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Hypertrophic burn scars can occur due to imbalances in the healing process and affect quality of life. They can be assessed with the Patient and Observer Scar Assessment Scale (POSAS). This is an assessment instrument with both a patient scale and an observer scale. This study aimed to assess the reliability and validity of the POSAS score to measure the quality of scars in evaluating burns that produce scar tissue. It also aimed to determine similarities in the assessment of scar tissue using the POSAS score according to observers and patients. This cross-sectional study had a sample of 30 patients, including 19 women (63%). Assessments were performed before the initial treatment procedure and 1 and 6 months after. The post-incision scar tissue assessment results using the POSAS instrument were expressed as a score: 5-50 (observer), 6-60 (patient), or 11-110 (both total). The highest degree of burns was superficial-mid-dermal (20 patients; 67%). The POSAS assessment by doctors and patients tended to be the same and decreased at both months 1 and 6 after the treatment procedure. The mean total score was 51.3 ± 12.1 before treatment, 44.2 ± 9.5 at month 1, and 30.3 ± 5.9 at month 6. This study shows that in evaluating burns that produce hypertrophic scars, similarities exist in the POSAS score according to observers and patients. Precautions at the beginning of the observation will affect the POSAS score., (© 2024 Euro-Mediterranean Council for Burns and Fire Disasters.)

Background and Aims: In patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM), it is unclear if response to cardiac myosin inhibition varies with older age or a longer duration of diagnosis. This study evaluated the response of these subgroups to mavacamten therapy for all primary, secondary, and exploratory endpoints in the EXPLORER-HCM trial (ClinicalTrials.gov: NCT03470545)., Methods: Patients were stratified by age (≤60 vs. >60 years) and duration of HCM diagnosis (≤5 vs. >5 years). To estimate treatment differences and evaluate age and diagnosis duration by treatment interaction, analysis of covariance was used to model changes in continuous endpoints and a generalized linear model was used for binary endpoints., Results: Older patients were more frequently female (53% vs. 29%), with a lower prevalence of pathogenic/likely pathogenic HCM gene variants (17% vs. 36%), lower mean peak oxygen consumption (pVO 2 ) (17.6 vs. 21.1 ml/kg/min), and a higher mean NT-proBNP level (817 vs. 592 ng/L) but similar NYHA classes and quality of life scores. Patients with a longer vs. shorter diagnosis duration had similar mean ages (59.0±11.6 vs. 57.9±12.3 years) but more family history of HCM (38% vs. 16%) and a higher mean NT-pro BNP level (938±118 vs. 494±145 ng/ml). No differences were observed in improvement in peak oxygen consumption, NYHA class, or patient-reported outcomes among older patients and those with a longer duration of diagnosis., Conclusions: In EXPLORER-HCM, mavacamten treatment had a similar benefit for all primary, secondary, and exploratory endpoints in patients with symptomatic, obstructive HCM regardless of age or duration of diagnosis., Competing Interests: Declaration of competing interest Wang: Research grant to institution from BMS and Cytokinetics. Advisory board (consultant) for BMS, Cytokinetics, and BioMarin. Speakers bureau for BMS. Lakdawala: Consulting for BMS, Cytokinetics, Tenaya, Pfizer, and Akros. Abraham: None. Saberi: consulting for Cytokinetics and BMS. Owens: Consulting for BMS, Cytokinetics, Pfizer, Tenaya, Renovacor, Stealth, Edgewise, Lexicon, and Biomarin. Spertus: Consulting on patient-reported outcomes and evidence evaluation for Alnylam, AstraZeneca, Bayer, Merck, Janssen, BMS, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare. Research grants from BMS, Abbott Vascular and Janssen. Copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and Board of Directors for Blue Cross Blue Shield of Kansas City. Research support from BMS and Pfizer. Nilles, Wojdyla: None. Sehnert: Employee of BMS. Owner of stock/stock grants from BMS. Cresci: Institution research funding for clinical trial from Imbria Pharmaceuticals. Data Monitoring Committee for Cytokinetics. Bach: Institution research funding for clinical trials from BMS and Cytokinetics., (Copyright © 2024. Published by Elsevier Inc.)

Aims: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM., Methods: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years., Results: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m 2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities., Conclusion: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Pompe disease (PD) is a rare progressive autosomal recessive disorder resulting from the deficiency of acid alpha-glucosidase (GAA) enzyme activity. Due to its multisystemic involvement, PD leads to significant morbidity and impacts patients' quality of life. Despite the availability of approved disease-modifying treatments, the prompt diagnosis and management of PD, which are crucial for patient outcomes, still present several challenges. This scoping review aimed to synthesize the evidence regarding methods for screening, diagnosing, and following up PD. We searched articles in English and Spanish published from 2017 to February 8, 2022, across 11 databases (i.e., Cochrane Database of Systematic Reviews, Directory of Open Access Journals (DOAJ), Epistemonikos, Ingenta Connect, Medline/PubMed, SAGE, SciELO Citation Index, ScienceDirect, Springer Link, Virtual Health Library, and Wiley Online Library). We included primary studies (i.e., case reports, case series, cross-sectional studies, case controls, cohorts, clinical trials, and qualitative studies), reviews, and guidelines that described at least one assessment method for patients with confirmed clinical, genetic, or biochemical PD. Two independent reviewers screened and extracted data from articles, with a third reviewer solving conflicts. We synthesized data with narrative summaries and descriptive statistics. After screening 2,139 titles and abstracts, we included 96 eligible articles. Cross-sectional studies (n = 30) and guidelines (n = 1) were the most and least prevalent designs, respectively. Most studies targeted late-onset PD (LOPD, n = 48) and infantile-onset PD (IOPD, n = 21). Eleven articles described newborn screening programs, highlighting their potential to improve PD prevalence estimations and still limited availability among countries. Overall, 81 articles documented clinical manifestations of PD. Hypotonia (n = 7) and hypertrophic cardiomyopathy (n = 7) were the most documented for IOPD, while progressive muscle weakness (n = 21) and dyspnea (n = 11) were the most prevalent for LOPD. We found 26 articles reporting biochemical assays, with dried blood spots (DBS) for GAA enzyme deficiency detection being the most cited (n = 19). We also noted a lack of standardization in documenting DBS results. Additionally, 21 articles mentioned genetic studies, with next-generation sequencing emerging as the gold standard for identifying mutated alleles. Functional studies were the most utilized to follow up with patients. However, monitoring strategies for pediatric and adult PD lacked consensus, and only one article assessed patients' quality of life. This review comprehensively evaluated the literature on PD screening, diagnosis, and follow-up methods, identifying prevalent techniques within each assessment category. We emphasized the need for a more standardized approach to reporting biochemical assays, genetic testing, and clinical presentations. Our review also underscored the critical lack of standardization in PD follow-up. Addressing these gaps will enhance the comparability of future research findings and improve the quality of PD-related healthcare. Limitations of this review included restricting eligible languages and publication years to the latest five, the methodological heterogeneity of selected articles, and the lack of individual study bias assessment., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: The Rare Diseases Community declare(s) a grant from FONTAR (Fondo Tecnológico Argentino) of the Agencia Nacional de Promoción de la investigación, el Desarrollo y la Innovación (Ministerio de Ciencia, Tecnología e Innovación). The Rare Diseases Community received financial support from FONTAR under grant number ANR 25000 2022 F2 032/22. FONTAR did not contribute to the design, data collection, analysis, interpretation, manuscript preparation, or decision to submit this manuscript. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nunes Campos et al.)

