Shaping the future of kidney genetics in Australia: proceedings from the KidGen policy implementation workshop 2023.

The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients. Key insights from the workshop are documented in the proceedings.

Implementation and Evaluation of a National Multidisciplinary Kidney Genetics Clinic Network Over 10 Years.

Introduction: Diagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes. Methods: This pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics (KGCs). We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022. Results: We successfully established and expanded a nationwide network of 20 clinics as of 2022; concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1506 kidney patients, of whom 1322 received their test results. We assessed barriers to implementation in the nephrology context, and where possible, applied real-time solutions to improve clinical processes over 10 years. Conclusion: Developing a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to health care system funding.

Vildagliptin promotes diabetic foot ulcer healing through autophagy modulation.

The study aimed to investigate the molecular mechanisms underlying the effects of Vildagliptin on the healing of diabetic foot ulcers (DFUs). The research compared patients who received 12 weeks of Vildagliptin treatment to those who did not. Various molecular markers associated with wound healing were measured. Wound fluid samples were collected from DFUs using a filter paper absorption technique, and total RNA was extracted for quantitative real-time PCR (qPCR). The results showed that the autophagy marker NUP62 was significantly downregulated in the Vildagliptin group at week 12 compared to baseline (median expression 0.57 vs. 1.28; P = 0.0234). No significant change was observed in the placebo group (median expression 1.61 vs. 1.48; P = 0.9102). Both groups showed substantial downregulation of RIPK3, a necroptosis marker, at week 12 compared to their respective baselines. In addition to its effects on blood sugar levels, Vildagliptin may promote DFU healing by reducing autophagy in patients with diabetes.

Efficacy of transfer form implementation for adult burn patients between institutions to the Israeli National Burn Center.

Burns are serious injuries associated with significant morbidity and mortality. In Israel, burn patients are often transferred between facilities. However, unstructured and non-standardized transfer processes can compromise the quality of patient care and outcomes. In this retrospective study, we assessed the impact of implementing a transfer form for burn management, comparing two populations: those transferred before and after the transfer form implementation. This study included 47 adult patients; 21 were transferred before and 26 after implementing the transfer form. We observed a statistically significant improvement in reporting rates of crucial information obtained by Emergency Room clinicians and inpatient management indicators. Introducing a standardized transfer form for burn patients resulted in improved communication and enhanced primary management, transfer processes, and emergency room preparation. The burns transfer form facilitated accurate and comprehensive information exchange between clinicians, potentially improving patient outcomes. These findings highlight the importance of structured transfer processes in burn patient care and emphasize the benefits of implementing a transfer form to streamline communication and optimize burn management during transfers to specialized burn centers.

Evaluation of treatment parameters for focused-extracorporeal shock wave therapy in knee osteoarthritis patients with bone marrow lesions: a pilot study.

OBJECTIVES: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesions. In addition, to investigate pathophysiological changes based on imaging and biomarker measures. METHODS: Using a single-case experimental design, a total of 12 participants were randomly allocated in 4 equal groups of 3 to receive different dosages of focused-extracorporeal shock wave therapy. Each group received either 4 or 6 sessions of 1500 or 3000 shocks over 4 or 6 weekly sessions. Participants underwent repeated measurements during the baseline, intervention, and post-intervention phases for Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, aggregated locomotor function score and pressure pain threshold. Imaging and inflammatory biomarker outcomes were measured at baseline and 3 months following the intervention. RESULTS: The group receiving the highest dosage of focused-extracorporeal shock wave therapy showed clinical improvements superior to those of participants in the other 3 groups. Statistically significant changes during the follow-up phase in contrast to baseline measurements for the WOMAC score (Tau-U= -0.88, p < 0.001), aggregated locomotor function score (Tau-U= -0.77, p = 0.002), and pressure pain threshold (Tau-U= 0.54, p = 0.03) were observed. Bone marrow lesion and inflammatory cytokines demonstrated no change. CONCLUSION: A dose-dependent effect for focused-extracorporeal shock wave therapy on osteoarthritis-related symptoms was suggested. However, these improvements were not associated with changes in the underlying pathophysiological mechanisms.

