Multiparameter immunoprofiling for the diagnosis and differentiation of progressive versus nonprogressive nontuberculous mycobacterial lung disease-A pilot study.

Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (p <0.05; AUC-ROC = 0.831; Sensitivity = 75% [95% CI: 34.9-96.8]; Specificity = 90% [95% CI: 55.5-99.7]) between progressors and nonprogressors. Significant differences in the ratios of antigen-specific IFN-γ ELISpot responses were also seen for RD1-nil/PPD-nil and RD1-nil/anti-CD3-nil between patients with nonprogressive vs. progressive NTM-LD. Our results suggest that multiparameter immunoprofiling can accurately identify patients with NTM-LD and may identify patients at risk of disease progression. A larger longitudinal study is needed to further evaluate this novel immunoprofiling approach.

Coarctation of Aorta With Tricuspid Aortic Valve Is Not Associated With Ascending Aortic Aneurysm.

BACKGROUND: Aortic aneurysm is common in patients with coarctation of aorta (COA), but it is unclear whether the risk of aortic aneurysms is due to COA or related to the presence of other risk factors such as bicuspid aortic valve (BAV) and hypertension. OBJECTIVES: The purpose of this study was to assess the relationship among COA, BAV, and thoracic aortic aneurysms. METHODS: A total of 867 patients with COA (COA group) were matched 1:1:1 to 867 patients with isolated BAV (BAV group) and 867 patients without structural heart disease (SHD) (no-SHD group). The COA group was further subdivided into a COA+BAV subgroup (n = 304 [35%]), and COA with tricuspid aortic valve (TAV) (COA+TAV subgroup [n = 563 (65%)]). Aortic dimensions were assessed at baseline and at 3, 5, and 7 years. RESULTS: Compared with the no-SHD group, the COA+BAV subgroup had larger aortic root diameter (37 mm [Q1-Q3: 30-43 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001) and mid ascending aorta dimeter (34 mm [Q1-Q3: 29-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P = 0.008). Similarly, the BAV group had larger aortic root diameter (37 mm [Q1-Q3: 30-42 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001), and mid ascending aorta dimeter (35 mm [Q1-Q3: 30-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P < 0.001). Compared with the COA+TAV subgroup, the COA+BAV subgroup and BAV group were associated with larger aortic root and mid ascending aorta diameter at baseline and follow-up. The risk of acute aortic complications was low in all groups. CONCLUSIONS: These findings suggest that BAV (and not COA) was associated with ascending thoracic aorta dimensions, and that patients with COA+TAV were not at a greater risk of developing ascending aortic aneurysms as compared with patients without SHD.

Right Heart Reverse Remodeling and Prosthetic Valve Function After Transcatheter vs Surgical Pulmonary Valve Replacement.

BACKGROUND: There are limited data about postprocedural right heart reverse remodeling and long-term prosthesis durability after transcatheter pulmonary valve replacement (TPVR) and how these compare to surgical pulmonary valve replacement (SPVR). OBJECTIVES: This study sought to compare right heart reverse remodeling, pulmonary valve gradients, and prosthetic valve dysfunction after TPVR vs SPVR. METHODS: Patients with TPVR were matched 1:2 to patients with SPVR based on age, sex, body surface area, congenital heart lesion, and procedure year. Right heart indexes (right atrial [RA] reservoir strain, RA volume index, RA pressure, right ventricular [RV] global longitudinal strain, RV end-diastolic area, and RV systolic pressure) were assessed at baseline (preintervention), 1 year postintervention, and 3 years postintervention. Pulmonary valve gradients were assessed at 1, 3, 5, 7, and 9 years postintervention. RESULTS: There were 64 and 128 patients in the TPVR and SPVR groups, respectively. Among patients with TPVR, 46 (72%) and 18 (28%) received Melody (Medtronic) vs SAPIEN (Edwards Lifesciences) valves, respectively. The TPVR group had greater postprocedural improvement in RA reservoir strain and RV global longitudinal strain at 1 and 3 years. The TPVR group had a higher risk of prosthetic valve dysfunction mostly because of a higher incidence of prosthetic valve endocarditis compared to SPVR but a similar risk of pulmonary valve reintervention because some of the patients with endocarditis received medical therapy only. Both groups had similar pulmonary valve mean gradients at 9 years postintervention. CONCLUSIONS: These data suggest a more favorable right heart outcome after TPVR. However, the risk of prosthetic valve endocarditis and prosthetic valve dysfunction remains a major concern.

