Carfilzomib, thalidomide, and dexamethasone are safe and effective in relapsed and/or refractory multiple myeloma: final report of the single-arm, multicenter, phase II ALLG MM018/AMN002 study.

This multicenter, phase II study of the Australasian Lymphoma and Leukemia Group and the Asian Myeloma Network investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d) (KTd) in patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. Patients received induction with up to 12 28-day cycles of carfilzomib (20 mg/m2 intravenously in cycle 1 on days 1 and 2, then 56 mg/m2 [36 mg/m2 for patients ≥75 years] from day 8 onwards), thalidomide 100 mg orally in the evening and weekly dexamethasone 40 mg (20 mg for patients ≥75 years). During maintenance, thalidomide was omitted, while carfilzomib was continued on days 1, 2, 15, and 16 with fortnightly dexamethasone. The primary endpoint was progression-free survival. Secondary endpoints were overall response rate, overall survival, duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years [range, 41.9-84.5]) were enrolled and followed up for a median of 26.4 months (range, 1.6-54.6). The median progression-free survival was 22.3 months (95% confidence interval: 15.7-25.6) and the 2-year progression-free survival was 46.3% (95% confidence interval: 35.1-52.8). The median overall survival was not reached and the 2-year overall survival was 73.8% (95% confidence interval: 62.9-81.9). The overall response rate was 88% (73% had a very good partial response or better). There was no difference in the depth of response, progression-free survival or overall survival comparing Asian and non-Asian cohorts (P=0.61). The safety profile of KTd was consistent with that of each individual drug. KTd is well tolerated and effective in patients with relapsed and/or refractory multiple myeloma irrespective of Asian or non-Asian ethnicity and provides an alternative treatment option, particularly in circumstances in which the use of carfilzomib, lenalidomide, and dexamethasone (KRd) is limited by access, cost, or renal impairment.

Coma Blister After Trazodone Misuse: A Case Report.

ABSTRACT: Coma blisters are epidermal and subepidermal bullous lesions that can arise throughout the body after a prolonged impairment of consciousness. Coma blister-like lesions have been well-documented in adults after barbiturate-induced intoxication. More recently, other drugs and substances have been associated with the development of these bullae, which has broadened the scope of medications that put patients at risk of developing coma blister-like lesions. We present a unique case of a noncomatose patient who developed coma blister-like lesions after trazodone misuse. This case illustrates the need to further investigate the mechanism behind drug-induced coma bullae-like lesions so that clinicians can better identify and discontinue drugs that precipitate such lesions.

Mechanisms of Thrombosis in Heparin-Induced Thrombocytopenia and Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are rare, iatrogenic immune-mediated conditions with high rates of thrombosis-related morbidity and mortality. HIT is a long-recognized reaction to the administration of the common parenterally administered anticoagulant heparin (or its derivatives), while VITT is a new, distinct syndrome occurring in response to adenovirus-based vaccines against coronavirus disease 2019 and potentially other types of vaccines. A feature of both HIT and VITT is paradoxical thrombosis despite a characteristic low platelet count, mediated by the presence of platelet-activating antibodies to platelet factor 4. Several additional factors have also been suggested to contribute to clot formation in HIT and/or VITT, including monocytes, tissue factor, microparticles, endothelium, the formation of neutrophil extracellular traps, complement, procoagulant platelets, and vaccine components. In this review, we discuss the literature to date regarding mechanisms contributing to thrombosis in both HIT and VITT and explore the pathophysiological similarities and differences between the two conditions.

Cutaneous changes in diabetic patients: Primed for aberrant healing?

Cutaneous manifestations affect most patients with diabetes mellitus, clinically presenting with numerous dermatologic diseases from xerosis to diabetic foot ulcers (DFUs). Skin conditions not only impose a significantly impaired quality of life on individuals with diabetes but also predispose patients to further complications. Knowledge of cutaneous biology and the wound healing process under diabetic conditions is largely limited to animal models, and studies focusing on biology of the human condition of DFUs remain limited. In this review, we discuss the critical molecular, cellular, and structural changes to the skin in the hyperglycaemic and insulin-resistant environment of diabetes with a focus specifically on human-derived data. Elucidating the breadth of the cutaneous manifestations coupled with effective diabetes management is important for improving patient quality of life and averting future complications including wound healing disorders.

