Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities. Wnt signaling is involved in increasing bone mineral density, bone homeostasis and apoptotic processes. It has been shown that type 2 diabetes mellitus is strongly associated with gene variants of the Wnt signaling pathway, specifically polymorphisms of TCF7L2 (transcription factor 7 like 2), which is an effector transcription factor of this pathway. METHODS: Bone samples of 19 T2DM patients and 7 T2DM patients with additional Charcot arthropathy were compared to 19 non-diabetic controls. qPCR analysis for selected members of the Wnt-signaling pathway (WNT3A, WNT5A, catenin beta, TCF7L2) and bone gamma-carboxyglutamate (BGLAP, Osteocalcin) was performed and analyzed using the 2-ΔΔCt- Method. Statistical analysis comprised one-way analysis of variance (ANOVA). RESULTS: In T2DM patients who had developed Charcot arthropathy WNT3A and WNT5A gene expression was down-regulated by 89 and 58% compared to healthy controls (p < 0.0001). TCF7L2 gene expression showed a significant reduction by 63% (p < 0.0001) and 18% (p = 0.0136) in diabetic Charcot arthropathy. In all diabetic patients BGLAP (Osteocalcin) was significantly decreased by at least 59% (p = 0.0019). CONCLUSIONS: For the first time with this study downregulation of members of the Wnt-signaling pathway has been shown in the bone of diabetic patients with and without Charcot arthropathy. This may serve as future therapeutic target for this severe disease.

The role of serum C-reactive protein in the diagnosis of periprosthetic shoulder infection.

INTRODUCTION: There is a paucity of literature regarding serum C-reactive protein (CRP) in the evaluation of a shoulder periprosthetic joint infection (PJI). The purpose of the current study was to establish cutoff values for diagnosing shoulder PJI and evaluate the influence of the type of infecting microorganism and the classification subgroups according to last proposed International Consensus Meeting (ICM) criteria on the CRP level. MATERIALS AND METHODS: A retrospective analysis of all 136 patients, who underwent septic or aseptic revision shoulder arthroplasty in our institution between January 2010 and December 2019, was performed. Shoulder PJI was defined according to the last proposed definition criteria of the ICM. Serum CRP levels were compared between infected and non-infected cases, between infection subgroups, as well as between different species of infecting microorganisms. A receiver-operating characteristic (ROC) analysis was performed to display sensitivity and specificity of serum CRP level for shoulder PJI. RESULTS: A total of 52 patients (38%) were classified as infected, 18 meeting the criteria for definitive infection, 26 for probable infection and 8 for possible infection. According to the ROC curve, an optimized serum CRP threshold of 7.2 mg/l had a sensitivity of 69% and specificity of 74% (area under curve = 0.72). Patients with definitive infection group demonstrated significantly higher median serum CRP levels (24.3 mg/l), when compared to probable, possible infection groups and PJI unlikely group (8 mg/l, 8.3 mg/l, 3.6 mg/l, respectively, p < 0.05). The most common isolated microorganism was Cutibacterium acnes in 25 patients (48%) followed by coagulase-negative staphylococci (CNS) in 20 patients (39%). Patients with a PJI caused by high-virulent microorganisms had a significantly higher median serum CRP level compared to patients with PJI caused by low-virulent microorganisms (48 mg/l vs. 11.3 mg/l, p = 0.04). CONCLUSIONS: Serum CRP showed a low sensitivity and specificity for the diagnosis of shoulder PJI, even applying cutoffs optimized by receiver-operating curve analysis. Low-virulent microorganisms and patients with probable and possible infections are associated with lower CRP levels compared to patients with definitive infection and infections caused by high-virulent microorganisms. LEVEL OF EVIDENCE: Diagnostic Level III.

Current management of trimalleolar ankle fractures.

