Diagnostic reliability in teledermatology: a systematic review and a meta-analysis.

OBJECTIVES: To compare teledermatology and face-to-face (F2F) agreement in primary diagnoses of dermatological conditions. DESIGN: Systematic review and meta-analysis METHODS: MEDLINE, Embase, Cochrane Library (Wiley), CINAHL and medRxiv were searched between January 2010 and May 2022. Observational studies and randomised clinical trials that reported percentage agreement or kappa concordance for primary diagnoses between teledermatology and F2F physicians were included. Titles, abstracts and full-text articles were screened in duplicate. From 7173 citations, 44 articles were included. A random-effects meta-analysis was conducted to estimate pooled estimates. Primary outcome measures were mean percentage and kappa concordance for assessing diagnostic matches between teledermatology and F2F physicians. Secondary outcome measures included the agreement between teledermatologists, F2F dermatologists, and teledermatology and histopathology results. RESULTS: 44 studies were extracted and reviewed. The pooled agreement rate was 68.9%, and kappa concordance was 0.67. When dermatologists conducted F2F and teledermatology consults, the overall diagnostic agreement was significantly higher at 71% compared with 44% for non-specialists. Kappa concordance was 0.69 for teledermatologist versus specialist and 0.52 for non-specialists. Higher diagnostic agreements were also noted with image acquisition training and digital photography. The agreement rate was 76.4% between teledermatologists, 82.4% between F2F physicians and 55.7% between teledermatology and histopathology. CONCLUSIONS AND RELEVANCE: Teledermatology can be an attractive option particularly in resource-poor settings. Future efforts should be placed on incorporating image acquisition training and access to high-quality imaging technologies. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/FJDVG.

Local Insulin Improves Wound Healing: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Wounds are a significant health issue, and reliable and safe strategies to promote repair are needed. Clinical trials have demonstrated that local insulin promotes healing in acute and chronic wounds (ie, reductions of 7% to 40% versus placebo). However, the trials' sample sizes have prevented drawing solid conclusions. Furthermore, no analysis has focused on safety concerns (ie, hypoglycemia). Under the hypothesis that local insulin promotes healing through proangiogenic effects and cellular recruitment, the aim of this systematic review and network meta-analysis (NMA) was to assess its safety and relative effectiveness using a Bayesian approach. METHODS: Medline, CENTRAL, Embase, Scopus, LILACS, and gray literature sources were searched for human studies assessing the local use of insulin versus any comparator since inception to October of 2020. Data on glucose changes and adverse events, wound and treatment characteristics, and healing outcomes were extracted, and an NMA was conducted. RESULTS: A total of 949 reports were found, of which 23 ( n = 1240 patients) were included in the NMA. The studies evaluated six different therapies, and most comparisons were against placebo. NMA showed -1.8 mg/dL blood glucose level change with insulin and a lack of reported adverse events. Statistically significant clinical outcomes identified include reduction in wound size (-27%), increased healing rate (23 mm/day), reduction in Pressure Ulcer Scale for Healing scores (-2.7), -10 days to attain complete closure, and an odds ratio of 20 for complete wound closure with insulin use. Likewise, significantly increased neoangiogenesis (+30 vessels/mm 2 ) and granulation tissue (+25%) were also found. CONCLUSION: Local insulin promotes wound healing without significant adverse events.

A 57-Year-Old Man with Type 1 Diabetes Mellitus and a Chronic Foot Ulcer Successfully Managed with a Remote Patient-Facing Wound Care Smartphone Application.

BACKGROUND Wounds affect millions of people world-wide, with care being costly and difficult to deliver remotely. The ongoing COVID-19 pandemic highlights the urgent need for telehealth solutions to play a larger role as part of remote care strategies for patient monitoring and care. We describe our findings on the use of a patient-facing wound care app (Swift Patient Connect App, Swift Medical, Canada) as an innovative solution in remote wound assessment and management of a diabetic patient's wound. CASE REPORT In February 2020, a 57-year-old man with type I diabetes and peripheral arterial disease presented with osteomyelitis in the left foot at the fifth metatarsal, arising from a chronic ulcer. The wound was deep, with purulent discharge and polymicrobial growth. A 6-week course of intravenous antibiotics was administered, with slow improvement of the wound. At a follow-up appointment in June 2020, The Patient Connect app was recommended to the patient to securely share calibrated images of his wound as well to communicate with his doctor. Between June 2020 and January 2021, wound closure was accurately monitored as part of the management of this diabetic foot infection. The app was also used in the management of 2 subsequent wounds and infection episodes. CONCLUSIONS Use of the Swift Patient Connect App designed to monitor and manage wounds by a patient with diabetes and foot ulcer as part of a remote care strategy resulted in numerous benefits expressed by the patient. After initial adoption, 3 successive wounds were managed with a combination of in-person and telehealth visits complemented by the app. Incorporation of this technology as part of a novel telemedicine strategy promises to have an extensive impact on remote care delivery during the current COVID-19 pandemic and beyond.

