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    Weston General Hospital,Weston Area Health NHS Trust

    EST. 1986
    300论文总数
    4,939引用总数

    Weston General Hospital is an NHS district general hospital in the town of Weston-super-Mare, Somerset, England, operated by University Hospitals Bristol and Weston NHS Foundation Trust. As of June 2019[update], the hospital had 261 beds and around 1,800 clinical and non-clinical staff.It has a part-time Accident & Emergency department, an intensive care unit, an oncology and haematology day unit, and a day case unit. The hospital also has a 12-bed private unit, The Waterside Suite, wholly owned by the hospital trust, with profits being re-invested into the main hospital.

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    R Ahmad
    R Ahmad
    Department of Trauma & Orthopaedic Surgery, Weston General Hospital
    论文:15引用:0H-index:0
    Lindsay K Smith
    Lindsay K Smith
    University of the West of England, Bristol
    论文:8引用:0H-index:0
    Guo Shi-Gong
    Guo Shi-Gong
    Department of Rehabilitation Medicine, Southmead Hospital
    论文:5引用:0H-index:0
    Robert F Spencer
    Robert F Spencer
    Dept Trauma & Orthopaed, Weston Gen Hosp
    论文:5引用:0H-index:0
    VG Langkamer
    VG Langkamer
    Weston General Hospital
    论文:4引用:0H-index:0
    Laura Yarram
    Laura Yarram
    Bristol Genetics Laboratory, Southmead Hospital
    论文:4引用:0H-index:0
    Graham Bayly
    Graham Bayly
    Bristol Royal Infirm, Univ Hosp Bristol NHS Fdn Trust
    论文:4引用:0H-index:0
    Sharon D. Whatley
    Sharon D. Whatley
    5Department of Medical Biochemistry and Immunology, University Hospital of Wales
    论文:4引用:0H-index:0
    Bartlett Amy
    Bartlett Amy
    Weston General Hospital
    论文:4引用:0H-index:0

    论文(300)

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    1National Survey of Protocols for Day-Case Hip and Knee Arthroplasty in the UK
    Tomos A Edwards, Jamie Large, Jonathan M R French, Jonathan T Evans,Mike R Reed,Michael R Whitehouse, Day Case Collaborative, Aaron B Y Ng, Abel Hosea, Akhilesh Pradhan, Akshay Date, Alexander Charalambous,

    Aims: Day-case joint arthroplasty, where patients are discharged on the day of surgery, is increasingly used to meet rising demand in a resource-efficient manner. NHS England guidance states that all patients should be placed on an ambulatory pathway (zero to one night stay). However, little is known about the prevalence, structure, and implementation of day-case protocols across the UK. Methods: An online survey was sent to all NHS institutions performing hip or knee arthroplasty. Respondents reported the presence of day-case, ambulatory (zero to one night stay), or generic enhanced recovery protocols. Data were collected across 21 questions covering key perioperative domains and analyzed descriptively, and model health system data was used to assess length of stay (LoS). Results: Overall, 63 responses were received covering 86 hospitals (56 trusts), of which 78 (91%) perform day-case surgery. In total, 41 (48%) had a dedicated day-case protocol, 23 (27%) had ambulatory protocols, and 15 (17%) used generic enhanced recovery pathways. Only 22% of hospitals with a day-case pathway placed all patients on it by default. Protocol content showed substantial variation, including the use of sedation as part of anaesthesia (49%), presence of therapy services beyond 17:00 (59%), and nurses competent in assessing day zero mobility (56%). One third of hospitals had no mechanism for patients to contact out-of-hours support. LoS was shorter in hospitals using day-case or ambulatory protocols when compared with those that did not, however, this did not reach statistical significance. Conclusion: While day-case joint arthroplasty is widely performed in the NHS, dedicated protocols are used in fewer than half of hospitals, and considerable variation exists. These results can be used collaboratively by hospitals that are trying to establish pathways, and to guide further research aiming to identify best practice and provide standardization for day-case protocols. Cite this article: Bone Jt Open 2026;7(5):651–658.

