Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin–phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.

Serum albumin and body mass index (BMI, kg/m²) have been associated with outcomes following acute myocardial infarction (AMI). Aiming to assess whether the mortality risk inflicted by hypoalbuminemia (<3.5 g/dL) in this context is influenced by BMI, we conducted a retrospective analysis of AMI survivors hospitalized during 2004–2017. Stratified by admission-time albumin level and BMI, eligible cases were evaluated for all-cause mortality up to 10 years after discharge. A total of 6283 individuals (74.1% males, mean age 64.1 ± 13.1 years, 44.3% with ST-elevation MI) were included. Of them, 22.7% had hypoalbuminemia and 1.2%, 41.0%, and 28.6% were underweight (BMI < 18.5), overweight (BMI 25–30), and obese (BMI ≥ 30), respectively. Over a median of 7.9 (IQR, 4.8–10.0) years of follow-up, 42.5% of patients died. Hypoalbuminemia was independently associated with a heightened mortality risk overall (AdjHR = 1.54, 95%CI 1.42–1.67, p < 0.001), accounted for by the normal weight (AdjHR = 1.73, 95%CI 1.50–1.99, p < 0.001), overweight (AdjHR = 1.55, 95%CI 1.35–1.79, p < 0.001), and class 1 obesity (BMI 30–35) (AdjHR = 1.37, 95%CI 1.12–1.68, p = 0.002) subgroups. Upon interaction analysis, the mortality risk imposed by hypoalbuminemia was most pronounced among individuals with normal BMI. In conclusion, hypoalbuminemia constituted a negative prognostic marker for long-term survival in AMI patients with normal or mildly elevated but not reduced or severely increased BMI. Pending further research, addressing hypoalbuminemia based on BMI range may prove beneficial.

BACKGROUND: Patients with paradoxical low-flow, low-gradient severe aortic stenosis exhibit low transvalvular flow rate (Q), while maintaining preserved left ventricular ejection fraction. Severe mitral regurgitation (MR) also causes a low-flow state, adding complexity to diagnosis and management. This study aimed to examine the impact of severe MR on outcomes in paradoxical low-flow, low-gradient severe aortic stenosis. METHODS: Data from an institutional echo database identified 1189 patients with adjudicated severe aortic stenosis (aortic valve area ≤1.0 cm ² ), low transaortic gradients (mean gradient <40 mm Hg), preserved left ventricular ejection fraction (≥50%), and low-flow rate (Q ≤210 mL/s) to confirm paradoxical low-flow, low-gradient severe aortic stenosis. Subgroups were based on MR severity (severe and non-severe). Clinical outcomes included all-cause mortality, aortic valve replacement, heart failure hospitalizations, and a composite outcome. RESULTS: In the severe MR group (n=80), patients had lower flow rates, increased left ventricular dimensions, and a more eccentric hypertrophy pattern compared with non-severe MR (n=1109). Over a follow-up of up to 5 years, severe MR correlated with higher all-cause mortality ( P =0.02) and aortic valve replacement rates ( P =0.012). After multivariable adjustment, severe MR was independently associated with increased all-cause mortality risk (hazard ratio=1.43; P =0.011) and composite outcome (hazard ratio=1.64; P <0.001). Aortic valve replacement significantly reduced mortality at every MR degree, with the most substantial impact in severe MR (hazard ratio=0.18; P <0.001). Propensity-adjusted models demonstrated a stronger aortic valve replacement impact with increasing MR degree ( P _interaction =0.044). CONCLUSIONS: Severe MR in paradoxical low-flow, low-gradient severe aortic stenosis is associated with adverse outcomes and distinctive left ventricular remodeling. Aortic valve replacement improves survival across all MR grades, with greater impact in severe MR.

