Clinical and Experimental Medicine

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000–2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7749 BSI in 5159 patients, 58% associated with neutropenia. Gram-negatives were the main causative pathogens (58.3%), more frequent in neutropenic than non-neutropenic patients (3308/5309, 62.3% vs 1932/3678, 52.5%, p < 0.001). Amongst 8987 isolates the most common were E. coli (15.4%) and Pseudomonas spp. (14.2%). Pseudomonas spp. (16.6% vs 10.7%, p < 0.001), Klebsiella spp. (11.6% vs 6.8%, p < 0.001), viridans-group streptococci (4.4% vs 1.2%, p < 0.001) and E. faecium (2.4% vs 0.9%, p < 0.001) were more common in neutropenic than non-neutropenic patients, while S. aureus was less common (5.9% vs 15.6%, p < 0.001). Several antimicrobial resistance rates increased over time and had higher prevalence in neutropenic than non-neutropenic patients, including ciprofloxacin-resistant E. coli (94/758, 12.4% vs 42/506, 8.3%, p = 0.021), trimethoprim-sulfamethoxazole-resistant E. coli (366/764, 47.9% vs 191/517, 36.9%, p < 0.001), penicillin-resistant streptococci (51/236, 21.6% vs 28/260, 10.8%, p < 0.001) and vancomycin-resistant enterococci (46/250, 18.4% vs 9/144, 6.3%, p < 0.001). Carbapenem-resistant Pseudomonas spp. (OR 7.32, 95%CI 2.78–19.32) and fungi, including yeasts and moulds (OR 3.33, 95%CI 2.02–5.48) were associated to the highest odds of 30-day case-fatality at a multivariable logistic regression analysis. Neutropenia was associated with survival (OR 0.66, 95%CI 0.55–0.78). Differences were observed in the BSI epidemiology according to neutropenic status, with an overall increase of resistance over time associated to adverse outcome.

Endogenous malondialdehyde and diene conjugate levels, the susceptibility of apolipoprotein B-containing lipoproteins to copper-induced lipid peroxidation, and antibody titer against oxidized low-density lipoproteins were increased, but serum antioxidant activity was unchanged in obese women. Serum cholesterol, low-density lipoproteincholesterol, and trigliceride levels were also elevated, but high-density lipoprotein-cholesterol levels remained unchanged in obese women. In vitro, oxidation of apolipoprotein B-containing lipoproteins and levels of antibody against oxidized low-density lipoprotein correlated with body mass index, serum total cholesterol, and low-density lipoproteincholesterol levels in obese women. These results indicate that obesity is associated with increases in endogenous lipid peroxides, oxidation of low-density lipoproteins, and lipids in serum.

The aim of this study is to investigate the clinical and pathological features and outcome of glomerulonephritis with crescents among adult patients. This is a retrospective study of all cases of crescentic GN seen over a 9-year period (2001–2010). Histological features were assessed, and renal function at baseline and end of follow-up period was recorded. Results among different etiological groups at baseline and end of follow-up period were compared. The mean age in the whole group was 35.6 years (16.2), with the lowest mean in the lupus nephritis (LN) group [27.7 years (9.9)] and the highest in the pauciimmune glomerulonephritis (PIGN) group (P = 0.001). There were 72 cases enrolled in the study. LN accounted for 49.3% of the cases, PIGN for 26.5%, other immune complex glomerulonephritis (ICGN) for 19% and post-infectious GN accounted for 6.3% The majority (85.7%) of the patients had renal impairment at presentation (mean serum creatinine levels were 247 (85) μmol/l, 412 (75) μmol/l and 230 (141) μmol/l in LN, PICN and ICGN, respectively (P = 0.05). Women accounted for 85.3, 76.5 and 36.2% of the patients in LN, PICN and ICGN, respectively (P = 0.025). By the end of the follow-up period of 26 (22.9) months, 25.8% of the patients were requiring dialysis (16.70% in the LN group, 50% in PIGN and 25% in ICGN (P = 0.05) and 21.7% had nephrotic range proteinuria (16.7, 1 and 33.3%, respectively (P = 0.4). Using logistic multivariate analysis, the only independent factors found to predict need for dialysis of prognosis were percent of sclerosed glomeruli (P = 0.05) and presence of ATN (P = 0.028). Baseline proteinuria or SCr, gender and number of glomeruli with crescents, on the other hand, did not impact prognosis. Using linear regression multivariate analysis, SCr, protein excretion and activity score at biopsy did not influence change in SCr or final SCr during the follow-up period. Using ANOVA to compare the groups of LN, PIGN and ICGN), we found significant differences only in gender between LN and ICGN (P = 0.035), in percent glomerular global sclerosis (between LN and PIGN (P = 0.007) and between LN and ICGN (P = 0.012) and in age (between LN and PIGN (P = 0.006). Almost half of our patients with CrGN were due to LN which is higher than that reported by others where PIGN was the more prevalent etiology. Patients with PICN were older and had worse prognosis. This could be explained by the higher number of globally sclerosed glomeruli in the PIGN group.

