Should all patients with polymyalgia rheumatica have a vascular ultrasound assessment?

There is a growing appreciation that both giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely interrelated conditions that have significant overlap in aetiology, clinical characteristics and treatment regimens. Subclinical GCA in PMR is becoming increasingly recognised, and there is evolving evidence that this may be a more aggressive disease phenotype than PMR. Ultrasound (US) lends itself well as a screening tool for GCA in PMR; it is inexpensive, non-invasive, widely available, lacks ionising radiation, may be performed at the bedside and is recommended by EULAR as a first-line investigation for suspected GCA. There is insufficient evidence to currently recommend that all patients with PMR should have a US assessment for vascular involvement. However, as clinical and laboratory parameters alone do not accurately diagnose patients with subclinical GCA, we suggest that vascular US will be increasingly performed by rheumatologists in practice to identify these patients with PMR, preferably as part of larger prospective outcome studies.

Targeted Therapy in Rheumatoid-Arthritis-Related Interstitial Lung Disease.

Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation. Parenchymal lung involvement or interstitial lung disease (ILD) is a significant cause of morbidity and mortality and there is a paucity of evidence-based guidance on how to best treat RA-ILD. This review article aims to evaluate the evidence from cohort studies and best real word data from registries. Extensive discussion of the relative merits and drawbacks of glucocorticoids, various biologics, small molecules and anti-fibrotics is presented. The limited available guidelines in RA-ILD are also discussed and a rational treatment algorithm is offered.

Janus Kinase Inhibitors in Rheumatoid Arthritis: An Update on the Efficacy and Safety of Tofacitinib, Baricitinib and Upadacitinib.

Janus kinase inhibitors (JAKis) are the most recent new drug class to arrive to the market for rheumatoid arthritis (RA) treatment. While they have proven to be a very effective treatment option, there remains significant concern regarding the risk of cardiovascular events, thrombosis and malignancy, particularly given the findings of the post-marketing ORAL Surveillance study and FDA black box warnings. This article reviews the key findings of the most impactful cohort of studies and registry data since ORAL Surveillance. It also evaluates the role of JAKis in practice and offers guidance on risk stratifying patients and determining their suitability for a JAKi.

Musculoskeletal education in undergraduate medical curricula-A systematic review.

Rheumatic and musculoskeletal diseases encompass a vast spectrum of up to 200 conditions that are increasingly prevalent, with significant associated disability and socioeconomic burden. Their impact is pervasive, with musculoskeletal conditions being the second leading cause of years lived with disability worldwide, in addition to the 9th most common cause of disability-adjusted life years. It is therefore imperative that all graduating medical physicians are competent in their management, and that the quality of undergraduate musculoskeletal education is commensurate with patient and societal needs. A systematic literature review was conducted between April 1, 2021 and June 1, 2021 assessing the quality of undergraduate musculoskeletal education in medical schools. Educational interventions in musculoskeletal medicine were also included. Quality assessment appraisal of the studies was done using a Mixed Methods Appraisal Tool. One thousand and thirty-three titles were screened, and 44 studies were included in the final analysis. Our analysis of these studies showed that the quality of undergraduate musculoskeletal education, as determined by the cognitive mastery and clinical confidence of undergraduate medical students remains inadequate. Multiple educational interventions were assessed with mixed results. Despite the prevalence, and burden associated with rheumatic and musculoskeletal diseases, the musculoskeletal education of undergraduate medical students remains inadequate. Urgent international collaboration is required to devise teaching strategies and curriculum initiatives that are globally and reproducibly applicable and effective. Further research into educational interventions and teaching strategies is also required.

Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? A systematic review and meta-analysis.

OBJECTIVES: Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis. METHOD: Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis. RESULTS: A total of 5 RCTs were included. Patients were randomized to tofacitinib (n = 474), filgotinib (n = 65), upadacitinib (n = 1281) or placebo (n = 937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P < .00001, I2 = 19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P < .00001, I2 = 66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P = .001, I2 = 82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P < .00001, I2 = 0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P < .00001, I2 = 0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P < .00001, I2 = 0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P = .0001, I2 = 0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P = .001, I2 = 0%) vs placebo. CONCLUSION: This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.

Giant cell arteritis: what is new in the preclinical and early clinical development pipeline?

