Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.

Rapid enzymatic burn debridement: A review of the paediatric clinical trial experience.

NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy-seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty-three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III-b follow-up study (9 NXB and 8 SOC). The average long-term modified Vancouver Scar Scale scores were 3.4 for NXB-treated wounds vs 4.4 for SOC-treated wounds (NS). There were no significant treatment-related adverse events. Additional studies are needed to strengthen these results.

Effect of Botulinum Toxin A on Muscle Healing and its Implications in Aesthetic and Reconstructive Surgery.

BACKGROUND: Muscle activity contributes to the enhancement of facial aging deformity, blepharospasm, cerebral palsy spasticity, trismus, torticollis, and other conditions. Myotomy of the involved muscles in order to reduce the deformity has variable success rates due to muscle healing and regeneration of activity. OBJECTIVES: The goal of this study was to investigate whether blocking striated muscle activity with Botulinum toxin (BtxA) during the healing time after myotomy alters the healing process and reduces long-term muscle activity. METHODS: Eighteen Sprague Dawley rats where divided into 3 groups: group A (n = 7) underwent myotomy of their Latisimus Dorsi muscle; group B (n = 7) underwent myotomy and injection of BtxA into their severed muscle; group C (n = 4) injection of BtxA only. Muscle strength was tested periodically using a grip test. RESULTS: Starting at week 16 and until the termination of study at week 22, group B (Myotomy + BtxA) showed significant reduction in muscle power compared to the two control groups. CONCLUSIONS: Addition of BtxA injection into a muscle immediately after myotomy may interfere with muscle healing and contribute to a more successful long-term result.

Bromelain-based enzymatic debridement of chronic wounds: A preliminary report.

Sharp debridement is currently considered most effective for debridement of chronic wounds; however, some patients do not have access to or cannot be treated by surgical methods. This study was designed to provide a first impression of the safety and efficacy of bromelain-based enzymatic debridement of chronic wounds. Two consecutive single-arm studies assessing the enzymatic debridement efficacy of a concentrate of proteolytic enzymes enriched in bromelain in chronic wounds was conducted in 2 medical centres. Patients were treated with up to 11 consecutive 4-hour enzymatic debridement sessions and then treated until wound closure. Twenty-four patients with chronic wounds of different aetiologies were enrolled. All wounds achieved an average of 68% ± 30% debridement in an average of 3.5 ± 2.8 enzymatic debridement 4-hour sessions. Seventeen responding wounds (venous, diabetic, pressure, and post-traumatic aetiologies) achieved an average 85% ± 12% debridement in 3.2 ± 2.5 applications. Seven non-responding wounds (arterial and post-surgical aetiologies) achieved an average 26% ± 13% debridement in 4.3 ± 3.5 applications. No treatment-related serious adverse events were observed, and the only adverse event attributed to the enzymatic debridement was pain. These preliminary results indicate the potential safety and efficacy of bromelain-based enzymatic debridement in chronic wounds. Larger controlled studies are needed to further investigate this indication.

Facial Reconstruction of a Mucormycosis Survivor by Free Rectus Abdominis Muscle Flap, Tissue Expansion, and Ocular Prosthesis.

Invasive sinonasal mucormycosis is a rare fungal infection that usually occurs in immunocompromised or diabetic patients, and it is often fatal. The authors present a case of a woman patient suffering from systemic lupus erythematosus and diabetes mellitus treated with prednisone, presenting with a rapidly progressive rhino-orbital-cerebral mucormycosis. She was successfully treated with combined intravenous antifungal therapy and radical debridement followed by complex defect reconstruction with a free vertical rectus abdominis myocutaneous flap, tissue expander, and ophthalmic prosthesis.

Defensive Medicine Among Plastic and Aesthetic Surgeons in Israel.