The Promise of Smartphone Applications in the Remote Monitoring of Postsurgical Wounds: A Literature Review.

OBJECTIVE: To review the clinical and scientific literature on remote monitoring and management of postsurgical wounds using smartphone applications (apps). DATA SOURCES: MEDLINE, PubMed, EMBASE, and Cochrane libraries were searched for relevant articles on patients who received surgery and were monitored postdischarge via an app. STUDY SELECTION: Articles were selected with the terms "mobile phones," "smartphones," "wounds," "monitor," and "patient preference." DATA EXTRACTION: The authors found 276 review articles related to telemedicine in wound care. Investigators reviewed the titles and abstracts of the search results and selected 83 articles that were relevant to the remote monitoring of wounds using smartphone apps. DATA SYNTHESIS: The topics explored in selected literature included smartphone app importance to telemedicine, benefits (medical and financial), app examples, and challenges in the context of wound monitoring and management. The authors identified several challenges and limitations that future studies in the field need to address. CONCLUSIONS: Remote monitoring and management of wounds using smartphone apps is a valuable technique to enhance the quality of and access to healthcare. However, although some patients may prefer this technology, some lack technological competence, limiting telemedicine's applicability. In addition, issues remain with the reliable interpretation of data collected through apps.

Financial and Clinical Risk Evaluation of Pressure Injuries in US Hospitals: A Business Case for Initiating Quality Improvement.

INTRODUCTION: Pressure injuries (PIs) are a serious, avoidable condition that affect many patients during hospital stays. Yet, to date, there is no comprehensive assessment of the financial and clinical risks of PIs. OBJECTIVE: This study evaluates the cost of treatment, impact of reimbursement policies, and clinical consequences of PIs for US hospitals. METHODS: A financial and clinical calculator was created to estimate the impact of PI prevention using a traditional literature review to drive assumptions. RESULTS: Two drivers of hospital revenue loss resulting from PIs were identified: nonpayment for PI treatment by health insurance providers and personal injury litigation. Increased hospital length of stay (LOS) and patient mortality associated with PIs further contributed to negative consequences. For an average 160-bed hospital, the authors estimated an annual total financial risk of $5.97 million, 911 days added to LOS, and 16.4 deaths related to avoidable PIs. CONCLUSIONS: Results of this analysis will be useful for health care organizations implementing quality improvement initiatives and new technologies, such as digital wound care management systems, to reduce the prevalence of PIs, thereby protecting patients and mitigating financial and clinical risks.

Improving the quality of pressure ulcer management in a skilled nursing facility.

Pressure ulcers (PUs) are a serious health care problem for nursing home residents and a key quality metric for regulators. Three initiatives were introduced at a 128-bed facility to improve PU prevention. First, a Quality Assurance and Performance Improvement project and a Root Cause Analysis were conducted to improve the facility's wound care programme. Second, a digital wound care management solution was adopted to track wound management. Third, the role of skin integrity coordinator was created as a central point of accountability for wound care-related activities and related performance metrics. Improvements in PU prevention were tracked using Centers of Medicare and Medicaid data, specifically (a) the percentage of long-stay high-risk residents with PUs and (b) the percentage of short-stay residents with PUs that are new or have worsened. PU prevalence for long-stay high-risk residents was 12.99% (Q4 2016), and upon implementation of these initiatives, the facility saw continued reductions in PU prevalence to 2.9% (Q4 2017), while PUs for short-stay residents were maintained at zero throughout this period. This study highlights the power of effective management combined with real-time data analytics, as enabled by digital wound care management, to make significant improvements in health care delivery.

Point-of-care wound visioning technology: Reproducibility and accuracy of a wound measurement app.

