Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model.

Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG were evaluated postmortem. Data, except lameness data, were analyzed using a mixed-effects model; lameness data were analyzed as ordinal data using a cumulative logistic model. CLO did not have any measurable effects on the skeleton of sheep. SBB showed changes over time (p ≤ 0.03), with increases in bone formation and decreases in some bone resorption markers. TC biopsies showed increasing bone volume fraction, trabecular spacing and thickness, and reduced trabecular number on day 165 versus day 84 (p ≤ 0.04). These changes may be attributed to exercise or growth. The absence of a treatment effect may be explained by the lower CLO dose used in large animals compared to humans. Further research is needed to examine whether low doses of bisphosphonates may be used in active juvenile populations for analgesia without evidence of bone changes.

The effects of osteopathic manipulative treatment on pain and disability in patients with chronic low back pain: a single-blinded randomized controlled trial.

CONTEXT: The evidence for the efficacy of osteopathic manipulative treatment (OMT) in the management of low back pain (LBP) is considered weak by systematic reviews, because it is generally based on low-quality studies. Consequently, there is a need for more randomized controlled trials (RCTs) with a low risk of bias. OBJECTIVES: The objective of this study is to evaluate the efficacy of an OMT intervention for reducing pain and disability in patients with chronic LBP. METHODS: A single-blinded, crossover, RCT was conducted at a university-based health system. Participants were adults, 21-65 years old, with nonspecific LBP. Eligible participants (n=80) were randomized to two trial arms: an immediate OMT intervention group and a delayed OMT (waiting period) group. The intervention consisted of three to four OMT sessions over 4-6 weeks, after which the participants switched (crossed-over) groups. The primary clinical outcomes were average pain, current pain, Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v1.0 pain interference and physical function, and modified Oswestry Disability Index (ODI). Secondary outcomes included the remaining PROMIS health domains and the Fear Avoidance Beliefs Questionnaire (FABQ). These measures were taken at baseline (T0), after one OMT session (T1), at the crossover point (T2), and at the end of the trial (T3). Due to the carryover effects of OMT intervention, only the outcomes obtained prior to T2 were evaluated utilizing mixed-effects models and after adjusting for baseline values. RESULTS: Totals of 35 and 36 participants with chronic LBP were available for the analysis at T1 in the immediate OMT and waiting period groups, respectively, whereas 31 and 33 participants were available for the analysis at T2 in the immediate OMT and waiting period groups, respectively. After one session of OMT (T1), the analysis showed a significant reduction in the secondary outcomes of sleep disturbance and anxiety compared to the waiting period group. Following the entire intervention period (T2), the immediate OMT group demonstrated a significantly better average pain outcome. The effect size was a 0.8 standard deviation (SD), rendering the reduction in pain clinically significant. Further, the improvement in anxiety remained statistically significant. No study-related serious adverse events (AEs) were reported. CONCLUSIONS: OMT intervention is safe and effective in reducing pain along with improving sleep and anxiety profiles in patients with chronic LBP.

Diabetic Myonecrosis of the Axilla: A Novel Case With Severe Clinical Features.

Diabetic myonecrosis is a rare and poorly understood complication of long-standing, inadequately controlled diabetes mellitus. Theoretical mechanisms contributing to the pathophysiology of diabetic myonecrosis include microvascular complications due to advanced glycation end-products, ischemia-reperfusion injuries, and dysregulated coagulation-fibrinolysis activity. Case reports of diabetic myonecrosis most commonly describe diabetic patients with chronically poor glycemic control who experience isolated swelling and severe pain in a unilateral lower limb with no signs of infection or systemic toxicity. Due to the rarity of this condition, there are currently no treatment guidelines. This case describes a 58-year-old male with a history of uncontrolled diabetes who presented with diabetic ketoacidosis with mixed hypovolemic and septic shock. Diabetic myonecrosis was incidentally discovered in the patient's right latissimus dorsi with CT imaging and subsequent surgical exploration. Spontaneous diabetic myonecrosis may mimic several other serious conditions and elicit suboptimal management strategies, particularly in the context of atypical presentations.

