Carbon nanotubes and materials based on carbon nanotubes have many perceived applications in the field of biomedicine. Several highly promising examples have been highlighted in the literature, ...ranging from their use as growth substrates or tissue scaffolds to acting as intracellular transporters for various therapeutic and diagnostic agents. In addition, carbon nanotubes have a strong optical absorption in the near-infrared region (in which tissue is transparent), which enables their use for biological imaging applications and photothermal ablation of tumors. Although these advances are potentially game-changing, excitement must be tempered somewhat as several bottlenecks exist. Carbon nanotube-based technologies ultimately have to compete with and out-perform existing technologies in terms of performance and price. Moreover, issues have been highlighted relating to toxicity, which presents an obstacle for the transition from preclinical to clinical use. Although many studies have suggested that well-functionalized carbon nanotubes appear to be safe to the treated animals, mainly rodents, long-term toxicity issues remains to be elucidated. In this report, we systematically highlight some of the most promising biomedical application areas of carbon nanotubes and review the interaction of carbon nanotubes with cultured cells and living organisms with a particular focus on in vivo biodistribution and potential adverse health effects. To conclude, future challenges and prospects of carbon nanotubes for biomedical applications will be addressed.
Contamination of food during processing is recognized as a main transmission route of
To prevent microbial contamination, biocides are widely applied as disinfectants in food processing plants. ...However, there are concerns about the development of antimicrobial resistance in foodborne pathogens due to widespread biocide usage. In our study, 93
isolates from German food production facilities were (i) tested for biocide and antibiotic susceptibility using broth microdilution assays, (ii) analyzed for links between reduced biocide susceptibility and antibiotic resistance, and (iii) characterized by whole-genome sequencing, including the detection of genes coding for biocide tolerance, antibiotic resistance, and other virulence factors. Fifteen
isolates were tolerant to benzalkonium chloride (BAC), and genes conferring BAC tolerance were found in 13 of them. Antibiotic resistance was not associated with biocide tolerance. BAC-tolerant isolates were assigned to 6 multilocus sequence type (MLST) clonal complexes, and most of them harbored internalin A pseudogenes with premature stop codons or deletions (
= 9). Our study demonstrated a high genetic diversity among the investigated isolates including genotypes that are frequently involved in human infections. Although
adaptation studies to biocides have raised concerns about increasing cross-resistance to antibiotics, our results do not provide evidence for this phenomenon in field isolates.
Foodborne pathogens such as
can persist in food production environments for a long time, causing perennial outbreaks. Hence, bacterial pathogens are able to survive cleaning and disinfection procedures. Accordingly, they may be repeatedly exposed to sublethal concentrations of disinfectants, which might result in bacterial adaptation to these biocides. Furthermore, antibiotic coresistance and cross-resistance are known to evolve under biocide selection pressure
Hence, antimicrobial tolerance seems to play a crucial role in the resilience and persistence of foodborne pathogens in the food chain and might reduce therapeutic options in infectious diseases.
Endoprosthetic reconstruction of massive bone defects has become the reconstruction method of choice after limb-sparing resection of primary malignant tumors of the long bones. Given the improved ...survival rates of patients with extremity bone sarcomas, an increasing number of patients survive but have prosthetic complications over time. Several studies have reported on the outcome of first endoprosthetic complications. However, no comprehensive data, to our knowledge, are available on the likelihood of an additional complication and the associated risk factors, despite the impact of this issue on the affected patients.
(1) What are the types and timing of complications and the implant survivorship free from revision after the first complication? (2) Does survivorship free from repeat revision for a second complication differ by anatomic sites? (3) Is the type of first complication associated with the risk or the type of a second complication? (4) Are patient-, tumor-, and treatment-related factors associated with a higher likelihood of repeat revision?
Between 1993 and 2015, 817 patients underwent megaprosthetic reconstruction after resection of a tumor in the long bones with a single design of a megaprosthetic system. No other prosthetic system was used during the study period. Of those, 75% (616 of 817) had a bone sarcoma. Seventeen patients (3%) had a follow-up of less than 6 months, 4.5% (27 of 599) died with the implant intact before 6 months and 43% (260 of 599 patients) underwent revision. Forty-three percent of patients (260 of 599) experienced a first prosthetic complication during the follow-up period. Ten percent of patients (26 of 260) underwent amputation after the first complication and were excluded from further analysis. Second complications were classified using the classification of Henderson et al. to categorize surgical results. Briefly, this system categorizes complications as wound dehiscence (Type 1); aseptic loosening (Type 2); implant fractures or breakage and periprosthetic fracture (Type 3); infection (Type 4); and tumor progression (Type 5). Implant survival curves were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) were estimated with their respective 95% CIs in multivariate Cox regression models.
