Optimization and advances in negative pressure wound therapy for the management of necrotizing fasciitis in the upper limb

Abstract

Necrotizing fasciitis (NF) is a rapidly progressing, life-threatening soft tissue infection, with upper limb NF posing a particularly serious threat to patient survival and quality of life. Negative pressure wound therapy (NPWT) has shown considerable advantages in accelerating wound healing and mitigating functional impairment. A retrospective study by Lipatov et al. demonstrated that NPWT significantly reduced the time needed for wound closure preparation while enhancing the success rate of local repair. Despite its benefits, certain limitations highlight the need for further optimization. This paper investigates the potential for personalized dynamic regulation of NPWT, its integration with adjunctive therapies, and the role of multidisciplinary collaboration. Furthermore, it explores the incorporation of advanced technologies such as artificial intelligence, imaging modalities, and biomaterials, presenting novel pathways for the personalized management and global standardization of NF treatment.

Key Words: Artificial intelligence; Biomaterials; Hyperbaric oxygen therapy; Necrotizing fasciitis; Negative pressure wound therapy; Personalized medicine; Tissue engineering; Wound healing

Core Tip: This study explores the optimization of negative pressure wound therapy (NPWT) for the management of upper limb necrotizing fasciitis (NF), a life-threatening condition. It highlights the advantages of NPWT in accelerating wound healing and improving functional outcomes while addressing its limitations. Key innovations discussed include adaptive NPWT with dynamic pressure regulation, adjunctive therapies such as platelet-rich plasma and antimicrobial dressings, and the integration of advanced technologies like artificial intelligence, imaging modalities, and biomaterials. The findings emphasize the importance of personalized, multidisciplinary approaches and emerging technologies in enhancing treatment efficacy and global standardization of care for NF.

TO THE EDITOR

Necrotizing fasciitis (NF) is a highly lethal and rapidly progressing soft tissue infection, with a 30-day in-hospital mortality rate of up to 40%, particularly when delays in diagnosis and treatment result in irreversible tissue damage[1,2]. Upper limb NF represents approximately 6%–27% of all cases. Due to the essential role of fine motor functions in the hand and wrist, structural damage in these areas can profoundly affect patients' daily lives and occupational capabilities. This underscores the critical importance of minimizing complications and prioritizing the improvement of functional outcomes as key areas of research[3].

Against this backdrop, Lipatov et al[4] conducted a retrospective analysis to systematically evaluate the therapeutic efficacy of negative pressure wound therapy (NPWT) in upper limb NF. Their findings highlighted the significant advantages of NPWT in accelerating wound closure preparation and enhancing both cosmetic and functional outcomes. The study revealed that the wound closure preparation time in the NPWT group was significantly reduced from 29 days with conventional treatment to just 11 days (P = 0.00001), effectively shortening the duration by approximately two-thirds. This improvement not only increased surgical efficiency but also lowered hospitalization costs. Furthermore, 83.3% of patients in the NPWT group achieved wound healing through local tissue repair, compared to only 44.4% in the conventional group. These results underscore the substantial benefits of NPWT in minimizing scar contracture and preserving limb functionality.

Building on this context, Lipatov et al[4] conducted a retrospective analysis to systematically assess the therapeutic efficacy of NPWT in managing upper limb NF. Their findings demonstrated the significant advantages of NPWT in expediting wound closure preparation and improving both cosmetic and functional outcomes. The study showed that the NPWT group experienced a marked reduction in wound closure preparation time, from 29 days with conventional treatment to just 11 days (P = 0.00001), effectively shortening the duration by approximately two-thirds. This advancement not only enhanced surgical efficiency but also significantly reduced hospitalization costs. Moreover, 83.3% of patients treated with NPWT achieved wound healing through local tissue repair, a substantial improvement compared to the 44.4% success rate in the conventional treatment group. These results underscore NPWT's remarkable efficacy in minimizing scar contracture and preserving limb functionality.

CRITICAL ANALYSIS AND DIRECTIONS FOR IMPROVEMENT

Methodological insights

The study by Lipatov et al[4] utilized a retrospective design, enabling the rapid summarization of existing clinical data, particularly for rare conditions such as upper limb NF. However, the inherent limitations of a retrospective approach cannot be ignored. Subjective factors may influence treatment decisions and data recording, thereby increasing the risk of bias[5]. Specifically, single-center studies may not adequately capture the variability in practices across different healthcare institutions, including differences in surgical team expertise, resource availability, and patient demographics, which can potentially limit the generalizability of the findings[5]. Furthermore, statistical analyses based on historical case data may fail to account for potential confounding factors, such as patients' socioeconomic status, lifestyle, or early care interventions, all of which could significantly influence treatment outcomes[6,7].

