Midterm results of modular hinge total knee arthroplasty using cementless osseointegrating stems: low fixation associated complications and good functional outcome in primary and revision knee arthroplasty.

PURPOSE: This study aimed to investigate functional outcome and complications after primary and revision modular H-TKA using hybrid fixation with cementless stems. METHODS: Between 2015 and 2018, 48 patients with 50 implants were included after hybrid implantation of a single design H-TKA system using cementless osseointegrating stems and modular components. Complications and clinical outcome were analysed using Knee Society Score (KSS), the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) and the Short-Form Health Survey 12 (SF-12) score. RESULTS: Indications for implantation were aseptic revision (n = 29, 58%), primary TKA (n = 19, 38%) and two-stage septic revisions (n = 2, 4%). Complications were reported in 26% (n = 12), whereas complications associated with hybrid fixation occurred in 5 (10%) cases, with 2 (4%) requiring revision surgery for aseptic loosening and 3 (6%) treated with an adapted postoperative protocol for perioperative fractures. Implant survivorship was 84% after a mean follow-up of 54 months. Postoperative KSS significantly improved from 51.50 (12-100) to 78.36 (41-99; p < 0.001). The mean WOMAC score was 19.26 (0-55), SF-12 PCS was 41.56 points (22.67-57.66) and SF-12 MCS was 49.21 points (23.87-63.21). CONCLUSION: Hybrid modular implantation in H-TKA provides satisfactory clinical and functional results in primary and revision TKA. Clinical outcomes significantly improve with reduced pain, increased mobility, and good-to-excellent functional scores after implantation. Whilst implant survival is comparable to previous studies and complications associated with hybrid fixation are low, general complication rates are comparably high.

The use of EPR spectroscopy to study transcription mechanisms.

Electron paramagnetic resonance (EPR) spectroscopy has become a promising structural biology tool to resolve complex and dynamic biological mechanisms in-vitro and in-cell. Here, we focus on the advantages of continuous wave (CW) and pulsed EPR distance measurements to resolve transcription processes and protein-DNA interaction. The wide range of spin-labeling approaches that can be used to follow structural changes in both protein and DNA render EPR a powerful method to study protein-DNA interactions and structure-function relationships in other macromolecular complexes. EPR-derived data goes well beyond static structural information and thus serves as the method of choice if dynamic insight is needed. Herein, we describe the conceptual details of the theory and the methodology and illustrate the use of EPR to study the protein-DNA interaction of the copper-sensitive transcription factor, CueR.

Standardised step by step approach to adnexectomy by Vaginal Natural Orifice Transluminal Endoscopic Surgery.

Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) combines the advantages of vaginal surgery with those of laparoscopic surgery. Feasibility of vNOTES for other indications such as hysterectomy, ovarian cystectomy and myomectomy has been established. In this article, we describe a standardised step by step process to perform adnexal surgery by vNOTES.

[Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. German version]. / Implementierung eines standardisierten Test-Kits zur Diagnostik von periprothetischen Infektionen in der klinischen Routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Changes in circulating exosome molecular profiles following surgery/(chemo)radiotherapy: early detection of response in head and neck cancer patients.

BACKGROUND: Head and neck cancers (HNSCC) are highly immunosuppressive. Plasma-derived exosomes of HNSCC patients carry immunomodulatory molecules, and their cargo correlates with clinical parameters. Here, we evaluated the exosomal molecular profile for early detection of treatment failure in locally advanced HNSCC patients treated with conventional therapy. METHODS: Plasma from 17 HNSCC patients was collected before, during, and after treatment by surgery with adjuvant (chemo)radiation and at recurrence. Exosomes were isolated by size-exclusion chromatography. Total exosomal protein (TEP) was used to estimate exosome load and on-bead flow cytometry to evaluate relative fluorescence intensity (RFI) of tumour-associated and immunoregulatory proteins on exosomes. Exosomal effects on the activity of and adenosine production by T cells was assessed by flow cytometry and mass spectrometry. RESULTS: TEP and the ratio of tumour-/immune-cell-derived exosomes varied during and after therapy with an overall decrease in the tumour-free follow-up but an increase at recurrence. RFI values of immunoregulatory proteins on exosomes, their ability for T cell inhibition and adenosine production changed during and after therapy. PD-L1 was the earliest discriminator for treatment failure and disease-free survival. CONCLUSIONS: Monitoring of plasma exosomes during therapy represents a promising opportunity for early detection of treatment failure and risk stratification to delay/avoid recurrence.

Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Associationbetween hyperoxia and mortality in severely burned patients.

INTRODUCTION: The use of oxygen is a key component of acute burn resuscitation, particularly when there is concern for carbon monoxide toxicity or inhalation injury. Prior studies of critically-ill patients have shown an association between early hyperoxia and increased mortality. There are no studies to date evaluating outcomes related to excessive oxygen administration in burn patients. METHODS: We conducted a retrospective analysis of 219 severely burned patients to quantify the average amount of oxygen given during initial resuscitation, the level of carbon monoxide exposure, and to determine if early exposure to supratherapeutic oxygen was associated with increased hospital mortality or ventilator-associated pneumonia (VAP). The models were adjusted for inhalation injury and total body surface area (TBSA) burned. RESULTS: Early hyperoxia in severely burn patients is common and possibly associated with increased overall mortality, although the results were inconclusive and after adjusting for burn-specific scoring systems, we found a negative correlation between hyperoxia and mortality. Confirmed carbon monoxide poisoning was relatively uncommon, but also associated with increased mortality. Patients with elevated carboxyhemoglobin did not receive more oxygen compared to others within the cohort. CONCLUSIONS: Burn patients are exposed to higher concentrations of pure oxygen compared to other critically-ill patients, presumably for empiric treatment of carbon monoxide poisoning. Our data showed a liberal use of oxygen therapy across all patients. Considering the potentially negative effects of hyperoxia, this study exposes either a gap in clinical research or need for clearer indications.

Sub-cycle dynamics in relativistic nanoplasma acceleration.

The interaction of light with nanometer-sized solids provides the means of focusing optical radiation to sub-wavelength spatial scales with associated electric field enhancements offering new opportunities for multifaceted applications. We utilize collective effects in nanoplasmas with sub-two-cycle light pulses of extreme intensity to extend the waveform-dependent electron acceleration regime into the relativistic realm, by using 106 times higher intensity than previous works to date. Through irradiation of nanometric tungsten needles, we obtain multi-MeV energy electron bunches, whose energy and direction can be steered by the combined effect of the induced near-field and the laser field. We identified a two-step mechanism for the electron acceleration: (i) ejection within a sub-half-optical-cycle into the near-field from the target at >TVm-1 acceleration fields, and (ii) subsequent acceleration in vacuum by the intense laser field. Our observations raise the prospect of isolating and controlling relativistic attosecond electron bunches, and pave the way for next generation electron and photon sources.

[Using social network analysis to examine care for older drug users in three major cities in Germany : Results of a pilot study]. / Soziale Netzwerkanalyse der Versorgungsstrukturen für ältere Drogenabhängige in drei deutschen Großstädten : Ergebnisse einer Pilotstudie.

BACKGROUND: Compared with the general population, chronic drug addicts already start showing typical aging problems by the age of 40 years. The increasing number of older drug addicts leads to questions of what an adequate health and social care should look like. This discussion particularly takes place in the context of a sufficient integration of different care systems. A sufficient integration requires an improvement in the networking of substance treatment, nursing care and medical care services. OBJECTIVE: The purpose of this study was to investigate the care structure of older people who use drugs and the services involved in a social network analysis. This was a descriptive design of the pilot study. The study objective was to gain first-hand knowledge about the health and social care situation, the quality of care concerning this client group and to identify supply gaps. Therefore, the three regions Cologne, Dusseldorf and Frankfurt/Main were exemplarily examined. MATERIAL AND METHODS: The data for the social network analysis was gathered by a quantitative online questionnaire. Therefore, especially central network members were contacted and asked to participate. The survey was conducted in two waves. RESULTS: In total, 65 practitioners of all surveyed cities participated in the second wave. The centrality measures assessed indicated that in all regions institutions of the substance abuse service network hold central positions in terms of conveying information. The moderate density values of the networks suggest that there are sufficient cooperation structures. Care deficits were identified most frequently in the areas of housing and nursing care. CONCLUSION: The results provide the first systematic insights and a description of the cooperation practice in the care system. Because of the limitations, further research and practice issues are raised.

Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to assess the feasibility and safety of fast-track hospitalizations in a selected cohort of patients with stroke. METHODS: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion-weighted imaging were included. Neurological deficits of the included patients were non-disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared - fast-track hospitalizations (≤72 h) and long-term hospitalizations (>72 h). The primary end-point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3-6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). RESULTS: Amongst the 521 patients who met the inclusion criteria, fast-track hospitalizations were performed in 79 patients (15%). In the fast-track group, seven patients (8.9%) met the primary end-point, compared to 37 (8.4%) in the long-term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42-2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end-point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51-3.16, P = 0.61). The costs of fast-track hospitalizations were lower, on average, by $4994. CONCLUSIONS: Fast-track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long-term hospitalizations.

Melanomas vs. nevi in high-risk patients under long-term monitoring with digital dermatoscopy: do melanomas and nevi already differ at baseline?

BACKGROUND: What lesions to select for a most efficient dermatoscopic monitoring of patients with multiple nevi remains an unresolved issue. OBJECTIVE: To compare the grade of atypia of melanomas and nevi of the same patient at baseline. METHODS: Prospective observational study using 236 dermatoscopic baseline images (59 quartets from 59 patients, each including one melanoma detected during follow-up and three nevi). Dermatologists (n = 26) were asked to assess the 'grade of dermatoscopic atypia' on a numerical scale and to identify the melanomas. RESULTS: On average, each dermatologist identified 24 of 59 melanomas (40%, range: 11-37). The number of correct picks was greater for dermatologists with moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17; P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4-2.6) and 3.0 for melanomas (95% CI: 2.9-3.1, P < 0.001). LIMITATIONS: Rating dermatologists were informed that each quartet of images included one melanoma creating substantial deviation from a real-life situation. CONCLUSION: A significant proportion of melanomas detected during follow-up cannot be differentiated from nevi at baseline. This necessitates the additional inclusion of less atypical lesions for monitoring.

Collective Deceleration of Laser-Driven Electron Bunches.

Few-fs electron bunches from laser wakefield acceleration (LWFA) can efficiently drive plasma wakefields (PWFs), as shown by their propagation through underdense plasma in two experiments. A strong and density-insensitive deceleration of the bunches has been observed in 2 mm of 10^{18} cm^{-3} density plasma with 5.1 GV/m average gradient, which is attributed to a self-driven PWF. This observation implies that the physics of PWFs, usually relying on large-scale rf accelerators as drivers, can be studied by tabletop LWFA electron sources.

Internal pH regulation facilitates in situ long-term acclimation of massive corals to end-of-century carbon dioxide conditions.

The resilience of tropical corals to ocean acidification depends on their ability to regulate the pH within their calcifying fluid (pHcf). Recent work suggests pHcf homeostasis under short-term exposure to pCO2 conditions predicted for 2100, but it is still unclear if pHcf homeostasis can be maintained throughout a corals lifetime. At CO2 seeps in Papua New Guinea, massive Porites corals have grown along a natural seawater pH gradient for decades. This natural gradient, ranging from pH 8.1-7.4, provides an ideal platform to determine corals' pHcf (using boron isotopes). Porites maintained a similar pHcf (~8.24) at both a control (pH 8.1) and seep-influenced site (pH 7.9). Internal pHcf was slightly reduced (8.12) at seawater pH 7.6, and decreased to 7.94 at a site with a seawater pH of 7.4. A growth response model based on pHcf mirrors the observed distribution patterns of this species in the field. We suggest Porites has the capacity to acclimate after long-time exposure to end-of-century reduced seawater pH conditions and that strong control over pHcf represents a key mechanism to persist in future oceans. Only beyond end-of-century pCO2 conditions do they face their current physiological limit of pH homeostasis and pHcf begins to decrease.

MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma.

In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors in a rat hepatoma model (P<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these miRNAs. Attenuation of luciferase expression by the corresponding miRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two miRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared with the control vector (6.40 and 0.26%, respectively; P<0.05). In tumor, miR-122 had a nonsignificant trend towards decreased (∼50%) expression, whereas miR-26 had no significant effect on tumor expression. To our knowledge, this is the first work using differentially expressed miRNAs to de-target transgene expression in an orthotopic hepatoma model and to identify miR-26a, in addition to miR-122, for de-targeting liver. Considering the heterogeneity of miRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease.

Modeling of a segmented electrode for desynchronizing deep brain stimulation.

