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Ticks are important vectors of several human and animal pathogens. In this study, we estimated the prevalence of important tick-borne infections in questing ticks from an area in Southwestern France (Hautes-Pyrénées) inhabited by Pyrenean chamois (Rupicapra pyrenaica pyrenaica) experiencing high tick burden. We examined adult and nymph ticks collected by the flag dragging method from 8 to 15 sites in the Pic de Bazès during the years 2009, 2011, 2013 and 2015. PCR assays were conducted on selected ticks for the detection of Borrelia burgdorferi s.l., Babesia spp., Rickettsia spp., spotted fever group (SFG) Rickettsia and Anaplasma phagocytophilum. Randomly selected positive samples were submitted for sequence analysis. A total of 1971 questing ticks were collected including 95 males, 101 females and 1775 nymphs. All collected ticks were identified as Ixodes ricinus. Among them, 696 ticks were selected for pathogen detection and overall prevalence was 8.4% for B. burgdorferi s.l.; 0.4% for Babesia spp.; 6.1% for A. phagocytophilum; 17.6% for Rickettsia spp.; and 8.1% for SFG Rickettsia. Among the sequenced pathogens, we detected in this population of ticks the presence of Babesia sp. EU1 and Rickettsia helvetica, as well as Rickettsia monacensis for the first time in France. The detection of these pathogens in the Pic de Bazès highlights the potential infection risks for visitors to this area and the Pyrenean chamois population.

Aims: The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders., Methods: Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 10 3 or 1 × 10 6 colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 10 3 or 1 × 10 6 CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash., Results: The first part of the study showed that low-grade infection was more significant in 400 µm cylinders than cylinders with larger pore sizes (p < 0.05). The second part of the study showed that saline wash alone was ineffective in eradicating both low- and high-grade infections. Saline plus PVA-VAN/TOB-P eradicated the titanium cylinder-associated infections, as manifested by negative cultures of the washouts and supported by scanning electron microscopy and histology., Conclusion: Porous titanium cylinders were vulnerable to bacterial infection and biofilm formation that could not be treated by saline irrigation alone. Application of PVA-VAN/TOB-P directly into the surgical site alone or after saline wash represents a feasible approach for prevention and/or treatment of porous implant-related infections., Competing Interests: D. C. Markel reports consulting fees and speaker payments from Smith & Nephew and Stryker, holds stock or stock options in HOPCo/Arboretum Ventures, receipt of equipment, materials, drugs, medical writing, gifts, or other services from OREF/Stryker, all of which are unrelated to this study. D. C. Markel also sits on the monitoring board or advisory board of the Michigan Orthopedic Society/Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI). D. C. Markel is an editorial or governing board member of Arthroplasty Today and Journal of Arthroplasty, and also reports research support from Ascension Providence Hospital, stock or stock options in Plymouth Capital, and IP royalties from Smith & Nephew, all of which are unrelated to this study., (© 2024 Markel et al.)

Objective: This study aimed to assess the public's knowledge of stroke before and after viewing an educational video about stroke risk factors, preventive measures, and alarming signs., Methods: A single-arm interventional study was conducted in Lebanon using a 3-minute video-based education about stroke. A pre- and post-structured questionnaire compared the level of knowledge about stroke., Results: The study included 685 participants. Knowledge of stroke, risk factors, warning signs, treatment, and preventive measures significantly increased post-educational video sessions. A higher baseline knowledge score was associated with a family history of stroke (Beta = 1.76) and being a healthcare professional (Beta = 3.35). Participants between 25 and 34 years (Beta=-1.39) and those with a high risk of stroke (Beta=-1.03) were significantly associated with a lower knowledge score., Conclusion: This study demonstrated the effectiveness of a video-based educational tool to raise awareness about stroke. Short, targeted audio-visual resources using lay language can convey health education messages and influence behavioral changes. The community can benefit from a large-scale educational campaign that targets different socio-economic statuses to enhance knowledge of stroke and save lives., (© 2024. The Author(s).)

Cellular infiltration into electrospun nanofibers (NFs) is limited due to the dense structure and small pore sizes. We developed a programmed NF collector that can fabricate porous NFs with desired pore sizes and thickness. Previously we demonstrated improved cellular proliferation and differentiation of osteoblasts, osteoclasts, and fibroblasts with increased pore sizes of polycaprolactone (PCL) NF in-vitro. This study investigated in-vivo host cell migration and vascular ingrowth within porous NF sheets implanted subcutaneously in a mouse model. Two types of PCL NFs with well-defined pore sizes were created using varying speeds of the NF collector: NF-zero (no movement, pore size 14.4 ± 8.9 µm 2 ) and NF-high (0.232 mm/min, pore size 286.7 ± 381.9 µm 2 ). The NF obtained by using classical flat NF collector (2D NF, pore size 1.09 ± 1.7 µm 2 ) was a control. The three formulae of NFs were implanted subcutaneously in 18 BALB/cJ mice. Animals were killed 7 and 28-days after implantation (n = 3 per group per time point). The tissue with implanted NFs were collected for histologic analysis. Overall, 7-day samples showed little inflammatory response. At 28-days, the degree of tissue penetration of PCL NF sheet matrices was linked to pore size and area. NFs with the largest pore area had more efficient tissue migration and new blood vessel formation compared to those with smaller pore sizes. No newly formed blood vessels were observed in the 2D NF group. A porous NF scaffold with controllable pore size has potential for tissue repair/regeneration in situ with potential for many applications in orthopaedics., (© 2024 Orthopaedic Research Society.)

Background: There is a desire in orthopaedics to have soft tissue, particularly tendon, grow into metallic implants. With the introduction of three-dimensional (3D) printed porous metal implants, we hypothesized that tendons could directly attach to the implants. However, the effects of the porous metal structure on tissue growth and penetration into the pores are unknown. Using a rat model, we investigated the effect of pore size on tendon repair fixation using 3D printed titanium implants., Methods: There were three experimental groups of eight Sprague Dawley rats (n = 24) plus control (n = 3). Implants had defined pore sizes of 400µm (n = 8), 700µm (n = 8), and 1000µm (n = 8). A defect was created in the Achilles tendon and the implant positioned between cut ends and secured with suture. Specimens were harvested at twelve weeks. Half the specimens underwent mechanical testing to assess tensile load to failure. The remaining specimens were fixed and processed for hard tissue histological analysis., Results: The average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. The 700µm and 1000µm specimens performed similarly, while the 400µm showed significant differences vs control (p = 0.039), vs 1000µm (p = 0.010), and approached significance vs 700µm (p = 0.066). There was increasing ingrowth as pore size increased. Histology showed fibrous tendon tissue within and around the implants, with collagen fibers organized in bundles., Conclusions: Tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon ingrowth onto/into an implant at the time of revision arthroplasty., Competing Interests: The senior author, David Markel, is a paid consultant for Stryker and Smith & Nephew. Dr. Markel serves on the editorial board of the Journal of Arthroplasty and Arthroplasty Today, and he is a board member for MARCQI and the Michigan Orthopedic Society. The rest of the authors have no conflict of interest to declare.