Despite these limitations, the rigor exhibited by Lipatov et al[4] in patient selection is noteworthy. The study clearly defined inclusion and exclusion criteria, excluding factors such as diabetes and steroid use that might impact wound healing, thereby ensuring homogeneity within the study population and enhancing the reliability of data analysis. This meticulous case selection provides a strong foundation for interpreting the study results. However, reliance on data from a single clinical center does restrict the external validity and broader applicability of the findings[8].

To further validate the efficacy of NPWT in the treatment of upper limb NF, future research should adopt multi-center, prospective study designs. This approach would allow for the inclusion of larger, more representative patient cohorts from diverse clinical settings. Multi-center trials can mitigate potential regional or systemic biases inherent in single-center studies and evaluate the consistency of treatment outcomes across various healthcare environments, thereby providing more robust evidence for the establishment of global treatment standards[9].

Additionally, multi-center studies would enhance statistical power by increasing sample sizes, enabling more detailed subgroup analyses. For instance, the impact of NPWT efficacy on different age groups, pathological characteristics, or comorbidities could be systematically explored, laying a solid foundation for the development of more personalized and targeted treatment strategies.

Optimization of NPWT

The pressure settings for NPWT are categorized into two primary modes: Continuous and dynamic. Continuous mode applies a consistent negative pressure of -125 mmHg, making it particularly effective for providing stable support to fragile or unstable tissue structures. In contrast, dynamic mode involves cyclic fluctuations between the target and minimum negative pressures, with a baseline range of 20–90 mmHg. Typically, dynamic pressure oscillates between -25 mmHg and -125 mmHg, with pressure differentials reaching up to 5–300 mmHg[10,11].

Compared to the traditional intermittent mode, dynamic mode maintains a minimum negative pressure of -25 mmHg throughout the cycle. This feature helps to minimize dressing leakage and reduce patient discomfort while simultaneously enhancing granulation tissue formation and improving perfusion at the wound edges.

For patients experiencing pain or discomfort, the negative pressure can be lowered (e.g., to > -75 mmHg) to improve tolerance and comfort[12]. Optimal pressure settings should always be tailored to the specific wound characteristics and the individual needs of the patient to ensure effective and personalized care.

In their study, Lipatov et al[4] utilized a fixed pressure setting of 120 mmHg, a standard widely accepted in NPWT. However, the optimal pressure can vary significantly depending on wound characteristics such as size, depth, severity of infection, and local tissue perfusion. For example, higher negative pressures may improve tissue perfusion and reduce the infection burden in wounds with deep infections or compromised blood flow. Conversely, excessive pressure in superficial or fragile tissues may cause mechanical damage or exacerbate necrosis[13].

To maximize therapeutic outcomes, it is essential to tailor pressure settings to the specific characteristics of the wound[14]. Dynamic pressure adjustments, guided by real-time monitoring of factors such as tissue oxygen saturation or exudate volume, can further enhance the effectiveness of NPWT[15].

Adaptive NPWT, an emerging technology, is currently gaining significant attention. Unlike traditional fixed-pressure systems, adaptive NPWT alternates between high and low-pressure cycles, offering enhanced tissue perfusion, promoting neovascularization, and accelerating granulation tissue formation[14,16,17]. Studies have shown that this intermittent pressure mechanism effectively reduces pressure habituation within the wound bed, thereby improving the efficacy of NPWT in long-term applications[16].

Building on the findings of Lipatov et al[4], future research should investigate the potential of adaptive NPWT in the management of NF, particularly for complex or chronic wounds where conventional approaches may be less effective.

The study reported a dressing change interval of 2 to 3 days, aligning with current clinical practice standards. However, frequent dressing changes can increase healthcare costs, strain medical resources, and cause discomfort for patients. Research suggests that extending the dressing change interval to 5 days or longer is both safe and feasible for wounds with minimal exudate or well-controlled infection. Nonetheless, the potential risks associated with prolonged intervals must be carefully evaluated[18,19].

Future research could utilize randomized controlled trials (RCTs) to explore the effects of dressing change intervals on clinical outcomes and cost-effectiveness. For instance, in wounds with low exudate levels, it would be valuable to determine whether extended intervals can significantly reduce material costs and healthcare workloads while maintaining or enhancing therapeutic efficacy. Furthermore, the use of antimicrobial dressings, such as those incorporating silver ions or iodine, could further extend dressing durability and optimize patient management[20,21].