Altered platelet function contributes to the prothrombotic state in type 2 diabetes mellitus (DM), potentially influencing long-term cardiovascular risk. Mean platelet volume (MPV), a readily available marker of platelet size and activity, has been linked to adverse cardiovascular outcomes, yet its prognostic value in DM is less defined. This study evaluated the association between MPV and the composite MPV × platelet count (MPV × PLT) with long-term cardiovascular outcomes in patients with DM without prior myocardial infarction (MI) or stroke. This retrospective cohort study used anonymized data from 88,710 patients with DM and no prior history of MI or stroke. Patients were classified into three equal-sized groups based on MPV and MPV*PLT values, with additional analysis of the lowest and highest 5 % of values. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, MI, and stroke. During a median follow-up of 8.9 years, a total of 8,828 (10.0 %) MACCE events occurred. MACCE rates were highest in the lowest (13.1 %) and highest (10.0 %) MPV groups (p < 0.001). Both low and high MPV × PLT values were independently associated with greater MACCE risk versus the middle group (adjusted hazard ratio 1.22, 95 % CI 1.11-1.33; and hazard ratio 1.47, 95 % CI 1.33-1.63; both p < 0.001). Extreme MPV and MPV × PLT values were independently associated with adverse long-term cardiovascular outcomes in patients with DM. These findings suggest that MPV and MPV × PLT may serve as cost-effective, readily available biomarkers for improving cardiovascular risk stratification in this high-risk population.

Atrial fibrillation (AF) is linked to adverse left atrial (LA) remodeling, including fibrosis and mechanical dysfunction. LA strain is an imaging marker of atrial function that may improve risk stratification for AF, but its predictive and prognostic value in the primary care population remains unclear. This study aimed to evaluate whether LA strain is associated with new-onset AF and adverse clinical outcomes after AF diagnosis. We performed a 2-part study within a longitudinal primary care cohort (2001-2019). In a nested case-control analysis, 216 patients with new-onset AF were compared with 216 age- and sex-matched controls. LA strain parameters, including peak atrial longitudinal strain (PALS), peak atrial contractile strain, and LA conduit strain (LACS), were measured using speckle-tracking echocardiography before AF onset. In 127 patients with new-onset AF, Cox models examined associations between LA strain and all-cause mortality, stroke, myocardial infarction, and heart failure hospitalization. Lower PALS and LACS were independently associated with more than 3-fold higher odds of AF (both P < .001). Addition of strain measures to the LA volume index improved discrimination (area under the curve 0.66-0.73 for PALS; 0.72 for LACS). Over 4.6 years of follow-up, lower PALS remained independently associated with all-cause mortality (HR 2.70; P = .02) and the composite outcome (HR 2.31; P = .02). In a primary care cohort, impaired LA strain was independently associated with new-onset AF and adverse outcomes after AF diagnosis, supporting its role in AF risk stratification.

Background: Patients with paradoxical low-flow, low-gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rate (Q), while maintaining preserved left ventricular ejection fraction (LVEF). Concomitant severe mitral regurgitation (MR) contributes to the low flow state, adding complexity to diagnosis and management. This study aimed to examine the impact of severe MR on outcomes in paradoxical LFLGAS. Methods: Data from an institutional echo database identified 1,189 patients with adjudicated severe aortic stenosis (AVA≤1.0 cm ² ), low transaortic gradients (mean gradient<40 mmHg), preserved LVEF (≥50%), and low flow rate (Q≤210 ml/sec), to confirm paradoxical LFLGAS. Subgroups were based on MR severity (severe and non-severe). Clinical outcomes included all-cause mortality, aortic valve replacement (AVR), heart failure hospitalizations, and a composite outcome. Results: In the severe MR group (n=80), patients had lower flow rates, increased LV dimensions and a more eccentric hypertrophy pattern compared to non-severe MR (n=1,109). Over a median 5-year follow-up, severe MR correlated with higher all-cause mortality (p=0.02) and AVR rates (p=0.012). After adjustment, severe MR was independently associated with increased all-cause mortality risk (HR=1.43, p=0.011) and composite outcome (HR=1.64, p<0.001). AVR significantly reduced mortality at every MR degree, with the most substantial impact in severe MR (HR=0.18, p<0.001). Propensity-adjusted models demonstrated a stronger AVR impact with increasing MR degree (p-for-interaction=0.044). Conclusions: Severe MR in paradoxical LFLGAS is associated with adverse outcomes and distinctive LV remodeling. Aortic valve replacement improves survival across all MR grades, with greater impact in severe MR.