William Tettelbach - Academia.edu (original) (raw)
Papers by William Tettelbach
Journal of wound care, Mar 1, 2024
Journal of Wound Care
As the US population continues to age, costs for hard-to-heal wounds are expected to rise and neg... more As the US population continues to age, costs for hard-to-heal wounds are expected to rise and negatively contribute to the long-term financial stability of Medicare, which is currently labelled a ‘high-risk’ program by the US Government Accountability Office. Within wound care, some skin substitutes, also known as cellular tissue products (CTPs), and now referred to as CAMPS (cellular, acellular, and matrix-like products), have demonstrated improved healing times and cost-effective usage. However, a dramatic increase in the number of CAMPs has led to controversy on reimbursement rates. For instance, in the third quarter of 2022, 30 of 68 CAMPs represented a disproportionate $256 million USD in costs, due to failures to report their average sales pricing. In its calendar year (CY) 2024 Proposed Rules, the Centers for Medicare and Medicaid Services (CMS) did not implement the proposal to package (‘bundle’) CAMPs products within the private office. Moreover, three Medicare Administrati...
Journal of Wound Care
Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently ... more Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exp...
FEBS Letters, May 7, 1990
Using a synthetic oligopeptide (CGGGTPEYLAPEGGK) crosslinked to keyhole limpet hemocyanin we have... more Using a synthetic oligopeptide (CGGGTPEYLAPEGGK) crosslinked to keyhole limpet hemocyanin we have raised polyclonal rabbit antibodies against a 9 residue homologous region found in the catalytic domain of most protein kinases. These antibodies reacted during Western immunoblotting with CAMP dependent protein kinase catalytic subunit, phosphorylase kinase y subunit and calcium calmodulin dependent protein kinase II which have homologous sequences of GTPEYLAPE, GTPSYLAPE and GTPGYLSPE, respectively. Five other protein kinases did not react with anti-GTPEYLAPE antibodies during Western immunoblot&rg. Affinity-purified antibodies were able to detect as little as 50 ng of CAMP dependent protein kinase and 200 ng of Ca*+/calmodulin dependent protein kinase II. Immunoblotting of A431 cell plasma membrane vesicles indicated the presence of an approximately 55 kDa protein that contains the conserved sequence and is likely to be a protein kinase. Antibodies directed against conserved sequences present in protein kinases, or possibly other enzymes, may be useful in identifying previously uncharacterized enzymes at the protein level.
Journal of Wound Care, May 1, 2023
Journal of Wound Care, Oct 2, 2022
Journal of Wound Care
Despite improvements in treatment methods and outcomes, burns remain one of the principal causes ... more Despite improvements in treatment methods and outcomes, burns remain one of the principal causes of mortality and morbidity worldwide. Burns involving the hands are estimated to occur in >80% of people with burns. Hand burns have also been associated with long-term social, psychological and physical consequences that can impede a patient's full reintegration to the community and decrease their overall quality of life. Clinically, when the trajectory towards complete re-epithelialisation stalls in deep burn wounds of the hand, skin grafting is indicated, but cosmetic problems often remain. A recent publication highlighted common complications for burns involving the hand such as scar disturbances (26%) and scar contractures (14%). Innovative approaches with the potential to reduce the occurrence of complicating scar disturbances and contractures are sought by healthcare providers specialising in burns. This case report describes a novel approach to wound closure using a topica...
Journal of Wound Care
There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenog... more There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.
International Wound Journal
Wounds-a Compendium of Clinical Research and Practice, Sep 1, 2022
Journal of Wound Care
Objective: Pyoderma gangrenosum (PG) is an often-misdiagnosed, painful, inflammatory and ulcerati... more Objective: Pyoderma gangrenosum (PG) is an often-misdiagnosed, painful, inflammatory and ulcerative skin disorder. It is an orphan disease, where standard wound treatments such as sharp surgical debridement are contraindicated. This retrospective case series sought to evaluate the application of dehydrated human amnion/chorion membrane (DHACM) as a skin substitute in cases that were refractory to a range of standard-of-care techniques. Method: This retrospective case series involved wounds which failed to close with standard escalating treatments, including anti-inflammatory and immunosuppressive therapies. Subjects were transitioned to DHACM and wound sizes were monitored until closure. Results: Wounds (n=5) for all three subjects had stalled with standard therapies for at least 2.5 months but responded quickly to routinely applied DHACM treatments, and closure was achieved in each case. Conclusion: This retrospective pilot case series examined the use of DHACM as an alternative wo...