Hypertrophic scars cause significant physical and emotional discomfort. Botulinum toxin type A (BTA) has shown promising outcomes in reducing scar formation. Research suggested its effectiveness in managing hypertrophic scars and keloids. This systematic review and meta-analysis were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled trials (RCTs). The included studies involved patients with hypertrophic scars treated with BTA. Five databases were searched from inception to August 2024. Studies were screened and selected by two independent reviewers. Data on study design, patient demographics, and interventions was extracted. The risk of bias (ROB) was assessed using the ROB revised tool developed by Cochrane (ROB2). Meta-analysis was performed using RevMan Web (The Cochrane Collaboration, London, UK) with a random-effects model due to high heterogeneity, calculating mean differences for the primary and secondary outcomes. Outcomes included Vancouver Scar Scale (VSS) scores, scar thickness, vascularity, pliability, and pigmentation. The systematic review identified 182 records from five databases. The screening process resulted in seven studies included in the final analysis after assessment for eligibility. The efficacy of BTA in treating hypertrophic scars and keloids was assessed. The meta-analysis showed that BTA significantly improved VSS scores, with a pooled mean difference of -1.69 (P = 0.01). However, BTA did not show a statistically significant effect on reducing scar height/thickness or improving vascularity. Scar pliability was significantly improved by BTA, with a pooled mean difference of -0.76 (P = 0.002), while there was no significant effect on pigmentation. High heterogeneity was observed across the studies. BTA could be used as an effective treatment for the components of hypertrophic scars and keloids, especially regarding their pliability and improving scar quality. However, for functions such as the change in scar height, vascularity, and pigmentation, more research is still required among larger RCTs. Future research should focus on refining the treatment regimens and the mode of action of BTA to the scar tissue., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Raslan et al.)

Objective: To investigate the correlation between MRI-based phenotypes (cartilage-meniscus, subchondral bone, and inflammatory) and radiography-based atrophic and hypertrophic phenotypes, aiming to demonstrate MRI's diagnostic capability in identifying complex osteoarthritis phenotypes that radiography cannot fully capture., Materials and Methods: This single-center retrospective study examined knee radiographs and MRIs of patients from November 2021 to April 2023 to identify osteoarthritis phenotypes. Radiographs were staged by the Kellgren-Lawrence system, and both modalities were classified into atrophic or hypertrophic phenotypes. MRIs were further classified into three phenotypes: cartilage-meniscus, subchondral bone, and inflammatory. Associations between phenotypes, Kellgren-Lawrence stage, age, and gender were analyzed with Pearson chi-square test and student T-test. Reliability measurements were evaluated using kappa statistic., Results: A total of 214 knees from 187 individuals (73.3% women, 26.7% men; mean age 57.1 ± 9.1 years) were included. The hypertrophic MRI phenotype was significantly associated with cartilage-meniscus and subchondral bone phenotypes (p < 0.001). Cartilage-meniscus and subchondral bone phenotypes were less prevalent in Kellgren-Lawrence stage 2 than in stages 3 and 4 (p < 0.001 and p = 0.004, respectively). The subchondral bone phenotype was more common in men (p = 0.022), and the cartilage-meniscus phenotype in the elderly (p < 0.001). Radiography and MRI had substantial agreement (Kappa = 0.637, p < 0.001) in diagnosing hypertrophic and atrophic phenotypes., Conclusion: The hypertrophic phenotype was associated with cartilage-meniscus and subchondral bone phenotypes, with lower prevalences in Kellgren-Lawrence stage 2 knees. MRI offers enhanced phenotypic characterization, which facilitates more precise and individualized management in osteoarthritis care. Despite limitations compared to MRI, radiography remains valuable for the evaluation of hypertrophic and atrophic phenotypes., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objectives: This study aims to delineate the temporal trends, prevalence, predictors, and outcomes of HF among HCM patients using the National Inpatient Sample (NIS) database, with a focus on optimizing therapeutic strategies and healthcare resources., Methods: We conducted a retrospective cohort analysis of anonymized data from the NIS spanning 2016 to 2019. The study population consisted of adults diagnosed with HCM based on specific ICD-10 diagnostic codes. Logistic regression was utilized to explore the association between HF and in-hospital mortality, adjusting for demographic and clinical factors., Results: Our analysis included 215,505 individuals, with 97,875 (45.4 %) experiencing HF. Patients with HF exhibited a higher burden of comorbidities such as diabetes and renal failure, and had increased odds of mortality (OR 1.41). The study also highlighted significant demographic disparities, with marked differences in outcomes based on race and gender. The economic analysis revealed higher healthcare costs and longer hospital stays associated with HF., Conclusion: HF significantly impacts mortality, healthcare costs, and hospitalization length in HCM patients, with substantial demographic and clinical disparities. This study underscores the importance of tailored management strategies and the need for continuous surveillance and research to address the challenges posed by HF in HCM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Dr Yadav reports personal fees from Johnson & Johnson Innovative Medicine, AbbVie Inc., Amgen, Aralez, Cipher, Arcutis, Bausch Health, Bristol Myers Squibb, Galderma, Incyte, Leo, Novartis, Paladin, Pfizer, Sanofi-Regeneron, Sun Pharma, and UCB outside the submitted work. Mr Sood has no conflicts of interest to declare.

