Elevated Lipoprotein(a) Levels: A Crucial Determinant of Cardiovascular Disease Risk and Target for Emerging Therapies.

Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20% of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients.

Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?

PURPOSE OF REVIEW: What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials. RECENT FINDINGS: Multiple long-term cardiovascular (CV) intervention trials have examined the effect of specific target-directed therapies on the MACE endpoint. Only one prospective study, STENO-2, has employed a multifactorial intervention comparing intensified versus conventional treatment of modifiable risk factors in T2D patients, and demonstrated a 20% absolute CV risk reduction. If the absolute CV risk reduction in these trials is added to that in the only prospective multifactorial intervention trial (STENO-2), the unexplained CV risk is 44.1%. What are the clinical implications? Potential explanations for the unaccounted-for reduction in absolute CV risk in type 2 diabetes (T2D) patients are discussed. HYPOTHESIS: failure to take into account synergistic interactions between major cardiovascular risk factors is responsible for the unexplained CV risk in T2D patients. Simultaneous treatment of all major CV risk factors to recommended AHA/ADA guideline goals is required to achieve the maximum reduction in CV risk.

Impact Of body Mass Index on Cardiopulmonary Outcomes of COVID-19 Hospitalizations Complicated by Severe Sepsis.

Background: Body Mass Index (BMI) has a significant impact on Coronavirus disease (COVID-19) patient outcomes; however, major adverse cardiac and cerebrovascular outcomes in patients with severe sepsis have been poorly understood. Our study aims to explore and provide insight into its association. Methods: This is an observational study looking at the impact of BMI on COVID-19-severe sepsis hospitalizations. The primary outcomes are adjusted odds of all-cause in-hospital mortality, respiratory failure, and major adverse cardiac and cerebrovascular events (MACCE), which include acute myocardial infarction, cardiac arrest, and acute ischemic stroke. The secondary outcome was healthcare resource utilization. Coexisting comorbidities and patient features were adjusted with multivariable regression analyses. Results: Of 51,740 patients with severe COVID-19-sepsis admissions, 11.4% were overweight, 24.8% had Class I obesity (BMI 30-34.9), 19.8% had Class II obesity (BMI 35-39.9), and 43.9% had the categorization of Class III obesity (BMI >40) cohorts with age>18 years. The odds of MACCE in patients with class II obesity and class III obesity (OR 1.09 and 1.54; 95CI 0.93-1.29 and 1.33-1.79) were significantly higher than in overweight (p < 0.001). Class I, Class II, and Class III patients with obesity revealed lower odds of respiratory failure compared to overweight (OR 0.89, 0.82, and 0.82; 95CI 0.75-1.05, 0.69-0.97, and 0.70-0.97), but failed to achieve statistical significance (p = 0.079). On multivariable regression analysis, all-cause in-hospital mortality revealed significantly higher odds in patients with Class III obesity, Class II, and Class I (OR 1.56, 1.17, and 1.06; 95CI 1.34-1.81, 0.99-1.38, and 0.91-1.24) vs. overweight patients (p < 0.001). Conclusions: Patients with Class II and Class III obesity had significantly higher odds of MACCE and in-hospital mortality in COVID-19-severe sepsis admissions.

COVID-19-associated familial acute disseminated encephalomyelitis (ADEM): A case report.

BACKGROUND: Several neurological complications are being reported in hospitalized patients with severe COVID-19 infection. This is presumed due to direct spread of infection or due to immunological response. Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory and demyelinating disorder of the central nervous system that is often preceded by infection or vaccination. Very few cases of ADEM have been reported in the literature that are associated with COVID-19 infection. CASE REPORT: Here we demonstrate familial cases of ADEM in a hospitalized father and son, who presented to the emergency department with fever and shortness of breath, later diagnosed with COVID-19, and subsequently requiring mechanical ventilation. Both patients developed neurological symptoms with upper motor neuron involvement at approximately day 30 of admission. MRI of the brain demonstrated bilateral multifocal periventricular white matter FLAIR signal hyperintensities consistent with ADEM. The patients were treated with medium dose IV methylprednisolone with variable outcomes. The 49-year-old son developed severe residual neurological deficits with encephalomalacic changes on MRI which required extensive rehabilitation; meanwhile, the 68-year-old father predominantly had pulmonary sequelae including fibrosis and the development of a pneumatocele, but he had a better neurological outcome. CONCLUSION: To our knowledge, this is the first reported case report of ADEM involving father and son in severe COVID-19 infection. Final neurological outcomes in these patients appeared to be in line with the severity of COVID-19 infection. More research is needed to better understand the management of ADEM in patients with severe COVID-19 infection.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

