Impact of connective tissue diseases on complications following aesthetic surgery: A matched cohort study.

BACKGROUND: The association between connective tissue diseases (CTDs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma, and complications following aesthetic surgery is under-investigated. We hypothesized that the risk of complications following aesthetic surgery was higher in patients with these connective tissue disorders compared to matched non-CTD patients. METHODS: All patients diagnosed with RA, SLE, and scleroderma who underwent aesthetic surgery at our institution from 2003-2022 were reviewed. Demographic data, comorbidities, medications, procedures, and postoperative complications were collected. Non-CTD controls were identified for each procedure and matched 1:1 based on propensity scores derived from race, sex, body mass index, smoking status, and comorbidities. RESULTS: Six hundred 38 patients were included, comprising 319 (50%) patients diagnosed with CTD and 319 (50%) controls. The average age at surgery was 56.3 years. There were 129 complications. There were no differences between the CTD and non-CTD patients in number of total complications (69 versus 60, p = 0.38), major complications (23 versus 16, p = 0.25), or minor complications (46 versus 44, p = 0.73). Complications were not significantly different between CTD patients and controls who underwent blepharoplasty (p = 0.38), breast reduction (p = 0.91), abdominoplasty (p = 0.46), or rhytidectomy (p = 0.50). CTD patients who underwent breast augmentation had significantly more complications than matched non-CTD patients in bivariate analysis (7 versus 0, p = 0.018*) and multivariable logistic regression (OR: 10.2, 95% CI: 1.21 to 93.3, p = 0.039*). CONCLUSIONS: Most aesthetic surgeries can safely be performed in patients with CTDs. Patients seeking breast augmentation should be counseled on a potentially increased risk of postoperative complications.

A familial case of aortic dilatation with p.Tyr470Cys in TGFBR2 in which the phenotype included only vascular lesions.

Hereditary connective tissue diseases have different risks of aortic dissection depending on the causative gene. We report a family with no extravascular phenotype and a clinical diagnosis of familial thoracic aortic aneurysm and dissection, but genetic testing confirmed p.Tyr470Cys in TGFBR2, which is typically the responsible gene for Loeys-Dietz syndrome. Validation of the clinical diagnosis by genetic testing is warranted.

Clinical Outcomes After Distal Bypass in Patients With Chronic Limb-Threatening Ischemia due to Connective Tissue Disease.

OBJECTIVES: Chronic limb-threatening ischemia (CLTI) is mostly caused by arteriosclerosis, but is sometimes due to connective tissue disease. However, there is a limited knowledge of clinical outcomes of patients with CLTI with connective tissue disease. The objective of the study was to assess outcomes after distal bypass in these patients using global vascular guidelines. MATERIAL AND METHODS: Data from distal bypasses performed for CLTI at a single center from 2014 to 2023 were evaluated retrospectively. Clinical outcomes after distal bypass were compared for patients with CLTI with arteriosclerosis (AS group) and those with connective tissue disease (CD group). The primary endpoints were limb salvage and wound healing. RESULTS: Of the 282 distal bypasses performed for 222 patients with CLTI, 22 were conducted for 21 patients with connective tissue disease (CD group). The connective tissue disease was progressive systemic scleroderma (n = 11 patients), pemphigoid diseases (n = 2), polyarteritis nodosa (n = 2), rheumatoid arthritis (n = 2), and others (n = 4). Compared with the AS group, the CD group included more females (P = .007) and had greater oral steroid use (P < .001) and a higher Global Limb Anatomical Staging System (GLASS) inframalleolar (IM) modifier P2 (P < .001). The mean follow-up period of the whole cohort was 27 ± 22 months with no significant difference between the groups (P = .25), and 22 limbs required major amputation during this period. The 2-year limb salvage rate was significantly lower in the CD group compared to the AS group (75% vs 94%, P = .020). Wound healing was achieved in 220 (78%) limbs, and the 12-month wound healing rate was significantly lower in the CD group (52% vs 86%, P = .006). CONCLUSION: The low 2-year limb salvage and 12-month wound healing rates in patients with CLTI with connective tissue disease indicate that distal bypass may be challenging in these patients.

