Citations

Lipoprotein (a) is a complex lipid molecule that has sparked immense interest in recent years, after studies demonstrated its significant association with several cardiovascular conditions. Lp(a) promotes cardiovascular disease through its combined proatherogenic, pro-inflammatory, and prothrombotic effects. While the measurement of Lp(a) has become widely available, effective methods to reduce its concentration are currently limited. However, emerging data from ongoing clinical trials involving antisense oligonucleotides have indicated promising outcomes in effectively reducing Lp(a) concentrations. This may serve as a potential therapeutic target in the management and prevention of myocardial infarction, calcific aortic stenosis, and cerebrovascular accidents. In contrast, the role of Lp(a) in atrial fibrillation, in-stent restenosis, cardiac allograft vasculopathy, and bioprosthetic aortic valve degeneration remains unclear. This review article aims to thoroughly review the existing literature and provide an updated overview of the evidence surrounding the association of Lp(a) and these cardiovascular diseases. We seek to highlight controversies in the existing literature and offer directions for future investigations to better understand Lp(a)’s precise role in these conditions, while providing a summary of its unique molecular characteristics.

AbstractBackgroundDevelopment of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.MethodsThis is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.ResultsA total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%.ConclusionBrain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. image

AbstractBackgroundCytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher‐risk situations.MethodsA comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta‐analysis used the random‐effects model. The study protocol is registered in PROSPERO (no. CRD42022357028).ResultsSix retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta‐analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79–2.63). Heterogeneity between the studies was low (I2 = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07–0.54) but not graft loss (OR 0.67, 0.17–2.63). There was no significant difference in CMV relapse among kidney‐specific SOTR (OR 1.38, 95% CI 0.65–2.96).ConclusionEvidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective‐controlled trials, the decision about SP should depend on individualized risk‐profile assessments by experienced clinicians. image

Background: Surgical repair of full thickness biceps tears has demonstrated adequate outcomes in short and mid-term studies. However, data on the long-term outcomes of full thickness distal biceps injuries and their treatment are currently lacking. Purpose/Hypothesis: The purpose of this study was to report on patient demographics, injury characteristics, and long-term outcomes for patients with full-thickness distal biceps tears. It was hypothesized that complete distal biceps tears managed operatively would demonstrate robust clinical success at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with magnetic resonance imaging–confirmed, complete distal biceps tendon rupture sustained between 1996 and 2016 were identified. Patients were cross-referenced with a regional geographic database. Results: A total of 66 patients (3 female, 63 male) with a median age of 50.8 years (IQR, 41.5-60.4) and a median clinical follow-up of 14.7 years (IQR, 9.6-17.9 years) were included. Patients who sustained a full-thickness distal biceps tendon tear were likely to be in their early 50s, male, right-hand dominant, current/former smokers, and laborers with a history of traumatic injury during an intentional movement. Most of these patients had pain and supination weakness but no loss of range of motion. All included tears were treated operatively. At final follow-up, patients maintained a majority of near-normal range of motion (median total arc of flexion/extension 140° and supination/pronation 80°), excellent elbow flexion strength (91% of patients had full strength), and adequate elbow supination strength (76% of patients had full strength). The overall complication rate was 24%, with 16 out of 66 patients experiencing some type of complication between infection, rerupture, heterotopic ossification, reoperation, and nerve complications. Overall return to work was 98%, and 85% of those who returned to work did so without restrictions. Conclusion: Complete tears of the distal biceps were most common in patients 50 years of age, male sex, right-hand dominant, and current/former smokers. The most common profession was laborer, and injuries were primarily traumatic in nature during intentional activity. Patients managed operatively demonstrated high rates of success at long-term follow-up with respect to elbow function and clinical outcomes.