Identification of a Distinct Platelet Phenotype in the Elderly: ADP Hypersensitivity Coexists With Platelet PAR (Protease-Activated Receptor)-1 and PAR-4-Mediated Thrombin Resistance.

BACKGROUND: Thrombin (via PAR [protease-activated receptor]-1 and PAR-4) and ADP (via P2Y12 receptors) are potent endogenous platelet activators implicated in the development of cardiovascular disease. We aimed to assess whether platelet pathways alter with aging. METHODS: We characterized platelet activity in community-dwelling volunteers (n=174) in the following age groups: (1) 20 to 30 (young); (2) 40 to 55 (middle-aged); (3) ≥70 years (elderly). Platelet activity was assessed by aggregometry; flow cytometry (surface markers [P-selectin: alpha granule release, CD63: dense granule release, PAC-1: measure of conformationally active GPIIb/IIIa at the fibrinogen binding site]) measured under basal conditions and after agonist stimulation [ADP, thrombin, PAR-1 agonist or PAR-4 agonist]); receptor cleavage and quantification; fluorometry; calcium flux; ELISA. RESULTS: The elderly had higher basal platelet activation than the young, evidenced by increased expression of P-selectin, CD63, and PAC-1, which correlated with increasing inflammation (IL [interleukin]-1ß/IL-6). The elderly demonstrated higher P2Y12 receptor density, with greater ADP-induced platelet aggregation (P<0.05). However, elderly subjects were resistant to thrombin, achieving less activation in response to thrombin (higher EC50) and to selective stimulation of both PAR-1 and PAR-4, with higher basal PAR-1/PAR-4 cleavage and less inducible PAR-1/PAR-4 cleavage (all P<0.05). Thrombin resistance was attributable to a combination of reduced thrombin orienting receptor GPIbα (glycoprotein Ibα), reduced secondary ADP contribution to thrombin-mediated activation, and blunted calcium flux. D-Dimer, a marker of in situ thrombin generation, correlated with platelet activation in the circulation, ex vivo thrombin resistance, and circulating inflammatory mediators (TNF [tumor necrosis factor]-α/IL-6). CONCLUSIONS: Aging is associated with a distinctive platelet phenotype of increased basal activation, ADP hyperreactivity, and thrombin resistance. In situ thrombin generation associated with systemic inflammation may be novel target to prevent cardiovascular disease in the elderly.

Preventability of venous thromboembolism in hospitalised patients.

BACKGROUND: Hospital-acquired venous thromboembolism (VTE) is a major cause of morbidity and mortality. AIMS: To determine the proportion of patients with hospital-acquired VTE that are preventable. METHODS: This was a retrospective study of patients in two tertiary care hospitals in Sydney, Australia. Data were collected for patients with hospital-acquired VTE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) coding from January 2018 to May 2020. Patients were classified as low, moderate or high risk of developing a VTE during hospitalisation based on demographic and clinical factors. A hospital-acquired VTE was considered to be potentially preventable if there was suboptimal prophylaxis in the absence of contraindications. Suboptimal therapy included at least one of the following related to VTE prophylaxis: low dose, missed dose (prior to developing a VTE), suboptimal drug and delayed start (>24 h from admission). RESULTS: There were 229 patients identified with VTE based on ICD-10-AM coding. A subset of 135 patients were determined to have actual hospital-acquired VTE. Of these, there were no patients at low risk, 64% (87/135) at moderate risk and 44% (48/135) at high risk of developing a VTE. Most (65%; n = 88/135) patients had one or more contraindications to receive recommended prophylaxis. Overall, the proportion of patients who received suboptimal prophylaxis was 11% (15/135). CONCLUSION: Approximately one out of 10 hospital-acquired VTE are preventable. Hospitals should focus on measuring and reporting VTE that are preventable to provide a more accurate measure of the burden of VTE that can be reduced by improving care.

Tinzaparin for venous thromboembolism in patients with renal impairment: a single-centre, prospective pilot study.