Hypertrophic scarring is a significant complication post burn injury, especially for delayed healing after 3 weeks. Burn injuries healing prior to 3 weeks also have the potential to develop hypertrophic scarring, even when prescribed prophylactic conservative scar interventions. A retrospective chart audit reviewed 326 burn patients treated at a paediatric tertiary hospital from 2014 to 2019 who sustained a partial thickness burn, healed >14 days and did not receive skin grafting. A scar was deemed hypertrophic if >1 mm in height. Early hypertrophic scar prevalence was defined as 3-6 months post burn, while persistent hypertrophic scarring was defined as 12-18 months post burn. Median days to wound closure was 18. The prevalence of early and persistent hypertrophic scarring was 56.1% and 16.3%, respectively. Seventeen (5.2%) children underwent medical interventions for scar modulation. Early signs of hypertrophic scarring were seen in just over half the patients presenting to burn therapy and despite scar intervention, persistent hypertrophic scarring was seen in 16.3%. At both time points, just over half of the children presenting healed between 14 and 21 days. Therefore, children healing prior to 21 days have potential to develop hypertrophic scarring., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: The prognosis of hypertrophic cardiomyopathy (HCM) varies from mild disease with a normal life expectancy to heart failure and sudden cardiac death (SCD). The identification of patients who are at high risk for SCD remains challenging., Aims: In this study, we evaluated the prognostic value of papillary muscle-free strain in HCM patients., Methods and Results: Seventy-nine patients with a diagnosis of HCM were included in this study. Patients were divided into low/intermediate-risk (n = 57) and high-risk (n = 22) groups. Two-dimensional (2-D) echocardiography and strain imaging were performed for each patient. The mean age of the study population was 53.85 ± 15.88 years; 47 (59.5%) of them were male. During a mean follow-up duration of 74.45 ± 17.03 months, 12 patients died. A comparison of the low-intermediate and high-SCD risk groups revealed that patients in the high-SCD risk group had greater maximal wall thickness, interventricular septum thickness, posterior wall thickness, and left ventricular mass index (LVMI) and lower (less negative) global longitudinal, anterolateral papillary muscle (ALPM) and posteromedial papillary muscle (PMPM) free strain. Additionally, a history of syncope and ICD implantation were found to be more common in patients with high SCD risk scores. The SCD risk score was positively correlated with the global longitudinal strain, ALPM-free strain, and PMPM-free strain (r = .528, r = .658, and r = .600, respectively; p < .001 for all). Our results showed that the LVMI, presence of syncope, global longitudinal strain, and ALPM-free strain were predictors of death., Conclusions: Decreased papillary muscle-free strain values might have prognostic value in patients with HCM., (© 2024 Wiley Periodicals LLC.)

Background: Hypertrophic scars are contained within the site of injury and may regress over time, while keloids spread beyond the borders of the initial injury and do not regress. On histologic examination, hypertrophic scars tend to have collagen in a wavy, regular pattern, whereas keloids have no distinct pattern of collagen., Objective: To retrospectively analyze improvement in keloid and hypertrophic scars characteristics following treatment with Ablative 10600 nm and a non-Ablative 1570 nm Hybrid Laser Device., Methods: Treatment parameters with the ProScan Hybrid Mode were 40 W/1.3-1.5 ms for the CO2 and 12 W/4 ms for the 1570 nm in a 1:1 ratio. Outcomes were assessed based on physician scar grading as measured by the Vancouver Scar Scale and patient-reported satisfaction. Excel was used for data analysis, and a p value < 0.05 was considered statistically significant. Adverse events and patient pain were also recorded., Results: A total of 31 hypertrophic scars and 30 keloid scars were treated. There was a significant reduction in Vancouver Scar Scale scores for both hypertrophic and keloid scars (62% ± 8% and 58% ± 7%; p = 2.6E-17 and p = 8.29E-26, respectively). In a scar-based comparison, a statistically significant difference was observed for all measures reflecting favorable outcomes for hypertrophic scars (VSS, p = 1.1E-05; satisfaction, p = 0.0112; pain, p = 0.00081). Only one adverse event was reported, a superficial burn treated with topical antibiotics., Conclusions: The device was found to be safe and effective, with promising results for the treatment of hypertrophic and keloid scars., Level of Evidence Ii: 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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Objectives: This study aimed to investigate the presence and severity of inferior turbinate hypertrophy (ITH) in patients with hypertrophic scars (HTS)., Methods: This case-control study was conducted with patients diagnosed with HTS during dermatologic examination and a control group without HTS. An otolaryngologist evaluated the presence and severity of inferior turbinate hypertrophy by anterior rhinoscopy., Results: ITH was more common in patients with HTS compared to the control group (64%, and 34%, respectively) (p=0.014). In the HTS group, 48% of patients had grade 2, and 16% had grade 3 ITH; in the control group, 24% had grade 2, and 10% had grade 3 ITH (p=0.046). Also, ITH was higher in patients who complained of pruritus or pain (83%, and 80%, respectively) in the HTS than in asymptomatic HTS patients (p=0.020)., Conclusion: A higher number of patients with HTS had ITH compared to the control group, especially those who reported pruritus or pain associated with scar. Given the limited understanding of the full pathogenesis and treatment of HTS and ITH, their association potentially provides new insights into these related conditions., Competing Interests: The authors declare no conflicts of interest., (© Copyright 2024 by The Medical Bulletin of Sisli Etfal Hospital.)

Midventricular obstruction (MVO) is a rare form of hypertrophic cardiomyopathy (HCM). While surgical treatment for HCM is among the most technically challenging cardiac operations for acquired disease, surgery for MVO is rarely reported. A 38-year-old man was admitted to our hospital with a cough and dyspnea. Transthoracic and transesophageal echography and computed tomography revealed extensive left ventricular hypertrophy, extending from the anteroseptal wall to the apex, and marked papillary muscle hypertrophy. We underwent septal myectomy via aortotomy (Morrow procedure) and apical surgery. Extended myectomy provides the best exposure to the hypertrophied septum and improves the functional status of patients., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The Wnt signaling pathway is a key molecular process during fracture repair. Although much of what we now know about the role of this pathway in bone is derived from in vitro and animal studies, the same cannot be said about humans. As such, we hypothesized that Wnt signaling will also be a key process in humans during physiological fracture healing as well as in the development of a nonunion (hypertrophic and oligotrophic). We further hypothesized that the expression of Wnt-signaling pathway genes/proteins would exhibit a differential expression pattern between physiological fracture callus and the pathological nonunion tissues. We tested these two hypotheses by examining the mRNA levels of key Wnt-signaling related genes: ligands (WNT4, WNT10a), receptors (FZD4, LRP5, LRP6), inhibitors (DKK1, SOST) and modulators (CTNNB1 and PORCN). RNA sequencing from calluses as well as from the two nonunion tissue types, revealed that all of these genes were expressed at about the same level in these three tissue types. Further, spatial expression experiments identified the cells responsible of producing these proteins. Robust expression was detected in osteoblasts for the majority of these genes except SOST which displayed low expression, but in contrast, was mostly detected in osteocytes. Many of these genes were also expressed by callus chondrocytes as well. Taken together, these results confirm that Wnt signaling is indeed active during both human physiological fracture healing as well as in pathological nonunions., Competing Interests: None., (© 2024 The Author(s).)