Spincare System Demonstrates Safety and Efficacy in Treating Partial-Thickness Burns.

Partial-thickness burns are the most common form of burns, affecting the dermis and possibly resulting in scarring and infection. The Spincare System is a new device that uses electrospinning technology to create a temporary skin-like matrix that can be applied to wounds. This study evaluated the performance, safety, and efficacy of Spincare in treating superficial to partial-thickness burns not considered for surgery. A prospective single-arm, open-label, multicenter study was conducted in 3 adult burn units across Israel. Forty-four patients with superficial to intermediate burns of up to 10% of TBSA were enrolled. Spincare was applied to the wounds, and follow-up visits were performed on days 7, 14, and 21 and months 3 and 6 posttreatment. Thirty-one patients with 36 wounds completed the day 21 visit. The mean wound healing area on day 21 was 97.26 ± 9.41%, and the mean healing time was 12.8 ± 4.3 days. Only one moderate adverse event was observed concerning the treatment, and it is important to acknowledge the potential progression of this hypertrophic scar into a keloid. This study demonstrated that Spincare is a safe and effective device for treating superficial to intermediate partial-thickness burns. Spincare achieved rapid and complete wound healing with a low incidence of adverse events.

Notes to Factor Analysis Techniques for Construct Validity.

This paper introduces and discusses factor analysis techniques for construct validity, including some suggestions for reporting using the evidence to support the construct validity from exploratory and confirmatory factor analysis techniques. Construct validity is a vital part of psychological testing and a prerequisite to every measurement instrument, including aptitude, achievement, and interests. Research, particularly in nursing and the health sciences, depends on reliable and valid measurements. Therefore, a growing emphasis is on assessing validity regarding the structure of test variables commonly estimated by factor analysis techniques. However, it is not always clear how to report the analysis and use it to support the construct validity. Both exploratory and confirmatory factor analysis techniques provide vital evidence to support the construct validity. However, these are not the only available evidence for construct validity, and the researcher should always consider other sources of evidence to develop and support the construct validity of their intended measures. In addition, the collection and presentation of this evidence are not limited to a time, but the validity of constructs is a continuous process that leads to validating the underlying theories from which constructs have emerged.

Extracorporeal Shockwave Therapy (ESWT) in the Management of Diabetic Foot Ulcer: A Prospective Randomized Clinical Trial.

Diabetic foot ulcer (DFU) is the most common cause of prolonged hospitalization with a high cost of care due to unsatisfactory outcomes with the current mode of therapy. Extracorporeal shockwave therapy (ESWT) is a new technology in the care of nonhealing wounds. The study's main objective was to compare the healing parameters of DFUs between patients undergoing the standard of care (SOC) alone and ESWT + SOC. The secondary objective was to assess inflammatory markers in both study groups. The study was designed as a single-center, randomized trial to provide evidence on the effects of ESWT on DFU healing. Informed consent was obtained from all participants before enrolment. Forty-eight participants were recruited, enrolled, and randomly allocated into the 2 study groups. Twenty-five patients were allocated to the ESWT + SOC group, and 23 patients were allocated into the SOC-only group for a treatment period of 6 weeks. The univariate binary analysis showed more patients with healed DFU in the ESWT + SOC group than the SOC-only group at 6 weeks, though the difference did not reach statistical significance (OR = 3.2, p = .07). The adjusted multivariate binary analysis confirmed this finding; however, the effect size did not reach statistical significance at 6 weeks (OR = 3.9, p = .08). The level of circulating inflammatory markers was similar in both groups of patients. It is the author's opinion that there is a potential benefit of ESWT on diabetic wound healing with further research warranted to determine its role in treatment of DFU. A larger trial with a more extended treatment period is, however, needed to substantiate our findings.

