Evolving Global Etiology of Hepatocellular Carcinoma (HCC): Insights and Trends for 2024.

The epidemiology of HCC is changing all over the world and the incidence of HCC is expected to continue increasing over the next 30 years. The changes are in the predisposing factors. Hepatitis B and hepatitis C as predisposing etiologies are decreasing while NAFLD/MAFLD is increasing. The increase in MAFLD is so great that despite the decrease in hepatitis B and C, the overall incidence of HCC is increasing. HCC in persons below the age of 20 years has distinct characteristics different from that of HCC in adults. The changing etiology of hepatocellular carcinoma has implications for the early detection, prevention, the stage of HCC at time of detection and in the treatment of HCC. The extent of these changes and their significance are discussed.

MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells.

Ferroptosis plays a crucial role in the progression of diabetic wounds, suggesting potential therapeutic strategies to target ferroptosis. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli. Cinnamaldehyde (CA) is a specific TRPA1 agonist. In in vitro experiments, we observed that high glucose (HG) treatment induced endothelial cell ferroptosis, impairing cell function. CA successfully inhibited endothelial cell ferroptosis, improving migration, proliferation, and tube formation. Further mechanistic studies showed that CA-activated TRPA1-induced Ca2+ influx promoted the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-E 2-related factor 2 (Nrf2) translocation, which contributed to the elevation of glutathione peroxidase 4 (GPX4), leading to the inhibition of endothelial cell ferroptosis. In addition, CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel (CA@HA-Gel), allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner. The results showed that CA@HA-Gel inhibited wound endothelial cell ferroptosis and significantly promoted diabetic wound healing. In summary, the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.

The relationship between microRNAs and COVID-19 complications.

Over the past three years, since the onset of COVID-19, several scientific studies have concentrated on understanding susceptibility to the virus, the progression of the illness, and possible long-term complexity. COVID-19 is broadly recognized with effects on multiple systems in the body, and various factors related to society, medicine, and genetics/epigenetics may contribute to the intensity and results of the disease. Additionally, a SARS-CoV-2 infection can activate pathological activities and expedite the emergence of existing health issues into clinical problems. Forming easily accessible, distinctive, and permeable biomarkers is essential for categorizing patients, preventing the disease, predicting its course, and tailoring treatments for COVID-19 individually. One promising candidate for such biomarkers is microRNAs, which could serve various purposes in understanding diverse forms of COVID-19, including susceptibility, intensity, disease progression, outcomes, and potential therapeutic options. This review provides an overview of the most significant findings related to the involvement of microRNAs in COVID-19 pathogenesis. Furthermore, it explores the function of microRNAs in a broad span of effects that may arise from accompanying or underlying health status. It underscores the value of comprehending how diverse conditions, such as neurological disorders, diabetes, cardiovascular diseases, and obesity, interact with COVID-19.

The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. Methods: MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score. Results: We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001). Conclusion: Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury (AKI) group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (P<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (P<0.05). Conclusions: This study elucidated the optimal tacrolimus through level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

[The Expression of TP53TG1, LINC00342, MALAT1, H19, and MEG3 Long Noncoding RNAs in Type 2 diabetes mellitus].

Type 2 diabetes is a complex and multifactorial metabolic disorder. The frequency of type 2 diabetes has dramatically increased worldwide. Long noncoding RNAs play a regulatory role in pathological processes of type 2 diabetes. The aim of the study was to analyze TP53TG1, LINC00342, MALAT1, H19, and MEG3 lncRNAs in patients with type 2 diabetes and metabolic parameters, as well as the risk of diabetic retinopathy. Participants included 51 patients with diabetes and 70 healthy individuals. The expression of the TP53TG1 and LINC00342 genes was significantly decreased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was higher in diabetes patients. H19 gene expression was increased in the patients with diabetic retinopathy compared patients without retinopathy. TP53TG1, LINC00342, and MEG3 expression was decreased in patients with diabetic retinopathy and MALAT1 expression was increased. H19 is positively correlated with triglyceride levels; TP53TG1 and LINC00342 are positively correlated with HbA1c levels and fasting glucose levels. MALAT1 is negatively correlated with HDL levels and positively correlated with LDL levels. A decrease in the expression level of TP53TG1 and LINC00342 and an increase in the level of MALAT1 in diabetes, as well as an association with glycemic control, indicate the role of the studied noncoding RNAs in the development of type 2 diabetes mellitus and retinopathy and can be considered as candidates for early diagnosis of type 2 diabetes.

