Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

The diagnostic accuracy of temporal artery ultrasound and temporal artery biopsy in giant cell arteritis: A single center Australian experience over 10 years.

AIM: To assess the diagnostic accuracy of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis in patients with suspected giant cell arteritis (GCA) over 10 years in an Australian center. METHOD: Patients presenting to Westmead Hospital with possible GCA from March 2011 to December 2020 were retrospectively identified. The following parameters were obtained from the medical record: clinical presentation, inflammatory markers, temporal artery ultrasound findings, and temporal artery biopsy report. Data were assembled in a 2 × 2 table; sensitivity and specificity of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis were calculated. RESULTS: Over the 10-year study period, 65 temporal artery ultrasounds were performed in 63 patients (n = 65; 61.9% female) with a mean ± standard deviation age of 69.6 ± 12.3 years. Thirteen out of 65 (20%) temporal artery ultrasounds had findings suggestive of GCA. Twenty patients (31.7%) had a clinical diagnosis of GCA irrespective of sonographic or biopsy findings. Compared with temporal artery biopsy, temporal artery ultrasound had a sensitivity of 71.4% and specificity of 93.3%. Compared with clinical diagnosis made by the treating rheumatologist, temporal artery ultrasound had a sensitivity of 55% and specificity of 95.3%. CONCLUSION: Temporal artery ultrasound is a useful non-invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.

Unmet needs in psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis with a highly variable clinical presentation that does not have a validated molecular or imaging test, making accurate diagnosis a challenge. Consequences of diagnostic delay include irreversible joint damage and significant morbidity. Over the past few decades, there have been major advances in the understanding and treatment of PsA, leading to more targeted therapies. However, there is no current method to predict optimal treatment strategy to achieve minimal disease activity and prevent medication-related adverse events in the management of early disease. PsA is also associated with other comorbidities that include metabolic syndrome and psychosocial burden; two areas that are often unaddressed in the clinical setting and have associated sequelae. This chapter focuses on key domains of unmet needs, which include diagnostic challenges, delay in diagnosis, prognostication systems and stratified medicine approaches and precision medicine strategies for established and emerging therapies.

Improving Imaging Modalities in Early Psoriatic Arthritis: The Role of Ultrasound in Early Diagnosis of Psoriatic Arthritis.

Objective: Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA. Methods: We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions. Results: A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia. Conclusion: Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions.

Is the Use of Intraoperative Frozen Section During Pancreaticoduodenectomy Justified?

BACKGROUND: Intraoperative frozen section (IFS) is routinely utilized by many surgeons during pancreaticoduodenectomy. However, its utility has not been rigorously studied. METHODS: Patients who underwent pancreaticoduodenectomy between 2006 and 2015 were identified from institutional data. Measures of diagnostic accuracy of frozen section and multivariate logistic regression are reported. RESULTS: The cohort included 1076 patients. Of resected specimens, 73.3% were malignant. IFS and final pathologic review (the gold standard) were discrepant for (1) pathologic diagnosis or (2) resection margin status in 5.3% and 3.3% of cases. The sensitivity, specificity, and accuracy of IFS for histologic determination of malignancy were 97.2%, 95.3%, and 96.7% respectively. For resection margins, they were 92.3%, 99.3%, and 96.8%, respectively. Positive bile duct and neck margins were revised intraoperatively 62% and 65% of the time, respectively; positive uncinate margins were never resected but led surgeons to avoid revision of a second positive margin in 13% of cases (4.2% of all PDA). Operative changes were rarely noted in the presence of benign disease (n = 11, 1.0%); conversion to total pancreatectomy based on positive margins was performed in just 13 cases (1.2%). Upon multivariable analysis, a positive neck margin proved to be the greatest predictor for a revised resection margin (AOR 16.9 [4.8-59.8]), whereas a positive uncinate margin or a diagnosis of chronic pancreatitis was protective against IFS-driven operative changes (AOR 0.25 [0.09-0.73]; AOR 0.16 [0.13-0.19]). CONCLUSIONS: IFS is highly accurate and guides reresection of margins. However, selective omission of IFS may be justified for cases where benign disease is suspected.

Fully covered self-expanding metal stents versus lumen-apposing fully covered self-expanding metal stent versus plastic stents for endoscopic drainage of pancreatic walled-off necrosis: clinical outcomes and success.

