Vitamin K3 (Menadione) is a multifunctional microbicide acting as a photosensitizer and synergizing with blue light to kill drug-resistant bacteria in biofilms.

Cutaneous bacterial wound infections typically involve gram-positive cocci such as Staphylococcus aureus (SA) and usually become biofilm infections. Bacteria in biofilms may be 100-1000-fold more resistant to an antibiotic than the clinical laboratory minimal inhibitory concentration (MIC) for that antibiotic, contributing to antimicrobial resistance (AMR). AMR is a growing global threat to humanity. One pathogen-antibiotic resistant combination, methicillin-resistant SA (MRSA) caused more deaths globally than any other such combination in a recent worldwide statistical review. Many wound infections are accessible to light. Antimicrobial phototherapy, and particularly antimicrobial blue light therapy (aBL) is an innovative non-antibiotic approach often overlooked as a possible alternative or adjunctive therapy to reduce antibiotic use. We therefore focused on aBL treatment of biofilm infections, especially MRSA, focusing on in vitro and ex vivo porcine skin models of bacterial biofilm infections. Since aBL is microbicidal through the generation of reactive oxygen species (ROS), we hypothesized that menadione (Vitamin K3), a multifunctional ROS generator, might enhance aBL. Our studies suggest that menadione can synergize with aBL to increase both ROS and microbicidal effects, acting as a photosensitizer as well as an ROS recycler in the treatment of biofilm infections. Vitamin K3/menadione has been given orally and intravenously worldwide to thousands of patients. We conclude that menadione/Vitamin K3 can be used as an adjunct to antimicrobial blue light therapy, increasing the effectiveness of this modality in the treatment of biofilm infections, thereby presenting a potential alternative to antibiotic therapy, to which biofilm infections are so resistant.

Development of a Low-Resource Operating Room and a Wide-Awake Orthopedic Surgery Program During the COVID-19 Pandemic.

Introduction. The COVID-19 pandemic resulted in significant medication, supply and equipment, and provider shortages, limiting the resources available for provision of surgical care. In response to mandates restricting surgery to high-acuity procedures during this period, our institution developed a multidisciplinary Low-Resource Operating Room (LROR) Taskforce in April 2020. This study describes our institutional experience developing an LROR to maintain access to urgent surgical procedures during the peak of the COVID-19 pandemic. Methods. A delineation of available resources and resource replacement strategies was conducted, and a final institution-wide plan for operationalizing the LROR was formed. Specialty-specific subgroups then convened to determine best practices and opportunities for LROR utilization. Orthopedic surgery performed in the LROR using wide-awake local anesthesia no tourniquet (WALANT) is presented as a use case. Results. Overall, 19 limited resources were identified, spanning across the domains of physical space, drugs, devices and equipment, and personnel. Based on the assessment, the decision to proceed with creation of an LROR was made. Sixteen urgent orthopedic surgeries were successfully performed using WALANT without conversion to general anesthesia. Conclusion. In response to the COVID-19 pandemic, a LROR was successfully designed and operationalized. The process for development of a LROR and recommended strategies for operating in a resource-constrained environment may serve as a model for other institutions and facilitate rapid implementation of this care model should the need arise in future pandemic or disaster situations.

Maintaining Access to Orthopaedic Surgery During Periods of Operating Room Resource Constraint: Expanded Use of Wide-Awake Surgery During the COVID-19 Pandemic.

INTRODUCTION: Wide-awake local anesthesia no tourniquet (WALANT) presents a nonstandard anesthetic approach initially described for use in hand surgery that has gained interest and utilization across a variety of orthopaedic procedures. In response to operating room resource constraints imposed by the COVID-19 pandemic, our orthopaedic service rapidly adopted and expanded its use of WALANT. METHODS: A retrospective review of 16 consecutive cases performed by 7 surgeons was conducted. Patient demographics, surgical details, and perioperative outcomes were assessed. The primary end point was WALANT failure, defined as intraoperative conversion to general anesthesia. RESULTS: No instances of WALANT failure requiring conversion to general anesthesia occurred. In recovery, one patient (6%) required narcotics for pain control, and the average postoperative pain numeric rating scale was 0.6. The maximum pain score experienced was 4 in the patient requiring postoperative narcotics. The average time in recovery was 42 minutes and ranged from 8 to 118 minutes. CONCLUSION: The WALANT technique was safely and effectively used in 16 cases across multiple orthopaedic subspecialties, including three procedures not previously described in the literature. WALANT techniques hold promise for use in future disaster scenarios and should be evaluated for potential incorporation into routine orthopaedic surgical care.

Semiconductor diode laser device adjuvanting intradermal vaccine.

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application. Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301nm light that costs less than $4000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic.

Laser vaccine adjuvants. History, progress, and potential.

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.