Background: Scarring, a pervasive issue spanning across medical disciplines, lacks a comprehensive terminology for effective communication, patient engagement, and outcome assessment. Existing scar classification systems are constrained by specific pathologies, physician-centric features, and inadequately account for emerging technologies. This study refrains from proposing yet another classification system and instead revisits the foundational language of scar morphology through a theme analysis of primary patient complaints., Method: Data encompassing five years of a high-volume scar practice was analysed. Primary complaints were aggregated into collective descriptors and further organized into theme domains. The resulting hierarchical map of presenting complaints revealed five key domains: Loss of Function, Contour, Texture, Vector, and Colour Presenting complaints were codified into 42 items, which were then categorised into 14 collective descriptor terms. The latter were in turn organised into five overarching themes., Result: Loss of Function, accounting for 10% of primary concerns, signifies reduced function attributed solely to the scar. Contour, encompassing 41% of concerns, pertains to scar height, shape, and depth. Texture, representing 12% of concerns, denotes tactile variations such as hardness, roughness, and moisture. Vector, comprising 13% of concerns, refers to scar tissue tension and associated distortions. Colour, the concern in 24% of cases, encompasses variations in pigmentation, vascularity, and exogenous pigments., Discussion: Standardized terminology enhances patient care, communication, and research. This study underscores the fundamental question of "what bothers the patient," reviving a patient-centred approach to scar management. By prioritizing themes based on patient complaints, this study innovatively integrates function, aesthetics, and patient experience. In conclusion, this study pioneers a paradigm shift in scar management by presenting a patient-driven theme framework that offers a common language for healthcare professionals and patients. Embracing this language harmonizes scar treatment, fosters innovation, and transforms scars from silent reminders into stories of resilience and healing., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interest whatsoever in the production of this manuscript This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

The healing of bone fractures can become aberrant and lead to nonunions which in turn have a negative impact on patient health. Understanding why a bone fails to normally heal will enable us to make a positive impact in a patient's life. While we have a wealth of molecular data on rodent models of fracture repair, it is not the same with humans. As such, there is still a lack of information regarding the molecular differences between normal physiological repair and nonunions. This study was designed to address this gap in our molecular knowledge of the human repair process by comparing differentially expressed genes (DEGs) between physiological fracture callus and two different nonunion types, hypertrophic (HNU) and oligotrophic (ONU). RNA sequencing data revealed over ∼18,000 genes in each sample. Using the physiological callus as the control and the nonunion samples as the experimental groups, bioinformatic analyses identified 67 and 81 statistically significant DEGs for HNU and ONU, respectively. Out of the 67 DEGs for the HNU, 34 and 33 were up and down-regulated, respectively. Similarly, out of the 81 DEGs for the ONU, 48 and 33 were up and down-regulated, respectively. Additionally, we also identified common genes between the two nonunion samples; 8 (10.8 %) upregulated and 12 (22.2 %) downregulated. We further identified many biological processes, with several statistically significant ones. Some of these were related to muscle and were common between the two nonunion samples. This study represents the first comprehensive attempt to understand the global molecular events occurring in human nonunion biology. With further research, we can perhaps decipher new molecular pathways involved in aberrant healing of human bone fractures that can be therapeutically targeted., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acne scarring is common and can occur even with effective acne management. In addition, patients with acne scarring suffer from significant psychosocial morbidity, including depression and suicidality. Despite the availability and advancement of therapeutic modalities, treatment for acne scarring is not always optimized and often overlooked in patients with acne encounters. Using acne scarring assessment tools and identifying specific acne scar subtypes allows for a tailored therapeutic approach. Part I of this continuing medical education series covers the pathophysiology and morphology of textural and pigmented acne scars, scarring assessment tools, and medical treatment options. The principles reviewed will aid in approaching and initiating acne scar treatment in the outpatient setting., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Myofibromas are rare mesenchymal tumors with a predilection for the head, neck, and oral cavity. Primarily affecting infants and young children, these tumors typically manifest as superficial painless nodules. Diagnosis is confirmed through histopathological examination of a biopsy, revealing nodules characterized by spindle cell proliferation. To our knowledge, only two cases of pinna myofibroma have been previously reported in the literature., Case Presentation: Here, we present the case of a three-year-old male who developed a myofibroma of the left auricle following trauma to the area one year earlier. The patient underwent surgical resection without any postoperative complications. The patient later returned with a lesion consistent with hypertrophic scar., Conclusions: This study aims to provide a comprehensive review of the clinical presentation, histopathologic and immunohistochemical features, and surgical management of this unique case of myofibroma of the pinna., (© 2024. The Author(s).)

Background: Hypertrophic cardiomyopathy (HCM) affects millions of individuals worldwide. In severe cases, it can cause life-threatening conditions such as left ventricular outflow tract (LVOT) obstruction, mitral regurgitation (MR), and sudden cardiac death, making surgical treatment necessary. This study aimed to report the long-term outcomes of HCM patients undergoing septal myectomy or mitral valve replacement (MVR) and compare the results between different types of surgeries., Methods: This was a retrospective cohort study on HCM patients who underwent surgical treatment in an Iranian referral center between 2005 and 2021. Patients were divided into three groups according to the type of surgery received: septal myectomy, MVR, or a combination of both surgeries. Patient characteristics, surgical and echocardiographic features, and in-hospital and long-term outcomes were reported and compared between the three groups., Results: A total of 102 patients with an average age of 53.3 ± 16.9 were included. Twenty-six patients had septal myectomy, 23 had MVR, and 53 had combined septal myectomy and MVR surgery. All surgeries were associated with a significant reduction in interventricular septum thickness and LVOT gradients. After a median of 6.8-year follow-up time, patients with an isolated septal myectomy had significantly lower mortality and major adverse cardiac and cerebrovascular events rates than the other groups., Conclusion: Isolated septal myectomy showed better long-term survival rates and can correct HCM-related MR, while MVR should be preserved only for intrinsic valve defects. More extensive studies are needed to confirm these findings and achieve a comprehensive guideline on surgical treatment of HCM., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Introduction: Fetal and postnatal hypertrophy develop in response to such different exposures or illnesses the mother suffers during gestation as anti-infectious and physical agents, obesity, hypertension, diabetes, and even advanced maternal age. This gives rise to high comorbidities in the newborn; therefore, looking for alternatives that contribute to cardiac homeostasis is quite necessary to inhibit the overgrowth of myocytes. Boron-derivative compounds could play a key role in exerting a repairing effect on chronic cardiac damage induced during gestation., Methodology: The cardiotoxic effect of 6.4, 12 and 100 mg/kg of sodium tetraborate administered by oral delivery route to healthy pregnant mice was assessed. After that, the use of the chemical compound was tested in the treatment of pregnant mice previously subjected to isoproterenol (fetal hypertrophy model) on the fifth day post coitus. Prior to the sacrifice of the pups of mice an electrocardiography (ECG) was done. Morphological and histological changes of heart were assessed in newborn pups. As a damage marker, the concentration of p38 nitrogen-activated protein kinases were evaluated by using Western Blot and the levels of malondialdehyde (MDA) as well as glutathione antioxidants (GSH) and glutathione peroxidase (GPx) were tested by spectrometry. Moreover, the mRNA expression for early response genes (c-jun, c-fos y c-myc), late response (GATA-4, Mef2c, NFAT) and heart damage (ANP and BNP) was measured by qPCR real time., Results: The supply of 6,4 and 12 mg/kg-sodium tetraborate favored ventricular remodeling with histological alterations. By comparison, 100 mg/kg of sodium tetraborate administered during the fetal stage did not alter neither the cardiac morphology of six-week old pups nor the p38/P-p38MAPK ratio remained the same and no oxidative stress was observed. When pregnant females treated with isoproterenol were treated with 100 mg/kg sodium tetraborate during the fetal stage, an improvement in contractility was detected in the pups with an actual reduction in myocardial fibrosis and oxidative stress, but cardiac mass increased. In addition, the expression levels of c-jun, c-myc, GATA-4, MEF2c and ANP mRNA declined in comparison with CTR. However, the hypertrophic damage mechanism was sustained by c-fos, NFAT and BNP expressions., Conclusions: The set of results achieved suggests that high concentrations of sodium tetraborate have no cardiotoxic effects. Furthermore, sodium tetraborate mitigates hypertrophy induced during pregnancy, thereby improving contractibility, reducing oxidative stress and stimulating cell proliferation. Therefore, sodium tetraborate could be an excellent prophylactic treatment administered by delivery oral route during pregnancy when there is a risk of developing fetal left ventricular hypertrophy (LVH)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Introduction: Hypertrophic scarring is a common and debilitating consequence of burn scars. While there is limited evidence for current treatment options, laser therapy has been shown to be effective, low risk and minimally invasive. This study assesses the use of carbon dioxide lasers and intense pulsed light devices in the treatment of hypertrophic burn scars., Methods: In this case series, patients were recruited from a hypertrophic burn scar waitlist and completed a Patient and Observer Scar Assessment Scale prior to and six weeks after laser therapy. The Nordlys (intense pulsed light) and CO 2 RE (carbon dioxide) systems from Candela Medical were used, with a range of settings used depending on the assessment of the burn scar. The differences between scores were calculated for the total Patient and Observer Scar Assessment Scale score, pain, itch, colour, stiffness, thickness, irregularity and the overall opinion of the scar. Statistical analysis was completed using a paired, two-tailed student T test., Results: A total of 31 patients were recruited for this trial with a range of scar locations, surface areas and mechanism of burn injury. The calculated difference in mean showed a significant reduction for the overall Patient and Observer Scar Assessment Scale score (1.93, p < 0.0001), pain (1.39, p  =  0.0002), itch (1.84, p  =  0.0002), colour (1.97, p < 0.0001), stiffness (2.47, p < 0.0001), thickness (2.1, p < 0.0001), irregularity (1.89, p < 0.0001) and overall opinion (1.58, p  =  0.0003)., Conclusion: Current management options for hypertrophic scarring have limited evidence. Laser therapy presents a minimally invasive procedure that can be completed under topical anaesthetic and has shown to be effective following a single treatment of combined carbon dioxide laser and intense pulsed light device therapy., Lay Summary: Many people will suffer a burn injury throughout their life and up to almost 3 out of 4 people with burn injuries will suffer from hypertrophic scars (a thickened, red and itchy scar). These scars cause distress both due to their appearance and their reduction of function, particularly over a joint or muscle. Laser therapy, in which different wave lengths of light (pulsed light) or gas (carbon dioxide) target the scar, has been found to be effective and have minimal side effects in the management of hypertrophic scars. While individual lasers have been assessed and found to be effective and low risk, the combined use of multiple lasers on the same scar has not been extensively studied. We studied the effectiveness of both light and gas laser therapies on hypertrophic scars. Patients with hypertrophic scars completed a questionnaire that focused on their perspective of their scar (pain, itch, stiffness, thickness, irregularity, overall opinion) prior to the treatment. The patients then underwent laser therapy (with local anaesthetic gel) with either pulsed light and/or carbon dioxide (gas) laser. The type of laser used was decided by the clinician performing the therapy depending on scar location and thickness. Patients then re-completed the subjective survey six weeks following the laser therapy, and the results compared. We learnt that laser therapy (both light, gas and a combination of both) are effective (and low risk) in reducing the subjective burden of the scar for the patient., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

