Shedding new light for nurses: Enhancing pressure injury prevention across skin tones with sub-epidermal moisture assessment technology.

AIM(S): To assess the effectiveness of sub-epidermal moisture (SEM) assessment technology in the detection of early-stage pressure damage in a critical care unit (CCU) and dark skin tone patients and its impact on hospital-acquired pressure injury (HAPI) incidence. DESIGN: Quality improvement study employing Kurt Lewin's change model emphasizing planning, implementation, evaluation and sustainable change. METHODS: The study evaluated 140 adult patients admitted to the CCU over a 24-week period, from July to December 2022. Retrospective analysis of standard PI care pathways was performed in 90 patients admitted during a 12-week pre-implementation period. Fifty patients were admitted through the subsequent 12-week implementation period. SEM assessments were performed daily at the sacrum and heels and interventions were applied based on SEM assessments; SEM delta ≥0.6 indicating localized oedema or persistent focal oedema. Statistical analyses were performed on anonymized data. RESULTS: Pre-implementation HAPI incidence was 8.9% (N = 8/90). All eight patients were African American with varying skin tones. A 100% reduction in HAPI incidence was achieved in the implementation period which included 35 African American patients. The relative risk of HAPI incidence was 1.6 times higher in the pre-implementation group. CONCLUSION: Implementing SEM assessment technology enabled equitable PI care for all population types and resulted in a 100% reduction of PIs in our CCU. Objective SEM assessments detected early-stage PIs, regardless of skin tone and enabled providing interventions to specific anatomies developing tissue damage as opposed to universal preventive interventions. IMPLICATIONS: PI care pathways relying on visual and tactile skin assessments are inherently biased in providing equitable care for dark skin tone patients. Implementing SEM assessments empowers healthcare practitioners in driving objective clinical interventions, eliminates bias and enables positive PI health outcomes. IMPACT: Implementing SEM assessment technology had three main effects: it detected early tissue damage regardless of skin tone (detection effect), enabled anatomy-specific interventions (treatment effect) and prevented PIs across all population types (prevention effect). The authors have adhered to the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. What does this paper contribute to the wider global clinical community? Addressing health inequities in pressure injury prevention; Demonstrated effectiveness across patient populations; Resource optimization and enhanced patient safety.

Lichen planopilaris with significant post-inflammatory pigmentary alteration.

Lichen planopilaris is an uncommon dermatological manifestation of lichen planus of the scalp and results in cicatricial alopecia. We present a patient with lichen planopilaris and significant post-inflammatory pigmentary alteration, confirmed by histopathology. The patient's case represents a clinically important variation from an expected typical pattern of dyschromia at periphery of alopecic zones in lichen planopilaris.

Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor on T cells essential for maintaining T cell homeostasis and tolerance to self. Mice lacking CTLA-4 develop an early onset, fatal breakdown in T cell tolerance. Whether this autoimmune disease occurs because of the loss of CTLA-4 function in regulatory T cells, conventional T cells, or both is unclear. We show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. However, CTLA-4 expression in conventional T cells prevents aberrantly activated T cells from infiltrating and fatally damaging nonlymphoid tissues. These results demonstrate that CTLA-4 has a dual function in maintaining T cell tolerance: CTLA-4 in regulatory T cells inhibits inappropriate naïve T cell activation and CTLA-4 in conventional T cells prevents the harmful accumulation of self-reactive pathogenic T cells in vital organs.

Cutting edge: Dab2 is a FOXP3 target gene required for regulatory T cell function.

FOXP3-expressing regulatory T (Treg) cells are vital for maintaining peripheral T cell tolerance and homeostasis. The mechanisms by which FOXP3 target genes orchestrate context-dependent Treg cell function are largely unknown. In this study we show that in mouse peripheral lymphocytes the Drosophila Disabled-2 (Dab2) homolog, a gene that is involved in enhancing TGFbeta responses, is exclusively expressed in FOXP3+ regulatory T cells. Dab2 is a direct target of FOXP3, and regulatory T cells lacking DAB2 are functionally impaired in vitro and in vivo. However, not all aspects of Treg cell function are perturbed, and DAB2 appears to be dispensable for Treg cell function in maintaining naive T cell homeostasis.

Alternative Treatment Approaches to Small Intestinal Bacterial Overgrowth: A Systematic Review.

