Functional substrate mapping of atrium in patients with atrial scar: A novel method to predict critical isthmus of atrial tachycardia.

Atrial tachycardia (AT) is a common rhythm disorder, especially in patients with atrial structural abnormalities. Although voltage mapping can provide a general picture of structural alterations which are mainly secondary to prior ablations, surgery or pressure/volume overload, data is scarce regarding the functional characteristics of low voltage regions in the atrium to predict critical isthmus of ATs. Recently, functional substrate mapping (FSM) emerged as a potential tool to evaluate the functionality of structurally altered regions in the atrium to predict critical sites of reentry. Current evidence suggested a clear association between deceleration zones of isochronal late activation mapping (ILAM) during sinus/paced rhythm and critical isthmus of reentry in patients with left AT. Therefore, these areas seem to be potential ablation targets even not detected during AT. Furthermore, abnormal conduction detected by ILAM may also have a role to identify the potential substrate and predict atrial fibrillation outcome after pulmonary vein isolation. Despite these promising findings, the utility of such an approach needs to be evaluated in large-scale comparative studies. In this review, we aimed to share our experience and review the current literature regarding the use of FSM during sinus/paced rhythm in the prediction of re-entrant ATs and discuss future implications and potential use in patients with atrial low-voltage areas.

Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar-related ventricular tachycardia.

INTRODUCTION: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. METHODS: In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. RESULTS: Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. CONCLUSIONS: Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.

Applications of ultrasound elastography to hand and upper limb disorders.

Ultrasound elastography is a recently developed method for accurate measurement of soft tissue stiffness in addition to the clinician's subjective evaluation. The present review briefly describes the ultrasound elastography techniques and outlines clinical applications for tendon, muscle, nerve, skin and other soft tissues of the hand and upper limb. Strain elastography provides a qualitative evaluation of the stiffness, and shear-wave elastography generates quantitative elastograms superimposed on a B-mode image. The stiffness in degenerative tendinopathy and/or tendon injury was significantly lower than in a normal tendon in several studies. Elastography is also a reliable method to evaluate functional muscle activity, compared to conventional surface electromyography. The median nerve is consistently stiffer in patients with carpal tunnel syndrome than in healthy subjects, on whatever ultrasound elastography technique. Elastography distinguishes normal skin from scars and can be used to evaluate scar severity and treatment. Elastography has huge clinical applications in musculoskeletal tissues. Continued development of systems and increased training of clinicians will expand our knowledge of elastography and its clinical applications in the future.

Exon skip-inducing variants in FLNA in an attenuated form of frontometaphyseal dysplasia.

Pathogenic variation in the X-linked gene FLNA causes a wide range of human developmental phenotypes. Loss-of-function is usually male embryonic-lethal, and most commonly results in a neuronal migration disorder in affected females. Gain-of-function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft-tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in FLNA that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain-of-function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the FLNA transcript, predicting the in-frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the FLNA filaminopathies.

Histochemical and Morphometrical Analyses of Scarless Wound Healing in Mouse Fetal Model.

OBJECTIVE: Scar formation is an inevitable outcome after craniofacial surgery in the congenital facial anomaly. Scarless healing is the ultimate treatment after the surgery. Therefore, we elucidate the mechanism underlying scarless healing during fetal development. METHODS: A full-thickness back skin excision (1 × 0.5 mm) was made at embryonic day 16.5 (E16.5) and 18.5 (E18.5) in fetal C57BL/6J mice and examined the histochemical and morphometrical findings of wound healing after 48 hours. RESULTS: The wound made at E16.5 showed almost complete re-epithelialization with fine reticular dermal collagen fibers, but not at E18.5. The ratio of CK5 positive area was significantly higher in the wound of E16.5 operation than in the E18.5. The wounds made at E18.5 showed granulation tissue formation which will lead to subsequent scar formation. The collagen fibers tended to be thinner in wound than in normal skin, while the decrease in the number of fibers but the increase in the straightness of fibers were evident in the wound at E18.5. CONCLUSION: Transition point of scarless healing seemed between E16.5 and E18.5 in mice, which may imply that the potential of epithelial regeneration and matrix formation was changed, possibly due to alteration of cell constitution and decrease in stemness, at that time.

Transverse upper abdominal scars in DIEP flaps: pushing the limit of donor site abdominal skin perfusion.

We present two immediate breast reconstruction cases utilising deep inferior epigastric perforator (DIEP) flaps in the presence of upper transverse abdominal scars and their outcomes. The available evidence in relation to its impact on abdominal skin perfusion and published clinical experience is reviewed.

Long-term prognostic factors of clinical success after interventional bronchoscopy in patients with scarring central airway stenosis.