    2026Bone & joint open(2026)
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    2Bi-atrial Structural and Mechanical Remodelling in Cirrhosis: an Echocardiographic Strain-Based Phenotyping Study
    Sameer Purra, Sheikh Jan Mohammad, Qayoom Yousuf, Shahnawaz Shah

    Abstract Background Cirrhosis is associated with a hyperdynamic circulatory state and chronic volume overload, which may lead to cardiac remodeling before overt ventricular dysfunction becomes evident. Conventional echocardiographic assessment relies largely on atrial size, potentially underestimating early atrial mechanical dysfunction. Objectives To evaluate left and right atrial structural and mechanical remodeling in patients with cirrhosis using echocardiography and atrial strain imaging, and to assess their relationship with liver disease severity. Methods In this cross-sectional study, patients with cirrhosis and age- and sex-matched healthy controls underwent comprehensive transthoracic echocardiography. Left atrial volume index and right atrial area index were measured using standard techniques. Left and right atrial reservoir strain were assessed using two-dimensional speckle-tracking echocardiography. Associations between atrial parameters and MELD-Na score were analyzed. Results Cirrhotic patients demonstrated significant impairment in both left and right atrial reservoir strain compared with controls, despite only modest differences in atrial size. A substantial proportion of patients exhibited preserved atrial dimensions with impaired atrial strain, indicating early mechanical dysfunction. Progressive deterioration in bi-atrial strain was observed across increasing MELD-Na categories. Conclusions Cirrhosis is associated with early bi-atrial mechanical dysfunction detectable by strain imaging, preceding overt atrial enlargement and conventional diastolic abnormalities. Atrial strain provides incremental insight into cirrhotic cardiomyopathy and may serve as a useful tool for early cardiovascular phenotyping in chronic liver disease.

    2026Annals of Clinical Cardiology(2026)
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    3Negative Pressure Intrusion Cementation Versus Tourniquet Use in Total Knee Arthroplasty: Optimising Cement Mantle Thickness.
    Omar Javed, Kassem Abu Ein, Morgan Montaque, Lindsay Smith,Riaz Ahmad

    Avoidance of tourniquet in total knee arthroplasty (TKA) has been shown in some studies to be associated with less serious adverse events (SAEs) than use of a tourniquet. Concerns about inadequate cementation leads to some surgeons using a tourniquet, to avoid implant failure from aseptic loosening. Negative pressure intrusion cementation (NPI) is an alternative technique to remove blood from the surgical field. It is unknown whether using NPI and no tourniquet gives a comparable cement mantle thickness (CMT) to TKA surgery with a tourniquet. This retrospective study compared two techniques for reducing blood during cementation in primary TKA–NPI vs. tourniquet—at a single centre (2016–2023). After screening 353 patients, 80 patients with adequate postoperative radiographs were included. CMT was measured in six zones according to a modified Knee Society Scoring System, creating a cumulative score for each patient. The Mann–Whitney U test was used to compare groups (non-parametric data), and the Intraclass Correlation Coefficient (ICC) was used to measure inter- and intra-observer reliability. There was a significant difference in CMT in favour of the group with NPI vs. tourniquet (median 12.43 mm vs. 10.67 mm, U = 596, p = 0.05), with a small effect size (r = 0.2). Inter- and intra-observer reliability were good and excellent respectively. This retrospective cohort study identified a small increase in cumulative CMT in primary TKA using NPI without tourniquet use compared with tourniquet use alone. This technique warrants further study to confirm its clinical significance and relationship to aseptic loosening.

    2026European Journal of Orthopaedic Surgery & Traumatology(2026)
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    4The Diagnostic Accuracy of 18F-Naf PET/CT Versus 99mtc Bone Scintigraphy for Detection of Skeletal Metastases: A Systematic Review and Meta-Analysis
    Tosif Quazi, Haroon Rashid, Aamir Shah, Elena Khalid

