Treatment outcome of the Masquelet technique in 195 infected bone defects-A single-center, retrospective case series.

BACKGROUND: The Masquelet technique is a surgical procedure for the reconstruction of bone defects. During the first step, an osteosynthetically stabilized defect is filled with a cement spacer. The spacer induces a foreign body membrane, called a Masquelet membrane. In a follow-up procedure, the spacer is replaced by a bone graft, which ossifies in the subsequent phase. MATERIAL AND METHODS: A total of 171 patients with 195 septic bone defects on the extremities that had been treated with the Masquelet procedure at the BG Klinikum in Hamburg, Germany, from 2011 to 2021 were retrospectively analysed, comparing patients who reached full weight and load bearing on the affected extremity to those who failed to do so. Defect size and configuration, microbiological results and treatment methods as well as comorbidities and epidemiologic data were analysed for factors influencing the treatment outcome. RESULTS: In all, 113[66%] of the patients were male, and 58[34%] were female, with an age distribution of 52 +/-16 years. Out of 171 patients, 24 patients had two defects. The number of patients that reached full weight bearing was 152[89%], the follow-up period was 2 +/-1 years (median +/- SD). Full weight bearing capability was negatively by the defect size as defects >62 mm tended to be less likely to reach full weight bearing than smaller defects. A secondary stabilization with an internal stabilization was applied in 58[34%] of all patients and positively influenced the attainment of full weight and load bearing. DISCUSSION: With 171 patients and 195 septic bone defects treated at a single centre with the Masquelet Technique, this study represents a comparably large cohort. Demographics, defect characteristics and treatment outcomes did not differ from those of other cohorts described in the literature. Defects larger than 62 mm showed lower chances to reach full weight bearing and can be defined as "critical defect size" for the Masquelet technique based on our data.

The effect of photodamage on the female Caucasian facial stratum corneum corneome using mass spectrometry-based proteomics.

BACKGROUND: The effect of photodamage on facial stratum corneum (SC) is still poorly understood. OBJECTIVE: To describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post-auricular (PA) site, a global analysis of photodamage on the skin will be developed leading to a better understanding of keratinocyte signalling pathways and identification of new molecular targets for the treatment of photoaged skin. METHODS: Female Caucasian subjects had nine consecutive tape strippings taken from their cheeks and PA site. Proteins were extracted and the trypsin-digested peptides were analysed by nanochromatography coupled to a high-resolution mass spectrometer. Data-dependent acquisition allowed protein identification that was processed by Paragon algorithm of Protein Pilot software. RESULTS: Changes in the levels of epidermal differentiation proteins were apparent indicating poor epidermal differentiation and SC maturation (keratins, cornified envelope (CE) proteins) on photoexposed cheeks. Differences in protease-anti-protease balance were observed for corneodesmolysis (favouring desquamation) and filaggrinolysis (favouring reduced filaggrin processing). 12R-LOX, a CE maturation enzyme, was reduced in photodamaged skin but not transglutaminases. Changes in signal keratinocyte transduction pathway markers were demonstrated especially by reduced levels of downstream signalling markers such as calreticulin (unfolded protein response; UPR) and increased level of stratifin (target of rapamycin; mTOR). Evidence for impaired proteostasis was apparent by reduced levels of a key proteasomal subunit (subunit beta type-6). Finally, key antioxidant proteins were upregulated except catalase. CONCLUSION: Clear examples of poor keratinocyte differentiation and associated metabolic and signalling pathways together with reduced SC maturation were identified in photodamaged facial SC. Corneocyte immaturity was evident with changes in CE proteins. Particularly, the reduction in 12R-LOX is a novel finding in photodamaged skin and supports the lack of SC maturation. Moreover, filaggrinolysis was reduced, whereas corneodesmolysis was enhanced. From our results, we propose that there is a poor cross-talk between the keratinocyte endoplasmic reticulum UPR, proteasome network and autophagy machinery that possibly leads to impaired keratinocyte proteostasis. Superimposed on these aberrations is an apparently enhanced mTOR pathway that also contributes to reduced SC formation and maturation. Our results clearly indicate a corneocyte scaffold disorder in photodamaged cheek SC.