BACKGROUND: Scarring central airway stenosis (SCAS) is a potentially life-threatening condition with debilitating symptoms. Interventional bronchoscopy is increasingly used to relieve symptoms in patients with SCAS, but recurrent stenosis is frequently observed. Little data exist on the long-term prognosis of interventional bronchoscopy for SCAS. We aimed to assess the prognostic factors of bronchoscopic interventions in patients with SCAS to optimize treatment. METHODS: This was a retrospective study that enrolled 119 consecutive patients with SCAS from January 2010 to April 2019 at our institution. Long-term clinical success was defined as airway stenosis < 50%, no limitation of physical activity, and a stable condition for > 12 months after the last interventional procedure. We compared patients' demographics, airway stenosis characteristics, and interventional procedures between the successful and unsuccessful groups, and identified significant predictors of long-term outcome with univariate and multivariate logistic regression. RESULTS: A total of 119 patients with 577 therapeutic bronchoscopies were included. Seventy-five (63%) patients were considered to have long-term clinical success. Older age, male gender, smoking, elevated C-reactive protein level, subglottic stenosis, stent or T-tube implantation, previous interventional treatment, and multiple procedures per year were potentially associated with unsuccessful long-term outcomes in the univariate analysis. Current smoker status (odds ratio [OR] 5.70, 95% confidence interval [CI] 1.35-24.17, P = 0.018), subglottic stenosis (OR 4.35, 95% CI 1.31-14.46, P = 0.017), and stent implantation (OR 4.96, 95% CI 1.33-18.48, P = 0.017) were associated with decreased odds of long-term success in the multivariate logistic regression analysis. Of note, there was no significant difference in odds of success between former smokers and nonsmokers. CONCLUSIONS: Current smoker status, subglottic stenosis, and stent implantation are independent factors associated with reduced long-term efficacy of interventional bronchoscopy for SCAS. Smoking cessation should be encouraged to improve the outcome of therapeutic bronchoscopy.

Coexistence of sinus bradycardia and junctional tachycardia in a patient with fibrotic atrial cardiomyopathy.

A 65-year-old woman was referred for catheter ablation in the treatment of persistent tachycardia after surgery for atrial fibrillation and mitral regurgitation. Bipolar voltage mapping of both atria revealed that severe and extensive atrial fibrosis isolated the sinoatrial node from the atrioventricular junction and led to the coexistence of sinus bradycardia and persistent junctional tachycardia.

Effectiveness and safety of ablative fractional CO2 laser for the treatment of burn scars: A case-control study.

BACKGROUND: Burn scars are a major clinical challenge. The aim of this study was to determine the effectiveness and safety of one treatment with the ablative fractional CO2 laser (AFL-CO2) compared to standard burn scar treatment. METHOD: From December 2014 to October 2018 patients were prospectively recruited and treatment effects analyzed by assessing various outcome parameters from the date of first consultation and after treatment. A case control study was conducted looking at the impact of one AFL-CO2 treatment compared to a cohort subjected to conventional conservative treatment. Adverse effects were noted at follow up. RESULTS: 187 patients were included, with 167 in the AFL-CO2, and 20 in the control cohort. Baseline demographics and scar characteristics showed no significant differences. Ultrasound measured scar thickness as well as the Vancouver Scar Scale (VSS) revealed a significant reduction in the treatment cohort, but no significant improvement in the control group. The POSAS-O was significantly improved in both cohorts. Subjective parameters (POSAS-P, DN4-Pain, and modified D4Pruritus scores) decreased significantly in the AFL-CO2 cohort but remained unchanged in the control group. The BSHS-B quality of life score increased significantly in the AFL-CO2 group, but worsened at the follow up of the untreated patients. Sub-domain analyses found the biggest differences in Affect, Body Image, Heat Sensitivity, Treatment and Work. Complications occurred in 5 patients (2.9%). CONCLUSIONS: This study demonstrates that AFL-CO2 is an effective and safe treatment modality for burn scars improving thickness, symptoms and quality of life of burn survivors when compared to conventional scar treatment.

Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis.

BACKGROUND: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS: We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS: We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS: These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.

Atypical Presentation of a Marjolin Ulcer After a Burn: A Case Report.

The development of a nonhealing ulcer on a chronic wound or scar should raise suspicions of the plastic surgeon or nurse regarding the potential for malignant degeneration to a Marjolin ulcer. Occasionally, a Marjolin ulcer may present as exophytic granulation tissue within a scar. Most Marjolin ulcers are well-differentiated injuries; however, because of their aggressive nature and poor prognosis, to ensure surgical success, diagnosis of Marjolin ulcer should be confirmed and treatment initiated as soon as possible.

Scar quality examination comparing titanium-coated suture material and non-coated suture material on flap donor sites in reconstructive surgery.

