Microbial reduction of prebagged human plasma using 405 nm light and its effects on coagulation factors.

Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm-2; ≤ 403 J cm-2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm-2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm-2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

Enhanced antimicrobial efficacy and energy efficiency of low irradiance 405-nm light for bacterial decontamination.

Due to its increased safety over ultraviolet light, there is interest in the development of antimicrobial violet-blue light technologies for infection control applications. To ensure compatibility with exposed materials and tissue, the light irradiances and dose regimes used must be suitable for the target application. This study investigates the antimicrobial dose responses and germicidal efficiency of 405 nm violet-blue light when applied at a range of irradiance levels, for inactivation of surface-seeded and suspended bacteria. Bacteria were seeded onto agar surfaces (101-108 CFUplate-1) or suspended in PBS (103-109 CFUmL-1) and exposed to increasing doses of 405-nm light (≤ 288 Jcm-2) using various irradiances (0.5-150 mWcm-2), with susceptibility at equivalent light doses compared. Bacterial reductions ≥ 96% were demonstrated in all cases for lower irradiance (≤ 5 mWcm-2) exposures. Comparisons indicated, on a per unit dose basis, that significantly lower doses were required for significant reductions of all species when exposed at lower irradiances: 3-30 Jcm-2/0.5 mWcm-2 compared to 9-75 Jcm-2/50 mWcm-2 for low cell density (102 CFUplate-1) surface exposures and 22.5 Jcm-2/5 mWcm-2 compared to 67.5 Jcm-2/150 mWcm-2 for low density (103 CFUmL-1) liquid exposures (P ≤ 0.05). Similar patterns were observed at higher densities, excluding S. aureus exposed at 109 CFUmL-1, suggesting bacterial density at predictable levels has minimal influence on decontamination efficacy. This study provides fundamental evidence of the greater energy efficacy of 405-nm light for inactivation of clinically-significant pathogens when lower irradiances are employed, further supporting its relevance for practical decontamination applications.

Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity.

Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm2. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.

Laboratory evaluation of the broad-spectrum antibacterial efficacy of a low-irradiance visible 405-nm light system for surface-simulated decontamination.

Purpose: Lighting systems which use visible light blended with antimicrobial 405-nm violet-blue light have recently been developed for safe continuous decontamination of occupied healthcare environments. This paper characterises the optical output and antibacterial efficacy of a low irradiance 405-nm light system designed for environmental decontamination applications, under controlled laboratory conditions. Methods: In the current study, the irradiance output of a ceiling-mounted 405-nm light source was profiled within a 3×3×2 m (18 m3) test area; with values ranging from 0.001-2.016 mWcm-2. To evaluate antibacterial efficacy of the light source for environmental surface decontamination, irradiance levels within this range (0.021-1 mWcm-2) at various angular (Δ Ï´=0-51.3) and linear (∆s=1.6-2.56 m) displacements from the source were used to generate inactivation kinetics, using the model organism, Staphylococcus aureus. Additionally, twelve bacterial species were surface-seeded and light-exposed at a fixed displacement below the source (1.5 m; 0.5 mWcm-2) to demonstrate broad-spectrum efficacy at heights typical of high touch surfaces within occupied settings. Results: Results demonstrate that significant (P≤0.05) inactivation was successfully achieved at all irradiance values investigated, with spatial positioning from the source affecting inactivation, with greater times required for inactivation as irradiance decreased. Complete/near-complete (≥93.28%) inactivation of all bacteria was achieved following exposure to 0.5 mWcm-2 within exposure times realistic of those utilised practically for whole-room decontamination (2-16 h). Conclusion: This study provides fundamental evidence of the efficacy, and energy efficiency, of low irradiance 405-nm light for bacterial inactivation within a controlled laboratory setting, further justifying its benefits for practical infection control applications.

Viricidal Efficacy of a 405-nm Environmental Decontamination System for Inactivation of Bacteriophage Phi6: Surrogate for SARS-CoV-2.