Diagnostic and Prognostic Role of Left Ventricular Strain Imaging in Adults with Coarctation of aorta.

The relative diagnostic and prognostic performance of left ventricular (LV) global longitudinal strain (LVGLS) compared with LV ejection fraction (LVEF) and the role of LVGLS for detecting the early stages of LV systolic dysfunction in adults with repaired coarctation of the aorta are unknown. This study aimed to address these knowledge gaps. We used a retrospective cohort study of adults with repaired coarctation of the aorta who underwent transthoracic echocardiogram (2003 to 2020). LV systolic function was assessed using LVEF (derived from volumetric analysis) and LVGLS (derived from speckle-tracking echocardiography). Of the 795 patients (age 36 ± 14 years), the mean LVEF and LVGLS were 62 ± 11% and 21 ± 4%, respectively. The prevalence of LV systolic dysfunction was higher when assessed using LVGLS than using LVEF (20% vs 6%, p <0.001). Of 795 patients, 94 (12%) patients died, of which 75 (9%) died from cardiovascular causes. LVGLS provided more robust prognostic power in predicting the all-cause mortality than LVEF, as evidenced by a higher C-statistic (0.743, 95% confidence interval 0.730 to 0.755 vs 0.782, 95% confidence interval 0.771 to 0.792, p <0.001). Furthermore, patients with normal LVEF in the setting of reduced LVGLS had a higher risk of all-cause mortality (than patients with normal LVGLS and LVEF) and were at risk for a temporal decrease in LVEF during follow-up. These findings suggest that the use of LVGLS for risk stratification can help identify high-risk patients and provide opportunities for interventions, which would, in turn, improve clinical outcomes. Further studies are required to empirically test these postulates.

Prognostic Role of Tricuspid Annular Plane Systolic Excursion/Right Ventricular Systolic Pressure Ratio in Coarctation of Aorta.

Background: Right ventricular (RV) systolic dysfunction and pulmonary hypertension are associated with mortality in adults with coarctation of aorta (COA). The tricuspid annular plane systolic excursion/RV systolic pressure (TAPSE/RVSP) ratio is a validated noninvasive tool for the assessment of RV-pulmonary arterial (RV-PA) coupling in patients with PA hypertension, but similar data are lacking in adults with COA. The purpose of this study was to assess the relationship between the TAPSE/RVSP ratio and outcomes in this population. Methods: A retrospective cohort study of adults with repaired COA was performed. RV systolic dysfunction was defined as RV free wall strain ≥-24% at baseline, whereas new-onset RV systolic dysfunction was defined RV free wall strain ≥-24% during follow-up. Results: Of 661 patients, TAPSE, RVSP, and TAPSE/pulmonary artery systolic pressure ratio were 22 ± 6 mm, 34 ± 12 mm Hg, and 0.71 (0.48-0.89) mm/mm Hg, respectively. Of 661 patients, 152 (23%) had RV systolic dysfunction at baseline, and TAPSE/RVSP <0.43 mm/mm Hg was the optimal threshold to detect RV systolic dysfunction. TAPSE/RVSP <0.43 mm Hg was associated with RV systolic dysfunction (adjusted odds ratio: 3.11 [1.83-6.19], P = 0.004). Of 509 patients with normal RV systolic function, 42 (8%) and 36 (7%) developed new-onset RV systolic dysfunction and new-onset right heart failure, respectively, during follow-up. TAPSE/RVSP <0.43 mm/mm Hg was associated with new-onset RV systolic dysfunction (adjusted hazard ratio: 1.95 [1.46-2.77], P = 0.008) and new-onset right heart failure (adjusted hazard ratio: 0.81 [0.68-0.92], P = 0.005). Conclusions: The TAPSE/RVSP ratio can potentially be used to identify patients at risk for new-onset RV systolic dysfunction and right heart failure and provide opportunity for proactive interventions to prevent adverse outcomes.