Background: Periprosthetic joint infection remains a major problem. The bactericidal efficacy of commercial irrigation solutions for the treatment of infection is not well established in the presence of porous titanium (Ti) implants. This study compared the in vitro efficacy of five irrigation solutions on infected three-dimensional-printed porous Ti discs., Methods: Titanium discs (2 × 4 mm, 400, 700, and 1,000 μm) were infected with S. aureus (1 × 10 6 colony-forming unit/mL) and incubated for 3 hours or 3 days to create acute or chronic infection with biofilm. Discs were irrigated with saline, antibiotic, or antiseptic solutions, then repeatedly sonicated. Sonicates were cultured for bacterial quantification. Statistical analyses were performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc testing (P < .05 significance). Biofilms were visualized by scanning electron microscopy., Results: Saline irrigation was ineffective in both groups. In acute infections with 400 μm pores, differences were found with saline versus solution #3 (P = .015) and #4 (P = .015). Solution #4 had the lowest bacterial counts for all pore sizes. For biofilm, irrigation with saline, solutions #1, #2, and #3 inadequately cleared bacteria in all pore sizes. Lower remaining concentrations were observed in #4 with 400μm pores compared to saline (P = .06) and #2 (P = .039). The scanning electron microscopy showed a reduction of biofilm in samples washed with #4., Conclusions: Irrigation of infected porous Ti discs with saline, solutions #1 and #2 failed to reduce the bacterial load. The 400 μm discs consistently had more bacteria despite irrigation, highlighting the difficulty of removing bacteria from small pores. Solutions #3 and #4 reduced bacteria acutely, but only #4 demonstrated efficacy in clearing biofilm compared to saline. These results should be considered when treating periprosthetic joint infection in the presence of porous components and the potential presence of biofilm., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Periprosthetic joint infection (PJI) remains common and problematic. We hypothesized that using a bioceramic that provided rapid release of the antibiotics (vancomycin [VAN] or VAN and tobramycin [VAN and TOB]) from a polyvinyl-alcohol-composite (PVA) combined with a delayed and sustained antibiotic release from polymeric-dicalcium-phosphate-dihydrate (PDCPD) ceramic would inhibit S. aureus-associated implant infections., Methods: A total of 50 male Sprague Dawley rats were randomly divided into 5 groups-I: negative control; II: bacteria only; III: bacteria + saline wash; IV: bacteria + PVA-VAN-PDCPD, and V: bacteria + PVA-VAN-TOB-PDCPD. A porous titanium (Ti) implant was press-fit into the rat knee. S. aureus-containing broth was added into the joint space creating a PJI. After 1 week, the joints from groups III to V were washed with saline and the fluid collected for bacterial quantification. This was followed by saline irrigation treatment (groups III to V) and application of the antibiotic-loaded PVA-PDCPD bioceramic (groups IV and V). On day 21, joint fluid was collected, and the implants harvested for bacterial quantification., Results: No bacteria were isolated from the negative control (group I). The positive control (group II) was positive on both days 7 and 21. Bacteria were still present on day 21 in the fluid and implant in group III. Groups (IV and V) showed a decrease in the bacterial burden in the fluid and implant on day 21. There were significant differences in bacteria levels in the collected wash fluid and on the implant at day 21 between the saline wash (group III) and treatment groups (IV and V)., Conclusions: In this animal model of acute periprosthetic infection, treatment with PVA-VAN-PDCPD and PVA-VAN/TOB-PDCPD reduced bacterial load in the infected joint and the infected Ti implant. Application of PVA-VAN-PDCPD and/or PVA-VAN/TOB-PDCPD after saline irrigation could be used as an addition to the treatment of PJI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm 2 ) was greater than controls and EM0 (0.390 mm 2 and 0.0 mm 2 , respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm 2 ). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.

Aims: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion., Methods and Results: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [r sp ] = -0.64, p = 0.002) and change in device S3 (r sp  = -0.53, p = 0.014). In the haemodialysis cohort (n = 21), B-lines and TI were strongly correlated before (r sp  = -0.71, p < 0.001) and after (r sp  = -0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (r sp  = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (r sp  = 0.230, p = 0.204). There were no device-related adverse events., Conclusions: A non-invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cancer patients are often treated with radiation, therefore increasing their exposure to high energy emissions. In such cases, medical errors may be threatening or fatal, inducing the need to innovate new methods for maximum reduction of irreversible events. Training is an efficient and methodical tool to subject professionals to the real world and heavily educate them on how to perform with minimal errors. An evolving technique for this is Serious Gaming that can fulfill this purpose, especially with the rise of COVID-19 and the shift to the online world, by realistic and visual simulations built to present engaging scenarios. This paper presents the first Serious Game for Lung Cancer Radiotherapy training that embodies Biomedical Engineering principles and clinical experience to create a realistic and precise platform for coherent training., Methods: To develop the game, thorough 3D modeling, animation, and gaming fundamentals were utilized to represent the whole clinical process of treatment, along with the scores and progress of every player. The model's goal is to output coherency and organization for students' ease of use and progress tracking, and to provide a beneficial educational experience supplementary to the users' training. It aims to also expand their knowledge and use of skills in critical cases where they must perform crucial decision-making and procedures on patients of different cases., Results: At the end of this research, one of the accomplished goals consists of building a realistic model of the different equipment and tools accompanied with the radiotherapy process received by the patient on Maya 2018, including the true beam table, gantry, X-ray tube, CT Scanner, and so on. The serious game itself was then implemented on Unity Scenes with the built models to create a gamified authentic environment that incorporates the 5 main series of steps; Screening, Contouring, External Beam Planning, Plan Evaluation, Treatment, to simulate the practical workflow of an actual Oncology treatment delivery for lung cancer patients., Conclusion: This serious game provides an educational and empirical space for training and practice that can be used by students, trainees, and professionals to expand their knowledge and skills in the aim of reducing potential errors., (© 2024. The Author(s).)

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects., (© 2024 Wiley Periodicals LLC.)

