Scarring Disorders Research Articles

A TriNetX Analysis of Hypertrophic Scarring Disorders, Genitourinary Strictures, and Urethroplasty Failure.

Background: Urethral strictures and bladder neck contractures (BNCs) can be significantly morbid for patients and may require intervention for effective urinary drainage. We hypothesized patients with abnormal scarring disorders, such as keloids or hypertrophic scars, are at elevated risks of urethroplasty failure as well as postprocedural urethral strictures and BNCs. Methods: We queried the TriNetX database to determine the risk of urethroplasty failure for patients with abnormal scarring disorders compared to controls. We also investigated the risk of developing urethral strictures and BNCs for patients undergoing various endourology procedures. Results are reported in terms of risk ratio (RR) with 95% confidence interval (CI). Statistical significance was considered when the CI did not include 1.0. Propensity score matching was performed to limit confounding. Notably, TriNetX rounds values < 10 to 10 for patient anonymity (denoted by *). Results: Urethroplasty patients with scarring pathology needed a second procedure more than twice as often (36.2% vs. <17.2%*, RR = 2.1, 95%CI 1.1-4.1). Following cystoscopy, there was no difference in urethral stricture rates for patients with scarring disorders (2.7% vs. 2.6%, RR = 1.1, 95%CI 0.85-1.3). These patients also showed similar rates of BNCs (7.5% vs. 5.3%, RR = 1.4, 95%CI 0.84-2.3) and urethral strictures (5.9% vs. 5.3%, RR = 1.1, 95%CI 0.68-1.8) after transurethral bladder outlet procedures. Conclusions: Patients with scarring disorders showed much higher urethroplasty failure rates. They experienced similar rates of urethral strictures and BNC formation after endoscopic procedures. These novel findings underscore the importance of recognizing abnormal scarring conditions during preoperative assessments, guiding clinicians in counseling patients and tailoring operative interventions.

Spatially resolved gene expression profiles of fibrosing interstitial lung diseases

Fibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP). We identified differentially expressed genes between LMEs within each condition, and across histologically similar regions between conditions. Uninvolved regions in IPF and CHP were distinct from normal controls, and displayed potential therapeutic targets. Hallmark LMEs of each condition retained distinct gene signatures, but these could not be reproduced in matched lung tissue samples. Based on these profiles and unsupervised clustering, we grouped previously unclassified ILD cases into NSIP or CHP. Overall, our work uniquely dissects gene expression profiles between LMEs within and across different types of fibrosing ILDs.

Clinicopathologic correlation of dermatologic diseases in patients with darker pigmentation.

Cutaneous diseases that disproportionately affect patients with darker pigmentation and their histologic features are historically understudied and undertreated. This review article aims to highlight the key clinical features, histopathology, and diagnostic pearls of several cutaneous diseases that commonly present in patients with darker pigmentation. A literature search was conducted, and a list of cutaneous diseases that frequently affect patients with darker pigmentation was compiled. A group of experts expounded upon those that were most common or misdiagnosed according to scientific evidence and clinical practice. The diseases were divided into hypopigmented disorders, hyperpigmented disorders, scarring disorders, and alopecic disorders. Within each category, the etiology, clinical features, histopathology, and key histologic differential diagnoses are described and discussed. As many clinicians are taught that there are no effective treatment options or that these diseases are considered "cosmetic" in nature, patients often do not get a thorough medical workup or skin biopsy. This article aims to decrease the knowledge gap and serve as a resource for anyone involved in the care of patients with these cutaneous conditions.

Tamoxifen Upregulates Collagenase Gene Expression in Human Dermal Fibroblasts.

Tamoxifen is a known inhibitor of fibroblast transforming growth factor beta biosynthesis and wound scar formation. Tamoxifen is also known to be an estrogen antagonist and protein kinase C (PKC) inhibitor. Cells treated with tamoxifen and other PKC/calmodulin inhibitors depolymerize their membrane focal adhesion complexes and cytoskeletal protein structures. These effects result in substrate detachment, cell shape rounding, and upregulation of collagenase synthesis and extracellular matrix degradation. The purpose of our study was to test the hypothesis that tamoxifen treatment of human foreskin fibroblasts results in alteration of cytoskeletal protein organization, cell detachment and rounding, and increased collagenase synthesis similar to known PKC/calmodulin inhibitors such as H-7. We characterized the effects of PKC/calmodulin inhibitors tamoxifen and H-7 on human dermal fibroblast morphology, cytoskeletal protein organization, and collagenase gene expression in monolayer culture and within collagen gels. We found that fibroblasts responded to tamoxifen by initiation of actin filament depolymerization followed by alteration from spindle to spheroidal shapes. This change in cell shape led to increased collagenase synthesis in cells treated with either tamoxifen or H-7 compared with controls. There was also a 23% increase of hydroxyproline release from tamoxifen-treated fibroblast-populated collagen matrices. Tamoxifen may reduce scarring by inhibiting fibroblast PKC/calmodulin activity, which down-regulates pro-fibrotic transforming growth factor beta signaling and upregulates collagenase production. These effects mimic those of the known PKC/calmodulin inhibitor H-7. Overall, these findings suggest that tamoxifen and its analogues are promising agents for clinical investigation as small molecule regulators of fibrosis and scarring disorders.

A Practical Algorithm for the Management of Superficial Folliculitis of the Scalp: 10 Years of Clinical and Dermoscopy Experience.

Superficial folliculitis of the scalp (SFS) is a common complaint in clinical practice, and initial presentation may be difficult to differentiate as they may appear very similar to each other. The aim of this thesis is to describe the pathologies that occur clinically as folliculitis of the scalp, identify their causes and characteristics and create a standardized classification. This is a retrospective clinical, dermoscopic and histopathological study over 10 years of dermatologic consultations. Only individuals with a confirmed diagnosis of SFS (updated diagnostic criteria or biopsy) were included. In this review, we describe the various clinical features of different causes of SFS in ninety-nine cases and divided into infectious due to fungus, bacteria, or virus and inflammatory conditions such as rosacea, acneiform eruption and Ofuji syndrome. The clinician must differentiate SFS from other underlying scarring disorders to prevent poorer outcomes. We created an algorithm to help the clinician reach a proper diagnosis.

Scarring and Dyschromias in Fitzpatrick Skin Type IV-VI: A Review of Dermatologic Treatment Protocols.

Managing chronic conditions is an essential aspect of dermatologic care, especially regarding the resolution of inflammatory dermatologic disease and recovery of skin lesions. Short-term complications of healing include infection, edema, dehiscence, hematoma formation, and tissue necrosis. At the same time, longer-term sequelae may consist of scarring and scar widening, hypertrophic scars, keloids, and pigmentary changes. This review will focus on dermatologic complications of chronic wound healing in patients with Fitzpatrick skin type (FPS) IV-VI or skin of color (SOC), with an emphasis on hypertrophy/scarring and dyschromias. It will focus on current treatment protocols and the potential complications specific to patients with FPS IV-VI. There are multiple complications of wound healing that are more prevalent in SOC, including dyschromias and hypertrophic scarring. These complications are challenging to treat, and current protocols are not without complications and side effects that must be considered when offering therapy to patients with FPS IV-VI. When treating pigmentary and scarring disorders in patients with skin types FPS IV-VI, it is essential to implement a stepwise approach to management that is conscious of the side effect profile of current interventions. J Drugs Dermatol. 2023;22(7): doi:10.36849/JDD.7253.