A second complication occurred in 49% of patients (115 of 234) after a median of 17 months (interquartile range IQR 5 to 48) after the surgery for the first complication. The time to complication did not differ between the first (median 16 months; IQR 5 to 57) and second complication (median 17 months; IQR 5 to 48; p = 0.976). The implant survivorship free from revision surgery for a second complication was 69% (95% CI 63 to 76) at 2 years and 46% (95% CI 38 to 53) at 5 years. The most common mode of second complication was infection 39% (45 of 115), followed by structural complications with 35% (40 of 115). Total bone and total knee reconstructions had a reduced survivorship free from revision surgery for a second complication at 5 years (HR 2.072 95% CI 1.066 to 3.856; p = 0.031) compared with single joint replacements. With the numbers we had, we could not show a difference between the survivorship free of revision for a second complication based on the type of the first complication (HR 0.74 95% CI 0.215 to 2.546; p = 0.535). We did not detect an association between total reconstruction length, patient BMI, and patient age and survivorship free from revision for a second complication. Patients had a higher risk of second complications after postoperative radiotherapy (HR 1.849 95% CI 1.092 to 3.132; p = 0.022) but not after preoperative radiotherapy (HR 1.174 95% CI 0.505 to 2.728; p = 0.709). Patients with diabetes at the time of initial surgery had a reduced survivorship free from revision for a second complication (HR 4.868 95% CI 1.497 to 15.823; p = 0.009).
Patients who undergo revision to treat a first megaprosthetic complication must be counseled regarding the high risk of future complications. With second complications occurring relatively soon after the first revision, regular orthopaedic follow-up visits are advised. Preoperative rather than postoperative radiotherapy should be performed when possible. Future studies should evaluate the effectiveness of different approaches in treating complications considering implant survivorship free of revision for a second complication.
Level III, therapeutic study.
Aims: Vibrio identification by means of traditional microbiological methods is time consuming because of the many biochemical tests that have to be performed to distinguish closely related species. ...This work aimed at evaluating the use of MALDI‐TOF mass spectrometry for the rapid identification of Vibrio (V.) spp. as an advantageous application to rapidly discriminate the most important Vibrio spp. and distinguish Vibrio spp. from closely related bacterial species like Photobacterium damselae and Grimontia hollisae and other aquatic bacteria like Aeromonas spp.
Methods and Results: Starting from sub‐colony amounts of pure cultures grown on agar plates, a very simple sample preparation procedure was established and combined with a rapid and automated measurement protocol that allowed species identification within minutes. Closely related species like Vibrio alginolyticus and Vibrio parahaemolyticus or Vibrio cholerae and Vibrio mimicus could thus be differentiated by defining signatures of species‐identifying biomarker ions (SIBIs). As a reference method for species designation and for determination of relationships between strains with molecular markers, partial rpoB gene sequencing was applied.
Conclusions: The MALDI‐TOF MS‐based method as well as the rpoB sequence‐based approach for Vibrio identification described in this study produced comparable classification results. The construction of phylogenetic trees from MALDI‐TOF MS and rpoB sequences revealed a very good congruence of both methods.
Significance and Impact of the Study: Our results suggest that whole‐cell MALDI‐TOF MS‐based proteometric characterization represents a powerful tool for rapid and accurate classification and identification of Vibrio spp. and related species.
Endoprosthetic reconstruction of massive bone defects has become the reconstruction method of choice after limb-sparing resection of primary malignant tumors of the long bones. Given the improved ...survival rates of patients with extremity bone sarcomas, an increasing number of patients survive but have prosthetic complications over time. Several studies have reported on the outcome of first endoprosthetic complications. However, no comprehensive data, to our knowledge, are available on the likelihood of an additional complication and the associated risk factors, despite the impact of this issue on the affected patients.
(1) What are the types and timing of complications and the implant survivorship free from revision after the first complication? (2) Does survivorship free from repeat revision for a second complication differ by anatomic sites? (3) Is the type of first complication associated with the risk or the type of a second complication? (4) Are patient-, tumor-, and treatment-related factors associated with a higher likelihood of repeat revision?
Between 1993 and 2015, 817 patients underwent megaprosthetic reconstruction after resection of a tumor in the long bones with a single design of a megaprosthetic system. No other prosthetic system was used during the study period. Of those, 75% (616 of 817) had a bone sarcoma. Seventeen patients (3%) had a follow-up of less than 6 months, 4.5% (27 of 599) died with the implant intact before 6 months and 43% (260 of 599 patients) underwent revision. Forty-three percent of patients (260 of 599) experienced a first prosthetic complication during the follow-up period. Ten percent of patients (26 of 260) underwent amputation after the first complication and were excluded from further analysis. Second complications were classified using the classification of Henderson et al. to categorize surgical results. Briefly, this system categorizes complications as wound dehiscence (Type 1); aseptic loosening (Type 2); implant fractures or breakage and periprosthetic fracture (Type 3); infection (Type 4); and tumor progression (Type 5). Implant survival curves were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HR) were estimated with their respective 95% CIs in multivariate Cox regression models.
