Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis.

The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB-DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59-fold (95% confidence interval (CI) 2.25-5.73), 1.55-fold (95% CI 1.39-1.72), and 2.09-fold (95% CI 1.71-2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16-fold in low/middle-vs. 1.73-fold in high-income countries), background TB incidence (2.05-fold in countries with >50 vs. 1.89-fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44-fold in Asia vs. 1.71-fold in Europe and 1.73-fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03-fold) and/or blood testing for DM (3.10-fold), as well as uncontrolled DM (3.30-fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO "End TB Strategy" for reducing TB incidence

A novel combined bioactivity / chemoactivity holistic approach for the evaluation of dietary supplements

There is increasing evidence that the excessive generation of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent from the harmful effects of free radicals on human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. In the first step, this approach includes in vitro studies to evaluate the antioxidant activity of the dietary supplements by measuring the parameters of free radical scavenging capacity, of reducing power activity, as well as, their ability to protect biomolecules from oxidation. Furthermore, the evaluation of their antimutagenic and antigenotoxic effects is also presented. SubsequentlySub, the specific effects of the dietary supplements were examined in three cancer cell lines (HepG2, HeLa, MKN45), by measuring redox biomarkers such as glutathione, reactive oxygen species and thiobarbituric acid reactive substances, using flow cytometry and spectrophotometry. Our results indicate that all the dietary supplements exhibit high antioxidant, antimutagenic, antigenotoxic and lipid protective activity. The most prominent result is their capability to induce oxidative damage on cancer cells via the critical decrease of the levels of their intracellular glutathione, as well as the increase of ROS and lipid peroxidation levels after the administration of non-cytotoxic concentrations. We suggest that the proposed methodology could constitute a valuable tool for the characterization of dietary supplements based on their chemical and functional properties. © 2021 Elsevier Lt

Acinetobacter infections: a growing threat for critically ill patients

There has been increasing concern regarding the rise of Acinetobacter infections in critically ill patients. We extracted information regarding the relative frequency of Acinetobacter pneumonia and bacteraemia in intensive-care-unit (ICU) patients and the antimicrobial resistance of Acinetobacter isolates from studies identified in electronic databases. Acinetobacter infections most frequently involve the respiratory tract of intubated patients and Acinetobacter pneumonia has been more common in critically ill patients in Asian (range 4–44%) and European (0–35%) hospitals than in United States hospitals (6–11%). There is also a gradient in Europe regarding the proportion of ICU-acquired pneumonias caused by Acinetobacter with low numbers in Scandinavia, and gradually rising in Central and Southern Europe. A higher proportion of Acinetobacter isolates were resistant to aminoglycosides and piperacillin/tazobactam in Asian and European countries than in the United States. The data suggest that Acinetobacter infections are a growing threat affecting a considerable proportion of critically ill patients, especially in Asia and Europe

The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection: An Individual Patient Data Meta-Analysis of 1952 Patients

Introduction: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. Methods: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). Results: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56\u20133.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24\u20132.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70\u20134.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36\u20133.59; I2 = 58%). Conclusion: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials

The Impact of carbapenem resistance on mortality in patients with klebsiella pneumoniae bloodstream infection: an individual patient data meta-analysis of 1952 patients

Introduction: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. Methods: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). Results: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56–3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24–2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70–4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36–3.59; I2 = 58%). Conclusion: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials