Pressure injury pain over time among nursing home residents.

OBJECTIVE: Examine pressure injury (PrI) pain severity, stability, and current treatment of PrI pain among nursing home (NH) residents using two assessment tools and a descriptive cohort study design. BACKGROUND: PrI pain affects quality of life of NH residents yet, best assessment methods, stability of PrI pain, and how to take care of the pain are not well known. METHODS: Data collected from 33 residents with PrI (stages 1-4) from 4 NHs. All PrI were staged and assessed using the Bates-Jensen Wound Assessment Tool (BWAT) to determine severity. Verbal Response Scale (VRS) and Pain Assessment in Advanced Dementia (PAINAD) were used to assess general and PrI pain 3 times a day for two days within one week. Data classified as: no, mild, moderate, or severe pain. Proportions of participants with different levels of PrI pain were calculated. T tests were conducted to examine differences across time; VRS and PAINAD were examined for agreement. RESULTS: Participants were 74 % female, 49 % white, 58 % cognitively intact, 58 % functionally dependent, and had mean age of 82 years old. The majority (52 %; n = 17) were full thickness PrI, stage 3 (n = 5), stage 4 (n = 7), unstageable (n = 5). The majority of participants (82 %; n = 27) reported PrI pain on at least one of six assessments over the two days; with 57 % mild, 26 % moderate and 16 % severe pain. More severe pain occurred in afternoon. No differences existed across days. Although there was a positive relationship between VRS and PAINAD in pain assessments (r = 0.38, P<.05), the agreement between the two scales, as indicated by Cohen's kappa (K = 0.19, p=.28), was found to be poor. Of those with PrI pain, 22 % had pain documented in the Minimum Data Set (MDS). Only 42 % of participants who reported PrI pain received pain medication within 12 h of initial pain assessment. Out of 28 participants who received routine pain medication for general pain, 18 of them reported experiencing no pain. CONCLUSION: While VRS and PAINAD scores exhibited a relationship, their agreement was limited. Documentation of PrI pain on the Minimum Data Set (MDS) was found to be inadequate. Notably, 40 % of participants reported higher levels of PrI pain in the afternoon, suggesting this time may be opportune for PrI pain assessment and management. Interestingly, participants who received medication for general pain did not report PrI pain, suggesting that treatment of general pain may effectively alleviate PrI pain symptoms.

Decreasing Intraoperative Skin Damage in Prone-Position Surgeries.

OBJECTIVE: To determine if subepidermal moisture (SEM) measures help detect and prevent intraoperative acquired pressure injuries (IAPIs) for prone-position surgery. METHODS: In this clinical trial of patients (n = 39 preintervention, n = 48 intervention, 100 historical control) undergoing prone-position surgery, researchers examined the use of multidimensionally flexible silicone foam (MFSF) dressings applied preoperatively to patients' face, chest, and iliac crests. Visual skin assessments and SEM measures were obtained preoperatively, postoperatively, and daily for up to 5 days or until discharge. Electronic health record review included demographic, medical, and surgery data. RESULTS: Of the 187 total participants, 76 (41%) were women. Participants' mean age was 61.0 ± 15.0 years, and 9.6% were Hispanic (n = 18), 9.6% were Asian (n = 18), 6.9% were Black or African American (n = 13), and 73.8% were White (n = 138). Participants had a mean Scott-Triggers IAPI risk score of 1.5 ± 1.1. Among those with no erythema preoperatively, fewer intervention participants exhibited postoperative erythema on their face and chest than did preintervention participants. Further, fewer intervention participants had SEM-defined IAPIs at all locations in comparison with preintervention participants. The MFSF dressings overcame IAPI risk factors of surgery length, skin tone, and body mass index with fewer IAPIs in intervention participants. CONCLUSIONS: Patients undergoing prone-position surgeries developed fewer IAPIs, and SEM measures indicated no damage when MFSF dressings were applied to sites preoperatively. The SEM measures detected more damage than visual assessment.

Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the ISG15 gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/ß signalling. Due to this dual role, ISG15 deficiency can present with various clinical phenotypes, ranging from susceptibility to mycobacterial infection to autoinflammation characterised by necrotising skin lesions, intracerebral calcification, and pulmonary involvement. In this report, we describe novel variants found in two different families that result in complete ISG15 deficiency and severe skin ulceration. Whole exome sequencing identified a heterozygous missense p.Q16X ISG15 variant and a heterozygous multigene 1p36.33 deletion in the proband from the first family. In the second family, a homozygous total ISG15 gene deletion was detected in two siblings. We also conducted further analysis, including characterisation of cytokine dysregulation, interferon-stimulated gene expression, and p-STAT1 activation in lymphocytes and lesional tissue. Finally, we demonstrate the complete and rapid resolution of clinical symptoms associated with ISG15 deficiency in one sibling from the second family following treatment with the Janus kinase (JAK) inhibitor baricitinib.

Development of a decision support tool to prevent community acquired pressure injuries for use in the spinal cord injury clinic using the delphi technique.

STUDY DESIGN: Delphi Technique. OBJECTIVES: Describe the development of a decision support tool to prevent community-acquired pressure injuries (CAPrIs) in individuals with spinal cord injury (SCI) for use in SCI clinics, called the Community-Acquired Pressure Injury Prevention-Field Implementation Tool (CAPP-FIT). SETTING: Veteran Health Administration Hospital, Chicago, Illinois, USA. METHODS: Concept mapping of current pressure injury (PrI) guidelines and qualitative research describing risks, actions, and resources needed to prevent CAPrIs associated with SCI were used to develop 40 veteran checklist items (Items) along with 37 associated provider actions (Actions) for the tool. The Delphi technique was used to refine Items and Actions with a panel of interprofessional SCI providers (n = 15), veterans with SCI (n = 4), and caregivers (n = 3) to determine consensus on a 4-point Likert scale (strongly agree-strongly disagree) for each Item and Action. A 75% agreement was set for responses rated as strongly agree or agree. RESULTS: Panelists were 60% female, 62% White, 33% veterans with SCI or caregivers, 33% wound care certified with a mean age of 59 years. Two survey rounds were required for consensus for 41 Item and 38 Action CAPP-FIT. Response rate was 95% for both rounds. Delphi round 1 showed all but two Actions affirming agreement above 75%. Substantive comments from panelists required revision to 5 Items and 9 Actions and one additional Item/Actions related to coping, meeting threshold percent agreement in Round 2. CONCLUSIONS: The CAPP-FIT could become a useful tool for Veterans living with SCI, caregivers, and SCI providers.

Preventing Community-Acquired Pressure Injuries in Spinal Cord Injury: Online Healthcare Provider Curriculum.

PURPOSE: The aim of this study was to develop and pilot an educational curriculum for healthcare providers to better understand community-acquired pressure injury (CAPrI) prevention in veterans living with spinal cord injury (SCI). METHODS: The Thomas six-step process model guided curricular development and evaluation. Curriculum development followed six steps: (1) problem identification and general needs assessment from a literature review and qualitative research triangulating provider and veteran perspectives of CAPrI prevention in SCI, (2) target needs assessment using a focus group with 14 experienced practicing interprofessional SCI providers, (3) creation of module goals and objectives with content review from experts ( n = 8), (4) development of curriculum content and educational strategies, (5) implementation of a pilot ( n = 4), and (6) evaluation of satisfaction and curriculum content via survey and focus group. RESULTS: A five-module online curriculum was evaluated positively and is available publicly. Modules include (1) CAPrI Prevention Clinical Guidelines for the Provider, (2) CAPrI Prevention from the Veteran Perspective, (3) Building Collaborative Relationships, (4) Accessing Resources, and (5) Team Approach. Pilot participants stated objectives were met; they were satisfied with the module. The participants did recommend some changes. CLINICAL RELEVANCE: Understanding CAPrI prevention can inform rehabilitation nursing care. CONCLUSIONS: An asynchronous educational curriculum can support nurses in integrating preventive care in community-dwelling veterans living with SCI.

Using Technology to Detect Erythema Across Skin Tones.