To develop a risk assessment scale for pathological scarring and validate its psychometric properties. This was a methodological study. Researchers developed the scale based on a literature review, qualitative study and Delphi expert consultation. Subsequently, 409 patients participated in the study to test the psychometric properties of the scale. We evaluated construct validity, content validity, internal consistency reliability, and interrater reliability. The researchers developed a scale consisting of three dimensions and 12 items. Factor analysis extracted a total of four common factors that accounted for 62.22% of the total variance. The results revealed that the item-content validity index (I-CVI) ranged from 0.67 to 1, while the scale-content validity index (S-CVI) was 0.82. Internal consistency reliability: Cronbach's α of the items ranged from 0.67 to 0.76, while Cronbach's α of the whole scale was 0.74. Interrater reliability: the Kappa number was 0.73. The final scale showed adequate construct validity, content validity, and reliability. It is appropriate for use in research and clinical practice settings to identify patients with a risk of pathological scarring. Further study is needed to confirm the scale's validity and reliability in other settings and populations., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Employing animal models to study heart failure (HF) has become indispensable to discover and test novel therapies, but their translatability remains challenging. Although cytoskeletal alterations are linked to HF, the tubulin signature of common experimental models has been incompletely defined. Here, we assessed the tubulin signature in a large set of human cardiac samples and myocardium of animal models with cardiac remodeling caused by pressure overload, myocardial infarction or a gene defect. We studied levels of total, acetylated, and detyrosinated α-tubulin and desmin in cardiac tissue from hypertrophic (HCM) and dilated cardiomyopathy (DCM) patients with an idiopathic (n = 7), ischemic (n = 7) or genetic origin (n = 59), and in a pressure-overload concentric hypertrophic pig model (n = 32), pigs with a myocardial infarction (n = 28), mature pigs (n = 6), and mice (n = 15) carrying the HCM-associated MYBPC3 2373insG mutation. In the human samples, detyrosinated α-tubulin was increased 4-fold in end-stage HCM and 14-fold in pediatric DCM patients. Acetylated α-tubulin was increased twofold in ischemic patients. Across different animal models, the tubulin signature remained mostly unaltered. Only mature pigs were characterized by a 0.5-fold decrease in levels of total, acetylated, and detyrosinated α-tubulin. Moreover, we showed increased desmin levels in biopsies from NYHA class II HCM patients (2.5-fold) and the pressure-overload pig model (0.2-0.3-fold). Together, our data suggest that desmin levels increase early on in concentric hypertrophy and that animal models only partially recapitulate the proliferated and modified tubulin signature observed clinically. Our data warrant careful consideration when studying maladaptive responses to changes in the tubulin content in animal models., (© 2023. The Author(s).)

Background: Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families., Objectives: The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes., Methods: A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants., Results: Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P  = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up., Conclusions: The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives., Competing Interests: Dr Nielsen has received funding from the 10.13039/501100006356University of Southern Denmark and 10.13039/100004339an unrestricted grant from Sanofi Aventis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Competing Interests: Disclosures Dr Tromp is supported by the National University of Singapore Start-up grant, the tier 1 grant from the Ministry of Education, and the Clinical Scientist-Individual Research Grant (CS-IRG) New Investigator Grant from the National Medical Research Council; has received consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche diagnostics and Us2.ai, owns patent US-10702247-B2 unrelated to the present work. Dr van der Meer received grant support or consultancy fees from: Novartis, Pharma Nord, Pfizer, Ionis, Astra Zeneca, Vifor Pharma, Pharmacosmos, BridgeBio, NovoNordisk. The other authors report no conflicts.

