Jaideep Banerjee

Background: CAMPs (cellular and acellular matrix products) can facilitate wound closure and improve clinical outcomes in patients with diabetic lower extremity ulcers (DLEU), however, there is a lack of comparative data between different CAMPs. The objective of this study was to use real-world evidence to compare the clinical and economic outcomes of hospital care for DLEU patients treated with a minimally manipulated human umbilical tissue (STRAVIX ^◊ ) or other acellular CAMPs. Methods: This retrospective analysis was conducted on patients with DLEU treated with the CAMPs using data from the Premier PINC AI Healthcare Database. Each patient’s earliest inpatient encounter was designated as the index admission. The analysis groups included a cellular human umbilical tissue allograft (STRAVIX) and four different acellular CAMPs (aCAMPs). To balance baseline covariates, inverse probability of treatment weighting (IPTW) was applied. Subsequently, IPTW-adjusted generalized linear models were utilized to estimate healthcare-related outcomes and hospital-related costs. Results: 2,626 DLEUs patients with STRAVIX and 10,002 DLEUs patients with aCAMPs were identified. Compared to the patients treated with aCAMPs, the patients who had STRAVIX in addition to standard of care had significantly lower odds of having an infection reaction, dehiscence, minor and major amputations, after index admission discharge. The number of DLEU related follow-up visits was 17-23% lower, debridement related visits were 19-23% lower and the incidence of all-cause readmission was 22-25% lower in Stravix patients compared to aCAMP patients. The length of hospital stay days was 3% lower and the cost of all-cause visits was 20-25% lower in STRAVIX treated patients compared to aCAMP patients. Conclusion: This large data set demonstrates improved clinical outcomes in patients who had STRAVIX in addition to standard surgical management, when compared to certain acellular CAMPs.

Background: Standard of Care (SoC) with multilayer compression therapy along with proper wound management, may not be sufficient to close all venous ulcers and needs advanced therapies. Methods: In this multicenter, prospective, randomized, controlled, open‐label trial, 351 patients were screened, 200 were eligible and enrolled and were randomized 1:1 to LPM (lyopreserved cellular placental membrane) plus SoC or SoC alone for up to 12 weeks. Patients were enrolled between June 2018 and November 2020 at 30 sites across the United States. Outcome measures included complete closure of the index ulcer (primary), reduction in wound size, rate of closure, quality of life, and adverse events. Results: ITT analysis revealed that wounds treated with weekly applications of LPM as an adjunct to standard of care, reduced in size significantly more than SoC alone, at the end of 4, 8, and 12 graft applications, indicating a faster progression to closure. There was a statistically 1.72 higher relative risk or 72% higher probability of wound closure with LPM compared to the SoC group during the study period for wounds with an initial size of 3–25 cm ² . Use of LPM as an adjunct was able to close statistically larger‐sized wounds on average. There was also a statistically significant fivefold improvement in quality of life (overall physical symptoms and daily life) over baseline, in the LPM treated patients as compared to the control group. Conclusion: LPM and standard of care, significantly closed more venous leg ulcers and faster than standard of care alone and improved the quality of life for patients, suggesting that the use of aseptically processed LPM is a safe and effective treatment option in the healing of chronic venous leg ulcers. Trial Registration: ClinicalTrials.gov ID: NCT03629236, Study to Evaluate Safety and Efficacy of GrafixPL for the Treatment of Venous Leg Ulcers. ( https://clinicaltrials.gov/study/NCT03629236 ).

Significance: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant review focuses on the efficacy of cellular, acellular and matrix-like products (CAMPs) in th...

Background and Aims: This study considers the cost‐effectiveness of commonly used cellular, acellular, and matrix‑like products (CAMPs) of human origin also known as human cell and tissue products (HCT/Ps) in the management of diabetic foot ulcers.Methods: We developed a 1‐year economic model assessing six CAMPs [cryopreserved placental membrane with viable cells (vCPM), bioengineered bilayered living cellular construct (BLCC), human fibroblast dermal substitute (hFDS), dehydrated human amnion chorion membrane (dHACM), hypothermically stored amniotic membrane (HSAM) and human amnion membrane allograft (HAMA) which had randomized controlled trial evidence compared with standard of care (SoC). CAMPs were compared indirectly and ranked in order of cost‐effectiveness using SoC as the baseline, from a CMS/Medicare's perspective.Results: The mean cost, healed wounds (hw) and QALYs per patient for vCPM is $10,907 (0.914 hw, 0.783 QALYs), for HAMA $11,470 (0.903 hw, 0.780 QALYs), for dHACM $15,862 (0.828 hw, 0.764 QALYs), for BLCC $18,430 (0.816 hw, 0.763 QALYs), for hFDS $19,498 (0.775 hw, 0.757 QALYs), for SoC $19,862 (0.601 hw, 0.732 QALYs) and $24, 214 (0.829, 0.763 QALYs) for HSAM respectively. Over 1 year, vCPM results in cheaper costs overall and better clinical outcomes compared to other CAMPs. Following probabilistic sensitivity analysis, vCPM has a 60%, HAMA 40% probability of being cost‐effective then dHACM, hFDS, BLCC, and lastly HSAM using a $100,000/healed wound or QALY threshold.Conclusions: All CAMPs were shown to be cost‐effective when compared to SoC in managing DFUs. However, vCPM appears to be the most cost‐effective CAMP over the modelled 52 weeks followed by HAMA, dHACM, hFDS, BLCC, and HSAM. We urge caution in interpreting the results because we currently lack head‐to‐head evidence comparing all these CAMPs and therefore suggest that this analysis be updated when more direct evidence of CAMPs becomes available.

