Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

PURPOSE OF REVIEW: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. RECENT FINDINGS: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

Mortality and Ankylosing Spondylitis in the US population: leading causes and associated factors.

OBJECTIVE: Ankylosing Spondylitis (AS) is a chronic inflammatory condition that affects the axial skeleton. Recent studies have shown that mortality risk is higher in AS patients and that it is possibly related to disease activity and duration. Our aim was to investigate the leading causes and factors associated with mortality in hospitalized AS patients in the USA. METHODS: This is a case-control study using the Cerner Health Facts® database between 2015 and 2017. The search was done using ICD codes and administrative claims. Cases were hospitalized AS patients who died during that hospitalization, while controls were patients who survived. In addition to demographics, we collected data on the inpatient use of medications such as NSAIDs, as well as different comorbidities and systemic disease manifestations. The discharge diagnoses for deceased patients were collected to infer causes of mortality. Analysis of association was performed using chi-square tests, t-tests, Wilcoxon rank-sum tests, and logistic regression methods. RESULTS: The leading causes of death were cardiovascular, infectious, respiratory, and traumatic. The Elixhauser comorbidity index was the factor most associated with mortality (p-value < 0.0001), with congestive heart failure and renal disease the most contributing. Drug use disorder was associated with mortality (adjusted OR = 10.9; p = 0.001). Inpatient NSAIDs use was not associated with increased odds for mortality (p-value 0.33). CONCLUSION: Cardiovascular and renal comorbidities are associated with mortality and need to be targeted early on to lower the odds of mortality as patients age. Strategies to prevent opioid and drug abuse should be strengthened in the AS population. Key Points • Cardiovascular and renal comorbidities are associated with mortality and need to be screened for and targeted early on to lower the odds of mortality as patients age. • Drug use disorder including opioid dependence is associated with mortality, and strategies to prevent opioid and drug abuse should be strengthened in the AS population.

Wedge resection versus lobectomy in T1 lung cancer patients: a propensity matched analysis.

OBJECTIVES: Performing wedge resection rather than lobectomy for primary lung cancer remains controversial. Recent studies demonstrate no survival advantage for non-anatomical resection compared to lobectomy in patients with early-stage lung cancer. The objective of this study was to investigate whether in patients with T1 tumours, non-anatomical wedge resection is associated with equivalent survival to lobectomy. METHODS: This was a retrospective cohort study of patients who underwent lung resection at the Lancashire Cardiac Centre between April 2005 and April 2018. Patients were subjected to multidisciplinary team discussion. The extent of resection was decided by the team based on British Thoracic Society guidelines. The primary outcome was overall survival. Propensity matching of patients with T1 tumours was also performed to determine whether differences in survival rates exist in a subset of these patients with balanced pre-operative characteristics. RESULTS: There were 187 patients who underwent non-anatomical wedge resection and 431 patients who underwent lobectomy. Cox modelling demonstrated no survival difference between groups for the first 1.6 years then a risk of death 3-fold higher for wedge resection group after 1.6 years (HR 3.14, CI 1.98-4.79). Propensity matching yielded 152 pairs for which 5-year survival was 66.2% for the lobectomy group and 38.5% for the non-anatomical wedge group (SMD = 0.58, p = 0.003). CONCLUSIONS: Non-anatomical wedge resection was associated with significantly reduced 5-year survival compared to lobectomy in matched patients. Lobectomy should remain the standard of care for patients with early-stage lung cancer who are fit enough to undergo surgical resection.

Early Re-Exploration versus Conservative Management for Postoperative Bleeding in Stable Patients after Coronary Artery Bypass Grafting: A Propensity Matched Study.