Background: Commercially available irrigation solutions are used to reduce bacterial contamination and prevent surgical site infections. However, the effect of these solutions on the healing capacity of tissue has not been well-established. The purpose of this study was to investigate the effects of 5 commercially available irrigation solutions on host tissue in a murine model., Methods: There were 5 treatment groups: bacitracin, Clorpactin, Irrisept, Prontosan, Bactisure, and normal saline control. The irrigation solutions were applied to the wound for 30 seconds or 1 minute, as per the manufacturer's instructions, and then washed with normal saline. Mice were sacrificed at 3 days and 10 days. The tissue was examined histologically for inflammation, edema, granulation tissue formation, and re-epithelialization. Granulation tissue formation and re-epithelialization were surrogates for effective wound healing., Results: All of the irrigation solutions had negative effects on host tissue in the acute phase. The inflammation and edema were improved in the later phase (10 days). Recovery and healing of the open wounds were observed for all groups at 10 days. The antiseptic irrigation solutions had similar cytotoxic effects on host tissue at 3 days and did not have delayed or compromised wound healing at 10 days when compared to normal saline control., Conclusions: Single short-duration use of these commercially available antiseptic irrigation solutions appears to be safe in an uninfected wound. Data from this study will provide surgeons with useful information regarding the safety of using antiseptic wound irrigation solutions intraoperatively for prevention of surgical site infections., (© 2023 The Authors.)

Background: Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL)., Materials and Methods: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test., Results: In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003)., Conclusion: A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.

The heterogeneity of Italian manufacturing processes results in the production of a large variety of pork products. In Sardinia, boars are raised and butchered to produce charcuterie. These animals are castrated before slaughter as androstenone would otherwise taint the meat, rendering it unfit for human consumption. However, to date, the literature concerning surgical orchiectomy in adult boars is limited. The goal of this study is to assess whether a sutureless swine orchiectomy procedure is feasible. Additionally, this study aims to determine the appropriate traction force needed to tie knots in the deferens duct of pigs of different weights and ages. Two groups were created: the first (n = 91) underwent orchiectomy by suture ligation; the second (n = 20) was castrated using the sutureless technique. Deferens ducts of animals in the first group (n = 182) were collected following castration, and their tensile strength was measured. Pearson's linear correlation was used to determine the relationship between the maximum traction force and weight and age groups. A correlation of 0.99 and 0.96 was shown between traction force and age and traction force and weight, respectively. In accordance with these results, sutureless castration was performed on 20 animals, calibrating the pulling force needed according to the age and weight of the boars. No complications were observed during the feasibility study, thus validating sutureless orchiectomy in adult boars.

Introduction: Multiple irrigation solutions are used in orthopedic surgeries although there are limited studies on their lasting effects on human tissues. The purpose of this work was to investigate the cytotoxic effects of the irrigation solutions Bacitracin, Clorpactin (sodium oxychlorosene), Irrisept (0.05% chlorhexidine gluconate), and Bactisure (ethanol 1%, acetic acid 0.6%, sodium acetate 0.2%, benzalkonium chloride 0.013%, and water) on 3D cultures of human fibroblasts., Methods: Two independent experiments with 6 replicates were performed for the following conditions: Control (saline), bacitracin, Clorpactin, Irrisept, and Bactisure. Human fibroblast cell sheets were exposed to these solutions (1 or 2 min), followed by three washes with warm saline. Cell sheets were then cultured for additional 5- and 7-day posttreatment. Cell viability was measured using the alamarBlue (AB) assay. The more cytotoxic the irrigant, the lower the AB reduction., Results: For 1-min exposure time, significant differences in AB reduction were noted in Clorpactin, Irrisept, and Bactisure groups compared to control at both 5 days (Clorpactin p = 0.0003, Irrisept p = 7.31 × 10 -15 , Bactisure p = 6.86 × 10 -14 ) and 7 days posttreatment (all groups p < 0.0001). The results were similar in the 2-min exposure groups. Bacitracin-treated fibroblasts displayed no significant difference at all measurement times compared to control., Discussion: Impacts of irrigation solution exposure on cell viability were varied. Irrisept and Bactisure showed the highest cell toxicity even after a brief exposure (1 min), while bacitracin and Clor-pactin exposure showed smaller impacts on cell viability as compared to saline controls. This in vitro study provided insight into the effects of the irrigants on human cells and provides the groundwork essential to move to in vivo studies. Our findings raised the concern that some irrigation solutions may have negative impacts on wound healing and healthy cellular response., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background: Despite desirable microbicidal actions of irrigation solutions in surgical site infection treatment, several studies demonstrate potential cytotoxic effects. This study investigated tissue damage caused by irrigation solutions in the presence or absence of infection., Methods: Air pouches were created in 60 mice and evenly divided into 2 groups as infected with Staphylococcus aureus and control. Groups were then subdivided both by type of solution and by timing after irrigation. Solutions included control (0.9% saline), bacitracin (33 IU/ml), 0.2% sodium oxychlorosene, 0.05% chlorhexidine gluconate, and 0.013% benzalkonium chloride., Results: Inflammation decreased in infected pouches compared to the sterile ones for all solutions except bacitracin on day 0 and for all on day 7. On day 0, infected pouches had increased necrosis with bacitracin ( P  = .006), chlorhexidine gluconate ( P  = .18), and benzalkonium chloride ( P  = .07); on day 7, there was decreased necrosis in infected pouches for all solutions ( P < .05) except for sodium oxychlorosene ( P  = .18). Edema decreased in infected pouches on day 0 for all solutions. On day 7, infected pouches had decreased edema with 0.9% saline, bacitracin, and benzalkonium chloride ( P < .05) and increased edema with chlorhexidine gluconate ( P < .05) and sodium oxychlorosene ( P  = .069). Bacitracin allowed for more bacteria growth than sodium oxychlorosene ( P  = .024), chlorhexidine gluconate ( P  = .025), and benzalkonium chloride ( P  = .025)., Conclusions: The presence of bacteria led to less immediate tissue inflammation and edema, while tissue necrosis varied over time. The current study may guide surgeons on which solution to use and whether to irrigate a possibly sterile wound or joint., (© 2022 The Authors.)