Background: Broad-spectrum antibiotics are the first-line treatment for small intestinal bacterial overgrowth (SIBO). However, many antibiotics have a considerable side-effect profile and SIBO commonly reoccurs after successful eradication with antibiotics. Alternative therapies such as probiotics, therapeutic diets, and herbal medicines have been used to individualize SIBO management, particularly in recalcitrant cases. Objectives: The objective of this review is to evaluate the role of alternative therapies in SIBO treatment. Data Sources: EMBASE, MEDLINE, and the Cochrane Central Register were systematically searched for clinical studies evaluating alternative therapies in the management of SIBO. Study Eligibility Criteria: Human studies in which an alternative intervention was used to treat SIBO were included. Alternative interventions were defined as an intervention that included a probiotic supplement, herbal preparation, or a dietary change. Randomized controlled trials (RCTs), nonrandomized clinical trials with or without a control, and crossover studies were included. Study Appraisal: The following information was extracted from the selected studies: study type, study participants, SIBO subtype, intervention, comparison, outcome measures, relevant results, relevant side effects, and Jadad score. Results: Eight studies met inclusion criteria. The studies evaluated probiotics (n = 5), therapeutic diet (n = 1), and herbal medicines (n = 2). Among these studies, there were four RCTs, two open-label single-arm studies, one randomized, double-blind crossover study, and one two-arm open-label study with crossover. Main results are summarized. Limitations: There may be studies not captured by the defined search criteria. Additionally, studies used different methodologies in both breath testing and measurement of clinical symptoms, making it difficult to draw conclusions on SIBO eradication and symptom improvement across studies. Conclusions and Implications: Our findings suggest preliminary evidence for a role of alternative therapies in the treatment of SIBO. However, robust clinical trials are generally lacking. Existing studies tend to be small and lack standardized formulations of treatment. Breath testing protocols and clinical symptom measurement greatly varied between studies. Large-scale, randomized, placebo-controlled trials are needed to further evaluate the best way to utilize alternative therapies in the treatment of SIBO.

Psoriasis and hypertension severity: results from a case-control study.

BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients.

Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical negative regulator of immune responses. Uniquely among known inhibitory receptors, its genetic ablation results in a fulminating and fatal lymphoproliferative disorder. This central regulatory role led to the development of antibodies designed to block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer. Despite their preclinical efficacy and promising clinical activity against late stage metastatic melanoma, the critical cellular targets for their activity remains unclear. In particular, debate has focused on whether the effector T cell (T(eff)) or regulatory T cell (T reg cell) compartment is the primary target of antibody-mediated blockade. We developed a mouse expressing human instead of mouse CTLA-4, allowing us to evaluate the independent contributions of CTLA-4 blockade of each T cell compartment during cancer immunotherapy in an in vivo model of mouse melanoma. The data show that although blockade on effector cells significantly improves tumor protection, unicompartmental blockade on regulatory cells completely fails to enhance antitumor responses. However, concomitant blockade of both compartments leads to a synergistic effect and maximal antitumor activity. We conclude that the combination of direct enhancement of T(eff) cell function and concomitant inhibition of T reg cell activity through blockade of CTLA-4 on both cell types is essential for mediating the full therapeutic effects of anti-CTLA-4 antibodies during cancer immunotherapy.

CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3(+) regulatory T cells. CTLA-4-deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4-deficient and -sufficient bone marrow (BM)-derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4(-/-) T cells in trans by CTLA-4-sufficient T cells is a reversible process that requires the persistent presence of FOXP3(+) regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3(+) regulatory T cell function in vivo.

Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.

alphabeta and gammadelta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gammadelta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gammadelta T cell development while opposing alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gammadelta T cells but not alphabeta T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.

STAT5 is required for thymopoiesis in a development stage-specific manner.

Diverse cytokines necessary for normal lymphopoiesis and lymphocyte homeostasis activate STAT5 in responder cells. Although STAT5 has been suggested to be a central molecular effecter of IL-7 function, its essential role during IL-7-dependent T cell development in vivo remained unclear. Using Stat5(-/-) mice we now show that STAT5 is essential for various functions ascribed to IL-7 in vivo. STAT5 is required for embryonic thymocyte production, TCRgamma gene transcription, and Peyer's patch development. In sharp contrast, normal STAT5 is dispensable for adult thymopoiesis. In peripheral lymphocytes, STAT5 is primarily required for the generation and/or maintenance of gammadelta T cells and TCRgammadelta(+) intraepithelial lymphocytes. Collectively, these results demonstrate that STAT5 is critical for many, but not all, aspects of steady state lymphoid lineage development and maintenance and suggest the existence of previously undocumented cytokine signaling traits and/or cytokine milieu during adult thymopoiesis.

The lymphoproliferative defect in CTLA-4-deficient mice is ameliorated by an inhibitory NK cell receptor.

T-cell responses are regulated by activating and inhibiting signals. CD28 and its homologue, cytotoxic T-lymphocyte antigen 4 (CTLA-4), are the primary regulatory molecules that enhance or inhibit T-cell activation, respectively. Recently it has been shown that inhibitory natural killer (NK) cell receptors (NKRs) are expressed on subsets of T cells. It has been proposed that these receptors may also play an important role in regulating T-cell responses. However, the extent to which the NKRs modulate peripheral T-cell homeostasis and activation in vivo remains unclear. In this report we show that NK cell inhibitory receptor Ly49A engagement on T cells dramatically limits T-cell activation and the resultant lymphoproliferative disorder that occurs in CTLA-4-deficient mice. Prevention of activation and expansion of the potentially autoreactive CTLA-4(-/-) T cells by the Ly49A-mediated inhibitory signal demonstrates that NKR expression can play an important regulatory role in T-cell homeostasis in vivo. These results demonstrate the importance of inhibitory signals in T-cell homeostasis and suggest the common biochemical basis of inhibitory signaling pathways in T lymphocytes.