What is slough? Defining the proteomic and microbial composition of slough and its implications for wound healing.

Slough is a well-known feature of non-healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with slow-to-heal wounds and visible slough were enrolled. Aetiologies included venous stasis ulcers, post-surgical site infections and pressure ulcers. Patient co-morbidities and wound healing outcome at 3-months post-sample collection was recorded. Debrided slough was analysed microscopically, through untargeted proteomics, and high-throughput bacterial 16S-ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S-profiling found slough microbial communities to associate with wound aetiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood-clot formation and immune processes. To predict variables associated with wound healing, protein, microbial and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates-Jensen Wound Assessment Score and were enriched for anaerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterise wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilised biomarker.

Does an early, balanced resuscitation strategy reduce the incidence of hypofibrinogenemia in hemorrhagic shock?

Objectives: Some centers have recommended including concentrated fibrinogen replacement in massive transfusion protocols (MTPs). Given our center's policy of aggressive early balanced resuscitation (1:1:1), beginning prehospital, we hypothesized that our rates of hypofibrinogenemia may be lower than those previously reported. Methods: In this retrospective cohort study, patients presenting to our trauma center November 2017 to April 2021 were reviewed. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen <150 or rapid thrombelastography angle <60. Univariate and multivariable analyses assessed risk factors for HYPOFIB. Inverse probability of treatment weighting analyses assessed the relationship between cryoprecipitate administration and outcomes. Results: Of 29 782 patients, 6618 level 1 activations, and 1948 patients receiving emergency release blood, <1%, 2%, and 7% were HYPOFIB. HYPOFIB patients were younger, had higher head Abbreviated Injury Scale value, and had worse coagulopathy and shock. HYPOFIB had lower survival (48% vs 82%, p<0.001), shorter time to death (median 28 (7, 50) vs 36 (14, 140) hours, p=0.012), and were more likely to die from head injury (72% vs 51%, p<0.001). Risk factors for HYPOFIB included increased age (OR (95% CI) 0.98 (0.96 to 0.99), p=0.03), head injury severity (OR 1.24 (1.06 to 1.46), p=0.009), lower arrival pH (OR 0.01 (0.001 to 0.20), p=0.002), and elevated prehospital red blood cell to platelet ratio (OR 1.20 (1.02 to 1.41), p=0.03). Among HYPOFIB patients, there was no difference in survival for those that received early cryoprecipitate (within 2 hours; 40 vs 47%; p=0.630). On inverse probability of treatment weighted analysis, early cryoprecipitate did not benefit the full cohort (OR 0.52 (0.43 to 0.65), p<0.001), nor the HYPOFIB subgroup (0.28 (0.20 to 0.39), p<0.001). Conclusions: Low rates of hypofibrinogenemia were found in our center which treats hemorrhage with early, balanced resuscitation. Previously reported higher rates may be partially due to unbalanced resuscitation and/or delay in resuscitation initiation. Routine empiric inclusion of concentrated fibrinogen replacement in MTPs is not supported by the currently available data. Level of evidence: Level III.

Applications of blood plasma derivatives for cutaneous wound healing: A mini-review of clinical studies.

Skin injuries are a global healthcare problem. Chronic ulcers do not heal in a timely fashion, so it is essential to help the body with skin repair. There are some treatments that have been applied to chronic ulcers. One of these treatments is growth factor (GF) therapy. Platelet-rich plasma (PRP) and Platelet-poor plasma (PPP) are two types of plasma derivatives containing many GFs important for wound healing. Several works have reported their application in wound healing and tissue regeneration. The use of autologous PRP is now an adequate alternative in regenerative medicine. It was also demonstrated that PPP is a hemostatic agent for wounds. This review has studied the latest clinical studies, which have applied PRP and PPP to patients with chronic wounds.

Impact of comorbidities in severely injured patients with blunt chest injury: A population-based retrospective cohort study.