Prosthesis with antibiotic-eluting nanofibrous (NF) coating represents coating alternative to prevent periprosthetic joint infection (PJI). In this study, four formulas of erythromycin (EM)-embedded both in core and sheath components of coaxial PCL/PLGA-PVA NF coatings were developed: EM 0 (no EM), EM 100 (100 μg/mL), EM500 (500 μg/mL) and EM1000 (1000 μg/mL). EM doping altered the physicochemical and structural properties of NFs to some extent, including the increase of NF porosity and surface wettability. A sustained EM release from EM-NFs for >4 weeks was observed. Eluents collected from EM-NFs showed strong zone of inhibition (ZOI) to Staphylococcus aureus growth and the sizes of ZOI positively related to the amount of EM released. EM-NFs were nontoxic to rat bone marrow stem cells (rBMSCs). Cell growth was significantly enhanced when comparing rBMSCs cultured on EM-NFs (EM0 and EM 100) to those cultured on NF-free control. Cell differentiation (ALP activity) was notably enhanced by EM100, compared to control and EM0. Eluents from EM-NFs on rBMSCs were also investigated. The presence of 10% EM-NF eluents inhibited the growth of rBMSCs, which was proportional to the amount of EM doped. The ALP activity was notably enhanced by eluents from EM-NFs with the highest activity in EM100 compared to control and EM0. Our data indicate that EM-doped PCL/PLGA-PVA coaxial NF coatings have a great potential to be applied as a new implant coating matrices. Further in vivo testing in animal models is currently planned that should represent the first step in predicting the clinical outcomes of EM-eluting NF coating approach.

Background: The efficacy of saline irrigation for treatment of periprosthetic infection (PJI) is limited by the presence of contaminated medical devices. This study evaluated treatment efficacy of locally placed polyvinyl alcohol (PVA)/bioceramic composite doped with vancomycin (PVA-VAN-P) or vancomycin and tobramycin (PVA-VAN/TOB-P) after saline irrigation in a mouse pouch infection model., Methods: Sutures were implanted into air pouches of BALB/cJ mice, then inoculated with Staphylococcus aureus. Mice were randomized into 6 groups (n = 6 each): (1) no bacteria; (2) bacteria without saline wash; (3) saline wash only; (4) saline wash + PVA-P; (5) saline wash + PVA-VAN-P, and (6) saline wash + PVA-VAN/TOB-P. After 7 days, pouches were washed with saline alone or with additional injection of 0.2 mL of the composites. Sacrifice occurred 14 days after the washout. Histology was performed on the pouch tissues and bacteria cultures on the washout fluid., Results: Bacterial culture (optical density) showed that infection persisted after saline irrigation (0.10 ± 0.14) but was effectively eradicated by the addition of PVA-VAN-P (0.05 ± 0.09) and PVA-VAN/TOB-P (0.002 ± 0.003, P < .05). These effects were confirmed by histology. Importantly, no residues of the PVA-P were detected in either the pouch washouts or pouch tissues., Conclusion: PJI is common and problematic, and few innovations have changed clinical practice and/or outcome. Our data confirmed that the effect of saline irrigation was very limited in the presence of contaminated sutures. PVA-VAN/TOB-P was biodegradable, biocompatible, and effective in eradicating bacterial retention after saline irrigation. Application of PVA-VAN/TOB-P after saline irrigation could be an option for treatment of PJI and should be evaluated in future PJI animal models., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In 1995, to reduce the transmission of Tuberculosis (TB) the Centers for Disease Control and Prevention recommended that all patients discharged from hospitals be required to have chest x-rays (i.e., radiography) performed before admission to long term care facilities (LTCFs). Previously independently living patients (PILPs) who undergo elective total knee replacement (TKA) surgery are a population at higher risk to end up in LTCFs for rehabilitation. By 2017, the incidence of TB was 9,105 cases compared to 22,762 in 1995. However, the recommendations that hospitals be required to perform a chest x-ray in all patients (including PILPs) being transferred to LTCF's have remained in place. The purposes of this study were to: a) determine the incidence of TB-positive chest x-rays in PILPS discharged to LTCFs after undergoing elective TKA surgery, and b) assess the cost (i.e., both financial and possible exposure to unnecessary radiation) of mandated chest x-rays before hospital discharge to LTCF for PILPs., Methods: Retrospective 2012-2017 patient chart data were collected from the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) to identify all elective TKAs for PILPs performed at two Ascension participating centers. Study data included sex, age, body mass index (BMI), length of stay, comorbidities, and chest x-ray results before discharge. Patients who underwent surgery for fracture, infection, trauma, or malignancy were excluded from the study. Categorical data were analyzed using Fisher's exact test and Student's t-test were used for continuous data., Results: The authors identified 4,041 total elective TKA's, from which 500 PILPs were discharged to a LTCF due to functional, medical and/or social concerns. Chest x-rays were associated with 500 (100%) negative findings for TB. Overall hospital costs for chest x-rays for patient's being discharged to an extended care facility totaled $90,848., Conclusions: The mandated use of chest x-rays for TB screening of PILPs undergoing elective surgery TKA prior to discharge to LTCFs appear to place an unnecessary financial burden on the healthcare system. The mandatory use of x-rays for assessment of possible TB infection before transfer to LTCFs appears to also expose PILPs unnecessarily to radiation. Although further studies are needed to verify these results, the authors recommend that perhaps instead chest x-rays should be reserved for patients with specific comorbidities (e.g., patients on immunosuppressive therapy, with HIV, etc.) or for those patients residing in LTCFs prior to surgery., Competing Interests: Support for the Michigan Arthroplasty Registry Collaborative Quality Initiative is provided by Blue Cross and Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program. The opinions, beliefs and viewpoints expressed by the author do not necessarily reflect the opinions, beliefs, and viewpoints of BCBSM or any of its employees.

Designing hydrogels for controlled drug delivery remains a big challenge. We developed a calcium polyphosphate hydrogel (CPP) as matrix for delivery of vancomycin (VCM) and erythromycin (EM) by unique ionic binding and physical wrapping. In this continuing study, we investigated if gel discs prepared by mechanical compaction (at 3000 psi pressure, C-discs) is superior to that of discs prepared by regular manual compaction (M-discs) for the release of VCM and EM (10 wt.%). Data demonstrated a significant reduction of burst release of VCM and EM in C-discs (1.8% and 5%, respectively) as compared to that from M-discs within 72 hr (55% and 60%, respectively, p < 0.05). In addition, C-discs significantly extended the VCM release (1500 hr) and EM (800 hr) as compared to M-discs (160 and 96 hr, respectively, p < 0.05). The VCM released from C-discs retained its bactericidal activity much longer (1500 hr) than that from M-discs (700 hr, p < 0.05). Raman Spectroscopy indicated an ionic bond of both VCM and EM with fully hydrated polyphosphate chains of CPP hydrogel matrix for both M-discs and C-discs. Micro CT showed that C-discs had much denser microstructures and less number/depth of microcracks as a result of high pressure. We propose that CPP hydrogel represents an excellent tool for the controllable and sustained delivery of VCM and EM. Extensive experiments are currently underway to evaluate the potential impacts of the modification of compaction techniques, other antibiotics, gel concentrations on the drug release, degradation behavior and infection control both in vitro and in vivo., (© 2021 Wiley Periodicals LLC.)

