Subsequent Scarring Research Articles

Astrocyte‐to‐neuron reprogramming for spinal cord repair

Traumatic spinal cord injury (SCI) disrupts neural pathways and results in the devastating tissue damage and loss of function, with subsequent reactive gliosis and tissue scarring that limits further loss, but also limits endogenous repair. One therapeutic strategy gaining some attention in recent years is cellular reprogramming, which harnesses advances in cellular engineering to directly convert cells from one phenotype to another. The present work explores strategies for converting either mature or developing astrocytes into neurons. Our initial experiments have begun exploring viral targeting of glial cells to promote doxycycline‐inducible overexpression of neurogenic transcription factors (TFs) Ascl1 or a combination of microRNAs (miRs) miR124, miR9/9*, for neuronal conversion. Our primary goal was to establish optimal conditions for consistent and efficient reprogramming of developing spinal glia and mature reactive spinal astrocytes.Primary astrocyte cultures were generated from postnatal days 2‐3 (P2‐3) rat cortex and spinal cord, and then were activated with TGFβ (Transforming growth factor beta) one day prior to viral transduction. Fifteen days following doxycycline administration, astrocytes took on a typical neuronal morphology. Immunocytochemistry confirmed that these cells were positive for neuronal markers MAP2, NeuN and TAUR1, and negative for GFAP. Multielectrode array recordings of converted cells revealed spontaneous firing consistent with neuronal activity.These preliminary results confirm that cortical and spinal astrocytes can be efficiently reprogrammed into neurons by either Ascl1 or miRs. Advances in cellular reprogramming are providing novel ways to manipulate the cytoarchitecture of the injured cervical spinal cord. Our ongoing work is now using this same approach to modify developing glial precursors that can be harness for their pro‐reparative properties for spinal cord repair.

Clonal Tracing of Heart Regeneration.

Cardiomyocytes in the adult mammalian heart have a low turnover during homeostasis. After myocardial injury, there is irreversible loss of cardiomyocytes, which results in subsequent scar formation and cardiac remodeling. In order to better understand and characterize the proliferative capacity of cardiomyocytes, in vivo methods have been developed to track their fate during normal development and after injury. Lineage tracing models are of particular interest due to their ability to record cell proliferation events over a long period of time, either during development or in response to a pathological event. This paper reviews two well-studied lineage-tracing, transgenic mouse models—mosaic analysis with double markers and rainbow reporter system.

Marjolin's ulcer: A case report of a rare but preventable lesion

Marjolin's ulcer (MU) is a rare cutaneous malignancy first described in 1828. MU arises in the setting of injured skin with subsequent chronic scarring or ulceration and eventual malignant transformation. While most cases of MU are associated with burn scars, less common settings have included traumatic wounds, venous stasis ulcers, osteomyelitis and pressure sores. MU may develop at any age but tends to affect older individuals. This is likely due to the typically long latency period from inciting event to malignant transformation, which averages 30 to 35 years. A male predilection exists. Lesions occur at any anatomic site, but the lower extremities and the head and neck region are most frequently affected. The predominant malignancy in MU is squamous cell carcinoma (8090%) followed by cases of basal cell carcinoma and malignant melanoma. The treatment of choice is wide surgical resection. MU is typically an aggressive malignancy with a high recurrence rate and poor 5-year survival. A 70 year-old woman from Togo had suffered a burn injury to the left side of her head many years previously. The wounded skin remained unchanged for decades, but recently developed an enlarging ulcer. Incisional biopsy of the ulcerated tissue resulted in a final diagnosis of keratinizing squamous cell carcinoma. Given the clinical setting, the lesion was deemed consistent with a MU. MU is thought to be a largely preventable form of cutaneous malignancy. Proper wound management, including efforts to minimize infection and healing by secondary intention, substantially reduces the risk of malignant transformation. For this reason, MU has a propensity to affect disadvantaged individuals living in poverty who have limited access to proper or adequate healthcare.