Usefulness of Timed Up and Go (TUG) Test for Prediction of Adverse Outcomes in Patients Undergoing Thoracolumbar Spine Surgery.

BACKGROUND: Spine surgery rates have increased and the high postoperative morbidity in these patients result in increased costs. Consequently, it is essential to identify patients at risk of adverse outcomes. OBJECTIVE: To assess whether preoperative Timed Up and Go (TUG) test performance can predict high-grade postoperative complications. METHODS: A prospective cohort study of patients undergoing elective thoracolumbar spine surgery in a tertiary care hospital between 2017 and 2018. Patients were assessed preoperatively and assigned to the slow-TUG group if unable to perform or test performance time was ≥18.4 s. Primary outcome: high-grade postoperative complications. Secondary outcomes: overall complications, length of stay (LOS), discharge to healthcare facility, readmission and emergency department (ED) presentation. Patients were followed-up until 6 wk after surgery. RESULTS: One hundred three patients (mean age 62.95 ± 10.97 yr) were enrolled. Slow-TUG group were more likely to be classified as American Society of Anaesthesiology (ASA) class 3 (74.1% vs 47.4%, P = .02), non-independent (25.9% vs 5.3%, P < .01), and frail (92.3% vs 42.1%, P < .01). TUG was an independent predictor of high-grade complications (adjusted odds ratio (OR): 4.97, 95% CI: 1.18-22.47), overall complications (OR: 3.77, 95% CI: 1.33-11.81), discharge to a skilled-nursing facility (OR: 3.2, 95% CI: 1.00-10.70), readmission within 6 wk of surgery (OR: 9.14, 95% CI: 2.39-41.26) and LOS (adjusted incident rate ratio (IRR): 1.45, 95% CI: 1.16-1.80). CONCLUSION: Compared to traditional risk factors, TUG is an important predictor of adverse postoperative outcomes and may be used preoperatively to identify high-risk thoracolumbar surgery patients.

A novel technique of endoscopic submucosal dissection for circumferential ileocecal valve adenomas with terminal ileum involvement: the "doughnut resection" (with videos).

BACKGROUND: Ileocecal valve (ICV) lesions are difficult to resect endoscopically and patients are often referred for laparoscopic colectomy. ICV involvement has been shown to be related to technical failure and tumor recurrence after endoscopic mucosal resection (EMR) and represents a challenge for endoscopic submucosal dissection (ESD). Few publications have focused specifically on endoscopic management of ICV lesions. METHODS: We developed a novel ESD technique, the "doughnut resection," for circumferential ICV adenomas with terminal ileum involvement. Two circumferential mucosal incisions are performed, one in the ileum and the other in the cecum, followed by submucosal dissection of the disk of tissue between the two incisions around a guiding stent placed across the valve that helps guide the dissection as it crosses the valve orifice. The lesion is removed en bloc in the shape of a "doughnut" with two concentric assessable lateral margins. The underwater ESD technique and a gastroscope were used to facilitate the resection. RESULTS: Seven patients received the doughnut resection. The median patient age was 67 years. All patients had prior biopsy and three had prior endoscopic resection (1-6 times). The median specimen diameter was 4.5 cm (range 3-8). All resections were en bloc and R0. There was no perforation, delayed bleeding, or other clinically significant adverse events. After a median follow-up of 21 months (range 12-32), there was no tumor recurrence. CONCLUSION: The "doughnut resection" is a feasible, safe, and effective method to remove circumferential ICV lesions endoscopically even for patients with multiple prior tumor manipulations.