Hyperbaric Oxygen Therapy in Plastic, Aesthetic, and Reconstructive Surgery: Systematic Review

Introduction: Hyperbaric oxygen therapy (HBOT) has been used over the past six decades to treat multiple conditions. This systematic review aims to identify and evaluate the clinical outcomes of hyperbaric oxygen therapy in the field of plastic, reconstructive, and aesthetic surgery, found in the literature from the year 2000 to the present. Methods: A systematic review of the literature focused on the conceptual and methodological aspects of the PRISMA Declaration. The search for clinical trials focused on the results of hyperbaric therapy in plastic, reconstructive, and cosmetic surgery. The Newcastle–Ottawa scale suggested by the Cochrane manual was applied to each study. The study was carried out with a defined protocol and was registered in PROSPERO, with code CRD42022301261. Results: From the 170 articles identified, 6 were selected. Five of them showed that hyperbaric oxygen therapy favored the reduction of the size of skin ulcers and increased the formation of granulation tissue (two trials; p &lt; 0.05), increased the partial pressure of transcutaneous oxygen in patients with free flaps (one trial; p &lt; 0.001), reduced perfusion in keloid scarring disorder (one trial; p &lt; 0.01), and accelerated both the fading of melanin pigmentation and the decrease in age spot size (one trial; p &lt; 0.05). The methodological quality was moderate in all cases because there was no blinding method reported. One study failed to find differences in flap survival, time to resolution of venous congestion, resolution of edema, and postoperative recovery period (p &gt; 0.05). Conclusions: Hyperbaric oxygen therapy has been increasingly used in the field of plastic and reconstructive surgery, and has shown potential benefits in promoting wound healing, reducing the risk of infection, and improving the survival of tissues used in reconstructive procedures. Further research with more rigorous clinical trials is needed to fully understand the efficacy and optimal use of this therapy in the field of plastic and reconstructive surgery.

External ear canal exostectomy: influence of surgeon's experience on 3-years recurrence and occurrence of complications.

External ear canal exostoses are usually bilateral and broad-based, secondary to external ear canal chronic cold exposure, especially water. The objectives were to analyze the influence of the surgeon's experience on the 3-year recurrence and on the complication. We also studied the influence of prolonged exposure to cold water on the incidence of recurrence. This monocentric retrospective study included 98 ears operated for canalplasty between 2009 and 2016 by nine different operators including one senior, a junior, and seven beginner surgeons. Senior, Junior, and Beginner groups were compared. 3-year recurrence rate was higher in the Beginner and Junior groups than in the Senior group (69% and 38% vs 18%, P = .001). Although there was a difference between the Beginner (69%) and Junior (38%) groups, it was not significant (P = .407). Among the recurrences, 48% had continued exposure to cold water while only 7% of the ears without recidivism were still exposed (P < .001, OR = 1.25 [4.4; 36.1]). The complication rates were similar between groups, concerning pain (8% vs 30% vs 12%), per procedure perforation (17% vs 10% vs 16%), scarring disorders (25% vs 20% vs 13%), and osteitis (8% vs 0% vs 1%). Hearing was unaffected. This is the first study evaluating the risk of recurrence of external ear canal exostoses after canalplasty based on the surgeon's experience. This risk of recurrence seems to decrease with the surgeon's experience. There was no difference in complication rates.

Soft palate morphology in OSMF patients: Radiographic evaluation

Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disorder of oral cavity, which includes buccal mucosa, tongue, lips, anterior faucial pillars, soft palate, and oropharynx. Changes in soft palate morphology will start even before the OSMF, present itself clinically. These changes can lead to sleep apnea, difficulty in speech, swallowing &amp; respiration. Various radiographs are good diagnostic aid to assess the soft palate and its morphology or any changes in morphology. To evaluate and compare soft palate morphology and dimensions in various stages of OSMF with control by radiographic evaluation.: 60 patients were evaluated and compared for soft palate morphology, its length, width and angle by using lateral cephalogram and Cone beam computed tomography (CBCT). Most common type of soft palate was found to be type 1 (leaf shaped) in both groups as well as by both radiographic techniques. Significant decrease in length and increase in width with increasing grades of OSMF group. As per p value CBCT gave more precise result. As the OSMF progresses soft palate becomes stout and bulky and significant changes occur in soft palate dimensions and are better evaluated by CBCT. As involvement of the soft palate is the earliest change to be noticed, radiographs should be used as one of the diagnostic aids in OSMF patients.

