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Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.
Lin, M, Xu, F, Sun, J, Song, J, Shen, Y, Lu, S, Ding, H, Lan, L, Chen, C, Ma, W, et al
Critical care (London, England). 2024;(1):213
Abstract
BACKGROUND The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.
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Evolution of Metabolic Syndrome in Newly Diagnosed Type 2 Diabetes Mellitus Asian-Indian Patients Over the Last 15 Years using Adult Treatment Panel III of the National Cholesterol Education Program, World Health Organization, and International Diabetes Federation Criterion.
Tuteja, HS, Nassikar, N, Panikar, K, Tiwaskar, M, Walwalkar, S, Sachdev, I, Kamble, S, Kadir, P, Mahajan, A, Joshi, S, et al
The Journal of the Association of Physicians of India. 2024;(6):39-43
Abstract
AIM: A retrospective observational study was undertaken to assess the changing trends in the incidence of metabolic syndrome (MetS) in Asian-Indian patients with newly diagnosed type 2 diabetes (T2D) using Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria. The overall and gender-wise pattern of MetS and its components were also evaluated. MATERIALS AND METHODS Newly diagnosed T2D patients (n = 10,950)visiting Dr Panikar's Diabetes Care Centre from 2004 to 2019 with retrievable electronic medical records were selected. The incidence of MetS in these patients was studied using NCEP-ATP III, WHO, and IDF criteria in three separate timelines, namely, group I (2004-2008), group II (2009-2013), and group III (2014-2019). Overall and gender-wise, the incidence of various components of the MetS was also studied and compared across the three groups. All data were analyzed by using the Statistical Software Statistical Package for the Social Sciences (SPSS) version 10.0. Continuous variables were summarized by the number of observations (mean, standard deviation or median with minimum and maximum) and categorical values (calculating frequencies with percentages). Chi-square was used to estimate the incidence of MetS using different criteria and gender-wise patterns of the MetS components for the three periods. Other variables, such as mean body mass index (BMI), were assessed by applying variance analysis (ANOVA test). All values were reported based on a two-sided ANOVA test, and all the statistical tests were interpreted at a 5% level of significance. RESULTS In the current study, the overall incidence of MetS observed among the study population was 80.9, 65.4, and 69.8% using NCEP-ATP III, WHO, and IDF criteria, respectively. The incidence of MetS across the three timelines (i.e., from 2004 to 2019) with all the diagnostic criteria showed a steady increase. An analysis of the individual components of MetS revealed a high incidence of central obesity across all subgroups, followed by hypertension and dyslipidemia. Central obesity was prevalent in nearly 85.9% of patients in 2014-2019 vs 78.6% in the 2004-2008 subgroup. Similarly, the incidence of hypertension and overall dyslipidemia [i.e., high triglycerides (TGs) and low high-density lipoprotein-cholesterol (HDL-C)] was 77.8% and 68.2% in the former vs 67.9% and 59.6% in the latter, respectively. The incidence of all three MetS components, along with fasting sugar, showed a statistically significant and progressive increase over the years, with prevalence in group III (2014-2019) being the highest. Women were found to be more centrally obese and more dyslipidemic compared to men, whereas men were found to be more hypertensive. CONCLUSION The study shows a high incidence of MetS in Asian-Indian patients with newly diagnosed T2D. The incidence of MetS was significantly higher with the NCEP-ATP III diagnostic criteria than with WHO and IDF criteria. A steady rise in the incidence of MetS was observed over the study period of 2004-2019. Among the components of MetS, the incidence of central obesity, elevated TG levels, and low HDL-C were found to be higher in the female population than in males, whereas the incidence of hypertension was higher in males. Stringent lifestyle measures, along with appropriate pharmacological management, might help mitigate the risks associated with MetS.
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Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.
Parthipan, M, Feng, G, Breunis, H, Timilshina, N, Emmenegger, U, Hansen, A, Tomlinson, G, Matthew, A, Clarke, H, Santa Mina, D, et al
Journal of geriatric oncology. 2024;(3):101720
Abstract
INTRODUCTION Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.
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Does living alone influence fall risk among Swiss older adults aged 60+? A pooled observational analysis of three RCTs on fall prevention.
