Crush injury with significant soft tissue loss managed utilising biological and dynamic tissue systems: a case study.

Major traumatic crush injuries are difficult to manage, with high morbidity, requiring prolonged, complex treatment with many procedures. Free-flap reconstruction is often used yet full functionality still may not be regained. In this case study of a traumatic crush injury of the anterior distal tibia, ankle and foot of a 48-year-old male patient, we opted for an alternative management strategy using a combination of a dynamic tissue system (DTS) and biological xenografts (porcine urinary bladder matrix and a multi-tissue platform). The DTS was kept in place in an outpatient setting for four weeks postoperatively and removed after that time. At the 3-month follow-up, the wound was significantly smaller at about 15% of the original size. The wound healed completely before 6-month follow-up. Our patient's traumatic crush injury was successfully healed using an alternative management strategy, DTS and biologic xenografts.

IL-10 Signaling Elicited by Nivolumab-Induced Activation of the MAP Kinase Pathway Does Not Fully Contribute to Nivolumab-Modulated Heterogeneous T Cell Responses.

Immune checkpoint inhibitor (ICI) therapy has revolutionized anti-cancer treatment for many late-stage cancer patients. However, ICI therapy has thus far demonstrated limited efficacy for most patients, and it remains unclear why this is so. Interleukin 10 (IL-10) is a cytokine that has been recognized as a central player in cancer biology with its ability to inhibit anti-tumor T cell responses. Recent studies suggest that IL-10 might also exert some intrinsic anti-tumor T cell responses, and clinical studies using recombinant IL-10 alone or in combination with ICI are underway. This paradoxical effect of IL-10 and its underlying mechanisms impacting ICI-modulated T cell responses remain poorly understood. In this study, using an in vitro mixed lymphocyte reaction assay, we found that treatment with ICIs such as the anti-programmed cell death receptor-1 (PD-1) mAb nivolumab elicits a strong expression of IL-10. While neutralization of IL-10 signaling with an anti-IL-10 specific mAb significantly decreases the production of IFN-γ by T cells in a cohort of donor cells, the opposite effect was observed in other donor cells. Similarly, neutralization of IL-10 signaling significantly decreases the expression of T cell activation markers Ki67 and CD25, as well as the production of Granzyme B in a cohort of donor cells, whereas the opposite effect was observed in others. Furthermore, we found that nivolumab and IL-10 differentially modulate the signal transducer and activator of transcription 3 (STAT3) and AKT serine-threonine kinase pathways. Finally, we found that nivolumab activates the mitogen-activated protein kinase (MAPK) pathway, which in turn is responsible for the observed induction of IL-10 production by nivolumab. These findings provide new insights into the mechanisms underlying anti-PD-1-modulated T cell responses by IL-10, which could lead to the discovery of novel combination treatments that target IL-10 and immune checkpoint molecules.

The Role of Hypoxia and Hypoxia Signaling in Skeletal Muscle Physiology.

Hypoxia and hypoxia signaling play an integral role in regulating skeletal muscle physiology. Environmental hypoxia and tissue hypoxia in muscles cue for their appropriate physiological response and adaptation, and cause an array of cellular and metabolic changes. In addition, muscle stem cells (satellite cells), exist in a hypoxic state, and this intrinsic hypoxic state correlates with their quiescence and stemness. The mechanisms of hypoxia-mediated regulation of satellite cells and myogenesis are yet to be characterized, and their seemingly contradicting effects reported leave their exact roles somewhat perplexing. This review summarizes the recent findings on the effect of hypoxia and hypoxia signaling on the key aspects of muscle physiology, namely, stem cell maintenance and myogenesis with a particular attention given to distinguish the intrinsic versus local hypoxia in an attempt to better understand their respective regulatory roles and how their relationship affects the overall response. This review further describes their mechanistic links and their possible implications on the relevant pathologies and therapeutics.

Current Applications of Artificial Intelligence in Billing Practices and Clinical Plastic Surgery.