OBJECTIVE: To examine the effectiveness of the ColorMeter DSM III (ColorMeter; Cortex Technology) at grouping individuals by skin tone and measuring erythema/skin discoloration after erythema induction across skin tones. METHODS: This pre/post experimental study induced erythema on a convenience sample of 61 healthy adults. Skin tone at baseline was measured using the ColorMeter, Munsell Soil Color Chart 5YR (Munsell), and Pantone SkinTone Guide (Pantone) and compared with the Eumelanin Human Skin Colour Scale (Eumelanin Scale) groupings. Erythema and melanin values on the arm immediately and after recovery time were compared with baseline values. Melanin was measured at five body regions on the face and arm. RESULTS: Participants were predominantly women (64% [n = 39] women, 36% [n = 22] men) and young (mean, 28.8 ± 14.3 years); 5% (n = 3) were Hispanic, 26% (n = 16) Asian, 29% (n = 18) Black, 38% (n = 23) White, and 7% (n = 4) identified with more than one race. ColorMeter lightness (L*) and melanin measures were strongly correlated with both Munsell and Pantone values. Munsell skin tone groups were not aligned with Eumelanin Scale groupings. Most participants were in the Eumelanin intermediate-low group, and this changed depending on which body location melanin value was used. The change in erythema from baseline did not differ significantly across skin tone groups at the ulnar head, but on the forearm at the delayed time point, significant differences existed between light and both medium and dark skin tone groups (P = .001; 95% CI, 0.04-0.37). CONCLUSIONS: The ColorMeter provides an effective objective measure of skin tone and erythema/discoloration across various skin tones and may improve on current standards for detection. The proposed Eumelanin Scale-Modified provides additional sensitivity for persons with medium skin tones.

Neuroinflammation, autoinflammation, splenomegaly and anemia caused by bi-allelic mutations in IRAK4.

We describe a novel, severe autoinflammatory syndrome characterized by neuroinflammation, systemic autoinflammation, splenomegaly, and anemia (NASA) caused by bi-allelic mutations in IRAK4. IRAK-4 is a serine/threonine kinase with a pivotal role in innate immune signaling from toll-like receptors and production of pro-inflammatory cytokines. In humans, bi-allelic mutations in IRAK4 result in IRAK-4 deficiency and increased susceptibility to pyogenic bacterial infections, but autoinflammation has never been described. We describe 5 affected patients from 2 unrelated families with compound heterozygous mutations in IRAK4 (c.C877T (p.Q293*)/c.G958T (p.D320Y); and c.A86C (p.Q29P)/c.161 + 1G>A) resulting in severe systemic autoinflammation, massive splenomegaly and severe transfusion dependent anemia and, in 3/5 cases, severe neuroinflammation and seizures. IRAK-4 protein expression was reduced in peripheral blood mononuclear cells (PBMC) in affected patients. Immunological analysis demonstrated elevated serum tumor necrosis factor (TNF), interleukin (IL) 1 beta (IL-1ß), IL-6, IL-8, interferon α2a (IFN-α2a), and interferon ß (IFN-ß); and elevated cerebrospinal fluid (CSF) IL-6 without elevation of CSF IFN-α despite perturbed interferon gene signature. Mutations were located within the death domain (DD; p.Q29P and splice site mutation c.161 + 1G>A) and kinase domain (p.Q293*/p.D320Y) of IRAK-4. Structure-based modeling of the DD mutation p.Q29P showed alteration in the alignment of a loop within the DD with loss of contact distance and hydrogen bond interactions with IRAK-1/2 within the myddosome complex. The kinase domain mutation p.D320Y was predicted to stabilize interactions within the kinase active site. While precise mechanisms of autoinflammation in NASA remain uncertain, we speculate that loss of negative regulation of IRAK-4 and IRAK-1; dysregulation of myddosome assembly and disassembly; or kinase active site instability may drive dysregulated IL-6 and TNF production. Blockade of IL-6 resulted in immediate and complete amelioration of systemic autoinflammation and anemia in all 5 patients treated; however, neuroinflammation has, so far proven recalcitrant to IL-6 blockade and the janus kinase (JAK) inhibitor baricitinib, likely due to lack of central nervous system penetration of both drugs. We therefore highlight that bi-allelic mutation in IRAK4 may be associated with a severe and complex autoinflammatory and neuroinflammatory phenotype that we have called NASA (neuroinflammation, autoinflammation, splenomegaly and anemia), in addition to immunodeficiency in humans.

Pressure Injury Data Reconciliation in a Randomized Controlled Trial.