Braendle, K, Egli, A, Bischoff-Ferrari, H, Freystaetter, G
BMJ open. 2024;(5):e081413
Abstract
OBJECTIVES Falling and living alone have been identified as public health challenges in an ageing society. Our study investigates whether living alone influences fall risk in community-dwelling older adults in Switzerland. DESIGN AND METHODS Secondary analysis of three randomised controlled trials investigating how different doses of vitamin D and an exercise programme may influence the risk of further falls in people 60+ at risk of falling. We used logistic regression to examine the association between living alone and the odds of becoming a faller, and negative binomial regression to examine the association between living alone and the rate of falls. We assessed both any falls and falls with injury. All analyses were adjusted for sex, body mass index, age, grip strength, comorbidities, use of walking aids, mental health, trial and treatment group. Predefined subgroups were by sex and age. RESULTS Among 494 participants (63% women; mean age was 74.7±7.5 years) 643 falls were recorded over 936.5 person-years, including 402 injurious falls. Living alone was associated with a 1.76-fold higher odds of becoming a faller (OR (95% CI)=1.76 (1.11 to 2.79)). While the odds did not differ by sex, older age above the median age of 74.6 years increased the odds to 2.19-fold (OR (95% CI)=2.19 (1.11 to 4.32)). The rate of total or injurious falls did not differ by living status. CONCLUSIONS Community-dwelling older adults living alone have a higher odds of becoming a faller. The increased odds is similar for men and women but accentuated with higher age. TRIAL REGISTRATION NUMBERS ZDPT NCT01017354, NFP53: NCT00133640, OA: NCT00599807.
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Phase Angle as a Reliable Biomarker of Frailty to Predict Postoperative Outcomes in Patients Undergoing Off-Pump Coronary Artery Grafting: A Prospective Observational Study.
Kwon, JH, Bang, YJ, Kwon, EJ, Kim, WJ, Kim, WS, Cho, HS, Min, JJ
Journal of cardiothoracic and vascular anesthesia. 2024;(1):109-117
Abstract
OBJECTIVE To elucidate the association between phase angle (PA) and a composite adverse outcome in patients requiring off-pump coronary artery bypass grafting (OPCAB). DESIGN A prospective observational study. SETTING High-volume single center. PARTICIPANTS A total of 229 adult patients who underwent OPCAB from May 2019 to October 2020. INTERVENTIONS Each patient underwent bioelectrical impedance analysis, including PA assessment before surgery (PApre), immediately postoperatively (PApost), and 1 day postoperatively (PAPOD1), using an Inbody S10. Frailty index and nutritional assessments also were obtained before surgery. MEASUREMENTS AND MAIN RESULTS Patient outcomes were assessed using a composite adverse outcome comprising death, myocardial infarction, revascularization, new-onset atrial fibrillation, acute kidney injury, stroke, postoperative pulmonary complications, wound complications, sepsis, reoperation, and/or delirium occurring during hospitalization and over the following year. Patients for whom composite adverse outcomes were reported had lower PApre than those without complications (5.4 ± 0.9 v 6.0 ± 0.9, p < 0.001). The PA was significantly associated with in-hospital and 1-year composite postoperative outcomes. The odds ratios (OR, [95% confidence interval]) for PApre by time were in-hospital complications (0.435 [0.314, 0.604], p < 0.001; 1-year complications: 0.459 [0.330, 0.638], p < 0.001) and PAPOD1 (OR, in-hospital complications: 0.400 [0.277, 0.576], 1-year complications: 0.429 [0.298, 0.619], p < 0.001). The PApre was significantly associated with days alive and out of hospital until 1 year. The cut-off value of PApre for optimal prediction of in-hospital complications was 6.0 (area under the curve: 0.691 [0.623-0.758], p < 0.001). CONCLUSION Low PA as an indicator of frailty is associated with adverse postoperative outcomes after OPCAB. Low PA may be employed as a noninvasive and practical tool for the prediction of prognosis in patients with coronary artery disease.
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Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study.