    Objectives: To compare the diagnostic accuracy of 18F-sodium fluoride (NaF) PET/CT (Positron Emission Tomography/Computed Tomography) and 99mTc(Technitium-99m) bone scintigraphy for detecting skeletal metastases across malignancies using head-to-head, patient-level studies. Methods: A systematic search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library was conducted up to March 2025 following PRISMA 2020 guidelines. Eligible studies directly compared NaF PET/CT and 99mTc scintigraphy in the same patients and provided extractable 2×2 data. Quality was assessed with QUADAS-2 (quality assessment of diagnostic accuracy studies). Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated using a bivariate random-effects model. Narrative synthesis was performed for studies without full 2×2 tables. Results: Six studies met inclusion, with four eligible for meta-analysis (prostate, breast, thyroid, renal, and nasopharyngeal cancers; n=468 patients). Pooled sensitivity and specificity of NaF PET/CT were 0.96 (95% CI, 0.91–0.99) and 0.93 (95% CI, 0.88–0.97), respectively, compared with 0.72 (95% CI, 0.63–0.80) and 0.81 (95% CI, 0.71–0.89) for 99mTc bone scintigraphy. The pooled DOR for NaF PET/CT was 342.1 versus 23.5 for bone scintigraphy. Heterogeneity was low-to-moderate. Narrative synthesis of two additional studies confirmed consistent superiority of NaF PET/CT. Conclusions: NaF PET/CT demonstrates significantly higher sensitivity, specificity, and overall diagnostic accuracy than 99mTc bone scintigraphy for detecting skeletal metastases across malignancies. Supported by multiple head-to-head studies and meta-analyses, NaF PET/CT is well positioned to replace bone scintigraphy as the reference standard in oncologic practice. Future work should assess cost-effectiveness, multicancer prospective validation, and integration with PET/MRI platforms. Introduction Bone metastases represent a frequent and serious complication of advanced malignancies, especially prostate, breast, lung, thyroid, and renal cancers, and are associated with significant morbidity, pain, and skeletal-related events that negatively impact survival and quality of life (1). Accurate and early detection of skeletal metastases is therefore essential for appropriate staging, prognostication, and treatment planning. For decades, 99mTc-methylene diphosphonate (MDP) bone scintigraphy has served as the reference standard for detecting osseous metastases. While widely available and cost-effective, its diagnostic performance is hampered by limited spatial resolution and suboptimal specificity, particularly in differentiating malignant from benign degenerative or inflammatory changes (2). The addition of SPECT or SPECT/CT has improved localization, but sensitivity remains modest for small or early lesions (2, 5). NaF PET/CT has emerged as a powerful alternative owing to its favorable pharmacokinetics, rapid blood clearance, and high affinity for hydroxyapatite crystals at sites of active bone remodeling (3, 4). These properties provide markedly higher bone-to-background ratios and superior image quality compared with 99mTc-based tracers. The integration of PET technology further enhances lesion detection through higher spatial resolution, tomographic capability, and quantitative assessment. Multiple head-to-head studies have demonstrated the superiority of NaF PET/CT over conventional scintigraphy. Even-Sapir et al. (5) showed significantly higher sensitivity in patients with high-risk prostate cancer, while Ota et al. (7) reported similar findings in differentiated thyroid carcinoma. Abikhzer et al. (8) extended these observations to breast cancer, and Gerety et al. (9) found that NaF PET/CT detected all lesions in renal cell carcinoma compared with only 29% by bone scintigraphy. More recently, Wang et al. (6) confirmed the superior diagnostic accuracy of NaF PET/CT in nasopharyngeal carcinoma. Jambor et al. (14) further validated its performance against MRI, demonstrating NaF PET/CT as the most accurate modality in high-risk prostate cancer. Early studies by Schirrmeister et al. (20) also highlighted its potential in breast cancer patients. Systematic reviews and meta-analyses corroborate these findings. Sheikhbahaei et al. (1) and Perera et al. (16) demonstrated pooled sensitivities exceeding 90% and specificities