Background: Burn injury is a sudden and traumatic injury that affects a large part of the population worldwide, who are placed at high risk of developing hypertrophic scars (HTS). HTS are a fibrotic scar resulting in painful contracted and raised scarring, affecting mobility in joints and work life, as well as cosmetically. The aim of this research was to enhance our understanding of the systematic response of monocytes and cytokines in wound healing after burn injury, in order to develop novel approaches to prevention and treatment of HTS., Methods: Twenty-seven burn patients and thirteen healthy individuals were recruited in this study. Burn patients were stratified by burn total body surface area (TBSA). Peripheral blood samples were taken post-burn injury. Serum and peripheral blood mononuclear cells (PBMCs) were separated from the blood samples. This research investigated cytokines IL-6, IL-8, IL1RA, IL-10, and chemokine pathways SDF-1/CXCR4, MCP-1/CCR2, RANTES/CCR5 during the wound healing process in burn patients with varying severity of injuries by using enzyme-linked immunosorbent assays. PBMCs were stained for monocytes and the chemokine receptors by flow cytometry. Statistical analysis was done by one-way ANOVA with a Tukey correction, and regression analysis was performed using Pearson's Correlation analysis., Results: The CD14 + CD16 - monocyte subpopulation is larger in patients who developed HTS at 4-7 days. The CD14 + CD16 + monocyte subpopulation is smaller in the first week of injury, where it is similar after 8 days. Burn injury increased CXCR4, CCR2, and CCR5 expressions in CD14 + CD16 + monocytes. Increases in MCP-1 at 0-3 days after burn injury was positively correlated with burn severity. IL-6, IL-8, RANTES, and MCP-1 significantly increased with increasing burn severity., Conclusions: Monocytes and their chemokine receptors, as well as systemic levels of cytokines in wound healing of burn patients and scar development will require ongoing assessment to enhance our understanding of the abnormal wound healing after burn injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Aims and Objectives: This study explored the physical and psychological effects of scar massage on burn patients., Background: Hypertrophic scar development is highly prevalent following burn injuries. Scar massage may have physical and psychological effects, although evidence of its effectiveness for burn scar improvement remains inconsistent., Design: A systematic review and meta-analysis of randomised controlled trials and quasi-experimental trials., Methods: This study was conducted following the Centre of Reviews and Dissemination guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature, PubMed, EMBASE, and Chinese Electronic Periodical Services were searched for studies published between January 1990 and February 2022. Quality was assessed using the Joanna Briggs Institute (JBI) Appraisal Checklist. The final recommendation strength was assessed according to the JBI recommendation rating. A meta-analysis was performed using Review Manager Version 5.4 software with a random-effect model., Results: Seven studies (420 participants) investigating scar massage for burn patients were included. The scar massage sessions lasted 5-30 min and were delivered by massage therapists 1-3 times a week for 12 weeks. Overall, scar massage decreased pain levels (standardised mean difference [SMD]: -2.39; 95% confidence interval [CI]: -3.96 to -0.83), improved scar thickness (mean difference: -0.05; 95% CI: -0.1 to -0.0), reduced pruritus (SMD: -1.89; 95% CI: -2.95 to -0.82) and reduced anxiety (SMD: -1.52; 95% CI: -2.73 to -0.32), but no significant effect on depression(SMD: -0.92; 95% CI:-2.28 to 0.44)., Conclusions: The meta-effects of scar massage among burn patients are significantly improved scar formation and reduced pruritus and anxiety. Providing scar massage is feasible and effective for burn patients. Future research should evaluate its long-term effects., Relevance to Clinical Practice: Scar massage is relatively convenient and effective in preventing and alleviating hypertrophic burn scarring. Further research can provide detailed suggestions for effective scar massage implementation., (© 2022 John Wiley & Sons Ltd.)

Osteoarthritis (OA) is the main pathogenic factor in diseases that cause joint deformities. As the main manifestation of the progress of OA, cartilage degradation has been closely associated with the degeneration of chondrocytes, which is induced by inflammatory factors and other trauma factors. Autophagy and apoptosis are the main mechanisms for cells to maintain homeostasis and play crucial roles in OA. Under the influence of external environmental factors (such as aging and injury), the metabolism of cells can be altered, which may affect the extent of autophagy and apoptosis. With the progression of OA, these changes can alter the cell phenotypes, and the cells of different phenotypes display distinct differences in morphology and function. In this review, we have summarized the alteration in cell metabolism, autophagy, and the extent of apoptosis during OA progression and its effects on the cell phenotypes to provide new ideas for further research on the mechanisms of phenotypic transition and therapeutic strategies so as to reverse the cell phenotypes., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Introduction and Objectives: Missense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain., Methods: We recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy., Results: Eleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC., Conclusions: FLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Since its introduction, laparoscopic pyloromyotomy (LP), has become increasingly popular in many countries. We have noticed an attenuated trend in Germany. The aim of this study was to analyse the distribution of open and LP in Germany. The national database of administrative claims data of the Institute for the Remuneration System in Hospitals (InEK) was analysed regarding numbers of patients with pyloromyotomy in the years 2019-2021. The German quality reports of the hospitals of 2019 and 2020 were analyzed regarding the number of procedures performed per hospital and pediatric surgical department. A total of 2050 patients underwent pyloromyotomy. The incidence of hypertrophic pylorus stenosis (HPS) was 699 and 657 patients in 2019 and 2021, respectively. Regarding age, 31.1% were admitted before 28 days of age. LP gradually increased from 216 patients (30.9%) in 2019 to 239 patients (36.4%) in 2021. Thirty-three laparoscopic operations (4.8%) were converted to an open approach. In 24 of all patients, there was an injury to the stomach, in 20 patients to the duodenum, needing repair with sutures. Analysis of the quality reports indicated that 44% of pediatric surgical departments performed LP. Although LP has became more prevalent in Germany recently, about two thirds of patients still undergo an open procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Leonhardt, Muensterer, Alsweed and Schmedding.)

Background Massive earlobe scarring/keloid formation can occur after ear piercing in individuals of African descent. Case report: A 14-year-old African girl with pierced ears in childhood presented with two progressively growing and disfiguring tumors on both earlobes. The maximum diameter of each lesion was 5.5 centimeters, and the weight of each lesion was approximately 20 grams. Histologically, there was a mixed pattern of keloid and hypertrophic scarring. Discussion: Massive keloids can occur after ear piercing in childhood. It is unclear why some individuals develop these massive keloids.