BACKGROUND: Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin and standard of care in cancer-associated VTE (CA-VTE). Tinzaparin has the highest molecular weight of all LMWH and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20 mL/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20 mL/min and in CA-VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. AIMS: We aim to confirm the deliverability of tinzaparin in patients with renal insufficiency. METHODS: Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50 mL/min with an indication for anticoagulation. Tinzaparin was given as a subcutaneous injection at 175 units/kg as a single daily dose, rounded to the nearest vial size. Tinzaparin anti-Xa levels were tested at Days 2, 7 and 14 (±1 day) and transition to oral anticoagulants were allowed at clinician discretion. RESULTS: No accumulation of tinzaparin was seen into Day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor) and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and body surface area-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on Day 2, and this effect was lost when patients with CrCl >50 mL/min were excluded. Data from our cohort confirm the deliverability of therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50 mL/min. Bleeding and death outcomes were also comparable to other trials using tinzaparin in CA-VTE. CONCLUSION: For patients with renal insufficiency, tinzaparin represents an attractive alternative anticoagulant with once-daily administration in a range of potential indications.

Etiology, management, and outcomes of pediatric telogen effluvium: A single-center study in the United States.

BACKGROUND/OBJECTIVES: Telogen effluvium (TE) is a diffuse, rapidly occurring non-scarring alopecia that can be a significant source of distress for patients and caregivers. To date, the disorder has not been extensively studied in a US pediatric patient population. This study aims to characterize the epidemiology, management, and disease course of pediatric TE. METHODS: A retrospective single-center analysis was conducted at the University of Miami including pediatric medical records from 2009 to 2021 with at least one clinic visit coded with the diagnosis of TE. RESULTS: 76 patients presented with a wide range of age at onset and hair loss duration. 67% of patients (n = 51) had an identified trigger, the most common being emotional stress and acute febrile illness, followed by nutritional deficiencies (specifically iron, ferritin, and vitamin D). Observation was the most common therapeutic approach. Of patients who had a follow-up evaluation (39%), different treatments resulted in similar rates of improvement. CONCLUSIONS: The results of this study demonstrate the variability in potential TE triggers, physical exam findings, and management in children, similar to what is currently observed and practiced in adult patients. Appropriate work-up for common triggers should be included during the initial visit. Greater evidence-based treatment approaches are needed for pediatric TE.

Impact of diabetes and modifiable risk factors on pancreatic cancer survival in a population-based study after adjusting for clinical factors.

PURPOSES: Our study aimed to examine the impact of diabetes, smoking and BMI on pancreatic cancer survival in a population-based setting by adjusting both sociodemographic and clinical factors and measuring their attributable risk. METHODS: Data on pancreatic adenocarcinoma patients diagnosed in 2011-2017 were acquired from the Louisiana Tumor Registry. Diabetes, smoking, height, and weight were abstracted from medical records and linked with Hospital Inpatient Discharge Data to enhance the completeness of the diabetes data. The Cox regression model was used to assess effect sizes of diabetes, smoking, and BMI on cancer-specific survival and survival rate. The partial population attributable risk was employed to measure the attributable risk of these risk factors. RESULTS: Of the 3,200 eligible patients, 34.6% were diabetics, 23.9% were current smokers, and 52.3% had BMI ≥ 25 kg/m2. After adjusting for sociodemographic and clinical factors, diabetic patients had an increased cancer-specific death risk of 15% (95% CI, 1.06-1.25), 36% (95% CI, 1.19-1.44) for current smokers, and 24% (95% CI, 1.00-1.54) for patients with a BMI ≥ 40 when compared to their counterparts. Diabetic current smokers had significantly lower 2- and 3-year adjusted cancer-specific survival rates, 13.1% and 10.5%, respectively. By eliminating diabetes and modifiable risk factors, an estimated 16.6% (95% CI, 6.9%-25.9%) of the cancer-specific deaths could be avoided during a nine-year observational period between 2011 and 2019. CONCLUSIONS: Diabetes and smoking contributed substantially to the reduction of pancreatic cancer survival even after controlling for sociodemographic and clinical factors; however, BMI ≥ 35 was observed to increase risk of mortality among stage III-IV patients only.

Colchicine as a Modulator of Platelet Function: A Systematic Review.

