Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.

Update on Perioperative Medication Management for the Hand Surgeon: A Focus on Diabetes, Weight Loss, Rheumatologic, and Antithrombotic Medications.

Diabetes mellitus and obesity are growing health concerns. New pharmacologic interventions have recently begun to play a more notable role in the treatment pathway of these separate but related conditions. In particular, glucagon-like peptide-1 receptor agonists, such as semaglutides (Ozempic, Wegovy) and tirzepatide (Mounjaro), and sodium glucose co-transporter 2 inhibitors, such as dapagliflozin (Farxiga) and empagliflozin (Jardiance), have emerged as treatment options. Multiple clinical trials have demonstrated their efficacy in regulating metabolism, improving glycemic control, and managing long-term weight reduction. However, glucagon-like peptide-1 receptor agonists have also been associated with gastrointestinal side effects, including delayed gastric emptying as well as regurgitation and aspiration during general anesthesia or deep sedation, and sodium glucose co-transporter 2 inhibitors have been associated with severe diabetic ketoacidosis. Therefore, discontinuation of these medications before surgery is imperative. Given the popularity of these medications among the general public, it is essential for hand surgeons, to understand how to appropriately manage them perioperatively. The objective of this article was to review these new diabetes mellitus and weight loss medications, including their mechanisms of action, indications for use, and perioperative management guidelines. Additionally, we will take this opportunity to review perioperative guidelines for other common medications relevant to patients undergoing procedures involving the hand and upper extremity such as antithrombotic medications and rheumatoid arthritis-related immunosuppressive medications. Finally, we will describe how the electronic medical record system can be used to optimize perioperative medication management in this population.

Modeling the Lifetime Impact of Reconstructive Plastic Surgery Training: Implications for Building Capacity in Global Surgery.

Background: Training local surgeons and building local surgical capacity is critical to closing the gap in unmet surgical burden in low- and middle-income country (LMIC) settings. We propose a conceptual framework to quantify the impact of a single surgeon's training across multiple generations of trainees. Methods: A literature review was conducted to identify existing models for quantifying the impact of training. A model to estimate the attributable impact of surgical training was devised, based on a surgeon's attributable impact on a trainee and the lifetime number of cases trainees would perform. A quantitative survey was sent to high-income country and LMIC-based surgeons to determine the model's inputs across eight index procedures in reconstructive plastic surgery. Results: We found no existing models for quantifying the multigenerational impact of training in surgery, medicine, or nonmedical fields. Twenty-eight US-based academic plastic surgeons and 19 LMIC-based surgeons representing 10 countries provided responses. The lifetime impact of multigenerational surgical training ranged from 4100 attributable cases (skin graft) to 51,900 attributable cases (cleft lip repair) in high-income countries and from 18,200 attributable cases (carpal tunnel release) to 134,300 attributable cases (cleft lip repair) in LMICs. Conclusions: There is a sizeable impact in the first generation of training, and this impact is even greater in the second generation of training, highlighting the importance of a "multiplier effect," particularly in LMIC settings. Given the paucity of surgeons, this multiplier effect is critical in closing the surgical gap, as efforts are underway to train new cohorts of reconstructive plastic surgeons.

The Development and Validation of Data Elements and Process Steps for an Electronic Health Record for Hand Surgery Outreach Trips.

Background The surgical burden in low- and middle-income countries (LMICs) as reported by the number of surgical cases per capita is great. To improve global health and help address this burden, there has been a rise in surgical outreach to LMICs. In high-income countries, an electronic health record (EHR) is used to document and communicate data critical to the quality of care and patient safety. Despite this, there is little guidance or precedence on the data elements or processes for utilizing an EHR on outreach trips. We validated data elements and process steps for utilizing an EHR for hand surgery outreach trips. Methods We conducted a literature review to identify data elements collected during surgical outreach trips. A future-state process map for the collection and documentation of data elements within an EHR was developed through literature review and semistructured interviews with experts in global outreach. An expert consortium completed a modified RAND/University of California at Los Angeles Delphi process to evaluate the importance and feasibility of each data element and process step. Results In total, 65 data elements (e.g., date of birth) and 24 process steps (e.g., surgical site marking) were validated for use in an EHR for hand surgery outreach trips to LMICs. Conclusion This validated portfolio of data elements/process steps can serve as the foundation for pilot testing of an EHR to document and communicate critical patient data on hand surgery outreach trips. Utilization of an EHR during outreach trips to LMICs may serve to improve the safety and quality of care provided. The validated data elements/process steps can serve as a guide for EHR development and implementation of other surgical specialties.

A New Model of Global Reconstructive Surgery Training With Reduced Carbon Footprint of Outreach.

This economic evaluation compares carbon dioxide emissions from air transportation for surgical mission trips vs team training trips.