OBJECTIVE: To advance pressure injury (PrI) research in individuals with spinal cord injury (SCI) by describing lessons learned and recommendations for future research, ultimately promoting PrI prevention and more effective wound care. This paper describes the detailed procedures undertaken to collect and reconcile PrI data and summarizes the types of discrepancies identified. DESIGN: Secondary analyses of PrI data collected between 2009 and 2014 in a randomized controlled trial (parent study). SETTING: Participants in the parent study were recruited from a large rehabilitation center in the Los Angeles area that serves primarily individuals with limited resources. PARTICIPANTS: 232 participants with SCI and a history of 1 or more medically serious PrI (MSPrI) in the previous 5 years. INTERVENTIONS: Participants in the parent study were randomized to a 12-month PrI prevention intervention led by an occupational therapist, or to usual care. MAIN OUTCOME MEASURES: Relations among PrI characteristics, data sources (phone interviews, skin checks, paper and electronic medical records [MRs]), and treatment condition, and sensitivity of 6 different data sources in detecting MSPrIs. RESULTS: The majority (62%) of MSPrIs were in the pelvic region. MRs detected 82% of the MSPrIs overall, making it the most sensitive data source, and scheduled skin checks were the second-most sensitive data source, finding 37% of the MSPrIs. CONCLUSIONS: MR review is the preferred method for ascertaining MSPrIs in clinical trials of interventions designed to reduce the incidence of these injuries. When multiple sources of information are used, careful reconciliation of reports is necessary to ensure accuracy.

A rapid turnaround gene panel for severe autoinflammation: Genetic results within 48 hours.

There is an important unmet clinical need for fast turnaround next generation sequencing (NGS) to aid genetic diagnosis of patients with acute and sometimes catastrophic inflammatory presentations. This is imperative for patients who require precise and targeted treatment to prevent irreparable organ damage or even death. Acute and severe hyper- inflammation may be caused by primary immunodeficiency (PID) with immune dysregulation, or more typical autoinflammatory diseases in the absence of obvious immunodeficiency. Infectious triggers may be present in either immunodeficiency or autoinflammation. We compiled a list of 25 genes causing monogenetic immunological diseases that are notorious for their acute first presentation with fulminant inflammation and which may be amenable to specific treatment, including hemophagocytic lymphohistiocytosis (HLH); and autoinflammatory diseases that can present with early-onset stroke or other irreversible neurological inflammatory complications. We designed and validated a pipeline that enabled return of clinically actionable results in hours rather than weeks: the Rapid Autoinflammation Panel (RAP). We demonstrated accuracy of this new pipeline, with 100% sensitivity and 100% specificity. Return of results to clinicians was achieved within 48-hours from receiving the patient's blood or saliva sample. This approach demonstrates the potential significant diagnostic impact of NGS in acute medicine to facilitate precision medicine and save "life or limb" in these critical situations.

Lentiviral Mediated ADA2 Gene Transfer Corrects the Defects Associated With Deficiency of Adenosine Deaminase Type 2.

Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive disease caused by bi-allelic loss-of-function mutations in ADA2. Treatment with anti-TNF is effective for the autoinflammatory and vasculitic components of the disease but does not correct marrow failure or immunodeficiency; and anti-drug antibodies cause loss of efficacy over time. Allogeneic haematopoietic stem cell transplantation may be curative, but graft versus host disease remains a significant concern. Autologous gene therapy would therefore be an attractive longer-term therapeutic option. We investigated whether lentiviral vector (LV)-mediated ADA2 gene correction could rescue the immunophenotype of DADA2 in primary immune cells derived from patients and in cell line models. Lentiviral transduction led to: i) restoration of ADA2 protein expression and enzymatic activity; (ii) amelioration of M1 macrophage cytokine production, IFN-γ and phosphorylated STAT1 expression in patient-derived macrophages; and (iii) amelioration of macrophage-mediated endothelial activation that drives the vasculitis of DADA2. We also successfully transduced human CD34+ haematopoietic stem progenitor cells (HSPC) derived from a DADA2 patient with pure red cell aplasia and observed restoration of ADA2 expression and enzymatic activity in CD34+HSPC, alongside recovery of stem-cell proliferative and colony forming unit capacity. These preclinical data now expand the evidence for the efficacy of gene transfer strategies in DADA2, and strongly support clinical translation of a lentivirus-mediated gene therapy approach to treat DADA2.

Bid from the Association for the Advancement of Wound Care.

The Association for the Advancement of Wound Care sets out its bid for the WUWHS 2026 Congress to be held in Chicago, Illinois, US.