Diagnosis and management of spontaneous coronary artery dissection: Two cases and a review of the literature.

Introduction and importance: Spontaneous coronary artery dissection (SCAD) is a rare but potentially fatal condition, often underdiagnosed despite its significance in acute coronary syndrome (ACS). The true prevalence remains uncertain due to diagnostic challenges. Identifying SCAD cases is crucial for reducing mortality and morbidity, especially considering the recurrence risk. The authors present two cases highlighting the importance of multimodality imaging in diagnosing and managing SCAD. Case presentation: Case 1: A 53-year-old man with a history of brain aneurysm presented with chest pain and shortness of breath. Despite negative EKGs and stress tests, coronary computed tomography angiography (CCTA) revealed non-obstructive dissection flaps. Medical management improved his condition.Case 2: A 55-year-old woman with no significant medical history experienced recurrent chest pain. Initial tests were negative, but CCTA revealed SCAD. Further screening uncovered undiagnosed fibromuscular dysplasia. Clinical discussion: SCAD poses diagnostic challenges, often mimicking other cardiac conditions. Traditional tests may yield negative results, necessitating advanced imaging techniques like CCTA. Recognizing SCAD's association with connective tissue disorders (CTD) is vital for comprehensive patient care. The authors' cases emphasize the importance of a systematic approach to diagnosing chest pain, including noninvasive modalities and considering underlying etiologies. Conclusion: SCAD diagnosis requires a high index of suspicion, especially when traditional cardiac tests are inconclusive. Beyond treatment, patients should undergo further evaluation for CTDs, particularly in those with minimal risk factors for atherosclerosis. Increased awareness and a multimodal diagnostic approach are crucial for timely intervention and improved outcomes in SCAD patients. Learning objectives: The authors aim to increase awareness regarding different clinical presentations of SCAD to decrease the risk of missed or late diagnosis. The authors' case series also signifies the multimodal imaging approach's role in evaluating chest pain. Upon diagnosis of SCAD, it is imperative to go beyond treatment and implement a reverse algorithmic strategy to discover any underlying causes and risk factors for SCAD predisposition.

Efficacy and safety of oral versus intravenous cyclophosphamide in treatment of connective tissue disease-related interstitial lung disease.

OBJECTIVE: Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. METHODS: The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. RESULTS: CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. CONCLUSION: Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.

Potential involvement of connective tissue growth factor in chondrocytes apoptosis of Kashin-Beck disease.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteoarthropathy characterized by excessive chondrocytes apoptosis. T-2 toxin exposure has been proved to be its etiology. Connective tissue growth factor (CTGF) exerts a profound influence on cartilage growth and metabolism. We investigated the potential role of CTGF in KBD development and examined CTGF alterations under T-2 toxin stimulation. METHODS: The levels of CTGF and chondrocyte apoptosis-related markers in cartilage and primary chondrocytes from KBD and control groups were measured using qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence. We analyzed expression changes of these genes in response to T-2 toxin. Apoptosis rates of chondrocytes induced by T-2 toxin were measured by flow cytometry and TUNEL assay. The active pharmaceutical ingredient targeting CTGF was screened through Comparative Toxicogenomics Database, and molecular docking was performed using AutoDock Tools. RESULTS: The CTGF levels in KBD cartilage and chondrocytes were significantly elevated and positively associated with the levels of apoptosis-related genes. T-2 toxin exposure increased CTGF and apoptosis-related gene levels in chondrocytes, with apoptosis rates rising alongside T-2 toxin concentration. Curcumin was identified as targeting CTGF and exhibited effective binding. It could down-regulate CTGF, apoptosis-related genes, such as Cleaved caspase 3 and BAX, and also significantly reduce apoptosis rate in chondrocytes treated with T-2 toxin. CONCLUSION: CTGF plays a crucial role in the development of KBD. Curcumin has shown potential in inhibiting CTGF levels and reducing chondrocyte apoptosis, highlighting its promise as a therapeutic agent for preventing cartilage damage in KBD. Our findings provided valuable insights into the pathogenesis of KBD and could promote the development of novel therapeutic strategies for this debilitating disease.