The highly transmittable nature of SARS-CoV-2 has increased the necessity for novel strategies to safely decontaminate public areas. This study investigates the efficacy of a low irradiance 405-nm light environmental decontamination system for the inactivation of bacteriophage phi6 as a surrogate for SARS-CoV-2. Bacteriophage phi6 was exposed to increasing doses of low irradiance (~0.5 mW cm-2 ) 405-nm light while suspended in SM buffer and artificial human saliva at low (~103-4 PFU mL-1 ) and high (~107-8 PFU mL-1 ) seeding densities, to determine system efficacy for SARS-CoV-2 inactivation and establish the influence of biologically relevant suspension media on viral susceptibility. Complete/near-complete (≥99.4%) inactivation was demonstrated in all cases, with significantly enhanced reductions observed in biologically relevant media (P < 0.05). Doses of 43.2 and 172.8 J cm-2 were required to achieve ~3 log10 reductions at low density, and 97.2 and 259.2 J cm-2 achieved ~6 log10 reductions at high density, in saliva and SM buffer, respectively: 2.6-4 times less dose was required when suspended in saliva compared to SM buffer. Comparative exposure to higher irradiance (~50 mW cm-2 ) 405-nm light indicated that, on a per unit dose basis, 0.5 mW cm-2 treatments were capable of achieving up to 5.8 greater log10 reductions with up to 28-fold greater germicidal efficiency than that of 50 mW cm-2 treatments. These findings establish the efficacy of low irradiance 405-nm light systems for inactivation of a SARS-CoV-2 surrogate and demonstrate the significant enhancement in susceptibility when suspended in saliva, which is a major vector in COVID-19 transmission.

Violet-blue 405-nm Light-based Photoinactivation for Pathogen Reduction of Human Plasma Provides Broad Antibacterial Efficacy Without Visible Degradation of Plasma Proteins.

In transfusion medicine, bacterial contamination can occur in ex vivo stored blood plasma, and there are continued efforts to improve blood safety and reduce the risk of transfusion-transmitted infections. Visible 405-nm violet-blue light has demonstrated potential for in situ pathogen reduction in ex vivo stored plasma and platelet concentrates. This study investigates the broad-spectrum antibacterial efficacy and compatibility potential of 405-nm light for treatment of blood plasma. Human plasma seeded with bacteria at a range of densities (101 -103 , 104 -106 , 107 -108 CFU mL-1 ) was exposed to 360 J cm-2 405-nm light (1 h at 0.1 W cm-2 ), with this fixed dose selected based on the initial analysis of inactivation kinetics. One-dimensional protein mobility analysis and measurement of advanced oxidation protein products (AOPP) was conducted to evaluate compatibility of the antimicrobial dose with plasma proteins and, identify upper levels at which protein degradation can be detected. Broad-spectrum antibacterial efficacy was observed with a fixed treatment of 360 J cm-2 , with 98.9-100% inactivation achieved across all seeding densities for all organisms, except E. coli, which achieved 95.1-100% inactivation. At this dose (360 J cm-2 ), no signs of protein degradation occurred. Overall, 405-nm light shows promise for broad-spectrum bacterial inactivation in blood plasma, while preserving plasma protein integrity.

Complications Associated with Peripheral Nerve Blocks.

Outpatient orthopedic surgery is gradually becoming the standard across the country, as it has been found to significantly lower costs without compromising patient care. Peripheral nerve blocks (PNBs) are largely what have made this transition possible by providing patients excellent pain control in the immediate postoperative period. However, with the increasing use of PNBs, it is important to recognize that they are not without complications. Although rare, these complications can cause patients a significant amount of morbidity. It is important for surgeons to know the risks of peripheral nerve blocks and to inform their patients.

Comparing 4-Year Changes in Patient-Reported Outcomes Following Ankle Arthroplasty and Arthrodesis.