Barriers to the Success of Recreational Groups for Persons With Dementia.

BACKGROUND: This paper describes barriers to engagement in the context of group activities attended by nursing home residents with dementia. OBJECTIVE: The goal is to clarify the presence and types of barriers to group activities for persons with dementia. METHODS: Therapeutic recreation staff (TRs) who conducted the group activities, and trained research observers (ROs) independently identified barriers occurring during group activity sessions through ratings and open-ended comments, which were analyzed via a mixed-method approach. RESULTS: Barriers were related to specific participant, environmental, and group session characteristics. Most frequently noted barriers were participant-related, pertaining to apathy and challenging behavior. Noise was the most frequent environmental barrier. Overall, ROs reported more barriers than TRs, yet TRs reported the barrier of inappropriate topic more frequently than ROs. CONCLUSIONS: The study suggests that the number and specific types of barriers are associated with negative engagement outcomes. Insight into these barriers is the first step toward addressing them and minimizing their effects.

Soccer-related injuries utilization of U.S. emergency departments for concussions, intracranial injuries, and other-injuries in a national representative probability sample: Nationwide Emergency Department Sample, 2010 to 2013.

Soccer participation in the United States (U.S.) has increased over time, and injuries as well as interest to prevent injuries has become more common. This study described Emergency Department (ED) visits related to concussions, intracranial injuries (ICI), and all-other injuries attributed to soccer play; described healthcare cost and length of hospital stay of soccer-related injuries; and determined independent predictors of concussions, ICI, and all-other soccer injuries leading to ED visits. The study examined soccer-related weighted discharge data from the Nationwide Emergency Department Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Weighted tabular analysis of univariate and bivariate analyses and weighted and adjusted logistic regression models were conducted. A total of 480,580 of U.S. ED visits related to soccer injuries were available for analysis between 2010 to 2013. Generally, 98% of soccer-related ED visits resulted in routine (treat-and-release) visits. However, the odds of transfer to a short-term hospital following ED evaluation and treatment was more than 37-fold higher for soccer-injured youth and adults diagnosed with ICI when compared to all-other soccer injuries; additionally, these patients showed 28-fold higher odds of being admitted for inpatient care at the ED-affiliated hospital. For concussion, soccer-injured patients with concussion showed nearly 1.5-fold higher odds of being transferred to a short-term hospital than did those with any other soccer injury. Soccer-related ED visits cost more than 700 million in U.S. dollars from 2010 to 2013. Notable differences were noted between concussions, ICI, and all-other soccer injuries presenting to U.S. ED. Albeit underestimated given that this study excludes other forms of health care and treatment for injuries, such as outpatient clinics, over the counter medications and treatment, and rehabilitation, healthcare cost associated with soccer-related injuries presenting to ED is high, and remarkably costly in those with an ICI diagnosis.

The identification of biophysical parameters which reflect skin status following mechanical and chemical insults.

BACKGROUND: Skin is constantly exposed to mechanical and chemical insults, in the form of prolonged loading, overhydration or exposure to irritants. An array of non-invasive biophysical tools has been adopted to monitor the changes in skin response. The present study aims to identify a set of robust parameters sensitive to mechanical and chemical challenges to skin integrity. MATERIALS AND METHODS: Eleven healthy participants were recruited to evaluate the skin response following mechanical loading, tape stripping, overhydration and chemical irritation. Forearm skin responses were recorded at baseline and at three time points following the insult. Measurements included transepidermal water loss, sub-epidermal moisture, erythema and laser Doppler imaging. Thresholds were informed by basal values, and the sensitivity of parameters to detect skin changes was evaluated. RESULTS: High degree of variability in skin response was observed with selected biophysical parameters, such as sub-epidermal moisture, laser Doppler imaging and erythema, even in the absence of an applied insult. Temporal skin response revealed distinct response profiles during each evoked insult. Indeed, the sensitivity of the biophysical parameters was influenced by the threshold values and time point of measurement. Some statistically significant correlations were determined between the biophysical parameters. CONCLUSION: The study revealed that thresholds derived from single biophysical parameters were limited in detecting skin changes following insults. A complementary evaluation using combined parameters has the potential to provide a more sensitive assessment. Further research is required to identify robust biophysical parameters, to aid the early detection of skin damage in clinical settings.