INTRODUCTION: Blunt chest injuries result in up to 10 % of major trauma admissions. Comorbidities can complicate recovery and increase the mortality rate in this patient cohort. A better understanding of the association between comorbidities and patient outcomes will facilitate enhanced models of care for particularly vulnerable groups of patients, such as older adults. AIMS: i) compare the characteristics of severely injured patients with blunt chest injury with and without comorbidities and ii) examine the relationship between comorbidities and key patient outcomes: prolonged length of stay, re-admission within 28 days, and mortality within 30 days in a cohort of patients with blunt chest injury admitted after severe trauma. METHODS: A retrospective cohort study using linked data from the NSW Trauma Registry and NSW mortality and hospitalisation records between 1st of January 2012 and 31st of December 2019. RESULTS: After adjusting for potential confounding factors, patients with severe injuries, chest injuries, and comorbidities were found to have a 34 % increased likelihood of having a prolonged length of stay (OR = 1.34, 95 %I = 1.17-1.53) compared to patients with no comorbidities. There was no difference in 30-day mortality for patients with a severe chest injury who did or did not have comorbidities (OR = 1.05, 95 %CI = 0.80-1.39). No significant association was found between comorbidities and re-admission within 28 days. CONCLUSION: Severely injured patients with blunt chest injury and comorbidities are at risk of prolonged length of stay.

Microneedle System with Biomarker-Activatable Chromophore as Both Optical Imaging Probe and Anti-bacterial Agent for Combination Therapy of Bacterial-Infected Wounds and Outcome Monitoring.

Wounds infected with bacteria, if left untreated, have the potential to escalate into life-threatening conditions, such as sepsis, which is characterized by widespread inflammation and organ damage. A comprehensive approach to treating bacterial-infected wounds, encompassing the control of bacterial infection, biofilm eradication, and inflammation regulation, holds significant importance. Herein, a microneedle (MN) patch (FM@ST MN) has been developed, with silk fibroin (SF) and tannic acid-based hydrogel serving as the matrix. Encapsulated within the MNs are the AIEgen-based activatable probe (FQ-H2O2) and the NLRP3 inhibitor MCC950, serving as the optical reporter/antibacterial agent and the inflammation regulator, respectively. When applied onto bacterial-infected wounds, the MNs in FM@ST MN penetrate bacterial biofilms and gradually degrade, releasing FQ-H2O2 and MCC950. The released FQ-H2O2 responds to endogenously overexpressed reactive oxygen species (H2O2) at the wound site, generating a chromophore FQ-OH which emits noticeable NIR-II fluorescence and optoacoustic signals, enabling real-time imaging for outcome monitoring; and this chromophore also exhibits potent antibacterial capability due to its dual positive charges and shows negligible antibacterial resistance. However, the NLRP3 inhibitor MCC950, upon release, suppresses the activation of NLRP3 inflammasomes, thereby mitigating the inflammation triggered by bacterial infections and facilitating wound healing. Furthermore, SF in FM@ST MN aids in tissue repair and regeneration by promoting the proliferation of epidermal cells and fibroblasts and collagen synthesis. This MN system, free from antibiotics, holds promise as a solution for treating and monitoring bacterially infected wounds without the associated risk of antimicrobial resistance.

Sodium alginate/carboxycellulose/polydopamine composite microspheres for rapid hemostasis of deep irregular wounds.

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.

Synergetic effects of sericin and turmeric on burn wound healing in mice.

Burn wounds are one of the most hazardous issues globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice of 2 months of age (each weighing 29-30 g) were arbitrarily distributed in seven groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of Glutathione (4.9±0.1umol/L), Catalase (6.0±0.2mmol/ml), Glutathione Peroxidase (183.4±5.1U/L), Superoxide dismutase (194.6±5.1 U/ml) were significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8±0.1umol/L, 3.5±0.1mmol/ml, 87.8±3.0U/L, and 92.0±4.8U/ml respectively). The minimum levels of Malondialdehyde (3.8±0.2mmol/L) were noticed in TNPs group contrary to the negative control (7.4±0.2mmol/L). The restoration of the epidermis was also observed to be faster in TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups.

Large Penetrating Wounds to the Chest Managed With Immediate Chest Wall Reconstruction Using Biologic Mesh, Titanium Plates, and Rotational Tissue Flaps.

Large open chest wall wounds can be difficult to manage due to full-thickness tissue loss with underlying rib fractures and exposed lung parenchyma. Historically, the use of synthetic material has been discouraged in the traumatic setting with the concern that it may be associated with an increased risk of infection. We present 4 patients with large open injuries to the thorax-one from blunt and three from penetrating trauma. We describe our initial management followed by prompt surgical repair using biologic mesh, titanium rib spanning plates, and rotational tissue flaps with Z-plasty of the skin for definite closure. All patients did well post-operatively without complications or wound infections. With the appropriate management, we suspect there may be an advantage in performing immediate reconstruction and closure in large open thoracic injuries utilizing biologic mesh and titanium rib spanning plates with a lower risk of infection than previously believed.