Chatziralli, I, Agapitou, C, Dimitriou, E, Kapsis, P, Kazantzis, D, Machairoudia, G, Georgiadis, O, Theodossiadis, G, Theodossiadis, P
Seminars in ophthalmology. 2024;(1):96-101
Abstract
PURPOSE To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece. METHODS ADMIRE was a prospective, observational cohort study of patients with DME. Efficacy was assessed by change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month 36 after treatment with intravitreal aflibercept in treatment-naive patients and previously treated patients. Safety was evaluated by recording any patients-reported events. RESULTS Participants in the study were 94 patients with DME, 70 treatment naive and 24 previously treated with ranibizumab. At month 36 of the follow-up period, the mean change in BCVA was +7.4 letters compared to baseline (p < .001). The mean change in BCVA in treatment-naive patients was +8.9 letters and differed significantly compared to previously treated patients (+5.9 letters, p = .041). In addition, patients who received a loading dose of 5 monthly injections at the initiation of treatment provided better VA outcomes (+11.4 vs. +6.1 letters, p < .001). Accordingly, the mean CST at month 36 (369.6 ± 72.8 μm) was significantly decreased compared to baseline (479.2 ± 68.3 μm, p < .001). Overall, the mean number of injections at month 36 was 13.4. Safety analysis showed that the reported ocular adverse events during the 36-month study period were mild and not sight-threatening. CONCLUSION Intravitreal aflibercept was found to be safe and effective for the treatment of DME in real-life in a Greek population. Treatment-naive patients and those who received a loading dose of five consecutive monthly injections at initiation of treatment exhibited better outcomes, suggesting that early and effective treatment may prevent vision loss.
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The Association Between Short-Acting β2-Agonist Over-Prescription, and Patient-Reported Acquisition and Use on Asthma Control and Exacerbations: Data from Australia.
Price, D, Jenkins, C, Hancock, K, Vella, R, Heraud, F, Le Cheng, P, Murray, R, Beekman, M, Bosnic-Anticevich, S, Botini, F, et al
Advances in therapy. 2024;(3):1262-1283
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Abstract
INTRODUCTION In Australia, short-acting β2-agonists (SABA) are available both over the counter (OTC) and on prescription. This ease of access may impact SABA use in the Australian population. Our aim was to assess patterns and outcome associations of prescribed, acquired OTC and reported use of SABA by Australians with asthma. METHODS This was a cross-sectional study, using data derived from primary care electronic medical records (EMRs) and patient completed questionnaires within Optimum Patient Care Research Database Australia (OPCRDA). A total of 720 individuals aged ≥ 12 years with an asthma diagnosis in their EMRs and receiving asthma therapy were included. The annual number of SABA inhalers authorised on prescription, acquired OTC and reported, and the association with self-reported exacerbations and asthma control were investigated. RESULTS 92.9% (n = 380/409) of individuals issued with SABA prescription were authorised ≥ 3 inhalers annually, although this differed from self-reported usage. Of individuals reporting SABA use (n = 546) in the last 12 months, 37.0% reported using ≥ 3 inhalers. These patients who reported SABA overuse experienced 2.52 (95% confidence interval [CI] 1.73-3.70) times more severe exacerbations and were 4.51 times (95% CI 3.13-6.55) more likely to have poor asthma control than those who reported using 1-2 SABA inhalers. Patients who did not receive SABA on prescription (43.2%; n = 311/720) also experienced 2.71 (95% CI 1.07-7.26) times more severe exacerbations than those prescribed 1-2 inhalers. Of these patients, 38.9% reported using OTC SABA and other prescription medications, 26.4% reported using SABA OTC as their only asthma medication, 13.2% were prescribed other therapies but not SABA OTC and 14.5% were not using any medication. CONCLUSION Both self-reported SABA overuse and zero SABA prescriptions were associated with poor asthma outcomes. The disconnect between prescribing authorisation, OTC availability and actual use, make it difficult for clinicians to quantify SABA use.
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12-Month Real-Life Efficacy of the MiniMed 780G Advanced Closed-Loop System in Patients Living with Type 1 Diabetes: A French Observational, Retrospective, Multicentric Study.
