Giant cell arteritis in patients with systemic sclerosis: a case series.

OBJECTIVES: Giant cell arteritis (GCA) in patients with systemic sclerosis (SSc) is rare, and optimal treatment strategies for this group of patients have not been defined. We aim to describe the first case series of GCA/SSc overlap. METHODS: A single-institution retrospective study was performed reviewing all patients that had diagnosis codes for both SSc and GCA between January 1, 1996, and December 31, 2020. Demographic characteristic, clinical presentation, diagnostic modality, treatment, and outcome data were abstracted. Diagnosis of both SSc and GCA by a rheumatologist was required for inclusion. RESULTS: Eight patients were retrospectively identified, all of which were female. Seven patients fully met both respective ACR/EULAR classification criteria sets. One patient fulfilled GCA criteria and had 8/9 points for SSc criteria plus an oesophagogram which was consistent with clinical diagnosis of SSc. Three patients had a previous history of scleroderma renal crisis (SRC) prior to glucocorticoid initiation for GCA. No episodes of SRC occurred following initiation of glucocorticoids. Three patients were treated with tocilizumab. One patient developed a diverticular perforation while on tocilizumab requiring colonic resection and colostomy, one patient discontinued tocilizumab after a medication-unrelated complication and one patient has remained on treatment and in remission. CONCLUSIONS: Herein we present the largest single-institution series of patients with a history of GCA and SSc, an uncommon combination. Glucocorticoid treatment for GCA did not precipitate SRC, even in those with prior history of SRC. Further investigation regarding the benefit of tocilizumab in patients with SSc and GCA is required.

Wide complex tachycardia discrimination tool improves physicians' diagnostic accuracy.

BACKGROUND: Timely and accurate discrimination of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular WCT (SWCT) is critically important. Previously we developed and validated an automated VT Prediction Model that provides a VT probability estimate using the paired WCT and baseline 12-lead ECGs. Whether this model improves physicians' diagnostic accuracy has not been evaluated. OBJECTIVE: We sought to determine whether the VT Prediction Model improves physicians' WCT differentiation accuracy. METHODS: Over four consecutive days, nine physicians independently interpreted fifty WCT ECGs (25 VTs and 25 SWCTs confirmed by electrophysiological study) as either VT or SWCT. Day 1 used the WCT ECG only, Day 2 used the WCT and baseline ECG, Day 3 used the WCT ECG and the VT Prediction Model's estimation of VT probability, and Day 4 used the WCT ECG, baseline ECG, and the VT Prediction Model's estimation of VT probability. RESULTS: Inclusion of the VT Prediction Model data increased diagnostic accuracy versus the WCT ECG alone (Day 3: 84.2% vs. Day 1: 68.7%, p 0.009) and WCT and baseline ECGs together (Day 3: 84.2% vs. Day 2: 76.4%, p 0.003). There was no further improvement of accuracy with addition of the baseline ECG comparison to the VT Prediction Model (Day 3: 84.2% vs. Day 4: 84.0%, p 0.928). Overall sensitivity (Day 3: 78.2% vs. Day 1: 67.6%, p 0.005) and specificity (Day 3: 90.2% vs. Day 1: 69.8%, p 0.016) for VT were superior after the addition of the VT Prediction Model. CONCLUSION: The VT Prediction Model improves physician ECG diagnostic accuracy for discriminating WCTs.

Activities of Daily Living and Outcomes in Patients with Advanced Heart Failure.

BACKGROUND: Functional debility is associated with worse outcomes in the general heart failure population, but the prevalence of difficulty with activities of daily living and clinical significance once patients develop advanced heart failure requires further examination. METHODS: This was a population-based, retrospective cohort study of Olmsted County, Minnesota adults with advanced heart failure from 2007-2018. Difficulty with 9 activities of daily living was assessed by questionnaire. Predictors of difficulty were assessed by a proportional odds model. Associations of difficulty with activities of daily living with mortality and hospitalization were examined using Cox and Andersen-Gill models. RESULTS: Among 765 patients with advanced heart failure, 565 (73.9%) reported difficulty with activities of daily living at diagnosis. Of those, 257 (45%) had moderate and 148 (26%) had severe difficulty. Independent predictors of difficulty included female sex (odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.36; P = .001), older age (OR per 10-year increase 1.17; 95% CI, 1.05-1.31; P = .005), dementia (OR 1.85; 95% CI, 1.06-3.24; P = .031), depression (OR 1.75; 95% CI, 1.28-2.40; P = .001), and morbid obesity (OR 1.49; 95% CI, 1.04-2.13; P = .031). Estimated 2-year mortality was 61.5%, 64.2%, and 67.6% in patients with no/minimal, moderate, and severe difficulty, respectively. The adjusted hazard ratios (95% CI) for death were 1.08 (0.90-1.28) and 1.17 (0.95-1.43) for moderate and severe difficulty, respectively, vs no/minimal difficulty (P = .33). There were no statistically significant associations of difficulty with activities of daily living and hospitalization risks. CONCLUSIONS: Most patients with advanced heart failure have difficulty completing activities of daily living and are at high risk of mortality regardless of impairment in activities of daily living.

Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression.

Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.