BACKGROUND: The rate of total ankle arthroplasty (TAA) is increasing relative to ankle arthrodesis (AA) for patients seeking surgical treatment for end-stage ankle arthritis. Patients and providers would benefit from a more complete understanding of the rate of improvement, the average length of time to achieve maximal function and minimal pain, and whether there is a greater decline in function or an increase in pain over time following TAA compared with AA. The objectives of this study were to compare treatment changes in overall physical and mental function and ankle-specific function, as well as pain intensity at 48 months after TAA or AA in order to determine if the improvements are sustained. METHODS: This was a multisite prospective cohort study that included 517 participants (414 TAA and 103 AA) who presented for surgical treatment. Participants were compared 48 months after surgery using the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living and Sports subscales (0 to 100 points), the Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores (0 to 100 points), and pain scores (0 to 10 points). RESULTS: Both groups achieved significant improvement in the 2 FAAM measures, the SF-36 PCS score, and all of the pain measures at 48 months after surgey (p < 0.001). Mean improvements from baseline in patients undergoing TAA for the FAAM Activities of Daily Living, FAAM Sports, and SF-36 scores were at least 9 points, 8 points, and 3.5 points, respectively, which were higher than in those undergoing AA. Mean improvements in worst and average pain were at least 0.9 point higher in patients undergoing TAA than in those undergoing AA at 12, 24, and 36 months. These differences were attenuated by 48 months. For both treatments, all improvements from baseline to 24 months had been maintained at 48 months. CONCLUSIONS: When both procedures are performed by the same group of surgeons, patients who undergo TAA or AA for end-stage ankle arthritis have significant improvement in overall function, ankle-specific function, and pain at 48 months after surgery, with better functional improvement in the TAA group. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Complete Inactivation of Blood Borne Pathogen Trypanosoma cruzi in Stored Human Platelet Concentrates and Plasma Treated With 405 nm Violet-Blue Light.

The introduction of pathogen reduction technologies (PRTs) to inactivate bacteria, viruses and parasites in donated blood components stored for transfusion adds to the existing arsenal toward reducing the risk of transfusion-transmitted infectious diseases (TTIDs). We have previously demonstrated that 405 nm violet-blue light effectively reduces blood-borne bacteria in stored human plasma and platelet concentrates. In this report, we investigated the microbicidal effect of 405 nm light on one important bloodborne parasite Trypanosoma cruzi that causes Chagas disease in humans. Our results demonstrated that a light irradiance at 15 mWcm-2 for 5 h, equivalent to 270 Jcm-2, effectively inactivated T. cruzi by over 9.0 Log10, in plasma and platelets that were evaluated by a MK2 cell infectivity assay. Giemsa stained T. cruzi infected MK2 cells showed that the light-treated parasites in plasma and platelets were deficient in infecting MK2 cells and did not differentiate further into intracellular amastigotes unlike the untreated parasites. The light-treated and untreated parasite samples were then evaluated for any residual infectivity by injecting the treated parasites into Swiss Webster mice, which did not develop infection even after the animals were immunosuppressed, further demonstrating that the light treatment was completely effective for inactivation of the parasite; the light-treated platelets had similar in vitro metabolic and biochemical indices to that of untreated platelets. Overall, these results provide a proof of concept toward developing 405 nm light treatment as a pathogen reduction technology (PRT) to enhance the safety of stored human plasma and platelet concentrates from bloodborne T. cruzi, which causes Chagas disease.

Effectiveness and Safety of Ankle Arthrodesis Versus Arthroplasty: A Prospective Multicenter Study.