Integration of artificial intelligence (AI), specifically with natural language processing and machine learning, holds tremendous potential to enhance both clinical practices and administrative workflows within plastic surgery. AI has been applied to various aspects of patient care in plastic surgery, including postoperative free flap monitoring, evaluating preoperative risk assessments, and analyzing clinical documentation. Previous studies have demonstrated the ability to interpret current procedural terminology codes from clinical documentation using natural language processing. Various automated medical billing companies have used AI to improve the revenue management cycle at hospitals nationwide. Additionally, AI has been piloted by insurance companies to streamline the prior authorization process. AI implementation holds potential to enhance billing practices and maximize healthcare revenue for practicing physicians.

Laparoscopic management of combined cholecystogastric and cholecystocolonic fistulae.

Cholecystogastric and cholecystocolonic fistulae are rare sequelae of longstanding cholelithiasis and can complicate surgical management. Our case involves a male patient in his early 40s with a history of chronic cholelithiasis who presented to the emergency department with severe abdominal pain. Findings on imaging were consistent with acute calculous cholecystitis. During laparoscopic cholecystectomy, the presence of both cholecystogastric and cholecystocolonic fistulae was discovered. Fistula resection with cholecystectomy in a one-step approach using indocyanine green (ICG) angiography was performed. The patient improved and was discharged 3 days later. Laparoscopic management complemented by ICG angiography is a viable surgical approach in patients with cholecystogastric and cholecystocolonic fistulae.

Acellular collagen-glycosaminoglycan matrix promotes functional recovery in a rat model of volumetric muscle loss.

Aim: Volumetric muscle loss (VML) is a composite loss of skeletal muscle, which heals with fibrosis, minimal muscle regeneration, and incomplete functional recovery. This study investigated whether collagen-glycosaminoglycan scaffolds (CGS) improve functional recovery following VML. Methods: 15 Sprague-Dawley rats underwent either sham injury or bilateral tibialis anterior (TA) VML injury, with or without CGS implantation. Results: In rats with VML injuries treated with CGS, the TA exhibited greater in vivo tetanic forces and in situ twitch and tetanic dorsiflexion forces compared with those in the non-CGS group at 4- and 6-weeks following injury, respectively. Histologically, the VML with CGS group demonstrated reduced fibrosis and increased muscle regeneration. Conclusion: Taken together, CGS implantation has potential augment muscle recovery following VML.

Volumetric muscle loss (VML) is a large injury to skeletal muscle. VML heals with scarring, little muscle regeneration, and incomplete strength recovery. The current treatment for VML involves transferring muscle from one part of the body to the injury site. However, this is limited by weakness of the donor site and incomplete recovery of muscle function. Therefore, other treatments have been developed to aid in muscle healing. One such treatment involves using three dimensional templates, known as scaffolds, to aid in muscle regeneration. Our goal is to determine whether a collagen­glycosaminoglycan scaffold (CGS), which is already used for other medical purposes, can improve healing of VML injuries in rats. CGS placement in rat muscle injuries resulted in decreased scarring, increased muscle regeneration, and increased strength recovery compared with the non-CGS group.

VEGFA Promotes Skeletal Muscle Regeneration in Aging.

Aging is associated with loss of skeletal muscle regeneration. Differentially regulated vascular endothelial growth factor (VEGF)A with aging may partially underlies this loss of regenerative capacity. To assess the role of VEGFA in muscle regeneration, young (12-14 weeks old) and old C57BL/6 mice (24,25 months old) are subjected to cryoinjury in the tibialis anterior (TA) muscle to induce muscle regeneration. The average cross-sectional area (CSA) of regenerating myofibers is 33% smaller in old as compared to young (p < 0.01) mice, which correlates with a two-fold loss of muscle VEGFA protein levels (p = 0.02). The capillary density in the TA is similar between the two groups. Young VEGFlo mice, with a 50% decrease in systemic VEGFA activity, exhibit a two-fold reduction in the average regenerating fiber CSA following cryoinjury (p < 0.01) in comparison to littermate controls. ML228, a hypoxia signaling activator known to increase VEGFA levels, augments muscle VEGFA levels and increases average CSA of regenerating fibers in both old mice (25% increase, p < 0.01) and VEGFlo (20% increase, p < 0.01) mice, but not in young or littermate controls. These results suggest that VEGFA may be a therapeutic target in age-related muscle loss.

