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Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular diseases (CVDs), as reported by multiple Mendelian randomization studies and large epidemiological studies. When elevated Lp(a) is combined with other risk factors, most notably elevated low-density lipoprotein cholesterol (LDL-C), a synergistic atherogenic effect has been reported. However, the current literature is conflicting regarding how Lp(a) interacts in the context of controlled LDL-C levels (e.g., <70 mg/dL) and whether reducing LDL-C can modify the atherogenic effect of Lp(a). In some studies, elevated Lp(a) was still significantly associated with a higher risk of cardiovascular events, despite controlled levels of LDL-C. In contrast, multiple studies have reported attenuation of the cardiovascular risk mediated by elevated Lp(a) with lower LDL-C levels. Moreover, the relationship between Lp(a) and triglycerides, high-density lipoprotein, and very low-density lipoprotein remains unclear. In this literature review, we summarize and discuss the current evidence regarding the interactions between Lp(a) and other lipid molecules, how they contribute to the pathogenesis of CVD, and future perspectives, particularly in the current era where promising targeted Lp(a)-lowering therapies are under development.

ABSTRACTBackground and AimsChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is difficult to distinguish from mimicking disorders, with misdiagnosis resulting in IVIG overutilization. We evaluate a clinical‐electrophysiological model to facilitate CIDP versus mimic neuropathy prediction.MethodsUsing the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 CIDP guidelines we derived 26 clinical and 144 nerve conduction variables. The model was generated and validated utilizing total CIDP (n = 129) and mimics (n = 309); including (1) IgG4‐nodopathies; (2) POEMS (polyneuropathy–organomegaly–endocrinopathy–monoclonal protein‐skin changes); (3) anti‐myelin‐associated‐glycoprotein; (4) paraneoplastic; (5) Waldenström B‐cell lymphoma; (6) diabetic neuropathies; (7) amyloidosis; (8) Charcot–Marie–Tooth; (9) motor neuropathies/neuronopathies; and (10) idiopathic‐inflammatory‐myopathies.ResultsWe analyzed 9282 clinical and 51 408 electrophysiological data points. Univariate analysis identified 11 of 26 clinical variables with significant odds ratios. A multivariate regression model using four clinical and two electrophysiologic variables achieved 93% area‐under‐curve (95% CI 91–95): progression over 8 weeks (OR 40.66, 95% CI 5.31–311.36), absent autonomic involvement (OR 17.82, 95% CI 2.93–108.24), absent muscle atrophy (OR 16.65, 95% CI 3.27–84.73), proximal weakness (OR 3.63, 95% CI 1.58–8.33), ulnar motor conduction velocity slowing < 35.7 m/s (OR 5.21, 95% CI 2.13–12.76), and ulnar motor conduction block (OR 13.37, 95% CI 2.47–72.40). A web‐based probability calculator (https://news.mayocliniclabs.com/cidp‐calculator/) was developed, with 100% sensitivity and 68% specificity at a 92% probability threshold. Specificity improved to 93% when considering “red flags,” electrophysiologic criteria, and laboratory testing.InterpretationA probability calculator using clinical electrophysiological variables assists CIDP differentiation from mimics, with scores below 92% unlikely to have CIDP. The highest specificity is achieved by considering clinical “red flags,” electrophysiologic demyelination, and laboratory testing.

Background: Pulmonary hypertension (PH) is a complex condition associated with significant morbidity and mortality. Traditional diagnostic and management approaches for PH often face limitations, leading to delays in diagnosis and potentially suboptimal treatment outcomes. Artificial intelligence (AI), encompassing machine learning (ML) and deep learning (DL) offers a transformative approach to PH care. Materials and Methods: We systematically searched PubMed, Scopus, and Web of Science for original studies on AI applications in PH, using predefined keywords. Out of more than 500 initial articles, 45 relevant studies were selected. Risk of bias was evaluated using PROBAST (Prediction model Risk of Bias Assessment Tool). Results: This review examines the potential applications of AI in PH, focusing on its role in enhancing diagnosis, disease classification, and prognostication. We discuss how AI-powered analysis of medical data can improve the accuracy and efficiency of detecting PH. Furthermore, we explore the potential of AI in risk stratification, leading to treatment optimization for PH. Conclusions: While acknowledging the existing challenges and limitations and the need for continued exploration and refinement of AI-driven tools, this review highlights the significant promise of AI in revolutionizing PH management to improve patient outcomes.

