Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).

Assessing the Value of Imaging Data in Machine Learning Models to Predict Patient-Reported Outcome Measures in Knee Osteoarthritis Patients.

Knee osteoarthritis (OA) affects over 650 million patients worldwide. Total knee replacement is aimed at end-stage OA to relieve symptoms of pain, stiffness and reduced mobility. However, the role of imaging modalities in monitoring symptomatic disease progression remains unclear. This study aimed to compare machine learning (ML) models, with and without imaging features, in predicting the two-year Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for knee OA patients. We included 2408 patients from the Osteoarthritis Initiative (OAI) database, with 629 patients from the Multicenter Osteoarthritis Study (MOST) database. The clinical dataset included 18 clinical features, while the imaging dataset contained an additional 10 imaging features. Minimal Clinically Important Difference (MCID) was set to 24, reflecting meaningful physical impairment. Clinical and imaging dataset models produced similar area under curve (AUC) scores, highlighting low differences in performance AUC < 0.025). For both clinical and imaging datasets, Gradient Boosting Machine (GBM) models performed the best in the external validation, with a clinically acceptable AUC of 0.734 (95% CI 0.687-0.781) and 0.747 (95% CI 0.701-0.792), respectively. The five features identified included educational background, family history of osteoarthritis, co-morbidities, use of osteoporosis medications and previous knee procedures. This is the first study to demonstrate that ML models achieve comparable performance with and without imaging features.

Ablation Versus Antiarrhythmic Drugs as First-Line Therapy for Treatment-Naive Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Evidence on the relative safety and efficacy of atrial fibrillation catheter ablation and antiarrhythmic drugs (AADs) as the first-line therapy for patients with treatment-naive atrial fibrillation (AF) remains disputed. Digital databases were queried to identify relevant randomized controlled trials. The incidence of recurrent AF, major adverse cardiovascular events, and its components (all-cause death, nonfatal stroke, and bleeding) were compared using the DerSimonian and Laird method under the random-effects model to calculate pooled unadjusted risk ratio (RR) with 95% confidence intervals (CIs). A total of 6 randomized controlled trials consisting of 1,120 patients (574 ablation and 549 AADs) were included in the final analysis. Over a median follow-up of 1 year, the risk of any AF recurrence (RR 0.54, 95% CI 0.39 to 0.75) was significantly lower in patients receiving ablation than in patients receiving AADs. However, there was similar risk of major adverse cardiovascular events (RR 2.65, 95% CI 0.61 to 11.46), trial-defined composite end point of adverse events (RR 0.71, 95% CI 0.28 to 1.80), stroke (RR 2.42, 95% CI 0.22 to 26.51), all-cause mortality (RR 1.98, 95% CI 0.28 to 13.90), and procedure/medication failure (RR 2.65, 95% CI 0.61 to 11.46) with both therapies. In conclusion, in patients presenting with treatment-naive AF, ablation as a first-line therapy lowers the risk of AF recurrence with no associated increase in major adverse events, stroke, and mortality compared with AADs.

Arthroscopic management of large subchondral talar cyst: a novel treatment strategy.

Subchondroplasty is a novel and minimally invasive technique used to treat large subchondral talar cysts. It avoids soft tissue scarring, the need for osteotomies, bone grafting and its associated complications as seen with conventional approaches. Subchondroplasty involves arthroscopically approaching the cyst and injecting it with calcium phosphate paste injection, which undergoes an endothermic process and crystallizes in a manner that resembles cancellous bone to fill the defect. This case series presents two patients who underwent subchondroplasty: a 44-year-old female nurse with atraumatic right ankle pain of 2 years with a CT scan revealing a large subchondral cyst over the medial talar dome and a 55-year-old male chemical plant worker with left ankle pain following a biking accident 6 years ago whose CT scan too showed a large subchondral cyst in the medial talus. Both tolerated the surgery well, with significant reductions noted in MOXFQ scores at the 1-year follow-up.

Dipyridamole-induced STEMI: case report and review of the literature.

Dipyridamole nuclear myocardial perfusion imaging is a safe and useful modality for assessing myocardial ischemia. It is the modality of choice for cardiac risk stratification in patients who are unable to exercise. Intravenous dipyridamole causes coronary vasodilation and may result in heterogeneity of coronary blood flow in significant coronary artery disease. Ischemic electrocardiographic changes following pharmacological stress testing are less likely to occur compared with exercise stress tests. Ischemia is more likely to be present in the form of ST depression, with ST-segment elevation being exceedingly rare. We present the case of a 73-year-old patient who developed ST-segment elevation myocardial infarction following pharmacologic stress testing.

Polypill Therapy in Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials.

The effectiveness of polypill therapy in the prevention and treatment of cardiovascular disorders is still unclear. This meta-analysis aimed to assess the efficacy of polypill therapy in reducing cardiovascular risk factors. We conducted a systematic search of PubMed, Cochrane CENTRAL, SCOPUS, and Google Scholar for randomized controlled trials (RCTs) that evaluated polypill therapy for cardiovascular diseases, hypertension, or dyslipidemia. We included 18 RCTs with a total of 20,463 participants in our analysis. Pooled effect estimates were reported as Odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Polypill therapy was associated with a statistically significant reduction in systolic blood pressure (SBP) (OR: -0.33, 95% CI [-0.64, -0.03]; P-value = 0.03), diastolic blood pressure (DBP) (OR: -0.70, 95% CI [-1.20, -0.21]; P-value = 0.005), and total cholesterol level (OR: -1.25, 95% CI [-1.82, -0.68]; P-value < 0.0001). Polypill therapy also showed improved adherence (OR 2.18, 95% CI [1.47, 3.24]; P-value = 0.0001). However, there was no statistically significant benefit in the reduction of all-cause mortality, major cardiovascular events, and LDL-c levels. The use of polypill therapy is associated with a statistically significant reduction in SBP, DBP, and total cholesterol levels, as well as improved adherence. Further research is needed to determine its impact on hard clinical outcomes such as mortality and major cardiovascular events.