Neuroimmunomodulatory Effect of NO on Chronic Wound Healing After Photodynamic Therapy.

Neuroimmunomodulation is the capacity of the nervous system to regulate immune processes. The existence of neurotransmitter receptors in immune cells enables this phenomenon to take place. Neuronal mediators possess the capacity to direct and control several occurrences during the wound healing process. Nitric oxide (NO) functions as a neuromodulator, playing a crucial role in the regulation of vascular tone and blood pressure with antimicrobial properties. Photodynamic therapy has been shown to augment the function of immune cells involved in the healing process of venous leg ulcers. Nitric oxide can be secreted into the extracellular environment by these cells. In lesions treated with PDT, the synthesis of iNOs (the enzyme that releases NO) increased, as demonstrated by the experimental results. Therefore the significance of PDT in enhancing the clinical condition of the lesion is thus highlighted.

Role of Bovine Colostrum Dressing on Chronic Non-Healing Wounds in Comparison to Conventional Dressing: A Case-Control Study.

Colostrum has been shown to be suitable for oral and/or topical applications. Colostrum decreases the amount of discharge from wounds and also accelerates healing, leading to a decrease in the number of dressings. In this study, 40 patients with chronic non-healing wounds were divided into two groups, considering the inclusion and exclusion criteria. Group I included 15 patients with conventional dressings, and Group II included 25 patients with added topical colostrum dressings. All patients were assessed at the time of presentation and after 21 days. The results of the present study indicate that colostrum powder dressings may be used as an adjunct in the management of chronic non-healing wounds.

Efficacy of Hyaluronic Acid/Collagenase Ointment in the Treatment of Chronic Wounds: A Retrospective Observational Study.

BACKGROUND: Chronic wounds, including diabetic ulcers, posttraumatic ulcers, and pressure sores, present a significant challenge in healthcare due to their complex nature and resistance to conventional treatments. This retrospective observational study aimed to evaluate the efficacy of an ointment containing hyaluronic acid and collagenase in treating such wounds. METHODS: The study included 70 patients with various chronic wounds treated in our clinic from January 1, 2020, to October 1, 2023. The patients were selected according to specific inclusion and exclusion criteria, and comprehensive baseline data was collected. The treatment involved the application of a hyaluronic acid and collagenase ointment, followed by regular follow-up and data analysis. RESULTS: Significant improvements in wound bed scores (WBS) were observed, with a reduction in healing times for all types of wounds. High patient satisfaction rates were reported, along with efficient debridement and notable pain reduction. Diabetic ulcers showed the most significant improvement in terms of healing time and WBS. CONCLUSIONS: Hyaluronic acid and collagenase ointment demonstrated promising results in the treatment of chronic wounds. This treatment may offer a valuable addition to current wound care practices, particularly in challenging cases such as diabetic ulcers. More research is recommended, including randomized controlled trials, to validate these findings.

Transcutaneous oximetry values in chronic ulcer patients during Hyperbaric treatment at 1.4 ATA compared to 2 ATA.

Chronic wounds have a significant impact on a patient's quality of life. Different pathologies, such as poor blood supply and tissue breakdown, may lead to inadequate oxygenation of the wound. Hyperbaric oxygen (HBO2) is a widely used treatment for an increasing number of medical practices. A new so-called "hyperbaric treatment" trend has emerged. The use of low-pressure, soft-sided, or inflatable chambers represents a growing trend in hyperbaric medicine. Used in professional settings as well as directly marketed to individuals for home use, they are promoted as equivalent to clinical hyperbaric treatments provided in medical centers. However, these chambers are pressurized to 1.3 atmospheres absolute (ATA) on either air or with an oxygen concentrator, both generate oxygen partial pressures well below those used in approved hyperbaric centers for UHMS-approved indications. A total of 130 consecutive patients with chronic ulcers where tested. TcPO2 was measured near the ulcer area while the patient was breathing 100% O2 at 1.4 ATA for five and 10 minutes. The average TcPO2 at 1.4 ATA after 10 minutes of O2 breathing was 161 mmHg (1-601 mmHg, standard deviation 137.91), compared to 333 mmHg in 2 ATA (1-914±232.56), p < 0.001. Each electrode tested was also statistically significant, both after five minutes of O2 breathing and after 10 minutes. We have not found evidence supporting the claim that 1.4 ATA treatment can benefit a chronic ulcer patient. The field of HBO2 is constantly evolving. We have discovered new ways to treat previously incurable ailments. Nevertheless, it is important to note that new horizons must be examined scientifically, supported by evidence-based data. The actual effect of 1.4 ATA on many ailments is yet to be determined.