Objectives: Hypertrophic cardiomyopathy (HCM) often requires repeated enhanced cardiac magnetic resonance (CMR) imaging to detect fibrosis. We aimed to develop a practical model based on cine imaging to help identify patients with high risk of fibrosis and screen out patients without fibrosis to avoid unnecessary injection of contrast., Methods: A total of 273 patients with HCM were divided into training and test sets at a ratio of 7:3. Logistic regression analysis was used to find predictive image features to construct CMR model. Radiomic features were derived from the maximal wall thickness (MWT) slice and entire left ventricular (LV) myocardium. Extreme gradient boosting was used to build radiomic models. Integrated models were established by fusing image features and radiomic models. The model performance was validated in the test set and assessed by ROC and calibration curve and decision curve analysis (DCA)., Results: We established five prediction models, including CMR, R1 (based on the MWT slice), R2 (based on the entire LV myocardium), and two integrated models (I CMR+R1 and I CMR+R2 ). In the test set, I CMR+R2 model had an excellent AUC value (0.898), diagnostic accuracy (89.02%), sensitivity (92.54%), and F1 score (93.23%) in identifying patients with positive late gadolinium enhancement. The calibration plots and DCA indicated that I CMR+R2 model was well-calibrated and presented a better net benefit than other models., Conclusions: A predictive model that fused image and radiomic features from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility., Key Points: • Hypertrophic cardiomyopathy is prone to fibrosis, requiring patients to undergo repeated enhanced cardiac magnetic resonance imaging to detect fibrosis over their lifetime follow-up. • A predictive model based on the entire left ventricular myocardium outperformed a model based on a slice of the maximal wall thickness. • A predictive model that fused image and radiomic features from the entire left ventricular myocardium had excellent diagnostic performance, robustness, and clinical utility., (© 2022. The Author(s).)

Background: Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy. Currently, hypertrophy pathways responsible for HCM have not been fully elucidated. Their identification could serve as a nidus for the generation of novel therapeutics aimed at halting disease development or progression. Herein, we performed a comprehensive multi-omic characterization of hypertrophy pathways in HCM., Methods: Flash-frozen cardiac tissues were collected from genotyped HCM patients (n=97) undergoing surgical myectomy and tissue from 23 controls. RNA sequencing and mass spectrometry-enabled deep proteome and phosphoproteomic assessment were performed. Rigorous differential expression, gene set enrichment, and pathway analyses were performed to characterize HCM-mediated alterations with emphasis on hypertrophy pathways., Results: We identified transcriptional dysregulation with 1246 (8%) differentially expressed genes and elucidated downregulation of 10 hypertrophy pathways. Deep proteomic analysis identified 411 proteins (9%) that differed between HCM and controls with strong dysregulation of metabolic pathways. Seven hypertrophy pathways were upregulated with antagonistic upregulation of 5 of 10 hypertrophy pathways shown to be downregulated in the transcriptome. Most upregulated hypertrophy pathways encompassed the rat sarcoma-mitogen-activated protein kinase signaling cascade. Phosphoproteomic analysis demonstrated hyperphosphorylation of the rat sarcoma-mitogen-activated protein kinase system suggesting activation of this signaling cascade. There was a common transcriptomic and proteomic profile regardless of genotype., Conclusions: At time of surgical myectomy, the ventricular proteome, independent of genotype, reveals widespread upregulation and activation of hypertrophy pathways, mainly involving the rat sarcoma-mitogen-activated protein kinase signaling cascade. In addition, there is a counterregulatory transcriptional downregulation of the same pathways. Rat sarcoma-mitogen-activated protein kinase activation may serve a crucial role in hypertrophy observed in HCM.

Background: Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM., Methods: A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve., Results: Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers ( P <0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P =0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P <0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P <0.005)., Conclusions: Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.

Background: Nonunions remain a challenging post-traumatic complication that often leads to a financial and health burden that affects the patient's quality of life. Despite a wealth of knowledge about fracture repair, especially gene and more recently miRNA expression, much remains unknown about the molecular differences between normal physiological repair (callus tissue) and a nonunion. To probe this lack of knowledge, we embarked on a study that sought to identify and compare the human miRNAome of normal bone to that present in a normal fracture callus and those from two different classic nonunion types, hypertrophic and oligotrophic., Methods: Normal bone and callus tissue samples were harvested during revision surgery from patients with physiological fracture repair and nonunions (hypertrophic and oligotrophic) and analyzed using histology. Also, miRNAs were isolated and screened using microarrays followed by bioinformatic analyses, including, differential expression, pathways and biological processes, as well as elucidation of target genes., Results: Out of 30,424 mature miRNAs (from 203 organisms) screened via microarrays, 635 (∼2.1%) miRNAs were found to be upregulated and 855 (∼2.8%) downregulated in the fracture callus and nonunion tissues as compared to intact bone. As our tissue samples were derived from humans, we focused on the human miRNAs and out of the 4223 human miRNAs, 86 miRNAs (∼2.0%) were upregulated and 51 (∼1.2%) were downregulated. Although there were similarities between the three experimental samples, we also found specific miRNAs that were unique to individual samples. We further identified the predicted target genes from these differentially expressed miRNAs as well as the relevant biological processes, including specific signaling pathways that are activated in all three experimental samples., Conclusion: Collectively, this is the first comprehensive study reporting on the miRNAome of intact bone as compared to fracture callus and nonunion tissues. Further, we identify specific miRNAs involved in normal physiological fracture repair as well as those of nonunions., The Translational Potential of This Article: The data generated from this study further increase our molecular understanding of the roles of miRNAs during normal and aberrant fracture repair and this knowledge can be used in the future in the development of miRNA-based therapeutics for skeletal regeneration., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2023 Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society.)

Pressure overload hypertrophy of the left ventricle is a common result of many cardiovascular diseases. Androgens show anabolic effects in skeletal muscles, but also in myocardial hypertrophy. We carefully reviewed literature regarding possible effects of androgens on specific left ventricular hypertrophy in pressure overload conditions excluding volume overload conditions or generel sex differences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schafstedde and Nordmeyer.)