The microtubule inhibitor and anti-inflammatory agent colchicine is used to treat a range of conditions involving inflammasome activation in monocytes and neutrophils, and is now known to prevent coronary and cerebrovascular events. In vitro studies dating back more than 50 years showed a direct effect of colchicine on platelets, but as little contemporary attention has been paid to this area, we have critically reviewed the effects of colchicine on diverse aspects of platelet biology in vitro and in vivo. In this systematic review we searched Embase, Medline, and PubMed for articles testing platelets after incubation with colchicine and/or reporting a clinical effect of colchicine treatment on platelet function, including only papers available in English and excluding reviews and conference abstracts. We identified 98 relevant articles and grouped their findings based on the type of study and platelet function test. In vitro, colchicine inhibits traditional platelet functions, including aggregation, clotting, degranulation, and platelet-derived extracellular vesicle formation, although many of these effects were reported at apparently supraphysiological concentrations. Physiological concentrations of colchicine inhibit collagen- and calcium ionophore-induced platelet aggregation and internal signaling. There have been limited studies of in vivo effects on platelets. The colchicine-platelet interaction has the potential to contribute to colchicine-mediated reduction in cardiovascular events, but there is a pressing need for high quality clinical research in this area.

Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice.

Little is known about the physiological role of beta-2-glycoprotein I (ß2GPI) despite it being the major auto-antigen in the antiphospholipid syndrome. A systematic study of the role of ß2GPI in thrombus formation in vivo has not been performed to date. Herein, we report that ß2GPI deficient (-/-) mice have enhanced thrombus formation compared to wild type (WT) mice in a laser-induced arteriole and venule model of thrombosis. Furthermore, neutrophil accumulation and elastase activity was enhanced in thrombi of ß2GPI -/- compared with WT mice. The antithrombotic function of ß2GPI is dependent on its fifth domain (domain V); intravenous administration of the ß2GPI domain deletion mutant lacking domain V (human recombinant domain I-IV) had no effect on platelet and fibrin thrombus size in ß2GPI -/- or WT mice. On the contrary, intravenous administration of human recombinant domain V significantly inhibited platelet and fibrin thrombus size in both ß2GPI -/- mice and WT mice. These findings reveal a major role for ß2GPI as a natural anticoagulant and implicate domain V of ß2GPI as a potential antithrombotic therapy.

The utility of flow cytometric platelet forward scatter as an alternative to mean platelet volume.

The use of mean platelet diameter (MPD) to classify inherited thrombocytopenia (IT) has been demonstrated in several studies. Alternatively, the mean platelet volume (MPV) may be used, but in macrothrombocytopenia this may not be available. We hypothesized that platelet forward scatter (FSC) measurements using flow cytometry may be used for the size-based classification of IT. The study aimed to assess the ability of platelet FSC to measure platelet size and whether it could be used as an alternative to the MPD or MPV.Blood samples were obtained from individuals undergoing investigation for inherited platelet function disorders (IPFD, n = 40) or platelet number disorders (IPND, n = 46). A hematology analyzer was used to obtain MPV and platelet counts, flow cytometry to measure platelet FSC and ImageJ software to measure MPD from stained blood smears. The International Society of Thrombosis and Hemostasis (ISTH) Bleeding Assessment Tool (BAT) was used to calculate bleeding scores.Twenty-nine(63%) of IPND patients had an MPV that could not be reported. A significant correlation to platelet FSC was found to the MPD (p < .0001) and MPV (p < .0001) and an inverse correlation with platelet count (p < .0001). No significant correlation was found between FSC and bleeding history. In conclusion, platelet FSC is an alternative to MPV and may be used in macrothrombocytopenia where the MPV is not recorded.

Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder.

Variants of the Diaphanous-Related Formin 1 (DIAPH-1) gene have recently been reported causing inherited macrothrombocytopenia. The essential/"diagnostic" characteristics associated with the disorder are emerging; however, robust and complete criteria are not established. Here, we report the first cases of DIAPH1-related disorder in Australia caused by the autosomal dominant gain-of-function DIAPH1 R1213X variant formed by truncation of the protein within the diaphanous auto-regulatory domain (DAD) with loss of regulatory motifs responsible for autoinhibitory interactions within the DIAPH1 protein. We affirm phenotypic changes induced by the DIAPH1 R1213X variant to include macrothrombocytopenia, early-onset progressive sensorineural hearing loss, and mild asymptomatic neutropenia. High-resolution microscopy confirms perturbations of cytoskeletal dynamics caused by the DIAPH1 variant and we extend the repertoire of changes generated by this variant to include alteration of procoagulant platelet formation and possible dental anomalies.