Anatomical variability of sub-epidermal moisture and its clinical implications.

BACKGROUND: Technologies have been developed to monitor changes in dermal oedema, indicative of the early signs of pressure ulcers. However, there is limited information on the effects of regional differences in tissue morphology on these sub-epidermal moisture (SEM) parameters. This study was designed to investigate the absolute SEM readings across different anatomical sites using a commercial device. METHODS: Twenty-four healthy participants were recruited to evaluate basal SEM values at different bony prominences, sampled by an experienced operator. RESULTS: Distinct differences were observed in unloaded SEM values across different anatomical sites, notably between the upper and lower extremities. A high degree of variability was observed in particular sites, such as the heels. Moreover, SEM values at certain locations revealed significant relationships with age, BMI and gender (p < 0.05). CONCLUSION: The study revealed a high level of variability between and within anatomical sites in a healthy cohort of participants. Determining the changes in local skin and sub-dermal tissue status using SEM may require consideration of both site specific and individual demographic factors, with further research needed in cohorts at risk of pressure ulcers.

Developing a decision support tool to prevent community-acquired pressure injuries in spinal cord injury in ambulatory care: A nurse-led protocol for mix methods research.

BACKGROUND: There is a lack of formal guidelines and decision support tools to prevent community-acquired pressure injuries (CAPrIs) in Veterans with spinal cord injury (SCI). PURPOSE: In this article we present our research protocol that describes our plans to create and test a decision support tool to prevent CAPrIs in SCI. METHODS: In Aim 1, we identified mental-models of CAPrI prevention from the perspectives of Veterans (using photovoice, guided tours), and Veterans Health Administration SCI providers (using interviews), and triangulation to compare the two mental-models. This led to a decision support tool developed and validated using Delphi approaches in Aim 2 and will be followed by tool automation and system redesign for pilot implementation in Aim 3. FINDINGS: The nurse-led research protocol provides a map to systematically explore, address and translate research into evidence-based practice. DISCUSSION: Refinement of the protocol will guide future research and implementation.

Natural History of Pressure Injury Among Ethnically/Racially Diverse Nursing Home Residents: The Pressure Ulcer Detection Study.

The current observational study provides descriptive data on 270 pressure injuries (PrIs) among 142 racially/ethnically diverse nursing home (NH) residents over 16 weeks. Weekly assessments were conducted with the Bates-Jensen Wound Assessment Tool. NH data were obtained from public government websites. NH, resident, and PrI characteristics across race/ethnicity groups were compared using analysis of variance and chi-square. Participants were 62% female and 89% functionally dependent. More Black and Asian individuals had peripheral vascular disease. More Black individuals had persistent trunk and Stage 4 PrIs. Black and Hispanic individuals had normal skin color surrounding PrIs. More Asian individuals had PrIs surrounded by purple/red discolored skin. More Black individuals' heel PrIs were unstageable, necrotic, and showed no granulation. Black and Hispanic individuals exhibited more deep tissue injury. No NH or prevention differences existed. Health disparities found validate administrative data results. Differences in PrI characteristics should be further examined among diverse NH residents. [Journal of Gerontological Nursing, 47(3), 37-46.].

Subepidermal Moisture and Pressure Injury in a Pediatric Population: A Prospective Observational Study.

