Social determinants of health, the microbiome, and surgical injury.

ABSTRACT: Post-injury infection continues to plague trauma and emergency surgery patients fortunate enough to survive the initial injury. Rapid response systems, massive transfusion protocols, the development of level 1 trauma centers, etc., have improved the outcome for millions of patients worldwide. Yet despite this excellent initial care, patients still remain vulnerable to post-injury infections that can result in organ failure, prolonged critical illness and even death. While risk factors have been identified (degree of injury, blood loss, time to definitive care, immunocompromise, etc.) they remain probabilistic, not deterministic, and do not explain outcome variability at the individual case level. Here, we assert that analysis of the social determinants of health, as reflected in the patient's microbiome composition (i.e. community structure, membership) and function (metabolomic output), may offer a "window" with which to define individual variability following traumatic injury. Given emerging knowledge in the field, a more comprehensive evaluation of biomarkers within the patient's microbiome, from stool-based microbial metabolites to those in plasma and those present in exhaled breath, when coupled with clinical metadata and machine learning, could lead to a more deterministic assessment of an individual's risk for a poor outcome and those factors that are modifiable. The aim of this piece is to examine how measurable elements of the social determinants of health and the life-history of the patient may be buried within the ecologic memory of the gut microbiome. Here we posit that interrogation of the gut microbiome in this manner may be used to inform novel approaches to drive recovery following a surgical injury.

IDEAL Phase 2a Results: Posterior Rectus Sheath Flap for Hiatal Augmentation in Complex Paraesophageal Hernias.

OBJECTIVE: To report the developmental phase results of posterior rectus sheath hiatal flap augmentation (PoRSHA), a promising surgical innovation for large and recurrent paraesophageal hernias. BACKGROUND: Durable hernia repair for large paraesophageal hernias continues to be a surgical challenge. PoRSHA addresses the challenges of current and historical approaches to complex paraesophageal hernias and demonstrates significant promise as a successful alternative approach. METHODS: Using the IDEAL framework, we outline the technical modifications made over the first 27 consecutive cases using PoRSHA. Outcomes measured included hernia recurrence on routine imaging at 6 months and 2 years, development of a postoperative abdominal wall eventration and incidence of solid food dysphagia. RESULTS: Twenty-seven patients at our single institution with type III (n=12), type IV (n=7), or recurrent (n=8) paraesophageal hernias underwent PoRSHA. Surgery was safely and successfully carried out in all cases. Stability of the technique was reached after 16 cases, resulting in 4 main repair types. At an average follow-up of 11 months, we observed no radiologic recurrences, no abdominal eventrations or hernias at the donor site, and 1 patient with occasional solid food dysphagia that resolved with dilation. CONCLUSIONS: PoRSHA can not only be safely added to conventional hiatal hernia repair with appropriate training but also demonstrates excellent short-term outcomes. While the long-term durability with 5-year follow-up is still needed, here we provide cautious optimism that PoRSHA may represent a novel solution to the long-standing high recurrence rates observed with current complex PEH repair.

Rationale behind phosphate therapy to modulate the gut microbiome and protect against surgery-related infection.

Despite major advances in infection control and the ever increasing use of broader spectrum antibiotics in surgery, postoperative infections continue to occur under the best of care and in the best institutions. Postoperative infections, also termed "surgical site infections (SSIs), can range from superficial wound infections to deep organ space infections. SSIs can be superficial and only require medical treatment (i.e antibiotics), whereas others such as deep organ space infections resulting from an anastomotic leak can require multiple surgeries leading to sepsis and occasionally shock and death. Many if not most stakeholders in the field including surgeons, infectious disease specialists, infection control nurses, etc., in general advocate the use of prophylactic antibiotics and the enforcement of greater levels of sterility reasoning that all postoperative infections must arise from some type of direct contamination event. In this piece, the alternative view is presented that today, in the era of mandated asepsis protocols, enhanced recovery programs, and enforcement of prophylactic antibiotics in all cases, many if not most postoperative infections and SSIs occur from pathogens endogenous to the patient not from sources exogenous to the patient. It is also suggested that applying broader antibiotic coverage in elective surgery is neither an evolutionarily stable strategy nor inexorable in the context of emerging knowledge in the field of gut ecology. Here this concept is reviewed and the rationale behind using agents that preserve the gut microbiome and attenuate pathogen virulence in lieu of applying broader spectrum antibiotics and greater levels of sterility.