IntroductionPilonidal cyst is a disorder of the skin characterized by highly inflamed soft tissue and recurrent infections and can result in chronic sinuses and cysts that become intermittently occluded and form abscess, thus significantly reducing patient quality of life[1]. An infected hair follicle extends and ruptures into the subcutaneous tissue, forming a pilonidal abscess which can form a sinus track extending to deeper subcutaneous cavities. Pilonidal cysts are often associated with high recurrence due to frequent pathogenic microbes and chronically inflamed tissue. Obese patients with high BMI have a higher risk of recurrence of pilonidal sinus disease after surgical intervention. Although pilonidal disease is a benign disorder, it can be painful, leading to poor quality of life and delayed absence from work. It is estimated that pilonidal disease affects roughly 70,000 patients annually in the US alone[1]. Over the past 50 years, the incidence of this disease has risen continuously in European and North American young men[2].Incision and drainage (I&D) are the initial procedures to manage the wound, however, simple I&D procedures are associated with a 15–40% reoccurrence rate requiring revisional surgeries[3]. Surgical excision is the current standard of care and is intended to remove pits or sinuses and debride hair and foreign body[4]. The resultant wound defect can be closed primarily or with a flap or via excision with healing by secondary intention[1].Management of such wounds is still unsatisfactory as the options lead to either considerable discomfort (“open” method) or increase the recurrence rate (“closed” method). Therefore, alternative approaches have been explored in recent years. Amniotic allografts have been explored as an effective option due to their structural matrix and growth factors required for healing. Over the last couple of decades, this technology has been successfully used in randomized clinical trials for patients with chronic ulcers and in prospective cohort studies in patients with diabetes and complex surgical wounds with exposed tendon, muscle and bone [5]. Amniotic tissue allografts have also been recently reported to have a significantly lesser recurrence rates than standard of care in diabetic wounds[6]. They can therefore be a viable option to close the excision thus avoiding discomfort to the patient but potentially preventing long term recurrence.While amnion or amnion-chorion allografts are thin and designed for weekly clinic applications with a focus on treating full thickness ulcers, umbilical tissue allografts, which also have the amnion layer and are much thicker, suture-able and can be effective with a single application. With the development of the lyopreservation technique, it is now possible to process the tissues and store at room temperature while preserving the native components of the tissues[7]. STRAVIX PL is a shelf stable human umbilical tissue allograft that aids in covering hard-to-treat wounds, including those with exposed structures or hardware and is similar to the cryopreserved STRAVIX that has been commercially available in the US for a while[7, 8]. It can be used as a cover or wrap for tendon, ligament, bone, nerve repair or soft tissue sites in various surgical procedures from head to toe and can provide a barrier under incisions. The tissue is manufactured using proprietary processes allowing retention of all native components such as extracellular matrix rich in hyaluronic acid, growth factors and native cells of the tissue. It is durable, strong and conforming, can be easily sutured, about 1 to 3 millimeters thick, intimately adapts to injured tissue to form adhesion barrier, arthroscopic and robotic procedure friendly and easy to maneuver and apply. STRAVIX family of grafts have been shown to improve closure rates of challenging wounds as a cover[8, 9] and is suitable for a wide range of surgical procedures, particularly those involving high-risk patients. In this retrospective case series, we report the results of using STRAVIX PL for management of recurrent closure of pilonidal cyst wounds.

Critical Issue: Chronic nonhealing wounds of the lower extremities resulting in major amputations are a major health problem worldwide. Significance: Diabetes and ischemia are two major etiologies of nonhealing wounds of the lower extremities. Hyperglycemia from diabetes and oxidative stress from ischemia activate polyadenosine diphosphate (ADP)-ribose polymerase-1 (PARP-1), which is a nuclear enzyme that is best known for its role in DNA repair. However, the exact function of PARP-1 in ischemic/diabetic wound healing has not been well studied. Recent Advances: Poly-ADP-ribose (PAR) polymer has been detected in the wound bed and many of the PARylation-related reactions (oxidative stress response, expression of inflammatory cytokines and chemokines, cell proliferation, and migration) are important in the wound healing process. However, the role of PARP-1 in wound healing and the potential of targeting PARP-1 therapeutically in wounds are only recently being elucidated, with much still unknown. This review summarizes the recent advances in this field, highlighting some of the mechanisms through which PARP-1 may affect normal wound closure. Future Directions: The review also presents a perspective on some of the downstream targets of PARP-1 that may be explored for their role in wound healing and discusses about the therapeutic potential of PARP inhibitors for wound healing.