Key biomarkers in type 2 diabetes patients: A systematic review.

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. RESULTS: We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] µIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. CONCLUSIONS: Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.

Management of acute kidney disease in type 2 diabetes: the potential role of GLP-1 RAs and SGLT2-Is.

Acute kidney disease (AKD) is defined as subacute damage and/or loss of kidney function occurring 7 to 90 days after acute kidney injury (AKI), and bearing a high risk of progression to chronic kidney disease. Current management of AKD is non-specific and includes prevention of repeated AKI, early and regular follow-up by a nephrologist, resumption and dose adjustment of statins and renin-angiotensin system inhibitors, optimization of blood pressure control, nutrition management, and nephrotoxin avoidance. Recently, SGLT2i and GLP1- RAs have emerged as potential therapeutic tools preventing the transition from acute to chronic kidney disease due to their efficacy in preserving renal function.

Effect of Gestational Diabetes Mellitus on Newborn Hearing: A Systematic Review.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with several adverse health conditions in newborns such as preterm birth, hyperbilirubinemia, macrosomia, respiratory distress. However, the effect of GDM on the hearing sensitivity of newborns is still unclear. The study aimed to explore the effect of GDM on newborn hearing. The study aimed to explore the effect of GDM on newborn hearing. METHOD: A systematic search was conducted using PubMed, Scopus, and CHINAL databases. Keywords like "gestational diabetes," "diabetic pregnancies," "hearing loss," "hearing impairment," and "hearing disorder" were used to form a search string. The Rayyan software was used for screening procedure. The full-length articles were shortlisted, extracted, and appraised. RESULTS: The 7 articles were included in the review. Findings suggest that hearing loss is more prevalent in newborns with GDM pregnancies than in non-GDM pregnancies. In addition, OAE findings were "referred during the first hearing screening of newborns with GDM pregnancies." The refer rate of the first bilateral hearing screening was higher for newborns with GDM pregnancies. Furthermore, children of diabetic pregnancies were found to be at risk of bilateral hearing loss, particularly sensorineural in nature. CONCLUSION: The present systematic review suggests an association between GDM and a higher refer rate in hearing screening. A multidisciplinary collaboration between gynecologists, pediatricians, and audiologists can smoothen the early detection of hearing loss in newborns with GDM pregnancies, leading to early intervention and better clinical outcomes to improve the quality of life of affected newborns.

Salivary microbiome and biomarker characteristics of diabetics with periodontitis.

OBJECTIVE: To examine the characteristics of the salivary microbiome in Type 2 diabetes mellitus (T2DM) patients with or without periodontitis. BACKGROUND: Periodontitis has been identified as clear sequelae of T2DM. This chronic oral disease also impacts the management of the clinical features of diabetes. The oral microbiome characteristics in T2DM with and without periodontitis, as well as the response of this oral microbiome to nonsurgical therapy have not been well described. Knowledge of key oral biological features could help address the observed poorer clinical presentation of T2DM patients. METHODS: The oral microbiome in saliva of adult cohorts periodontally healthy/non-diabetic (non-periodontitis; NP; n = 31), T2DM without periodontitis (DWoP; n = 32), and T2DM with periodontitis (DWP; n = 29) were characterized by microbial molecular analysis using V3-V4 sequencing and Luminex or ELISA techniques for salivary host analytes. RESULTS: Phyla distribution showed DWP with significantly lower levels of Firmicutes and Actinobacteria and higher levels of Fusobacteria and Spirochetes compared to the healthier groups. Approximately 10% of the detected microbial species showed significant differences in frequency and level of colonization among the DWP, DWoP, and NP samples. A subset of bacteria were significantly correlated with clinical disease features, as well as a specific repertoire of salivary analytes, in particular matrix metalloproteinase (MMP)8/MMP9, interleukin-1ß, B-cell activating factor, and resistin differed between the groups and were related to specific taxa. Principal component analysis that identified a majority of the DWP subjects microbiome was unique based upon an array of 27 taxa out of up to 255 detected in the saliva samples. CONCLUSION: T2DM patients with periodontitis show unique oral microbiome and salivary analyte composition compared to diabetics or non-diabetic persons without periodontitis. Specific members of the oral microbiome relate directly to the clinical disease features and/or salivary biomolecules in T2DM individuals.