Peptide YY: A Paneth cell antimicrobial peptide that maintains Candida gut commensalism.

The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility whereas others regulate the microbiota. We have found that peptide YY (PYY1-36), but not endocrine PYY3-36, acts as an antimicrobial peptide (AMP) expressed by gut epithelial paneth cells (PC). PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Although PC-PYY shows some antibacterial activity, it displays selective antifungal activity against virulent Candida albicans hyphae-but not the yeast form. PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming that selects for the yeast phenotype. Hence, PC-PYY is an antifungal AMP that contributes to the maintenance of gut fungal commensalism.

What Is the Role of the Gut in Wound Infections?

Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and silently travel to the wound site where they release their infectious payload. Genetic tracking of microbes at the strain level is now possible with genetic sequencing techniques and can clarify the origin of microbes that cause wound infections. An emerging field of dietary prehabilitation to modulate the microbiome before surgery is being described to improve infection-related outcomes from surgery.

Western Diet-induced Transcriptional Changes in Anastomotic Tissue Is Associated With Early Local Recurrence in a Mouse Model of Colorectal Surgery.

OBJECTIVE: To determine the timeframe and associated changes in the microenvironment that promote the development of a diet-induced local-regional recurrence in a mouse model of colorectal surgery. BACKGROUND: Postoperative recurrence and metastasis occur in up to 30% of patients undergoing attempted resection for colorectal cancer (CRC). The underlying mechanisms that drive the development of postoperative recurrences are poorly understood. Preclinical studies have demonstrated a diet and microbial-driven pathogenesis of local-regional recurrence, yet the precise mechanisms remain undefined. METHODS: BALB/C mice were fed a western diet (WD) or standard diet (SD), underwent a colon resection and anastomosis, given an Enterococcus faecalis enema on postoperative day (POD) 1, and subjected to a CT26 cancer cell enema (mimicking shed cancer cells) on POD2. Mice were sacrificed between POD3 and POD7 and cancer cell migration was tracked. Dynamic changes in gene expression of anastomotic tissue that were associated with cancer cell migration was assessed. RESULTS: Tumor cells were identified in mice fed either a SD or WD in both anastomotic and lymphatic tissue as early as on POD3. Histology demonstrated that these tumor cells were viable and replicating. In WD-fed mice, the number of tumor cells increased over the early perioperative period and was significantly higher than in mice fed a SD. Microarray analysis of anastomotic tissue found that WD-fed mice had 11 dysregulated genes associated with tumorigenesis. CONCLUSIONS: A WD promotes cancer cells to permeate a healing anastomosis and migrate into anastomotic and lymphatic tissue forming viable tumor nodules. These data offer a novel recurrence pathogenesis by which the intestinal microenvironment promotes a CRC local-regional recurrence.

The role of dietary prehabilitation on anastomotic healing.

PURPOSE OF REVIEW: As the microbiome takes center stage in biomedical research and emerging medical treatments, here we review the scientific basis and role of dietary modulation to prevent anastomotic leakage. RECENT FINDINGS: It is becoming increasingly clear that dietary habits have a profound influence on an individual's microbiome and that the microbiome plays a key and causative role in anastomotic leak etiology and pathogenesis. A review of recent studies indicates that the gut microbiome can become significantly shifted in composition, community structure and function within an extremely short time period of 2 or 3 days simply by changing one's diet. SUMMARY: From a practical standpoint to improve outcome from surgery, these observations, when paired with next generation technology, suggest that it is now possible to manipulate the microbiome of surgical patients to their advantage prior to surgery. This approach will allow surgeons to modulate the gut microbiome with the endpoint of improving the outcome from surgery. Thus a new emerging field termed 'dietary prehabilitation' is now gaining popularity and similar to smoking cessation, weight loss and exercise, may be a practical method to prevent postoperative complications including anastomotic leak.

Rationale for Colonic Pre-Habilitation Prior to Restoration of Gastrointestinal Continuity.

The emergence of the gut microbiome as a complex ecosystem that plays a key role in human heath and disease has touched virtually every aspect of medical and surgical care. With the advent of next-generation technology to interrogate the microbiome at the level of its membership, community structure and production of metabolites, applying measures by which the gut microbiome can be manipulated to the advantage of both the patient and provider is now possible. Among the many proposed methods, the most practical and promising is dietary pre-habilitation of the gut microbiome prior to high-risk anastomotic surgery. In this review, we will outline the scientific rationale and molecular underpinning that support dietary pre-habilitation as a practical and deliverable method to prevent complications after high-risk anastomotic surgery.

