SummaryDiabetes has been recognized as an important risk factor for a variety of intracellular bacterial infections, but research into the dysregulated immune mechanisms contributing to the impaired host-pathogen interactions is in its infancy. Diabetes is characterized by a chronic state of lowgrade inflammation due to activation of pro-inflammatory mediators and increased formation of advanced glycation end products. Increased oxidative stress also exacerbates the chronic inflammatory processes observed in diabetes. The reduced phagocytic and antibacterial activity of neutrophils and macrophages provides an intracellular niche for the pathogen to replicate. Phagocytic and antibacterial dysfunction may be mediated directly through altered glucose metabolism and oxidative stress. Furthermore, impaired activation of natural killer cells contributes to decreased levels of interferon-c, required for promoting macrophage antibacterial mechanisms. Together with impaired dendritic cell function, this impedes timely activation of adaptive immune responses. Increased intracellular oxidation of antigen-presenting cells in individuals with diabetes alters the cytokine profile generated and the subsequent balance of T-cell immunity. The establishment of acute intracellular bacterial infections in the diabetic host is associated with impaired T-cell-mediated immune responses. Concomitant to the greater intracellular bacterial burden and potential cumulative effect of chronic inflammatory processes, late hyper-inflammatory cytokine responses are often observed in individuals with diabetes, contributing to systemic pathology. The convergence of intracellular bacterial infections and diabetes poses new challenges for immunologists, providing the impetus for multidisciplinary research.
The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy-dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D.
BACKGROUND Systematic review (SR) abstracts are frequently relied upon to guide clinical decision-making. However, there is mounting evidence that the quality of abstract reporting in the medical literature is suboptimal. OBJECTIVE To appraise SR abstract reporting quality in neurosurgical journals and identify factors associated with improved reporting. METHODS This study systematically surveyed SR abstracts published in 8 leading neurosurgical journals between 8 April 2007 and 21 August 2017. Abstracts were identified through a search of the MEDLINE database and their reporting quality was determined in duplicate using a tool derived from the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Abstracts (PRISMA-A) statement. All SR abstracts that provided comparison between treatment strategies were eligible for inclusion. Descriptive statistics were utilized to identify factors associated with improved reporting. RESULTS A total of 257 abstracts were included in the analysis, with a mean of 22.8 (±25.3) included studies. The overall quality of reporting in included abstracts was suboptimal, with a mean score of 53.05% (±11.18). Reporting scores were higher among abstracts published after the release of the PRISMA-A guidelines (M = 56.52; 21.74-73.91) compared with those published beforehand (M = 47.83; 8.70-69.57; U = 4346.00, z = –4.61, P < .001). Similarly, both word count (r = 0.338, P < .001) and journal impact factor (r = 0.199, P = .001) were associated with an improved reporting score. CONCLUSION This study demonstrates that the overall reporting quality of abstracts in leading neurosurgical journals requires improvement. Strengths include the large number abstracts assessed, and its weaknesses include the fact that only neurosurgery-specific journals were surveyed. We recommend that attention be turned toward strengthening abstract submission and peer-review processes.
Abstract. In countries with a high-burden of tuberculosis (TB), it has been well established that there is an increased incidence of TB among patients with diabetes. However, in countries with a low burden of TB there are conflicting reports. This study aimed to determine if diabetes was associated with TB in patients admitted to a teaching hospital in tropical Australia. A 20-year retrospective study found patients with comorbid diabetes were seven times overrepresented in the TB patient population when compared with the general population. This study demonstrates a strong association between TB and diabetes regardless of TB endemicity.Globally, tuberculosis (TB) is the single leading bacterial cause of death.1 The increasing emergence of comorbid immune suppressing conditions has accounted for the resurgence in TB.2,3 Patients with diabetes and prediabetes have an increased risk of bacterial infections and demonstrate a poorer prognosis. 4,5 Current estimates reveal patients with diabetes have on average a 3-fold risk of developing active TB when compared with the general population. In some regions, up to 50% of TB is associated with diabetes. 6,7 In low-burden TB countries such an association has not been reported and has been attributed to better glycemic control among all patients with diabetes. 8,9 It has been suggested that the association of TB and diabetes may not be a problem in these countries with a low burden of TB. The prevalence of comorbid TB and diabetes also remains ill-defined in many tropical areas within the Western Pacific region for both lowand high-burden TB countries, warranting further investigations. 1,8,9 The aim of this study was to determine if diabetes was a risk factor associated with TB in a low-burden tropical region by examining medical records and determining if TB patients had evidence of preexisting diabetes.We undertook a 20-year retrospective investigation in a defined group of patients with culture-confirmed TB admitted to a tertiary referral hospital in tropical Australia (#QTHS/HREC/ 43). In total, 69 patients were identified with TB between 1995 and 2014 and included in the analysis. The χ 2 test with Yates correction was used to assess whether a significant association existed between diabetes and TB and clinical outcomes.Comorbid TB and diabetes occurred in 23.2% (N = 16) of patients. There was a significant association between TB and diabetes (P < 0.0001) when compared with the general population of the region. Patients with diabetes were seven times overrepresented in the TB patient population (OR = 6.6; 95% CI = 3.788-11.60) in comparison to the general population. Almost half (N = 7; 43.8%) of the diabetic patients were recorded as having poorly controlled diabetes, as assessed by fasting blood glucose (> 6.0 mmol/L) and HbA1c levels (> 6.5%).Overseas-born individuals and indigenous Australians were overrepresented in patients with TB alone and comorbid diabetes when compared with the general population. The majority of overseas-born patients originated from hig...
BACKGROUND There is mounting evidence that the search strategies upon which systematic reviews (SRs) are based frequently contain errors are incompletely reported or insensitive. OBJECTIVE To appraise the quality of search strategies in the 10 leading specialty neurosurgical journals and identify factors associated with superior searches. METHODS This research-on-research study systematically surveyed SRs published in the 10 leading neurosurgical journals between 01/10/2017 and 31/10/2019. All SRs were eligible for assessment using a predefined coding manual that was adapted from the preferred reporting items for systematic reviews and meta-analyses (PRISMA), a measurement tool to assess systematic reviews (AMSTAR), and Cochrane Collaboration guidelines. The PubMed interface was used to search the MEDLINE database, which was supplemented by individual journal searches. Descriptive statistics were utilized to identify factors associated with improved search strategies. RESULTS A total of 633 articles were included and contained a median of 19.00 (2.00-1654.00) studies. Less than half (45.97%) of included search strategies were considered to be reproducible. Aggregated reporting score was positively associated with in-text reference to reporting guideline adherence (τb = 0.156, P < .01). The number of articles retrieved by a search (τb = 0.11, P < .01) was also associated with the reporting of a reproducible search strategy. CONCLUSION This study demonstrates that the search strategies used in neurosurgical SRs require improvement. In addition to increasing awareness of reporting standards, we propose that this be achieved by the incorporation of PRISMA and other guidelines into article submission and peer-review processes. This may lead to the conduct of more informative SRs, which may result in improved clinician decision-making and patient outcomes.
Abstract. Diabetes predisposes patients to bacterial infections. Although diabetes confers susceptibility to tuberculosis, the association between nontuberculous mycobacterial (NTM) infections and diabetes remains unknown. A retrospective chart analysis of patients in northern Australia during a 20-year period with soft tissue NTM infections revealed that patients with diabetes were three times overrepresented in comparison to the general population (odds ratio = 3.13). There was a statistically significant association between NTM infections and diabetes in this patient cohort (P = 0.0082).There are over 150 nontuberculous mycobacterial (NTM) species which are capable of causing disease in humans.
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