Chronic Neurocognitive, Neuropsychological, and Pulmonary Symptoms in Outpatient and Inpatient Cohorts After COVID-19 Infection.

Neuropsychological symptoms associated with post-COVID-19 conditions may prevent patients from resuming normal activities at home or work. We report a retrospective, cross-sectional evaluation of neuropsychological and cardiopulmonary outcomes in 2 groups of patients: outpatients with mild enough infection to be spared from hospitalization and those who required inpatient admission. We hypothesized a dose-response model of post-COVID symptom severity in which persistent consequences would be more severe in those who experienced worse acute infections. In a dedicated COVID clinic, 321 patients were seen (33% outpatient, 67% inpatient). Outpatients skewed female, White, non-Hispanic, and younger. Outpatients had worse insomnia (measured with insomnia severity index) and were less able to resume their usual activities (EQ-5D-5L usual activities scale), despite inpatients experiencing worse cognition (Montreal Cognitive Assessment), having greater obesity (body mass index), decreased exercise tolerance (6-minute-walk distance), and more exertional oxygen desaturation. In both groups, insomnia worsened while cognition improved significantly with time from infection to testing while controlling for patient age; other variables did not. In logistic regression, female sex, higher MoCA score, EQ-5D-5L "usual activities" subscore, less oxygen desaturation with exertion, and longer time from infection remained as significant associations with outpatient status. Our study demonstrated that the functional sequelae of post-COVID-19 conditions in patients with mild acute disease have the potential to be as severe as that in patients who have recovered from severe illness.

Rurality as a Risk Factor for Pulmonary Health Disparities.

Rural populations experience significant pulmonary health disparities compared with urban populations. Patients in rural communities experience health determinants including high smoking prevalence, worse nutrition, lower educational attainment, specific occupational exposures, decreased health-care access, as well as unique cultural and political drivers of health. This article describes social determinants of pulmonary health relevant in rural communities, describes examples of existing pulmonary disparities in rural populations, and highlights health policies with potential to mitigate disparities.

Surgical Management of a Retained Appendicolith Following Laparoscopic Appendectomy.

Appendicitis is one of the most common surgical emergencies, and surgical intervention remains the gold standard for curative treatment. Although laparoscopic appendectomy is associated with less pain, shorter hospital stays, and earlier mobilization, it is also more frequently complicated by postoperative abscesses. Retained appendicoliths are a rare complication that can serve as a nidus for repeated infections. Laparoscopic removal of the stone can provide definitive source control and reduce repeated hospital admissions. There are many surgical approaches for retrieval and this case, in particular, describes a laparoscopic hand-assisted approach while simultaneously using an interventional radiologic drain to assist with localization.

Cecal Volvulus Through an Internal Hernia Created by an Elongated Fallopian Tube.

Internal hernias result from abdominal viscera protruding through a congenital or acquired defect in the peritoneum or the mesentery of the abdominal cavity. They are less common than external hernias, and the overall incidence is rare. Internal hernias carry a high mortality rate if there is no immediate surgical intervention and can lead to complications such as bowel perforation, ischemia, and necrosis. There are multiple classifications, and a rare subtype identified in only a select few cases involves the fallopian tube. This case documents the development of a cecal volvulus due to the cecum herniating through an aperture created by a normal-appearing fallopian tube attaching to the retroperitoneum.  A 78-year-old female with multiple comorbidities was admitted for abdominal pain lasting 3-4 days, nausea, emesis, and poor oral tolerance. Computerized tomography imaging revealed a complete large bowel obstruction secondary to a cecal volvulus, and she was taken emergently for an exploratory laparotomy. Intra-operatively, a distended cecum was noted, herniated through a loop created by the right fallopian tube tethering its free end to the left pelvis. Upon decompression of the bowel, the fallopian tube released itself from the retroperitoneum. The cecum and right fallopian tube were noted to be ischemic and resected with an ileo-transverse anastomosis. Internal hernias that involve the fallopian tubes are a rare variation of an already uncommon condition. However, they should be included in the differential diagnosis when evaluating a female patient for intestinal obstruction since it can develop into a life-threatening condition that requires prompt surgical attention.