BACKGROUND: Newer designs and techniques of total ankle arthroplasty (TAA) have challenged the assumption of ankle arthrodesis (AA) as the primary treatment for end-stage ankle arthritis. The objective of this study was to compare physical and mental function, ankle-specific function, pain intensity, and rates of revision surgery and minor complications between these 2 procedures and to explore heterogeneous treatment effects due to age, body mass index (BMI), patient sex, comorbidities, and employment on patients treated by 1 of these 2 methods. METHODS: This was a multisite prospective cohort study comparing outcomes of surgical treatment of ankle arthritis. Subjects who presented after nonoperative management had failed received either TAA or AA using standard-of-treatment care and rehabilitation. Outcomes included the Foot and Ankle Ability Measure (FAAM), Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores, pain, ankle-related adverse events, and treatment success. RESULTS: Five hundred and seventeen participants underwent surgery and completed a baseline assessment. At 24 months, the mean improvement in FAAM activities of daily living (ADL) and SF-36 PCS scores was significantly greater in the TAA group than in the AA group, with a difference between groups of 9 points (95% confidence interval [CI] = 3, 15) and 4 points (95% CI = 1, 7), respectively. The crude incidence risks of revision surgery and complications were greater in the AA group; however, these differences were no longer significant after adjusting for age, sex, BMI, and Functional Comorbidity Index (FCI). The treatment success rate was greater after TAA than after AA for those with an FCI of 4 (80% versus 62%) and not fully employed (81% versus 58%) but similar for those with an FCI score of 2 (81% versus 77%) and full-time employment (79% versus 78%). CONCLUSIONS: At 2-year follow-up, both AA and TAA were effective. Improvement in several patient-reported outcomes was greater after TAA than after AA, without a significant difference in the rates of revision surgery and complications. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Step Activity After Surgical Treatment of Ankle Arthritis.

BACKGROUND: Ambulatory activity is reduced in patients with ankle arthritis. In this study, we measured step activity over time in 2 treatment groups and secondarily compared step activity with results of patient-reported outcome measures (PROMs). METHODS: Patients who were treated with either ankle arthrodesis or ankle arthroplasty wore a step activity monitor preoperatively and at 6, 12, 24, and 36 months postoperatively. Changes from preoperative baseline in total steps per day and per-day metrics of low, medium, and high-activity step counts were measured in both treatment groups. Step activity was compared with each subject's PROM scores as reported on the Musculoskeletal Function Assessment (MFA) and the Short Form-36 (SF-36) physical function and bodily pain subscales. RESULTS: Of the 3 activity levels, combined group high-activity step counts showed the greatest increase (mean of 278 steps [95% confidence interval (CI), 150 to 407 steps], a 46% improvement from preoperatively). At 6 months, the mean high-activity step improvement for the arthroplasty group was 194 steps compared with a mean decline of 44 steps for the arthrodesis group (mean 238-step difference [95% CI, -60 to 536 steps]). By 36 months postoperatively, the greater improvement in high-activity steps for the arthroplasty versus the arthrodesis group was no longer present. There were no significant pairwise differences in improvement based on surgical treatment method at any individual follow-up time point. For a within-patient increase of 1,000 total steps, there was a mean change in the MFA, SF-36 physical function, and SF-36 bodily pain scores of -1.8 (95% CI, -2.4 to -1.2), 3.8 (95% CI, 2.8 to 4.8), and 2.8 (95% CI, 1.8 to 3.9), respectively (p < 0.0001 for all associations). There was no evidence that the association differed by study visit, or by study visit and surgical procedure interaction (p > 0.10). CONCLUSIONS: Surgical treatment of ankle arthritis significantly improves ambulatory activity, with greater change occurring at high activity levels. Improvement may occur more quickly following arthroplasty than arthrodesis, but at 3 years, we detected no significant difference between the 2 procedures. Step counts, while associated with PROMs, do not parallel them, and thus may be a useful supplementary measure, particularly in longitudinal studies. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Non-ionizing 405 nm Light as a Potential Bactericidal Technology for Platelet Safety: Evaluation of in vitro Bacterial Inactivation and in vivo Platelet Recovery in Severe Combined Immunodeficient Mice.