Substrate stiffness regulates type II diabetic fibroblast phenotype and metabolic activity.

In people living with diabetes, impaired wound healing is a major concern as the formation of ulcerated wounds can drastically reduce both the effectiveness of the healing process and the quality of life of the patient. The healing of dermal wounds in particular involves a patient's fibroblasts building up a strong extracellular matrix of mostly collagen I and collagen III fibers, which the cells of diabetic patients struggle to do. Extracellular matrix stiffness, and growth substrate stiffness in general, have already been shown to have a significant effect on the growth and development of already existent cells, and in diabetic dermal fibroblasts, morphological and physiological characteristics associated with the healing process appear to be altered from their healthy state. In this study we utilized a PDMS surface with a stiffness comparable to a wound environment (16 kPa) and a softer surface (0.2 kPa) to study the effects on diabetic and normal fibroblasts. We found diabetic fibroblast morphology became more fibroblast like when placed on the softer surfaces. This was demonstrated by a 15.6% decrease in the aspect ratio and a 16.4% increase in the circularity. The presence of the stress fibers was decreased by 19.4% in diabetic fibroblasts when placed on a softer surface. The proliferation rate of the diabetic fibroblasts was unaffected by the change in stiffness, but the metabolic activity greatly decreased (76%) on the softer surface. The results suggest that the softer surface may have a therapeutic effect on diabetic fibroblast metabolic activity. Further studies could focus on investigating this relationship and utilize it in tunable biomaterials to facilitate and accelerate the healing process for diabetic wounds.

Low-level photodynamic therapy in chronic wounds.

BACKGROUND: Chronic wounds refer to those that can't reconstruct anatomical and physical functional integrity, and are usually associated with signs of microbial infection. Current therapies include debridement and dressing change, local or systemic application of antibiotics, and medical dressing care, which are not ideal for the healing of chronic wounds. OBJECTIVE: To explore the efficacy and safety of photodynamic therapy (ALA-PDT) for the treatment of chronic infectious wounds. MATERIALS AND METHODS: ALA-PDT was used in ten patients with persistent wound infections and systemic complications who did not respond to conventional treatment. 5 % ALA solution was applied to the wound surface after debridement, incubated for 3 h with light protection, and then irradiated with red light for 20 min. This procedure was repeated every two weeks, and any adverse reactions were recorded. After the end of three treatments, the patients were followed up for 3 months. RESULTS: Patients who exhibit resistance to traditional therapies demonstrate a favorable therapeutic outcome with ALA-PDT, although complications may impede wound healing. All participants successfully underwent ALA-PDT treatment and subsequent monitoring, with 90 % achieving complete healing. Common adverse reactions to ALA-PDT encompass treatment-related pain, temporary erythema, and swelling, all of which are well-tolerated by patients without enduring severe consequences. CONCLUSIONS: ALA-PDT proves to be an efficacious intervention for managing chronic wounds, irrespective of the presence of localized infections or systemic complications.

The role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammation index in predicting the necessity for surgery and therapeutic surgery in patients with anterior abdominal stab wounds.