above 95% for NaF PET/CT in prostate cancer, markedly outperforming bone scintigraphy. Evangelista et al. (18) and Fan et al. (12) extended these observations across multiple malignancies, confirming consistently superior diagnostic accuracy. Reviews by Langsteger et al. (11), Mick et al. (10), Bastawrous et al. (4), and Lindenberg et al. (15) emphasize NaF PET/CT’s role in routine oncologic imaging, while Beheshti et al. (12) published EANM (European Association of Nuclear Medicine) guidelines formalizing technical protocols and clinical applications. Despite robust evidence, most prior reviews included lesion-based analyses or heterogeneous designs, limiting their direct applicability to clinical decision-making. To address these limitations, the present systematic review and meta-analysis focuses strictly on patient-level, head-to-head comparisons of NaF PET/CT versus 99mTc bone scintigraphy, providing pooled estimates of sensitivity and specificity across multiple cancer types. Methods Literature Search Strategy We conducted a systematic literature search of PubMed, Embase, Scopus, and Web of Science from inception through March 2025 to identify studies comparing NaF PET or PET/CT with 99mTc-based bone scintigraphy (planar or SPECT) for detection of skeletal metastases. Search terms combined synonyms for “sodium fluoride,” “PET/CT,” “bone scintigraphy,” “skeletal metastasis,” and cancer-specific keywords (e.g., prostate, breast, lung, thyroid, nasopharyngeal, renal cell carcinoma). Reference lists of retrieved ar-ticles and relevant reviews were also screened. The review process followed PRISMA-DTA guidelines, and a flow diagram is shown in Figure 1. Eligibility Criteria Studies were included if they: - Enrolled patients with histologically confirmed or clinically suspected malignancy at risk of bone metastasis; - Performed both NaF PET/CT (or PET alone) and 99mTc bone scintigraphy in the same patient cohort or in contemporaneous comparative cohorts; - Reported sufficient per-patient diagnostic data to construct a 2×2 contingency table (true positive, false positive, true negative, false negative). Studies were excluded: - if they only reported lesion-level data; - did not include a direct comparison, or duplicated previously published cohorts; - Studies without extractable patient-level data were retained for narrative synthesis only. Data Extraction and Quality Assessment Two reviewers independently extracted study characteristics, patient demographics, technical details of imaging protocols, and diagnostic accuracy outcomes (Table 1). For eligible studies, 2×2 contingency data were extracted to calculate sensitivity and specificity for each modality. If raw 2×2 data were unavailable but sufficient secondary data were provided (e.g., reported sensitivity and denominators), reconstructed values were derived and flagged accordingly. Studies lacking such reconstruction were included in the narrative-only table. Risk of bias was assessed using the QUADAS-2 tool, evaluating domains of patient selection, index test, comparator test, reference standard, and flow/timing. Statistical Analysis Sensitivity and specificity with 95% confidence intervals (CIs) were calculated using the Clopper–Pearson exact method. Forest plots were generated for each modality (Figures 2–3). Pooled estimates were obtained using a random-effects model (DerSimonian–Laird) applied on the logit scale. Summary results are provided in Table 2. A ROC scatter plot was constructed for NaF PET/CT (3) to illustrate study-level performance distribution. Narrative-only studies were synthesized descriptively to contextualize findings in additional cancer populations. Results The initial search identified 750 records (732 from databases and 18 from other sources). After removal of duplicates, 600 records were screened by title and abstract, of which 40 full-text articles were assessed. Ultimately, 7 studies were included in the quantitative synthesis and 2 were retained for narrative-only analysis (Figure 1). The 7 quantitative studies comprised 476 patients across diverse malignancies: prostate (two studies), lung (two studies), nasopharyngeal carcinoma (one study), differentiated thyroid carcinoma (one study), and breast cancer (one reconstructed dataset). Five were head-to-head comparisons, and two were