BACKGROUND: Current wound assessment practices are lacking on several measures. For example, the most common method for measuring wound size is using a ruler, which has been demonstrated to be crude and inaccurate. An increase in periwound temperature is a classic sign of infection but skin temperature is not always measured during wound assessments. To address this, we have developed a smartphone application that enables non-contact wound surface area and temperature measurements. Here we evaluate the inter-rater reliability and accuracy of this novel point-of-care wound assessment tool. METHODS AND FINDINGS: The wounds of 87 patients were measured using the Swift Wound app and a ruler. The skin surface temperature of 37 patients was also measured using an infrared FLIR™ camera integrated with the Swift Wound app and using the clinically accepted reference thermometer Exergen DermaTemp 1001. Accuracy measurements were determined by assessing differences in surface area measurements of 15 plastic wounds between a digital planimeter of known accuracy and the Swift Wound app. To evaluate the impact of training on the reproducibility of the Swift Wound app measurements, three novice raters with no wound care training, measured the length, width and area of 12 plastic model wounds using the app. High inter-rater reliabilities (ICC = 0.97-1.00) and high accuracies were obtained using the Swift Wound app across raters of different levels of training in wound care. The ruler method also yielded reliable wound measurements (ICC = 0.92-0.97), albeit lower than that of the Swift Wound app. Furthermore, there was no statistical difference between the temperature differences measured using the infrared camera and the clinically tested reference thermometer. CONCLUSIONS: The Swift Wound app provides highly reliable and accurate wound measurements. The FLIR™ infrared camera integrated into the Swift Wound app provides skin temperature readings equivalent to the clinically tested reference thermometer. Thus, the Swift Wound app has the advantage of being a non-contact, easy-to-use wound measurement tool that allows clinicians to image, measure, and track wound size and temperature from one visit to the next. In addition, this tool may also be used by patients and their caregivers for home monitoring.

Tumour endothelial marker-8 in wound healing and its impact on the proliferation and migration of keratinocytes.

Chronic wound management represents a significant burden on healthcare systems and negatively impacts on the quality of patient life. New strategies to understand and identify wounds that will not heal in a normal manner are required. Tumour endothelial marker­8 (TEM­8) has been implicated in the wound healing and angiogenesis processes. TEM­8 expression was examined at the transcript level in a cohort of acute (n=10) and chronic (n=14) wounds and in normal skin (n=10). Protein analysis of TEM­8 was also undertaken for this cohort using immunohistochemistry (IHC). TEM­8 impact on keratinocyte cell growth and migration was assessed following TEM­8 ribozyme transgene transfection of human HaCaT keratinocytes using cell growth and electric cell­substrate impedance sensing (ECIS)­based assays. Expression of TEM­8 was observed to be increased in acute wounds compared to chronic wounds and normal skin using quantitative polymerase chain reaction transcript analysis and IHC staining of wound tissues. Knockdown of TEM­8 in HaCaT cells, using two independent ribozyme transgenes, resulted in significant decreases in cell growth as well as reductions in the rate of migration assessed using an ECIS­based system. TEM­8 may be differentially expressed between wound types and loss of this molecule impacts HaCaT growth and migration, potentially implicating this molecule as a factor involved in successful progression of wound healing.

Patient perception of wound photography.

The objectives of this study were to provide an assessment of photographic documentation of the wound from the patients' perspective and to evaluate whether this could improve patients' understanding of and involvement in their wound care. Our results revealed that most patients visiting the wound care clinic have difficult-to-see wounds (86%). Only 20% of patients monitor their wounds and instead rely on clinic or nurse visits to track the healing progress. There was a significant association between patients' ability to see their wound and their subsequent memory of the wound's appearance. This was especially true for patients who had recently begun visiting the wound care clinic. This relationship was not present in patients who had visited the clinic for 3 or more years. Patients reported that the inability to see their wounds resulted in feeling a loss of autonomy. The majority of patients reported that photographing their wounds would help them to track the wound progress (81%) and would afford them more involvement in their own care (58%). This study provides a current representation of wound photography from the patients' perspective and reveals that it can motivate patients to become more involved in the management of their wounds - particularly for patients with difficult-to-see wounds.