BACKGROUND: Wound healing and scar quality after trauma are subject to impairment through excessive wound healing, chronic wound or even surgical site infections. Optimizing the process of scar formation and skin healing is crucial in virtually all fields of medicine. In this regard, we tested the possible usage and advantages of titanium coated suture material. METHODS: We performed a prospective observational cohort study including 30 patients who underwent soft tissue reconstruction. One half of the donor flap site was sutured with titanium coated suture material, while the other half was closed with non-coated sutures. Scar quality of the donor flap site was assessed by photographs and POSAS scores on days 2-5, 14, 42, 72 and 180 postoperatively. RESULTS: No difference between the titanium coated sutures and non-coated sutures was seen in the POSAS assessment, neither for the patient scale at 14, 42, 72 and 180 days, nor for the observer scale on the same dates. Comorbidities like diabetes, chronic renal failure and smoking as well as the BMI of each patient affected the wound healing process to an equal degree on both sides of the suture. CONCLUSIONS: No difference between the titanium coated and non-titanium-coated suture material was seen in the POSAS assessment in regard to scar quality and wound healing. The titanium-coated suture material can be considered to be equally as effective and safe in all qualities as the non-titanium-coated suture material, even in patients with comorbidities. Clinical trial register This study is registered at the German Clinical Trials Register (DRKS) under the registration number DRKS00021767. ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021767 ).

The Role of Dermal Regenerative Templates in Complex Lower Extremity Wounds.

Dermal regenerative templates (DRTs) provide an option for management of complex lower extremity wounds. DRTs may be used to achieve definitive wound closure by serving as a scaffold for local tissue infiltration. Healing with a DRT interface leads to histologic and structural properties similar to native skin. DRTs can be applied over deep wounds with exposed critical structures that may have required a local or free flap. DRTs are a valuable option for lower extremity limb reconstruction.

Novel Biomedical Functions of Surfactin A from Bacillus subtilis in Wound Healing Promotion and Scar Inhibition.

Surfactin produced by Bacillus subtilis is a powerful biosurfactant in food, cosmetics, and pesticide industries. However, its suitability in wound healing applications is uncertain. In this article, we determined the effects of surfactin A from B. subtilis on wound healing, angiogenesis, cell migration, inflammatory response, and scar formation. The results indicated that 80.65 ± 2.03% of surfactin A-treated wounds were closed, whereas 44.30 ± 4.26% of the vehicle-treated wound areas remained open on day 7 (P < 0.05). In mechanisms, it upregulated the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), accelerated keratinocyte migration through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, and regulated the secretion of proinflammatory cytokines and macrophage phenotypic switch. More attractive, surfactin A showed a seductive capability to inhibit scar tissue formation by affecting the expression of α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß). Overall, the study revealed a new function and potential of surfactin A as an affordable and efficient wound healing drug.

Activin-mediated alterations of the fibroblast transcriptome and matrisome control the biomechanical properties of skin wounds.

Matrix deposition is essential for wound repair, but when excessive, leads to hypertrophic scars and fibrosis. The factors that control matrix deposition in skin wounds have only partially been identified and the consequences of matrix alterations for the mechanical properties of wounds are largely unknown. Here, we report how a single diffusible factor, activin A, affects the healing process across scales. Bioinformatics analysis of wound fibroblast transcriptome data combined with biochemical and histopathological analyses of wounds and functional in vitro studies identify that activin promotes pro-fibrotic gene expression signatures and processes, including glycoprotein and proteoglycan biosynthesis, collagen deposition, and altered collagen cross-linking. As a consequence, activin strongly reduces the wound and scar deformability, as identified by a non-invasive in vivo method for biomechanical analysis. These results provide mechanistic insight into the roles of activin in wound repair and fibrosis and identify the functional consequences of alterations in the wound matrisome at the biomechanical level.

The Northwestern Abdominoplasty Scar Model: A Tool for High-Throughput Assessment of Scar Therapeutics.

Significance: Scar management is an important concern in plastic surgery. Scar models that best mimic in vivo human scarring are essential for understanding scar development and progression, assessing the efficacy of therapeutics, and providing reliable and valid research outcomes. Recent Advances: In 2016, Lanier et al. proposed a new in vivo patient model, the Northwestern Abdominoplasty Scar Model, that overcomes the prior limitations of both animal and human models, with greater representativeness of the human scarring process, expedited recruitment, smaller sample requirements, and greater flexibility in the types and number of interventions that can be studied simultaneously. Critical Issues: Existing animal models suffer from limitations that impede generalization to human scars. Human scar studies are difficult to conduct and rarely used due to recruitment difficulties, ethical concerns regarding purposeful wounding, and inherent variability based on location, type of scar, and the heterogeneity of the host response between humans. Although overcoming many of these hurdles, the Northwestern Abdominoplasty Scar Model still has a few limitations. In addition, there remains a need for further study of and comparison between the Northwestern Abdominoplasty Scar Model and existing human and animal models, to inspire more widespread acceptance of a standardized human scar model. Future Directions: The Northwestern Abdominoplasty Scar Model is a critical stepping stone toward better human scar models. This model hopefully will inspire other in vivo patient models utilizing elective surgery to overcome recruitment and ethical concerns.