Understanding vaccine-induced thrombotic thrombocytopenia (VITT).

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare, but serious, syndrome characterised by thrombocytopenia, thrombosis, a markedly raised D-dimer and the presence of anti-platelet factor-4 (PF4) antibodies following COVID-19 adenovirus vector vaccination. VITT occurs at a rate of approximately 2 per 100 000 first-dose vaccinations and appears exceedingly rare following second doses. Our current understanding of VITT pathogenesis is based on the observations that patients with VITT have antibodies that bind to PF4 and have the ability to form immune complexes that induce potent platelet activation. However, the precise mechanisms that lead to pathogenic VITT antibody development remain a source of active investigation. Thrombosis in VITT can manifest in any vascular bed and affect multiple sites simultaneously. While there is a predilection for splanchnic and cerebral venous sinus thrombosis, VITT also commonly presents with deep vein thrombosis and pulmonary embolism. Pillars of management include anticoagulation with a non-heparin anticoagulant, intravenous immunoglobulin and 'rescue' therapies, such as plasma exchange for severe cases. VITT can be associated with a high mortality rate and significant morbidity, but awareness and optimal therapy have significantly improved outcomes in Australia. A number of questions remain unanswered, including why VITT is so rare, reasons for the predilection for thrombosis in unusual sites, how long pathological antibodies persist, and the optimal duration of anticoagulation. This review will provide an overview of the presentation, diagnostic workup and management strategies for patients with VITT.

Epigenetic regulation of cellular functions in wound healing.

Stringent spatiotemporal regulation of the wound healing process involving multiple cell types is associated with epigenetic mechanisms of gene regulation, such as DNA methylation, histone modification and chromatin remodelling, as well as non-coding RNAs. Here, we discuss the epigenetic changes that occur during wound healing and the rapidly expanding understanding of how these mechanisms affect healing resolution in both acute and chronic wound milieu. We provide a focussed overview of current research into epigenetic regulators that contribute to wound healing by specific cell type. We highlight the role of epigenetic regulators in the molecular pathophysiology of chronic wound conditions. The understanding of how epigenetic regulators can affect cellular functions during normal and impaired wound healing could lead to novel therapeutic approaches, and we outline questions that can provide guidance for future research on epigenetic-based interventions to promote healing. Dissecting the dynamic interplay between cellular subtypes involved in wound healing and epigenetic parameters during barrier repair will deepen our understanding of how to improve healing outcomes in patients affected by chronic non-healing wounds.

Platelet procoagulant potential is reduced in platelet concentrates ex vivo but appears restored following transfusion.

BACKGROUND: The procoagulant profile of platelet concentrates (PCs) following transfusion has been difficult to evaluate due to lack of specific markers. This study aimed to characterize procoagulant platelets in PCs and the effect of transfusion. STUDY DESIGN AND METHODS: Buffy coat-derived PCs from 12 donors were pooled, split, then stored conventionally, cold (2-6°C) or cryopreserved (-80°C). Procoagulant platelet profiles were assessed by flow cytometry (GSAO+ /P-selectin+ ), lactadherin-binding, and calibrated automated thrombogram, during storage, unstimulated, or after thrombin and collagen stimulation and compared with blood from healthy volunteers. Platelet activation (P-selectin) and procoagulant platelet formation potential were measured (flow cytometry) in patients receiving clinically indicated conventional PC transfusion. RESULTS: Independent of significant increases with storage, procoagulant platelet proportions with and without agonist stimulation were significantly blunted in conventionally stored PCs (stimulated day 5 conventional PC 4.2 ± 1.3%, healthy volunteer blood 11.1 ± 2.9%; p < .0001). Cryopreserved PCs contained the highest proportion of procoagulant platelets (unstimulated: cryopreserved 25.6 ± 1.8% vs. day 5 conventional 0.5 ± 0.1% vs. day 14 cold-stored 5.8 ± 1.0%, p < .0001), but demonstrated minimal increase with agonist. Transfusion of PCs was associated with an increase in procoagulant platelets (2.2 ± 1.4% vs. 0.6 ± 0.2%; p = .004) and reversal of the blunted agonist response (15.8 ± 5.9% vs. 4.0 ± 1.6%; p < .0001). Procoagulant responses post-transfusion were significantly higher than healthy controls, suggesting a priming effect. The P-selectin agonist response was not restored upon transfusion (79.4 ± 13.9% vs. 82.0 ± 2.5%). CONCLUSION: Storage blunts the procoagulant platelet response to agonist stimulation in PCs. Despite this, conventionally stored PCs have high procoagulant potential following transfusion, with a discordant, persistent reduction in P-selectin response.