Background: Direct attachment of tendons to metallic implants is important in orthopedics. Tissue integration depends on scaffold microstructure and composition. This study evaluated the effect of pore size of titanium on the viability and function of fibroblasts and tenocytes in a dynamic bioreactor., Methods: Standardized Ti porous cylinders with 3 pore sizes (400, 700, and 1000 μm) were seeded with fibroblasts or tenocytes (4500 cells/μL) in silicon tubes. Cells were analyzed via alamarBlue (AB) assay in addition to scanning electron microscopy at day 7 (fibroblasts) or day 8 (tenocytes) and day 15. AB functions as a cell health indicator where functional living cells reduce the resazurin dye (blue) in the solution to resorufin (pink), and cell viability can be quantified via spectroscopy., Results: At day 7, fibroblasts cultured on all sizes reduced AB, with significant differences noted between 400 vs 1000 μm ( P  = .013) and 700 vs 1000 μm ( P  = .001). At day 15, fibroblasts reduced AB on all sizes with a significant difference noted between 700 vs 1000 μm ( P  = .004). Fibroblasts on all 3 pore sizes increased AB reduction from day 7 to day 15. Tenocytes reduced AB with significant differences between the 400 vs 700 μm ( P  = .049) and the 400 vs 1000 μm pore sizes at day 8. In contrast, tenocyte reduction of AB decreased from day 8 to day 15. Scanning electron microscopy performed on fibroblast cylinders showed fibroblasts reached the surface of the cylinders, confirming interconnectivity., Conclusions: While both fibroblasts and tenocytes penetrated the pores, fibroblasts preferred larger size, whereas tenocytes favored smaller size. Results are encouraging since soft-tissue attachment to a metallic scaffold is difficult but clinically desirable. Future studies could be performed in an in vivo animal model., (© 2021 The Authors.)

Background: CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known., Objective: We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression., Methods: Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done., Results: Compared to adenomas, CD15 expression was significantly higher in MSA (p= 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p= 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients., Conclusions: CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression.

A self-setting, injectable polymeric dicalcium phosphate dehydrate bone graft substitute that is mechanically strong and has excellent cohesion was developed. We assessed the performance of erythromycin-loaded polymeric dicalcium phosphate dehydrate cement. Its properties include drug release, growth inhibition against Staphylococcus aureus and biocompatibility with osteoblastic MC3T3 cells. The impact of erythromycin loading on cement injectability, setting time, and mechanical strength were also evaluated. A sustained, low burst release of erythromycin was observed. Eluents collected from erythromycin-loaded cement showed a considerable zone of inhibition for up to 28 days. Direct contact of erythromycin-loaded cement discs with agar plate showed a similarly sizable zone of inhibition for up to 22 days. Degraded ceramic residues had strong zones of inhibition as well. While the erythromycin-loaded cement was injectable, a notable delay of the setting time was observed (49.2 ± 6.8 min) as compared with control (drug-free cement, 12.2 ± 2.6 min). A slight increase in compressive strength (60.83 ± 6.28 MPa) was observed in erythromycin-loaded cement as compared with control (59.41 ± 6.48 MPa). Erythromycin-loaded cement was biocompatible although reduced cell growth was observed in the presence of the cement eluent. We propose that the bactericidal efficacy of erythromycin-loaded cement was caused by the combined effects of erythromycin released and exposed on the contact surface of degrading ceramics. Our data may elucidate the future application of polymeric dicalcium phosphate dehydrate bone graft substitute for the treatment of orthopedic infections and opportunities to use other antibiotics and applications considering its comparable handling and mechanical strength to poly (methyl methacrylate) cements., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Surgeons use various irrigation solutions to minimize the risk of prosthetic joint infection after total joint arthroplasty. The toxicity of these solutions is an important consideration in their use. This study investigates the effect of irrigation solutions Bacitracin, Clorpactin (sodium oxychlorosene), and Irrisept (chlorhexidine) on osteoblast cytotoxicity and proliferation., Methods: Four replicates of 6 conditions at 3 time points (1, 2, and 4 min) were tested: control (normal saline), Bacitracin (33 IU/ml), Clorpactin (0.05%, 0.1%, 0.2%), and Irrisept (0.05% chlorhexidine gluconate). Human osteoblasts were cultured at 37°C and 5% CO 2 until confluent monolayers were obtained. The treatment solution was applied, and cells were washed 3x with warm phosphate-buffered saline and then supplemented with a fresh medium. Phase-contrast images were taken before and after treatment. The cytotoxicity and proliferation of the treated cells was measured for all conditions on day 3 and day 5 after treatment using the alamarBlue assay., Results: All test conditions showed morphological changes to cells after treatment; controls did not. Cells demonstrated curling and detachment. This effect was the worst and permanent with Irrisept, whereas other treatments showed a return to normal morphology after 1 week. All treatments showed increased %alamarBlue reduction after 5 days except Irrisept, which showed decreased reduction. There was no statistically significant time or dose dependence with Clorpactin treatment., Conclusions: Clorpactin and Bacitracin are damaging to human osteoblast cells in vitro as compared with normal saline. This damage is at least partially reversible as shown by morphology and cell viability assay. Irrisept caused more damage than either Clorpactin or Bacitracin, and the damage was not reversible., (© 2021 Published by Elsevier Inc. on behalf of The American Association of Hip and Knee Surgeons.)

