Stereologische Untersuchungen der Gas-Austauschregion der Lunge und der Innervation der Trachea bei der tumorkachektischen Maus

In der vorliegenden Arbeit wurden Trachea und Lunge von C57Bl6-Mäusen untersucht, bei denen durch subkutane Injektion eines definierten Depots von Lewis-Lung-Carcinoma-Zellen in die Nackenregion eine Tumorkachexie erzeugt wurde. Diese war durch Gewichtsverlust, Anämie und pro-inflammatorische Stoffwechsellage charaterisiert. Im Vergleich mit der Kontrollgruppe sollten folgende Fragestellungen überprüft werden: 1. Da es verschiedene Arbeiten gibt, die bei ausgeprägter Kalorienreduktion einen emphysemähnlichen Zustand der Lunge beschrieben haben, sollte untersucht werden, ob bei Tumorkachexie ebenfalls eine Verminderung der Alveolaroberfläche im Sinne eines Emphysems auftritt. 2. In der Literatur ist außerdem beschrieben, dass Kalorienreduktion zu einer Verminderung der Menge und Funktion des pulmonalen Surfactants führt. Es wurde daher die Hypothese untersucht, ob Tumorkachexie ebenfalls zu Veränderungen des intra-alveolären und intrazellulären Surfactants führt. 3. In demselben Tiermodell wurde gezeigt, dass die Innervation des linksventrikulären Myokards bei Tumorkachexie verringert ist. Hier sollte am Beispiel der Trachea untersucht werden, ob eine solche Hypoinnervation auch bei den Atemwegen auftritt. 4. Zusätzlich sollte explorativ der trophische Zustand der Trachea analysiert werden. Im Vordergrund der verwendeten Methodik standen stereologische und immunhistochemische licht- und elektronenmikroskopische Techniken, die durch andere Methoden wie quantitative RT-PCR und differentielle Surfactant-Zentrifugation ergänzt wurden. Die Ergebnisse der Arbeit lassen sich wie folgt zusammenfassen: 1. Anders als bei Kalorienreduktion konnte in der vorliegenden Arbeit kein Hinweis auf einen emphysemähnlichen Zustand bzw. eine Verminderung der dem Gasaustausch dienenden Alveolaroberfläche gefunden werden. Dies lässt sich möglicherweise auf vom Tumor gebildete und sezernierte Wachstumsfaktoren zurückführen, die einen Abbau der Alveolaroberfläche verhindern. 2. Analog zur Kalorienreduktion konnte eine Verminderung der intrazellulären Surfactantspeicher dargestellt werden bei gleichzeitig unverändertem Gleichgewicht zwischen aktiven und inaktiven intra-alveolären Surfactantformen. 3. Die Innervation der Trachea war auf etwa die Hälfte der Kontrollwerte reduziert, was in etwa den Befunden am Herzen entspricht. Da die meisten Nervenfasern des linken Ventrikels dem sympathischen Nervensystem zuzuordnen sind, während bei der Trachea die meisten Nervenfasern parasympathisch oder sensorisch sind, spricht dies für einen systemischen Effekt der Tumorkachexie auf das periphere Nervensystem. 4. Mit Ausnahme der rasterelektronenmikroskopischen Darstellung des Trachealepithels ließ sich kein quantitativer Unterschied hinsichtlich der Morphologie der einzelnen am Wandaufbau der Trachea beteiligten Gewebe feststellen. Ein sicheres morphologisches Korrelat für die klinisch bei kachektischen Patienten beobachtete Dyspnoe ließ sich in der vorliegenden Arbeit nicht darstellen. Allerdings könnte eine Verminderung des Surfactants durchaus mit einer erhöhten Atemarbeit vergesellschaftet sein und eine verminderte Innervation der Atemwege zu einer Fehlregulation des normalen Atmungsvorgangs und dessen subjektiver Wahrnehmung im Sinne einer Dyspnoe beitragen. Die Ergebnisse können daher Grundlage für weitere Untersuchungen der für Tumorpatienten quälenden Dyspnoe sein und helfen, neue Ansatzpunkte für zukünftige Therapien dieses Symptoms zu finden.In the present work, the trachea and lungs of C57Bl6 mice were studied, in which, by subcutaneous injection of a defined depot of Lewis lung carcinoma cells in the neck region, a tumor cachexia was produced. This was charaterised by weight loss, anemia, and pro-inflammatory metabolism. Compared with a control group, the following questions should be examined: 1. Because there are several works that describe an emphysema like condition of the lungs in a situation of pronounced reduction in caloric intake, it should be examined whether under conditions of cancer cachexia alveolar surface area reduction with emphysema like conditions can be observed. 2. In the literature it is also described that caloric reduction leads to a reduction in the amount and function of pulmonary surfactant. Therefore, the hypothesis was investigated whether tumor cachexia also leads to changes of the intra-alveolar and intracellular surfactant. 3. In the same animal model it has been shown that the innervation of the left ventricular myocardium is decreased in cancer cachexia. It should be examined, whether hypoinnervation also occurs in the tracheal airways. 4. Moreover, the trophic state of the trachea should be analyzed exploratively. In the middle of the methodology stereological and immunohistochemical light and electron microscopy techniques were used, which were supplemented by other methods such as quantitative RT-PCR and surfactant differential centrifugation. The results of this work can be summarized as followed: 1. Unlike in reduced caloric intake an emphysema-like state or a reduction in the gas exchange serving alveolar surface could not be found in the present study. This may possibly be attributed to by the tumor formed and secreted growth factors which prevent the degradation of the alveolar surface. 2. Similar to the calorie reduction a decrease in intracellular surfactantorganell could be shown. At the same time the natural balance between active and inactive intra-alveolar surfactant was maintained. 3. The innervation of the trachea was reduced to about half of the control group, which corresponds approximately to the findings of the heart. Since most nerve fibers of the left ventricle are attributable to the sympathetic nervous system, while at the trachea most nerve fibers are parasympathetic or sensory, this indicates a systemic effect of cachexia on the peripheral nervous system. 4. With the exception of the scanning electron microscope view of the tracheal epithelium no quantitative difference in the morphology of the different tissues involved in the wall structure of the trachea could be ascertained. An unambiguous morphological correlate for the clinically observed dyspnea cachectic patients could not be shown in the present work. However, a reduction of the surfactant may well be associated with an increased respiratory work and a reduced innervation of the airways may contribute to a dysregulation of the normal breathing process and its subjective perception in the sense of dyspnea. The results could be the basis for further investigations of the dyspnea of tumor patients and help to find new targets for future therapies of this symptom