Expression of Metalloproteinases and Type I and III Collagens during Healing of Excisional Skin Wound on the Abdomen and Back in Rats.

The study was carried out using a novel rat model developed in our laboratory, namely16 mm diameter circular excisional wounds were generated on the abdomen which resulted in minimal scarring. Restoration of the skin integrity was completed by day 60 after the wounding surgery. By this time, regenerates on the abdomen were stronger than on the back (at, respectively, 58 and 17.4 % of the tensile strength of the intact skin at corresponding location) and the ratio of type I and type III collagens in regenerates on the abdomen reached the level of intact skin at the same location. On days 3 to 14, the ratio of Mmp9/Timp1 expression levels on the abdomen was higher than on the back. On days 20 and 30, the Mmp9/Timp1 ratio on the abdomen was identical to the level of intact skin, whereas the increased MMPs expression levels on the back were maintained until day 30. It has been shown for the first time that according to functional and molecular characteristics, wound healing on the abdomen of an adult rat is more similar to complete regeneration than scarring repair of the back skin.

Stereotactic arrhythmia radioablation for refractory scar-related ventricular tachycardia.

BACKGROUND: Recently, stereotactic radiosurgery has been applied to arrhythmias (stereotactic arrhythmia radioablation [STAR]), with promising results reported in patients with refractory scar-related ventricular tachycardia (VT), a cohort with known high morbidity and mortality. OBJECTIVE: Herein, we describe our experience with STAR, detailing its early and mid- to long-term results. METHODS: This is a pilot prospective study of patients undergoing STAR for refractory scar-related VT. The anatomical target for radioablation was defined on the basis of the clinical VT morphology, electroanatomic mapping, and study-specific preprocedural imaging with cardiac computed tomography. The target volume was treated with a prescription radiation dose of 25 Gy delivered in a single fraction by CyberKnife in an outpatient setting. Ventricular arrhythmias and radiation-related adverse events were monitored at follow-up to determine STAR efficacy and safety. RESULTS: Five patients (100% men; mean age 63 ± 12 years; 80% with ischemic cardiomyopathy; left ventricular ejection fraction 34% ± 15%) underwent STAR. Radioablation was delivered in 82 ± 11 minutes without acute complications. During a mean follow-up of 12 ± 2 months, all patients experienced clinically significant mid- to late-term ventricular arrhythmia recurrence; 2 patients died of complications associated with their advanced heart failure. There were no clinical or imaging evidence of radiation-induced complications in the organs at risk surrounding the scar targeted by radioablation. CONCLUSION: Despite good initial results, STAR did not result in effective arrhythmia control in the long term in a selected high-risk population of patients with scar-related VT. The safety profile was confirmed to be favorable, with no radiation-related complications observed during follow-up. Further studies are needed to explain these disappointing results.

Demographic and Burn Injury-Specific Variables Associated with Limited Joint Mobility at Discharge in a Multicenter Study.

Burn scar contractures. Existing research on contractures is limited by incomplete analysis of potential contributing variables and differing protocols. This study expands the exploration of contributing variables to include surgery and rehabilitation treatment-related factors. Additionally, this study quantifies direct patient therapy time and patient exposure to rehabilitation prevention therapies. Data from subjects enrolled in the prospective Burn Patient Acuity Demographics, Scar Contractures and Rehabilitation Treatment Related to Patient Outcome Study (ACT) were analyzed to determine variables related to a limited range of motion (limROM) in seven joints and 18 motions (forearm supination) at discharge. Chi-squared and Student's t-test were used accordingly. Multivariate analysis was performed at the patient and joint motion level to control for confounders. Of the 300-member study group, 259 (86.3%) patients had limROM at discharge. Variables independently related to the development of moderate-to-severe limROM on the patient level were larger TBSA, having skin grafted and prolonged bed rest. Variables independently related to moderate-severe limROM on the joint motion level were the percentage of cutaneous functional unit (CFU) burned (P = .044), increase in the length of stay, weight gain, poor compliance with rehabilitation therapy and lower extremity joint burns. Rates of limROM are increased in patients who had larger burns, required surgery, had a greater percentage of the associated CFU burned, and had lower extremity burns. Attention to adequate pain control to ensure rehabilitation tolerance and early ambulation may also decrease limROM at discharge and quicker return to pre-burn activities and employment.