Vitamin A-Induced Hypercalcemia in Burn Patients: A Case Study.

Vitamin and steroid supplementation such as oxandrolone are commonly given to speed the recovery process in severe burn injuries. Vitamin A is administered concurrently with steroids because of its pro-inflammatory and positive effects on wound healing. However, vitamin A supplementation warrants caution as hypercalcemia can result from vitamin A overdose. Our case involves an 18-year-old male injured in an oil field explosion who presented with 55% total body surface area (TBSA) partial- and full-thickness burns. Following successful resuscitation, he was given vitamin A, oxandrolone, vitamin C, and zinc sulfate as part of the standard vitamin supplementation. On hospital day (HD) 33, serum calcium levels were noted to be elevated and increased to 13 mg/dL a few days later. Parathyroid hormone and vitamin D levels were found to be within normal range, and urine analysis showed normal calcium excretion. Subsequent assessment of vitamin A levels revealed significantly elevated levels at 93 mcg/dL. Vitamin A supplementation was discontinued, and the patient was discharged on HD 42. At the 1-month follow-up, serum calcium levels were normal, which links the hypercalcemia to vitamin A overdose. This case highlights the importance of considering vitamin A overdose as a cause for asymptomatic hypercalcemia with a normal parathyroid and vitamin D workup. While routine, vitamin A supplementation in burn patients calls for assessment of both serum calcium and vitamin A levels throughout the hospital stay to prevent hypercalcemia and its negative effects.

Two surgeons' collaboration to close an extreme open abdomen with loss of domain utilizing the abdominal dynamic tissue system and porcine urinary bladder matrix.

Acute open abdomen with loss of domain is an extremely difficult surgical scenario, and secondary complications are common. This case describes a 33-year-old woman who initially underwent an elective, laparoscopic endometrioma resection during which a complete iatrogenic transection of the left ureter and part of the sigmoid mesentery occurred. After discharge 5 days later, she was immediately readmitted for worsening abdominal pain. During the emergency abdominal reexploration, an ischemic, perforated sigmoid colon was removed and large volume paracentesis was performed due to fecal contamination. Nine additional reexplorations over 2 months resulted in an extreme acute open abdomen with loss of domain. Viscera was protected with negative pressure wound therapy, but primary myofascial closure was not feasible. Through surgical collaboration between two institutions, an abdominal dynamic tissue system was installed, which achieved primary myofascial closure 31 days after installation. Nine days later, complete wound closure utilizing porcine urinary bladder matrix was accomplished. This case highlights the successful achievement of primary myofascial closure and complete wound healing without a surgical site infection or hernia development in this heavily contaminated abdomen using dynamic tissue system biomechanics with porcine urinary bladder matrix biologics.

Alternative management of delayed spontaneous oesophageal perforation by endoscopic stenting.

Boerhaave's syndrome or spontaneous perforation of the oesophagus is a life-threatening condition that carries high mortality. Delayed diagnosis has a mortality rate of 20%-50%. While surgical intervention has been the mainstay of treatment, advancements in endoscopy and oesophageal stenting have allowed for alternative management. Our case involves a 33-year-old man with self-induced emesis and DKA. After 10 days in the ICU, he developed a large right pleural effusion, which was treated with chest tube placement. Upper GI study confirmed delayed Boerhaave's syndrome. A self-expanding stent was inserted followed by percutaneous endoscopic gastrostomy (PEG) for decompression and jejunal extension for nutrition. He developed empyema and underwent right thoracotomy for washout and lung decortication. Stent was exchanged once due to recurrent leak following migration and removed after 40 days. Endoscopic stent placement with PEG with jejunal extension followed by thoracotomy is a viable alternative to primary repair of delayed oesophageal perforation.