Behavior Intervention Response Team: Piloting an Effective Means to Manage Patient- and Family-Disruptive Behaviors.

GOAL: This article describes the development and implementation of a behavior intervention response team (BIRT). Pilot data indicate the successful implementation of BIRT interventions with patients and families and the positive staff response to these interventions. METHODS: Patient- and family-disruptive behaviors are increasing in hospitals. Those behaviors arise from stress, financial burdens, and the mental weight of the patient's medical condition on the family. These distressed patients and their families tax an already overwhelmed staff, exacerbating the caregivers' exhaustion, depersonalization, and frustration. We recognized the need to proactively address these disruptions at our children's hospital with an interdisciplinary response. Disciplines engaged in the BIRT development included risk management, behavioral health, child life, service excellence, patient and family services, social work, and chaplaincy. Following multiple brainstorming sessions, we created a comprehensive, clear intervention strategy to engage with a disruptive patient or family. The BIRT was developed to work with both the family and their medical team to intervene at the first signs of potential disruption. PRINCIPAL FINDINGS: With the BIRT, we were able to reduce disruptive behaviors and limit the subsequent removal of problematic individuals from the facility. Of the families who worked with the BIRT, 75.8% required no postintervention follow-up. PRACTICAL APPLICATIONS: The development of a BIRT can help head off disruptive behaviors and improve family-medical team relationships to support the highest quality and safest healthcare.

Monoallelic Mutations in the Translation Initiation Codon of KLHL24 Cause Skin Fragility.

The genetic basis of epidermolysis bullosa, a group of genetic disorders characterized by the mechanically induced formation of skin blisters, is largely known, but a number of cases still remain genetically unsolved. Here, we used whole-exome and targeted sequencing to identify monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding kelch-like protein 24 (KLHL24) in 14 individuals with a distinct skin-fragility phenotype and skin cleavage within basal keratinocytes. Remarkably, mutation c.1A>G occurred de novo and was recurrent in families originating from different countries. The striking similarities of the clinical features of the affected individuals point to a unique and very specific pathomechanism. We showed that mutations in the translation initiation codon of KLHL24 lead to the usage of a downstream translation initiation site with the same reading frame and formation of a truncated polypeptide. The pathobiology was examined in keratinocytes and fibroblasts of the affected individuals and via expression of mutant KLHL24, and we found mutant KLHL24 to be associated with abnormalities of intermediate filaments in keratinocytes and fibroblasts. In particular, KLHL24 mutations were associated with irregular and fragmented keratin 14. Recombinant overexpression of normal KLHL24 promoted keratin 14 degradation, whereas mutant KLHL24 showed less activity than the normal molecule. These findings identify KLHL24 mutations as a cause of skin fragility and identify a role for KLHL24 in maintaining the balance between intermediate filament stability and degradation required for skin integrity.

UV-B-induced cutaneous inflammation and prospects for antioxidant treatment in Kindler syndrome.

Kindler syndrome (KS), a rare, autosomal recessive disorder comprises mechanical skin fragility and photosensitivity, which manifest early in life. The progression of the disorder is irreversible and results in tissue damage in form of cutaneous and mucosal atrophy and scarring and epithelial cancers. Here, we unravel molecular mechanisms of increased UV-B sensitivity of keratinocytes derived from KS patients. We show that the pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, are upregulated in KS skin and in UV-B irradiated KS keratinocytes. These cytokines are dependent on p38 activation, which is increased in the absence of kindlin-1 and induced by higher ROS levels. Other dysregulated cytokines and growth factors were identified in this study and might be involved in paracrine interactions contributing to KS pathology. We show a direct relationship between kindlin-1 abundance and UV-B induced apoptosis in keratinocytes, whereas kindlin-2 overexpression has no compensatory effect. Importantly, low levels of kindlin-1 are sufficient to relieve or rescue this feature. Reduction of pro-inflammatory cytokines and of UV-B induced apoptosis is a valid therapeutic goal to influence long term complications of KS. Here, we demonstrate that antioxidants and the plant flavonoid luteolin represent feasible topical therapeutic approaches decreasing UV-B induced apoptosis in two-dimensional and organotypic KS cultures. We provide evidence for potential new therapeutic approaches to mitigate the progressive course of KS, for which no cure is available to date. Furthermore, we established organotypic KS models, a valuable in vitro tool for research with a morphology similar to the skin of patients in situ.

Vitamin E-enriched medium cross-linked polyethylene in total knee arthroplasty (VIKEP): clinical outcome, oxidation profile, and wear analysis in comparison to standard polyethylene-study protocol for a randomized controlled trial.