INTRODUCTION: Giant Cell Arteritis (GCA) is the most common systemic vasculitis worldwide. For decades, glucocorticoids have represented the mainstay of treatment, at the expense of toxic systemic effects owing to prolonged courses of high-dose treatment regimens. The search for effective drugs permitting lower glucocorticoid treatment regimens in GCA has been afrustrating one. The recent successful therapeutic application of tocilizumab, an interleukin-6 receptor inhibitor, has transformed the treatment of GCA and catalyzed research exploring other promising therapeutic targets. AREAS COVERED: This review explores emerging drugs in preclinical and clinical development for the management of GCA, in addition to synthesizing data on the current standard of care therapeutic agents. Drug therapies were identified by search of MEDLINE and PubMed in addition to trials from registries (clinicaltrials.gov, clinicaltrialsregister.eu, pubmed.gov) from theyear 2010. EXPERT OPINION: Tocilizumab has revolutionized the treatment of GCA. However, much remains to be learned about its optimal usage in GCA and asubstantial minority of pa tients do not achieve sustained glucocorticoid-free remission. Numerous exciting new agents are under investigation to fill this treatment gap in GCA, with the GM-CSF inhibitor mavrilimumab, and IL-12/23 blockade with ustekinumab providing promise through targeting the GCA pathogenic pathway in its proximal portion.

SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients. METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models. RESULTS: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. CONCLUSION: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate.

'All disease begins in the gut'-the role of the intestinal microbiome in ankylosing spondylitis.

Ankylosing spondylitis is a chronic, debilitating arthritis with a predilection for the axial skeleton. It has a strong genetic predisposition, but the precise pathogenetic mechanisms involved in its development have not yet been fully elucidated. This has implications both for early diagnosis and for effective management. Recently, alterations in the intestinal microbiome have been implicated in disease pathogenesis. In this review, we summarize studies assessing the intestinal microbiome in AS pathogenesis, in addition to synthesizing the literature exploring the postulated mechanisms by which it exerts it pathogenic potential. Finally, we review studies analysing manipulation of the microbiome as a potential therapeutic avenue in AS management.

Does Premedication with Mucolytic Agents Improve Mucosal Visualization during Oesophagogastroduodenoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Gastric Cancer (GC) is the fourth most common malignancy worldwide and the second leading cause of cancer-related mortality for both sexes. The gold standard for diagnosing GC is oesophagogastroduodenoscopy (OGD). Excess mucus on the gastric mucosa impairs the detection of early GC. AIM: To synthesize available evidence of the effect of premedication with a mucolytic agent among adults undergoing elective nontherapeutic OGD, compared to placebo or other mucolytic agents, on mucosal visibility during OGD. METHODS: A systematic review was conducted. PubMed, EMBASE, CINAHL, Cochrane central register of controlled trials (CENTRAL), and Web of Science were searched for relevant studies. A random-effects meta-analysis was performed to determine the mean difference in total mucosal visibility score (TMVS) between the pooled mucolytic agents and control. Subgroup analyses were performed to determine the mean TMVS difference for simethicone versus control and the impact of different timings and doses of mucolytic premedication. RESULTS: 13 studies, involving 11,086 patients, including 6178 females (55.7%), with a mean age of 53.4 were identified and 6 of these were brought forward to meta-analysis. This revealed a mean difference of -2.69 (95% CI -3.5, -1.88) in total mucosal visibility scores (TMVS) between the pooled mucolytic agents and control. For simethicone, the mean difference was -2.68 (95% CI -4.94, -0.43). A simethicone dose of 133 mg was most effective with a mean difference of -4.22 (95% CI -5.11, -3.33). Assessing timing of administration across all mucolytic agents revealed a mean difference for the >20 minutes group of -3.68 (95% CI -4.77, -2.59). No adverse events were reported in any included trials. CONCLUSIONS: Regular use of premedication with mucolytic agents prior to routine OGD is associated with improved TMVS with no reported adverse events.

Is There a Role for Tranexamic Acid in Upper GI Bleeding? A Systematic Review and Meta-Analysis.