BACKGROUND: Postoperative bleeding requiring re-exploration in cardiac surgery has been associated with complications impacting short-term outcomes and perioperative survival. Many aspects of decision-making for re-exploration still remain controversial, especially in hemodynamically stable patients with significant but not acutely cumulating chest drain output. We investigated the impact of re-exploratory surgery on short-term outcomes in a "borderline population" of CABG patients who experienced significant non-acute bleeding, but that were not in critically hemodynamic unstable conditions. METHODS: A prospectively collected database of 8287 patients undergoing primary isolated elective CABG was retrospectively interrogated. A population of hemodynamically stable patients experiencing significant non-acute or rapidly cumulating bleeding (>1000 mL of blood loss in 12 h, <200 mL per hour in the first 5 h) with normal platelet and coagulation tests was identified (N = 1642). Patients belonging to this group were re-explored (N = 252) or treated conservatively (N = 1390) based on the decision of the consultant surgeon. Clinical outcomes according to the decision-making strategy were compared using a propensity score matching (PSM) approach. RESULTS: After PSM, reoperated patients exhibited significantly higher overall blood product consumption (88.4% vs. 52.6% for red packed cells, p = 0.001). The reoperated group experienced higher rates of respiratory complications (odds ratio 5.8 [4.29-7.86] with p = 0.001 for prolonged ventilation), prolonged stay in intensive care unit (coefficient 1.66 [0.64-2.67] with p = 0.001) and overall length of stay in hospital (coefficient 2.16 [0.42-3.91] with p = 0.015) when compared to conservative management. Reoperated patients had significantly increased risk of multiorgan failure (odds ratio 4.59 [1.37-15.42] with p = 0.014) and a trend towards increased perioperative mortality (odds ratio 3.12 [1.08-8.99] with p = 0.035). CONCLUSIONS: Conservative management in hemodynamically stable patients experiencing significant but non-critical or emergency bleeding might be a safe and viable option and might be advantageous in terms of reduction of postoperative morbidities and hospital stay.

Adenoid cystic carcinoma of the trachea mimicking asthma.

Adenoid cystic carcinoma (ACC) is primarily a salivary gland tumour that rarely involves the respiratory tract. A 58-year-old lady was admitted with worsening dyspnoea, cough and wheezing for 2 days. CT pulmonary angiogram was done due to persistent dyspnoea which revealed a 12 mm mass protruding into the posterior aspect of the trachea with multiple enlarged nodes. There was a complete collapse of the left lower lobe and right middle lobe with right upper lobe pulmonary embolism which was thought to be contributing to her hypoxia. She was struggling with secretion clearance and initial measures to clear her secretions were not successful. She was treated with a tracheal stent, followed by an interval endoscopic ultrasound-guided biopsy of the tracheal wall lesion which revealed ACC. She was referred to cardiothoracic surgeons for excision of the tumour after discussing in MDT. Surgery followed by radiotherapy is advised in cases with incomplete resection margins.

Repair of a Late Presentation Thoracic Aortic Aneurysm following Coarctation Repair.

We report the case of a 44-year-old gentleman who underwent coarctation repair at the age of 7 years. He was lost to follow-up and represented. Computed tomography scan demonstrated a 9.8-cm diameter aortic aneurysm involving the distal aortic arch and proximal descending aorta. Open surgery was performed to repair the aneurysm. The patient made an unremarkable recovery. He was followed up 12 weeks later, and significant improvement in preoperative symptoms was observed. This case demonstrates the importance of long-term follow-up.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

PURPOSE OF REVIEW: This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. RECENT FINDINGS: The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.

Novel therapies in axial spondyloarthritis.

Over the past two decades, advancements in understanding the pathogenesis of axial spondyloarthritis have led to discoveries of new therapeutic targets, particularly the interleukin-17, tumor necrosis factor axis, and Janus kinase-signal transducer and activator of transcription pathway. While many of the available agents have proven to be efficacious and safe for the treatment of axial spondyloarthritis, a remarkable percentage of patients either fail or cannot tolerate these medications. This has prompted researchers to look for new targets that would maximize efficacy and minimize toxicity. In this article, we review novel agents that were recently approved, in trials, and possible future targets or mechanisms. We also discuss their role as it pertains to the prevention of radiographic progression and the management of extra-musculoskeletal manifestations.

A Case of Anti-Jo-1 Myositis with Unique Biopsy Findings.