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders like Parkinson's disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates nerve fibers and cell bodies in the vicinity. Even though the different target nuclei display considerable differences in their anatomical structure, only few types of electrodes are currently commercially available. It is desirable to adjust the electric field and in particular the volume of tissue activated around the electrode with respect to the corresponding target nucleus in a such way that side effects can be reduced. Furthermore, a more selective and partial activation of the target structure is desirable for an optimal application of novel stimulation strategies, e.g., coordinated reset neuromodulation. Hence we designed a DBS electrode with a segmented design allowing a more selective activation of the target structure. We created a finite element model (FEM) of the electrode and analyzed the volume of tissue activated for this electrode design. The segmented electrode activated an area in a targeted manner, of which the dimension and position relative to the electrode could be controlled by adjusting the stimulation parameters for each electrode contact. According to our computational analysis, this directed stimulation might be superior with respect to the occurrence of side effects and it enables the application of coordinated reset neuromodulation under optimal conditions.

[New radiological techniques to investigate patients suffering from chronic kidney disease]. / Nouvelles techniques radiologiques pour les patients insuffisants rénaux.

Radiological investigations using gadolinium or intravenous iodinated contrast products are used cautiously in patients suffering from chronic kidney disease because of their risk of acute kidney injury and systemic nephrogenic fibrosis. In this article, we review several radiological alternatives that can be useful to obtain renal anatomical and/or functional information in this patient population. The basic principles, indications, and advantages and limitations of Doppler ultrasound with measurement of the resistance index, contrast-enhanced ultrasound, and a technique called BOLD-MRI (blood-oxygenation level dependent-MRI) are discussed.

Potent, tumor-specific gene expression in an orthotopic hepatoma rat model using a Survivin-targeted, amplifiable adenoviral vector.

Ideal cancer gene therapies should have high tumor specificity and efficacy, and allow systemic administration to target metastases. We recently developed a bi-directional, two-step transcriptional amplification (TSTA) system driven by the tumor-specific Survivin promoter (pSurv) to amplify the correlated expression of both the reporter gene firefly luciferase (FL) and therapeutic gene tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we compare the specificity and potency of an adenovirus carrying this system (Ad-pSurv-TSTA-TRAIL-FL) to a nonspecific vector (Ad-pCMV-FL) in an orthotopic hepatocellular carcinoma (HCC) rat model after systemic administration. At 24 h after injection of Ad-pCMV-FL, bioluminescence imaging revealed a trend (P=0.30) towards greater FL expression in liver versus tumor. In striking contrast, Ad-pSurv-TSTA-TRAIL-FL showed increased FL activity within the tumor compared with the liver (P<0.01), a strong trend towards reduced liver expression compared with Ad-pCMV-FL (P=0.07), and importantly, similar FL levels within tumor compared with Ad-pCMV-FL (P=0.32). Hence, this vector shows potent, tumor-specific transgene expression even after extensive liver transduction and may be of significant value in avoiding hepatotoxicity in HCC patients. Future studies will explore the benefits of tumor-specific TRAIL expression in this model, the potential to target metastases and the extension of this vector for the treatment of other Survivin-positive tumors is warranted.

Bochdalek hernia in the adult: demographics, presentation, and surgical management.

BACKGROUND: Bochdalek hernias are a very rare form of diaphragmatic hernias. There are no robust studies that reveal the true natural history of this disease process. The aim of this study was to summarize clinically relevant data for the purpose of assisting surgeons with the work-up, diagnosis, and treatment of adult patients with Bochdalek hernia. METHODS: A literature search was performed using PubMed, Google scholar, EMBASE and the following keywords: Bochdalek hernia, congenital diaphragmatic hernia, and posterolateral hernia. All case reports and series after 1955 that pertained to adults were included in the review. The following data points were queried: age, sex, presentation, studies utilized during work-up, laterality, surgical approach, hernia sac management, specific minimally invasive surgical techniques, and follow-up. RESULTS: A total of 124 articles comprising 173 patients met the inclusion criteria. Based on the data provided, several conclusions regarding this disease process can be made. Most patients present with symptoms related to their hernia (86%). Pain is the most common complaint (69%). While laparotomy is the most widely used surgical approach (38%), minimally invasive surgical techniques have gained popularity since their first report in 1995. Laparoscopic repair can be performed with a low complication rate (7%) and short hospital stay (4 days). CONCLUSIONS: Using modern surgical techniques to include laparoscopy, repair can be performed safely, with a short hospital stay, and with minimal morbidity or mortality.