Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit

Background

In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated.

Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

High frequency of MYC gene amplification is a common feature of radiation‐induced sarcomas. Further results from EORTC STBSG TL 01/01

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.     

Cardiac resynchronization therapy in patients with a narrow QRS complex.

OBJECTIVES: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI). BACKGROUND: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied. METHODS: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%. RESULTS: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]). CONCLUSIONS: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.     

Total ankle replacement for posttraumatic arthritis: Similar outcome in postfracture and instability arthritis: a comparison of 90 ankles

Background and purpose

Most studies on total ankle replacement (TAR) have used a case mix of patients. We evaluated the outcome of TAR performed for end-stage arthritis either because of fracture or ligamentous injury.

Patients and methods

We prospectively followed 88 consecutive patients (50 postfracture ankles and 40 ankles with instability arthritis (2 bilateral)) who underwent TAR between 2001 and 2009. Mean follow-up for both groups was 5 years.

Results

Preoperative varus deformity of 10° or more was present in 23 ankles in the instability group. At 6 years, survival with revision or salvage fusion as an endpoint was 87% (95% CI: 74–99) in the postfracture group and 79% (95% CI: 63–94) in the instability group. Progressive periprosthetic osteolysis was seen in 23 ankles, and required salvage fusion in 6. The number of reoperations was similar in both groups. Clinical outcome, as assessed with 2 ankle scores and 2 questionnaires, showed good results and was similar at the latest follow-up.

Interpretation

The outcome was similar in the postfracture and instability groups and also similar to that reported in series including a case mix of patients. In contrast to earlier reports, preoperative frontal plane deformity in this series was not identified as a risk factor for failure.Most published articles on total ankle replacement (TAR) have presented results from mixed cohorts of patients suffering from end-stage ankle arthritis of several different etiologies, such as posttraumatic arthritis, primary arthritis, and rheumatoid arthritis (Buechel et al. 2003, Wood et al. 2008, Bonnin et al. 2011, Rippstein et al. 2011, Barg et al. 2013, Zaidi et al. 2013). To our knowledge, there have been no studies on TAR concentrating exclusively on patients withposttraumatic arthritis, but some studies have focused on TAR in combined cohorts of posttraumatic and primary osteoarthritis (Saltzman et al. 2010, Bai et al. 2010, Flavin et al. 2013).This is surprising, as posttraumatic arthritis is considered to be the most frequent cause of ankle arthritis (Saltzman et al. 2005).2 subgroups of posttraumatic arthritis should be distinguished: (1) postfracture arthritis, secondary to an intra- or juxta-articular fracture; and (2) ligamentous posttraumatic arthritis, secondary to a single severe ankle sprain or as a result of recurrent or chronic instability (Valderrabano et al. 2009). We refer to the latter as instability arthritis. Patients suffering from end-stage instability arthritis frequently present with a varus deformity of the ankle as a result of both lateral ligament laxity and asymmetric cartilage loss medially (Harrington 1979, Doets et al. 2008, Ryssman and Myerson 2011).We evaluated the medium-term outcome of TAR for end-stage posttraumatic ankle arthritis and compared it for postfracture arthritis and for instability arthritis. Our research questions were whether patients treated with TAR for instability arthritis—as they more frequently have a deformity and perhaps also residual instability after TAR—will have worse results with respect to (1) implant survival, (2) the number of reoperations, and (3) ankle-specific and general patient- and physician-based outcomes.     

Increased risk of revision for infection in rheumatoid arthritis patients with total hip replacements

Background and purpose — Medical treatment of rheumatoid arthritis (RA) has changed dramatically over the last 15 years, including immune modulation. We investigated the risk of revision for infection after primary total hip replacement (THR) in patients with rheumatoid arthritis over a 16-year period, and compared it with that in THR patients with osteoarthritis (OA).

Patients and methods — We identified 13,384 THRs in RA patients and 377,287 THRs in OA patients from 1995 through 2010 in a dataset from the Nordic Arthroplasty Register Association (NARA). Kaplan-Meier survival curves, with revision for infection as the endpoint, were constructed. Cox regression analyses were performed to calculate the relative risk (RR) of revision for infection adjusted for age, sex, fixation technique, and year of primary surgery.

Results — RA patients had a 1.3 times (95% CI 1.0–1.6) higher risk of revision for infection. After 2001, this risk increased more for RA patients than for OA patients. During the first 3 months and from 8 years postoperatively, the risk of revision for infection was higher in RA patients with THRs fixated with antibiotic-loaded cement than in corresponding OA patients.

Interpretation — We found a slightly higher overall risk of revision for infection in RA patients than in OA patients, but this difference was only present after 2001. In THRs with antibiotic-loaded cement, the risk of very early and late infections leading to revision was higher in RA patients than in OA patients.