Time-Limited Trials of Intensive Care Unit Care.

This Teachable Moment discusses time-limited trials, "an agreement between clinicians and a patient/family to use certain medical therapies over a defined period to see if the patient improves or deteriorates according to agreed-on clinical outcomes.".

Efficacy of Tourniquet Use in Total Knee Arthroplasty: A Retrospective Cohort Review.

Background: The use of a tourniquet has become widely accepted as standard practice during total knee arthroplasty (TKA). There are conflicting outcomes in using a tourniquet during TKA. This brings to question the role a tourniquet has in TKA. Therefore, we conducted a retrospective cohort study to examine the effects of TKA with and without the use of a tourniquet. Methods: A total of 120 patients (n = 60 underwent TKA with tourniquet and n = 60 underwent TKA without tourniquet) were included in this study. Patient medical records were retrospectively reviewed for preoperative and postoperative data. The Gross formula, a validated formula for calculating blood loss, was used to calculate each patient's total blood loss. Statistical analysis was performed using independent t-tests, Mann-Whitney U tests, and/or chi-square tests. Significance was determined using an alpha level of P < .05. Results: There was no statistically significant difference (P = .49) in the amount of total blood loss between patients undergoing TKA with a tourniquet and those without (199.6 ± 92.2 mL vs 211.1 ± 88.1 mL, respectively). However, there were statistically significant differences in the operating room time (P = .005), surgery time (P = .008), and functional return of postoperative straight leg raise (P < .001) between groups. Conclusions: This study supports existing evidence that tourniquet use during TKA does not significantly alter blood loss and presents evidence that using a tourniquet during TKA may add additional cost and increase surgical time without benefit.

The Impact of Circular Exercise Diameter on Bone and Joint Health of Juvenile Animals.

Circular exercise is used in many equestrian disciplines and this study aimed to determine if circle diameter impacts juvenile animal forelimb bone and joint health. On day 0, 24 calves at 9 weeks of age were assigned the following exercise treatments: small circle (12 m clockwise), large circle (18-m clockwise), treadmill, or non-exercised control. Exercise was initiated at 1.1−1.5 m/s for 5 min/d and increased 5 min weekly until reaching 30 min/d. On day 49, synovial fluid was collected from multiple joints, cartilage was collected from the proximal surface of fused third and fourth metacarpi (MC III and IV), and forelimbs underwent computed tomography scans. A statistical analysis (PROC mixed) was performed in SAS 9.4. The inside leg of the small circle treatment had a larger MC III and IV dorsopalmar external diameter than the outside (p = 0.05). The medial proximal phalanx had a greater mediolateral diameter than the lateral proximal phalanx of the small circle treatment (p = 0.01). Fetlock nitric oxide was greater in the large circle and treadmill treatments (p < 0.0001). Cartilage glycosaminoglycan concentration was greater in the outside leg of the small circle exercise treatment than the inside leg (p = 0.03). Even at slow speeds, circular exercise diameter can impact joint and bone health, but faster speeds may have greater alterations.

Time, graft, sex, geographic location, and isokinetic speed influence the degree of quadriceps weakness after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: Although quadriceps weakness after ACL reconstruction (ACLR) is well documented, the magnitude of reported weakness varies considerably. Such variation raises the possibility that certain patients may be more susceptible to quadriceps weakness after ACLR. This meta-analysis identified factors explaining between-study variability in quadriceps weakness post-ACLR. METHODS: Studies between 2010 and 2020 were screened for the following criteria: human subjects, unilateral ACLR, and strength reported both for the ACLR leg and the uninjured or healthy-control leg. 122 studies met the criteria, resulting in 303 and 152 Cohen's d effect sizes (ESs) comparing ACLR legs to uninjured legs (a total of 4135 ACLR subjects) and to healthy controls (a total of 1,507 ACLR subjects vs. 1-193 healthy controls), respectively. Factors (time, graft, sex, activity, mass/height, geographic area, concomitant injury, and type of strength testing) that may affect study ES were examined. RESULTS: Meta-regressions indicated an association between time post-ACLR and study ESs (P < 0.001) and predicted full recovery (ES = 0) to occur at 54-59 months post-ACLR. When compared to uninjured legs, patients with patellar tendon autografts had greater deficits than studies using hamstring tendon autografts (P = 0.023). When compared to uninjured legs, studies including only males reported greater deficits than studies combining males and females (P = 0.045); whereas when compared to healthy controls, studies combining males and females reported greater deficits than studies with males (P = 0.013). When compared to controls, studies from USA reported greater deficits than studies from Europe (P = 0.003). Increased isokinetic-testing speed was associated with smaller deficits (P ≤ 0.025). Less than 25% of patients achieved a between-limb symmetry in quadriceps strength > 90% between 6 and 12 months post-ACLR. CONCLUSION: Time post-surgery, graft, sex, geographic location, and isokinetic speed influenced the magnitude of post-ACLR quadriceps weakness. Patients with patellar tendon autografts demonstrated greater between-limb asymmetry in quadriceps strength, while female strength deficits were underestimated to a greater extent. A slower isokinetic speed provided a more sensitive assessment of quadriceps strength post-ACLR. The overwhelming majority of patients were returning to sport with significantly impaired quadriceps strength. LEVEL OF EVIDENCE: III.

How Individuals With Low Back Pain Conceptualize Their Condition: A Collaborative Modeling Approach.

Low back pain (LBP) is complex. This study aimed to use collaborative modeling to evaluate conceptual models that individuals with LBP have of their condition, and to compare these models with those of researchers/clinicians. Twenty-eight individuals with LBP were facilitated to generate mental models, using "fuzzy cognitive maps," that represented conceptualization of their own LBP and LBP "in general." "Components" (ie, causes, outcomes and treatments) related to pain, disability and quality of life were proposed, along with the weighted "Connections" between Components. Components were classified into thematic categories. Weighting of Connections were summed for each Component to judge relative importance. Individual models were aggregated into a metamodel. When considering their own condition, participants' models included 19(SD = 6) Components and 43(18) Connections with greatest weight on "Biomechanical" components. When considering LBP in general, models changed slightly. Patient models contrasted the more complex models of researchers/clinicians (25(7) Components; 77(42) Connections), with most weight on "Psychological" components. This study provides unique insight into how individuals with LBP consider their condition, which is largely biomedical and narrower than clinician/researcher perspectives. Findings highlight challenges for changing public perception of LBP, and provide a method with potential utility to understand how individuals conceptualize their condition. PERSPECTIVE: Collaborative modeling was used to understand how individuals with low back pain conceptualize their own condition, the condition in general, and compare this with models of expert researchers/clinicians. Data revealed issues in how individuals with back pain conceptualize their condition, and the method's potential utility for clinical evaluation of patients.

Evaluation of Within- and Between- Session Reliability of the TekscanTM Hoof System With a Glue-on Shoe.

A current trend in equine research is technology development to minimize the subjective nature of gait analysis. One such technology is the Tekscan Hoof System, which records force and area loaded by the hooves during motion. The objective of this study was to determine the test-retest reliability of the Tekscan Hoof System between two sessions, and the recordings within those sessions. Four mature Standardbred geldings wore Tekscan Hoof System sensors on both front hooves, secured by glue-on shoes (SoundHorse Technologies). Horses were exercised in AM and PM sessions. In each session, horses walked and trotted for three recordings of at least 10 steps. Statistical analysis was performed in SAS 9.4 with fixed effects of gait, horse, leg, and recording nested within session (significance at P ≤ .05). Intraclass Correlation Coefficients (ICC; 3,k) and confidence intervals between AM and PM sessions and recordings were calculated with SPSS. Average force and area were higher in AM sessions than PM sessions (P < .0001). Between AM and PM sessions, ICC for the walk had good reliability (0.96, 95% CI = 0.80 - 0.99) and excellent reliability at the trot (0.98, 95% CI = 0.91-0.99). Within the AM and PM sessions, reliability was excellent at both the walk, and trot (ICCs > 0.96). The Tekscan Hoof System has been found to have excellent reliability within sessions. Caution should be taken when comparing between sessions, as the system is found to have lower force and area output during later sessions due to potential sensor damage.

The effects of osteopathic manipulative treatment on pain and disability in patients with chronic neck pain: A single-blinded randomized controlled trial.

BACKGROUND: Neck pain (NP) affects up to 70% of individuals at some point in their lives. Systematic reviews indicate that manual treatments can be moderately effective in the management of chronic, nonspecific NP. However, there is a paucity of studies specifically evaluating the efficacy of osteopathic manipulative treatment (OMT). OBJECTIVE: To evaluate the efficacy of OMT in reducing pain and disability in patients with chronic NP. DESIGN: Single-blinded, cross-over, randomized-controlled trial. SETTING: University-based, osteopathic manipulative medicine outpatient clinic. PARTICIPANTS: Ninety-seven participants, 21 to 65 years of age, with chronic, nonspecific NP. INTERVENTIONS: Participants were randomized to two trial arms: immediate OMT intervention or waiting period first. The intervention consisted of three to four OMT sessions over 4 to 6 weeks, after which the participants switched groups. MAIN OUTCOME MEASURES: Primary outcome measures were pain intensity (average and current) on the numerical rating scale and Neck Disability Index. Secondary outcomes included Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) health domains and Fear Avoidance Beliefs Questionnaire. Outcomes obtained prior to the cross-over allocation were evaluated using general linear models and after adjusting for baseline values. RESULTS: A total of 38 and 37 participants were available for the analysis in the OMT and waiting period groups, respectively. The results showed significantly better primary outcomes in the immediate OMT group for reductions in average pain (-1.02, 95% confidence interval [CI] -1.72, -0.32; p = .005), current pain (-1.02, 95% CI -1.75, -0.30; p = .006), disability (-5.30%, 95% CI -9.2%, -1.3%; p = .010) and improved secondary outcomes (PROMIS) related to sleep (-3.25, 95% CI -6.95, -1.54; p = .003), fatigue (-3.26, 95% CI -6.04, -0.48; p = .022), and depression (-2.59, 95% CI -4.73, -0.45; p = .018). The effect sizes were in the clinically meaningful range between 0.5 and 1 standard deviation. No study-related serious adverse events were reported. CONCLUSIONS: OMT is relatively safe and effective in reducing pain and disability along with improving sleep, fatigue, and depression in patients with chronic NP immediately following treatment delivered over approximately 4 to 6 weeks.

Inactivation of multidrug-resistant bacteria and bacterial spores and generation of high-potency bacterial vaccines using ultrashort pulsed lasers.

Multidrug-resistant organisms (MDROs) represent a continuing healthcare crisis with no definitive solution to date. An alternative to antibiotics is the development of therapies and vaccines using biocompatible physical methods such as ultrashort pulsed (USP) lasers, which have previously been shown to inactivate pathogens while minimizing collateral damage to human cells, blood proteins, and vaccine antigens. Here we demonstrate that visible USP laser treatment results in bactericidal effect (≥3-log load reduction) against clinically significant MDROs, including methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Escherichia coli. Bacillus cereus endospores, which are highly resistant to conventional chemical and physical treatments, were also shown to be effectively inactivated by USP laser treatment, resulting in sporicidal (≥3-log load reduction) activity. Furthermore, we demonstrate that administration of USP laser-inactivated E. coli whole-cell vaccines at dosages as low as 105 cfu equivalents without adjuvant was able to protect 100% of mice against subsequent lethal challenge. Our findings open the possibility for application of USP lasers in disinfection of hospital environments, therapy of drug-resistant bacterial infections in skin or bloodstream via pheresis modalities, and in the production of potent bacterial vaccines.

Change in End-Tidal Co2 After Mini-Fluid Challenge to Determine Fluid Responsiveness.

Distributive shock is a major cause of morbidity and mortality in the ICU. IV fluid resuscitation is a vital intervention to improve cardiac output and end-organ perfusion during the initial resuscitation and for those who remain fluid responsive. Noninvasive measures of fluid responsiveness are lacking. The aim of this study is to assess whether changes in end-tidal co2 after mini-fluid challenge, or 250 mL bolus, can predict fluid responsiveness in mechanically ventilated patients with distributive shock. DESIGN: Single-center prospective study. SETTING: Patients were enrolled from 2019 to 2021 from the medical ICU within a single academic hospital. PATIENTS: Thirty-eight patients with paired measurements of fluid responsiveness as determined by bioreactance who were admitted to the ICU with a diagnosis of distributive shock and on mechanical ventilation. INTERVENTIONS: Stroke volume index (SVI), cardiac index, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and ETco2 were measured before and after completion of a mini-fluid challenge. Test characteristics of change in ETco2 (ΔETco2) greater than or equal to 2 after mini-fluid challenge to determine fluid responsiveness were calculated with percentage change in SVI greater than or equal to 10% used as the reference standard. MEASUREMENTS AND MAIN RESULTS: The sensitivity and specificity of a ΔETco2 greater than or equal to 2 mm Hg as a predictor of a change in SVI greater than or equal to 10% following a mini-fluid challenge were 20.0% and 91.3%, respectively. The area under the receiver operating characteristic curve was 0.62. CONCLUSIONS: A ΔETco2 greater than or equal to 2 mm Hg after mini-fluid challenge has limited test performance for determining fluid responsiveness in intubated patients with distributive shock.

Impact of Gait and Diameter during Circular Exercise on Front Hoof Area, Vertical Force, and Pressure in Mature Horses.

Circular exercise can be used at varying gaits and diameters to exercise horses, with repeated use anecdotally relating to increased lameness. This work sought to characterize mean area, mean vertical force, and mean pressure of the front hooves while exercising in a straight line at the walk and trot, and small (10-m diameter) and large circles (15-m diameter) at the walk, trot, and canter. Nine mature horses wore TekscanTM Hoof Sensors on their forelimbs adhered with a glue-on shoe. Statistical analysis was performed in SAS 9.4 with fixed effects of leg, gait, and exercise type (PROC GLIMMIX) and p < 0.05 as significant. For all exercise types, the walk had greater mean pressure than the trot (p < 0.01). At the walk, the straight line had greater mean area loaded than the large circle (p = 0.01), and both circle sizes had lower mean vertical force than the straight line (p = 0.003). During circular exercise at the canter, the outside front limb had greater mean area loaded than at the walk and trot (p = 0.001). This study found that gait is an important factor when evaluating circular exercise and should be considered when exercising horses to prevent injury.

Stability threshold during seated balancing is sensitive to low back pain and safe to assess.

Challenging trunk neuromuscular control maximally using a seated balancing task is useful for unmasking impairments that may go unnoticed with traditional postural sway measures and appears to be safe to assess in healthy individuals. This study investigates whether the stability threshold, reflecting the upper limits in trunk neuromuscular control, is sensitive to pain and disability and is safe to assess in low back pain (LBP) patients. Seventy-nine subjects with non-specific LBP balanced on a robotic seat while rotational stiffness was gradually reduced. The critical rotational stiffness, KCrit, that marked the transition between stable and unstable balance was used to quantify the individual's stability threshold. The effects of current pain, 7-day average pain, and disability on KCrit were assessed, while controlling for age, sex, height, and weight. Adverse events (AEs) recorded at the end of the testing session were used to assess safety. Current pain and 7-day average pain were strongly associated with KCrit (current pain p < 0.001, 7-day pain p = 0.023), reflecting that people experiencing more pain have poorer trunk neuromuscular control. There was no evidence that disability was associated with KCrit, although the limited range in disability scores in subjects may have impacted the analysis. AEs were reported in 13 out of 79 total sessions (AE Severity: 12 mild, 1 moderate; AE Relatedness: 1 possibly, 11 probably, 1 definitely-related to the study). Stability threshold is sensitive to pain and appears safe to assess in people with LBP, suggesting it could be useful for identifying trunk neuromuscular impairments and guiding rehabilitation.

Antimicrobial laser-activated sealants for combating surgical site infections.

Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.