Background: Electrocardiography (ECG), as an easily accessible modality, is usually helpful in hypertrophic cardiomyopathy (HCM) diagnosis. The purpose of this study was to evaluate the role of ECG in differentiating between obstructive (OHCM) and non-obstructive (NOHCM) HCM., Methods: The present study is a cross-sectional analysis of HCM patients referred to our center between 2008 and 2017. The study variables included age, sex, clinical presentation, medications, and ECG characteristics including PR interval, QRS width, QTc duration, Tpeak-Tend interval, QRS axis, QRS transition, ventricular hypertrophies, atrial abnormalities, ST-T abnormalities, and abnormal Q waves., Results: The HCM sample consisted of 200 patients (55% males; age 45.60±15.50 y) from our HCM database. We compared the clinical and ECG characteristics of 143 NOHCM patients with those of 57 OHCM patients. The OHCM group was significantly younger than the NOHCM group (age =41.7 vs 47.0 y; P=0.016). The initial clinical presentation was similar between the 2 forms (P>0.05), and palpitations were the dominant symptom. Baseline ECG intervals, including PR (155.6 vs 157.9 ms), QRS (82.5 vs 82.0 ms), and QTc (430.5 vs 433.0 ms), were similar (all Ps>0.050). There were no differences regarding baseline rhythm, atrial abnormalities, QRS transition, ventricular hypertrophies, axis changes, ST-T changes, and abnormal Q waves between the HCM groups (all Ps>0.05)., Conclusion: The present study showed that standard 12-lead ECG had no role in distinguishing patients with the obstructive and non-obstructive forms of HCM., (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Background: A systematic review was performed to deliver a critical view of clinical and research practice on hypertrophic cardiomyopathy (HCM) in Saudi Arabia. Scopus, PubMed, and Google Scholar databases were searched for original articles reporting clinical and/or imaging findings among HCM patients in Saudi Arabia. Of 559 records identified, 3 studies and 1 abstract were included, involving 169 patients., Methods: The mean age ranged between 40and 56 years, up to 93.3% were males. A family history of HCM was reported in one study (5%), and sudden cardiac death was investigated in two studies (9% and 13%). Dyspnea was the most frequent symptom (60-68.7%) reported, followed by chest pain (12.5%-73.3%)., Results: Regarding complications, atrial fibrillation was reported among 0-25% of the patients, mitral regurgitations among 13.3-50%, and ventricular tachycardia among 5-12.5%. Imaging parameters were inadequately documented and suggested a high prevalence of left atrial enlargement, SVI + RV5 > 35 mm, blocks, and asymmetric septal hypertrophy., Conclusion: The ejection fraction was reported by two studies with a mean±SD of 68±13% and 77.2±8.07%. The researchers stress the paucity, low quality, and disparity in time of original studies about HCM in Saudi Arabia and recommend conducting national multicenter studies, with appropriate design, notably using screening-based recruitment methods., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Hypertrophic cardiomyopathy (HCM) patients are closely related to LA functional impairment. Left atrial (LA) strain provides more insight into LA function. The study aimed to investigate the left atrial dysfunction of HCM patients by rapid semi-automatic method and determine the predictive value of left atrial long-axis strain (LAS) for atrial fibrillation (AF)., Methods: We enrolled 372 HCM patients and 100 healthy participants to assess the LA functional parameters. LAS was obtained by semi-automated tracking of the distance between the mid-posterior point of LA wall which is defined as the intersection of the LA long axis and the posterior wall, and the origins of the mitral valve. The inferior and anterior mitral valve annular insertion points on the 2-chamber view and the lateral and septal insertion points on the 4-chamber view were chosen as the origins of the mitral valve. The clinical outcome was defined as detecting the onset of AF., Results: The LA strain values were analyzed as 20.8 ± 7.48% for ε s , 9.81 ± 5.09% for ε e , and 10.91 ± 4.24% for ε a in HCM patients, which decreased significantly compared with normal controls. Significant correlations were detected between LV functional parameters and LA strain. During a median follow-up of 61 months, 44 (11.8%) patients developed AF. In the Cox regression analysis, LA strain was identified as a significant predictor of the onset of AF., Conclusions: HCM patients had impairment of LA strain before LA enlargement and reduced EF. LA-LAS can be used as a predictive value for predicting the occurrence of AF in HCM patients., Key Points: • Fast semi-automated long-axis strain analysis by CMR is feasible and effective for evaluating the LA longitudinal function. • Hypertrophic cardiomyopathy patients show significant impairment of left atrial strain before LA enlargement. • The left atrial long-axis strain was an independent predictor of atrial fibrillation in hypertrophic cardiomyopathy., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Acne vulgaris is a troubling skin disease known to have both physiologic and psychological effects on patients. Acne scars, a frequent complication, can further impact patients' quality of life. Scars result from an impairment in the healing process. Acne scars can be categorized as follows: atrophic scars (including ice pick, rolling, boxcar subtypes) and trophic (including hypertrophic and keloid scars), the latter being less common. Though various treatment approaches have been suggested, there is a lack of high-quality evidence on effective, type-specific acne scar approaches. Herein, we aim to review the current evidence for treating various acne scars., Competing Interests: The authors have no conflicts to disclose., (Copyright 2022 by SkinCareGuide.com Ltd. Skin Therapy Letter© is published 6 times annually by SkinCareGuide.com Ltd, 1003 - 1166 Alberni Street, Vancouver, British Columbia, Canada, V6E 3Z3. All rights reserved. Reproduction in whole or in part by any process is strictly forbidden without prior consent of the publisher in writing.)

Aims: To describe results from genetic testing for cardiomyopathies in a national laboratory for genetic testing in Norway since 2003., Methods and Results: Retrospective data collection from the laboratory information management system at Unit for Cardiac and Cardiovascular Genetics, Oslo University hospital. Data from 4408 probands and 3008 relatives were available. Three probands had two variants, nine had incidental findings of variants not related to their cardiomyopathy diagnosis. Of the remaining 4396 probands, 65.1% were males, age at genetic testing was 50.9 (±18.1) years and 6.1% were under the age of 18. A likely pathogenic or pathogenic variant (216 different variants including 67 novel) was detected in 574 probands, corresponding to a hit-rate of genetic testing of 13.1% in total, 11.9% in hypertrophic, 14.1% in dilated, and 14.9% in arrhythmogenic right ventricular cardiomyopathy. Of the 3008 relatives, 47.6 % were males, age at genetic testing was 39.3 (±20.5) years, 17.9% were under the age of 18, and 43.2% were positive for the variant found in their family. Probands and relatives combined, 1/2809 persons in Norway were found to be heterozygous for a cardiomyopathy variant. Next Generation Sequencing provided more findings in dilated cardiomyopathy, especially in TTN accounting for 44.2% of all variants. Otherwise, the majority of variants were found in the classical sarcomeric and desmosomal genes., Conclusion: Genetic testing provided a genetic basis of the cardiomyopathy in 13.1% of probands, and subsequent family testing identified almost three times as many variant-positive relatives which could be offered preventive follow-up., Competing Interests: Conflicts of interest: M.P.B. reports personal fees from Sanofi and Amgen outside the submitted work. T.T.S. and T.P.L. report no conflicts of interest outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Although skin scarring is considered by some to be a minor, unavoidable consequence in response to skin injury, for many patients, cosmetically unsightly scars may cause uncomfortable symptoms and loss of function plus significant psycho-social distress. Despite their high prevalence and commonality, defining skin scars and their optimal management has proven problematic. Therefore, a literature search to assess the current evidence-base for scarring treatment options was conducted, and only those deemed Levels of Evidence 1 or 2 were included. Understanding the spectrum of skin scarring in the first instance is imperative, and is mainly comprised of four distinct endotypes; Stretched (flat), Contracted, Atrophic, and Raised for which the acronym S.C.A.R. may be used. Traditionally, scar assessment and response to therapy has employed the use of subjective scar scales, although these are now being superseded by non-invasive, objective and quantitative measurement devices. Treatment options will vary depending on the specific scar endotype, but fall under one of 3 main categories: (1) Leave alone, (2) Non-invasive, (3) Invasive management. Non-invasive (mostly topical) management of skin scarring remains the most accessible, as many formulations are over-the-counter, and include silicone-based, onion extract-based, and green tea-based, however out of the 52 studies identified, only 28 had statistically significant positive outcomes. Invasive treatment options includes intralesional injections with steroids, 5-FU, PDT, and laser with surgical scar excision as a last resort especially in keloid scar management unless combined with an appropriate adjuvant therapy. In summary, scar management is a rapidly changing field with an unmet need to date for a structured and validated approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Basson and Bayat.)