Bacterial contamination of ex vivo stored platelets is a cause of transfusion-transmitted infection. Violet-blue 405 nm light has recently demonstrated efficacy in reducing the bacterial burden in blood plasma, and its operational benefits such as non-ionizing nature, penetrability, and non-requirement for photosensitizing agents, provide a unique opportunity to develop this treatment for in situ treatment of ex vivo stored platelets as a tool for bacterial reduction. Sealed bags of platelet concentrates, seeded with low-level Staphylococcus aureus contamination, were 405 nm light-treated (3-10 mWcm-2) up to 8 h. Antimicrobial efficacy and dose efficiency was evaluated by quantification of the post-treatment surviving bacterial contamination levels. Platelets treated with 10 mWcm-2 for 8 h were further evaluated for survival and recovery in severe combined immunodeficient (SCID) mice. Significant inactivation of bacteria in platelet concentrates was achieved using all irradiance levels, with 99.6-100% inactivation achieved by 8 h (P < 0.05). Analysis of applied dose demonstrated that lower irradiance levels generally resulted in significant decontamination at lower doses: 180 Jcm-2/10 mWcm-2 (P = 0.008) compared to 43.2 Jcm-2/3 mWcm-2 (P = 0.002). Additionally, the recovery of light-treated platelets, compared to non-treated platelets, in the murine model showed no significant differences (P = >0.05). This report paves the way for further comprehensive studies to test 405 nm light treatment as a bactericidal technology for stored platelets.

Frequency and Impact of Adverse Events in Patients Undergoing Surgery for End-Stage Ankle Arthritis.

BACKGROUND: This study summarized the frequency and functional impact of adverse events (AEs) that occur after surgery for end-stage ankle arthritis (ESAA) to inform decision making. METHODS: This was a multisite prospective cohort study to compare ankle arthroplasty to ankle arthrodesis in the treatment of ESAA among 6 participating sites. We compared the risk and impact of nonankle AEs and ankle-specific AEs versus no AEs controlling for potential confounding factors, including operative procedure using multinomial logistic regression. We estimated differences in postoperative functional outcomes by AE occurrence using linear mixed effects regression. Among 517 patients who had surgery for ankle arthritis and completed the full baseline assessment, follow-up scores were available in 494 (95%) patients. RESULTS: There were a total of 628 reported AEs (477 in the arthroplasty group and 151 in the arthrodesis group). These occurred in 261 (63%) arthroplasty patients and 67 (65%) arthrodesis patients. There were 50 (8%) ankle-specific AEs. The risk of an ankle-specific AE was slightly higher in the arthrodesis group versus the arthroplasty group, odds ratio (OR) 1.84, 95% confidence interval (CI, 0.85, 3.98). The OR for the risk of non-ankle-specific AE versus no AE was 0.96, 95% CI (0.57, 1.61) for those receiving arthrodesis compared to arthroplasty. Compared to patients with no AEs, those experiencing ankle-specific AEs had significantly less improvement in Foot and Ankle Ability Measure Sports and activities of daily living (ADL) subscores and worst pain outcomes; however, both groups improved significantly in all measures except mental health. CONCLUSIONS: Ankle-specific AEs were infrequent and only weakly associated with operative procedure. Although patients improved in all functional outcomes except mental health, regardless of AE occurrence, ankle-specific AEs negatively impacted patient improvement compared to those with no AEs or a nonankle AE. The logistical effort and cost of tracking nonankle AEs does not seem to be justified. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Review of the Comparative Susceptibility of Microbial Species to Photoinactivation Using 380-480 nm Violet-Blue Light.