BACKGROUND: The gliding surface of total knee endoprostheses is exposed to high loads due to patient weight and activity. These implant components are typically manufactured from ultra-high molecular weight polyethylene (UHMWPE). Crosslinking of UHMWPE by ionizing radiation results in higher wear resistance but induces the formation of free radicals which impair mechanical properties after contact with oxygen. Medium-crosslinked UHMWPE enriched with vitamin E (MXE) provides a balance between the parameters for a sustainable gliding surface, i.e., mechanical strength, wear resistance, particle size, and oxidation stability. Therefore, a gliding surface for knee endoprostheses made up from this material was developed, certified, and launched. The aim of this study is to compare this new gliding surface to the established predecessor in a non-inferiority design. METHODS: This multicenter, binational randomized controlled trial will enroll patients with knee osteoarthritis eligible for knee arthroplasty with the index device. Patients will be treated with a knee endoprosthesis with either MXE or a standard gliding surface. Patients will be blinded regarding their treatment. After implantation of the devices, patients will be followed up for 10 years. Besides clinical and patient-related outcomes, radiological data will be collected. In case of revision, the gliding surface will be analyzed biomechanically and regarding the oxidative profile. DISCUSSION: The comparison between MXE and the standard gliding surface in this study will provide clinical data to confirm preceding biomechanical results in vivo. It is assumed that material-related differences will be identified, i.e., that the new material will be less sensitive to wear and creep. This may become obvious in biomechanical analyses of retrieved implants from revised patients and in radiologic analyses. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04618016. Registered 27 October 2020, https://clinicaltrials.gov/study/NCT04618016?term=vikep&checkSpell=false&rank=1 . All items from the World Health Organization Trial Registration Data Set can be found in Additional file 1.

Rotating Hinge Prosthesis for Primary and Revision Knee Arthroplasty: Comparison and Indications.

BACKGROUND: Rotating hinge knee prostheses are typically used in revision and severe primary total knee arthroplasty (TKA). For these challenging patient groups, currently only few studies with mid- or even long-term follow-up and adequate patient numbers are available. In addition, a more specific definition is needed of the indications for a rotating hinge prothesis in primary patients beyond the use in bone defects. METHODS: In this prospective study, 170 primary and 62 revision TKA patients were included who received a rotating hinge knee prosthesis at the study centre between the years 2009 and 2014. Of these, 98 primary and 22 revision TKA patients were available for 5-year functional and clinical follow-up examinations. Prosthesis survival in both patient groups could be compared up to a 9-year follow-up. RESULTS: Postoperatively, functional results including range of motion (ROM) and clinical scores like the Oxford Knee Score (OKS) and subscales of the Knee Society Score (KSS) improved better in patients treated for primary knee arthroplasty than for revision patients. Besides the patient group (primary vs. revision TKA), no overall influencing factors (age, body mass index, gender, etc.) regarding functional results could be identified in a multiple linear regression analysis. The revision rate of primary patients was significantly lower than in the revision patients, with an 8-year Kaplan-Meier prosthesis survival of 88% in the Primary and 60% in the Revision group. CONCLUSION: The prosthesis provides promising results in severe primary and revision knee arthroplasty. In addition to commonly agreed recommendations regarding the use of rotating hinge knee prostheses for primary surgery, six specific indications are proposed and discussed here as a base for scientific debate.

Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment.

Kindler syndrome, a distinct type of epidermolysis bullosa, is a rare disorder caused by mutations in FERMT1, encoding kindlin-1. Most FERMT1 mutations lead to premature termination codons and absence of kindlin-1. Here we investigated the molecular and cellular consequences of a naturally occurring FERMT1 mutation, c.299_301del resulting in a single amino acid deletion, p.R100del. The mutation led to a 50% reduction of FERMT1 mRNA and 90% reduction of kindlin-1 protein in keratinocytes derived from the patient, as compared with control cells. The misfolded p.R100del kindlin-1 mutant was lysosomally degraded and launched a homeostatic unfolded protein response. Sodium-phenylbutyrate significantly increased kindlin-1 mRNA and protein levels and the area of mutant cells, acting as a chemical chaperone and probably also as a histone deacetylase inhibitor. In a recombinant system, low levels of wild-type or p.R100del mutant kindlin-1 were sufficient to improve the cellular phenotype in respect of spreading and proliferation as compared with kindlin-1 negative keratinocytes. The study of this hypomorphic mutation provides evidence that low amounts of kindlin-1 are sufficient to improve the epidermal architecture and Kindler syndrome cellular phenotype and proposes a personalized chaperone therapy for the patient.