The role of the NLRP3 inflammasome in atherosclerotic disease: Systematic review and meta-analysis.

Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that the NLRP3 [NOD (nucleotide oligomerization domain)-, LRR (leucine-rich repeat)-, and PYD (pyrin domain)-containing protein 3] inflammasome is a key mediator in the development, progression, and destabilization of atherosclerotic plaques. This review aims to evaluate the current literature on the role of NLRP3 in human atherosclerosis. This systematic review was registered on the PROSPERO database (ID = CRD42022340039) and involved the search of a total of 8 databases. Records were screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies were included and quality assessed using the NIH: NHLBI tool. Six were eligible for meta-analysis using RevMan 5.4.1. We identified 20 relevant articles representing 3388 participants. NLRP3 mRNA levels and downstream cytokines, interleukin (IL)-1ß and IL-18 were found to be associated with atherosclerotic disease. Fold changes in NLRP3 mRNA levels were most strongly associated with high risk atherosclerotic disease, compared to controls [0.84 (95 % CI: 0.41-1.28)]. IL-1ß mRNA fold change was more robustly associated with high-risk atherosclerotic disease [0.61 (95 % CI: 0.10-1.13)] than IL-18 [0.47 (95 % CI: 0.02-0.91)]. NLRP3, IL-1ß, and IL-18 are associated with high-risk atherosclerotic disease. However, given the scope of this review, the role of this inflammasome and its cytokine counterparts in acting as prognosticators of coronary artery disease severity is unclear. Several upstream activators such as cholesterol crystals are involved in the canonical or non-canonical activation of the NLRP3 inflammasome and its downstream cytokines. These findings highlight the necessity for further research to delineate the exact mechanisms of NLRP3 inflammasome activation and potential drug targets.

Exploring the motivation of health professionals to engage with research at various career stages.

BACKGROUND: Research is crucial for improved healthcare and better patient outcomes, but there is a current shortage of clinician-researchers who can connect research and practice in the health professions field. This study aimed to investigate the effect of career stage, previous training and involvement in research on health professionals' (HPs) motivations to engage in research while in public hospital clinical roles. HPs' perceived motivation concerning the importance, value, and barriers attributed to research during different career stages were examined. METHODS: A mixed methods study design was adopted for this research. An online survey developed based on the Expectancy-Value-Cost (EVC) theory was distributed to HPs (doctors, nurses, midwives, and allied health professionals) in three North Queensland Public Hospitals. Data analysis included descriptive and inferential statistics for the quantitative data and content analysis for the qualitative text responses. RESULTS: Three hundred and fifty-five responses were received. Prior research training and involvement in research influenced respondents' perceptions about the importance, attitude, motivators, and barriers to research. Attainment value was the overarching motivation for involvement in research and research training for all career stages and all professional HP groups. Positive attitude to research was significantly higher (P = 0.003) for the allied health group (27.45 ± 4.05), followed by the medical (26.30 ± 4.12) and then the nursing and midwifery group (25.62 ± 4.21). Perceived importance and attitude attributed to research were significantly higher (P < 0.05) for those who had research training (26.66 ± 3.26 and 28.21 ± 3.73) compared to those who did not have research training (25.77 ± 3.77 and 23.97 ± 3.53). Significantly higher (P < 0.05) perceptions of organisational and individual barriers were reported among early career (50.52 ± 7.30) respondents compared to their mid-career (48.49 ± 8.14) and late career (47.71 ± 8.36) counterparts. CONCLUSION: The findings from this study provide valuable insights into the factors that influence HPs' motivation for research. The results underscore the importance of professional group, involvement in research, exposure to research training, career stage, gender, and organisational support in shaping HPs' attitudes, values, and perceived barriers to research. Understanding these factors can inform the development of targeted strategies to enhance research engagement among HPs and promote evidence-based practice in healthcare.

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.

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.

Impact of Research Training on Newly Graduated Health Professionals' Motivation to Undertake Research.