Antimicrobial violet-blue light is an emerging technology designed for enhanced clinical decontamination and treatment applications, due to its safety, efficacy and ease of use. This systematized review was designed to compile the current knowledge on the antimicrobial efficacy of 380-480 nm light on a range of health care and food-related pathogens including vegetative bacteria, bacterial endospores, fungi and viruses. Data were compiled from 79 studies, with the majority focussing on wavelengths in the region of 405 nm. Analysis indicated that Gram-positive and Gram-negative vegetative bacteria are the most susceptible organisms, while bacterial endospores, viruses and bacteriophage are the least. Evaluation of the dose required for a 1 log10 reduction of key bacteria compared to population, irradiance and wavelength indicated that microbial titer and light intensity had little effect on the dose of 405 nm light required; however, linear analysis indicated organisms exposed to longer wavelengths of violet-blue light may require greater doses for inactivation. Additional research is required to ensure this technology can be used effectively, including: investigating inactivation of multidrug-resistant organisms, fungi, viruses and protozoa; further knowledge about the photodynamic inactivation mechanism of action; the potential for microbial resistance; and the establishment of a standardized exposure methodology.

Comparison of Treatment Outcomes of Arthrodesis and Two Generations of Ankle Replacement Implants.

BACKGROUND: We analyzed self-reported outcomes in a prospective cohort of patients treated with ankle arthrodesis or total ankle replacement (TAR) during a time of transition from older to newer-generation TAR implants. METHODS: We performed a prospective cohort study comparing outcomes in 273 consecutive patients treated for ankle arthritis with arthrodesis or TAR between 2005 and 2011. Adult patients with end-stage ankle arthritis who were able to walk and willing and able to respond to surveys were included in the study. Patients were excluded when they had another lower-limb problem that might affect walking. At baseline and at 6, 12, 24, and 36-month follow-up visits, participants completed a pain score, a Musculoskeletal Function Assessment (MFA), and a Short Form-36 (SF-36) survey. RESULTS: There was significant mean improvement in most outcomes after surgery regardless of procedure. In general, the greatest improvement occurred during the first 6 months of follow-up. Linear mixed-effects regression adjusted for differences at baseline in age, body mass index (BMI), and surgery type showed that at 6 months the scores were improved by a mean (and standard error) of 12.6 ± 0.7 (33%) on the MFA, 22.0 ± 1.4 (56%) on the SF-36 Physical Functioning (PF) scale, 32.4 ± 1.6 (93%) on the SF-36 Bodily Pain (BP) scale, and 4.0 ± 0.2 (63%) on the pain rating scale. The mean improvements in the MFA and SF-36 PF scores over the 3-year follow-up period were significantly better after the TARs than after the arthrodeses, with differences between the 2 groups of 3.6 ± 1.6 (p = 0.023) and 7.5 ± 2.9 (p = 0.0098), respectively. The differences between the 2 groups were slightly greater when only the newer TAR devices were compared with the arthrodeses (MFA = 3.8 ± 1.8 [p = 0.031], SF-36 PF = 8.8 ± 3.3 [p = 0.0074], SF-36 BP = 7.3 ± 3.6 [p = 0.045], and pain score = 0.8 ± 0.4 [p = 0.038]). CONCLUSIONS: Patients reported improved comfort and function after both surgical treatments. The average improvement in the MFA and SF-36 PF scores was better after TAR than after arthrodesis, particularly when the TAR had been done with later-generation implants. Younger patients had greater functional improvements than older patients. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Assessment of the potential for resistance to antimicrobial violet-blue light in Staphylococcus aureus.