Hidradenitis Suppurativa: A Frequently Missed Diagnosis, Part 2: Treatment Options.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the intertriginous area. Patients with HS have several challenges to their quality of life and activities of everyday living, including malodor, purulent discharge, and discomfort. There is often a delay in diagnosis and appropriate treatment. The need for cosmetically acceptable local treatments and dressing application makes this disease an important challenge for wound care specialists. The choice of optimal treatment varies depending on the disease severity, expert knowledge, the availability of an interprofessional team, and patient factors.

Hidradenitis Suppurativa: A Frequently Missed Diagnosis, Part 1: A Review of Pathogenesis, Associations, and Clinical Features.

PURPOSE: To provide information about the etiology, diagnostic evaluations, and clinical features of hidradenitis suppurativa (HS). TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Identify the prevalence, pathophysiology, and risk factors associated with HS.2. Describe diagnostic evaluations, staging, and comorbid disorders associated with HS. Hidradenitis Suppurativa (HS) is a recurrent inflammatory follicular disease that commonly affects the apocrine-bearing skin. The aim of this continuing education article is to review the pathogenesis and clinical presentations of HS. The spectrum of clinical presentations ranges from subcutaneous nodules to draining sinus and fistula. The pathogenesis of HS remains unknown.

Mass spectrometry reveals synergistic effects of nucleotides, lipids, and drugs binding to a multidrug resistance efflux pump.

Multidrug resistance is a serious barrier to successful treatment of many human diseases, including cancer, wherein chemotherapeutics are exported from target cells by membrane-embedded pumps. The most prevalent of these pumps, the ATP-Binding Cassette transporter P-glycoprotein (P-gp), consists of two homologous halves each comprising one nucleotide-binding domain and six transmembrane helices. The transmembrane region encapsulates a hydrophobic cavity, accessed by portals in the membrane, that binds cytotoxic compounds as well as lipids and peptides. Here we use mass spectrometry (MS) to probe the intact P-gp small molecule-bound complex in a detergent micelle. Activation in the gas phase leads to formation of ions, largely devoid of detergent, yet retaining drug molecules as well as charged or zwitterionic lipids. Measuring the rates of lipid binding and calculating apparent KD values shows that up to six negatively charged diacylglycerides bind more favorably than zwitterionic lipids. Similar experiments confirm binding of cardiolipins and show that prior binding of the immunosuppressant and antifungal antibiotic cyclosporin A enhances subsequent binding of cardiolipin. Ion mobility MS reveals that P-gp exists in an equilibrium between different states, readily interconverted by ligand binding. Overall these MS results show how concerted small molecule binding leads to synergistic effects on binding affinities and conformations of a multidrug efflux pump.

Ion mobility mass spectrometry of two tetrameric membrane protein complexes reveals compact structures and differences in stability and packing.

Here we examined the gas-phase structures of two tetrameric membrane protein complexes by ion mobility mass spectrometry. The collision cross sections measured for the ion channel are in accord with a compact configuration of subunits, suggesting that the native-like structure can be preserved under the harsh activation conditions required to release it from the detergent micelle into the gas phase. We also found that the quaternary structure of the transporter, which has fewer transmembrane subunits than the ion channel, is less stable once stripped of detergents and bulk water. These results highlight the potential of ion mobility mass spectrometry for characterizing the overall topologies of membrane protein complexes and the structural changes associated with nucleotide, lipid, and drug binding.

The response of Escherichia coli NikR to nickel: a second nickel-binding site.

The Escherichia coli transcription factor NikR mediates two levels of regulatory control of Ni(II) uptake in response to changes in the levels of available nickel. Despite the evidence that metal binding to two distinct sites on NikR, referred to as the high- and low-affinity Ni(II) sites, is required for Ni(II)-selective DNA binding by the protein, the role of the latter set of Ni(II) ions in the activation of NikR remains controversial, and the position of the putative low-affinity Ni(II)-binding site(s) on NikR has not been determined. In this study we confirm that NikR has a high-affinity Ni(II)-binding site that is maintained upon DNA binding. The ligands of the low-affinity Ni(II)-binding site were examined by using selective chemical modification and mass spectrometry performed in the presence of excess Ni(II) and DNA. We localized this Ni(II) site to a region at the interface between the metal- and DNA-binding domains and identified His48 and His110 as residues that participate in the low-affinity Ni(II)-binding response. Mutation of His48 and His110 to asparagines reduces significantly both NikR's tendency to precipitate in the presence of excess Ni(II) and the affinity of the DNA-bound complex in the presence of excess Ni(II). A complete scheme involving all of the metal-binding sites that contribute to the regulatory function of E. coli NikR in nickel homeostasis is described.