Diagnostic Accuracy for Periprosthetic Joint Infection Does Not Improve by a Combined Use of Glucose and Leukocyte Esterase Strip Reading as Diagnostic Parameters

The diagnosis of periprosthetic infections (PJI) can be challenging in clinical practice because the clinical presentations of aseptic loosening and low-grade infections are similar. Semiquantitative evaluation of leukocyte esterase (LE) in synovial fluid using a urine strip test has already established itself as a diagnostic method over the past decade. The analysis of LE in synovial fluid leads to a high number of false-positive test results. In the present study, the value of a combined semiquantitative determination of glucose and LE in synovial fluid to improve the diagnosis of PJI was investigated. Over a 4-year period, 145 synovial samples were collected from patients who developed joint effusion after arthroplasty. LE and glucose test strips were considered as an index test for the diagnosis of PJI. A ++ or +++ LE and a negative glucose test strip reading were considered as positive test results. Modified diagnostic criteria for PJI as recommended by the Musculoskeletal Infection Society (MSIS) served as the reference test, except that intraoperative findings were excluded. Forty-six out of 145 samples were classified as septic complication according to the reference test. In regard to PJI, our data showed that combined use of LE and glucose strip test reading displayed a 98.0% specificity (95% confidence interval (CI): 95.2% to 100%), a 50% sensitivity (95% CI: 35.6% to 64.4%), a 92% positive predictive value (95% CI: 81.4% to 100.0%), and an 80.3% negative predictive value (95% CI: 73.2% to 87.4%). In contrast, the exclusive analysis of LE on the urine strip to diagnose PJI demonstrated a 90.9% specificity (95% CI: 85.2% to 96.6%), a 67.4% sensitivity (95% CI: 53.8% to 80.9%), a 77.5% positive predictive value (95% CI: 64.6% to 90.4%), and an 85.7% negative predictive value (5% CI: 79.0% to 92.4%). A combination of LE and glucose test pad reading is considered superior as a potential “rule-in” method for the diagnosis of PJI compared with LE test pad analysis alone. However, combined LE and glucose synovial fluid testing also demonstrated lower test sensitivity and thus diagnostic accuracy compared with LE analysis alone. Therefore, combined glucose and LE test pad analysis does not represent a sufficient diagnostic standard to exclude PJI with certainty

Management, outcome, and novel classification system of periprosthetic fractures in patients with transcutaneous osseointegrated prosthetic systems (TOPS)—a retrospective cohort analysis