BACKGROUND: Antimicrobial violet-blue light in the region of 405 nm is emerging as an alternative technology for hospital decontamination and clinical treatment. The mechanism of action is the excitation of endogenous porphyrins within exposed microorganisms, resulting in ROS generation, oxidative damage and cell death. Although resistance to 405 nm light is not thought likely, little evidence has been published to support this. This study was designed to establish if there is potential for tolerance development, using the nosocomial pathogen Staphylococcus aureus as the model organism. METHODS: The first stage of this study investigated the potential for S. aureus to develop tolerance to high-intensity 405 nm light if pre-cultured in low-level stress violet-blue light (≤1 mW/cm2) conditions. Secondly, the potential for tolerance development in bacteria subjected to repeated sub-lethal exposure was compared by carrying out 15 cycles of exposure to high-intensity 405 nm light, using a sub-lethal dose of 108 J/cm2. Inactivation kinetics and antibiotic susceptibility were also compared. RESULTS: When cultured in low-level violet-blue light conditions, S. aureus required a greater dose of high-intensity 405 nm light for complete inactivation, however this did not increase with multiple (3) low-stress cultivations. Repeated sub-lethal exposures indicated no evidence of bacterial tolerance to 405 nm light. After 15 sub-lethal exposures 1.2 and 1.4 log10 reductions were achieved for MSSA and MRSA respectively, which were not significantly different to the initial 1.3 log10 reductions achieved (P = 0.242 & 0.116, respectively). Antibiotic susceptibility was unaffected, with the maximum change in zone of inhibition being ± 2 mm. CONCLUSIONS: Repeated sub-lethal exposure of non-proliferating S. aureus populations did not affect the susceptibility of the organism to 405 nm light, nor to antibiotics. Culture in low-level violet-blue light prior to 405 nm light exposure may increase oxidative stress responses in S. aureus, however, inactivation still occurs and results demonstrate that this is unlikely to be a selective process. These results demonstrate that tolerance from repeated exposure is unlikely to occur, and further supports the potential development of 405 nm light for clinical decontamination and treatment applications.

Management of Tarsometatarsal Joint Injuries.

Joint disruptions to the tarsometatarsal (TMT) joint complex, also known as the Lisfranc joint, represent a broad spectrum of pathology from subtle athletic sprains to severe crush injuries. Although injuries to the TMT joint complex are uncommon, when missed, they may lead to pain and dysfunction secondary to posttraumatic arthritis and arch collapse. An understanding of the appropriate anatomy, mechanism, physical examination, and imaging techniques is necessary to diagnose and treat injuries of the TMT joints. Nonsurgical management is indicated in select patients who maintain reduction of the TMT joints under physiologic stress. Successful surgical management of these injuries is predicated on anatomic reduction and stable fixation. Open reduction and internal fixation remains the standard treatment, although primary arthrodesis has emerged as a viable option for certain types of TMT joint injuries.

Open Reduction and Internal Fixation Versus Primary Arthrodesis for Lisfranc Injuries.

Management of injuries to the tarsometatarsal (Lisfranc) joint complex continues to generate heated debate. Arthrodesis of the Lisfranc joint complex has historically been reserved as a salvage procedure for failed treatment. Recently, primary arthrodesis has emerged as a viable treatment alternative to open reduction and internal fixation for these injuries. The objective of this article was to examine the current literature regarding open reduction and internal fixation versus primary arthrodesis of Lisfranc injuries.

New Proof-of-Concept in Viral Inactivation: Virucidal Efficacy of 405 nm Light Against Feline Calicivirus as a Model for Norovirus Decontamination.

The requirement for novel decontamination technologies for use in hospitals is ever present. One such system uses 405 nm visible light to inactivate microorganisms via ROS-generated oxidative damage. Although effective for bacterial and fungal inactivation, little is known about the virucidal effects of 405 nm light. Norovirus (NoV) gastroenteritis outbreaks often occur in the clinical setting, and this study was designed to investigate potential inactivation effects of 405 nm light on the NoV surrogate, feline calicivirus (FCV). FCV was exposed to 405 nm light whilst suspended in minimal and organically-rich media to establish the virucidal efficacy and the effect biologically-relevant material may play in viral susceptibility. Antiviral activity was successfully demonstrated with a 4 Log10 (99.99%) reduction in infectivity when suspended in minimal media evident after a dose of 2.8 kJ cm-2. FCV exposed in artificial faeces, artificial saliva, blood plasma and other organically rich media exhibited an equivalent level of inactivation using between 50-85% less dose of the light, indicating enhanced inactivation when the virus is present in organically-rich biologically-relevant media. Further research in this area could aid in the development of 405 nm light technology for effective NoV decontamination within the hospital environment.