Background: Transforming growth factor-β (TGFβ) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFβ and its signaling cascade in breast cancer remain unclear., Objective: To investigate the relationship between TβRII expression, clinic-pathological characteristics, and prognostic significance of TβRII expression in clinical stage III breast cancer., Methods: Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TβRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry., Results: TβRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TβRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors., Conclusions: These findings suggest the usage of therapeutic drugs that target TGFβ in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFβ pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Background: For high-tensile strength sutures, past research has largely focused on mechanical properties or bacterial adherence across various manufacturers., Purpose: This study investigated high-tensile strength sutures with different shapes but otherwise identical composition. The purpose was to evaluate the differences between high-tensile strength suture wire and suture tape relative to bacterial adherence and bacterial retention after washout., Study Design: Controlled laboratory study., Methods: Sutures were implanted in dorsal air pouches of 72 BALB/cJ mice. Experimental pouches were inoculated with Staphylococcus aureus ; no bacteria were used in the control conditions. The mice were randomized into 3 groups: group 1 underwent suture extraction 7 days after implantation; group 2 underwent an irrigation procedure, followed by immediate suture extraction on day 7; and group 3 underwent an irrigation procedure on day 7, with delayed suture extraction on day 14 after implantation. The sutures were evaluated using confocal microscopy; electron microscopy; and spectrophotometry, through which optical density, as measured by the amount of scattered light, is directly correlated with the number of bacteria. Histological assessment was performed on the pouches., Results: Optical density (mean ± SD) was significantly higher for FiberTape sutures than for FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.0550 ± 0.0081 vs 0.0162 ± 0.006 [ P = .0054]; group 2, 0.0225 ± 0.0049 vs 0.0056 ± 0.0006 [ P = .0045]; group 3, 0.055 ± 0.0222 vs 0.0043 ± 0.0005 [ P = .0103]). Additionally, groups 2 and 3 showed statistically significant results at the 4-hour time points (group 2, 0.0384 ± 0.0087 vs 0.0145 ± 0.0042 [ P = .0280]; group 3, 0.0532 ± 0.0159 vs 0.0101 ± 0.0025 [ P = .0058]). The wash fluid also demonstrated significantly greater optical density for the FiberTape than the FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.1657 ± 0.0319 vs 0.0317 ± 0.008 [ P = .0063]; group 2, 0.0522 ± 0.0156 vs 0.0127 ± 0.0022 [ P = .0219]; group 3, 0.1707 ± 0.0205 vs 0.0191 ± 0.0053 [ P < .0001]). No bacterial growth occurred in the control conditions. Histological assessment revealed only mild inflammation in the control groups as compared with more severe responses in the experimental groups at all time points., Conclusion: FiberTape was associated with increased bacterial adhesion as well as retention as compared with FiberWire in an in vivo murine wound model., Clinical Relevance: This study demonstrates that suture design influences the occurrence of and ability to clear surgical infection and must be considered when selecting high-tensile strength sutures in a clinical setting., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.M.B. has received educational support from DePuy Synthes and Pinnacle. D.C.M. has received consulting fees and royalties from Stryker and honoraria from Halyard Health and Avanos Medical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Background: Breast tumors are composed of phenotypically diverse groups of cells; however, it is unclear which of these cells contribute to tumor development. Breast cancer management usually targets proliferating cells, but as breast cancer stem cells are slowly cycling, they may escape these targets whenever they are not actively proliferating. This may explain the occurrence of recurrences and failure of the treatment., Aim: To assess the impact of the BCSC expression on progression-free survival (PFS), overall survival (OS), and tumor response in metastatic breast cancer patients and to correlate the BCSC expression with different clinicopathological parameters., Material: This prospective study enrolled 76 de novo metastatic breast cancer patients recruited from the Oncology Center, Mansoura University, Egypt, with a minimum age 31 years and a maximum of 70 years. Pretreatment BCSC markers (CD44 and CD24) were assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissues from a primary or metastatic site. Patients received different lines of treatment, hormonal or chemotherapy, according to their biological subtypes. Anti-Her2 was added for Her2-positive patients., Results: Thirty-three patients (43.4%) were premenopausal and 43 patients (56.6%) were postmenopausal. Bone-only metastasis was seen in 12 patients (15.7%), however, visceral ± bone metastasis was seen in 64 patients (84.3%). BCSC markers (CD44+ve and CD24-ve) were expressed in 32 patients (42.1%), while 44 patients (57.9%) were not expressing BCSC markers. Out of 32 patients expressing BCSC, 22 patients (68%) were premenopausal and 28 patients (87.5%) were with high-grade (GIII) disease. BCSC was significantly presented in triple negative subtype breast cancer as there were 32 patients with the BCSC expression, and out of them, 15 patients (46.9%) had triple negative disease, 10 patients (31.3%) had luminal subtype, and seven patients (21.9%) were Her2-amplified, while there were 44 patients without BCSC expression, and out of them, 30 patients (68.2%) were of the luminal subtype, no patient (20.5%) had triple negative disease, and five patients (11.4%) were Her2-amplified (P 0.006). Twenty-four patients (31.5%) presented with visceral crisis; out of them, 17 patients (70.1%) were expressing BCSC which also denoted more aggressive disease. Seventy-four patients were candidates for the response assessment. BCSC-expressing patients showed poor response compared to non-BCSC (16.1% responsive versus 51.2%, respectively), with a significance relation ( P  0.003). The BCSC expression was associated with both significant short PFS (median, 18 months vs. 35 months; P =0.001) and short OS (median, 26 months vs. 43 months; P =0.003). In multivariate analysis; BCSC expression was an independent prognostic factor for poor OS ( P =0.055) along with the molecular subtype ( P =0.012), Her2 status ( P =0.011), and histologic grade ( P =0.037)., Conclusion: This study further validates the BCSC expression as a poor prognostic biomarker correlated with poor response, short PFS and OS. So, it could be used as a marker for tailoring treatment with different lines of therapies in further studies. The BCSC expression was highly presented in the triple negative subtype which is an aggressive disease that lacks different targets. So, targeting BCSC may carry a hope in future for this group of patients., Competing Interests: All authors declared that they have no conflicts of interest., (Copyright © 2020 M. A. Elbaiomy et al.)

Background: Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients., Aim: We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS., Results: We found high expression (LEF1 high ) was associated with better OS ( p = 0.02) and EFS ( p = 0.019) compared to LEF1 low , low serum Gal.3 level had better OS ( p = 0.014) and EFS ( p = 0.02) compared to high serum Gal.3 level. LEF1 high less likely to carry a FLT3-ITD ( p = 0.047) compared to LEF1 low patient, also LEF1 high characterized by favorable risk ( p = 0.02) than LEF1 low patients. While patients with higher Gal-3 levels characterized by poor risk ( p = 0.02) than lower Gal.3 lels, also more likely to carry a FLT3-ITD with borderline significance ( p = 0.054). Combined LEF1 high /Gal.3 low patients had lower baseline blast percentages ( p = 0.02), favorable risk ( p = 0.01), less likely to carry FLT3-ITD ( p = 0.02), higher CR rate ( p = 0.055), shorter time to CR (0.001) than other groups. Among high Gal.3 level group, LEF1 high expression improved OS and EFS (20 and 15 months respectively) vs LEF1 low expression (13 and 8 months respectively)., Conclusion: We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level., Competing Interests: All authors declared that he/she had no conflicts of interest., (Copyright © 2019 M. A. ElBaiomy et al.)