A trimalleolar ankle fracture is considered unstable and treatment is generally performed operatively. Computed tomography is important for the operative planning by providing an elaborated view of the posterior malleolus.Trimalleolar ankle fractures have a rising incidence in the last decade with up to 40 per 100,000 people per year. With a growing number of elderly patients, trimalleolar ankle injuries will become more relevant in the form of fragility fractures, posing a particular challenge for trauma surgeons.In patients with osteoporotic trimalleolar ankle fractures and relevant concomitant conditions, further evidence is awaited to specify indications for open reduction and internal fixation or primary transfixation of the ankle joint.In younger, more demanding patients, arthroscopic-assisted surgery might improve the outcome, but future research is required to identify patients who will benefit from assisted surgical care.This review considers current scientific findings regarding all three malleoli to understand the complexity of trimalleolar ankle injuries and provide the reader with an overview of treatment strategies and research, as well as future perspectives. Cite this article: EFORT Open Rev 2021;6:692-703. DOI: 10.1302/2058-5241.6.200138.

Emergency room as primary point of access in the German healthcare system : Objective evaluation and interview of motivation for ER entrance of 235 ER patients in a German hospital.

BACKGROUND: The importance of emergency rooms (ERs) as everyday healthcare suppliers is growing. Due to increasing patient flows, hospitals are forced to raise physicians' and caregivers' headcount continuously to meet the new demand of patients seeing the ER as primary point of contact in non-emergency situations. Patients from various cultural and educational backgrounds approach the ER for different reasons. Detailed understanding of these reasons and their roots is key to be able to offer guidance for patients as well as planning and staffing of hospitals in the future. AIM: This study examines motivation for the entrance to the medical system via the ER in Germany via an anonymized patient survey. Evaluation in regard to socioeconomic and medical reasons is taken into account. MATERIALS AND METHODS: Over the course of 210 h in the ER, a total of 235 patients were interviewed in the surgical emergency room of Klinikum rechts der Isar in the year 2016. Focus was set on standard cases to allow for facilitated comparability. Heavily injured patients were excluded from the study. RESULTS: The main reasons for patients entering the ER were immediate help (45.9%) and treatment by a specialist (35.4%). Furthermore, the location/good accessibility (47.9%) and prior positive experience with the emergency room (20.7%) were decisive reasons for choosing the hospital over the outpatient sector. Analysis of demands of patients in relation to their migration background and their religious confession showed no significant difference between groups. CONCLUSION: Younger patients tend to more often access the ER instead of an outpatient clinic or doctor in private practice. As a survey suits the less urgent patients, our research describes this population in detail. The need for better information of patients regarding treatment options becomes apparent. The study's outcomes aim to teach physicians as well as operators how to influence resource management in the healthcare system by meaningful information of patients. Further research may evaluate long-term results of information measures.

[Delayed occurrence of compartment syndrome of the upper arm after shovelling snow by a patient under oral anticoagulation]. / Verzögert auftretendes Oberarmkompartmentsyndrom nach Schneeschaufeln unter oraler Antikoagulation.

This article reports the case of an 81-year-old male patient under treatment with oral anticoagulation who suffered delayed compartment syndrome of the upper arm from arterial capillary hemorrhage after shovelling snow. The diagnosis was made 48 h after the initial symptoms in the emergency surgical department of the Klinikum rechts der Isar (München) with the presence of clear neurological deficits. Following computed tomography angiography (CTA) imaging an emergency dermatofasciotomy was carried out as well as a vascular ligature via a medial approach. Compartment syndromes are the result of pathologically elevated tissue pressure and as a rule with a rapid clinical course. A delayed diagnosis can therefore lead to irreversible tissue and nerve damage up to the loss of the extremity. Compartment syndromes are particularly frequent in the lower extremities whereas those of the upper extremities are rare. This case report is intended to raise awareness for an insidiously occurring compartment syndrome of the upper arm due to repetitive microtrauma (in this case shovelling snow) and arterial peripheral vascular hemorrhage with simultaneous anticoagulation. The necessary diagnostic and treatment steps are also elucidated.

The Munich Ankle Questionnaire (MAQ): a self-assessment tool for a comprehensive evaluation of ankle disorders.