Thyroid cancer and autoimmune connective tissue disorders.

There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 separate diseases because of their relatively high incidence rates in the population. They can arise from each other due to the increased risk of thyroid cancer in patients with idiopathic inflammatory myositis, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and systemic lupus erythematosus. Moreover, in some scarce cases, CTDs may act as the paraneoplastic syndromes of thyroid cancer. The presence of CTDs may impact the diagnostic process, especially distorting the results of imaging tests or falsely indicating the increase of thyroglobulin or calcitonin. Finally, TSH suppression is a crucial element of the treatment of differentiated thyroid cancer, which may decrease bone mineral density and increase the risk of osteoporosis by accelerating bone turnover and shortening the bone remodeling cycle. The aim of this review is to emphasise the vital aspects of this interrelationship. The authors discuss this phenomenon aiming at the explanation of possible linking mechanisms. The impact of selected CTDs on thyroid cancer management is presented, as well as the possible effects of cancer therapy on skeletal health.

EULAR recommendations for the treatment of systemic sclerosis: 2023 update.

OBJECTIVES: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies. METHODS: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review. The evidence derived was discussed and overarching principles, recommendations and future research agenda were iteratively developed with voting rounds. RESULTS: The task force agreed on 22 recommendations covering 8 clinical/organ domains including Raynaud's phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease (ILD), gastrointestinal manifestations and arthritis. Most new recommendations are related to skin fibrosis and ILD. These included novel recommendations for the use of mycophenolate mofetil, nintedanib, rituximab and tocilizumab for the treatment of these crucial disease manifestations. The recommendations also included first-line and second-line interventions, providing increased utility for rheumatology practitioners. Important additions to the future research agenda included consideration of novel interventions for the management of vascular, musculoskeletal and gastrointestinal manifestations and calcinosis, as well as for the local management of digital ulcers. CONCLUSION: These updated recommendations include the first set of synthetic and biological targeted therapies recommended for key fibrotic manifestations of SSc as well as first-line combination treatment for newly diagnosed pulmonary artery hypertension and prioritise a new research agenda for the coming years.

Association of fluoroquinolones with the risk of spontaneous pneumothorax: nationwide case-time-control study.

INTRODUCTION: Fluoroquinolones can cause severe collagen-associated adverse effects, potentially impacting the pulmonary connective tissue. We investigated the association between fluoroquinolones and spontaneous pneumothorax. METHODS: A case-time-control study was performed using the nationwide French reimbursement healthcare system database (SNDS). Cases were adults ≥18 years admitted for spontaneous pneumothorax between 2017 and 2022. For each case, fluoroquinolone use was compared between the risk period immediately preceding the admission date (days -30 to -1), and three earlier reference periods (days -180 to -151, -150 to -121, -120 to -91), adjusting for time-varying confounders. OR estimates were corrected for potential exposure-trend bias using a reference group without the event (matched on age, sex, chronic obstructive pulmonary disease history, calendar time). Amoxicillin use was studied similarly to control for indication bias. RESULTS: Of the 246 pneumothorax cases exposed to fluoroquinolones (63.8% men; mean age, 43.0±18.4 years), 63 were exposed in the 30-day risk period preceding pneumothorax and 128 in the reference periods. Of the 3316 amoxicillin cases (72.9% men; mean age, 39.4±17.6 years), 1210 were exposed in the 30-day risk period and 1603 in the reference ones. OR adjusted for exposure-trend and covariates was 1.59 (95% CI 1.14 to 2.22) for fluoroquinolones and 2.25 (2.07 to 2.45) for amoxicillin. CONCLUSION: An increased risk of spontaneous pneumothorax was associated with both fluoroquinolone and amoxicillin use, with an even higher association for amoxicillin. This strongly suggests the role of the underlying infections rather than a causal effect of the individual antibiotics and can be considered reassuring regarding a potential lung connective toxicity of fluoroquinolones.