Antisynthetase syndrome (ASS) or anti-Jo-1 antibody syndrome has a classic clinical presentation including arthritis, myositis, interstitial lung disease, mechanic hands, and/or Raynaud's phenomenon. The biopsy findings are distinctive from polymyositis or dermatomyositis. We describe an interesting case of ASS where a patient presented with significant muscle weakness, proteinuria, and interstitial lung disease. She also had positive Ro-52 antibodies in addition to anti-Jo-1 antibodies. Her biopsy findings were consistent with inflammatory necrotizing myositis.

Malignancy in ankylosing spondylitis: a cross-sectional analysis of a large population database.

BACKGROUND: Increased cancer-risk has been reported with rheumatoid arthritis and systemic lupus erythematosus, but the risk is poorly studied in ankylosing spondylitis (AS). Conflicting data in AS have been reported in Asia and Europe, with lack of US population-based studies. Our objective is to study the prevalence of cancer in patients with AS in the US. METHODS: Using the Explorys database, we performed a cross-sectional study. Data from AS patients and controls were stratified by 2 rheumatology visits, age groups, clinical characteristics, and frequency of cancers. The data were analyzed using a series of chi-square tests of independence as well as logistic regression to test for association between AS and cancer. RESULTS: 1410 AS patients (12.88%) had cancer. Female AS patients had a lower prevalence of cancer compared to controls (OR 0.840, 95% CI [0.769, 0.916]), while male AS patients had no statistically significant difference (OR 1.011, 95% CI [0.929, 1.099]). Among patients with AS, Skin cancers (squamous cell, malignant melanoma, and basal cell) and head and neck cancers were significantly increased. CONCLUSION: Our study demonstrated that the prevalence of "any-type-cancer" was not increased in AS patients compared to controls with no rheumatic disease. Skin, head, and neck cancers were more frequently seen in AS patients.

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer.

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.

Worldwide Differences in Clinical Phenotype of Axial Spondyloarthritis.

PURPOSE OF REVIEW: This review aims to describe the variations in the clinical presentation of axial spondyloarthritis (axSpA) across the globe. RECENT FINDINGS: We searched the PubMed database and screened more than 1360 articles; 60 of them were selected based on relevance to the topic being discussed and the goals of the review. Most of the clinical manifestations, including IBP, peripheral arthritis, and extra-articular involvement are seen in different regions of the world, but with appreciable clinical heterogeneity, possibly related to a smaller number of patients from some countries, and global variation in the prevalence of HLA-B27. For example, HLA-B27-positive patients have an earlier age of onset, higher prevalence of acute anterior uveitis, and greater familial occurrence. Peripheral arthritis and enthesitis are most commonly seen among axSpA patients from Latin America and Asia, whereas IBD appears to be slightly more common among Middle Eastern and North African patients. The main weakness encountered while reviewing these data is that some studies were small, and others were cross-sectional and retrospective; hence the inferences may have a selection bias. AxSpA is a very heterogenous disease with varied presentation across the globe, in part related to HLA-B27 positivity. It is imperative to further investigate the key regional differences as they impact timely disease recognition and initiation of early treatment. Therefore, there is a need for a large worldwide systematic study to capture the clinical picture of AxSpA in a more uniform manner.

Educational needs and challenges in axial spondyloarthritis.

PURPOSE OF REVIEW: Axial spondyloarthritis (axSpA) affects 0.5-1% of the population in many regions of the world. This review summarizes the challenges in medical education around axSpA with attention to evidence around delayed diagnosis, clinician familiarity with typical axSpA features, such as inflammatory back pain and adherence to accepted management principles. RECENT FINDINGS: Clinicians who commonly manage patients with chronic back pain or other typical axSpA features are not consistently aware of the concept of inflammatory back pain and common extra-spinal manifestations. Further, clinicians may not be familiar with the nonradiographic spectrum of axSpA. Management of patients with possible axSpA does not consistently follow principles that would establish an axSpA diagnosis, and diagnosis of axSpA remains delayed by 6-7 years on average, with evidence suggesting management disparities on the basis of sex and race in some cases. Referral recommendations have increased the probability of axSpA diagnosis up to about 40% and, may complement educational efforts in axSpA. SUMMARY: Educational efforts in axSpA should focus on providing front-line clinicians with a better understanding of inflammatory back pain, the nonradiographic form of axSpA, and accepted principles in axSpA management.