Microcirculatory Dysfunction in Patients With Diabetes Mellitus Detected by a Distributed System of Wearable Laser Doppler Flowmetry Analysers.

The paper is devoted to the study of perfusion and amplitude-frequency spectra of laser Doppler flowmetry (LDF) signals in patients with diabetes mellitus (DM) in different skin areas of the upper and lower extremities using a distributed system of wearable LDF analysers. LDF measurements were performed in the areas of the fingers, toes, wrists and shins. The mean perfusion values, the amplitudes of blood flow oscillations in endothelial, neurogenic, myogenic, respiratory and cardiac frequency ranges, and the values of nutritive blood flow were analysed. The results revealed a decrease in tissue perfusion and nutritive blood flow in the lower extremities and an increase in these parameters in the upper extremities in patients with DM. A decrease in the amplitudes of endothelial and neurogenic oscillations was observed. The obtained results confirm the possibility of using wearable LDF analysers to detect differences in the blood flow regulation in normal and pathological conditions.

Association of hypertension and long-term blood pressure changes with new-onset diabetes in the elderly: A 10-year cohort study.

AIM: To explore the correlation between new-onset diabetes (NOD), hypertension and blood pressure management among elderly individuals in China. MATERIALS AND METHODS: A cohort analysis involved 1380 participants aged 60 years or older, initially free of diabetes in 2008, from the Chinese Longitudinal Healthy Longevity Survey. Follow-up assessments occurred every 2-3 years. The relationship between hypertension, blood pressure changes and NOD was analysed using multivariable-adjusted Cox regression. RESULTS: By 2018, 102 participants developed diabetes, while 1278 remained without diabetes. The cumulative diabetes prevalence increased from 3.1% at 3 years to 7.4% at 10 years. Hypertension prevalence increased from 20.9% at baseline to 41.0% at 10 years, with higher rates in those diagnosed with diabetes during follow-up. Multivariate analysis identified age, gender, baseline hypertension and systolic blood pressure (SBP) as independent predictors of NOD. Hypertension combined with overweight/obesity significantly increased the risk of NOD (hazard ratio [HR] 2.837; 95% confidence interval [CI], 1.680-4.792). We evaluated participants' blood pressure management levels in 2008 and 2011, then tracked the onset of diabetes from 2011 to 2018. Compared with participants with an average SBP below 120 mmHg in 2008 and 2011, those with SBP of 140 mmHg or higher had an 8-fold higher risk of developing NOD (adjusted HR8.492, 95% CI 2.048-35.217, P = .003), the highest risk group. Participants with SBP of 130-139.9 mmHg also had a significantly increased risk (adjusted HR 5.065, 95% CI 1.186-21.633, P = .029), while those with SBP of 120-129.9 mmHg showed no significant difference (HR 2.730, 95% CI 0.597-12.481, P = .195). Consistently high SBP (≥ 130 mmHg) further increased NOD risk (adjusted HR 3.464, 95% CI 1.464-8.196, P = .005). CONCLUSIONS: Significant predictors of NOD included age, gender, baseline hypertension and blood pressure management. Maintaining SBP consistently below 130 mmHg may be an effective strategy to reduce the incidence of NOD in the general elderly population.

Exposure to aircraft noise exacerbates cardiovascular and oxidative damage in three mouse models of diabetes.