Journal of Wound Care
Objective: To determine the role of debridement when patients are using placental-derived allogra... more Objective: To determine the role of debridement when patients are using placental-derived allografts (PDAs), data from two prospective, multicentre, randomised controlled trials (RCTs) were evaluated for the quality or adequacy of debridement on diabetic foot ulcers (DFUs) treated with PDAs. Results were compared with real-world findings via a retrospective analysis of 2015–2019 Medicare claims for DFUs. Method: Debridement adequacy in the prospective RCTs was adjudicated by three blinded wound care specialists. Treatments included two PDAs, dehydrated human amnion/chorion membrane (DHACM, n=54) or dehydrated human umbilical cord (DHUC, n=101), compared with standard of care (SOC, n=110). The key outcome was the influence of adequate debridement on rates of complete closure within 12 weeks. Additionally, a retrospective analysis of 2015–2019 Medicare claims for DFUs that received routine debridement at intervals ranging from every 1–7 days (18,900 total episodes), 8–14 days (35,728 ...
Ostomy Wound Management, 2015
Journal of Wound Care, 2022
Objective: To evaluate the cost-effectiveness and budget impact of using standard care (no advanc... more Objective: To evaluate the cost-effectiveness and budget impact of using standard care (no advanced treatment, NAT) compared with an advanced treatment (AT), dehydrated human amnion/chorion membrane (DHACM), when following parameters for use (FPFU) in treating lower extremity diabetic ulcers (LEDUs). Method: We analysed a retrospective cohort of Medicare patients (2015–2019) to generate four propensity-matched cohorts of LEDU episodes. Outcomes for DHACM and NAT, such as amputations, and healthcare utilisation were tracked from claims codes, analysed and used to build a hybrid economic model, combining a one-year decision tree and a four-year Markov model. The budget impact was evaluated in the difference in per member per month spending following completion of the decision tree. Likewise, the cost-effectiveness was analysed before and after the Markov model at a willingness to pay (WTP) threshold of $100,000 per quality adjusted life year (QALY). The analysis was conducted from the...
L'invention concerne un systeme d'assistance a la prise de decision contenant des donnees... more L'invention concerne un systeme d'assistance a la prise de decision contenant des donnees stockees dans une base de connaissances, utilise selon un procede permettant a un clinicien d'obtenir des donnees relatives a un patient pour l'assistance a la prise de decision, ces donnees devant aider le clinicien pour le diagnostic et le traitement d'un etat pathologique. Le procede consiste a collecter (372) des donnees relatives a un patient en reponse a un questionnaire d'assistance a la prise de decision. Ce questionnaire comprend un nombre de questions dont certaines servent a l'assistance a la prise de decision, lesquelles concernent le patient et les membres de sa famille. Apres avoir ete collectees, les donnees relatives au patient sont evaluees (382) a l'aide de la base de connaissance pour generer (376) des donnees relatives au patient pour l'assistance a la prise de decision. Les donnees relatives au patient pour l'assistance a la prise de ...
Journal of Cutaneous Pathology, 1993
Melanoma growth stimulatory activity (MGSA/GRO), a cytokine originally characterized as an autocr... more Melanoma growth stimulatory activity (MGSA/GRO), a cytokine originally characterized as an autocrine growth factor for melanoma cells, is highly chemotactic for neutrophils and releases neutrophil elastase as well as other matrix-degrading enzymes. Previous work has demonstrated the presence of MGSA/GRO in melanocytic lesions and in the epidermal keratinocytes of non-lesional skin and psoriatic scale. Herein, MGSA/GRO localization was examined in a variety of human skin lesions exhibiting proliferative and/or differentiative disorders using immunohistochemical methods. Most lesions showed greater MGSA/GRO immunoreactivity in the more differentiated suprabasal keratinocytes of the stratum spinosum and stratum granulosum than in the stratum basalis, where the dividing basal cells are found. Hair follicles, sebaceous glands, and sweat glands were also frequently positive for MGSA/GRO. The highest level of immunoreactive MGSA/GRO in diseased epidermis was detected in verruca vulgaris, followed by psoriasis, keratoacanthoma, and squamous cell carcinoma. Detection of MGSA/GRO in basal cell carcinoma was variable, being present in the sclerosing variant and absent in the more common nodular variant. Melanocytic lesions stained less intensely for MGSA/GRO than keratinocytic lesions, where the levels of MGSA/GRO expression correlated with the inflammatory response and degree of keratinocyte differentiation.