BACKGROUND: In this diagnostic accuracy study, we examined the effectiveness of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) in predicting the need for surgical intervention in patients with anterior abdominal stab wounds (AASW) who exhibit unclear findings on physical examination yet remain hemodynamically stable. METHODS: Over a 7-year period, patients with AASW were retrospectively analyzed. Patients were divided into two groups as surgical (SG) and nonsurgical group (nSG). The SG were also divided into two groups as therapeutic surgery (TS) group and the non-therapeutic surgery (nTS) group. The groups were compared in terms of NLR, PLR values and SII scores. RESULTS: In a retrospective analysis of 199 patients with AASW, NLR, PLR and SII obtained during clinical follow-up of patients with AASW in whom the necessity for immediate surgery was unclear significantly predicted therapeutic surgery (p < 0.001 for all). These parameters did not show a significant difference in predicting the need for surgery at the admission. NLR showed an AUC of 0.971 and performed significantly better than PLR and SII (AUC = 0.874 and 0.902, respectively) in predicting TS. The optimal cut-off value for NLR was 3.33, with a sensitivity of 98.2%, a specificity of 90%, and a negative likelihood ratio of 0.02. Time from admission to surgery was significantly shorter in the TS group (p = 0.001). CONCLUSION: NLR, PLR and SII values may be useful in predicting therapeutic surgery during clinical follow-up in AASW patients with unclear physical examination findings and in whom immediate surgical decisions cannot be made.

Role of Negative Suction Therapy and Platelet-Rich Plasma in the Management of Delayed Post-operative Wound Healing: A Case Report.

Tibial Pilon fractures are rare yet devastating injuries. To classify these fractures, the Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification system is the most commonly used method. Out of all the different types, type C fractures are the most difficult to manage because the enormous energy involved in creating this type of injury typically severely destroys the soft tissue surrounding the fracture zone. As a result, long-term outcomes are frequently poor, and proper initial primary care is critical. Pilon fractures are injuries that are difficult to manage, considering the poor soft tissue envelope. These injuries often are associated with delayed wound healing and require staged management. Additional methods of treating the soft tissue envelope are currently being investigated and have shown promising results for the future. We share our experience in the management of AO type 43C3 grade I compound distal tibia fibular fracture with post-operative wound dehiscence, successfully managed with vacuum-assisted closure (VAC) and platelet-rich plasma (PRP) therapy.

Double-nylon purse-string suture in closing postoperative wounds following endoscopic resection of large (≥ 3 cm) gastric submucosal tumors.

BACKGROUND: Endoscopic full-thickness resection (EFTR) of gastric submucosal tumors (SMTs) is safe and effective; however, postoperative wound management is equally important. Literature on suturing following EFTR for large (≥ 3 cm) SMTs is scarce and limited. AIM: To evaluate the efficacy and clinical value of double-nylon purse-string suture in closing postoperative wounds following EFTR of large (≥ 3 cm) SMTs. METHODS: We retrospectively analyzed the data of 85 patients with gastric SMTs in the fundus of the stomach or in the lesser curvature of the gastric body whose wounds were treated with double-nylon purse-string sutures after successful tumor resection at the Endoscopy Center of Renmin Hospital of Wuhan University. The operative, postoperative, and follow-up conditions of the patients were evaluated. RESULTS: All tumors were completely resected using EFTR. 36 (42.35%) patients had tumors located in the fundus of the stomach, and 49 (57.65%) had tumors located in the body of the stomach. All patients underwent suturing with double-nylon sutures after EFTR without laparoscopic assistance or further surgical treatment. Postoperative fever and stomach pain were reported in 13 (15.29%) and 14 (16.47%) patients, respectively. No serious adverse events occurred during the intraoperative or postoperative periods. A postoperative review of all patients revealed no residual or recurrent lesions. CONCLUSION: Double-nylon purse-string sutures can be used to successfully close wounds that cannot be completely closed with a single nylon suture, especially for large (≥ 3 cm) EFTR wounds in SMTs.

Self-healing hydrogel based on poly (vinyl alcohol)-poly (lysine)-gum arabic accelerates diabetic wound healing under photothermal sterilization.

Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections. In this study, a self-healing antibacterial hydrogel (polyvinyl alcohol (PVA)-polylysine-gum arabic, PLG hydrogels) with near-infrared photothermal response was prepared by linking PVA and a novel polysaccharide-amino acid compound (PG) through borate bonding combined with freeze-thaw cycling. Subsequently, the hydrogel was modified by incorporating inorganic nanoparticles (modified graphene oxide (GM)). The experimental results showed that the PLGM3 hydrogels (PLG@GM hydrogels, 3.0 wt%) could effectively kill bacteria and promote diabetic wound tissue healing under 808-nm near-infrared laser irradiation. Therefore, this hydrogel system provides a new idea for developing novel dressings for treating diabetic wounds.