Lobach, Iryna

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

Purpose: Studies have shown a modest association between pericardial fat volume (PFV) and coronary artery disease (CAD), potentially mediated by local inflammation. We aimed to investigate the association between a new biomarker of pericardial fat inflammation, named pericardial fat enhancement (PFE), and the severity of CAD on coronary computed tomography angiography (CCTA). Materials and Methods: We evaluated 114 patients referred for CCTA from 2007 to 2011. PFV, presence of obstructive CAD, and the burden of CAD were determined. PFE was measured in 10 mm2 regions of interest, adjusted to aortic enhancement (aPFE). The population was divided into those with greater than median (G-PFE) versus less than median pericardial fat enhancement (L-PFE). Stratified adjusted logistic regressions were performed. A P-value <0.05 was considered significant. The study was approved by our institutional review board. Results: Patients were 54.3±14.8 years of age, and 57/114 (50%) were male individuals, with body mass index of 27.3±6.3. There was an independent association between CAD severity and PFV. There was a significant independent association between PFV and obstructive CAD (odds ratio=1.26, P=0.005), and PFV and burden of CAD (odds ratio=1.25, P=0.05) in those with greater PFE. However, there was no significant association between obstructive CAD and CAD burden in either adjusted model for patients with less PFE. Conclusions: Our results suggest that PFE influences significantly the relationship between PFV and CAD, supporting the hypothesis of local pericardial fat inflammation as a mechanism for CAD development.

Sarcopenia is associated with increased wait‐list mortality, but a standard definition is lacking. In this retrospective study, we sought to determine the optimal definition of sarcopenia in end‐stage liver disease (ESLD) patients awaiting liver transplantation (LT). Included were 396 patients newly listed for LT in 2012 at 5 North American transplant centers. All computed tomography scans were read by 2 individuals with interobserver correlation of 98%. Using image analysis software, the total cross‐sectional area (cm 2 ) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI), which normalizes muscle area to patient height, was then calculated. The primary outcome was wait‐list mortality, defined as death on the waiting list or removal from the waiting list for reasons of clinical deterioration. Sex‐specific potential cutoff values to define sarcopenia were determined with a grid search guided by log‐rank test statistics. Optimal search methods identified potential cutoffs to detect survival differences between groups. The overall median SMI was 47.6 cm 2 /m 2 : 50.0 in men and 42.0 in women. At a median of 8.8 months follow‐up, mortality was 25% in men and 36% in women. Patients who died had lower SMI than those who survived (45.6 versus 48.5 cm 2 /m 2 ; P < 0.001), and SMI was associated with wait‐list mortality (hazard ratio, 0.95; P < 0.001). Optimal search method yielded SMI cutoffs of 50 cm 2 /m 2 for men and 39 cm 2 /m 2 for women; these cutoff values best combined statistical significance with a sufficient number of events to detect survival differences between groups. In conclusion, we recommend that an SMI < 50 cm 2 /m 2 for men and < 39 cm 2 /m 2 for women be used to define sarcopenia in patients with ESLD awaiting LT. Liver Transplantation 23 625–633 2017 AASLD .