Background: Clinical research is vital for improved patient health outcomes. However, there has been a decline in the number of new researchers replacing an aging workforce. This is because multiple factors impact on newly graduated health professionals' (HPs) readiness and motivation to engage with research training and undertake research when taking up hospital clinical roles. Methods: Drawing on the Expectancy-Value-Cost (EVC) theory, a sequential explanatory mixed methods design involving cross-sectional survey and purposely sampled participant interview data was utilised to investigate the factors that impact on motivation to undertake research for three newly graduated HP groups (allied health, medical and nursing and midwifery). Survey data were subjected to descriptive and inferential statistical analysis, while interview data were thematically analysed to identify recurring themes. Framework analysis was utilised for triangulation of findings. Results: Participants' previous exposure to research training influenced their expectancy to undertake research. Participants who had previous research training reported significantly higher (P < 0.001) research confidence (Median (IQR) 3.0 (3.0-3.0)) compared to those who had no previous research training (Median (IQR) 0.0 (0.0-1.0)). However, in relation to types of values attached to research, participants who demonstrated intrinsic and attainment values were more engaged and motivated to undertake research despite a myriad of barriers compared to those who demonstrated utility value (P < 0.001). The qualitative data revealed six overarching themes in terms of factors that influence motivation (i) Importance of early immersion into formal research training (ii) Attitude to research (iii) Time constraints (iv) Poor visibility of research training opportunities (v) Lack of organisational support (vi) Low returns on effort. Conclusion: Research training builds confidence, however, to foster motivation for the uptake and continued engagement with research, educators would need to help new HPs see the intrinsic and attainment values of research as they move through the career pipeline.

Effect of glucagon-like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIMS: To determine the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on albuminuria in adult patients with type 2 diabetes mellitus (T2DM). METHODS: Medline Ovid, Scopus, Web of Science, EMCARE and CINAHL databases from database inception until 27 January 2022. Studies were eligible for inclusion if they were randomized controlled trials that involved treatment with a GLP-1RA in adult patients with T2DM and assessed the effect on albuminuria in each treatment arm. Data extraction was conducted independently by three individual reviewers. The PRISMA guidelines were followed regarding data extraction and quality assessment. Data were pooled using a random effects inverse variance model and all analysis was carried out with RevMan 5.4 software. The Jadad scoring tool was employed to assess the quality of evidence and risk of bias in the randomized controlled trials. RESULTS: The initial search revealed 2419 articles, of which 19 were included in this study. An additional three articles were identified from hand-searching references of included reviews. Therefore, in total, 22 articles comprising 39 714 patients were included. Meta-analysis suggested that use of GLP1-RAs was associated with a reduction in albuminuria in patients with T2DM (weighted mean difference -16.14%, 95% CI -18.42 to -13.86%; p < .0001) compared with controls. CONCLUSIONS: This meta-analysis indicates that GLP-1RAs are associated with a significant reduction in albuminuria in adult patients with T2DM when compared with placebo.

The efficacy of inflammatory markers in diagnosing infected diabetic foot ulcers and diabetic foot osteomyelitis: Systematic review and meta-analysis.

BACKGROUND: Diabetes foot ulcer (DFU) is a complication of diabetes mellitus. Accurate diagnosis of DFU severity through inflammatory markers will assist in reducing impact on quality of life. We aimed to ascertain the diagnostic test accuracy of commonly used inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and white cell count (WCC) for the diagnosis and differentiation between DFU grades based on the International Working Group on the Diabetic Foot classification system. METHODS: This systematic review explored studies that investigated one or more of the above-listed index tests aiding in diagnosing infected DFU. This review was registered on PROSPERO database (ID = CRD42021255618) and searched 5 databases including an assessment of the references of included studies. Records were manually screened as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A total of 16 studies were included which were assessed for quality using QUADAS-2 tool and meta-analysed using Meta-Disc v1.4. RESULTS: CRP had the greatest area under the curve (AUC) of 0.893 for diagnosing grade 2 DFU. This returned a pooled sensitivity and specificity of 77.4% (95% CI: 72% to 82%) and 84.3% (95% CI: 79% to 89%) respectively. In terms of diagnosing grade 3 DFU, procalcitonin had the highest AUC value of 0.844 when compared with other markers. The pooled sensitivity of PCT was calculated as 85.5% (95% CI: 79% to 90%) and specificity as 68.9% (95% CI: 63% to 75%). CONCLUSION: CRP and PCT are the best markers for diagnosing grade 2 and grade 3 DFU respectively. Other markers are also valuable when used in conjunction with clinical judgement. The findings accentuate the necessity of further research to establish standardised cut-off values for these inflammatory markers in diagnosing diabetic foot ulcers.