Mechanistic considerations for adenosine-lidocaine-magnesium (ALM) in controlling coagulopathy.

Adenosine-lidocaine-magnesium (ALM) mixture is a cardioplegic agent that improves survivability undisputedly in rodents, but not swine, models of hemorrhagic shock. However, despite protection from comorbid coagulopathy being the one common effect reported in both models, the underlying prothrombotic mechanism for ALM has not been fully elucidated. Here, we undertook a component-based approach focusing on individual drugs in the mixture to elaborate on the protective mechanism against coagulopathy within the frames of adenosine signaling and metabolic pathways. Additionally, the translational potential of small and large animal models of hemorrhagic shock for human survival is critically appraised, owing to substantial quantitative/qualitative differences between humans and rodents, particularly regarding the genetics of G protein-coupled receptors (GPCRs) interacting with ALM's constituents.

Female rats have a different healing phenotype than males after anterior cruciate ligament rupture with no intervention.

Little is known on the sex-specific healing responses after an anterior cruciate ligament (ACL) rupture. To address this, we compared male and female Sprague-Dawley rats following non-surgical ACL rupture. Hematology, inflammation, joint swelling, range of motion, and pain-sensitivity were analyzed at various times over 31-days. Healing was assessed by histopathology and gene expression changes in the ACL remnant and adjacent joint tissues. In the first few days, males and females showed similar functional responses after rupture, despite contrasting hematology and systemic inflammatory profiles. Sex-specific differences were found in inflammatory, immune and angiogenic potential in the synovial fluid. Histopathology and increased collagen and fibronectin gene expression revealed significant tissue remodeling in both sexes. In the ACL remnant, however, Acta2 gene expression (α-SMA production) was 4-fold higher in males, with no change in females, indicating increased fibroblast-to-myofibroblast transition with higher contractile elements (stiffness) in males. Females had 80% lower Pparg expression, which further suggests reduced cellular differentiation potential in females than males. Sex differences were also apparent in the infrapatellar fat pad and articular cartilage. We conclude females and males showed different patterns of healing post-ACL rupture over 31-days, which may impact timing of reconstruction surgery, and possibly clinical outcome.

Effects of vildagliptin on wound healing and markers of inflammation in patients with type 2 diabetic foot ulcer: a prospective, randomized, double-blind, placebo-controlled, single-center study.

INTRODUCTION: Diabetic foot ulcers (DFU) are one of the leading long-term complications experienced by patients with diabetes. Dipeptidyl Peptidase 4 inhibitors (DPP4is) are a class of antihyperglycemic medications prescribed to patients with diabetes to manage glycaemic control. DPP4is may also have a beneficial effect on DFU healing. This study aimed to determine vildagliptin's effect on inflammatory markers and wound healing. TRIAL DESIGN: Prospective, randomized, double-blind, placebo-controlled, single-center study. METHODS: Equal number of participants were randomized into the treatment and placebo groups. The treatment was for 12 weeks, during which the participants had regular visits to the podiatrist, who monitored their DFU sizes using 3D camera, and blood samples were taken at baseline, six weeks, and 12 weeks during the study for measurement of inflammatory markers. In addition, demographic characteristics, co-morbidities, DFU risk factors, and DFU wound parameters were recorded. RESULTS: 50 participants were recruited for the study, with 25 assigned to placebo and 25 to treatment group. Vildagliptin treatment resulted in a statistically significant reduction of HBA1c (p < 0.02) and hematocrit (p < 0.04), total cholesterol (p < 0.02), LDL cholesterol (p < 0.04), and total/HDL cholesterol ratio (P < 0.03) compared to the placebo group. Also, vildagliptin had a protective effect on DFU wound healing, evidenced by the odds ratio (OR) favoring the intervention of 11.2 (95% CI 1.1-113.5; p < 0.04) and the average treatment effect on the treated (ATET) for vildagliptin treatment group showed increased healing by 35% (95%CI; 10-60, p = 0.01) compared to placebo with the model adjusted for microvascular complications, smoking, amputation, dyslipidemia, peripheral vascular disease (PVD) and duration of diabetes. CONCLUSIONS: Vildagliptin treatment was effective in healing DFU in addition to controlling the diabetes. Our findings support the use of DPP4is as a preferred option for treating ulcers in patients with diabetes. Further studies on a larger population are warranted to confirm our findings and understand how DPP4is could affect inflammation and DFU healing.