BACKGROUND AND AIMS: Endoscopic transmural drainage/debridement of pancreatic walled-off necrosis (WON) has been performed using double-pigtail plastic (DP), fully covered self-expanding metal stents (FCSEMSs), or the novel lumen-apposing fully covered self-expanding metal stent (LAMS). Our aim was to perform a retrospective cohort study to compare the clinical outcomes and adverse events of EUS-guided drainage/debridement of WON with DP stents, FCSEMSs, and LAMSs. METHODS: Consecutive patients in 2 centers with WON managed by EUS-guided debridement were divided into 3 groups: (1) those who underwent debridement using DP stents, (2) debridement using FCSEMSs, (3) debridement using LAMSs. Technical success (ability to access and drain a WON by placement of transmural stents), early adverse events, number of procedures performed per patient to achieve WON resolution, and long-term success (complete resolution of the WON without need for further reintervention at 6 months after treatment) were evaluated. RESULTS: From 2010 to 2015, 313 patients (23.3% female; mean age, 53 years) underwent WON debridement, including 106 who were drained using DP stents, 121 using FCSEMSs, and 86 using LAMSs. The 3 groups were matched for age, cause of the pancreatitis, WON size, and location. The cause of the patients' pancreatitis was gallstones (40.6%), alcohol (30.7%), idiopathic (13.1%), and other causes (15.6%). The mean cyst size was 102 mm (range, 20-510 mm). The mean number of endoscopy sessions was 2.5 (range, 1-13). The technical success rate of stent placement was 99%. Early adverse events were noted in 27 of 313 (8.6%) patients (perforation in 6, bleeding in 8, suprainfection in 9, other in 7). Successful endoscopic therapy was noted in 277 of 313 (89.6%) patients. When comparing the 3 groups, there was no difference in the technical success (P = .37). Early adverse events were significantly lower in the FCSEMS group compared with the DP and LAMS groups (1.6%, 7.5%, and 9.3%; P < .01). At 6-month follow-up, the rate of complete resolution of WON was lower with DP stents compared with FCSEMSs and LAMSs (81% vs 95% vs 90%; P = .001). The mean number of procedures required for WON resolution was significantly lower in the LAMS group compared with the FCSEMS and DP groups (2.2 vs 3 vs 3.6, respectively; P = .04). On multivariable analysis, DP stents remain the sole negative predictor for successful resolution of WON (odds ratio [OR], 0.18; 95% confidence interval, 0.06-0.53; P = .002) after adjusting for age, sex, and WON size. Although there was no significant difference between FCSEMSs and LAMSs for WON resolution, the LAMS was more likely to have early adverse events (OR, 6.6; P = .02). CONCLUSIONS: EUS-guided drainage/debridement of WON using FCSEMSs and LAMSs is superior to DP stents in terms of overall treatment efficacy. The number of procedures required for WON resolution was significantly lower with LAMSs compared with FCSEMSs and DP stents.

Assessment of the new nodal classification for cutaneous squamous cell carcinoma and its effect on patient stratification.

BACKGROUND: The American Joint Committee on Cancer (AJCC) substantially changed the staging of cutaneous squamous cell carcinoma (SCC) in the seventh edition of its staging manual. Although the system is well established in mucosal SCC, very little data are available on its prognostic value in cutaneous SCC. METHODS: We conducted a multivariable analysis of 672 patients with metastatic cutaneous SCC from 2 prospective cancer center databases. RESULTS: The differentiation between N1 and N2 subgroups demonstrate little prognostic importance in cutaneous SCC, whereas survival is significantly worse for N3. CONCLUSION: Although the introduction of a unified N system for mucosal SCC and cutaneous SCC has added complexity, it does not translate into optimal distribution and stratification for metastatic cutaneous SCC.

Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK:

Comparison of the AJCC N staging system in mucosal and cutaneous squamous head and neck cancer.

OBJECTIVES/HYPOTHESIS: The American Joint Committee on Cancer (AJCC) substantially changed the staging of cutaneous squamous cell carcinoma (cSCC) in the seventh edition of its staging manual. Given that oral mucosal squamous cell carcinoma (mSCC) and cSCC behave differently and affect different patient populations, the aim of this study was to provide a side-by-side comparison and to evaluate the current nodal (N) grouping for cSCC alongside oral mSCC to determine whether the same system is justified. STUDY DESIGN: Retrospective analysis of prospectively collected data. METHODS: Multivariable analysis of 672 patients with metastatic cSCC and of 225 patients with metastatic mSCC from two prospective cancer-center databases. RESULTS: While, as expected, the N grouping functioned well in mSCC in terms of distribution and stratification of patients, it performed much less favorably in cSCC. In contrast to mSCC, the different N groups demonstrate much less prognostic importance in cSCC. CONCLUSION: Although the introduction of a unified N system for mSCC and cSCC has definite advantages, it does not translate into optimal distribution and stratification for metastatic cSCC. LEVEL OF EVIDENCE: 4.

Multidisciplinary vascular malformations clinic in Hong Kong.

OBJECTIVE: To review clinical characteristics, imaging modalities, and treatment outcomes of patients referred to a multidisciplinary clinic for management of vascular malformations. DESIGN: Retrospective case series. SETTING: Multidisciplinary vascular malformation out-patient referral clinic in a teaching hospital in Hong Kong. PATIENTS: The 141 attendees of the clinic from August 2005 to November 2011. MAIN OUTCOME MEASURES: Management and treatments offered, and responses to treatment. RESULTS: Of the 141 patients, 46% were diagnosed to have low-flow vascular malformations, 16% were diagnosed to have high-flow vascular malformations, and 15% were diagnosed to have a haemangioma. Prior to attending the clinic, approximately one third (32%) of the patients had a clinical diagnosis that was consistent with the final diagnosis. Overall, the radiological and clinical diagnoses were consistent in 43% of the patients. Magnetic resonance imaging and ultrasonography were the most commonly used imaging modalities. Of the 73 patients who received active treatment, 70% had a good response, 12% had minimal improvement, 8% had no change, and 7% had a recurrence or a major complication; in 3% of the patients the outcome was unknown. CONCLUSION: From this retrospective case series, it is evident that confusion still exists over vascular malformations and haemangiomas. Multidisciplinary clinics have a role in providing an accurate diagnosis and facilitating appropriate management and treatment plans. Magnetic resonance imaging and ultrasonography had demonstrable utility in determining the extent of the lesions and flow type.