Safety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective. To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods. 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results. A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions). Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (P < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions. Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio.

Effects of Echinaforce® treatment on ex vivo-stimulated blood cells.

The herb Echinacea purpurea, also called purple coneflower, is regarded as an immune modulator. This study examined changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration with an ethanolic extract of fresh Echinacea purpurea (Echinaforce(®)). Daily blood samples were ex vivo stimulated by LPS/SEB or Zymosan and analysed for a series of cytokines and haematological and metabolic parameters. Treatment reduced the proinflammatory mediators TNF-α and IL-1ß by up to 24% (p<0.05) and increased anti-inflammatory IL-10 levels by 13% (p<0.05) in comparison to baseline. This demonstrated a substantial overall anti-inflammatory effect of Echinaforce(®) for the whole group (n=28). Chemokines MCP-1 and IL-8 were upregulated by 15% in samples from subjects treated with Echinaforce(®) (p<0.05). An analysis of a subgroup of volunteers who showed low pre-treatment levels of the cytokines MCP-1, IL-8, IL-10 or IFN-γ (n=8) showed significant stimulation of these factors upon Echinaforce(®) treatment (30-49% increases; p<0.05), whereas the levels in subjects with higher pre-treatment levels remained unaffected. We chose the term "adapted immune-modulation" to describe this observation. Volunteers who reported high stress levels (n=7) and more than 2 colds per year experienced a significant transient increase in IFN-γ upon Echinaforce(®) treatment (>50%). Subjects with low cortisol levels (n=11) showed significant down-regulation of the acute-phase proteins IL1-ß, IL-6, IL-12 and TNF-α by Echinaforce(®) (range, 13-25%), while subjects with higher cortisol levels showed no such down-regulation. This is the first ex vivo study to demonstrate adapted immune-modulation by an Echinacea preparation. While Echinaforce(®) did not affect leukocyte counts, we speculate that the underlying therapeutic mechanism is based on differential multi-level modulation of the responses of the different types of leukocytes. Echinaforce(®) thus regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress.

[Definition of the Diagnosis Osteomyelitis-Osteomyelitis Diagnosis Score (ODS)]. / Zur Definition der Diagnose Osteomyelitis - Osteomyelitis-Diagnose-Score (ODS).

AIM: The disease "osteomyelitis" is characterised by different symptoms and parameters. Decisive roles in the development of the disease are played by the causative bacteria, the route of infection and the individual defense mechanisms of the host. The diagnosis is based on different symptoms and findings from the clinical history, clinical symptoms, laboratory results, diagnostic imaging, microbiological and histopathological analyses. While different osteomyelitis classifications have been published, there is to the best of our knowledge no score that gives information how sure the diagnosis "osteomyelitis" is in general. METHOD: For any scientific study of a disease a valid definition is essential. We have developed a special osteomyelitis diagnosis score for the reliable classification of clinical, laboratory and technical findings. The score is based on five diagnostic procedures: 1) clinical history and risk factors, 2) clinical examination and laboratory results, 3) diagnostic imaging (ultrasound, radiology, CT, MRI, nuclear medicine and hybrid methods), 4) microbiology, and 5) histopathology. RESULTS: Each diagnostic procedure is related to many individual findings, which are weighted by a score system, in order to achieve a relevant value for each assessment. If the sum of the five diagnostic criteria is 18 or more points, the diagnosis of osteomyelitis can be viewed as "safe" (diagnosis class A). Between 8-17 points the diagnosis is "probable" (diagnosis class B). Less than 8 points means that the diagnosis is "possible, but unlikely" (class C diagnosis). Since each parameter can score six points at a maximum, a reliable diagnosis can only be achieved if at least 3 parameters are scored with 6 points. CONCLUSION: The osteomyelitis diagnosis score should help to avoid the false description of a clinical presentation as "osteomyelitis". A safe diagnosis is essential for the aetiology, treatment and outcome studies of osteomyelitis.

The potential use of Echinacea in acne: control of Propionibacterium acnes growth and inflammation.