Aims: The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components., Patients and Methods: A total of 39 patients were recruited, with clinical follow-up of up to two years. Outcome was assessed using the Harris Hip Score (HHS, the 12-Item Short-Form Health Survey (SF-12), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a visual analogue scale (VAS) for pain. Blood concentrations of cobalt (Co), chromium (Cr), and serum cytokines were measured. Subpopulations of leucocytes were analyzed by flow cytometry., Results: The clinical performance was good. Blood Co levels (ref 1.0 µg/l) were mildly elevated in seven patients at three months, and two patients at two years' follow-up. The preoperative Cr levels were normal except for one patient with a detectable Cr (1.2 µg/l). Cr levels were detectable in three patients at three months, two patients at one year, and three patients at two years' follow-up. No patients had symptoms suggestive of failure. Although flow cytometry showed constant circulating leucocyte profiles, there was a significant reduction of serum interleukin (IL)-4, IL-5, and interferon gamma (IFNγ) postoperatively compared with the preoperative levels (p < 0.05)., Conclusion: These results suggest that THA using modular dual-mobility components is safe. This allows an opportunity to use a large femoral head and a thick polyethylene bearing surface, which is especially useful in revision procedures or high-risk situations when added stability is required. Cite this article: Bone Joint J 2019;101-B:1035-1041.

Introduction: The purpose of this study was to retrospectively evaluate blood metal ion levels and leukocyte profiles in patients with modular dual-mobility hip implant (MDM) during a postoperative follow-up up to 2 years., Methods: We recruited 49 patients in a retrospective cohort study and had postoperative follow-up up to 2 years. Blood concentrations of chromium (Cr), cobalt (Co) and serum cytokines were measured. Flow cytometry was used to quantify the subpopulations of leukocytes, including CD14 + and CD16 + monocytes, CD3 + T lymphocytes, CD19 + B lymphocytes, CD4 + Helper T-cells and CD45 + RA memory vs. naïve T-cells., Results: Clinical performances of implants were good during 2 years of follow-up. Cr levels were normal in all patients and only detectable in 1 patient (1.4µg/L, ref < 5.0µg/L). Co levels were mildly elevated in 4 patients at 1 year (mean 1.375µg/L, range 1.2-1.7µg/L, ref < 1.0µg/L) and in 2 patients at 2-year follow-up (both 1.2µg/L). Interestingly, Co level observed in 3 patients at 1 year converted to undetectable at their 2-year follow-up. Percentages of B cells, T cells and their subpopulations were within normal levels. There was no increase of CD16 + inflammatory monocytes., Discussion: With the recent introduction of MDM systems there is potential for metal ion release from the interface between the acetabular shell and CoCr liner. Clinical results have been good and metal levels undetectable or within acceptable ranges at 1-2 years. There was no evidence of activated immune response, as manifested by constant circulating leukocyte profiles and no increase of CD16 + inflammatory monocytes.

Background: Irrigation and débridement are frequently utilized in the management of surgical infections, but even with aggressive débridement, it is difficult to remove all the suture material from the tissues and retained suture material may harbor bacteria and/or biofilm. The degree to which barbed or braided sutures may differentially influence the risk of infection has not been defined in a well-controlled animal model., Questions/purposes: We compared braided and barbed monofilament sutures after irrigation of an infected mouse air pouch model to determine whether the suture type influenced the effectiveness of the irrigation. After irrigation of infected pouches, sutures were compared for (1) bacterial adherence and bacterial retention; (2) qualitative and quantitative pouch thickness and cellular density; and (3) quantitative biofilm formation., Methods: Soft tissue air pouches were created on the backs of 60 female, mature 10-week-old BALB/cJ mice by sequentially introducing air into the subcutaneous tissue and allowing the pouch to mature. The pouches were inoculated with Staphylococcus aureus and braided or barbed monofilament sutures were implanted. Pouch irrigation was performed Day 7 after suture implantation. Suture segments were collected before and after irrigation. After euthanasia on Day 14, pouch tissues with residual suture segments were collected for analysis: microbiologic analysis done using optical density as a measure of the concentration of bacteria in the culture (the larger concentration indicates higher number of bacteria) and histologic evaluation of the pouch tissues were semiquantitative, whereas environmental scanning electron microscopy (ESEM) and confocal analyses of the biofilm and bacteria on the sutures were qualitative., Results: Histologic evaluation of pouch tissue showed all groups had inflammatory responses. Quantitatively microbiology showed no difference in bacterial number calculated from the optical density (OD) values between the two suture materials at any time point in the irrigation group. In the no-irrigation group, for the Day 7 time point, mean (± SD) OD was greater in the barbed than the OD in the braided sutures (0.52 ± 0.12 versus 0.37 ± 0.16, mean difference 0.43 [95% confidence interval, 0.08-0.13]; p = 0.007). Qualitatively, ESEM showed more bacterial retention by braided sutures before and after irrigation. Confocal imaging of the sutures demonstrated penetration of biofilm into the interstices of braided sutures and less adhesion in barbed monofilament sutures. The quantification of the biomass showed no differences between groups at all time points (before-irrigation biomass was 11.2 ± 9.3 for braided versus 5.2 ± 4.7 for barbed sutures, p = 0.196; and after-irrigation biomass was 7.2 ± 7.5 for braided versus 3.3 ± 4.3 for barbed suture, p = 0.259)., Conclusions: All sutures can retain bacteria and biofilm, but it is rarely possible to remove all suture material at the time of irrigation to treat infection. After an irrigation procedure, qualitatively braided sutures appeared to harbor more bacteria and to retain more biofilm than barbed monofilaments., Clinical Relevance: When saline irrigation was used to simulate infection treatment in an infected mouse air pouch model, bacteria/biofilm was not completely eliminated from either braided or barbed monofilament sutures. The irrigation appeared to clear more bacteria and biofilm from the monofilament despite having barbs. Unfortunately, current technologies do not allow direct quantitative comparisons of biofilm retention. Clinicians should be aware that in the face of infection, any retained sutures may harbor bacteria despite irrigation.

The purpose of this study was to compare blood leukocyte profiles and metal ion concentrations between hip resurfacing arthroplasty (articular surface replacement) patients with and without revision. A total of 25 articular surface replacement patients were recruited (10 with stable implants and 15 undergoing revision). Blood concentrations of chromium (Cr) and cobalt (Co) were measured. Flow cytometry was used to quantify the subpopulations of leukocytes, including CD14 + monocytes, CD16 + monocytes, CD3 + T-lymphocytes, CD19 + B-lymphocytes, CD4 + helper T-cells, and CD45 + RA memory vs naïve T-cells. Patients undergoing revision had higher blood Co (mean, 10.85 µg/L) and Cr (mean, 3.19 µg/L) levels than patients with stable implants (mean Co, 3.06 µg/L; mean Cr, 1.07 µg/L) (P<.05). The number of CD4 + helper T-cells was higher in patients with stable implants (mean, 842±311 cells/µL) than in patients undergoing revision (mean, 591±208 cells/µL) (P<.05). There was a significant association between total metal ion levels (Co+Cr) and the number of CD14 + monocytes (P=.045) and inflammatory CD16 + monocytes (P=.046). The authors observed that the increase in blood metal ions was associated with an increase in CD16 + monocytes. They believe that continued analysis of blood leukocyte profiles may be helpful in defining differences among failed articular surface replacement, stable articular surface replacement, and failed metal-on-polyethylene implants. [Orthopedics. 2018; 41(3):e424-e431.]., (Copyright 2018, SLACK Incorporated.)