BACKGROUND: Defensive medicine (DM) includes medical practices that are aimed at avoiding liability rather than benefitting the patient. DM has not been well characterized among plastic surgeons. OBJECTIVES: The authors examined the extents of intended and unintended DM among members of the Israeli Society of Plastic and Aesthetic Surgery (ISPAS) and identified risk factors for DM. METHODS: A total of 108 ISPAS members were asked to complete a questionnaire that addressed physician attitudes toward DM and intended or unintended DM practices. RESULTS: Seventy-eight surgeons (72.2% response rate) returned the questionnaire, although some questionnaires were returned incomplete. Forty respondents acknowledged practicing DM (ie, DM group), and 33 respondents did not (ie, non-DM group). There were no between-group differences in gender, years of practice, or number of previous litigations. Thirty-one percent of respondents in the DM group indicated that they avoid certain surgical procedures, compared with 6% of respondents in the non-DM group (P = .008). In private practice, 66.2% of respondents stated that they obtain written informed consent twice before surgery, and 100% request preoperative blood-coagulation testing. In contrast, 40% and 74% of respondents in public practice, respectively, acknowledged these behaviors (for consent, P = .027; for testing, P = .0059). Sixty-three percent of respondents prescribe antibiotics for more than 24 hours postoperatively, and this practice was slightly more common in the DM group (34 prescribe antibiotics vs 21 in the non-DM group; P = .079). CONCLUSIONS: DM is highly integrated into the daily medical practices of plastic surgeons in Israel.

[REVIEW OF 30 YEARS OF RESEARCH AND DEVELOPMENT OF AN ENZYMATIC DEBRIDEMENT AGENT FOR BURNS].

INTRODUCTION: Early removal of burn eschar is a cornerstone of burn care. The most commonly practiced eschar removal technique for deep burns in modern burn care is surgical debridement but this technique is associated with surgical burden and leads to unnecessary excision of viable tissue. GOALS: To review 30 years of research and development of an enzymatic debridement agent for burns. METHODS: Studies performed during the last 30 years are reviewed in this manuscript. RESULTS: Patients who underwent enzymatic debridement had a significantly shorter time to complete debridement, the surgical burden was significantly lower, hand burns did not necessitate escharotomy, and the long term results were favorable. DISCUSSION: Early enzymatic debridement leads to an efficient debridement, preservation of viable tissue, a reduction in surgical burden and favorable long term results. CONCLUSION: We believe early enzymatic debridement will lead to better care for burn victims and perhaps, even to a paradigm shift in the treatment of burns.

Double Back Cut in Post-mastectomy Breast Skin (Fish-Shaped Skin Paddle) in Delayed Pedicled TRAM Flap Breast Reconstruction.

Breast reconstruction has become standard of care for female patients with breast cancer. The transverse rectus abdominis musculo-cutaneous flap (TRAMf) is the most common method of immediate or delayed autologous breast reconstruction following mastectomy. We share our experience with modified, double back cut of post-mastectomy skin in delayed pedicled TRAMf breast reconstruction, resulting in fish-shaped skin paddle. This sort of back cut is a simple, reliable way to obtain a natural, esthetically pleasant breast mound with inconspicuous hidden scars.

Total lip reconstruction with tendinofasciocutaneous radial forearm flap.

INTRODUCTION: Squamous cell carcinoma is a common tumour of lower lip. Small defects created by surgical resection may be readily reconstructed by linear closure or with local flaps. However, large tumours resection often results with microstomia and oral incompetence, drooling, and speech incomprehension. The goal of this study is to describe our experience with composite free radial forearm-palmaris longus tendon flap for total or near total lower lip reconstruction. PATIENTS AND METHODS: This procedure was used in 5 patients with 80-100% lip defect resulting from Squamous cell carcinoma. Patients' age ranged from 46 to 82 years. They are three male patients and two female. In 3 cases chin skin was reconstructed as well and in one case a 5 cm segment of mandible was reconstructed using radius bone. In one case where palmaris longus was missing hemi-flexor carpi radialis tendon was used instead. All patients tolerated the procedure well. RESULTS: All flaps totally survived. No patient suffered from drooling. All patients regained normal diet and normal speech. Cosmetic result was fair to good in all patients accept one. CONCLUSION: We conclude that tendino-fasciocutaneous radial forearm flap for total lower lip reconstruction is safe. Functional and aesthetic result approaches reconstructive goals.

Acute esophageal dilation mimicking serious pulmonary complication after post-bariatric abdominoplasty.