Most Common Long COVID Physical Symptoms in Working Age Adults Who Experienced Mild COVID-19 Infection: A Scoping Review.

BACKGROUND: One-third of patients who recover from COVID-19 present with long COVID. Their symptoms are broad, affecting their physical functioning and, ultimately, their quality of life. Many of those individuals who develop long COVID, possibly from a mild COVID-19 infection, are in the 18-65 age group. This prolongation of malaise directly influences national workforce economies. OBJECTIVES: To summarise the commonly reported physical symptoms of long COVID in order to inform potential adjustments in healthcare for the employable population. METHODS: The Embase, CINAHL, Medline, SCOPUS, and WHO COVID-19 databases were searched. The study selection process was based on the PRISMA guidelines. The extracted data were synthesised and presented narratively. RESULTS: 7403 studies were accessed, comprising 60 cohort studies and 10 case series/studies, representing 289,213 patients who met our criteria. The most frequently reported physical symptoms were fatigue (92%), shortness of breath (SOB) (81.8%), muscle pain (43.6%), and joint pain (34.5%). CONCLUSIONS: The range of reported physical symptoms was broad and varied; the main ones being fatigue, breathlessness/SOB, and pain. Similarities observed between long COVID and other post-acute infection syndromes may help formulate protocols to manage and promote recovery for long COVID patients. Inconsistencies were evident, particularly with a lack of adherence to the standardised definitions of long COVID.

Enablers and barriers to non-dispensing pharmacist integration into the primary health care teams of Aboriginal community-controlled health services.

BACKGROUND: The primary health care management of chronic disease affecting Aboriginal and Torres Strait Islander peoples requires healthcare quality and equity demands to be met, and systems that foster better team-based care. Non-dispensing pharmacists (NDPs) integrated within primary healthcare settings can enhance the quality of patient care, although factors that enable or challenge integration within these settings need to be better understood. OBJECTIVES: To investigate enabling factors and barriers influencing integration of NDPs within Aboriginal community-controlled health services delivering primary health care. This was achieved through qualitative evaluation of the Integrating Pharmacists within Aboriginal Community Controlled Health Services (IPAC) Trial exploring the perceptions of NDPs, community pharmacists, healthcare staff, managers, and Aboriginal and Torres Strait Islander patients of these services. METHODS: NDPs were employed across twenty urban, rural, and remote services in three Australian states and provided pre-defined medication-related roles to adult Aboriginal and Torres Strait Islander patients. Perceptions were elicited from online surveys, interviews, and focus groups. Transcripts were thematically analyzed using the constant comparison method to identify, compare, and refine emerging themes. RESULTS: One hundred and four participants informed the findings, including 24 NDPs, 13 general practitioners, 12 service managers, 10 community pharmacists, 17 health service staff, and 17 patients. Enablers of integration included: personal (previous experience with Aboriginal and Torres Strait Islander peoples, cultural awareness, skills, individual attributes); health service-related (induction programs, Aboriginal Health Worker support, team-building initiatives); and community-related factors (engaged community elders, leaders, cultural mentors, community pharmacy champions). Barriers to NDP integration included a lack of systems supports for patients and staff to adapt to NDP roles, health service factors, travel requirements, a lack of community linkages, and time and budget constraints. CONCLUSIONS: NDP integration within primary health care services has potential to enhance medication-related services to Aboriginal and Torres Strait Islander peoples if enabling factors are supported and health systems and adequate resources facilitate the integration of pharmacists within these settings.