PURPOSE: To describe relationships between subepidermal moisture (SEM) and visual skin assessment of pressure injury (PI) in children. DESIGN: Prospective descriptive study. SUBJECTS AND SETTING: Twenty-four participants aged 8 to 16 years recruited from a pediatric orthopedic unit in a children's hospital in Ireland. METHODS: Subepidermal moisture measured with the SEM scanner (Bruin Biometrics, Los Angeles, California) ranged from 0 to 7 picoFarads [pF], and visual observation of trunk and heels occurred daily for 3 days after admission to the unit and/or after surgery. Skin was assessed for discoloration categorized as blanchable erythema, stage 1 PI, or deep tissue injury (DTI). Any open wound PI was classified as stage 2, 3, 4, or unstageable. Demographic, medical, and pain data were collected. Chi-square test, t tests, analysis of variance, and regression were used to describe data and examine relationships. RESULTS: Participants were pediatric patients; 100% (n = 24) were white, 62% (n = 15) were female, 8 to 16 years of age (mean = 12.5 ± 2.5 years), and 29% (n = 7) had fractures and 71% (n = 17) surgery diagnoses. Blanchable erythema incidence was 21% (n = 5) and stage 1 PI incidence was 42% (n = 10); nearly all at heels. Deep tissue injury incidence was 4% (one sacral DTI). Stage 2 or greater PI incidence was 4% (one heel stage 2 PI). For skin that was assessed as normal in this pediatric population, SEM for trunk was 2.65 to 2.76 pF and for heels 2.37 to 2.41 pF. Subepidermal moisture for blanchable erythema and stage 1 PI was higher (range, 3.2-3.7 pF) and significant at trochanters and heels (left trochanter: P = .003; right trochanter: P = .02; right and left heels: P = .000). Nominal regression, controlling for participant and assessment day, showed SEM a predictor of erythema and stage 1 PI at heels. We also found that SEM was higher with pain (significant at sacrum and heels). CONCLUSIONS: In this pediatric population, SEM values over skin assessed as normal are lower than SEM values reported for normal skin in adults, 2.37 to 2.76 pF. Subepidermal moisture was significantly higher for blanchable erythema and stage 1 PI at trochanters and heels, and with the presence of pain at sacrum and heels. We recommend that SEM should be examined for detecting PIs in pediatric populations; SEM and pain should be explored in larger pediatric and adult populations.

A case of Myhre syndrome mimicking juvenile scleroderma.

BACKGROUND: Myhre syndrome is a genetic disorder caused by gain of function mutations in the SMAD Family Member 4 (SMAD4) gene, resulting in progressive, proliferative skin and organ fibrosis. Skin thickening and joint contractures are often the main presenting features of the disease and may be mistaken for juvenile scleroderma. CASE PRESENTATION: We report a case of a 13 year-old female presenting with widespread skin thickening and joint contractures from infancy. She was diagnosed with diffuse cutaneous systemic sclerosis, and treatment with corticosteroids and subcutaneous methotrexate recommended. There was however disease progression prompting genetic testing. This identified a rare heterozygous pathogenic variant c.1499 T > C (p.Ile500Thr) in the SMAD4 gene, suggesting a diagnosis of Myhre syndrome. Securing a molecular diagnosis in this case allowed the cessation of immunosuppression, thus reducing the burden of unnecessary and potentially harmful treatment, and allowing genetic counselling. CONCLUSION: Myhre Syndrome is a rare genetic mimic of scleroderma that should be considered alongside several other monogenic diseases presenting with pathological fibrosis from early in life. We highlight this case to provide an overview of these genetic mimics of scleroderma, and highlight the molecular pathways that can lead to pathological fibrosis. This may provide clues to the pathogenesis of sporadic juvenile scleroderma, and could suggest novel therapeutic targets.

Cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma gene.

OBJECTIVE: To report a series of patients with cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma (CBL) gene and examine the functional role of the identified mutant Cbl protein. We hypothesized that mutated Cbl fails to act as a negative regulator of the RAS-mitogen-activated protein kinases (MAPK) signaling pathway, resulting in enhanced vascular fibroblast proliferation and migration and enhanced angiogenesis and collateral vessel formation. METHODS: We performed whole-exome sequencing in 11 separate families referred to Great Ormond Street Hospital, London, with suspected genetic cause for clinical presentation with severe progressive cerebral arteriopathy. RESULTS: We identified heterozygous variants in the CBL gene in 5 affected cases from 3 families. We show that impaired CBL-mediated degradation of cell surface tyrosine kinase receptors and dysregulated intracellular signaling through the RAS-MAPK pathway contribute to the pathogenesis of the observed arteriopathy. Mutated CBL failed to control the angiogenic signal relay of vascular endothelial growth factor receptor 2, leading to prolonged tyrosine kinase signaling, thus driving angiogenesis and collateral vessel formation. Mutant Cbl promoted myofibroblast migration and proliferation contributing to vascular occlusive disease; these effects were abrogated following treatment with a RAF-RAS-MAPK pathway inhibitor. CONCLUSIONS: We provide a possible mechanism for the arteriopathy associated with heterozygous CBL variants. Identification of the key role for the RAS-MAPK pathway in CBL-mediated cerebral arteriopathy could facilitate identification of novel or repurposed druggable targets for treating these patients and may also provide therapeutic clues for other cerebral arteriopathies.