Microbial environment

Dominance of Staphylococcus aureus and Streptococcus pyogenes as key pathogens: The study by Lipatov et al[4] identified Staphylococcus aureus (38.9%) and Streptococcus pyogenes (61.1%) as the predominant pathogens responsible for upper limb NF. This finding is consistent with existing literature on the microbial profile of type II NF[22,23]. As common causative agents in both monomicrobial and polymicrobial infections, these bacteria drive disease progression through potent virulence factors—Streptococcus pyogenes produces enzymes such as streptokinase and streptodornase, while Staphylococcus aureus releases various toxins. These factors contribute to rapid tissue destruction, systemic inflammatory responses, and the frequent need for multiple debridement procedures.

In 11.1% of cases, no specific pathogen was isolated, likely due to limitations in sample collection, culture conditions, or the potential involvement of anaerobic infections[4,24].

This highlights the necessity of employing diverse diagnostic strategies in managing NF. Advanced molecular biology techniques, such as 16S rRNA gene sequencing, can play a pivotal role in identifying rare or elusive pathogens, thereby enabling the development of more accurate and targeted treatment plans[23,25].

Recommendations for integrating NPWT with adjunctive antimicrobial strategies: While NPWT has proven highly effective in wound management, its primary mechanisms focus on mechanically reducing local exudate, enhancing tissue perfusion, and promoting healing, with only limited direct antimicrobial effects. Given the high pathogenicity and potential resistance risks associated with Staphylococcus aureus and Streptococcus pyogenes, combining antimicrobial strategies with NPWT could further optimize therapeutic outcomes. (1) Antimicrobial-coated NPWT dressings. NPWT dressings infused with antimicrobial agents, such as silver ions, iodine, or polyhexamethylene biguanide, can directly eliminate pathogens and reduce bacterial loads. Studies have demonstrated that silver-ion dressings effectively minimize wound infections and, when combined with NPWT, significantly reduce the risk of antimicrobial resistance[20,21]; (2) Topical antibiotic application. Incorporating topical antibiotics, such as vancomycin or penicillin, into NPWT dressings provides precise antimicrobial effects. This localized approach efficiently eradicates pathogens while minimizing systemic side effects and reducing the selection pressure for antibiotic-resistant bacterial strains[26,27]; (3) Antimicrobial combination therapy. Dressings integrated with bioactive materials, such as chitosan or antimicrobial peptides, can deliver sustained antimicrobial effects during NPWT. These advanced materials not only inhibit bacterial proliferation but also stimulate fibroblast growth and angiogenesis, fostering an optimal microenvironment for wound healing[28,29]; and (4) Regular microbial monitoring and dynamic antimicrobial adjustment. Routine microbial monitoring during NPWT treatment, using wound exudate cultures or molecular diagnostic methods, is highly recommended. Dynamically adjusting antimicrobial strategies based on bacterial load or resistance patterns can significantly enhance therapeutic outcomes. Rapid diagnostic tools, including polymerase chain reaction and mass spectrometry, further enhance the precision and timeliness of antimicrobial interventions[30].

Integrating NPWT with adjunctive antimicrobial technologies represents a crucial step toward enhancing the treatment of NF. Future research should prioritize the development of innovative antimicrobial materials and investigate their synergistic mechanisms with NPWT. Furthermore, exploring multimodal therapies, such as combining antimicrobial NPWT with photodynamic therapy or electrotherapy, may offer novel solutions for managing refractory infections. By optimizing microbial environment management, the potential applications of NPWT can be significantly expanded, delivering more reliable and effective therapeutic options for clinical practice.

Adjunctive therapies and technologies

Advocating the integration of NPWT with advanced adjunctive methods: The study by Lipatov et al[4] highlighted the substantial benefits of NPWT in treating upper limb NF. However, the effectiveness of NPWT alone may be limited when addressing complex wounds. Integrating NPWT with advanced adjunctive therapies presents a promising opportunity to further enhance treatment outcomes, particularly by accelerating healing, minimizing complications, and improving patient prognosis.

Platelet-rich plasma

Accelerating granulation tissue formation: Platelet-rich plasma (PRP) is a blood concentrate abundant in growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-β, and vascular endothelial growth factor (VEGF) and others[31]. These bioactive molecules play a crucial role in accelerating granulation tissue formation and angiogenesis by promoting the proliferation of fibroblasts and endothelial cells.

Integrating PRP into NPWT can significantly enhance local tissue repair capacity[32]. Research has demonstrated that directly injecting PRP into wounds or incorporating it into NPWT dressings can effectively shorten healing time and boost the wound’s anti-infection capabilities. This combined approach is especially beneficial for treating complex wounds with deep tissue defects or impaired blood supply[33].