[Vitamin D and childhood disability: diseases of the musculoskeletal system and connective tissue in the Khanty-Mansi Autonomous Okrug - Ugra].

Vitamin D deficiency is more prevalent among children with musculoskeletal and connective tissue disorders (MSCTD), which plays a significant role in childhood disability, which ranks sixth in the structure of childhood disability in the Russian Federation. The aim of the research was to study of the relationship between the incidence of childhood disability associated with MSCTD and the state of vitamin D status of the population living in the territory of the Khanty-Mansiysk Autonomous Okrug - Ugra. Material and methods. A correlation analysis was carried out between the level of childhood disability (that arose in connection with MSCTD in children aged 0-17 years in the Khanty-Mansi Autonomous Okrug - Ugra in 2021) and the prevalence of severe vitamin D deficit [serum 25(OH)D <10 ng/ml] among the population (12 city and 5 district municipalities), using the INVITRO-Ural LLC database (31 595 anonymized measurements of vitamin D level in Ugra residents). In addition, a correlation analysis was conducted between the total incidence of certain types of MSCTD in the constituent entities of the Russian Federation and the geographical latitude of the administrative center of the subjects of the Federation. Results. In the Khanty-Mansi Autonomous Okrug - Ugra, the frequency of childhood disability resulting from MSCTD is associated with a statistically stable (p=0.01) directly proportional relationship with the prevalence of severe vitamin D deficit in the residents of the municipality territory. In the Russian Federation, the dependence of the general morbidity of MSCTD in children (arthropathy, juvenile arthritis, and damage to the tendon synovial membranes) is very stable (p<0.0001) directly proportional associated with the geographical latitude of the territory. This indicates the impact of reduced levels of ultraviolet radiation and, accordingly, the average blood level of vitamin D in the population high in latitudes, along with other reasons, on human health. Conclusion. Low levels of vitamin D have a negative impact on the activity of MSCTD in children and the associated disability. To justify the recommended daily dose and duration of vitamin D intake, which in some cases can reduce the activity of MSCTD, it is necessary to measure its initial level in the blood serum of patients at risk.

A Randomized Controlled Trial on the Timing of Soft-Tissue Augmentation in Immediate Implant Placement: Hard-Tissue Changes and Clinical Outcome.

AIM: To assess the impact of the timing of soft-tissue augmentation (STA) on mean buccal bone changes following immediate implant placement (IPP) in the anterior maxilla. MATERIALS AND METHODS: Patients with a failing tooth and intact buccal bone wall in the anterior maxilla (15-25) were enrolled in this randomized controlled trial. Following single IIP and socket grafting, they were randomly allocated to the control group (immediate STA performed during the same surgical procedure) or the test group (delayed STA performed 3 months later). Implants were placed with a surgical guide and immediately restored with an implant-supported provisional crown. Changes in bone dimensions were assessed using superimposed CBCT images taken prior to surgery and at 1-year follow-up. Clinical outcomes were registered at 1-year follow-up. RESULTS: Twenty patients were randomized to each group (control: 16 females, 4 males, mean age 57.6; test: 9 females, 11 males, mean age 54.2). Ten patients in the control group and 13 patients in the test group had a thick bone wall phenotype. Estimated marginal mean horizontal buccal bone loss at 1 mm below the implant shoulder was -0.553 and -0.898 mm for the control and test group, respectively. The estimated mean difference of 0.344 mm in favour of the control group was not significant (95% CI: -0.415 to 1.104; p = 0.363). Also at all other horizontal and vertical levels, no significant differences could be observed between the groups. The combination of socket grafting and STA enabled counteraction of any buccal soft-tissue loss (≥ 0 mm) at 1 mm below the implant shoulder in 82% of the patients in the control group and in 75% of the patients in the test group (p = 1.000). The clinical outcome was favourable in both groups, yet implants in the control group demonstrated slightly less marginal bone loss (median difference 0.20 mm; 95% CI: 0.00-0.44; p = 0.028). CONCLUSION: In patients with an intact and mainly thick buccal bone wall in the anterior maxilla, the timing of STA following IIP had no significant impact on mean buccal bone loss. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05537545.