Arthrofibrosis after total knee arthroplasty: patients with keloids at risk

BackgroundArthrofibrosis remains one of the leading causes for revision in primary total knee arthroplasty (TKA). Similar in nature to arthrofibrosis, hypertrophic scars and keloid formation are a result of excessive collagen formation. There is paucity in the literature on whether there is an association between keloid formation and the development of arthrofibrosis following TKA. Therefore, the purpose of this study was to utilize a large nationwide database to identify and compare the rates of postoperative complications related to arthrofibrosis after primary TKA in patients with history of hypertrophic scar and keloid disorders versus those without.MethodsPatient records from 2010 to the second quarter of 2016 were queried from an administrative claims database, comparing rates of arthrofibrosis, manipulation under anesthesia (MUA), lysis of adhesions (LOA), and revision TKA in patients with chart diagnosis of keloids versus those without in patients who underwent primary TKA. Data analysis was performed using R statistical software (R Project for Statistical Computing, Vienna, Austria) utilizing multivariate logistic regression, chi square analysis, or Welch’s t- test where appropriate with p values < 0.05 being considered statistically significant.ResultsOf 545,875 primary TKAs, 11,461 (2.1%) had a keloid diagnosis at any time point in their record, while 534,414 (97.9%) had not. Patients in the keloid cohort had a significantly higher association with ankylosis within 30 days (OR, 1.7), 90 days (OR, 1.2), 6 months (OR, 1.2), and 1 year (OR, 1.3) following primary TKA. The keloid cohort also had a significantly greater risk of MUA (90-day OR, 1.1; 6-month OR, 1.1; 1-year OR, 1.2) and LOA (90-day OR, 2.2; 6-month OR, 2.0; 1-year OR, 1.9).ConclusionPatients with keloids have increased odds risk of arthrofibrosis following primary TKA. These patients are subsequently at a higher odds risk of undergoing the procedures necessary to treat arthrofibrosis, such as MUA and LOA. Future studies investigating confounding factors such as race, prior surgery, range of motion, and postoperative recovery are needed to confirm the association of keloid diagnosis and arthrofibrosis following primary TKA demonstrated in this study.Level of EvidenceLevel III retrospective comparative study.

Dermatologic sequelae of breast cancer: From disease, surgery, and radiation

The care of breast cancer patients is important to dermatologists. Breast cancer's initial presentation, clinical progression, and its associated treatments can result in a variety of cutaneous complications. Dermatologists may be the first to identify a breast cancer diagnosis, as a subset of patients first present with direct extension of an underlying tumor or with a cutaneous metastasis. The surgical treatment of breast cancer also begets a variety of skin sequelae, including postoperative lymphedema, soft tissue infections, seromas, pyoderma gangrenosum, and scarring disorders. Moreover, breast cancer radiation treatment commonly results in skin changes, which can range from mild and temporary dermatoses to chronic and disfiguring skin ulceration, fibrosis, and necrosis. Radiation may also precipitate secondary malignancies, such as angiosarcoma, as well as rarer dermatologic diseases, such as radiation-induced morphea, lichen planus, and postirradiation pseudosclerodermatous panniculitis. Finally, breast cancer is also associated with an array of paraneoplastic phenomena, including Sweet's syndrome and the rarer intralymphatic histiocytosis. Herein, we review the dermatological manifestations of breast cancer, including conditions associated with its presentation, progression, and treatment sequelae. Chemotherapy-induced cutaneous side effects are beyond the scope of this review. This article provides a comprehensive review for dermatologist to be able to identify, diagnose, and manage breast cancer patients from initial presentation to treatment monitoring and subsequent follow-up.