Cirrhosis, Hepatocellular Carcinoma, and Locoregional Therapies

Cirrhosis is the development of damage and subsequent scarring of hepatic tissues leading to the development of fibrosis. The development of cirrhosis is one of the major risk factors for hepatocellular carcinoma (HCC). HCC is the sixth most common form of cancer worldwide and the fourth cause of cancer-related deaths. This is often because HCC is not diagnosed until it has reached advanced stages. In the United States and Europe, HCC is staged and managed according to the Barcelona Clinic Liver Cancer system. Treatment for HCC includes transplantation, surgical resection, locoregional radiology therapies, targeted systemic chemotherapy, and immunotherapy. This article is an overview of cirrhosis, HCC, and various treatment modalities and associated postprocedural syndromes.

Autologous skin micro-grafts and allogenic skin allograft for mitten hand deformity treatment in epidermolysis bullosa

<p><strong>Background:</strong> In the genetic skin blistering disorder dystrophic epidermolysis bullosa recurrent blisters and erosions on mechanically stressed areas, as the hands, result in subsequent scarring and development of pseudosyndactylies and contractures. In its most severe form, all fingers are constrained into a fist of scarred (“mitten-hand”-deformity). No causative therapy exists and only a surgical release of the fingers is possible. Hereby, the development of large skin defects is inevitable; the lack of healthy autologous skin for grafting remains a difficult challenge.</p><p><strong>Methods:</strong> We propose a new technique: It adopts a treatment strategy from the therapy of large extent burns and consists of a combination of autogenic and allogenic skin grafting.</p><p><strong>Results:</strong> We present a beneficial outcome in 18 mitten hand deformities treated with this technique. In all patients, the initial functional outcome was improved. Nearly all patients got a considerably widened grip span and durable skin conditions post-operatively. Mean follow-up was 3 years. Typically, recurrence of the scarring occurred from 6 months to 2 years after operation.</p><p><strong>Conclusions:</strong> This is the first report on the use of the combination of autogenous pinch skin grafts with allogenic (parental) skin overlay for skin defects in EB. It provides undisturbed wound healing under a “biological dressing”, furthermore, a temporary take of the parental skin was visible. Defects were permanently covered with skin of increased mechanical stability, hand function improved remarkably. However, long term follow-up showed beginning recurrence in most of the patients comparable to recurrence rates described in the literature.</p>

Prevention and treatment of CSF leaks in congenital complex spinal lipomas.

Congenital complex spinal lipomas (CSL) are challenging lesions to treat. Cerebrospinal fluid (CSF) leaks are feared complications due to the risk of infection, and subsequent scarring that may promote retethering. Much has been written in the literature on the surgical technique of CSL resection with less emphasis placed on the prevention and management of CSF leak. The authors describe the nuances in the prevention and management of CSF leaks in the context of CSL, including the operative approach, resection, closure and recommended postoperative care. CSF leaks are complications that can be minimized with deliberate steps and meticulous surgical technique.

Surgical Treatment of Iatrogenic Low Variety Anal Stenosis with Diamond Flap Anoplasty – A Prospective Study

Background: Anal stenosis results from loss of anoderm with subsequent fibrosis and scarring of underlying tissue. The condition represents a technical challenge in terms of surgical management. It is a serious complication of anorectal surgery, most commonly seen after surgical haemorrhoidectomy. However, stenosis can also occur after perianal circumferential burn due to application of herbal medicine by village doctors. Objective: This study was conducted to see the outcome of diamond-flap anoplasty for the treatment of moderate to severe anal stenosis. Patients and interventions: Unilateral diamond flaps anoplasty was performed for moderate to severe anal stenosis. Final anal calibre of 25 to 26 mm was targeted. The demographic characteristics, causes of anal stenosis, number of previous surgeries, anal stenosis severity, postoperative complications and the time of return to work were recorded. Results: From July 2012 to January 2017, 18 patients (12 males, 67% and 6 female patients, 33%) with a mean age of 34 years (range, 25-52) were treated. 15 of the patients had a history of previous haemorrhoidectomy and 3 had circumferential perianal chemical burn due to application of herbal medicine by village doctors. Five patients (28%) had moderate anal stenosis and 13 (72%) had severe anal stenosis. Preoperative, intraoperative, and 12-month postoperative anal calibration values were 9 ± 3 mm (range, 5-15), 25 ± 0.75 mm (range, 24- 26), and 25 ± 1 mm (range, 23-27). The clinical success rate was 98.9%. No severe postoperative complications were observed. Conclusion: Diamond-flap anoplasty is a highly successful method for the treatment of anal stenosis caused by previous haemorrhoidectomy and perianal circumferential chemical burn by herbal medicine. J Shaheed Suhrawardy Med Coll 2020; 12(2): 67-71