BACKGROUND: Epidemiology links noise to increased risk of metabolic diseases like diabetes and obesity. Translational studies in humans and experimental animals showed that noise causes reactive oxygen species (ROS)-mediated cardiovascular damage. The interaction between noise and diabetes, specifically potential additive adverse effects, remains to be determined. METHODS AND RESULTS: C57BL/6 mice were treated with streptozotocin (i.p. injections, 50 mg/kg/d for 5d) to induce type-1 diabetes, with S961 (subcutaneous osmotic minipumps, 0.57 mg/kg/d for 7d) or fed a high-fat diet (HFD, 20 weeks) to induce type-2 diabetes. Control and diabetic mice were exposed to aircraft noise to an average sound pressure level of 72 dB(A) for 4d. While body weight was unaffected, noise reduced insulin production in all diabetes models. The oral glucose tolerance test showed only an additive aggravation by noise in the HFD model. Noise increased blood pressure and aggravated diabetes-induced aortic, mesenteric, and cerebral arterioles endothelial dysfunction. ROS formation in cerebral arterioles, the aorta, the heart, and isolated mitochondria was consistently increased by noise in all models of diabetes. Mitochondrial respiration was impaired by diabetes and noise, however without additive effects. Noise increased ROS and caused inflammation in adipose tissue in the HFD model. RNA sequencing data and alteration of gene pathway clusters also supported additive damage by noise in the setting of diabetes. CONCLUSION: In all three models of diabetes, aircraft noise exacerbates oxidative stress, inflammation, and endothelial dysfunction in mice with pre-existing diabetes. Thus, noise may potentiate the already increased cardiovascular risk in diabetic patients.

Traffic noise significantly contributes to an increased risk of cardiometabolic diseases (including diabetes and obesity) in the general population via stress hormones, inflammation and oxidative stress, all of which contribute to impaired vascular function and high blood pressure. However, the extent to which noise affects pre-existing diabetes is not sufficiently explained, which prompted us to investigate the molecular mechanisms responsible for noise-mediated exacerbation of cardiometabolic complications in three different animal models with diabetes mellitus: Noise exposure in diabetic mice caused further impairment of insulin signalling, increased blood pressure, and damage of small and large blood vessels as well as oxidative stress in the aorta, brain, and heart.Our functional observations were supported by gene analyses indicating combined effects of noise and diabetes on gene groups related to inflammation and metabolism, suggesting a need for further studies in humans to investigate how noise impacts cardiovascular risk in vulnerable groups such as patients with diabetes.

Associations between periodontal disease severity and selected cardiometabolic risk factors.

OBJECTIVES: To explore associations between periodontal disease (PD) severity and cardiometabolic risk factors, including body mass index (BMI), age, Type 2 Diabetes Mellitus (T2DM) risk, sex, and hypertension (HTN) in patients at an urban dental school clinic. METHODS AND MATERIALS: A cross-sectional study design was used to analyze electronic health record data, including periodontal status, demographic characteristics, cardiometabolic risk factors and the American Diabetes Association Diabetes Risk Test (DRT) Score. Chi-square tests and ordinal logistic regression were conducted using SAS 9.4. RESULTS: Of those with available data (n=6,778), 44% were male, 70.2% were overweight/obese, and the mean age was 50.9 (SD=16.6) years. Associations between PD severity and BMI, sex, age, DRT score, and HTN were statistically significant (all p<0.0001) in bivariate analyses. Using logistic regression, HTN (p=0.0006), sex (p<0.0001), and age (p<0.0001) were significant predictors of severe PD which was most common in those with HTN (35.9%), males (31.7%), those >60 years (36.6%). The odds of having severe PD for those with HTN were 1.2 times that of those without HTN. Males were 1.7 times more likely to have severe PD than females. Those aged 40-49 years, 50-59 years, and >60 years were 2.9, 4.2, and 4.3 times more likely to have severe PD than those who were 18-39 years, respectively. CONCLUSION: All cardiometabolic risk factors were associated with PD severity in bivariate analyses. In the logistic regression model, being older, male, and having HTN were significant predictors of PD severity. Future research is needed with a more diverse sample.