The ability of early lung cancer diagnosis is an unmet need in clinical practice. Lung cancer metabolomic analyses conducted so far have demonstrated several abnormalities in cancer lipid profile providing a rationale for further study of blood lipidome of the patients. In the present research, we performed a targeted lipidome screening to select molecules that show promise for early lung cancer detection. The study was conducted on serum samples collected from newly diagnosed, stage I non-small cell lung cancer (NSCLC) patients and non-cancer controls. A high-throughput mass spectrometry-based platform with confirmed interlaboratory reproducibility was used. The analyzed profile consisted of acylcarnitines, sphingomyelins, phosphatidylcholines and lysophosphatidylcholines. Among the assayed lipid species, the significant differences between NSCLC and non-cancer subjects were observed in the group of phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPC), especially in the levels of lysoPC a C26:0; lysoPC a C26:1; PC aa C42:4; and PC aa C34:4. The metabolites mentioned above were used to create a multivariate classification model, which reliability was proved by permutation tests as well as external validation. Our study indicated choline-containing phospholipids as potential lung cancer markers. Further investigations of phospholipidome are crucial to better describe the shifts in metabolite composition occurring in lung cancer patients.

We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67–1.07; P = 0.16; I2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73–1.08; P = 0.24; I2: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28–0.62; P = 0.0001; I2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.

Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration, secondary synovial membrane inflammation and subchondral bone changes. In recent years, many studies have confirmed that interleukin-18 (IL-18) is involved in the inflammatory process of inflammatory joint diseases. In the present study, we investigated IL-18 levels in plasma, synovial fluid and articular cartilage of patients with primary knee OA (n = 33) to analyze their relationship with radiographic severity. Compared to healthy controls (n = 15), OA patients had higher plasma and synovial fluid IL-18 concentrations (45.8 ± 22.1 vs. 23.7 ± 13.6 pg/ml, P < 0.001 and 75.2 ± 40.1 vs. 28.3 ± 11.6 pg/ml, P < 0.001) as measured by enzyme-linked immunosorbent assay. Also, the percentage of immunofluorescent IL-18 positive cells in articular cartilage was significantly increased in OA compared to controls (46.5 ± 10.3 vs. 2.9 ± 1.7, P < 0.001). Moreover, plasma, synovial fluid and articular cartilage IL-18 significantly positively correlated with radiographic severity, respectively (r = 0.663, P < 0.001, r = 0.56, P = 0.001 and r = 0.884, P < 0.001). Subsequent analysis revealed that plasma, synovial fluid and articular cartilage IL-18 levels positively correlated with each other (r = 0.632, P < 0.001, r = 0.489, P = 0.004 and r = 0.620, P < 0.001). These data suggested that plasma, synovial fluid and articular cartilage IL-18 levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. Accordingly, our study supports the role of IL-18 in the pathophysiology of OA.

Oxidative modifications of apo-B-containing lipoproteins (LDL+VLDL) appear to play a role in atherogenesis. Increased atherosclerosis is one of the major causes of morbidity and mortality during ageing. The aim of this study was to investigate the susceptibility of serum and LDL+VLDL to lipid peroxidation in 12 young (6 months) and 12 old (22 months) rats. Serum endogenous malondialdehyde (MDA) and diene conjugate (DC) levels were found to be increased by 24.9% and 30.0% respectively, in old rats. In addition, 2,2′-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced lipid peroxide levels were increased in serum of old rats. Although serum vitamin E levels were significantly increased (27.4%), there was a significant decrease in cholesterol-adjusted vitamin E levels (14.3%) in old rats. Serum vitamin C and total sulphydryl levels were found to be decreased by 25.5% and 22.7% respectively. The ferric reducing ability of plasma (FRAP) was also lower (15.9%) in old rats. Endogenous DC and copper-induced MDA levels were significantly higher (65.1% and 26.7% respectively) in LDL+VLDL fractions obtained from EDTA-plasma by dextrane sulphate and MgCl2 solution in old rats. The propagation rate and maximal amount of DC increased, but the lag phase and t max were shortened in LDL+VLDL fractions of old rats. Our results clearly indicate that the susceptibility of whole serum and LDL+VLDL fractions to lipid peroxidation is increased in aged rats.