Rethinking Health Professionals' Motivation to Do Research: A Systematic Review.

BACKGROUND: Health professionals' engagement in translational health and medical research (HMR) is fundamental to evidence-based practice leading to better patient health outcomes. However, there is a decline in the number of health professionals undertaking research which has implications for patient health and the economy. Informed by the motivation-based expectancy-value-cost (EVC) and self determination theories (SDT), this systematic literature review examined the barriers and facilitators of health professionals' (HPs) motivation to undertake research. METHODS: The literature was searched between 2011 and 2021 for relevant peer-reviewed articles written in English, using CINAHL Complete, Informit, Medline Ovid, Medline (PubMed), Scopus, Web of Science and Google Scholar databases. This systematic review was performed and reported in accordance with the PRISMA guidelines. RESULTS: Identified barriers to HPs' engagement with research included the lack of knowledge, skills, and competence to conduct research, lack of protected research time, lack of funding and lack of organisational support. Integration of the findings of this review based on the EVC and SDT theories indicate that research capacity, ie, expectancy and competence is highly influenced by attitude, ie, the type of value (attainment, intrinsic or utility) and connection attributed to research. HPs who had very positive attitude towards research demonstrated all three values and were keen to take up research despite the barriers. Those who had a positive attitude were only motivated to do research because of its utility value and did not necessarily see it as having personal relevance for themselves. HPs who were unmotivated did not see any personal connection or relatedness to the research experience and saw no value in research. CONCLUSION: The attitude HPs hold in their value of research is a catalyst for motivation or amotivation to engage in research as it directly influences the relevance of barriers. Facilitators that expedite the research journey have been attributed to research training, mentorship programs and supportive organisational research culture. Motivation of HPs explored through EVC and SDT is critical to the maintenance of a research culture and the clinician-researcher development pipeline.

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.

Ischemic heart disease and its risk factors in patients with diabetic foot ulcers: A systematic review and meta-analysis.

AIMS: There is limited literature on IHD in DFU patients. This review aimed to determine the prevalence of and risk factors of IHD in patients with DFUs. METHODS: Seven electronic databases were searched from inception to April 2021. RESULTS: The prevalence of IHD in DFU patients ranged from 6.83% to 60.61% with a pooled mean of 25.85% (95% CI, 24.28%-27.32%). Several risk factors were identified including hypertension, male gender, smoking, and peripheral vascular disease. CONCLUSION: We identified multiple risk factors for IHD requiring early interventions to increase long-term quality of life for patients with DFUs.

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.

A Comparison of Clinical Characteristics and Outcomes Between Indigenous and Non-Indigenous Patients Presenting to Townsville Hospital Emergency Department With Chest Pain.

BACKGROUND: Indigenous Australians have a high rate of ischaemic heart disease (IHD). There is a paucity of local data for North Queensland regarding the clinical characteristics of Indigenous people who present to the emergency department (ED) with chest pain. The aim of the study is to compare the cardiovascular risk factors, social characteristics, and the clinical outcomes between Indigenous and non-Indigenous patients who presented with cardiac-related chest pain. METHODS: This is a retrospective single-centre audit. The data was collected through chart reviews of chest pain presentations to the Townsville University Hospital Emergency Department, Queensland, Australia, from January to December 2017. We categorised the patients into Indigenous and non-Indigenous groups and compared their cardiac risk factors and social characteristics. We further classified the patients into three diagnosis groups and we measured the clinical outcomes in the patients with a diagnosis of cardiac-related chest pain. We used a data linkage to the Registry of Births, Deaths and Marriages for the death outcomes. A multivariable analysis was done to determine the risk of major adverse cardiac event (MACE) for Indigenous vs non-Indigenous patients. RESULTS: Indigenous patients were over-represented making up 19.1% of the total cohort (compared with 11.1% of the North Queensland Indigenous population) and presented at a younger age (median age: 45 vs 52, p<0.005). Traditional cardiovascular risk factors were significantly higher in Indigenous patients. The incidence of discharge against medical advice was also higher (6.5% vs 2.7%, p<0.005). There was an underutilisation of the local chest pain pathway amongst the Indigenous group (35.8% vs 44.7%, p<0.005). In patients with a diagnosis of cardiac-related chest pain, the rate of receiving invasive coronary angiogram procedures was similar in both cohorts (44.5% vs 43.7%, p=0.836). With regards to outcomes, Indigenous patients suffered from acute coronary syndrome (ACS) at a younger median age (51 vs 64, p<0.005) and were more likely to have severe three vessel disease (17% vs 6%, p<0.005) leading to coronary bypass graft surgery (CABG) (19% vs 6%, p<0.005). When adjusted for age, gender, and comorbidities, Indigenous patients were more likely to have MACE within 1 year of their chest pain presentation, compared with non-Indigenous patients with the same diagnosis (adjusted odds ration [AOR]=2.0, 95% CI [1.1, 3.8], p=0.03). CONCLUSION: In our study, Indigenous patients carried a heavier burden of cardiovascular risk factors, presented at a younger age, with more severe coronary disease and had a higher rate of CABG. We found an underutilisation of the local chest pain protocol amongst the Indigenous cohort, which suggests a need to improve support structures in the ED. In our multivariable analysis, Indigenous patients suffered from a significantly higher MACE compared to non-Indigenous patients which indicates that more collaborative efforts are needed to improve the cardiovascular health of local Aboriginal and Torres Strait Islander people.

