Martin Berli

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue.

Recurrence of acute Charcot neuropathic osteoarthropathy after conservative treatment.

Background: Charcot neuropathic osteoarthropathy (CN) is a chronic, progressive-destructive process affecting the feet of patients with sensory neuropathy. Data on CN recurrence are underrepresented in the literature. The aim of the present study was to evaluate the rate of CN recurrence after its treatment and to find predisposing factors. Methods: Fifty-two patients (age 59 ± 11 years, 16 female) with acute CN with 57 affected feet were enrolled. Comorbidities, localization, and stage of disease at first diagnosis as well as ulcerations, need for surgery, noncompliance, and subsequent treatment (orthopedic footwear or orthotic treatment) during the course of therapy were recorded. During follow-up, the incidence of recurrence of CN was observed. Mean follow-up was 47 ± 40 months. Results: Diabetes was the most common reason for sensory neuropathy (79%). Recurrence of CN was seen in 13 feet (23%) with an interval of 27 ± 31 months (range, 3-102 months) after the end of initial immobilization. Patients with recurrence were immobilized for a shorter period of time and had a more advanced stage of CN at time of first diagnosis. Predictors of recurrence were noncompliance (odds ratio 19.7; confidence interval, 4.1-94.4; P < .001) and obesity (odds ratio 6.4; confidence interval, 1.6-25.9; P = .06). Conclusions: Recurrence of osteoarthropathic activity is a possible complication after conservative treatment of CN. Obesity and noncompliance are strong predictors for the recurrence of CN. Level of Evidence: Level III, retrospective comparative study.

Correlation of Systemic Inflammatory Markers With Radiographic Stages of Charcot Osteoarthropathy

Background: Charcot osteoarthropathy (COA) is characterized by a progressive destruction of bone and joint associated with neuropathy and is most common in the foot and ankle. Clinical manifestation of COA is frequently indistinguishable from other causes of pain, swelling, and erythema of the affected extremity, in particular, infection. Diagnosis of COA can be challenging in particular in early stages where radiographic changes are sparse. The presence of elevated systemic inflammatory parameters in the context of suspected infection may delay early diagnosis and treatment of COA. The aim of this retrospective analysis was to assess whether elevated systemic inflammatory parameters may be present, in particular in early stages of COA and thus not be used as an exclusion criterion for the diagnosis of COA. Methods: Forty-two patients (mean age 48.2 ± 9.4 years, 36 male, 6 female) with a diagnosis of unilateral COA were the subject of this retrospective study. The diagnosis of COA was confirmed by plain radiographs, magnetic resonance imaging and clinical course. Systemic inflammatory parameters were recorded at the time of referral. Acute stages (stages 0 and 1) were treated with a total contact cast (TCC) and protected weight bearing for a minimum of 6 weeks. For chronic stages (stages 2 and 3) custom-made shoes were prescribed. The feet were stratified into “acute” (Eichenholz stages 0 and 1) and “subacute/chronic” (Eichenholz stages 2 and 3) groups. Results: Statistically significant differences were observed for all recorded systemic inflammatory parameters (C-reactive protein level, WBC count, erythrocyte sedimentation rate) between the acute and subacute/chronic groups. No statistical difference was observed considering the anatomic pattern of involvement. Conclusion: The present study demonstrated that elevated systemic inflammatory parameters may be present in COA and can further be used to distinguish between acute and subacute stages of COA, based on the Eichenholtz classification. Thus, we suggest that elevated inflammatory markers should not be considered an exclusion criterion for the diagnosis of COA. Level of Evidence: Level III, retrospective comparative series.

Nonsurgical Treatment of Osteomyelitis of the Hallux Sesamoids: A Case Series and Literature Review

ABSTRACT The aim of the present study was to determine the effectiveness of nonsurgical treatment for osteomyelitis of the hallucal sesamoids. Osteomyelitis of the hallucal sesamoids in young and healthy patients is rare and might originate from hematogenous spread or after a puncture wound. In diabetic patients with peripheral neuropathy, it often results from direct contiguous seeding from adjacent ulceration. The superiority of surgical versus nonsurgical therapy is still debated. In our institution, all patients presenting with osteomyelitis of the hallucal sesamoids are first treated nonsurgically but eventually usually require a surgical procedure. We reviewed 18 patients with a clinical and radiologic diagnosis of osteomyelitis of the hallucal sesamoids treated in our institution during a 13‐year period (from January 2000 to December 2012). The inclusion criteria were a signal alteration on magnetic resonance imaging or bone lesions on computed tomography or conventional radiographs, combined with a deep ulcer with a positive probe‐to‐bone test. Nonsurgical therapy consisted of frequent wound treatment, immobilization, offloading in a cast or other orthotic device, and oral antibiotics. Of the 18 patients, 11 had diabetes, 16 had peripheral neuropathy, 11 had peripheral arterial disease, and 5 had immunosuppression. After a period of nonsurgical therapy ranging from 4 weeks to 9 months, 15 of 18 patients required surgical excision, internal resection, or amputation. In this patient population, we no longer consider nonsurgical therapy a viable option. Patients should be advised, before starting nonsurgical treatment, that the therapy will be long and demanding and very often results in a surgical procedure.

Ulcère hypertensif de Martorell

L’ulcere hypertensif de Martorell fait partie des causes les plus frequentes de plaies chroniques au niveau de la jambe. Toutefois, le diagnostic correct n’est souvent pas pose et une pyodermite gangreneuse ou une vascularite est souvent diagnostiquee a tort.