Summary Metabolic and bariatric surgeries (MBS), including Roux‐en‐Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), have proven effective in promoting long‐term diabetes remission among patients with type‐2 diabetes (T2D). In this multicentre retrospective cohort study, we investigated the effectiveness of RYGB and SG in achieving diabetes remission, specifically among patients with T2D and vascular complications, while accounting for similar baseline diabetes severity. Although various scores predict diabetes remission after bariatric surgery, they do not consider diabetes‐related vascular complications, which can influence outcomes even in patients with similar baseline T2D severity. We collected preoperative data on microvascular (retinopathy, nephropathy, neuropathy) and macrovascular comorbidities (coronary artery disease, cerebrovascular accidents, peripheral artery disease) to compare the efficacy of RYGB and SG. Among 961 patients analysed, those with vascular complications showed higher remission rates with RYGB (OR: 1.97) compared to SG, despite similar baseline diabetes severity. Notably, RYGB patients with microvascular complications had a significant advantage in achieving T2D remission (OR: 2.95). However, no significant differences in remission were observed in patients with macrovascular complications. These findings suggest that RYGB may be more effective than SG in specific patient populations, particularly those with microvascular complications, emphasizing the need for personalized treatment strategies.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (&lt;75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P &lt; 0.0001) and longer time to plateau (8.9 versus 3.5 months; P &lt; 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P &lt; 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P &lt; 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P &lt; 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.

SummaryGlobal obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus‐based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two‐round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence‐based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.

Introduction The International Prognostic Scoring System (IPSS) and its revised version (IPSS-R) were developed using datasets from patients (pts) with untreated MDS. The cytogenetic risk groups used in IPSS-R were expanded to 5 groups from the 3 used in IPSS. Among the new groups introduced in IPSS-R is the “very complex” karyotype (VCK) where ≥4 karyotypic abnormalities are seen compared to “complex karyotype (CK)” with only 3 abnormalities. However, the prognostic impact of VCK vs CK, as well as individual cytogenetic abnormalities and TP53 mutation (TP53mut) status within the CK and VCK subgroups in pts with MDS treated with hypomethylating agents (HMAs) has not been well studied. Hence, we analyzed these questions in a large cohort of HMA-treated MDS pts in the icMDS VALIDATE database. Methods The icMDS VALIDATE database contains MDS pts treated with frontline HMA monotherapy or HMA-based combinations from 22 specialized international centers. Pts with unknown HMA type, date of HMA initiation, missing age, missing sex, missing cytogenetic data, bone marrow or peripheral blood blasts ≥20%, or missing survival status were excluded. We performed time-to-event analyses using the Kaplan-Meier method and compared groups by the log-rank test. We measured overall survival (OS) from time of HMA initiation. VALIDATE protocol was exempted, acknowledged, or approved by all centers' IRBs. VALIDATE is supported by an independent grant from Abbvie. Results A total of 1940 pts were included. Median age was 70 (range: 18-99) years and 66% were men. According to IPSS-R cytogenetic risk groups, 1.9% (37) were very good, 43.4% (841) good, 15.5% (301) intermediate, 11.6% (226) poor, and 27.6% (535) very poor. By HMA type, 71% of pts were treated with azacitidine, 14% with decitabine, 6% with HMA and venetoclax, and 9% with another HMA combination. Approximately 28% of pts underwent allogeneic hematopoietic stem cell transplant (alloHSCT). The IPSS-R cytogenetic risk groups had different OS (p&lt;0.001)with median OS (mOS; months [mo], 95% CI) as follows: very good (43.4, 34.7-72.5), good (41.7, 36.4-46.8), intermediate (24.5, 23.1-32.4), poor (24.2, 19.2-28.5), and very poor (13.6, 12.5-14.5). The difference remained significant (p=0.001) after censoring at time of alloHSCT with mOS as follows: very good (40.4, 23.2-64.3), good (24.3, 22.2-26.3), intermediate (19.3, 15.1-22.2), poor (12.2, 10.3-14.8), and very poor (9.1, 8.2-19.7). Interestingly, the difference between mOS for intermediate and poor risk cytogenetics became more apparent after censoring at time of alloHSCT. Next, we compared the outcomes of pts with CK and VCK to non-complex karyotype (NCK) MDS. The mOS for pts with VCK MDS (13.6 mo, 12.5-14.5) was worse compared to pts with CK (19.9 mo, 19.9-16.8; p=0.004) and NCK (36.1 mo, 32.7-37.8; p&lt;0.001) MDS. Among the 1458 pts with available molecular data, more pts with VCK (75%, 330) MDS had a concurrent TP53mut compared to pts with CK (40%, 21; p&lt;0.001) and NCK (7%, 64 p&lt;0.001) MDS. Considering only patients with TP53mut MDS, mOS for pts with VCK (12.2, 11.1-13.9) was worse compared with NCK (24.2, 16-1-53.1; p&lt;0.001) but not with CK (19.9, 9.5-NR; p=0.9); the difference between CK and NCK was not significant (p=0.16). Among pts with TP53 wildtype (TP53WT) MDS, VCK (15.0, 13.2-18.2) had a similar mOS to TP53WT CK (18.8, 12.6-41.1; p=0.19) while both groups had worse mOS compared to TP53WT NCK (33.4, 30.1-37.0) (p=0.01). In a survival analysis of 616 pts with MDS with ≥3 cytogenetic abnormalities, -17/del(17p) (12.8 mo; p=0.009), inv(3)/t(3q)/del(3q) (10.9 mo; p=0.006), and del(7q) (12.1mo; p=0.024), though not -7 (12.6mo; p=0.23), were associated with lower mOS compared to the pts with MDS without these abnormalities (14.3mo). Conclusions Using one of the largest databases of HMA-treated MDS pts, we show that IPSS-R cytogenetic risk categories associate with significantly different survivals among HMA-treated MDS pts, even after censoring at time of alloHSCT. Importantly, VCK MDS was associated with worse mOS compared to CK and NCK MDS but not in pts with a concurrent TP53mut. Among pts with MDS with ≥3 chromosomal abnormalities, having -17/del(17p), inv(3)/t(3q)/del(3q), or del(7q) was associated with worse survival.