reconstructed data-sets based on published accuracy values (Table 1). The two narrative-only studies evaluated renal cell carcinoma and a multicenter mixed cohort of prostate and breast cancer. Diagnostic accuracy results are presented in Table 2. Across individual studies, NaF PET/CT demonstrated consistently higher sensitivity than 99mTc bone scintigraphy. For instance, in prostate cancer cohorts, NaF PET/CT achieved sensitivities of 0.95–1.00 compared with 0.60–0.75 for bone scintigraphy. Similar patterns were observed in lung and nasopharyngeal carcinoma studies. Specificity was also generally higher for NaF PET/CT (typically 0.90–1.00) compared with bone scintigraphy (0.70–0.90), although greater variability was noted when equivocal scintigraphy scans were classified as positive. When pooled using a random-effects model, 18F-NaF PET/CT achieved a sensitivity of 0.96 (95% CI 0.91–0.99) and specificity of 0.93 (95% CI 0.88–0.97), whereas bone scintigraphy achieved a pooled sensitivity of 0.72 (95% CI 0.63–0.80) and specificity of 0.81 (95% CI 0.71–0.89). Forest plots illustrate the per-study accuracy estimates for sensitivity and specificity of both modalities (Figures 2 & 3), while the ROC scatter plot demonstrates that NaF PET/CT results clustered tightly in the upper-left quadrant, reflecting both high sensitivity and high specificity across studies. The narrative synthesis reinforced these findings. In renal cell carcinoma, NaF PET/CT detected all 77 malignant bone lesions compared with only 29% detected by bone scintigraphy (Gerety et al. 2015). The multicenter MITNEC-A1 trial similarly confirmed the superiority of NaF PET/CT over 99mTc SPECT/CT in prostate and breast cancer, although raw 2×2 patient-level data were not available for pooling. Together, the pooled and narrative data highlight the consistent diagnostic advantage of 18F-NaF PET/CT over conventional bone scintigraphy in detecting skeletal metastases across multiple cancer types. Discussion This meta-analysis demonstrates that NaF PET/CT provides substantially superior diagnostic performance compared with 99mTc-methylene diphosphonate (MDP) bone scintigraphy in detecting skeletal metastases across malignancies. Our pooled results showed that NaF PET/CT achieved markedly higher sensitivity and specificity, consistent across cancer types and sensitivity analyses. These findings confirm that NaF PET/CT can overcome the limitations of conventional scintigraphy and offer improved staging accuracy, with significant implications for patient management. Comparison with Previous Literature Our results align closely with prior systematic reviews and meta-analyses. Sheikhbahaei et al. (1) reported pooled sensitivity of 91.9% and specificity of 97.1% for NaF PET/CT in prostate cancer, compared with 47.0% and 94.1% for bone scintigraphy. Evangelista et al. (18) also found pooled sensitivity exceeding 90% across malignancies, while Perera et al. (16) confirmed similar advantages in prostate cancer biochemical recurrence. More recently, Fan et al. (12) extended these findings in a contemporary meta-analysis, reaffirming the consistently higher diagnostic odds ratio of NaF PET/CT relative to scintigraphy. Collectively, these meta-analyses strengthen the evidence base and corroborate our pooled results. Head-to-head studies provide further support. Even-Sapir et al. (5) demonstrated that NaF PET/CT detected more metastases than scintigraphy in high-risk prostate cancer, while Gerety et al. (9) reported that NaF PET/CT identified all lesions in renal cell carcinoma compared with only 29% for scintigraphy. Ota et al. (7) confirmed these advantages in differentiated thyroid carcinoma, and Abikhzer et al. (8) found superior lesion detection in breast cancer. Wang et al. (6) extended the evidence to nasopharyngeal carcinoma, and Jambor et al. (14) prospectively compared NaF PET/CT with planar scintigraphy, SPECT, and MRI, demonstrating NaF PET/CT as the most accurate modality in prostate cancer. Early work by Schirrmeister et al. (20) also highlighted its diagnostic superiority in breast cancer. Together, these studies provide robust evidence across diverse malignancies. Biological Rationale for Superiority The diagnostic advantage of NaF PET/CT is grounded in its biological and technical features. 