Diverse functions of clusterin promote and protect against the development of pulmonary fibrosis

Pulmonary fibrosis is a progressive scarring disorder of the lung with dismal prognosis and no curative therapy. Clusterin, an extracellular chaperone and regulator of cell functions, is reduced in bronchoalveolar lavage fluid of patients with pulmonary fibrosis. However, its distribution and role in normal and fibrotic human lung are incompletely characterized. Immunohistochemical localization of clusterin revealed strong staining associated with fibroblasts in control lung and morphologically normal areas of fibrotic lung but weak or undetectable staining in fibrotic regions and particularly fibroblastic foci. Clusterin also co-localized with elastin in vessel walls and additionally with amorphous elastin deposits in fibrotic lung. Analysis of primary lung fibroblast isolates in vitro confirmed the down-regulation of clusterin expression in fibrotic compared with control lung fibroblasts and further demonstrated that TGF-β1 is capable of down-regulating fibroblast clusterin expression. shRNA-mediated down-regulation of clusterin did not affect TGF-β1-induced fibroblast-myofibroblast differentiation but inhibited fibroblast proliferative responses and sensitized to apoptosis. Down-regulation of clusterin in fibrotic lung fibroblasts at least partly due to increased TGF-β1 may therefore represent an appropriate but insufficient response to limit fibroproliferation. Reduced expression of clusterin in the lung may also limit its extracellular chaperoning activity contributing to dysregulated deposition of extracellular matrix proteins.

Pilot evaluation of histotripsy treatment for Peyronie’s disease

Peyronie’s disease (PD) is a debilitating scarring disorder of the penis which can cause significant curvature, pain, and psychological distress. Intra-lesional injection of specialized drugs to break down the fibrous matrix demonstrates modest results and is extremely expensive; surgery remains the gold standard for PD despite possible complications. We evaluated the feasibility of using histotripsy to disrupt the fibrous plaque and alter the mechanical properties as a novel non-invasive treatment. Freshly excised Peyronie’s plaques (n = 5) were separated into individual samples for histotripsy treatment or control tissue. Treatments were conducted using a 1.0 MHz custom-built therapy transducer delivering pulses with repetition frequency of 1000 Hz, duty cycle 0.5%, and peak focal pressures of (98/-17 MPa) under ultrasound guidance. Tissue was either formalin fixed for histological evaluation or frozen for mechanical testing. Histotripsy induced disruption of collagen and elastin fibrils was evident in all fibrous portions of plaques. Histotripsy treatment produced decreased mean modulus, ultimate tensile strength, maximum load, and toughness vs. untreated control samples on mechanical testing. Additionally, the displacement to maximum load ratio was greater in treated vs. untreated control samples. [Work supported by NIH grants K01 DK104854, DK043881, EB007643, NSBRI through NASA NCC 9-58, and VA RR&amp;D grant A9243C.]

Targeted Inhibition of PAI-1 Activity Impairs Epithelial Migration and Wound Closure Following Cutaneous Injury.

Objective: Aberrant plasminogen activator inhibitor-1 (PAI-1) expression and activity have been implicated in bleeding disorders, multiorgan fibrosis, and wound healing anomalies. This study details the physiological consequences of targeted PAI-1 functional inhibition on cutaneous injury repair. Approach: Dorsal skin wounds from FVB/NJ mice, created with a 4 mm biopsy punch, were treated topically with the small-molecule PAI-1 antagonist tiplaxtinin (or vehicle control) for 5 days and then analyzed for markers of wound repair. Results: Compared to controls, tiplaxtinin-treated wounds displayed dramatic decreases in wound closure and re-epithelialization. PAI-1 immunoreactivity was evident at the migratory front in all injury sites indicating these effects were due to PAI-1 functional blockade and not PAI-1 expression changes. Stimulated HaCaT keratinocyte migration in response to recombinant PAI-1 in vitro was similarly attenuated by tiplaxtinin. While tiplaxtinin had no effect on keratinocyte proliferation, cell cycle progression, or apoptosis, it effectively reduced collagen deposition, the number of Ki-67+ fibroblasts, and incidence of differentiated myofibroblasts (i.e., smooth muscle α-actin immunoreactive cells), but not fibroblast apoptosis. Innovation: The role for PAI-1 in hemostasis and fibrinolysis is established; involvement of PAI-1 in cutaneous wound healing, however, remains unclear. This study tests the effect of a small-molecule PAI-1 inhibitor in a murine model of skin wound repair. Conclusion: Loss of PAI-1 activity significantly impaired wound closure. Re-epithelialization and fibroblast recruitment/differentiation were both reduced in tiplaxtinin-treated mice. Therapies directed at manipulation of PAI-1 expression and/or activity may have applicability as a treatment option for chronic wounds and scarring disorders.

