Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum, empirical versus targeted.

AIM: To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy. METHODS: We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results. RESULTS: We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan-Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies. CONCLUSIONS: In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology.

Nonoperative Treatment of Anterior Glenoid Rim Fractures After First-Time Traumatic Anterior Shoulder Dislocation: A Study with 9-Year Follow-up.

Primary traumatic anterior shoulder dislocations can be associated with displaced anterior glenoid rim fractures. Nonoperative treatment of such fractures has been shown to have excellent results in a small cohort of patients; as such, we have been treating these fractures nonoperatively, regardless of fragment size and degree of displacement, provided that post-reduction computed tomography scans revealed an anteroposteriorly centered humeral head. The aim of this study was to analyze the medium- to long-term results of nonoperative treatment of displaced anterior glenoid rim fractures, assessing in particular the residual instability and development of osteoarthritis. METHODS: In a 2-center study, 30 patients with a mean age of 48 years (range, 29 to 67 years) were evaluated clinically with use of the Subjective Shoulder Value, Constant score, American Shoulder and Elbow Surgeons score, and Western Ontario Shoulder Instability index, as well as radiographically with use of radiographs and computed tomography scans at a mean follow-up of 9 years (range, 5 to 14 years). RESULTS: Fracture-healing was documented in all patients. Seven patients (23%) had post-fracture onset of osteoarthritis (5 with Samilson grade I and 2 with Samilson grade IV). Of these, 1 patient had recurrent instability that was successfully treated with hemiarthroplasty 9 years after the index injury (relative Constant score, 101%), and was excluded from further analysis. No other patient had a recurrent redislocation, subluxation, or positive apprehension. The other 6 patients with new-onset radiographic osteoarthritis were pain-free (mean Constant score pain scale, 15 points) with good shoulder function (relative Constant score, 84% to 108%). A total of 26 patients (90%) rated their functional outcome as good or very good, and 3 patients (10%) rated it as fair. The mean relative Constant score was 97% (range, 61% to 108%), the mean American Shoulder and Elbow Surgeons score was 92 points (range, 56 to 100 points), and the mean Western Ontario Shoulder Instability index score was 126 points (range, 0 to 660 points). All patients returned to full-time work. CONCLUSIONS: Nonoperative treatment of anterior glenoid rim fractures following primary traumatic anterior shoulder dislocation results in excellent clinical outcomes with a very low rate of residual instability and, thus, treatment failure. Asymptomatic radiographic osteoarthritis occurred in roughly 1 of 4 patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Activation of the vitamin D receptor selectively interferes with calcineurin-mediated inflammation: a clinical evaluation in the abdominal aortic aneurysm.

In vitro and in vivo studies attribute potent immune regulatory properties to the vitamin D receptor (VDR). Yet, it is unclear to what extend these observations translate to the clinical context of (vascular) inflammation. This clinical study evaluates the potential of a VDR agonist to quench vascular inflammation. Patients scheduled for open abdominal aneurysm repair received paricalcitol 1 µg daily during 2-4 weeks before repair. Results were compared with matched controls. Evaluation in a parallel group showed that AAA patients are vitamin D insufficient (median plasma vitamin D: 43 (30-62 (IQR)) nmol/l). Aneurysm wall samples were collected during surgery, and the inflammatory footprint was studied. The brief paricalcitol intervention resulted in a selective 73% reduction in CD4+ T-helper cell content (P<0.024) and a parallel 35% reduction in T-cell (CD3+) content (P<0.032). On the mRNA level, paricalcitol reduced expression of T-cell-associated cytokines IL-2, 4, and 10 (P<0.019). No effect was found on other inflammatory mediators. On the protease level, selective effects were found for cathepsin K (P<0.036) and L (P<0.005). Collectively, these effects converge at the level of calcineurin activity. An effect of the VDR agonist on calcineurin activity was confirmed in a mixed lymphocyte reaction. In conclusion, brief course of the VDR agonist paricalcitol has profound effects on local inflammation via reduced T-cell activation. The anti-inflammatory potential of VDR activation in vitamin D insufficient patients is highly selective and appears to be mediated by an effect on calcineurin-mediated responses.