The Role of the Gut Microbiome on the Development of Surgical Site Infections.

Despite advances in antisepsis techniques, surgical site infection remains the most common and most costly reason for hospital readmission after surgery. Wound infections are conventionally thought to be directly caused by wound contamination. However, despite strict adherence to surgical site infection prevention techniques and bundles, these infections continue to occur at high rates. The contaminant theory of surgical site infection fails to predict and explain most postoperative infections and still remains unproven. In this article we provide evidence that the process of surgical site infection development is far more complex than what can be explained by simple bacterial contamination and hosts' ability to clear the contaminating pathogen. We show a link between the intestinal microbiome and distant surgical site infections, even in the absence of intestinal barrier breach. We discuss the Trojan-horse mechanisms by which surgical wounds may become seeded by pathogens from within one's own body and the contingencies that need to be met for an infection to develop.

Biologically inspired gastrointestinal stapler design: "Getting to Zero" complications.

As next generation stapling devices enter the marketplace with robotic adaptations, tri-staple technology, preloaded reinforcement materials, etc., in this perspective piece we assert that a "refresh" in our understanding of the mechanisms of action of these devices is needed. While much attention has been paid to explain the mechanical features of one device versus another, it seems that little to no attention is being paid to understand how an intestinal anastomosis responds biologically to the variations in their use and design. Here we will review various aspects of gastrointestinal stapling in the context of emerging technology in the field and expose the gaps in knowledge that exist regarding the effect of gastrointestinal stapling on the biology of healing.

To Operate or Not? Balancing Advanced Imaging, Machine Learning, and the Doctor-Patient Relationship in Complex Clinical Decision Making.

Advances in high-resolution, cross-sectional imaging have changed the practice of medicine. These innovations have clearly benefited patient care yet have also led to a decreased dependence on the art of medicine, with its emphasis on obtaining a thoughtful history and thorough physical examination to elicit the same diagnosis that imaging provides. What remains to be determined is how physicians can balance these technological advances with their own ability to use clinical experience and judgment. This can be seen not only with the use of high-level imaging but also with the increasing use of machine-learning models throughout medicine. The authors contend that these should be seen not as a replacement for the physician, but as another tool in their arsenal in determining management decisions. These issues are salient for surgeons, who, given the serious undertaking required to operate on a person, must develop trust-based relationship with their patients. Navigating this new field brings with it several ethical conundrums that must be addressed, with the final goal being to provide optimal patient care without sacrificing the human element involved, from either the physician or the patient. The authors examine these less-than-simple challenges, which will continue to develop as physicians use the increasing amount of machine-based knowledge available to them.

Defeating Cancel Culture in Surgical Site Infection Research: A Plea to Include Microbial Cultures and Antibiotic Sensitivity Data.

Background: Despite advances in infection control measures, surgical site infections (SSIs) remain a real and present danger to patients. In most studies addressing SSI prevention measures, recommendations are often made in the absence of information such as culture results, the antibiotic agents used for prophylaxis, and antibiotic sensitivity data. The aim of this study is to document this latter claim by reviewing studies published in the last five years in highly read and cited surgical journals. Methods: A systematic review evaluating SSIs from four highly cited surgical journals, Annals of Surgery, the British Journal of Surgery, JAMA Surgery, and the Journal of the American College of Surgeons was conducted for articles published between 2016 and 2021. We focused our analysis on the following key features: how SSI is defined; bacterial culture information; antibiotic sensitivity data; and identification of the antibiotic chosen for prophylaxis. We hypothesized that, in most cases among the journals queried, this information would be unavailable. Results: Of the 71 studies included, 32 diagnosed SSIs based on criteria developed by the U.S. Centers for Disease Control and Prevention while five provided no definition of SSI. Of the 27 articles recommending increasing antibiotic usage, only one study performed antibiotic sensitivity testing to guide the antibiotic choice. Of 71 studies reviewed, only one reported all key features we considered to be important for SSI antibiotic decision-making; 46 reported none of the key features. Conclusions: Among publications addressing SSIs in four highly cited surgical journals, key information regarding diagnosis and with which to base antibiotic recommendations, is routinely unavailable.