UNLABELLED: Abdominoplasty is a frequent operative procedure among patients with massive weight loss following laparoscopic adjustable gastric banding (LAGB) surgery. After abdominoplasty, patients are carefully monitored and usually discharged from the clinic after overnight hospitalization. We report a case of acute esophageal dilation after abdominoplasty, following LAGB, mimicking a serious pulmonary complication. Three hours after a complete uneventful abdominoplasty, including reinforcement of the abdominal wall and removal of apron skin, a 39-year-old female patient developed cough and signs of respiratory distress. These symptoms were successfully treated by ventolin (salbutamol) inhalation. During the first night the patient required additional inhalation and was discharged from the hospital in good and stable condition. Three hours later she noticed respiratory distress and fever and was referred to the emergency room (ER). In the ER, a pulmonary embolism was suspected and the patient underwent CT angiography. On examination, acute severe esophageal dilation with fluid level was found. The esophageal diameter was 47 mm and the esophagus was compressing the mediastinum and trachea. The acute esophageal dilation was resolved after the gastric band was released by evacuation of saline solution from the subcutaneous port. The above-mentioned symptoms quickly disappeared during the next 2 h and the patient was discharged from the ER. We suggest complete gastric band release as a standard component of a bariatric surgery patient's preparation for abdominoplasty surgery. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Anacaulase-bcdb for the treatment of severe thermal burns.

INTRODUCTION: Accurate burn depth assessment and early excision of burn eschar with maximal dermal preservation are key concepts in the optimal care of burn injury. Although excision with knife has long since been standard of care, a newer technique for wound bed preparation utilizing a bromelain-based enzyme has gained popularity worldwide and may offer several advantages. AREAS COVERED: Here we report the pharmacologic properties, evidence for clinical efficacy, safety, and tolerability of anacaulase-bcdb for the treatment of deep partial thickness and full thickness burns. EXPERT OPINION: Anacaulase-bcdb is a safe, non-surgical, selective eschar removal agent. It offers advantages over surgical excision of burn with knife and fulfills two unmet needs: burn depth assessment and dermal preservation during excision. Evidence supports a faster time to complete eschar removal; reduced number of operations; reduction in the amount of autografting, length of stay, and blood loss; prevention of burn induced compartment syndrome; and improved cosmetic outcome.

Maternal pruritus gravidarum and its long-term effect on dermatological morbidity in the offspring.

PURPOSE: Pruritus gravidarum is characterized by general pruritus in the absence of primary skin lesions. In this study, we sought to evaluate whether the offspring (≤ 18 years) of mothers diagnosed with pruritus gravidarum, are at increased risk of long-term dermatology-related hospitalization. METHODS: A population-based, retrospective cohort study of all singleton deliveries between 1991 and 2021 was conducted at a tertiary medical center. Offspring of mothers diagnosed with pruritus gravidarum were compared to offspring of non-exposed mothers. First admission involving dermatological morbidity of the offspring were analyzed using ICD-9 codes. Kaplan-Meier survival curves were used to compare the cumulative hospitalization incidence between the groups and Cox regression models were utilized to adjust for confounding variables. RESULTS: A total of 849 women out of 356,356 deliveries that fulfilled the inclusion criteria were diagnosed with pruritus gravidarum during pregnancy (0.23%). Among offspring to mothers with pruritus gravidarum versus non-pruritus gravidarum mothers, hospitalization rates involving dermatological morbidity, were higher (7.1% vs. 4.6%, p < .001) a finding that was consistent with the Kaplan-Meier survival curve (Log rank p = .002). In the Cox regression model, pruritus gravidarum was found to be a significant independent risk factor for dermatological-related hospitalizations in the offspring after controlling for gestational age, hypertensive disorders, diabetic disorders, meconium-stained amniotic fluid exposure and fertility treatments (adjusted HR = 1.44, 95% CI 1.12-1.85, p = .004). CONCLUSIONS: Maternal pruritus gravidarum is an independent risk factor for long-term dermatology-related hospitalization in the offspring up to the age of 18 years.

Blood Stream Infections in Burns: A 14-Year Cohort Analysis.