Future studies should focus on exploring the synergistic effects of PRP preparation concentrations, dosing frequencies, and NPWT pressure levels to refine and optimize treatment protocols.

Bioengineered skin substitutes and scaffolds

Enhancing wound closure: For large tissue defects or chronic non-healing wounds, traditional skin grafting methods often face significant limitations. Bioengineered skin substitutes (e.g., Integra, Alloderm) and three-dimensional scaffold technologies are emerging as promising areas of research.

These innovative materials not only provide mechanical support but also mimic the extracellular matrix, fostering cell adhesion and proliferation to create a biologically compatible environment conducive to wound healing[34,35]. Integrating these materials with NPWT can substantially improve the quality of wound closure. For example, NPWT facilitates the integration of scaffolds with underlying tissues by maintaining sustained negative pressure, reducing the risk of displacement or infection of the substitutes.

Future advancements may focus on developing intelligent scaffolds infused with antimicrobial agents or growth factors, offering a dual benefit of infection control and accelerated healing[36,37].

Hyperbaric oxygen therapy

Reducing systemic inflammatory response and improving oxygenation: Hyperbaric oxygen therapy (HBOT) delivers high concentrations of oxygen under hyperbaric conditions, effectively enhancing local tissue oxygenation, promoting neovascularization, and stimulating collagen synthesis[38]. This therapy is particularly effective for wounds with severe ischemia or infection, as it significantly reduces systemic inflammatory response syndrome (SIRS) and decreases mortality rates in patients with NF.

When combined with NPWT, HBOT can improve microcirculation in compressed tissues, accelerate granulation tissue formation, and enhance anti-infective capabilities. Studies have shown that the synergistic effect of HBOT and NPWT can further reduce the need for debridement procedures and significantly shorten hospital stays. However, given the high equipment demands of HBOT, future research should focus on identifying the optimal timing, treatment frequency, and practical protocols for integrating HBOT with NPWT[36,37,39,40].

The integration of NPWT with advanced adjunctive technologies like HBOT provides expanded opportunities for treating NF. Future research should leverage multi-center clinical trials to systematically evaluate the efficacy and cost-effectiveness of these combined therapies. Additionally, the incorporation of artificial intelligence (AI) and machine learning offers the potential to optimize treatment decision-making further. For example, dynamic data analysis of wound healing could enable precise adjustments to PRP concentrations, NPWT pressure settings, and HBOT parameters, paving the way for truly personalized treatment plans.

EMERGING TRENDS AND OPPORTUNITIES IN NF TREATMENT

With advancements in medical technology, the treatment of NF is increasingly shifting toward precision, personalization, and multidisciplinary collaboration. The rise of AI and machine learning has opened new avenues for the early detection and tailored management of NF patients. AI-driven predictive models can seamlessly integrate real-time patient data, including vital signs, inflammatory markers, and wound characteristics, allowing clinicians to swiftly assess prognosis and identify high-risk individuals. This significantly enhances clinical decision-making by predicting the likelihood of complications such as SIRS or sepsis, enabling timely interventions and reducing mortality rates[41]. Furthermore, AI has the capacity to analyze large-scale patient datasets to develop personalized treatment strategies for complex cases, such as dynamically optimizing the pressure settings of NPWT and determining the appropriate timing for adjunctive therapies. As intelligent wearable devices become increasingly integrated with AI systems, the quality and efficiency of care for NF patients are anticipated to improve significantly[42].

Building on the latest research evidence, AI has shown considerable promise in advancing the field of NPWT. Machine learning algorithms have demonstrated exceptional performance in predicting wound healing outcomes, with studies reporting an area under the curve of 0.94, a sensitivity of 0.79, and a specificity of 0.876. By integrating multimodal data—such as clinical indicators, wound characteristics, and biomarkers—AI systems enable more accurate wound assessment and the development of personalized treatment plans[43].

In practical applications, deep learning-based automated wound segmentation and measurement systems excel in identifying wound areas and tissue types, achieving Intersection over Union values of 0.6964 for wound regions and 0.6421 for granulation tissue segmentation[43]. The synergy of these technologies not only improves the precision of NPWT but also provides robust data support for the design of individualized treatment strategies[44]. Nonetheless, further high-quality RCT are essential to establish their clinical utility and ensure broader adoption[45].