Long-term survival in patients who had CABG with or without prior coronary artery stenting.

OBJECTIVE: To conduct a large-scale, single-centre retrospective cohort study to understand the impact of prior percutaneous coronary intervention (PCI) on long-term survival of patients who then undergo coronary artery bypass graft (CABG). METHODS: Between 1999 and 2017, a total of 11 332 patients underwent CABG at a hospital in the UK. The patients were stratified into those who received PCI (n=1090) or no PCI (n=10 242) prior to CABG. A total of 1058 patients from each group were matched using propensity score matching. Kaplan-Meier estimates were used to assess risk-adjusted survival in patients with prior PCI. Cox proportional hazards (CoxPH) model was then used to assess the effect of prior PCI and other variables in patients undergoing CABG. RESULTS: The immediate postoperative outcome showed no difference in number of grafts per patients, blood transfusion, hospital stay or 30 days mortality between the groups. There was no significant difference in 5 years (90.8% vs 87.9), 10-year (76.5% vs 74.6%) and 15-year (64.4% vs 64.7%) survival between the non-PCI versus PCI groups. The Cox proportional hazards model further supports the null hypothesis as the PCI variable was found to be non-significant (CoxPH=1.03, p=0.75, CI=0.87-1.22) implying there was no difference in hazard of death for CABG patients with or without previous PCI. However, the model did yield information on the covariates that do affect the hazard of death. CONCLUSION: There is no difference in 5-year, 10-year and 15-year survival between patients undergoing CABG with or without prior PCI. However, certain patient, preoperative and intraoperative risk factors were identified with high hazard of death which needs to be investigated further.

Long-term survival following on-pump and off-pump coronary artery bypass graft surgery: a propensity score-matched analysis.

OBJECTIVES: Recent studies have once again brought into focus the long-term survival following off-pump coronary artery bypass grafting (OPCAB) compared with conventional on-pump coronary artery bypass grafting surgery (ONCAB). The aim of this study was to compare the long-term risk-adjusted survival rates in patients undergoing coronary artery bypass grafting (CABG) using these 2 techniques. METHODS: We undertook a propensity score-matched analysis of 10 293 patients who underwent CABG at our single institution between 2000 and 2016. A logistic regression model was fitted using 14 covariates and their 2-way interactions to calculate an estimated propensity score [area under curve (AUC) 0.69], from which 1:1 nearest neighbour matching was performed. Patient survival was assessed using the Kaplan-Meier method and log-rank test. RESULTS: Of the total cohort, 8319 patients had ONCAB and 1974 had OPCAB. Prior to matching, the OPCAB group had marginally higher EuroSCORE [3.7 ± 2.7 vs 3.5 ± 3, median (interquartile range) 3 (2-5) vs 3 (2-5), P = 0.016] and significantly lower average number of grafts per patient (2.39 ± 0.72 vs 2.75 ± 0.48, P < 0.001). Post-matching distributions between OPCAB and ONCAB showed a substantial improvement in balance in preoperative patient characteristics. The 2 surgery groups differed significantly in survival (P < 0.001). OPCAB demonstrated improved long-term survival at 10 years [84.8%, 95% confidence interval (CI) (82.7-86.9%) vs 75.8%, 95% CI (73.4-78.2%)] and 15 years [65.4%, 95% CI (61.4-69.6%) vs 58.5%, 95% CI (54.9-62.3%)]. Results of sensitivity analysis for 1:2 and 1:3 matched data were in concordance with these findings of survival. CONCLUSION: At our institution, selected patients who underwent OPCAB had lower in-hospital morbidity and improved long-term survival when compared with a matched population of ONCAB patients.