Introduction: Response assessment is used to evaluate effectiveness of hypomethylating agent (HMA)-based therapy in myelodysplastic syndromes/neoplasms (MDS) in clinical practice and trials. Recently, the clinical response criteria (IWG 2023) and the clinical-molecular risk assessment (IPSS-M) in MDS were published. However, it remains unknown whether the IWG 2023 response criteria have an independent impact on overall survival (OS) when adjusting for baseline IPSS-M risk. Additionally, the association of IWG 2023 response criteria with OS in patients (pts) undergoing allogeneic stem cell transplantation (allo-HCT) versus those who do not is unknown. Lastly, it is unclear if optimal time-to-transplant impacts OS in MDS pts who achieve a IWG 2023 defined remission with HMA therapy. We examined these questions in a large population of MDS pts within the multi-institutional international consortium for MDS (icMDS) VALIDATE database. Methods: High-risk MDS pts with IPSS ≥1.5 or IPSS-R &gt;3.5 treated with HMA-based therapy were included in the study. Baseline IPSS-M risk was stratified into very low/low/moderate low (VL+L+ML), moderate-high/high (MH+H), and very high (VH). Response to treatment was evaluated using the IWG 2023 criteria and grouped into: composite complete response (cCR) and no cCR. cCR included: complete response (CR), CR equivalent (CRequ), CR bilineage (CRbi), CR unilineage (CRuni), and CR with partial hematologic recovery (CRh). We analyzed the differential impact of achieving cCR on HMA-based therapy prior to transplant on OS in pts who either did or did not undergo allo-HCT, while adjusting for their baseline IPSS-M risk in Cox regression analysis. Optimal time-to-transplant was determined based on age and IPSS-M category as described by Tentori et al. (JCO 2024). Pts proceeding to allo-HCT were stratified on whether they underwent transplant within the optimal time-to-transplant timeframe after MDS diagnosis or not. VALIDATE protocol was exempted, acknowledged, or approved by all centers' IRBs. VALIDATE is supported by an independent grant from AbbVie. Results: We analyzed 762 MDS pts. The median age at MDS diagnosis was 68 years (range: 19-95 years) and 64% of pts were male. Distribution of the baseline IPSS-M risk was: VL+L+ML in 110 (14%) pts, MH+H in 347 (46%) pts, VH in 305 (40%) pts. Pts received azacitidine monotherapy, decitabine monotherapy, and HMA-based combination therapy (e.g. HMA + venetoclax) in 52%, 21%, and 28% of cases, respectively. A total of 282/762 (37%) pts achieved cCR as their best response to HMA-based therapy. The median OS for all pts was 18.7 months (95% CI: 16.6-21.3 months). Pts who did not undergo allo-HCT (n=436, 57%) had an improved median OS if they achieved cCR when compared to pts in the no cCR group in all IPSS-M risk groups (VL+L+ML: 23.5 months vs. 10.7 months; MH+H: 20.8 months vs. 11.6 months; VH: 13.8 months vs. 7.5 months). Cox analysis demonstrated an independent effect of cCR on OS in these pts when adjusted for baseline IPSS-M risk (cCR vs. no cCR: HR 0.60, 95% CI 0.48-0.76, p&lt;0.001). In contrast, in pts who subsequently received an allo-HCT (n=326, 43%), achieving cCR with HMA prior to allo-HCT did not provide an additional OS benefit, when adjusted for baseline IPSS-M risk (cCR vs. no cCR: HR 1.00, 95% CI 0.73-1.38, p=0.986). The median time-to-transplant was 6.7 months and 34% of transplanted MDS pts received their allo-HCT during the optimal timeframe. Among pts who achieved cCR with HMA-based therapy prior to allo-HCT, optimal time-to-transplant was associated with significantly improved OS (optimal vs. non-optimal timing: HR 0.55; p=0.033). Conclusion: Baseline IPSS-M risk and allo-HCT had an independent impact on OS, while IWG 2023 defined cCR had an independent effect on OS only in non-transplanted MDS pts. While this retrospective analysis occurred at large academic centers with specific expertise in the management of MDS, our data may have an impact on clinical practice: (i) failure to achieve cCR on HMA therapy prior to transplant should not impact the decision to proceed to allo-HCT, (ii) upfront allo-HCT without prior HMA therapy might also be an option if the clinical situation and availability of donors allow, and (iii) allo-HCT should ideally be performed during the timeframe that is considered optimal as defined by pt age and baseline IPSS-M.