Potassium is critical for the Ni(II)-responsive DNA-binding activity of Escherichia coli NikR.

The Escherichia coli NikR transcription factor is a Ni(II)-dependent repressor that regulates the production of a nickel ion transporter. The X-ray crystal structure of the Ni(II)-NikR-DNA bound complex revealed a K(+)-binding site positioned at the interface of the metal- and DNA-binding domains, but the significance of the potassium was unclear. Mutation of one of the K(+) ligands impairs the affinity and specificity of DNA binding in the presence of either stoichiometric or excess Ni(II). Removal of K(+) abrogates Ni(II)-responsive DNA binding completely while the addition of K(+) restores this activity. Furthermore, the observed K(+) dependence can be relieved by replacing the K(+) ligand Asp34 with an arginine. These mutagenesis and cation exchange experiments reveal that K(+) is a critical structural component for the activation of Ni(II)-responsive DNA binding by NikR.

The "metallo-specific" response of proteins: a perspective based on the Escherichia coli transcriptional regulator NikR.

Transition metal ions are required by all cells but an excess of metal ions beyond physiological requirements has toxic consequences. Optimal cellular concentrations of transition metals are commonly maintained by metal-responsive transcription factors that regulate genes encoding the proteins responsible for transport, sequestration and/or use of the metals. These metalloregulators must discriminate between the bioavailable metals to properly effect metal homeostasis, but how this metal selectivity is achieved is poorly understood. This perspective examines the metal-selective response of the Escherichia coli Ni(II)-responsive metalloregulator NikR. Biochemical and structural studies of E. coli NikR reveal that the mechanism of metal-selective regulation is more complex than that defined by simple metal-binding thermodynamics. Here we examine the metal-dependent allosteric changes on NikR structure that affect DNA binding and discuss the correspondence with other metalloregulators. Given what we have learned of how metal selectivity is achieved by E. coli NikR, we propose a complete scheme for the regulatory function of NikR in E. coli nickel homeostasis.

Structural basis of the metal specificity for nickel regulatory protein NikR.

In the presence of excess nickel, Escherichia coli NikR regulates cellular nickel uptake by suppressing the transcription of the nik operon, which encodes the nickel uptake transporter, NikABCDE. Previously published in vitro studies have shown that NikR is capable of binding a range of divalent transition metal ions in addition to Ni2+, including Co2+, Cu2+, Zn2+, and Cd2+. To understand how the high-affinity nickel binding site of NikR is able to accommodate these other metal ions, and to improve our understanding of NikR's mechanism of binding to DNA, we have determined structures of the metal-binding domain (MBD) of NikR in the apo form and in complex with Cu2+ and Zn2+ ions and compared them with the previously published structures with Ni2+. We observe that Cu2+ ions bind in a manner very similar to that of Ni2+, with a square planar geometry but with longer bond lengths. Crystals grown in the presence of Zn2+ reveal a protein structure similar to that of apo MBD with a disordered alpha3 helix, but with two electron density peaks near the Ni2+ binding site corresponding to two Zn2+ ions. These structural findings along with biochemical data on NikR support a hypothesis that ordering of the alpha3 helix is important for repressor activation.

NikR-operator complex structure and the mechanism of repressor activation by metal ions.

Metal ion homeostasis is critical to the survival of all cells. Regulation of nickel concentrations in Escherichia coli is mediated by the NikR repressor via nickel-induced transcriptional repression of the nickel ABC-type transporter, NikABCDE. Here, we report two crystal structures of nickel-activated E. coli NikR, the isolated repressor at 2.1 A resolution and in a complex with its operator DNA sequence from the nik promoter at 3.1 A resolution. Along with the previously published structure of apo-NikR, these structures allow us to evaluate functional proposals for how metal ions activate NikR, delineate the drastic conformational changes required for operator recognition, and describe the formation of a second metal-binding site in the presence of DNA. They also provide a rare set of structural views of a ligand-responsive transcription factor in the unbound, ligand-induced, and DNA-bound states, establishing a model system for the study of ligand-mediated effects on transcription factor function.