Infection control is necessary for improved burn wound regeneration. In this study contact burn wounds were induced on the dorsum of the rats and were infected with Pseudomonas aeruginosa (10⁷cfu/ml of saline) and left overnight (12–14 hours) to establish the infection. After 12 hours, the wounds were treated with PEGylated fibrin hydrogel containing 50 mgs of silver sulfadiazine (SSD) loaded chitosan microsphere (SSD-CSM-FPEG). On day 9, SSD-CSM-FPEG treated burn wounds further received adipose derived stem cell (5×10⁴ ASCs cells/ml) embedded in PEGylated fibrin hydrogel. Wounds were assessed for the healing outcomes such as neovascularization, granulation tissue formation, wound closure and collagen maturation. Analysis of bacterial load in the burn wound biopsies, demonstrated that SSD–CSM-FPEG significantly reduced bacterial infection, while overt infection was still observed in the untreated groups on day 14. Sequential treatment of infected wounds with SSD–CSM-FPEG followed by ASC-FPEGs (SSD-CSM-ASC-FPEG) significantly reduced bacterial colonization (9 log reduction) and pro-inflammatory cytokine (TNF-α) expression. A significant increase in neovascularization markers; NG2 and vWF was also observed. Histological analysis indicated the wounds treated with SSD-CSM-ASC-FPEG increased amount of dermal collagen matrix deposition, a thicker granulation tissue on day 21 and more mature collagen on day 28. This work demonstrates that the sequential treatment of infected burn wounds with SSD-CSM-FPEG followed by ASC-FPEG reduces bacterial infection as well as promotes neo-vascularization with improved matrix remodeling.

Objective: To better understand Acinetobacter baumannii pathogenesis and to advance drug discovery against this pathogen, we developed a porcine, full-thickness, excisional, monospecies infection wound model. Approach: The research was facilitated with AB5075, a previously characterized, extensively drug-resistant A . baumannii isolate. The model requires cyclophosphamide-induced neutropenia to establish a skin and soft tissue infection (SSTI) that persists beyond 7 days. Multiple, 12-mm-diameter full-thickness wounds were created in the skin overlying the cervical and thoracic dorsum. Wound beds were inoculated with 5.0 × 10 ⁴ colony-forming units (CFU) and covered with dressing. Results: A . baumannii was observed in the wound bed and on the dressing in what appeared to be biofilm. When bacterial burdens were measured, proliferation to at least 10 ⁶ CFU/g (log ₁₀ 6) wound tissue was observed. Infection was further characterized by scanning electron microscopy (SEM) and peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) staining. To validate as a treatment model, polymyxin B was applied topically to a subset of infected wounds every 2 days. Then, the treated and untreated wounds were compared using multiple quantitative and qualitative techniques to include gross pathology, CFU burden, histopathology, PNA-FISH, and SEM. Innovation: This is the first study to use A . baumannii in a porcine model as the sole infectious agent. Conclusion: The porcine model allows for an additional preclinical assessment of antibacterial candidates that show promise against A . baumannii in rodent models, further evaluating safety and efficacy, and serve as a large animal in preclinical assessment for the treatment of SSTI.

Annexin A7 (ANXA7) is a member of the multifunctional calcium or phospholipid-binding annexin gene family. While low levels of ANXA7 are associated with aggressive types of cancer, the clinical impact of ANXA7 in prostate cancer remains unclear. Tissue microarrays (TMA) have revealed several new molecular markers in human tumors. Herein, we have identified the prognostic impact of ANXA7 in a prostate cancer using a tissue microarray containing 637 different specimens. The patients were diagnosed with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival data (median 5.9 years) were available. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), syndecan-1 (CD-138) and ANXA7 were analyzed by immunohistochemistry. A bimodal distribution of ANXA7 was observed. Tumors expressing either high or no ANXA7 were found to be associated with poor prognosis. However, ANXA7 at an optimal level, in between high and no ANXA7 expression, had a better prognosis. This correlated with low Ki67, Bcl-2, p53 and high syndecan-1 which are known predictors of early recurrence. At Gleason grade 3, ANXA7 is an independent predictor of poor overall survival with a p-value of 0.003. Neoadjuvant hormonal therapy, which is known to be associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, was found to be associated with under-expression of ANXA7. The results of this TMA study identified ANXA7 as a new prognostic factor and indicates a bimodal correlation to tumor progression.