Imaging technologies are essential in the early diagnosis and treatment monitoring of NF. Among these, near-infrared spectroscopy (NIRS), a non-invasive technique, has shown significant potential for clinical application[46]. By measuring tissue oxygen saturation, NIRS can detect ischemic tissues before the onset of traditional clinical signs, enabling clinicians to quickly delineate the extent of the lesion and develop effective debridement plans. Moreover, NIRS offers real-time monitoring of oxygen supply changes in wound tissues, allowing for the assessment of NPWT’s impact on local blood flow and tissue metabolism, and facilitating precise adjustments to negative pressure settings. Similarly, ultrasound elastography and dynamic fluorescence imaging provide valuable tools for accurately localizing necrotic tissues and scientifically evaluating the required extent of debridement[46,47]. The integration of these advanced imaging modalities with NPWT holds the potential to significantly improve the accuracy and effectiveness of NF treatment.

The rapid advancements in biomaterials and 3D printing technology are revolutionizing wound repair by offering innovative solutions for complex tissue defects[48]. Bio-printed tissue scaffolds, tailored to the patient’s unique anatomical features, provide mechanical support to wounds while promoting tissue regeneration. In particular, personalized models generated from computed tomography or magnetic resonance imaging data, combined with 3D-printed porous scaffolds, facilitate accelerated cell migration and angiogenesis, thereby enhancing the quality of wound closure. Modern scaffolds are typically fabricated from biodegradable materials, such as polylactic acid or chitosan, which are gradually replaced by newly formed tissues during the healing process, eliminating the risk of rejection commonly associated with traditional grafts[49]. Furthermore, these scaffolds can be functionalized with growth factors (e.g., VEGF, PDGF) or antimicrobial agents (e.g., silver ions), achieving a dual function of promoting tissue repair and controlling infection. Compared to traditional skin grafts, tissue-engineered substitutes incorporating biomaterials demonstrate significant advantages in mechanical strength, biocompatibility, and healing efficiency[50].

The integration of AI, advanced imaging technologies, and biomaterials is transforming the treatment of NF, ushering in a new era of enhanced efficiency and precision. These innovations not only improve early diagnosis and therapeutic efficacy but also hold significant promise for achieving long-term functional recovery and enhancing patients' quality of life. Future research should prioritize the integration of multimodal data—including imaging, genomics, and real-time clinical information—to develop a more comprehensive and personalized patient management system. Moreover, accelerating the clinical translation of intelligent devices and advanced biomaterials is critical to further optimizing treatment outcomes, reducing costs, and delivering higher-quality, more cost-effective care to NF patients.

CONCLUSION

NPWT has proven to be a transformative tool in the treatment of NF. The study by Lipatov et al[4] further demonstrated its significant benefits in accelerating wound healing and enhancing both cosmetic and functional outcomes, particularly in patients with upper limb NF. However, despite the widespread recognition of NPWT's effectiveness, its application faces notable limitations, including the inflexibility of fixed pressure settings for complex wounds and the absence of dynamic adjustments tailored to individual patient needs. These challenges highlight the critical importance of integrating personalized and multidisciplinary treatment approaches alongside NPWT as a core therapeutic modality.

The complexity of NF arises not only from its pathological characteristics but also from patient-specific factors and potential comorbidities. Effective management requires a multidisciplinary approach, integrating expertise from fields such as surgery, infectious disease, radiology, and tissue engineering to provide comprehensive and holistic care.

Personalized treatment strategies should be tailored to the patient’s specific condition, microbial environment, and wound characteristics. These strategies may include dynamically adjusting NPWT parameters, incorporating antimicrobial dressings, or combining adjunctive therapies to optimize clinical outcomes and improve overall patient care.

Future research should prioritize the exploration of innovative technologies and hybrid treatment approaches to improve survival rates and enhance the quality of life for patients with NF. AI- and machine learning-driven predictive models can play a pivotal role in the early identification of high-risk patients, optimizing treatment decision-making, and enabling timely interventions.

Advanced imaging technologies, such as NIRS, offer precise evaluations of tissue perfusion and necrosis, providing scientific guidance for debridement procedures and dynamic adjustments to NPWT. Furthermore, the rapid advancements in biomaterials and 3D printing technologies present new opportunities for the personalized repair of complex wounds.

Integrating these technologies into multimodal treatment strategies can not only accelerate tissue regeneration but also significantly reduce complication rates, paving the way for more effective and individualized patient care. In addition to advancements in treatment techniques, it is crucial to focus on long-term functional recovery and psychological support for patients with NF. Early functional rehabilitation and psychological interventions are vital for enhancing patients' quality of life and overall well-being. Multi-center clinical trials will play a key role in validating the effectiveness of emerging technologies and hybrid therapies. These trials will not only improve the generalizability of findings but also provide strong evidence to support the development of global treatment standards, ensuring more consistent and effective care for NF patients worldwide.