18F-fluoride exchanges with hydroxyl groups in hydroxyapatite, localizing rapidly at sites of osteoblastic activity and enabling high lesion-to-background contrast (3). PET technology adds higher spatial resolution, tomographic capability, and the potential for quantitative analysis (10). Compared with 99mTc-MDP scintigraphy, which can be limited by low resolution and nonspecific uptake (2), NaF PET/CT allows earlier detection of subtle or small-volume metastases and more accurate delineation of disease extent. These features are particularly important in cancers such as prostate and breast, where early identification of osseous involvement may change treatment intent (5, 8, 11). Clinical Implications The importance of these results in a clinical context is substantial. Accurate detection of skeletal metastases informs staging, guides systemic therapy initiation, and influences radiotherapy planning. In prostate cancer, NaF PET/CT can distinguish patients who remain candidates for curative therapy from those requiring systemic treatment (11,16). In renal cell carcinoma, Gerety et al. (9) showed that reliance on bone scintigraphy alone risks understaging and suboptimal management. In thyroid and breast cancers, NaF PET/CT has demonstrated value in identifying clinically relevant metastases that may alter management (7, 8, 20). For nasopharyngeal carcinoma, Wang et al. (6) confirmed improved detection, highlighting its broader oncologic applicability. NaF PET/CT may also be valuable in treatment monitoring. Mick et al. (10) and Evangelista et al. (18) suggested that its quantitative capabilities can track therapeutic response more reliably than scintigraphy, which is subject to the “flare” phenomenon. This could make NaF PET/CT an important biomarker in clinical trials and routine practice. Guidelines and Consensus Statements Expert reviews and guidelines endorse the use of NaF PET/CT in oncologic imaging. Langsteger et al. (11) concluded that NaF PET/CT should be considered the preferred modality for detecting bone metastases in prostate cancer, and the European Association of Nuclear Medicine (EAN-M) has published procedural guidelines standardizing imaging protocols and clinical use (12). Bastawrous et al. (4) and Lindenberg et al. (15) emphasized its integration into routine clinical practice, while Hutchinson (13) highlighted its value in renal cell carcinoma. Together, these publications indicate a growing consensus that NaF PET/CT is poised to replace scintigraphy as the gold standard in many clinical contexts. Limitations Several limitations should be acknowledged. First, although we restricted our analysis to patient-level 2×2 data, some breast and lung studies required reconstructed tables, which may introduce bias (8, 20). Second, reference standards varied, often relying on composite imaging and follow-up rather than histopathological confirmation. Third, heterogeneity in imaging protocols exists across studies, though recent guidelines (12) provide standardized approaches. Finally, NaF PET/CT is not universally available, and cost, reimbursement, and radiation exposure remain barriers to adoption (11, 15). Future Directions Future research should focus on large, prospective, cancer-specific trials directly comparing NaF PET/CT with SPECT/CT and whole-body MRI. Jambor et al. (14) provided a model for such studies, integrating multimodality imaging in a prospective cohort. PET/MRI platforms incorporating NaF may further enhance diagnostic performance while reducing radiation dose. Health-economic evaluations are also needed to support policy decisions, as broader access will depend on demonstrated cost-effectiveness. Conclusion In summary, this meta-analysis confirms that NaF PET/CT significantly outperforms 99mTc bone scintigraphy for detecting skeletal metastases, offering higher sensitivity, specificity, and clinical utility. Supported by multiple head-to-head trials, meta-analyses, and international guidelines, NaF PET/CT is well positioned to become the reference standard for evaluating skeletal metastases across malignancies. Wider adoption into oncologic imaging pathways could improve staging accuracy, optimize treatment strategies, and ultimately improve patient outcomes. Correspondence to: Haroon Rashid Department of Radiodiagnosis Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J&K, India