INTRODUCTION: Upper gastrointestinal (GI) bleeding is associated with increased morbidity and mortality. Tranexamic acid (TXA) is an antifibrinolytic agent which is licensed in the management of haemorrhage associated with trauma. It has been suggested that tranexamic acid may be able to play a role in upper GI bleeding. However, there is currently no recommendation to support this. AIM: The aim of this study was to synthesise available evidence of the effect of TXA on upper GI bleeding. METHODS AND MATERIALS: A systematic review was conducted. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies. A random effects meta-analysis was performed to determine the risk ratio of primary and secondary outcomes pertaining to the use of TXA in upper GI bleeding. RESULTS: A total of 8 studies were included in this systematic review. The total number of patients in all studies was 12994 including 4550 females (35%) and 8444 males (65%). The mean age of participants in 6 of the studies was 59.3; however the mean age for either intervention or placebo group was not reported in two of the studies. All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, with the 95% CI ranging from 0.80 to 1.13, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and with a 95% CI ranging from 0.47 to 0.86, this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, the 95% CI extended from 0.62 to 1.39 and so was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant with a 95% CI ranging from 0.38 to 0.94. CONCLUSION: In conclusion, the use of TXA in upper GI bleeding appears to have a beneficial effect in terms of decreasing the risk of re-bleeding and decreasing the need for surgery. However, we could not find a statistically significant effect on need for blood transfusions, risk of thromboembolic events, or effect on mortality. Future randomised controlled trials may elucidate these outcomes.

Haemophagocytic Lymphohistiocytosis in an Elderly Patient after Recent Cardiac Surgery.

INTRODUCTION: The underlying pathophysiology of haemophagocytic lymphohistiocytosis (HLH) is characterised by excessive inflammation and tissue destruction secondary to abnormal immune activation. The term primary HLH refers to a genetic abnormality that predisposes to the condition whereas secondary refers to HLH being triggered by an underlying condition such as infection (often Epstein Barr Virus), autoimmune, or neoplastic disease. Its variable clinical presentation poses an obstacle to prompt diagnosis in the elderly patient. CASE: A 70-year-old Caucasian man was admitted to hospital from a convalescence center with symptoms of fatigue, fever, decreased oral intake, and increasing shortness of breath on exertion. The patient was three weeks after coronary artery bypass grafting. Over the next two weeks, the patient continued to deteriorate both clinically and biochemically. The patient met criteria for haemophagocytic lymphohistiocytosis, likely driven by EBV infection. Bone marrow biopsy supported the diagnosis with evidence of active phagocytosis. The patient was commenced on high-dose dexamethasone and reviewed by haematology with further molecular testing confirming the diagnosis. Discussion. LH is becoming more common in older patients. We propose that new guidelines be developed to aid its prompt diagnosis in this age group.

"Dr. Google" Will See You Now-Assessing the Quality of Information on Oesophageal Cancer on the Internet.

BACKGROUND: Increasingly, patients are consulting the internet for medical information, where the quality is highly variable. We must ensure patients are directed towards high-quality websites. This is particularly true of oesophageal cancer which is often detected at an advanced stage and is frequently fatal. We aim to assess the quality of information on oesophageal cancer available for patients on the Internet. METHODS AND MATERIALS: We searched the top 3 search engines for "Esophageal Cancer". We analysed the top 20 websites returned by Google and the top 10 websites returned by Yahoo and Bing. All free, English language websites which did not require a password were included. We excluded paid advertisement websites and websites for medical professionals. Duplicate websites were removed. Each website was then evaluated using the JAMA benchmarks, DISCERN tool, presence or absence of the Health On The Internet (HON) seal and the Esophageal Cancer Specific Content Score (ECSCS). RESULTS: The average JAMA score was 2 with only three of the eighteen unique websites scoring the maximum of 4 points (17%). The average DISCERN score was 51.5 (64%) with no website achieving the maximum of 80. The HON seal was present in only 5 websites (28%). The average ECSCS was 9.2 with only two websites achieving the maximum of 12 (11%). CONCLUSIONS: Whilst there are certainly websites providing high-quality information for patients in relation to oesophageal cancer, our study has identified obvious issues. We must ensure that only the highest-quality information is available on the Internet for patients.

A case of ectopic liver tissue adherent to the gallbladder.

We report a case of a 30-year-old lady who presented to the emergency department with a 1 day history of severe epigastric pain which radiated to the back. Focused history, physical exam findings, haematological and radiological investigations, including ultrasound scanning of the abdomen, supported the diagnosis of acute gallstone pancreatitis. She was managed conservatively and underwent elective laparoscopic cholecystectomy at a later date. Intraoperatively, there was noted to be a small nodule loosely adherent to the gallbladder serosa. Histology from this nodule revealed it to be a portion of anatomically normal liver parenchyma also referred to as ectopic liver tissue (ELT). ELT is a rare developmental abnormality in which normally functioning liver tissue develops at an extra-hepatic site. ELT is known to have an increased risk of neoplastic transformation and so we believe it to be of clinical importance.