVID symptoms and have a significant disease burden compared to non long COVID cases.
Topics: Humans; Spinal Cord Injuries; Male; Female; COVID-19; Case-Control Studies; Adult; Middle Aged; Bangladesh; Disabled Persons; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 38941308
DOI: 10.1371/journal.pone.0304824 -
Health Technology Assessment... Jun 2024Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment.
OBJECTIVE(S)
To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation).
DESIGN
A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out.
SETTING
Twenty-nine NHS orthopaedic units in the United Kingdom.
PARTICIPANTS
Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee.
INTERVENTIONS
Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol.
MAIN OUTCOME MEASURES
The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage.
RESULTS
Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent ( = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% ( = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent ( = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% ( = 248; surgical, = 128; rehabilitation, = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent ( = 65) of surgery patients did not reach their expected activity level compared to 73% ( = 63) in the rehabilitation arm. There were no differences between groups in surgical complications ( = 1 surgery, = 2 rehab) or clinical events ( = 11 surgery, = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, = 0.177), but with higher NHS healthcare costs (£1107, < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively.
LIMITATIONS
Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic.
CONCLUSIONS
Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation.
FUTURE WORK
Confirmatory studies and those to explore the influence of fidelity and compliance will be useful.
TRIAL REGISTRATION
This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367.
FUNDING
This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in ; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Male; Female; Anterior Cruciate Ligament Injuries; Adult; United Kingdom; Cost-Benefit Analysis; Anterior Cruciate Ligament Reconstruction; Quality of Life; Quality-Adjusted Life Years; Middle Aged; Young Adult; State Medicine; Joint Instability; Adolescent; Technology Assessment, Biomedical
PubMed: 38940695
DOI: 10.3310/VDKB6009 -
Annals of Agricultural and... Jun 2024Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid...
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid adenomas, ganglioneuromas of the digestive tract, and musculoskeletal abnormalities. The case is presented of a 31-year-old male patient with numerous polyps in the colon described as ganglioneuromas which are ectodermal neoplasms emerging from a proliferation of ganglionic cells of the sympathetic nervous system. The results show elevated levels of normetanephrine, which is an endogenous catecholamine metabolite, and has high diagnostic sensitivity as well as specificity in pheochromocytoma detection. The patient underwent partial thyreoidectomy due to a nodular goiter. He was admitted to the Department of Gastroenterology to lead a diagnostic pathway towards MEN 2B.
Topics: Humans; Male; Adult; Multiple Endocrine Neoplasia Type 2b; Ganglioneuroma
PubMed: 38940117
DOI: 10.26444/aaem/171736