Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis

INTRODUCTION: Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF. PATIENTS AND METHODS: Thirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC. RESULTS: During the initial two weeks of hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13 (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r = 0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC pathway was associated with systemic inflammation-triggered immune suppression. CONCLUSION: PC deficiency and decreased APC generation in severe AP probably contributed to a compromised anticoagulant and anti-inflammatory defence. The PC pathway defects were associated with the development of MOF. The data support feasibility of testing the use of APC or PC to improve the clinical outcome in AP

Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis

Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods: Thirty-five DMARD-naive patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results: High JAK3 phosphorylation in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes and low JAK2 phosphorylation in CD14(+) monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.Peer reviewe

Outcomes following the operative treatment of intra-articular fracture combined with medial patellofemoral ligament reconstruction after patellar dislocation

Abstract Purpose: We examine the outcomes following operative treatment of intra-articular fracture combined with medial patellofemoral ligament (MPFL) reconstruction after patella dislocation. Methods: Patients were retrospectively identified from medical records using diagnostic and surgical procedure codes. Radiological anatomical parameters and bony abnormalities of injured knees were assessed from magnetic resonance images (MRI). Inclusion criteria were traumatic patellar dislocation with chondral or osteochondral fracture and MPFL rupture, operative treatment of a chondral or osteochondral fracture combined with MPFL reconstruction, and minimum follow-up of 2 years. Outcomes were measured using the Kujala score, Tegner activity scale, and the Knee injury and Osteoarthritis Outcome Score Quality-of-Life subscale (KOOS-QLS). Results: During 2012 and 2015, 322 patients were treated because of patellar dislocation. Thirty-three patients had chondral or osteochondral fracture. Eleven patients (five males and six females) with a mean [standard deviation (SD)] age of 17.0 (6.5) years at the time of surgery met the inclusion criteria and were included. Five of the 11 patients had a subchondral and six an osteochondral fracture. Eight patients had a fracture in the patella and three in the femur. All patients had bony abnormalities in the knee. Nine out of 11 patients scored over 90/100 points on the Kujala scale and had good results on the Tegner scale [before surgery 5.0 (2.7) points versus after surgery 5.3 (1.6) points] and the KOOS-QLS [4.1 (4.2) points] outcome measures. Conclusion: The removal or fixation of the fracture fragment combined with MPFL reconstruction is a feasible option in the treatment of symptomatic osteochondral or subchondral fragment in traumatic patellar dislocation. The short-term outcomes are encouraging. Level of evidence: Level IV, retrospective case series