Impact of early diagnosis on surgical outcomes in patients with Loeys-Dietz syndrome.

Background: This study aimed to investigate the influence of early diagnosis (ED) on surgical outcomes in patients definitively diagnosed with Loeys-Dietz syndrome (LDS). Methods: A retrospective review was conducted on 38 patients with LDS who underwent aortic surgery at our institution between January 1995 and June 2022. The primary endpoint was freedom from aortic reoperation. Results: Among the patients, the median age at the initial surgery was 33 (range: 39-44) years, and 23 (60.5%) patients were male. Twenty-one (55.3%; aortic dissection or rupture (n = 2) and aneurysm (n = 19)) patients were diagnosed with LDS before the initial surgery (ED group). Meanwhile, the remaining 17 (44.7%; aortic dissection or rupture (n = 13) and aneurysm (n = 4)) patients were after surgery [delayed diagnosis (DD) group]. The ED group had significantly lower rates of emergency surgery and concomitant arch procedure (P < .001, respectively) but a higher rate of valve-sparing root surgery (P = .018) compared to the DD group. No in-hospital mortality was observed in either group. Nevertheless, the ED group had a shorter postoperative hospital stay (median difference: 3 days, P = .032) and a lower rate of aortic reoperation (P = .013). Conclusion: Early detection of LDS may help in preventing acute aortic syndrome, reducing the risk of aortic reoperation, and potentially shortening hospital stay. Careful medical management before surgery could contribute to better clinical outcomes and an improved quality of life for patients with LDS.

Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

AIM: Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. METHODS: We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. RESULTS: A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. CONCLUSIONS: In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

Post-lung transplant outcomes of connective tissue disease-related interstitial lung diseases compared with idiopathic interstitial pneumonia: a single-center experience in Japan.

OBJECTIVES: The aim of this study was to investigate the outcomes of lung transplantation for connective tissue disease-related interstitial lung disease (CTD-ILD) conducted at our institution, compared with those for idiopathic interstitial pneumonias (IIPs). METHODS: We retrospectively reviewed patients with CTD-ILD and IIPs who underwent lung transplantation at our hospital from July 2015 to October 2023. We compared patients' backgrounds, early complications within 28 days post-transplant (CTCAE grade 3 or higher), postoperative courses, and prognoses between the two groups. RESULTS: The CTD-ILD group (n = 19) and the IIPs group (n = 56) were compared. The CTD-ILD group had significantly higher preoperative use of corticosteroids and antifibrotic agents, mean pulmonary arterial pressure, anti-human leukocyte antigen antibody positivity, and donor age (p < 0.05). In addition, the CTD-ILD group had significantly longer operation times (579.0 vs 442.5 min), longer stays in the intensive care unit (17.0 vs 9.0 days) and hospital (58.0 vs 44.0 days); required more tracheostomies (57.9 vs 25.0%); and experienced more respiratory (52.6 vs 25.0%) and gastrointestinal (42.1 vs 8.9%) complications (p < 0.05). However, there were no significant differences in overall survival, nor chronic lung allograft dysfunction (CLAD)-free survival between the two groups. CONCLUSION: Perioperative complications, notably respiratory and gastrointestinal complications, were prevalent after lung transplantation among CTD-ILD patients. Despite this, long-term survival rates were comparable to those observed in IIP cases.