Abstract Aims Although the neuroanatomical distribution of tau and amyloid‐β is well studied in Alzheimer's disease (AD) (non)‐amnestic clinical variants, that of neuroinflammation remains unexplored. We investigate the neuroanatomical distribution of activated myeloid cells, astrocytes, and complement alongside amyloid‐β and phosphorylated tau in a clinically well‐defined prospectively collected AD cohort. Methods Clinical variants were diagnosed antemortem, and brain tissue was collected post‐mortem. Typical AD ( n = 10), behavioural/dysexecutive AD ( n = 6), posterior cortical atrophy (PCA) AD ( n = 3), and controls ( n = 10) were neuropathologically assessed for AD neuropathology, concurrent pathology including Lewy body disease, limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC), and vascular pathology. For quantitative assessment, we analysed the corticolimbic distribution of phosphorylated tau, amyloid‐β, CD68, MHC‐II, C4b, and glial fibrillary acidic protein (GFAP) using digital pathology. Results Phosphorylated tau was distinctly distributed in each variant. In all variants, amyloid‐β was neocortical‐dominant, with a notable increase in the middle frontal cortex of behavioural/dysexecutive AD. Typical AD and PCA AD had no concurrent Lewy body disease, whereas three out of six cases with behavioural/dysexecutive AD did. LATE‐NC stage >0 was observed in three AD cases, two typical AD (stage 1/3), and one behavioural/dysexecutive AD (stage 2/3). Vascular pathology was present in each variant. In typical AD, CD68 and MHC‐II were hippocampal‐dominant. In behavioural/dysexecutive AD, C4b was elevated in the middle frontal and inferior parietal cortex. In PCA AD, MHC‐II was increased in the fusiform gyrus, and GFAP in parietal cortices. Correlations between AD neuropathology and neuroinflammation were distinct within variants. Conclusions Our data suggests that different involvement of neuroinflammation may add to clinical heterogeneity in AD, which has implications for neuroinflammation‐based biomarkers and future therapeutics.

ObjectiveWe aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE‐specialized care.MethodsWe included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE‐specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays.ResultsThe study included 373 patients with SLE. The median time to access SLE‐specialized care was 1.1 (95% confidence interval [CI] 0.9–1.5) months, time to diagnosis was 30.6 (95% CI 18.9–48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9–8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE‐related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03–2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46–14.88) were associated with delays. Delays were associated with damage at first access to SLE‐specialized care (SDI ≥1; 30% vs 7%, P < 0.001).ConclusionPatients follow a heterogeneous pathway to receive care. One‐fourth of patients experienced delays accessing SLE‐specialized care, which was associated with disease‐related damage. Fewer manifestations, hematologic manifestations, or antiphospholipid antibodies were associated with delays.image

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common heart disorder characterized by the thickening of the heart muscle, particularly in the left ventricle, which increases the risk of cardiac complications. This study aims to analyze the expression of apoptosis-regulating genes (CASP8, CASP9, CASP3, BAX, and BCL2) in blood samples from HCM patients, to better understand their potential as biomarkers for disease progression. Methods: Quantitative real-time PCR (qPCR) was used to evaluate gene expression in blood samples from 93 HCM patients. The correlation between apoptosis-regulating genes was conducted and clinical parameters were integrated for feature importance and clustering analysis. Results: Most patients exhibited significant downregulation of CASP8, CASP9, and CASP3. In contrast, BAX expression was elevated in 71 out of 93 patients, while BCL2 was increased in 55 out of 93 patients. Correlation analysis revealed weak negative correlations between the BAX/BCL2 ratio and CASP gene expression. Conclusions: These findings suggest that reduced expression of apoptotic genes may indicate a protective cellular mechanism, which could serve as a biomarker for disease progression. Further studies are needed to investigate the potential for therapeutic modulation of these pathways to improve patient outcomes.

AbstractBackgroundThe clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS).MethodsPatients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis.ResultsOut of 2′938 patients, 222 (7.6%) patients died during 1‐year follow‐up. A more than 28.8‐fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18–2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5‐year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21–2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22–2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17–1.89, p =.001).ConclusionThis study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow‐up.