Acne is a chronic inflammatory disorder of skin follicles caused by the gram-positive bacterium Propionibacterium acnes. The possibility was investigated that a standardized preparation of Echinacea purpurea (Echinaforce®), with known antiviral, antiinflammatory and antibacterial properties, might provide a useful alternative treatment in the control of the disease. The herbal extract readily killed a standard laboratory strain of the bacterium and several clinical isolates. In cell culture models of human bronchial epithelial cells and skin fibroblasts, P. acne induced the secretion of substantial amounts of several pro-inflammatory cytokines, including IL-6 and IL-8 (CXCL8), as determined by means of cytokine-antibody arrays. However, the E. purpurea completely reversed this effect and brought the cytokine levels back to normal. Thus Echinaforce® could provide a safe two-fold benefit to acne individuals by inhibiting proliferation of the organism and reversing the bacterial-induced inflammation.

The efficacy of Echinacea in a 3-D tissue model of human airway epithelium.

We evaluated the antirhinovirus efficacy of a standardized preparation of Echinacea purpurea (Echinaforce) in a 3-dimensional organotypic model of normal human airway epithelium (EpiAirway tissue). Individual replicate tissue samples, maintained as inserts in culture for 3 days or 3 weeks, were infected with rhinovirus type 1A (RV1A), Echinacea alone, a combination of the two, or medium only. None of the treatments affected the histological appearance or integrity of the tissues, all of which maintained a high level of cell viability and preservation of cilia. RV infection resulted in increased mucopolysaccharide inclusions in the goblet cells, but this feature was reversed by Echinacea treatment. This result was confirmed by measurements of mucin secretion, which was stimulated by RV but reversed by Echinacea, suggesting that mucus production during colds could be ameliorated by Echinacea. We did not find evidence of virus replication, although the RV-infected tissues secreted substantial amounts of the pro-inflammatory cytokines IL-6 and IL-8 (CXCL8), and this response was reversed by Echinacea treatment. These results confirmed previous findings derived from studies of bronchial and lung epithelial cell lines, namely, that RV infection results in a substantial inflammatory response in the absence of virus replication.

Echinacea as an antiinflammatory agent: the influence of physiologically relevant parameters.

Numerous Echinacea preparations are available on the market for the prevention and treatment of cold and 'flu symptoms and inflammatory conditions associated with infections. Most of these preparations are consumed orally in the form of aqueous or ethanol extracts and tinctures. Since the recommended consumption normally involves a brief local exposure to the diluted preparation at an unspecified time in relation to the actual infection, then it is important that experimental models for the evaluation of Echinacea reflect these limitations. A line of human bronchial epithelial cells, in which rhinoviruses stimulate the production of pro-inflammatory cytokines, was used to evaluate several relevant parameters. The chemically characterized Echinacea preparation (Echinaforce) was capable of inhibiting completely the rhinovirus induced secretion of IL-6 (interleukin-6) and IL-8 (chemokine CXCL-8) in these cells, regardless of whether the Echinacea was added before or after virus infection, and in response to a range of virus doses. This inhibitory effect was also manifest under conditions resembling normal consumption with respect to the duration of exposure to Echinacea and the Echinacea dilution. It is concluded that under real life conditions of Echinacea consumption, the virus-induced stimulation of pro-inflammatory cytokines can be effectively reversed or alleviated.

Quantifying the predictive performance of prognostic models for censored survival data with time-dependent covariates.

Prognostic models in survival analysis typically aim to describe the association between patient covariates and future outcomes. More recently, efforts have been made to include covariate information that is updated over time. However, there exists as yet no standard approach to assess the predictive accuracy of such updated predictions. In this article, proposals from the literature are discussed and a conditional loss function approach is suggested, illustrated by a publicly available data set.

[Diagnostic image (347). A man with a swelling underneath his tongue]. / Diagnose in beeld (347). Een man met een zwelling onder zijn tong.

A 23-year-old man presented with a painless, growing swelling underneath his tongue due to a ranula, i.e. accumulation of saliva in the drainage canal of the sublingual salivary gland.

Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system.