Lablanche, S, Delagenière, J, Jalbert, M, Sonnet, E, Benichou, M, Arnold, N, Spiteri, A, Le Berre, JP, Renard, E, Chevalier, N, et al
Diabetes technology & therapeutics. 2024;(6):426-432
Abstract
Aim: To evaluate the evolution of glycemic outcomes in patients living with type 1 diabetes (T1D) after 1 year of use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. Methods: We conducted an observational, retrospective, multicentric study in 20 centers in France. The primary objective was to evaluate the improvement in glycemic control after 1-year use of AHCL. The primary endpoint was the variation of time in range (TIR) between pre-AHCL and after 1-year use of AHCL. Secondary objectives were to analyze the glycemic outcomes after 3, 6, and 12 months of AHCL use, the safety, and the long-term observance of AHCL. Results: Two hundred twenty patients were included, and 200 were analyzed for the primary endpoint. 92.7% of patients continued to use AHCL. After 1 year of use of AHCL, TIR was 72.5% ± 10.6% (+9.1%; 95% confidence interval [CI] [7.6-10.5] compared to pre-AHCL initiation, P < 0.001), HbA1c 7.1% ± 0.7% (-0.5%; 95% CI [-0.6 to -0.4]; P < 0.001), time below range 2.0% [1.0; 3.0] (0.0% [-2.0; 0.0], P < 0.001), and time above range 24.8% ± 10.9% (-7.3%; 95% CI [-8.8 to -5.7]; P < 0.001). More patients achieved the glycemic treatment goals of HbA1c <7.0% (45.1% vs. 18.1%, P < 0.001) and TIR >70% (59.0% vs. 29.5% P < 0.001) when compared with pre-AHCL. Five patients experienced severe hypoglycemia events and two patients experienced ketoacidosis. Conclusion: After 1 year of use of AHCL, people living with T1D safely improved their glucose control and a higher proportion of them achieved optimal glycemic control.
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Prevalence and Risk Factors of Chronic Kidney Disease in Patients With Type 2 Diabetes in China: Cross-Sectional Study.
Shi, L, Xue, Y, Yu, X, Wang, Y, Hong, T, Li, X, Ma, J, Zhu, D, Mu, Y
JMIR public health and surveillance. 2024;:e54429
Abstract
BACKGROUND Chronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease. OBJECTIVE This study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors. METHODS Baseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes. RESULTS A national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m2. Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA1c ≥7%, total cholesterol >5.18 μmol/L, LDL cholesterol >3.37 μmol/L, BMI ≥30 kg/m2, and hypertension. CONCLUSIONS In a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified. TRIAL REGISTRATION ClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471.
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Patient-reported muscle symptoms and their characterization in a hypertensive population eligible for statin therapy: An exploratory study.
Sarzani, R, Allevi, M, Giulietti, F, Sarnari, S, Scorcella, S, Di Agostini, A, Turri, P, Di Pentima, C, Spannella, F
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2024;(1):136-144
Abstract
BACKGROUND AND AIMS Statin-associated muscle symptoms (SAMS) are claimed to be frequent in clinical practice. We evaluated the prevalence and characteristics of patient-reported muscle symptoms (PRMS) attributed to drugs/nutraceuticals in hypertensive patients, focusing the attention on statin treatment. METHODS AND RESULTS Observational study on 390 consecutive outpatients. All patients were asked the following question: "Have you ever taken a drug/nutraceutical that you think gave you muscle symptoms?". Patients who answered "yes" were evaluated with a modified version of the SAMS-clinical index (SAMS-CI). Mean age: 60.5 ± 13.5 years (males 53.8%.). Patients who have ever taken a statin: 250. Patients who have never taken a statin: 140. Prevalence of PRMS (48.5% of the entire study population) did not differ between groups (p = 0.217). Only age, followed by number of drugs taken, was significantly associated with PRMS at multivariate analysis. A high prevalence of low scores to all the questions of "modified" SAMS-CI was found in both groups. Localization and pattern of PRMS did not differ between groups (p = 0.170). Timing of PRMS onset after starting the drug (p = 0.036) and timing of improvement after withdrawal (p = 0.002) were associated with statin therapy. CONCLUSION PRMS are highly prevalent among the hypertensive population and are believed to be drug-related, especially with aging and regardless of whether the drug taken is a statin or not. These findings are in line with the growing evidence that subjective muscle symptoms are often misattributed to statins, while they may more likely be related to the nocebo/drucebo effect or to other common undiagnosed conditions.
