Clinical characteristics of acute kidney injury associated with tropical acute febrile illness

Tropical acute febrile illness (TAFI) is one of the most frequent causes of acute kidney injury (AKI). The prevalence of AKI varies worldwide because there are limited reports available and different definitions are used. This retrospective study aimed to determine the prevalence, clinical characteristics, and outcomes of AKI associated with TAFI among patients. Patients with TAFI were classified into non-AKI and AKI cases based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of 1019 patients with TAFI, 69 cases were classified as having AKI, a prevalence of 6.8%. Signs, symptoms, and laboratory results were significantly abnormal in the AKI group, including high-grade fever, dyspnea, leukocytosis, severe transaminitis, hypoalbuminemia, metabolic acidosis, and proteinuria. 20.3% of AKI cases required dialysis and 18.8% received inotropic drugs. Seven patients died, all of which were in the AKI group. Risk factors for TAFI-associated AKI were being male (adjusted odds ratio (AOR) 3.1; 95% CI 1.3-7.4), respiratory failure (AOR 4.6 95% CI 1.5-14.1), hyperbilirubinemia (AOR 2.4; 95% CI 1.1-4.9), and obesity (AOR 2.9; 95% CI 1.4-6). We recommend clinicians investigate kidney function in patients with TAFI who have these risk factors to detect AKI in its early stages and offer appropriate management

Intestinal injury and the gut microbiota in patients with Plasmodium falciparum malaria

The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding parasite-induced intestinal injury and changes in the human intestinal microbiota composition in patients with Plasmodium falciparum malaria. During the blood stage of P. falciparum infection, infected red blood cells adhere to the vascular endothelium, leading to widespread microcirculatory obstruction in critical tissues, including the splanchnic vasculature. This process may cause intestinal injury and gut leakage. Epidemiological studies indicate higher rates of concurrent bacteraemia in severe malaria cases. Furthermore, severe malaria patients exhibit alterations in the composition and diversity of the intestinal microbiota, although the exact contribution to pathophysiology remains unclear. Mouse studies have demonstrated that the gut microbiota composition can impact susceptibility to Plasmodium infections. In patients with severe malaria, the microbiota shows an enrichment of pathobionts, including pathogens that are known to cause concomitant bloodstream infections. Microbial metabolites have also been detected in the plasma of severe malaria patients, potentially contributing to metabolic acidosis and other clinical complications. However, establishing causal relationships requires intervention studies targeting the gut microbiota

Proteomics Studies in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy and is associated with serious maternal and fetal complications such as pre-eclampsia and stillbirth. Further, women with GDM have approximately 10 times higher risk of diabetes later in life. Children born to mothers with GDM also face a higher risk of childhood obesity and diabetes later in life. Early prediction/diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. However, no biomarkers identified to date have been proven to be effective in the prediction/diagnosis of GDM. Proteomic approaches based on mass spectrometry have been applied in various fields of biomedical research to identify novel biomarkers. Although a number of proteomic studies in GDM now exist, a lack of a comprehensive and up-to-date meta-analysis makes it difficult for researchers to interpret the data in the existing literature. Thus, we undertook a systematic review and meta-analysis on proteomic studies and GDM. We searched MEDLINE, EMBASE, Web of Science and Scopus from inception to January 2022. We searched Medline, Embase, CINHAL and the Cochrane Library, which were searched from inception to February 2021. We included cohort, case-control and observational studies reporting original data investigating the development of GDM compared to a control group. Two independent reviewers selected eligible studies for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020185951. Of 120 articles retrieved, 24 studies met the eligibility criteria, comparing a total of 1779 pregnant women (904 GDM and 875 controls). A total of 262 GDM candidate biomarkers (CBs) were identified, with 49 CBs reported in at least two studies. We found 22 highly replicable CBs that were significantly different (nine CBs were upregulated and 12 CBs downregulated) between women with GDM and controls across various proteomic platforms, sample types, blood fractions and time of blood collection and continents. We performed further analyses on blood (plasma/serum) CBs in early pregnancy (first and/or early second trimester) and included studies with more than nine samples (nine studies in total). We found that 11 CBs were significantly upregulated, and 13 CBs significantly downregulated in women with GDM compared to controls. Subsequent pathway analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics resources found that these CBs were most strongly linked to pathways related to complement and coagulation cascades. Our findings provide important insights and form a strong foundation for future validation studies to establish reliable biomarkers for GDM

Low branched chain amino acids and tyrosine in Thai patients with type 2 diabetes mellitus treated with metformin and metformin-sulfonylurea combination therapies

Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population

Characteristics and associated factors of acute kidney injury among adult dengue patients: A retrospective single-center study.

Severe dengue cases have been increasingly reported in Thailand, and the under-reporting of acute kidney injury (AKI) in cases of dengue viral infection has become an obstacle in obtaining an accurate description of the true nature and epidemiology of AKI. Because AKI may lead to patient morbidity and mortality, an early diagnosis is important in preventing its onset in dengue patients. This study aimed to determine the prevalence, clinical and laboratory characteristics, and associated factors of AKI among adult dengue patients. This retrospective study reviewed admission data from the medical records of adult dengue patients admitted to the Bangkok Hospital for Tropical Diseases between January 2012 and November 2017 and stratified these patients into AKI and non-AKI groups using the Kidney Disease Improving Global Outcomes criteria (KDIGO). A total of 1,484 patients were included in the study, with 71 categorized into the AKI group. The prevalence of AKI was 4.8%. In the AKI group, the predominant age range was 18-40 years (71.8%), with a female to male ratio of 1:2.7. These patients showed significantly (P < 0.05) higher proportions of altered consciousness, dyspnea, low mean arterial blood pressure, high-grade fever, major bleeding, severe thrombocytopenia, hypoalbuminemia, severe transaminitis, coagulopathy, metabolic acidosis, rhabdomyolysis, proteinuria, hematuria, and pyuria. Our study established that older age, male sex, diabetes mellitus, obesity, severe dengue, and coexisting bacterial infection were significant associated factors for AKI in dengue by multivariate analysis. A total of 10 (14.1%) patients with AKI received dialysis, among which 9 (12.7%) patients from the AKI group died. Our findings suggest that an awareness of AKI, its early diagnosis, and evaluation of clinical and laboratory characteristics of dengue patients will help clinicians to initiate appropriate therapy for dengue-associated AKI

A Review of Cyclodextrin Encapsulation and Intelligent Response for the Release of Curcumin

To overcome the low water solubility and low bioavailability of curcumin (CUR), multiple delivery strategies have been proposed. Among these, cyclodextrin-based carriers have been widely used for the encapsulation and delivery of CUR. Cyclodextrins (CDs), as natural oligosaccharides, have been well known for their biodegradability, biocompatibility, non-toxicity, and internal hydrophobic and external hydrophilic structural features. This paper summarizes the recently reported CD-based carriers for encapsulating CUR. Particularly, the polymerization properties of CD self-assembly to enhance the encapsulation of CUR are discussed. In addition, the current progress on stimuli-responsive CD carriers for controlled release of CUR is described, which laid an important foundation for the development of CUR-based precision therapy in clinical practice. In conclusion, this review may provide ideas for the future development of a CD-based encapsulant for CUR