Usefulness of Procalcitonin in Diagnosing Diabetic Foot Osteomyelitis: A Pilot Study.

INTRODUCTION: Infected diabetic foot is the leading cause of hospital admissions for people with diabetes mellitus. Diabetic foot osteomyelitis (DFO) causes high morbidity and significant mortality. Current diagnostic tests for DFO are either expensive, invasive, or of low diagnostic yield. OBJECTIVE: The objective of the study was to determine whether serum levels of procalcitonin (PCT), an inflammatory marker, differ between DFO and diabetic foot ulcers without osteomyelitis (ie, cellulitis) as controls. The authors also aimed to assess the usefulness of PCT in diagnosing DFO. METHODS: A case-control study was designed comparing DFO with diabetic foot cellulitis as the control. Patients were classified as having osteomyelitis and cellulitis based on the International Working Group on the Diabetic Foot diagnostic criteria. Serum inflammatory markers PCT, adiponectin, C-reactive protein-1, osteoprotegerin (OPG), osteopontin (OPN), and interleukin 6 (IL-6) were analyzed in patients with DFO and controls. RESULTS: The median serum procalcitonin was significantly higher in the DFO group 108.5 pg/mL (range, 65.0-124.0 pg/mL) compared with 57.0 pg/mL (range, 37.2-77.0 pg/mL) controls (P = .02). Procalcitonin had a sensitivity of 79% compared with 50%, 63%, 66%, and 75% for adiponectin, OPG, OPN, and IL-6, respectively. Procalcitonin had a specificity of 70% compared with 50%, 71%, 70%, and 64%. Receiver operator characteristic curves showed a value of area under the curve of 0.73 and 0.77 for PCT and IL-6 compared with 0.4, 0.6, and 0.6 for adiponectin, OPG, and OPN, respectively. CONCLUSIONS: In this study, procalcitonin was a useful diagnostic test for DFOs and provided distinct diagnostic discrimination between DFO from cellulitis. It may serve as a useful marker for diagnosing DFO. Further studies in a larger population are needed to verify the findings.

Metabolic and Anthropometric Influences on Nerve Conduction Parameters in Patients with Peripheral Neuropathy: A Retrospective Chart Analysis.

BACKGROUND AND AIMS: Nerve conduction study (NCS) measures how fast an electrical impulse moves through the nerve and is a standard technique for diagnosing and assessing neurological diseases. Despite diabetes and obesity being a common accompaniment of peripheral neuropathy, their effects on NCS patterns have not been elucidated conclusively. Our study aimed to assess several anthropometric and metabolic factors with NCS outcomes to address this gap. RESEARCH DESIGN AND METHODS: This retrospective chart analysis study was conducted on subjects who underwent NCS between 1 January 2009 and 31 December 2019 at a regional hospital. Metabolic, anthropometric, demographical and NCS data were collected from patients' health records. RESULTS: In total, 120 subjects presenting with sensorimotor peripheral neuropathy symptoms were included in the study. Age, HbA1c, urea and ESR variables were significantly negatively associated with nerve conduction outcomes (Spearman's correlation rho between -0.210 and -0.456, p < 0.038). HbA1c and age consistently had the most substantial contribution to velocity and amplitude in all regression models (beta coefficients between -0.157 and 0.516, p < 0.001). Urea also significantly account for a large amount of variance in amplitude and velocity in the lower limbs. CONCLUSION: This study suggests that the severity of sensorimotor neuropathy is influenced by glycaemic control, age and uraemia. The interpretation of NCS results must consider these factors suggesting that improved glycaemic and uraemic control may improve nerve conduction outcomes.