Introduction!#!Transcutaneous osseointegrated prosthetic systems (TOPS) are anchored prosthetic systems for major limb loss. Sometimes TOPS patients suffer from periprosthetic fractures. The aim of this study was to analyze the management and outcomes of periprosthetic fractures in patients with TOPS and to introduce a novel classification system for this entity.!##!Material/methods!#!Since 2010, 140 patients were treated with TOPS after transfemoral amputation in two centers in Germany. Fifteen patients sustained periprosthetic fractures, with five intra- and ten postoperative fractures. The outcome was analyzed by Prosthesis Mobility Questionnaire (PMQ), K-level and prosthesis wear time per day. A subgroup analysis for the body mass index (BMI) was performed.!##!Results!#!All postoperative fractures were treated with implant-retaining osteosynthesis. Fourteen fractures healed without complications after a mean of 3 months. One postoperative fracture developed a clinically asymptomatic firm non-union. No Endo-Fixstem had to be removed. For the fracture and control group, a significant increase of the PMQ (p < 0.001) and K-level (p < 0.001) was observed after TOPS treatment compared to the preoperative baseline. Furthermore, the subgroup analysis showed a significant increase of the PMQ and K-level for both normal weight (p = 0.002) and overweight patients (p < 0.001). Of interest, overweight patients even showed a significantly higher increase in scores compared to normal weight patients, regardless of periprosthetic fracture.!##!Conclusion!#!Periprosthetic fractures do not necessarily worsen outcomes of TOPS treatment. Proper classification and standardized appropriate treatment strategies according to fracture morphology are paramount for reliably good outcomes. We recommend to not remove or exchange the implant (Endo-Fixstem) even if it is assembly. Higher BMI did not have an impact onto rehabilitation success after TOPS to major limb loss of the lower extremity

Patella baja after intramedullary nailing of tibial fractures, using an infrapatellar/transtendinous approach, predicts worse patient reported outcome

PURPOSE: After intramedullary nailing of tibial shaft fractures using an infrapatellar/transtendinous approach, several patients suffer anterior knee pain. We suspect that the approach is associated with soft tissue scars and the development of a postoperative patella baja. The goal of the study is to investigate whether the development of patella baja is associated with worse subjective outcomes. METHODS: We retrospectively analyzed all patients in our orthopedic trauma department between 2011 and 2020 who underwent tibial fracture fixation via intramedullary nailing via an infrapatellar/transtendinous approach. Pre- and postoperative lateral knee x-rays were evaluated by measurement of the Insall-Salvati Index, and nail tip position. All patients were asked to answer the self-assessment Kujala questionnaire and Lysholm questionnaire. RESULTS: We included 78 patients (age: 44 ± 18 years) with a minimum follow-up of 12 months. Mean follow up was 59 ± 25 months. We included 50 male and 28 female patients. Patella baja detected by Insall-Salvati Index could be observed in 8 (10.3%) patients. Patients with patella baja showed significant worse function measured by the Kujala score 54 ± 18 vs. 80 ± 14 (p < 0.01). Likewise, Lysholm score did show significant differences between both groups (60 ± 24 vs. 86 ± 11; p < 0.01). Nail tip position was not associated with worse subjective function. CONCLUSIONS: Patella baja in patients after tibial intramedullary nailing via an infrapatellar/transtendinous approach, is associated with worse subjective function and increased pain

Risk factors for dislocation after bipolar hemiarthroplasty: a retrospective case–control study of patients with CT data

Purpose!#!Bipolar hemiarthroplasty has been shown to have a lower rate of dislocation than total hip arthroplasty. However, as the influencing risk factors for bipolar hemiarthroplasty dislocation remain unclear, we aimed to analyse patient and surgeon-specific influencing risk factors for bipolar hemiarthroplasty dislocation.!##!Methods!#!We retrospectively analysed patients who were operated between 2012 and 2018 and had dislocated bipolar hemiarthroplasty and matched them to patients without a dislocated bipolar hemiarthroplasty, operated between 2018 and 2019. The study was limited to patients who received either a pre- or postoperative pelvic computed tomography. Besides demographic, morphologic, and physiologic data, we analysed duration of surgery; ASA score; Charlson Comorbidity Index; Almelo Hip Fracture Score; Parker Score; and acetabular morphology angles including acetabular anteversion angle, posterior acetabular sector angle, posterior wall angle, and acetabular roofing.!##!Results!#!We included nine patients with a dislocated bipolar hemiarthroplasty and 30 with a non-dislocated bipolar hemiarthroplasty. Patient-specific factors prompting a higher risk for dislocated bipolar hemiarthroplasty were longer duration of surgery (min) (115 ± 50 vs. 80 ± 27, p = 0.01); dementia (56% vs. 13%, p &amp;lt; 0.01); smaller posterior acetabular sector angle (°) (96 ± 6 vs. 109 ± 10, p &amp;lt; 0.01); and smaller posterior wall angle (°) (67 ± 6 vs. 77 ± 10, p = 0.02).!##!Conclusion!#!Dementia and insufficient posterior wall angle were associated with higher risk of dislocation in bipolar hemiarthroplasty