The duct of von Ebner's glands is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Introduction: We have recently demonstrated that Sox10-expressing (Sox10 +) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10 + cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae. Methods: In this study, we performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex and used inducible Cre mouse models to map the cell lineages of vEGs and/or connective tissue (including stromal and Schwann cells). Results: Transcriptomic analysis indicated that Sox10 expression was enriched in the cell clusters of vEG ducts that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and vEG ductal cells. In vivo lineage mapping showed that the traced cells were distributed in circumvallate taste buds concurrently with those in the vEGs, but not in the connective tissue. Moreover, multiple genes encoding pathogen receptors were enriched in the vEG ducts hosting Sox10 + cells. Discussion: Our data supports that it is the vEGs, not connective tissue core, that serve as the niche of Sox10 + taste bud progenitors. If this is also true in humans, our data indicates that vEG duct is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Safety and Efficacy of an Injectable Solution Enriched With Sodium Hyaluronate, Amino Acids, and Peptides in Relation to Superficial Facial Connective Tissues (Dermis and Retinacular Cutis).

BACKGROUND: Skin aging research often focuses on the dermis, overlooking the significance of the retinacular cutis (RC) in aging. This study aimed to investigate the efficacy, safety, and effect of an injectable solution containing hyaluronic acid, amino acids, and peptides, on facial sagging and laxity by targeting the RC. METHODS: This single-center observational study recruited 28 female volunteers aged 25-65 years. The participants received four monthly injections of the studied solution. Objective measures included skin hydration, elasticity, color, thickness, collagen density evaluated via DermaLab Combo and high-resolution ultrasound imaging. Subjective measures included participant satisfaction evaluated using the Global Aesthetic Improvement Scale (GAIS). Adverse effects were monitored throughout the study period. RESULTS: Significant improvements were observed in skin hydration, elasticity, and collagen density after treatment. Hydration increased by 25.9% at T1 (30 days after last session), sustaining a 15.9% increase at T2 (120 days after last session). Elasticity improved by 29.2% at T1 and 20.7% at T2. Collagen density increased by 20.27% at T1 and 16.71% at T2. Self-reported GAIS scores showed consistent increases. Adverse effects were minimal and included only transient ecchymosis and mild pain. CONCLUSION: Injections of the solution had a substantial hydrating effect, enhanced elasticity, and increased collagen density in the RC and dermis. Results persisted at the 120-day follow-up, indicating sustained benefits. Hence, this injectable solution may offer a safe and effective non-invasive treatment option for improving skin laxity and sagging, targeting the RC and other deep connective tissue such as retaining ligaments.

Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.

This review provides a personal overview of significant scientific developments in the thrombospondin field during the course of my career. Thrombospondins are multidomain, multimeric, calcium-binding extracellular glycoproteins with context-specific roles in tissue organisation. They act at cell surfaces and within ECM to regulate cell phenotype and signalling, differentiation and assembly of collagenous ECM, along with tissue-specific roles in cartilage, angiogenesis and synaptic function. More recently, intracellular, homeostatic roles have also been identified. Resolution of structures for the major domains of mammalian thrombospondins has facilitated major advances in understanding thrombospondin biology from molecule to tissue; for example, in illuminating molecular consequences of disease-causing coding mutations in human pseudoachrondroplasia. Although principally studied in vertebrates, thrombospondins are amongst the most ancient of animal ECM proteins, with many invertebrates encoding a single thrombospondin and the thrombospondin gene family of vertebrates originating through gene duplications. Moreover, thrombospondins form one branch of a thrombospondin superfamily that debuted at the origin of metazoans. The super-family includes additional sub-groups, present only in invertebrates, that differ in N-terminal domain organisation, share the distinctive TSP C-terminal region domain architecture and, to the limited extent studied to date, apparently contribute to tissue development and organisation. Finally, major lines of translational research are discussed, related to fibrosis; TSP1, TSP2 and inhibition of angiogenesis; and the alleviation of chronic cartilage tissue pathologies in pseudoachrondroplasia.