Surgical Science, 2022
Human placental allografts are the latest treatment modalities for diabetic ulcers, chronic wound... more Human placental allografts are the latest treatment modalities for diabetic ulcers, chronic wounds, limbs, and tendons for healing cascade and promoting granulation tissue coverage. Purion ® processed dehydrated human amnion/chorion membrane allografts (dHACM), decellularized human collagen matrix (dHCM), dehydrated umbilical cord (dHUC) and micronized dehydrated human amnion/chorion membrane allografts (mdHACM) have been the newest modality used to salvage injured human extremities with tendon and bone exposure. A 53-year-old male was assaulted and sustained second and third degree burns to both legs. The left extremity had a 9.5% total body surface area (%TBSA) burned. The right extremity had a 5.5% TBSA and three exposed tendons (Achilles/flexor digitorum longus/tibialis anterior), muscles, talar and tibial bones. Bilateral extremity pedal pulses were present, and all toes had less than two second capillary refill. Sensation, motor, and strength were normal. During the 48-day-hospital stay, the patient had eight operations: tangential excisional debridements of necrotic tissue with weekly wound dressing applications of dHACM and dHCM, on both legs. In addition, dHUC was applied over the exposed tendons on weeks 2-5. The exposed tendons were injected with mdHACM on weeks 4 and 5. Negative pressure wound therapy was applied at 125 mmHg for fourteen days over the wound surfaces covered with a nonadherent dressing, 3% bismuth tribromophenate petrolatum dressing with a glycerol-hydroxyethyl cellulose lubricant. At discharge for rehabilitation, 90% of the split-thickness-skin-graft (STSG) was viable over the right ankle joint, tendons and bone.
Undersea & Hyperbaric Medicine, 2015
The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been ex... more The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acut...
Journal of wound care, Mar 1, 2024
Journal of Wound Care
As the US population continues to age, costs for hard-to-heal wounds are expected to rise and neg... more As the US population continues to age, costs for hard-to-heal wounds are expected to rise and negatively contribute to the long-term financial stability of Medicare, which is currently labelled a ‘high-risk’ program by the US Government Accountability Office. Within wound care, some skin substitutes, also known as cellular tissue products (CTPs), and now referred to as CAMPS (cellular, acellular, and matrix-like products), have demonstrated improved healing times and cost-effective usage. However, a dramatic increase in the number of CAMPs has led to controversy on reimbursement rates. For instance, in the third quarter of 2022, 30 of 68 CAMPs represented a disproportionate $256 million USD in costs, due to failures to report their average sales pricing. In its calendar year (CY) 2024 Proposed Rules, the Centers for Medicare and Medicaid Services (CMS) did not implement the proposal to package (‘bundle’) CAMPs products within the private office. Moreover, three Medicare Administrati...
Journal of Wound Care
Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently ... more Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exp...
FEBS Letters, May 7, 1990
Using a synthetic oligopeptide (CGGGTPEYLAPEGGK) crosslinked to keyhole limpet hemocyanin we have... more Using a synthetic oligopeptide (CGGGTPEYLAPEGGK) crosslinked to keyhole limpet hemocyanin we have raised polyclonal rabbit antibodies against a 9 residue homologous region found in the catalytic domain of most protein kinases. These antibodies reacted during Western immunoblotting with CAMP dependent protein kinase catalytic subunit, phosphorylase kinase y subunit and calcium calmodulin dependent protein kinase II which have homologous sequences of GTPEYLAPE, GTPSYLAPE and GTPGYLSPE, respectively. Five other protein kinases did not react with anti-GTPEYLAPE antibodies during Western immunoblot&rg. Affinity-purified antibodies were able to detect as little as 50 ng of CAMP dependent protein kinase and 200 ng of Ca*+/calmodulin dependent protein kinase II. Immunoblotting of A431 cell plasma membrane vesicles indicated the presence of an approximately 55 kDa protein that contains the conserved sequence and is likely to be a protein kinase. Antibodies directed against conserved sequences present in protein kinases, or possibly other enzymes, may be useful in identifying previously uncharacterized enzymes at the protein level.