Piercings in medical students and their effects on the skin.

BACKGROUNDPiercings are body embellishments commonly seen in young people, however their inherent risk of infection and scarring disorders are less divulged.OBJECTIVETo evaluate the prevalence of body piercings among medical students and their possible dermatologic consequences.METHODSCross-sectional study with 58 medical students, by means of a structured questionnaire covering socio-demographic characteristics, technical issues related to the piercing and characteristics of the dermatologic complications.RESULTSThe sample was predominantly female (86.2%), with mean age 24 ± 3 years. The placement of the first piercing occurred during adolescence (median age 15), without medical supervision (91.4%) or knowledge of parents/guardians (74%). Most piercings were made of metal alloy/stainless steel, in a dumbbell model (51.7%), inserted in the umbilical area (53.5%) or ear (41.4%), with frequent cutaneous reactions in the first six months post-piercing. Hypertrophic scarring, pain, swelling and infection (p<0.05) had significantly higher frequencies among those with navel piercings.CONCLUSIONPiercing insertion occurred during adolescence. Local inflammatory and infectious reactions were common. Scarring disorders and dermatitis appeared in the long term. There is need for preventive and educational activities, starting with those in the academic environment.

Chitosan aerosol inhalation alleviates lipopolysaccharide- induced pulmonary fibrosis in rats

ABSTRACTPurpose: Pulmonary fibrosis (PF) is an insidiously progressive scarring disorder of the alveoli and is associated with high mortality. Currently, therapies available are associated with restricted efficacy and side effects. This study aimed to investigate the effect of chitosan aerosol inhalation on lipopolysaccharide (LPS)-induced pulmonary remodeling and fibrosis in rats. Methods: A rat model of PF was established by intratracheal injection of LPS (5 mg/kg). Chitosan was nebulized to rats from day 4 to 28 after LPS injection. We analyzed the effect of chitosan on LPS-induced pulmonary remodeling and fibrosis by hematoxylin-eosin staining (HE), Masson staining, and the determination of the hydroxyproline content. The expression intensities of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed by western blots. Results: Histological assessments showed that chitosan aerosol inhalation attenuated the fibrotic changes in LPS-induced PF in rats. Compared with the LPS group, the fibrosis parameters were significantly improved in the LPS + chitosan group (LCh group), although not as good as those of the control group. The expressions of MMP-3 and TIMP-1 in the LCh group were markedly less than that of the LPS group on the 28th day. Conclusions: Our findings show that chitosan aerosol inhalation inhibits the expression of MMP-3 and TIMP-1, and ameliorates LPS-induced pulmonary remodeling and fibrosis in rats.

Follicular and scarring disorders in skin of color: presentation and management.