Background: Shoulder arthroplasty is the fastest growing joint replacement surgery in the United States, and optimal postoperative pain management is critical to optimize outcomes for these surgeries. Liposomal bupivacaine (LB) has gained popularity for its potential to provide extended postoperative pain relief with possibly fewer side effects. The goal of this study was to assess the impact of LB compared with continuous interscalene nerve block (CISB) in terms of postoperative pain control, outpatient pain scores, and patient-reported and functional outcomes after shoulder arthroplasty surgery., Methods: A prospective randomized controlled clinical trial compared consecutive patients undergoing shoulder arthroplasty treated with CISB vs. LB with a single bolus interscalene block. The primary outcome measures included pain assessment up to 24 hours after surgery; in addition, all doses and times of narcotics administered during the inpatient stay were recorded. Patient-reported outcome measures for pain, satisfaction, and functional outcomes were recorded postoperatively., Results: A total of 70 of 74 consecutive patients who underwent shoulder arthroplasty were included in the study. The LB group had equivalent narcotic use, pain scores, and time to first narcotic rescue compared with the CISB group within the first 24 hours (P > .05). The LB group had higher American Shoulder and Elbow Surgeons score and Penn Shoulder Score at final follow-up. There was an increased number of complications and cost for the CISB group., Conclusion: This prospective randomized controlled trial demonstrated that LB provides excellent postoperative pain relief for shoulder arthroplasty patients. In addition, LB had fewer complications and lower cost, making it a promising addition to a multimodal pain regimen for shoulder arthroplasty., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Objective: To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ., Methods: Twelve rats were infused with saline (intravenous infusion, 0.2 mL/min/100 g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as lymphocyte velocity and density before, during, and after infusion., Results: A 10-fold increase in lymphocyte velocity (0.1-1 mm/s) and a sixfold increase in flow rate (0.1-0.6 μL/min), were observed post infusion, respectively. There were also increases in contraction frequency and fractional pump flow one minute post infusion. Time-averaged wall shear stress increased 10 fold post infusion to nearly 1.5 dynes/cm(2) . Similarly, maximum shear stress rose from 5 to 40 dynes/cm(2) ., Conclusions: Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymphocyte velocity, and shear stress were significant. Lymph pumping increased post infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymphocyte velocity, and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function., (© 2014 John Wiley & Sons Ltd.)

Problems associated with current bone substitutes led to an increased interest in tissue engineered surrogates with properties similar to natural bones. Commonly used materials lack the ultimate mechanical properties. In this study, we examined the influence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a crosslinking agent on the strength of collagen fibers. Collagen fibers are crosslinked with EDC, or EDC/N-hydroxysulfosuccinimide (Sulfo-NHS) in water or EDC in acetone. After which fibers are mineralized using calcium chloride and potassium phosphate. The mechanical properties of the treated fibers are measured using tensile testing. In addition, the effect of crosslinking on cellular behavior was tested by culturing bone marrow mesenchymal stem cells (BMMSCs) on modified fibers. We found that the mechanical properties of non-mineralized and mineralized collagen fibers are significantly affected by the crosslinking method. The tensile strength of single fibers is greatly improved by crosslinking with EDC in acetone. BMMSCs were found to attach and spread well on modified fibers confirming biocompatibility., (Copyright © 2012 Wiley Periodicals, Inc.)

One strategy for assessing efficacy of a liver transplant is to monitor perfusion and oxygenation after transplantation. An implantable optical sensor is being developed to overcome inadequacies of current monitoring approaches. To facilitate sensor design while minimizing animal use, a polydimethylsiloxane (PDMS)-based liver phantom was developed to mimic the optical properties of porcine liver in the 630-1000 nm wavelength range and the anatomical geometry of liver parenchyma. Using soft lithography to construct microfluidic channels in pigmented elastomer enabled the 2D approximation of hexagonal liver lobules with 15mm sinusoidal channels, which will allow perfusion with blood-mimicking fluids to facilitate the development of the liver perfusion and oxygenation monitoring system.

Cell and tissue responses to polymeric materials are orchestrated in part by the conformations of adsorbed plasma proteins. Thus, the chemical properties of a polymer membrane that govern protein adsorption behavior can play an important role in determining the biological properties of tissue engineered scaffolds derived from that polymer. In this study, we explored the role of membrane thickness as a factor influencing cell adhesion and proliferation on chitosan membranes with and without covalently attached glycosaminoglycans. Rat mesenchymal stem cells (MSCs) cultured on chitosan membranes of various thicknesses demonstrated significantly improved cell adhesion, spreading and proliferation as membrane thickness was increased. Rat hepatocytes displayed increased spreading on the substrate with increasing membrane thickness, similar to MSCs. Increased thickness reduced the overall crystallinity of the membrane, and the data indicate that the improved cellular responses were likely due to enhanced adsorption of serum vitronectin, presumably due to reduced membrane crystallinity. These results demonstrate that membrane thickness is an important design variable that can be manipulated in chitosan-based scaffolds to achieve enhanced cell spreading, proliferation and function., (Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The production of a fully functional bioartificial liver assist device (BLAD) would greatly enhance available treatment options for patients suffering from acute liver failure. Currently, inadequate oxygen provision to hepatocytes seeded within hollow fiber bioreactors hampers development of a viable hollow fiber-based BLAD. Experimentally, oxygen provision to primary rat hepatocytes cultured within hollow fiber bioreactors was measured, it was observed that supplementation with an oxygen carrier (bovine red blood cells at approximately 2% human hematocrit) did not significantly improve oxygenation compared to the absence of an oxygen carrier. Therefore, an oxygen transport model of an individual hollow fiber within the bioreactor was developed and simulated (up to approximately 10% human hematocrit) to more fully examine the effect of oxygen carrier supplementation on oxygenation within the bioreactor. The modeling analysis, supported via the experimental results, was utilized to predict optimal bioreactor operating conditions for the delivery of in vivo-like oxygen gradients to cultured hepatocytes in clinically relevant settings.