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Simon Tallowin, David N Naumann, Douglas M Bowley Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UKCorrespondence: Douglas M BowleyRoyal Centre for Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UKTel +44 7810 308 167Email dougbowley@nhs.netAbstract: Defence Healthcare Engagement (DHE) describes the use of military medical capabilities to achieve health effects overseas through enduring partnerships. It forms a key part of a wider strategy of Defence Engagement that utilises defence assets and activities, short of combat operations, to achieve influence. UK Defence Medical Services have significant recent DHE experience from conflict and stabilisation operations (e.g. Iraq and Afghanistan), health crises (e.g. Ebola epidemic in Sierra Leone), and as part of a long-term partnership with the Pakistan Armed Forces. Taking a historical perspective, this article describes the evolution of DHE from ad hoc rural health camps in the 1950s, to a modern integrated, multi-sector approach based on partnerships with local actors and close civil-military cooperation. It explores the evidence from recent UK experiences, highlighting the decisive contributions that military forces can make to healthcare leadership and quality of care overseas, particularly when conflict and health crisis outstrips the capacity of local healthcare providers to respond. Lessons identified include the need for long-term engagement with partners and the requirement for DHE activities to be closely coordinated with humanitarian agencies and local providers to prevent adverse effects on the local health economy and ensure a sustainable transition to civilian oversight.Keywords: military medicine, conflict, humanitarianism, coaching

Background: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes., Methods: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥ 24 h. Data from two different high-volume academic hospital centers were used, where all phenotypes were derived in MICU of Hospital-I (N = 3225). The derived phenotypes were validated in MICU of Hospital-II (N = 848), SICU of Hospital-I (N = 1112), and SICU of Hospital-II (N = 465). Clinical data from 24 h preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts., Results: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F = 123]), C (mild hypoxia [median P/F = 240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing the MICU of Hospital-II and SICUs from Hospital-I and -II. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p < 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy., Conclusion: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies., (© 2024. The Author(s).)

Objective: We investigated the potential of acute canagliflozin administration to mitigate acute kidney injury (AKI) and attenuate deleterious pro-inflammatory cytokine release in a clinically relevant swine model of severe renal ischemia reperfusion injury (IRI) induced by hemorrhage and aortic occlusion., Background: Long-term canagliflozin use attenuates renal function decline and reduces AKI in diabetes mellitus and heart failure patients. Whilst several reports indicate prophylactic SGLT2 inhibition prevents AKI in IRI, the efficacy of acute administration on IRI and inflammation is not known., Methods: Female swine (n=16) underwent controlled hemorrhage of 25% blood volume, followed by 90 min of aortic occlusion at the level of the renal ostia (via Resuscitative Endovascular Balloon Occlusion of the Aorta). A single 300 mg dose of oral canagliflozin or vehicle (saline) was delivered 5 mins into aortic occlusion. Hemodynamic monitoring, markers of renal function (serum creatinine, blood urea nitrogen, proteinuria and urinary neutrophil gelatinase-associated lipocalin) and serum cytokine concentrations (including interleukins: IL-1RA, IL-6, IL-8, IL-10, IL-18; and Tumor necrosis factor alpha) were analyzed after IRI, and during a 6h critical care phase., Results: Compared to controls, animals receiving canagliflozin had less severe AKI, improved creatinine clearance, reduced proteinuria, and significantly lower tubular damage as evidenced by histopathology and urinary NGAL. Furthermore, the pro-inflammatory cytokine IL-6 was markedly attenuated without reduction in anti-inflammatory cytokines (IL-1RA and IL-10)., Conclusions: A single dose of canagliflozin administered shortly into ischemic insult mitigates AKI and attenuates harmful pro-inflammatory cytokine release following trauma or surgery. These findings suggest a potential novel therapeutic role for canagliflozin in mitigating the effects of renal IRI worthy of further investigation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms., (© 2024. The Author(s).)

Introduction: Bariatric surgery has become one of the most rapidly growing subspecialty performed globally, and it has been well reported to be associated with low morbidity and mortality rates. Splenic abscess is a rare but serious complication of bariatric surgery that has not been previously systematically reviewed in the literature., Methods: The authors have performed a systematic review of the evidence that has looked into the pathophysiology, clinical presentation, and the management options of splenic abscess complicating bariatric surgery., Results: This systematic review has been unsurprisingly based on level-IV evidence due to the rarity of the explored condition. The final analysis included 27 relevant reported cases. The mean age was 38 years and the mean of the time interval between the initial operation and developing splenic abscess was 72 days, with the male to female ratio being 1:1.6. Laparoscopic sleeve gastrectomy was the initial operation in 85.2% of the patients. Nearly half of the patients did not have an objective evidence of local or systemic sepsis that could explain the abscess formation. Nonsurgical management was attempted in 14 patients, with 34% success rate only. Splenectomy was needed in 41.7% of the patients. No mortality was reported., Conclusions: Splenic abscess is a rare and rather late but serious complication of bariatric surgery that could result in splenectomy in a relatively young group of patients. It is more commonly reported following laparoscopic sleeve gastrectomy. Early diagnosis with intervention in a timely manner is crucial to avoid life threatening complications.

Introduction: The aim of this study was to assess the durability of superficial femoral artery (SFA) stents and factors that affect stent patency., Methods: A retrospective assessment of 214 SFA stent procedures between 2003 and 2012 was conducted from a prospectively compiled database. Patency rates and patient outcomes were compiled from case notes and computerized records. Stent patency was confirmed by either duplex scan or clinical examination (palpable distal pulse). Survival and patency were compared across a range of factors using Kaplan-Meier plots and log-rank tests. Factors found to be significant were further assessed by Cox regression models., Results: Data were analyzed for 214 limbs in 205 patients. Inclusion criteria included those patients who received an SFA stent for treatment of claudication or critical limb ischemia (CLI) with follow-up data. This gave a study group of 151 limbs divided into 76 claudicant and 75 patients with CLI (male-female ratio = 103:48, mean age 71 years, standard deviation 11.7). Seventy-one percent of procedures were elective and 29% were emergency procedures; 53% of procedures were carried out on a day case basis. Median follow-up was 11 months (range 1 day-89 months). Patency was significantly worse for patients with CLI (P = .009), with a 1- and 3-year patency of 63% and 34% compared to 79% and 60% in patients with claudication. Significant factors associated with patency included oral therapy controlled diabetes (P = .003), lesions located in either the mid-SFA (P = .029) or the mid-popliteal (P = .013), and periprocedural complications (P = .005). There was no significant difference in patency rates between insulin-dependent and nondiabetic patients (hazard ratio: 1.0, 95% confidence interval: 0.4-5.6, P = .983). The overall amputation rate for the total study group was 5%. Patients with 1- and 3-year survival were 98% and 96% in the claudication group and 74% and 51%, respectively, in the CLI group., Conclusion: SFA stents have superior outcomes in claudicants. Patency is related to severity of disease, diabetes, and location of disease., (© The Author(s) 2015.)