A second complication occurred in 49% of patients (115 of 234) after a median of 17 months (interquartile range IQR 5 to 48) after the surgery for the first complication. The time to complication did not differ between the first (median 16 months; IQR 5 to 57) and second complication (median 17 months; IQR 5 to 48; p = 0.976). The implant survivorship free from revision surgery for a second complication was 69% (95% CI 63 to 76) at 2 years and 46% (95% CI 38 to 53) at 5 years. The most common mode of second complication was infection 39% (45 of 115), followed by structural complications with 35% (40 of 115). Total bone and total knee reconstructions had a reduced survivorship free from revision surgery for a second complication at 5 years (HR 2.072 95% CI 1.066 to 3.856; p = 0.031) compared with single joint replacements. With the numbers we had, we could not show a difference between the survivorship free of revision for a second complication based on the type of the first complication (HR 0.74 95% CI 0.215 to 2.546; p = 0.535). We did not detect an association between total reconstruction length, patient BMI, and patient age and survivorship free from revision for a second complication. Patients had a higher risk of second complications after postoperative radiotherapy (HR 1.849 95% CI 1.092 to 3.132; p = 0.022) but not after preoperative radiotherapy (HR 1.174 95% CI 0.505 to 2.728; p = 0.709). Patients with diabetes at the time of initial surgery had a reduced survivorship free from revision for a second complication (HR 4.868 95% CI 1.497 to 15.823; p = 0.009).
Patients who undergo revision to treat a first megaprosthetic complication must be counseled regarding the high risk of future complications. With second complications occurring relatively soon after the first revision, regular orthopaedic follow-up visits are advised. Preoperative rather than postoperative radiotherapy should be performed when possible. Future studies should evaluate the effectiveness of different approaches in treating complications considering implant survivorship free of revision for a second complication.
Level III, therapeutic study.
Vibrio cholerae
belonging to the non-O1, non-O139 serogroups are present in the coastal waters of Germany and in some German and Austrian lakes. These bacteria can cause gastroenteritis and ...extraintestinal infections, and are transmitted through contaminated food and water. However, non-O1, non-O139
V. cholerae
infections are rare in Germany. We studied 18 strains from German and Austrian patients with diarrhea or local infections for their virulence-associated genotype and phenotype to assess their potential for infectivity in anticipation of possible climatic changes that could enhance the transmission of these pathogens. The strains were examined for the presence of genes encoding cholera toxin and toxin-coregulated pilus (TCP), as well as other virulence-associated factors or markers, including hemolysins, repeats-in-toxin (RTX) toxins,
Vibrio
seventh pandemic islands VSP-1 and VSP-2, and the type III secretion system (TTSS). Phenotypic assays for hemolysin activity, serum resistance, and biofilm formation were also performed. A dendrogram generated by incorporating the results of these analyses revealed genetic differences of the strains correlating with their clinical origin. Non-O1, non-O139 strains from diarrheal patients possessed the TTSS and/or the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, which were not found in the strains from ear or wound infections. Routine matrix-assisted laser desorption/ionization (MALDI-TOF) mass spectrometry (MS) analysis of all strains provided reliable identification of the species but failed to differentiate between strains or clusters. The results of this study indicate the need for continued surveillance of
V. cholerae
non-O1, non-O139 in Germany, in view of the predicted increase in the prevalence of
Vibrio
spp. due to the rise in surface water temperatures.
Two challenges for effectively exploiting the remarkable properties of single-walled carbon nanotubes (SWNTs) are the isolation of intact individual nanotubes from the raw material and the assembly ...of these isolated SWNTs into useful structures. In this study, we present atomic force microscopy (AFM) evidence that we can isolate individual peptide-wrapped SWNTs, possibly connected end-to-end into long fibrillar structures, using an amphiphilic α-helical peptide, termed nano-1. Transmission electron microscopy (TEM) and well-resolved absorption spectral features further corroborate nano-1's ability to debundle SWNTs in aqueous solution. Peptide-assisted assembly of SWNT structures, specifically in the form of Y-, X-, and intraloop junctions, was observed in the AFM and TEM images.