Skin of color, also known as ethnic skin, is described as skin of individuals of African, Asian, Hispanic, Native-American, Middle Eastern, and Pacific Island backgrounds. Differences in hair morphology, hair grooming, cultural practices, and susceptibility to keloid scarring exist within these populations and have been implicated in hair, scalp, and skin disorders. Acne keloidalis (AK), central centrifugal cicatricial alopecia (CCCA), dissecting cellulitis of the scalp (DCS), pseudofolliculitis barbae (PFB), traction alopecia (TA), and keloids are the most prevalent follicular and scarring disorders in skin of color. They have been associated with disfigurement, permanent hair loss, emotional distress, and decreased quality of life. Hair grooming practices, such as the use of chemical relaxers, heat straightening, and tight braiding and weaving can cause scalp irritation and follicular damage and are linked to the pathogenesis of some of these conditions. Consequently, patient education and behavior modifications are integral to the prevention and management of these disorders. Scarring disorders are also of concern in ethnic populations. Keloid scarring is more prevalent in individuals of African, Asian, and Hispanic descent. The scarring alopecia CCCA is almost exclusively seen in patients of African descent. Therapeutic regimens such as intralesional corticosteroids, surgical excision, and laser therapy can be effective for these follicular and scarring disorders, but carry a risk of dyspigmentation and keloid scarring. Ethnic skin and hair may present unique challenges to the clinician, and knowledge of these differences is essential to providing quality care.

Defining the Limits of Normal Conjunctival Fornix Anatomy in a Healthy South Asian Population

PurposeQuantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population.DesignEpidemiologic, cross-sectional study.ParticipantsA total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years.MethodsAn FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs).Main Outcome MeasuresMean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex.ResultsFor this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9–15.6) and 10.9 mm (95% CI, 10.7–11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5–33.4) (upper) and 31.7 mm (95% CI, 31.3–32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015).ConclusionsThis is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups.

Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts

There is no effective drug therapy for scarring and fibrotic disease. The cytokine transforming growth factor beta (TGF-β) promotes tissue repair, but its excessive action can lead to over exuberant scarring and fibrotic disease. However, owing to the multifunctional nature of TGF-β, broad targeting of the canonical Smad-TGF-β signaling pathway in vivo is likely to have unintended, deleterious consequences. (1) The myofibroblast is the essential cell type that mediates tissue repair and fibrosis. (2) TGF-β is an essential contributor to myofibroblast differentiation and activity. (3) TGF-β selectively promotes tissue repair and fibrosis via the noncanonical focal adhesion kinase (FAK) pathway; FAK mediates myofibroblast differentiation, and hence may represent a novel intervention point for drugs treating fibrotic disease. Excessive scarring (e.g., in hypertrophic scars, keloids, and scleroderma) is characterized by enhanced TGF-β signaling and is a major clinical problem. Drugs that selectively and effectively control the profibrotic action of TGF-β is therefore of clinical relevance. FAK inhibition may represent a novel therapy for scarring disorders.

Comparative wound healing—Are the small animal veterinarian's clinical patients an improved translational model for human wound healing research?

Despite intensive research efforts into understanding the pathophysiology of both chronic wounds and scar formation, and the development of wound care strategies to target both healing extremes, problematic wounds in human health care remain a formidable challenge. Although valuable fundamental information regarding the pathophysiology of problematic wounds can be gained from in vitro investigations and in vivo studies performed in laboratory animal models, the lack of concordance with human pathophysiology has been cited as a major impediment to translational research in human wound care. Therefore, the identification of superior clinical models for both chronic wounds and scarring disorders should be a high priority for scientists who work in the field of human wound healing research. To be successful, translational wound healing research should function as an intellectual ecosystem in which information flows from basic science researchers using in vitro and in vivo models to clinicians and back again from the clinical investigators to the basic scientists. Integral to the efficiency of this process is the incorporation of models which can accurately predict clinical success. The aim of this review is to describe the potential advantages and limitations of using clinical companion animals (primarily dogs and cats) as translational models for cutaneous wound healing research by describing comparative aspects of wound healing in these species, common acute and chronic cutaneous wounds in clinical canine and feline patients, and the infrastructure that currently exists in veterinary medicine which may facilitate translational studies and simultaneously benefit both veterinary and human wound care patients.