Provider perceptions and practices for appearance-related psychosocial distress caused by dermatologic disease in children.

BACKGROUND/OBJECTIVES: Differences in appearance are often stigmatized in society, and dermatologic disease can lead to psychological and social sequelae that significantly impact patient quality of life. However, discrepancy between patient-reported and physician-assessed psychological distress raises a question of how clinicians are prepared in recognizing and managing the psychosocial impact of a child's skin condition. We aim to identify current practices among healthcare providers toward properly addressing appearance-related psychosocial distress in pediatric dermatology patients. METHODS: Surveys assessing provider attitude and practices to appearance-related distress were distributed to members of the Society of Pediatric Dermatology via the Pediatric Dermatology Research Alliance, and Florida Chapter of American Academy of Pediatrics. RESULTS: Over half of respondents report encountering appearance-related psychosocial distress on a daily basis and believe screening to be important. However, only 14% use a validated screening tool and 18% screen all patients. Major obstacles to generalized screening were limited time and staffing. Self-reported knowledge and management of appearance-related psychosocial distress includes direct counseling and referrals to local support groups, mental health providers, specialized summer camps, and school-affiliated resources. Nevertheless, 86% expressed interest in learning more about appearance-related psychosocial distress, particularly about patient education and resources. CONCLUSIONS: Although clinicians frequently encounter appearance-related distress with pediatric dermatology patients, screening is selective and lacks standardization. Self-reported knowledge and management is comprehensive, but there is a need for increased training in patient education and resources.

Acute urticaria preceding other COVID-19-associated manifestations-A case report.

The novel coronavirus SARS-CoV-2 has been associated with a variety of dermatologic manifestations, often the predominant finding in otherwise asymptomatic or oligosymptomatic patients. Urticarial eruption is one example, but few cases have been reported among pediatric patients. We present a case of acute urticaria in a 6-month-old boy preceding other COVID-19 symptoms. The suspicion of a possible COVID-19-associated cutaneous manifestation prompted timely testing and diagnosis of SARS-CoV-2 infection.

Photodocumentation in skin of color.

Photodocumentation is an important tool utilized across medical specialties and plays an especially pivotal role in dermatology given the visual nature of the field. Although it has been well-established that dermatologic diseases manifest differently in dark skin compared to light skin, there is under-representation of images of dark skin in dermatology textbooks and other educational resources. It is essential for dermatologists to work toward increasing the availability of images of dermatologic disease in dark skin by improving their own ability to successfully photograph dark-skinned patients. In this article, we describe our nuanced approach to photographing skin of color in regards to the ideal background type, lighting, and camera settings.

Genomics of Human Fibrotic Diseases: Disordered Wound Healing Response.

Fibrotic disease, which is implicated in almost half of all deaths worldwide, is the result of an uncontrolled wound healing response to injury in which tissue is replaced by deposition of excess extracellular matrix, leading to fibrosis and loss of organ function. A plethora of genome-wide association studies, microarrays, exome sequencing studies, DNA methylation arrays, next-generation sequencing, and profiling of noncoding RNAs have been performed in patient-derived fibrotic tissue, with the shared goal of utilizing genomics to identify the transcriptional networks and biological pathways underlying the development of fibrotic diseases. In this review, we discuss fibrosing disorders of the skin, liver, kidney, lung, and heart, systematically (1) characterizing the initial acute injury that drives unresolved inflammation, (2) identifying genomic studies that have defined the pathologic gene changes leading to excess matrix deposition and fibrogenesis, and (3) summarizing therapies targeting pro-fibrotic genes and networks identified in the genomic studies. Ultimately, successful bench-to-bedside translation of observations from genomic studies will result in the development of novel anti-fibrotic therapeutics that improve functional quality of life for patients and decrease mortality from fibrotic diseases.