Carbon nanotubes have properties potentially useful in diverse electrical and mechanical nanoscale devices and for making strong, light materials. However, carbon nanotubes are difficult to ...solubilize and organize into architectures necessary for many applications. In the present paper, we describe an amphiphilic α-helical peptide specifically designed not only to coat and solubilize carbon nanotubes, but also to control the assembly of the peptide-coated nanotubes into macromolecular structures through peptide−peptide interactions between adjacent peptide-wrapped nanotubes. The data presented herein show that the peptide folds into an amphiphilic α-helix in the presence of carbon nanotubes and disperses them in aqueous solution by noncovalent interactions with the nanotube surface. Electron microscopy and polarized Raman studies reveal that the peptide-coated nanotubes assemble into fibers with the nanotubes aligned along the fiber axis. Most importantly, the size and morphology of the fibers can be controlled by manipulating solution conditions that affect peptide−peptide interactions.
ZusammenfassungDie Gelenkchirurgie gilt als eine der wichtigsten und erfolgreichsten Disziplinen der Chirurgie, dennoch treten Komplikationen, insbesondere in der Knieendoprothetik und der ...Kreuzbandchirurgie, auf. Eine wesentliche Erkrankung in diesem Zusammenhang stellt die Arthrofibrose dar. In dieser Übersichtsarbeit werden das zelluläre und molekulare Pathogenesekonzept der Arthrofibrose und das Spektrum der histopathologischen, immunhistochemischen Diagnostik und Differenzialdiagnostik dargestellt sowie eine Klassifikation in 1) gelenkendoprothesenassoziierte und nichtgelenkendoprothesenassoziierte Arthrofibrose vorgeschlagen. Grundlage der histopathologischen Diagnostik ist die standardisierte Gewebeentnahme mit anschließender Formalinfixierung. Bei Gelenkimplantatversagen und Fragestellung nach einer endoprothesenassoziierten Arthrofibrose kann die histopathologische Diagnostik gemäß der Konsensus-Klassifikation der „synovia-like interface membrane“ (SLIM) durchgeführt werden. Die Arthrofibrose ist durch eine Fibrosierung, eine hohe Fibroblastenzellularität mit dem immunhistochemischen Nachweis einer zytoplasmatischen β‑Catenin-Expression gekennzeichnet. Ab einem Grenzwert von 20 β-Catenin-positiven Fibroblasten pro „high-power field“ (HPF) ist das Vorliegen einer endoprothesenassoziierten Arthrofibrose wahrscheinlich. Die Diagnose einer nichtendoprothesenassoziierten Arthrofibrose kann gemäß dem Gelenkpathologiealgorithmus erfolgen. Die diffuse nichtendoprothesenassoziierte Arthrofibrose ist durch eine generalisierte Bindegewebsvermehrung im gesamten Gelenk gekennzeichnet; die lokalisierte, umschriebene Arthrofibrose zeichnet sich durch eine nodöse, zyklopsartige Fibrosierung aus. Die ursächliche Abklärung der Arthrofibrose basiert auf einer interdisziplinären Kooperation. Diese beinhaltet neben der histopathologischen Diagnostik klinisch-chirurgische, biomechanische, arthroskopische, mikrobiologische, labormedizinische und radiologische Befunde.
Purpose
This study first analyzes implant survival of this single design modular rotating hinge knee and identifies potential risk factors for failure and evaluates joint function using the ...postoperative WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, active flexion and extension deficit.
Methods
131 prostheses implanted for failure of prior total knee arthroplasty (
n
= 120) or complex primary procedures (
n
= 11) using a single modular implant (MUTARS—modular universal tumor and revision system GenuX, Implantcast, Buxtehude, Germany) between 2006 and 2014 including 73 patients treated for periprosthetic joint infection with a two-stage revision protocol were retrospectively identified. Implant survival was assessed using the Kaplan–Meier method; potential risk factors were identified using the log-rank test, as well as non-parametric analysis. Postoperative function was assessed using the WOMAC and measurement of range of motion.
Results
After a median follow-up of 62 months, 37 implants required implant revision (28%). Five-year survival was 69.7% 95% CI (confidence interval) 60.9–78.5 with periprosthetic (re-) infection being the main cause for failure (15%), followed by aseptic loosening (9%). In cases of periprosthetic infection, infection-free survival was 83% at 5 years (95% CI 74–92) with twelve patients suffering reinfection (16%).While body mass index (
p
= 0.75), age (
p
= 0.16) or indication for rotating hinge knee arthroplasty (
p
= 0.25) had no influence on survival, Charlson comorbidity score (CCI) (
p
= 0.07) and number of previous revision surgeries (
p
= 0.05) correlated with implant failure. There was trend (
p
= 0.1) for improved survival in fully cemented implants. Mean postoperative WOMAC was 127(range 55–191), 11 patients (15%) had limited knee extension.
Conclusions
Rotating hinge total knee arthroplasty using a single modular implant shows acceptable survival rates and function compared to previous studies with (re-)infection being the most relevant mode of failure. Patients with a high CCI and multiple previous surgeries are at increased risk for failure.
Level of evidence
Retrospective cohort study, III.
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