Influence of Ethnicity on Outcomes of Diabetes Inpatient Hypoglycemia: an Australian Perspective.

AIMS: To evaluate outcomes of diabetic inpatient hypoglycemia among Aboriginal and Torres Strait Islander (ATSI) compared with Australian Caucasian patients. METHODS: A retrospective audit of diabetic patients aged > 18 years admitted at a regional hospital general ward between April 1, 2015, and March 31, 2016, was analyzed. The database contains clinical information at the time of admission and initial discharge and readmission within 4 weeks thereafter. RESULTS: A total of 1618 (of 6027) patients were admitted with diabetes representing 23.7% of the total ward admissions, of which 484 (29.9%) had inpatient hypoglycemia. Of the 91 patients with available data analyzed, ATSI origin with inpatient hypoglycemia was associated with longer length of stay (LOS) (hazard ratio [HR], 2.1, 95% confidence interval [CI], 1.2-3.5), whereas severe hypoglycemia (≤ 2.2 mmol/L) in both ATSI and non-ATSI was significantly associated with longer LOS (HR, 2.3; 95% CI, 1.2-4.2). No significant differences in LOS were found for gender, age, and Carlson comorbidity index (CCI). The adjusted model for likelihood of readmission, gender, indigenous status, and CCI were not significant risk factors for readmission to the hospital. Readmitted patients were older (50-59 years vs < 50 years, P = 0.001; 60-69 years vs < 50 years, P = 0.032; 70+ years vs < 50 years, P = 0.031). CONCLUSION: We reported high rate of inpatient hypoglycemia in our study population. Indigenous Australian diabetic patients with inpatient hypoglycemia had significantly longer LOS compared with non-Indigenous Caucasian counterparts. Further prospective studies on a larger population are needed to confirm our findings.

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

BACKGROUND: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies. AIMS: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards. METHODS: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed. RESULTS: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years. CONCLUSION: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.

Using sacral nerve modulation to improve continence and quality of life in patients suffering from low anterior resection syndrome.

BACKGROUND: Sphincter preserving surgery for the treatment of rectal cancer is very often feasible, avoiding a permanent colostomy. It is well recognized that a large proportion of patients will experience altered bowel habit following low anterior resection (LAR). Faecal incontinence is a common symptom associated with LAR syndrome. The aim of this study is to evaluate the long-term improvement in continence and quality of life (QoL) in LAR patients treated with sacral nerve modulation. METHODS: Patients with ongoing faecal incontinence for >1 year after reversal of diverting ileostomy post ultra-LAR were selected for the study. Eligible patients underwent sacral nerve modulator implantation as a two-stage procedure. Bowel diaries and the Cleveland Clinic Faecal Incontinence Score were used to measure faecal incontinence and QoL. RESULTS: Twelve patients underwent permanent implantation of a sacral nerve stimulator. Median follow-up was 34 months (interquartile range (IQR) 20.25-62.5 months). The median improvement in faecal incontinence was 90% (IQR 76.25-98.75%) and the median improvement in patient QoL was 80% (IQR 71.25-93.75%). Patients who had previously been treated with biofeedback showed a median improvement in incontinence of 75% compared to 90% which was found in patients who had not had prior biofeedback treatment. The mean percentage improvement in patients with an internal anal sphincter defect was 80% compared to 90% seen in patients with an intact sphincter. CONCLUSIONS: The results of this study suggest that sacral nerve modulation should be more widely considered as an effective treatment strategy for patients with faecal incontinence following LAR.

Prevalence of low anterior resection syndrome at a regional Australian centre.