BACKGROUND: Blood stream infections are a significant cause of morbidity and mortality in burns, and pathogen identification is important for treatment. This study aims to characterize the microbiology of these infections and the association between the infecting pathogen and the hospitalization course. METHODS: We conducted a cohort study that included records of burn patients treated at the Soroka University Medical Center between 2007-2020. Statistical analysis of demographic and clinical data was performed to explore relationships between burn characteristics and outcomes. Patients with positive blood cultures were divided into four groups: Gram-positive, Gram-negative, mixed-bacterial, and fungal. RESULTS: Of the 2029 burn patients hospitalized, 11.7% had positive blood cultures. The most common pathogens were Candida and Pseudomonas. We found significant differences in ICU admission, need for surgery, and mortality between the infected and non-infected groups (p < 0.001). Pathogen groups differed significantly mean TBSA, ICU admission, need for surgery, and mortality (p < 0.001). Multivariate analysis showed flame (OR 2.84) and electric burns (OR 4.58) were independent risk factors for ICU admission and surgical intervention (p < 0.001). Gram-negative bacterial infection was found to be an independent predictor of mortality (OR = 9.29, p < 0.001). CONCLUSIONS: Anticipating specific pathogens which are associated with certain burn characteristics may help guide future therapy.

Relieving pain and distress symptoms in the outpatient burn clinic: The contribution of a medical clown.

CONTEXT: High levels of pain and emotional distress characterize the experience of patients, at burn outpatient clinic and reflect on their accompanying persons and the medical personal. OBJECTIVES: To examine the effect of a medical clown presence on: the patients' pain and distress levels as perceived by the patient and by their accompanying persons, and the emotional response of healthcare personnel. METHODS: A yearlong prospective observational comparative study in the burn outpatient clinic, operating twice a week, with a medical clown's presence once a week [Exposure Group - EG] versus clinic without clown presence [Non exposure Group- NEG]. Patients and accompanying persons filled pain [WBS, VAS] and emotional distress [SUDS] questionnaires regarding the patient's experience: before (T1) and after treatment (T2). The clinic personnel filled SUDS at the beginning and the end of the clinic working hours. RESULTS: Significantly lower WBS, VAS, and SUDS scores were reported at T2 in the EG as compared to the NEG both in patients and in the accompanying persons' evaluations. Personnel SUDS were affected in a similar manner. CONCLUSION: Presence of a medical clown induced a positive atmosphere in the clinic. It is possible that the effect of humor through stress reduction mechanism lessened agony. Furthermore, the distraction the clown evoked played a role in the decrease of pain and emotional distress. We recommend implementing psychosocial oriented interventions such as those performed by a medical clown to improve the emotional atmosphere in the ambulatory clinic of patients, accompanying persons and healthcare personnel.

[Axillary web syndrome--a variant of Mondor's disease, following excision of an accessory breast].

Cording, an unusual form of superficial thrombophlebitis, is a variant of the disease first described by Fage in 1870 and subsequently characterized by Henry Mondor in 1939 as sclerosing thrombophlebitis of the subcutaneous veins of the anterior chest wall. Similar lesions have also been found in the penis, groin, abdomen, arm, and axilla and have been reported under a variety of names. In the axilla the condition is termed axillary web syndrome (AWS) and is seen after axillary lymph node dissection and sentinel lymph node biopsy. A recent report suggests that pathophysiology of AWS is lymphatic in origin rather than venous. We report a unique case of unilateral AWS after excision of an axillary accessory breast and discuss the pathophysiology.

[Description of differential optical spectropolarimetric imaging system (DOSI) for non-invasive detection of skin tumors].

BACKGROUND: Most physicians diagnose skin malignancy using theoretical criteria and clinical experience. Apart from dermatoscopy, noninvasive means for skin tumors' diagnosis are highly expensive and are not in daily use. We developed a simple, handy and relatively inexpensive tool for non-invasive diagnosis of skin tumors. The Differential Optical Spectropolarimetric Imaging system (DOSI) is based on collecting information from the surface and depth of skin tumors, using the advantage of liquid crystal devices (LCDs]. OBJECTIVE: DOSI feasibility study in order to diagnose skin tumors non-invasively. METHOD: Skin tumor optical data was collected in order to create image indicators for specific skin tumors. Spectral images of skin tumors are captured before the lesion that was scheduled for removal was surgically excised. Repeating features of images of each tumor type (which was histologically diagnosed) that characterize the specific tumor and show distinction from the features of other tumors are recorded. RESULTS: The feasibility of DOSI has been demonstrated for research, but it is not yet mature for clinical use. Specific images, indicating specific skin tumors could not yet be reliably concluded. One relatively obvious characteristic for malignancy seems to be crescent-like and finger-like growth patterns. In the non-malignant lesions: crescent and finger-like structures are of less pronounced orders of magnitude. Crescents are more open and radius of curvature are of larger orders of magnitude than in malignant specimen. DISCUSSION: The advantage of using LCD is the ability to manipulate light electronically, without any movable components. LCDs are the building blocks of optical filters and polarization controllers. Using optical filters and polarization controllers, we are able to electronically manipulate the polarization and wavelength of our light source without any movable components. The light source emits different wavelengths (colors) that penetrate the tissue at different depths. The camera (CCD) captures the diffused reflected light from a skin lesion as a sequence of images for each polarization stage. By applying our novel method for each polarization stage we are able to overcome the noise of the diffused reflection and emphasize the scattering areas. Emphasizing the scattering areas provided images that may indicate malignancy. CONCLUSIONS: The feasibility of DOSI has been demonstrated. In order to obtain reliable diagnostic image indicators for specific skin tumors, more clinical tests are necessary.