Risk of fungal infection in patients with psoriasis receiving biologics: a retrospective single-center cohort study.

BACKGROUND: The risk of fungal infection in patients with psoriasis receiving biologics is not fully understood in clinical practice. OBJECTIVE: To assess the incidence and the risk of fungal infection onset in patients with psoriasis receiving biologics. METHODS: Retrospective cohort study of 592 psoriasis cases treated with biologics at a single center. RESULTS: Seventy-three (12.3%) of the 592 cases involved a fungal infection. Fungal infection occurrence was more frequently associated with the use of interleukin (IL)-17 inhibitors than of other biologics. The risk factors of fungal infection were the type of biologic agent (P = .004), age at the start of biologic therapy (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), and diabetes mellitus (OR: 2.40; 95% CI: 1.20-4.79). LIMITATIONS: The present, retrospective study did not include patients who did not receive biologic therapy. Moreover, the type of biologic agent used was changed in many cases. CONCLUSION: Psoriasis patients treated with IL-17 inhibitors were more likely to cause fungal infections, especially candidiasis, than other biologics. Moreover, the age at the start biologic therapy and diabetes mellitus onset were also independent risk factors of fungal infection.

Recent advances in precision nutrition and cardiometabolic diseases.

A growing body of research on nutrition omics has led to recent advances in cardiovascular disease epidemiology and prevention. Within the PREDIMED trial, significant associations between diet-related metabolites and cardiovascular disease were identified, which were subsequently replicated in independent cohorts. Some notable metabolites identified include plasma levels of ceramides, acyl-carnitines, branched-chain amino acids, tryptophan, urea cycle pathways, and the lipidome. These metabolites and their associated pathways have been associated with incidence of both cardiovascular disease and type 2 diabetes. Future directions in precision nutrition research include: a) developing more robust multimetabolomic scores to predict long-term risk of cardiovascular disease and mortality; b) incorporating more diverse populations and a broader range of dietary patterns; and c) conducting more translational research to bridge the gap between precision nutrition studies and clinical applications.

Longitudinal Patterns of Ankle-Brachial Index and Their Association With Progression of CKD in Patients With Type 2 Diabetes and Elevated Body Mass Index.

RATIONALE & OBJECTIVE: Ankle-brachial index (ABI) is used to screen for vascular complications in the setting of diabetes. This study sought to examine the relationship of longitudinal ABI data and chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D) and elevated body mass index (BMI). STUDY DESIGN: A post-hoc analysis of the Look AHEAD trial. SETTING & PARTICIPANTS: This study included 3,631 participants in the Look AHEAD trial with a baseline glomerular filtration rate (eGFR) >60 ml/min/1.73 m2. EXPOSURES: Average ABI and average annual change in ABI were calculated based on annual ABI measurements during the first 4 years of the study. OUTCOME: CKD progression, defined as kidney failure requiring maintenance dialysis or the occurrence of eGFR<60 ml/min/1.73 m2 with a drop of ≥30% at a follow-up visit relative to the first eGFR measurement. ANALYTICAL APPROACH: Restricted cubic spline and Cox proportional hazards models were fit to estimate associations and to explore non-linearity. RESULTS: Over a median follow-up of 10.1 years, 1,051 participants developed CKD progression. There was a reversed J-shaped relationship of CKD progression with average ABI (when ABI <1.17: HR (per SD decrement), 1.23; 95%CI, 1.06-1.42; when ABI ≥ 1.17: HR (per SD increment), 1.10; 95%CI, 1.00-1.22) and average annual change in ABI (when change in ABI <-0.007: HR (per SD decrement), 1.37; 95%CI, 1.12-1.66; when change in ABI ≥-0.007: HR (per SD increment), 1.13; 95%CI, 1.03-1.24). LIMITATIONS: Observational study, potential unmeasured confounding. CONCLUSIONS: Low and high average ABI, even at clinically normal values, as well as decreasing and increasing average annual ABI, were associated a higher risk of CKD progression in patients with T2D and elevated BMI. Monitoring ABI and its changes over time may facilitate CKD risk stratification in patients with T2D.