Journal of Wound Care, May 1, 2023
Journal of Wound Care, Oct 2, 2022
Journal of Wound Care
Despite improvements in treatment methods and outcomes, burns remain one of the principal causes ... more Despite improvements in treatment methods and outcomes, burns remain one of the principal causes of mortality and morbidity worldwide. Burns involving the hands are estimated to occur in >80% of people with burns. Hand burns have also been associated with long-term social, psychological and physical consequences that can impede a patient's full reintegration to the community and decrease their overall quality of life. Clinically, when the trajectory towards complete re-epithelialisation stalls in deep burn wounds of the hand, skin grafting is indicated, but cosmetic problems often remain. A recent publication highlighted common complications for burns involving the hand such as scar disturbances (26%) and scar contractures (14%). Innovative approaches with the potential to reduce the occurrence of complicating scar disturbances and contractures are sought by healthcare providers specialising in burns. This case report describes a novel approach to wound closure using a topica...
Journal of Wound Care
There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenog... more There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.
International Wound Journal
Wounds-a Compendium of Clinical Research and Practice, Sep 1, 2022
Journal of Wound Care
Objective: Pyoderma gangrenosum (PG) is an often-misdiagnosed, painful, inflammatory and ulcerati... more Objective: Pyoderma gangrenosum (PG) is an often-misdiagnosed, painful, inflammatory and ulcerative skin disorder. It is an orphan disease, where standard wound treatments such as sharp surgical debridement are contraindicated. This retrospective case series sought to evaluate the application of dehydrated human amnion/chorion membrane (DHACM) as a skin substitute in cases that were refractory to a range of standard-of-care techniques. Method: This retrospective case series involved wounds which failed to close with standard escalating treatments, including anti-inflammatory and immunosuppressive therapies. Subjects were transitioned to DHACM and wound sizes were monitored until closure. Results: Wounds (n=5) for all three subjects had stalled with standard therapies for at least 2.5 months but responded quickly to routinely applied DHACM treatments, and closure was achieved in each case. Conclusion: This retrospective pilot case series examined the use of DHACM as an alternative wo...
Journal of Wound Care
Objective: To determine the role of debridement when patients are using placental-derived allogra... more Objective: To determine the role of debridement when patients are using placental-derived allografts (PDAs), data from two prospective, multicentre, randomised controlled trials (RCTs) were evaluated for the quality or adequacy of debridement on diabetic foot ulcers (DFUs) treated with PDAs. Results were compared with real-world findings via a retrospective analysis of 2015–2019 Medicare claims for DFUs. Method: Debridement adequacy in the prospective RCTs was adjudicated by three blinded wound care specialists. Treatments included two PDAs, dehydrated human amnion/chorion membrane (DHACM, n=54) or dehydrated human umbilical cord (DHUC, n=101), compared with standard of care (SOC, n=110). The key outcome was the influence of adequate debridement on rates of complete closure within 12 weeks. Additionally, a retrospective analysis of 2015–2019 Medicare claims for DFUs that received routine debridement at intervals ranging from every 1–7 days (18,900 total episodes), 8–14 days (35,728 ...
Ostomy Wound Management, 2015
Journal of Wound Care, 2022
Objective: To evaluate the cost-effectiveness and budget impact of using standard care (no advanc... more Objective: To evaluate the cost-effectiveness and budget impact of using standard care (no advanced treatment, NAT) compared with an advanced treatment (AT), dehydrated human amnion/chorion membrane (DHACM), when following parameters for use (FPFU) in treating lower extremity diabetic ulcers (LEDUs). Method: We analysed a retrospective cohort of Medicare patients (2015–2019) to generate four propensity-matched cohorts of LEDU episodes. Outcomes for DHACM and NAT, such as amputations, and healthcare utilisation were tracked from claims codes, analysed and used to build a hybrid economic model, combining a one-year decision tree and a four-year Markov model. The budget impact was evaluated in the difference in per member per month spending following completion of the decision tree. Likewise, the cost-effectiveness was analysed before and after the Markov model at a willingness to pay (WTP) threshold of $100,000 per quality adjusted life year (QALY). The analysis was conducted from the...
L'invention concerne un systeme d'assistance a la prise de decision contenant des donnees... more L'invention concerne un systeme d'assistance a la prise de decision contenant des donnees stockees dans une base de connaissances, utilise selon un procede permettant a un clinicien d'obtenir des donnees relatives a un patient pour l'assistance a la prise de decision, ces donnees devant aider le clinicien pour le diagnostic et le traitement d'un etat pathologique. Le procede consiste a collecter (372) des donnees relatives a un patient en reponse a un questionnaire d'assistance a la prise de decision. Ce questionnaire comprend un nombre de questions dont certaines servent a l'assistance a la prise de decision, lesquelles concernent le patient et les membres de sa famille. Apres avoir ete collectees, les donnees relatives au patient sont evaluees (382) a l'aide de la base de connaissance pour generer (376) des donnees relatives au patient pour l'assistance a la prise de decision. Les donnees relatives au patient pour l'assistance a la prise de ...
Journal of Cutaneous Pathology, 1993
Melanoma growth stimulatory activity (MGSA/GRO), a cytokine originally characterized as an autocr... more Melanoma growth stimulatory activity (MGSA/GRO), a cytokine originally characterized as an autocrine growth factor for melanoma cells, is highly chemotactic for neutrophils and releases neutrophil elastase as well as other matrix-degrading enzymes. Previous work has demonstrated the presence of MGSA/GRO in melanocytic lesions and in the epidermal keratinocytes of non-lesional skin and psoriatic scale. Herein, MGSA/GRO localization was examined in a variety of human skin lesions exhibiting proliferative and/or differentiative disorders using immunohistochemical methods. Most lesions showed greater MGSA/GRO immunoreactivity in the more differentiated suprabasal keratinocytes of the stratum spinosum and stratum granulosum than in the stratum basalis, where the dividing basal cells are found. Hair follicles, sebaceous glands, and sweat glands were also frequently positive for MGSA/GRO. The highest level of immunoreactive MGSA/GRO in diseased epidermis was detected in verruca vulgaris, followed by psoriasis, keratoacanthoma, and squamous cell carcinoma. Detection of MGSA/GRO in basal cell carcinoma was variable, being present in the sclerosing variant and absent in the more common nodular variant. Melanocytic lesions stained less intensely for MGSA/GRO than keratinocytic lesions, where the levels of MGSA/GRO expression correlated with the inflammatory response and degree of keratinocyte differentiation.
Surgical Science, 2022
Human placental allografts are the latest treatment modalities for diabetic ulcers, chronic wound... more Human placental allografts are the latest treatment modalities for diabetic ulcers, chronic wounds, limbs, and tendons for healing cascade and promoting granulation tissue coverage. Purion ® processed dehydrated human amnion/chorion membrane allografts (dHACM), decellularized human collagen matrix (dHCM), dehydrated umbilical cord (dHUC) and micronized dehydrated human amnion/chorion membrane allografts (mdHACM) have been the newest modality used to salvage injured human extremities with tendon and bone exposure. A 53-year-old male was assaulted and sustained second and third degree burns to both legs. The left extremity had a 9.5% total body surface area (%TBSA) burned. The right extremity had a 5.5% TBSA and three exposed tendons (Achilles/flexor digitorum longus/tibialis anterior), muscles, talar and tibial bones. Bilateral extremity pedal pulses were present, and all toes had less than two second capillary refill. Sensation, motor, and strength were normal. During the 48-day-hospital stay, the patient had eight operations: tangential excisional debridements of necrotic tissue with weekly wound dressing applications of dHACM and dHCM, on both legs. In addition, dHUC was applied over the exposed tendons on weeks 2-5. The exposed tendons were injected with mdHACM on weeks 4 and 5. Negative pressure wound therapy was applied at 125 mmHg for fourteen days over the wound surfaces covered with a nonadherent dressing, 3% bismuth tribromophenate petrolatum dressing with a glycerol-hydroxyethyl cellulose lubricant. At discharge for rehabilitation, 90% of the split-thickness-skin-graft (STSG) was viable over the right ankle joint, tendons and bone.
Undersea & Hyperbaric Medicine, 2015
The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been ex... more The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acut...