Bioprosthetic aortic valve degeneration (BAVD) is a significant clinical concern following both transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). The increasing use of bioprosthetic valves in aortic valve replacement in younger patients and the subsequent rise in cases of BAVD are acknowledged in this review which aims to provide a comprehensive overview of the incidence, diagnosis, predictors, and management of BAVD. Based on a thorough review of the existing literature, this article provides an updated overview of the biological mechanisms underlying valve degeneration, including calcification, structural deterioration, and inflammatory processes and addresses the various risk factors contributing to BAVD, such as patient demographics, comorbidities, and procedural variables. The difficulties in early detection and accurate diagnosis of BAVD are discussed with an emphasis on the need for improved imaging techniques. The incidence and progression of BAVD in patients undergoing TAVR versus SAVR are compared, providing insights into the differences and similarities between the two procedures and procedural impacts on valve longevity. The current strategies for managing BAVD, including re-intervention options of redo surgery and valve-in-valve TAVR, along with emerging treatments are discussed. The controversies in the existing literature are highlighted to offer directions for future investigations to enhance the understanding and management of BAVD.

Background Lipoprotein(a) [Lp(a)] is an independent, causal risk factor for cardiovascular disease. However, it is still unclear whether controlling low-density lipoprotein cholesterol (LDL-C) to optimal levels can attenuate cardiovascular risk mediated by elevated Lp(a), especially in the setting of secondary prevention. Methods Adult patients with a baseline Lp(a) measurement who underwent percutaneous coronary intervention (PCI) and reached their LDL-C target levels (<70 mg/dl) at Mayo Clinic sites between 2006 and 2017 were included. Primary outcomes included major adverse cardiovascular events (MACE) and all-cause mortality. Kaplan–Meier curves were created to compare the survival probabilities among patients with Lp(a) ≥ 50 mg/dl compared with Lp(a) < 50 mg/dl. Multivariable Cox regression analyses were performed to quantify the association of elevated Lp(a) with our relevant outcomes and to control for possible confounders. Results In total, 878 patients (median age: 68 years, and 74% males) who underwent PCI were included for analysis. Of them, 29.7% had elevated Lp(a) ≥ 50 mg/dl. Kaplan–Meier curves did not reveal any significant difference in survival probabilities for elevated Lp(a) for any outcome including MACE (P = 0.91), all-cause mortality (P = 0.26), or the separate MACE components. Similarly, the multivariable analysis showed no significant association for MACE (hazard ratio: 1.07, 95% confidence interval: 0.84–1.37) or all-cause mortality (hazard ratio: 0.98, 95% confidence interval: 0.74–1.30). Conclusion In patients who underwent PCI and have their LDL-C controlled below 70 mg/dl, no significant association was found between elevated Lp(a) ≥ 50 mg/dl and risk for MACE or all-cause mortality.