BACKGROUND: With decreasing indication for abdominoperineal resection and an increase in sphincter preserving surgery, there is a growing population of patients who suffer from low anterior resection syndrome (LARS). The aim of this study is to use the LARS score to determine the prevalence of LARS at a regional centre in Australia and determine the effect of short- and long-course neoadjuvant therapy, anastomotic technique and interval from surgery will also be assessed. METHODS: Patients who had undergone an anterior resection (high, low or ultralow) at a regional centre over an 11-year period were identified. Eligible patients were contacted to complete a LARS score questionnaire. Results were analysed to determine the rate of major LARS and possible causative roles of certain patient and treatment-related variables. RESULTS: A total of 64 of 76 patients (84%) returned completed questionnaires. The prevalence of major LARS was 37.5%. Short-course neoadjuvant therapy appeared to be more likely to be associated with major LARS compared to long course (odds ratio (OR) = 2.4, 95% confidence interval (CI) 0.37-15.3, P = 0.35); however, this did not reach statistical significance. Rates of major LARS appear to decrease slowly over time and J-pouch colonic anastomosis appears to be slightly protective against major LARS (OR = 0.7, 95% CI 0.12-3.9, P = 0.70); however, neither results were statistically significant. CONCLUSION: The rate of major LARS at this regional centre is 37.5%. Larger prospective multicentre studies are required to determine impact of variables such as type of neoadjuvant therapy, anastomotic techniques and progression of LARS over time.

Serum procollagen type 1 N propeptide: A novel diagnostic test for diabetic foot osteomyelitis - A case-control study.

BACKGROUND: The objective of the study was to determine whether serum levels of procollagen type 1 N propeptide (P1NP), a bone formation turnover marker, differs between diabetic foot ulcer with osteomyelitis (DFO) and diabetic foot ulcers without osteomyelitis serving as controls. It was also aimed to assess the usefulness of P1NP in diagnosing DFO compared to other common inflammatory markers. MATERIALS AND METHODS: A case-control study was designed comparing the aforementioned groups. Patients were classified as osteomyelitis and controls based on the International Working Group diagnostic criteria. Serum P1NP and three other inflammatory markers, namely, C-reactive protein (CRP), white blood cells (WBC), and platelets were analyzed on patients with DFO and controls. RESULTS: The mean serum P1NP levels were significantly higher in the DFO group (n: 16), 10.5 ± 5.2 (ng/ml), than the control group (n: 11) 3.1 ± 2.8 (ng/ml), P = 0.001. P1NP showed the highest sensitivity/specificity 86.7%/80% compared to 70.6%/80%, 56.2%/45.4%, and 50%/37% for CRP, WBC and platelets, respectively. Receiver operator characteristic curves showed the best value of area under the curve of 0.9 for P1NP compared to 0.85, 0.54, and 0.46 for CRP, WBC, and platelets. CONCLUSION: We found marked elevation of serum P1NP in diabetic foot ulcer with bone infection with potential value in using it to diagnose DFO.

A meta-analysis of the prevalence of Low Anterior Resection Syndrome and systematic review of risk factors.

AIM: To summarize the reported prevalence and causative factors of Low Anterior Resection Syndrome (LARS) from studies using the LARS score. METHODS: A systematic literature search was conducted using Pubmed, Ovid Medline and the Cochrane database. Searches were performed using a combination of MeSH (medical subject headings) terms and key terms. Studies that were included used the LARS score as their primary collection tool. Studies were excluded if initial surgery was not for malignancy, or if the majority of LARS scores were from patients less than 1 year post initial surgery or closure of diverting stoma. Eligible studies were assessed with a validated quality assessment tool prior to performing a meta-analysis with quality effects model. Meta-analysis was conducted with prevalence estimates that had been transformed using the double arcsine method. RESULTS: Following the initial search and implementation of inclusion and exclusion criteria 11 studies were deemed suitable for meta-analysis. Meta-analysis found the estimated prevalence of major LARS was 41% (95% CI 34 -48). Where possible outlier studies were excluded, the prevalence was 42% (95%CI 35-48). Radiotherapy and tumour height were the most consistently assessed variables, both showing a consistent negative effect on bowel function. Defunctioning ileostomy was found to have a statically significant negative impact on bowel function in 4 of 11 studies. The majority of reported data has been produced by groups in Denmark and the United Kingdom with limited numbers provided by other locations. Available data is heterogenous with some variables having limited numbers, making meta-analysis of certain variables impossible. CONCLUSIONS: There is significant prevalence of Low Anterior Resection Syndrome following oncological rectal resection. A low anastomotic height or history of radiotherapy are major risk factors.