Facial Ultrasonography in acquired facial lipoatrophy

Facial lipoatrophy refers to the loss of adipose tissue and is manifested by flattening or indentation of the convex contours of the face while lipodystrophy is a wider term associated with abnormalities of fat tissue distribution and its metabolism, leading to excessive loss and/or accumulation of adipocytes. Although the management of facial lipoatrophy is very important for a patient’s social life and mental health, no treatment framework has been developed due to the unknown nature of the disease manifestation. Early recognition and treatment of the active stage of connective tissue diseases is of essential significance in prevention of subsequent scarring and atrophic lesions. Diagnostic techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography (USG), are used to measure the severity of the lipoatrophy. The present study was designed to provide sequential imaging to visualize the disease progression.

Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy

Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.

Burn Care in the Era of Rapid Enzymatic Debridement: Challenging the Dogma that Healing Beyond 21 Days Results in Hypertrophic Scarring

Deep burns are characterized by the presence of a necrotic eschar that delays healing and results in a local and systemic inflammatory response and following healing by secondary intention: heavy scarring. Early surgical debridement followed by grafting was a major advance in deep burn care and is now the standard of care, reducing mortality and hypertrophic scarring. Eschars have alternatively been managed by non-surgical, autolytic debridement, which often results in infection-inflammation, slow epithelialization, granulation tissue formation and subsequent scarring. Studies based on these traditional approaches have demonstrated an association between delayed wound closure (beyond 21 days) and scarring. Early enzymatic debridement with NexoBrid (NXB) followed by appropriate wound care is a novel minimally invasive modality that challenges the well-accepted dictum of a high risk of hypertrophic scarring associated with wound closure that extends beyond 21 days. This is not surprising since early and selective removal of only the necrotic eschar often leaves enough viable dermis and skin appendages to allow healing by epithelialization over the dermis. In the absence of necrotic tissue, healing is similar to epithelialization of clean dermal wounds (like many donor sites) and not healing by the secondary intention that is based on granulation tissue formation and subsequent scarring. If and when granulation islands start to appear on the epithelializing dermis, they and the inflammatory response generally can be controlled by short courses (1-3 days) of topically applied low strength corticosteroid ointments minimizing the risk of hypertrophic scarring, albeit with wound closure delayed beyond the magic number of 21 days. Results from multiple studies and field experience confirm that while deep burns managed with early enzymatic debridement often require more than 21 days to reepithelialize, long-term cosmetic results are at least as good as with excision and grafting.

Prospective Study to Evaluate the Safety and Efficacy of a New Surgical Tube Fixation Method: A Pilot Study.

Various tubes may be fixed to the skin by ligation using silk sutures after gastrointestinal surgery. We investigated the effects of a skin substitute, "Nonaht®," on pain and skin inflammation at the fixation sites of various tubes. The effects of tubes (abdominal drains, small intestinal feeding tubes, and bile duct drainage tubes) fixed in place using either silk sutures or Nonaht were compared for 1-3months. The median pain scores at the fixation site when abdominal drains were removed were 1.0 with silk sutures and 0 with Nonaht (p < 0.001). Scarring at the fixation site at postoperative month (POM) 1 occurred in 13 of 28 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). The median pain scores at the fixation site with long-term tubes on postoperative day (POD) 14 and POM 1 were 2.0 and 1.0, respectively, with silk sutures, and none at all time points with Nonaht (p < 0.001). Scarring at the fixation site at POM 3 occurred in all 10 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). Patients with conventional skin fixation of tubes using silk sutures were continuously aware of pain at the fixation site and developed skin damage and subsequent scar formation, especially for tubes inserted for ≥ 1month. The use of Nonaht may reduce the incidence of dermatitis and wound infections at tube fixation sites, thereby promoting early postoperative recovery.

Reduction in left atrial and pulmonary vein dimensions after ablation therapy is mediated by scar.