Effect of quilting on seroma formation in mastectomies: A meta-analysis.

BACKGROUND: Seroma is the most common complication following mastectomy and can require several days of drainage and lead to delayed wound healing, longer hospital stays, and an increased financial and emotional burden. Seroma formation is not well understood and but there is good evidence that closing the dead space via quilting can help reduce seroma formation. This study assessed randomized controlled trials and reviewed current literature to elucidate if there is a strong association between quilting sutures and seroma formation. METHODS: A systematic search of 5 databases using search terms similar to "seroma", "quilting", "flap fixation", "random", and "mastectomy". Data was extracted and Medcalc software used to perform a meta-analysis of the primary outcome: incidence of seroma formation, as well as secondary outcomes: volume and duration of drainage. RESULTS: Eleven randomized controlled trials with 2009 patients were included. Quilting with sutures greatly reduced the incidence of seroma formation compared with conventional closure (p < 0.001, RR 0.367 [95% CI 0.25, 0.539]; I2 = 63.56%) as well as duration of drainage (p = 0.015, SMD -1.657, SE 0.680 [95% CI -2.991, -0.324]; 8 studies, n = 1578; I2 = 98.98%). Quilting did not significantly affect volume of drainage. CONCLUSIONS: Quilting was found to be associated with lower seroma rates. Future studies should investigate the use of quilting in combination with other preventative techniques to search for a synergistic method that will further improve patient care.

Cell stiffness predicts cancer cell sensitivity to ultrasound as a selective superficial cancer therapy.

We hypothesize that the biomechanical properties of cells can predict their viability, with Young's modulus representing the former and cell sensitivity to ultrasound representing the latter. Using atomic force microscopy, we show that the Young's modulus stiffness measure is significantly lower for superficial cancer cells (squamous cell carcinomas and melanoma) compared with noncancerous keratinocyte cells. In vitro findings reveal a significant difference between cancerous and noncancerous cell viability at the four ultrasound energy levels evaluated, with different cell lines exhibiting different sensitivities to the same ultrasound intensity. Young's modulus correlates with cell viability (R 2 = 0.93), indicating that this single biomechanical property can predict cell sensitivity to ultrasound treatment. In mice, repeated ultrasound treatment inhibits tumor growth without damaging healthy skin tissue. Histopathological tumor analysis indicates ultrasound-induced focal necrosis at the treatment site. Our findings provide a strong rationale for developing ultrasound as a noninvasive selective treatment for superficial cancers.

Dry needling for scar treatment.

OBJECTIVE: To review current scientific knowledge as to the efficacy of dry needling of scars on pain and other related symptoms and explore the possible physiological mechanisms of action. METHODS: A narrative review of scientific literature published in English. RESULTS: Two randomized controlled trials found that dry needling of scars (using the classic "surrounding the dragon" technique in one study and intradermal needling in a second study) was more effective than sham or control interventions with respect to scar appearance and pain. Two case reports have suggested that scar needling generates a rapid decrease in pain and improvement of mobility in scarred tissues. Another two case reports have reported positive effects of scar needling on the wound healing process. These findings are supported by an animal study examining the effect of needling on the wound healing process and the physiological mechanisms of action underlying the technique. CONCLUSION: There is preliminary evidence that the "surrounding the dragon" needling technique is a beneficial treatment for patients suffering from scar pain and other scar-related symptoms and can facilitate wound healing and make this process less painful. Further high-quality studies should be conducted to verify/quantify the efficacy of this method, to better understand the underlying mechanisms of action underlying the effects of scar needling and to establish an effective intervention protocol.