Echinacea is a widely used herbal remedy for the prevention and treatment of the common cold. Recently, many new insights concerning the molecular mode of action of the main lipophilic constituents, the alkamides, have renewed interest in this plant. In order to compare the bioavailability of alkamides from liquid and tablet preparations of E. purpurea (Echinaforce) in humans and to study the effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover study with 10 (8 test, 2 placebo) volunteers has been performed. They received either 4 ml of the standardized E. purpurea (Echinaforce) tincture or 12 E. purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount (0.07 mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides. Liquid chromatography electrospray ionization ion-trap mass spectrometry was used to determine the content of alkamides in serum. It was found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid isobutylamides absorbed after oral application of the Echinaforce tincture appeared after 30 min (0.40 ng/ml serum). In comparison, the t(max) of tablets was 45 min with a C(max) of 0.12 ng/ml. An ex vivo stimulation of blood by LPS was carried out to measure the influence of E. purpurea on the innate and adaptive immune system. Both E. purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no significant changes in the concentration of IL-6 were observed. Although a quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed from the tablets, the study shows that the formulations trigger the same effects on the measured immune parameters.

Are KISS data representative of German intensive care units? Statistical issues.

OBJECTIVES: Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative. METHODS: We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR). RESULTS: Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system. CONCLUSION: For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.

[Principles of OSG arthrodesis in cases of joint infection]. / Prinzipien der OSG-Arthrodese bei Gelenkinfekt.

A chronic empyema of the ankle joint often develops after an open fracture or surgery. In the case of the destruction of the joint due to an infection, an arthrodesis should be performed. Normally we use an external fixator with two bone-nails placed into the calcaneus and two into the tibia. The arthrodesis is distracted and Septopal is permanently implemented. At 4-6 weeks after surgery the Septopal is removed, with distraction being reduced and a cancellous bone-graft taken from the dorsal iliac crest is performed to fill the bony defect. After bone healing, the external fixator is removed and the patient mobilized in a brace. Initially, weight-bearing is limited to 10 kg but is increased gradually to full weight. The brace is used for 6-9 months; later the patient is mobilized in orthopaedic shoes. In difficult cases, also in combination with a malposition which has to be corrected or a lengthening of the lower limb, we use the Ilizarov fixator. From 1993 to 2003 we performed arthrodeses of the ankle joint due to infectious destruction in 107 cases. In 82.2%, the empyema was caused by a fracture of the ankle joint and the following treatment. In 58% of the patients, we saw associated diseases such as obesity, alcohol abuse, diabetes and malposition of the foot. In 55% we found Staphylococcus aureus. In 86%, we used the external AO-fixator, in 14% the Ilizarov fixator. The patient retained the fixator for an average of 128 days. In our study, 92.1% of the 101 patients who had completed therapy showed a good stability an average of 4.5 years after the arthrodesis. In 5% we found partial stability, while three patients had to be amputated. In 57 patients (56.4), an arthrosis of the tarsal bones was found, and 38 patients (54.3%) of the 70 patients who at the time of the arthrodesis were still working could return to work.

[Initial experiences with shorter hospital stays after primary surgery for breast carcinoma]. / Eerste ervaringen met opnameduurverkorting na primaire chirurgie wegens mammacarcinoom.

OBJECTIVE: To describe some personal, medical and financial consequences of moving up the discharge of patients from hospital after an operation because of breast carcinoma. DESIGN: Descriptive. SETTING: Department of Oncological Surgery, Medical Centre, Leiden University, Leiden, the Netherlands. METHOD: Thirty-five patients with breast cancer were operated during the period March to August 1997. Thirteen patients of this group were discharged sooner after operation, with the drain still in situ; the other 22 remained in hospital until after removal of the drain. Medical and financial consequences were investigated. RESULTS: The patient characteristics of the two groups were similar. In the group discharged earlier, the number of postoperative days in hospital on average was 4.5 days smaller. The number of postoperative complications in the two groups were similar; development of seroma after removal of the drain occurred less frequently in the group discharged earlier. The financial savings amounted to an average of Dfl. 2497.-per patient. The patients discharged earlier were very satisfied. CONCLUSION: The orientative study suggests that moving up discharge after a breast cancer operation is a policy that is safe, financially advantageous and satisfactory to the patients.