BACKGROUND: There are many approved patient-related outcome measurement tools regarding ankle pathologies. However, there is none incorporating the range of motion (ROM) as an objective parameter. Most instruments focus on subjective parameters such as pain and impairment at work or daily living. Furthermore, the majority is only applicable to a specific pathology. Therefore, the objective of our study was to develop and validate the Munich Ankle Questionnaire (MAQ) as a universal self-assessment score including subjective and objective items. METHODS: The established McGuire Score, Bray Score, Ankle Hindfoot Score (AOFAS) and Olerud and Molander Score were analyzed for relevant items and subscales. Items of interest were then condensed and allocated to the respective subscales of the MAQ. The final MAQ consists of 6 items addressing general and demographic data and 12 items addressing three domains: pain (3 items), work and daily living (5 items), movement and ROM (4 items). The evaluation of validity, reliability and responsiveness of the MAQ was performed in a prospective clinical study including traumatic as well as degenerative ankle pathologies. RESULTS: In total, 148 patients (79 female, 69 male, median age 45 years) were included in the validation study. With intra-class correlation coefficients of at least 0.77, test-retest reliability was proven. Construct validity with a correlation coefficient of 0.82 and responsiveness with a correlation coefficient ranging from 0.42 to 0.47 were confirmed. CONCLUSION: The MAQ is a reliable and valid self-assessment measurement tool for the follow-up examination regarding subjective and objective parameters of traumatic and degenerative ankle pathologies. The MAQ has no limitation to specific disorders and allows a broad application.

Hyperinsulinemia reduces osteoblast activity in vitro via upregulation of TGF-ß.

Affecting more than 230,000,000 patients, diabetes mellitus is one of the most frequent metabolic disorders in developed countries. Among other complications, diabetic patients have an increased fracture risk and show delayed fracture healing. During the disease progression, these patients' blood glucose and insulin levels vary significantly. Thus, the aim of this study was to analyze the effects of glucose and insulin on primary human osteoblasts. Although, in the presence of insulin and glucose, proliferation of osteoblasts was increased (1.2- to 1.7-fold), their alkaline phosphatase activity and, consequently, production of mineralized matrix were significantly reduced down to 55 % as compared to control cells (p < 0.001). Interestingly, the observed effects were mainly due to stimulation with insulin. Increase in glucose did not alter osteoblasts' function significantly but further enhanced the effects of insulin. Expression of active and total transforming growth factor beta (TGF-ß) was increased by glucose and insulin. Stimulation with both glucose and insulin induced gene expression changes (e.g., osteocalcin, Runx2, Satb2, or Stat1) comparable to treatment with recombinant TGF-ß(1), further indicating osteoblasts' dysfunction. Inhibition of TGF-ß signaling completely abolished the negative effects of glucose and insulin. In summary, glucose and insulin treatment causes osteoblast dysfunction, which is accompanied by an increased TGF-ß expression. Blocking TGF-ß signaling abrogates the functional loss observed in glucose- and insulin-treated osteoblasts, thus identifying TGF-ß as a key regulator. Therefore, increased TGF-ß expression during diabetes may be a feasible pathogenic mechanism underlying poor bone formation in uncontrolled diabetes mellitus.

The Munich Myocardial Infarction Registry: impact of C-reactive protein and kidney function on hospital mortality in diabetic patients.

INTRODUCTION: The aim of this study was to analyse hospital mortality with regards to the presence of diabetes, elevation of C-reactive protein (CRP) levels and impaired kidney function (IKF) on admission. METHODS: All patients in the Munich Myocardial Infarction Registry (1999-2004, n = 2,015) were assessed. In both the diabetic (n = 770, 38%) and non-diabetic (n = 1,245, 61.2%) groups, CRP and kidney function on admission were analysed with regards to hospital outcome. RESULTS: In diabetic patients, both a CRP level >7 mg/L and a glomerular filtration rate (GFR) < 60 ml/min were independent risk factors for mortality (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.9 and OR 4.4, 95% CI 2.4-8.3, respectively). In non-diabetic patients with CRP levels equal or below the median and absence of IKF, hospital mortality was 0.7% whereas the presence of the triad of diabetes, CRP levels above the median and IKF increased hospital mortality to 23.5%. CONCLUSION: The registry demonstrates that the presence of the triad of diabetes, elevated CRP levels and reduced GFR on admission is associated with an excessive hospital mortality. Optimised early interventions are to be initiated to potentially overcome the unfavourable prognosis.