Acidosis and acute kidney injury in severe malaria

Background: In severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The relationship between plasma acids, urine acids and renal function was investigated in adult patients with acute falciparum malaria. Methods: Plasma and urinary acids which previously showed increased concentrations in proportion to disease severity in patients with severe falciparum malaria were quantified. Patients with uncomplicated malaria, sepsis and healthy volunteers served as comparator groups. Multiple regression and multivariate analysis were used to assess the relationship between organic acid concentrations and clinical syndromes, in particular AKI. Results: Patients with severe malaria (n = 90), uncomplicated malaria (n = 94), non-malaria sepsis (n = 19), and healthy volunteers (n = 61) were included. Univariate analysis showed that both plasma and creatinine-adjusted urine concentrations of p-hydroxyphenyllactic acid (pHPLA) were higher in severe malaria patients with AKI (p < 0.001). Multiple regression analysis, including plasma or creatinine-adjusted urinary acids, and PfHRP2 as parasite biomass marker as independent variables, showed that pHPLA was independently associated with plasma creatinine (β = 0.827) and urine creatinine (β = 0.226). Principal component analysis, including four plasma acids and seven urinary acids separated a group of patients with AKI, which was mainly driven by pHPLA concentrations. Conclusions: Both plasma and urine concentrations of pHPLA closely correlate with AKI in patients with severe falciparum malaria. Further studies will need to assess the potential nephrotoxic properties of pHPLA

MOESM1 of Acidosis and acute kidney injury in severe malaria

Additional file 1: Figure S1. Principal Component Analysis (PCA) results of plasma concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA) and p-hydroxyphenyllactic acid (pHPLA) with plasma creatinine of severe malaria patients with AKI (in blue) and without AKI(in red). Figure S2. Principal Component Analysis (PCA) results of corrected urine concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), p-hydroxyphenyllactic acid (pHPLA), methylmalonic acid (MMA), ethylmalonic acid, (EMA) and α-ketoglutaric acid (αKGA) with urinary creatinine of severe malaria patients with AKI (in blue) and without AKI (in red). Figure S3. Principal Component Analysis (PCA) results of plasma concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA) and p-hydroxyphenyllactic acid (pHPLA) of severe malaria patients with coma (in blue) and without coma (in red). Figure S4. Principal Component Analysis (PCA) results of corrected urine concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), p-hydroxyphenyllactic acid (HPLA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (αKGA) of severe malaria patients with coma (in blue) and without coma (in red). Figure S5. Principal Component Analysis (PCA) results of plasma concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA) and p-hydroxyphenyllactic acid (HPLA) of severe malaria patients with high parasite biomass (in blue) and without high parasite biomass (in red). Figure S6. Principal Component Analysis (PCA) results of corrected urine concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), p-hydroxyphenyllactic acid (HPLA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (αKGA) of severe malaria patients with high parasite biomass (in blue) and without high parasite biomass (in red). Figure S7. Principal Component Analysis (PCA) results of uncorrected urine concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), p-hydroxyphenyllactic acid (HPLA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (αKGA) of severe malaria patients with AKI (in blue) and without AKI (in red). Figure S8. Principal Component Analysis (PCA) results of uncorrected urine concentrations of L-lactic acid (LA), α-hydroxybutyric acid (αHBA), β-hydroxybutyric acid (βHBA), p-hydroxyphenyllactic acid (HPLA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-ketoglutaric acid (αKGA) with urinary creatinine of severe malaria patients with AKI (in blue) and without AKI (in red). Table S1a. Plasma and urine concentration range of organic acids detected in patients with severe malaria with coma (+/-). Table S1b. Plasma and urine concentration range of organic acids detected in patients with severe malaria with high biomass (+/-). Table S2. Summary of linear regression models in patients with severe falciparum malaria (N = 90), with plasma PfHRP2 concentrations and plasma or urinary acid concentrations as independent variables, and plasma or urinary creatinine concentrations as dependent variable. Table S3. Summary of linear regression models in patients with sepsis (N = 19), with plasma PfHRP2 concentrations and plasma or urinary acid concentrations as independent variables, and plasma or urinary creatinine concentrations as dependent. Table S4a. Partial Least Square Discriminant Analysis classification results of plasma concentration of 4 acids. Table S4b. Partial Least Square Discriminant Analysis classification results of corrected urine concentration of 7 acids