Ablative pulmonary vein isolation (PVI) decreases pulmonary vein (PV) and left atrial (LA) dimensions in atrial fibrillation (AF) patients. These changes are attributed to reverse structural remodeling following sinus rhythm restoration but evidence is lacking. We hypothesized that the downsizing is directly caused by the ablative energy and subsequent scar formation. We studied cardiac magnetic resonance imaging in 21 paroxysmal AF patients before and 3months after successful PVI and in healthy sheep (n=12) before and after PVI of the right PV only. PVI decreased the PV diameter in patients and sheep by 11.0(10.3) and 9.2(11.0)%, (p<0.001 and p=0.020), respectively. The control left PV in sheep were unchanged. A linear correlation existed between the extent of PV scar and PVI-induced decrease in PV diameter in patients.After PVI, the LA volume decreased (103(38) vs. 92(31)ml, pre- vs. post-ablation, respectively, p=0.006), while the right atrial (RA) volume was unchanged in patients. A decrease in active emptying fraction after ablation (26.5(10.7) vs. 21.8(10.6)%, pre- vs. post-ablation, p=0.031) was associated with reduced contractility of the PV walls (p=0.004). The contractility of the LA walls was unaltered (p=0.749). The ablation-induced PV diameter reduction was similar in patients with AF and healthy sheep without AF and was associated with PV scar extent. The volume only decreased in LA and not RA after PVI, and wall contractility decreased only in ablated sites. Therefore, the PVI-induced atrial downsizing is caused by the ablative energy and subsequent scar formation.

Corticosteroids in the Management of Infectious Keratitis: A Concise Review

Microbial keratitis is devastating corneal morbidity with a variable spectrum of clinical manifestations depending on the infective etiology. Irrespective of the varied presentation delayed treatment can lead to severe visual impairment resulting from corneal ulceration, possible perforation, and subsequent scarring. Corticosteroids with a potent anti-inflammatory activity reduce host inflammation, thus minimizing resultant scarring while improving ocular symptoms. These potential effects of corticosteroids have been applied widely to treat various corneal diseases ranging from vernal keratoconjunctivitis to dry eye disease. However, antimicrobial therapy remains the mainstay of treatment in microbial keratitis, whereas the use of adjunctive topical corticosteroid therapy remains a matter of debate. Understandably, the use of topical corticosteroids is a double-edged sword with pros and cons in the treatment of microbial keratitis. Herein we review the rationale for and against the use and safety of topical corticosteroids in the treatment of infective keratitis. Important considerations, including type, dose, efficacy, the timing of initiation of corticosteroids, use of concomitant antimicrobial agents, and duration of corticosteroid therapy while prescribing corticosteroids for microbial keratitis, have been discussed. This review intends to provide new insights into the therapeutic utility of steroids as adjunctive treatment of corneal ulcer.

External administration of moon jellyfish collagen solution accelerates physiological wound healing and improves delayed wound closure in diabetic model mice

IntroductionArtificial dermis is an effective therapeutic method for full-thickness dermal defects. However, the currently available artificial dermis made of porcine or bovine type I collagen has several limitations such as incomplete epithelialization and delayed migration of fibrogenic and angiogenic cells into the graft. We previously developed a composite dermal graft containing a mixture of moon jellyfish collagen and porcine type I collagen, and reported its stimulatory effect on both the re-epithelialization of the epidermis and the migration of fibrogenic and angiogenic cells into the graft. In the present study, we examined whether the same effect was observed by administering jellyfish collagen solution externally onto an artificial dermal graft made of bovine type I collagen.MethodsWe used a 6 mm full-thickness wound defect model. Moon jellyfish collagen was prepared as a concentrated 0.5% solution and dripped externally onto a transplanted artificial dermal graft made of bovine type I collagen. Wound repair and long-term dermal tissue remodeling were compared between mice administered jellyfish collagen solution on the bovine collagen graft and those transplanted with a composite dermal graft containing the same amounts of jellyfish and bovine collagens. The stimulatory effect of jellyfish collagen solution was also evaluated using diabetic dB/dB mice.ResultsExternal administration of jellyfish collagen solution onto the bovine collagen graft significantly accelerated wound closure compared to control saline. It also decreased the number of inflammatory cells infiltrating the wound and suppressed absorption of the transplanted graft, as well as reduced subsequent scar formation. Furthermore, external administration of jellyfish collagen solution onto the bovine collagen graft improved the delayed wound healing in diabetic model mice, and this effect was superior to that of the currently used basic fibroblast growth factor.ConclusionsExternal administration of moon jellyfish collagen solution onto a bovine collagen graft significantly accelerated physiological wound healing and prevented excessive scar formation. It also improved wound closure in diabetic model mice, confirming its therapeutic application for intractable skin ulcers caused by impaired wound healing.

Primary cicatricial alopecia: a literature review

The term cicatricial alopecia results from irreversible damage to epithelial stem cells located in the bulge region of the hair follicle with subsequent scarring. Based on the mechanism involved in follicular destruction, cicatricial alopecia is divided into primary and secondary forms. Primary cicatricial alopecia are divided into four groups according to their prominent inflammatory infiltrate: with lymphocytic, neutrophilic, mixed or nonspecific cell inflammation pattern.&#x0D; The review presents the main clinical, histological and dermatoscopic signs of various types of primary cicatricial alopecia.

Diplopia Following External Dacryocystorhinostomy with Intracystic Pawar Implant Implantation: The Tale of an Unheard Complication

Dacryocystorhinostomy (DCR) with Pawar intracystic implant placement is a simple and faster surgical option for treating epiphora. Its advantages being small length of incision (5-6 mm), minimal intraoperative and postoperative bleeding, and sparing of the medial palpebral ligament with no need of creating sac and nasal mucosal flaps anastomosis. The presence of holes at upper and lower end act as extra drainage channel. This makes it superior to conventional DCR with better success rate. Herein, we report a rare complication of diplopia following implantation of Pawar’s implant. We believe in the following chain of events with anterior displacement of implant, local inflammation was evoked, resulting in subsequent scarring and medial rectus fibrosis.

Should Isotretinoin be Stopped Prior to Surgery?

Should Isotretinoin be Stopped Prior to Surgery?

Missed abortion with a large fibroid challenging uterine evacuation – A rare case report

Fibroids in pregnancy are a commonly encountered clinical entity seen frequently in multigravidae than primigravida patients. Since they are usually asymptomatic, medical management is preferred which would delay the surgical enucleation until after delivery. However, the presence of fibroid may alter the uterine anatomy, which complicates uterine aspirations of abortions. In the present case report, we describe the laparoscopic enucleation of a large uterine fibroid followed by suction and evacuation of the missed abortion. This advanced laparoscopic approach is safe, it reduces the size of incision with subsequent postoperative scar and reduces intraoperative bleeding and aids in achieving good hemostasis. Thus, with safety and precautions, this advanced technique can be used in antepartum myomectomy.

A rare case of infectious crystalline keratopathy caused by Burkholderia cepacia

We report a unique case of infectious crystalline keratopathy (ICK) caused by Burkholderia cepacia in a 47-year-old patient with history of multiple penetrating keratoplasties (PKPs). Slit-lamp examination revealed a white nonsuppurative needle-like branching anterior stromal infiltrate. Microscopic examination of the Gram-stained smear showed gram-negative bacilli. Cultures revealed Burkholderia cepacia, which was multidrug resistant and sensitive to piperacillin/tazobactam. Based on antibiotic sensitivity report, patient was started fortified piperacillin-tazobactam (0.32%) eye drop on an hourly basis. After 8 weeks of aggressive therapy, the infiltrate resolved with subsequent corneal scarring and vascularization. To our knowledge, this is the first reported case of Burkholderia-related ICK. ICK, first described by Gorovoy et al.[1] in 1983, is an indolent keratitis with characteristic needle-like branching opacities in the absence of corneal or anterior segment inflammation.[2] The presence of an immunocompromised corneal state, such as chronic topical steroid use post PKP, is a known risk factor for the development of ICK. Other risk factors include surgical procedures such as lamellar keratoplasty, corneal cross-linking, laser-assisted in situ keratomileusis, pterygium excision, and trabeculectomy with 5- FU. Topical anaesthetic abuse as a risk factor has also been described.[3] Burkholderia is a group of Gram-negative bacteria, composed of at least 20 different species. We describe a case of Burkholderia keratitis presenting as ICK in a patient who underwent multiple PKPs and a history of long-term topical steroid therapy.

Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis.

The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day -1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient (r) of r=0.73 and r=0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.