The impact of carbon and nitrogen catabolite repression in microorganisms.

Organisms have cellular machinery that is focused on optimum utilization of resources to maximize growth and survival depending on various environmental and developmental factors. Catabolite repression is a strategy utilized by various species of bacteria and fungi to accommodate changes in the environment such as the depletion of resources, or an abundance of less-favored nutrient sources. Catabolite repression allows for the rapid use of certain substrates like glucose over other carbon sources. Effective handling of carbon and nitrogen catabolite repression in microorganisms is crucial to outcompete others in nutrient limiting conditions. Investigations into genes and proteins linked to preferential uptake of different nutrients under various environmental conditions can aid in identifying regulatory mechanisms that are crucial for optimum growth and survival of microorganisms. The exact time and way bacteria and fungi switch their utilization of certain nutrients is of great interest for scientific, industrial, and clinical reasons. Catabolite repression is of great significance for industrial applications that rely on microorganisms for the generation of valuable bio-products. The impact catabolite repression has on virulence of pathogenic bacteria and fungi and disease progression in hosts makes it important area of interest in medical research for the prevention of diseases and developing new treatment strategies. Regulatory networks under catabolite repression exemplify the flexibility and the tremendous diversity that is found in microorganisms and provides an impetus for newer insights into these networks.

Comparison of the Hemodynamic Response to Intra-Aortic Balloon Counterpulsation in Patients With Cardiogenic Shock Resulting from Acute Myocardial Infarction Versus Acute Decompensated Heart Failure.

The intra-aortic balloon pump (IABP) neither benefits nor harms patients with acute myocardial infarction (AMI) with cardiogenic shock (CS) but may stabilize those with chronic heart failure who decompensate into CS. We sought to compare its hemodynamic effects in these 2 populations. We performed a retrospective analysis of the hemodynamic effects of IABP for AMI or acute decompensated heart failure (ADHF) patients with hemodynamic evidence of CS. The primary outcome was cardiac output (CO) change following insertion. In total, 205 patients were treated for CS resulting from AMI (73; 35.6%) or ADHF (132; 64.4%). At baseline, both cohorts had significant hemodynamic compromise with mean arterial pressure 75.6 ± 12.3 mm Hg, CO 3.02 ± 0.84 L/min, and cardiac power index 0.26 ± 0.06 W/m2; these parameters were nearly identical between groups though ADHF-CS patients had a higher pre-IABP mean pulmonary artery (PA) pressure than AMI-CS patients. After IABP insertion, ADHF-CS patients had moderate CO augmentation whereas AMI-CS experienced almost no improvement (0.58 ± 0.79 L/min vs 0.12 ± 1.00 L/min; p = 0.0009). Intracardiac filling pressures were reduced by similar amounts in both cohorts. Systemic vascular resistance was reduced in patients with ADHF-CS but not in those with AMI-CS. In conclusion, following IABP insertion, ADHF-CS patients experience roughly a 5-fold greater CO augmentation compared with AMI-CS patients. Pre-IABP PA pressure differences and differential systemic vascular resistance reduction may explain these results and shed light on recent evidence supporting IABP use in ADHF-CS and curbing it in AMI-CS.

Clinical and hemodynamic effects of intra-aortic balloon pump therapy in chronic heart failure patients with cardiogenic shock.

BACKGROUND: The role of the intra-aortic balloon pump (IABP) in acute decompensated heart failure (HF) with cardiogenic shock (CS) is largely undefined. In this study we sought to assess the hemodynamic and clinical response to IABP in chronic HF patients with CS and identify predictors of response to this device. METHODS: We retrospectively reviewed all patients undergoing IABP implantation from 2011 to 2016 at our institution to identify chronic HF patients with acute decompensation and CS (cardiac index <2.2 liters/min/m2 and systolic blood pressure <90 mm Hg or need for vasoactive medications to maintain this level). Clinical deterioration on IABP was defined as failure to bridge to either discharge on medical therapy or durable heart replacement therapy (HRT; durable left ventricular assist device or heart transplant) with IABP alone. RESULTS: We identified 132 chronic HF patients with IABP placed after decompensation with hemodynamic evidence of CS. Overall 30-day survival was 84.1%, and 78.0% of patients were successfully bridged to HRT or discharge without need for escalation of device support. The complication rate during IABP support was 2.3%. Multivariable analysis identified ischemic cardiomyopathy (odds ratio [OR] 3.24, 95% confidence interval [CI] 1.16 to 9.06; p = 0.03) and pulmonary artery pulsatility index (PAPi) <2.0 (OR 5.04, 95% CI 1.86 to 13.63; p = 0.001) as predictors of clinical deterioration on IABP. CONCLUSIONS: Overall outcomes with IABP in acute decompensated chronic HF patients are encouraging, and IABP is a reasonable first-line device for chronic HF patients with CS. Baseline right ventricular function, as measured by PAPi, is a major predictor of outcomes with IABP in this population.