ALM Induces Cellular Quiescence in the Surgical Margin 3 Days Following Liver Resection, Hemorrhage, and Shock.

INTRODUCTION: The liver has a remarkable capacity to regenerate but not the resected lobe. Our aim was to examine the expression of a number of key genes of metabolism, proliferation, survival, and reprogramming 5 mm inside the resected margin following resuscitation with adenosine, lidocaine, and Mg2+ (ALM) therapy. MATERIALS AND METHODS: Anesthetized adult male Sprague-Dawley rats randomly assigned to ALM treatment (n = 10) or Saline controls (n = 10) underwent liver resection (60% left lateral lobe) and uncontrolled bleeding. After 15 min, 3% NaCl ± ALM bolus was administered, and after 60 min, a 4 h 0.9% NaCl ± ALM stabilization 'drip' was commenced. After 72 h monitoring (or high moribund score), histopathology, inflammatory mediators, and relative expression of key genes of tissue repair were measured in the remaining left lateral liver. RESULTS: ALM animals survived 72 h compared to 23 h for Saline controls (P = 0.002). In the surgical margin, ALM therapy showed preservation of cellular architecture, whereas controls had increased inflammation and diffuse necrosis. Liver proinflammatory cytokines were also 2- to 4-fold higher in Saline controls. ALM therapy dramatically suppressed (∼70%) gene expression of four adenosine receptors, metabolic signaling, autophagy, apoptosis, and cell proliferation compared to controls, including suppression of the Yamanaka factors by up to 85%. CONCLUSIONS: We conclude ALM therapy preserved hepatocyte architecture with less inflammation and necrosis 3 days after resection, hemorrhage, and shock. In addition, ALM induced cellular quiescence in the surgical margin, which may be a strategy for improved barrier protection and healing. Further studies are required to address this question.

The IFN-γ/miniTrpRS signaling axis: An insight into the pathophysiology of osteoporosis and therapeutic potential.

Osteoporosis results from dysregulated bone remodeling with increased osteoclast-mediated destruction of bones. We have recently shown in vitro the truncated tryptophanyl-tRNA synthetase (mini-TrpRS)-dependent action of interferon-gamma (IFN-γ) to promote myeloid lineage multinucleation, a fundamental step in the osteoclast formation. In particular, we found that IFN-γ readily induced monocyte aggregation leading to multinuclear giant cell formation that paralleled marked upregulation of mini-TrpRS. However, blockade of mini-TrpRS with its cognate amino acid and decoy substrate D-Tryptophan prevented mini-TrpRS signaling, and markedly reduced the aggregation of monocytes and multinucleation in the presence of IFN. The cell signaling mechanism executed by mini-TrpRS appears inevitably in any inflammatory environment that involves IFN-γ with outcomes depending on the cell type involved. Here, we elaborate on these findings and discuss the potential role of the IFN-γ/mini-TrpRS signaling axis in osteoporosis pathophysiology, which may eventually materialize in a novel therapeutic perspective for this disease.

Prevalence and risk factors of lower limb amputations in patients with diabetic foot ulcers: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The study aimed at determining prevalence and risk factors (RFs) of diabetic lower limb amputations (LLAs). METHODS: Electronic databases including PubMed, Medline, Web of Science, and Cochrane Library were searched from January 2003 to April 2021. RESULTS: Sixteen full-text published studies were reviewed. The prevalence of LLAs stood as high as 66%, with a combined prevalence of 19% (95% CI 10-29) using the random-effects model. The most prominent RFs for LLA were duration of diabetes mellitus (DM), age, renal impairment, and ethnic minority. Amongst Australians, Indigenous background is strongly associated with increased risk of the diabetic foot (DF) LLA. CONCLUSIONS: LLAs are considerably prevalent amongst patients with the DF and occur at even higher rates in patients with multimorbidity.