    2025Swiss Journal of Radiology and Nuclear Medicine(2025)
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    5P112 Obinutuzumab in the Treatment of Life Threatening ANCA-associated Vasculitis
    Shahriar Khan Shahjada, Terence K W Lim, Tom Bucknall, Maja Curuvija, Joanna Robson, Emyr Humphreys

    Granulomatosis with polyangiitis (GPA) is a form of ANCA-associated vasculitis (AAV) often treated with rituximab or cyclophosphamide. While effective, rituximab can cause serious hypersensitivity reactions, limiting its use. Obinutuzumab, a humanised type II anti-CD20 monoclonal antibody, is emerging as an alternative in rituximab-intolerant patients due to its enhanced B-cell cytotoxic effects. We present a case of severe GPA initially treated with rituximab and cyclophosphamide, complicated by multiple life-threatening events and a severe infusion reaction. Subsequent treatment with obinutuzumab led to clinical and serological remission, highlighting its potential as a therapeutic option in complex, rituximab-intolerant AAV. A 24-year-old man presented with a vasculitic rash, haemoptysis, diffuse pulmonary infiltrates, alveolar haemorrhage, and proteinuria. He tested positive for cANCA with a PR3 titre of 2134.6 U/mL (reference: 0.0–19.9). Initial treatment included intravenous methylprednisolone (1g for three days), followed by oral prednisolone (60 mg/day). Shortly after the first dose of rituximab (1g), he developed acute breathlessness; CT pulmonary angiography confirmed multiple pulmonary emboli, and therapeutic enoxaparin (1.5 mg/kg) was initiated. Days later, he suffered a cardiac arrest and was transferred to a tertiary centre for ECMO consideration. Cardiac MRI revealed post-arrest related biventricular failure and diffuse myocardial oedema. Rituximab was suspended, and he was commenced on plasma exchange, avacopan, and pulsed intravenous cyclophosphamide (CYCLOPS regimen). With ongoing refractory GPA, he developed pericarditis and worsening proteinuria. Rituximab was reintroduced but discontinued after 45 minutes due to a hypersensitivity reaction (itchy throat, lip swelling, dry cough, wheeze, and urticaria). Cardiac MRI had normalised by this time. He completed six months of anticoagulation with apixaban. At 6 months, CT Thorax showed multiple large cavitating lesions in both lungs. Two months later, he developed sudden expressive dysphasia. CT angiography confirmed a left middle cerebral artery infarct, and he was thrombolysed. MRI brain showed multifocal ischaemic changes consistent with CNS vasculitis. Anticoagulation was resumed due to atrial tachycardia, despite negative antiphospholipid antibody screens. Following multidisciplinary input, obinutuzumab was initiated (Day 1: 100 mg; Day 2: 900 mg; Day 14: 1g), to be repeated every six months for two years. This was given alongside monthly intravenous immunoglobulin and pulsed cyclophosphamide (12 total doses). Clinical condition improved significantly, with PR3 levels falling to 19.5 U/mL within three months. Subcutaneous methotrexate (20 mg weekly) was introduced to support steroid tapering. Follow up CT Thorax 4 months after obinutuzumab confirmed significant reduction in the number and size of the lung cavities. BSR and EULAR guidelines recommend rituximab or cyclophosphamide for induction of remission in organ- or life-threatening AAV. However, treatment can be complicated by severe intolerance or toxicity. In this case, initial therapy with glucocorticoids and rituximab was interrupted following a cardiac arrest, pulmonary embolism, and myocardial oedema. Cyclophosphamide, avacopan, and plasma exchange were subsequently introduced. Rituximab was re-administered after disease progression but triggered a severe hypersensitivity reaction, necessitating permanent withdrawal. Disease activity remained high, with central nervous system involvement and stroke, prompting exploration of alternative therapies. Obinutuzumab, a type II humanised anti-CD20 monoclonal antibody, induces more potent B-cell cytotoxicity and enhanced antibody-dependent cellular phagocytosis than rituximab. Though evidence for its use in AAV is currently limited, obinutuzumab has shown potential in refractory autoimmune conditions, particularly in rituximab-intolerant patients. In our case, obinutuzumab, in combination with intravenous immunoglobulin and pulsed cyclophosphamide, was well tolerated and led to rapid clinical and serological remission. This case supports the potential of obinutuzumab as an alternative B-cell depleting agent in complex AAV, particularly when standard treatments are contraindicated or ineffective. The ongoing OBIVAS trial (obinutuzumab in ANCA-associated vasculitis) will further clarify its role and safety profile in this setting. Importantly, this case also demonstrates the need for individualised treatment planning and early multidisciplinary input, particularly in severe, multisystem disease. Referral to centres of expertise can facilitate timely access to specialist interventions, ensure appropriate risk-benefit decisions, and optimise outcomes for patients with complex vasculitis. GPA is a complex condition requiring tailored immunosuppressive strategies, especially in severe or treatment-refractory cases. While rituximab is widely used for both induction and maintenance of remission, its use may be limited by infusion reactions or rare cardiovascular complications, including myocardial infarction, cardiogenic shock, and arrhythmias. This case underscores the importance of recognising and managing rituximab intolerance. Despite intensive treatment with corticosteroids, cyclophosphamide, plasma exchange, and avacopan, our patient experienced persistent disease activity and multiple life-threatening complications, including cardiac arrest and CNS vasculitis. Obinutuzumab, a type II humanised anti-CD20 monoclonal antibody, offers a mechanistically distinct option for B-cell depletion. In this patient, obinutuzumab was well tolerated and, when used alongside intravenous immunoglobulin and pulsed cyclophosphamide, induced rapid clinical and serological remission. ANCA and PR3 titres normalised within three months, and further relapses were prevented. Although current evidence for obinutuzumab in AAV is limited to case reports and small series, early experiences are encouraging. The OBIVAS trial will provide essential data to evaluate its safety and efficacy in a broader patient population. This case also highlights the vital role of specialist multidisciplinary teams and clinical networks of expertise in managing complex vasculitis. Collaborative care enabled timely access to alternative therapies and optimised decision-making in the face of drug intolerance and life-threatening complications. In summary, obinutuzumab may represent a viable and effective alternative for patients with GPA who are intolerant of rituximab. Personalised care and close collaboration with specialist centres are essential in navigating complex treatment pathways and improving outcomes in severe AAV.

    2025Rheumatology Advances in Practice(2025)
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