Contexte: La dysfonction systolique du ventricule droit (VD) et l'hypertension pulmonaire sont associées à des décès chez les adultes qui présentent une coarctation de l'aorte (CA). Le rapport entre l'excursion systolique du plan de l'anneau tricuspide (TAPSE pour tricuspid annular plane systolic excursion) et la pression systolique du VD (PSVD) est une méthode non invasive pour évaluer le couplage entre le VD et l'artère pulmonaire (VD-AP), qui a été validée chez les patients atteints d'hypertension de l'AP, mais pour laquelle on ne dispose pas de données similaires chez les adultes qui présentent une CA. La présente étude visait à évaluer la relation entre le rapport TAPSE/PSVD et les résultats de santé chez cette population de patients. Méthodologie: Nous avons mené une étude de cohorte rétrospective auprès d'adultes présentant une CA corrigée. La dysfonction systolique du VD était définie comme une déformation (strain) de la paroi libre du VD (DPLVD) ≥ -24 % au début de l'étude, et une dysfonction systolique inaugurale du VD était définie comme une DPLVD ≥ -24 % détectée lors du suivi. Résultats: Pour l'ensemble des 661 patients de l'étude, les valeurs pour la TAPSE, la PSVD et le rapport TAPSE/pression systolique de l'artère pulmonaire étaient respectivement de 22 ± 6 mm, 34 ± 12 mmHg et 0,71 (0,48-0,89) mm/mmHg. Parmi ces 661 patients, 152 (23 %) présentaient initialement une dysfonction systolique du VD, et un rapport TAPSE/PSVD < 0,43 mm/mmHg constituait le seuil optimal pour la détection d'une dysfonction systolique du VD. Un rapport TAPSE/PSVD < 0,43 mm/mmHg était par ailleurs associé à une dysfonction systolique du VD (rapport de cotes ajusté de 3,11 [1,83-6,19], p = 0,004). Au cours du suivi des 509 patients qui présentaient initialement une fonction systolique normale du VD, 42 patients (8 %) ont présenté une dysfonction systolique inaugurale du VD et 36 patients (7 %) ont présenté une insuffisance cardiaque droite inaugurale. Un rapport TAPSE/PSVD < 0,43 mm/mmHg était associé avec la dysfonction systolique inaugurale du VD (rapport des risques instantanés ajusté de 1,95 [1,46-2,77], p = 0,008), et avec l'insuffisance cardiaque droite inaugurale (rapport des risques instantanés ajusté de 0,81 [0,68-0,92], p = 0,005). Conclusions: Le rapport TAPSE/PSVD pourrait permettre de repérer les patients susceptibles de présenter une dysfonction systolique inaugurale du VD ou une insuffisance cardiaque droite inaugurale, ce qui ouvre la voie à des interventions en amont visant à prévenir les résultats défavorables pour ces patients.

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic disease characterized by inadequate or absent insulin production due to the autoimmune destruction of beta (ß) cells in the pancreas. It was once called "juvenile diabetes" since the disease frequently occurs in children, but it can also develop in adults. According to the International Diabetes Federation, an estimated 700 million adults will suffer from diabetes by 2045. Although the exact cause of diabetes remains unknown, it is hypothesized that genetic factors, environmental factors, and exposure to certain viruses play a role in the development of T1D. To date, exogenous insulin is the most common treatment for T1D. However, it is not a cure for the disease. Islet cell transplantation and pancreatic transplantation are two additional treatments that have gained popularity in recent years, but their clinical application may be limited by the need for high doses of immunosuppressants, the rarity of human cadaveric islets, and the need for extensive surgery in pancreatic transplantation. Mesenchymal stem cells (MSCs) are a highly promising novel treatment for T1D and their discovery has advanced biological sciences by allowing for modification of cell fate and the development of higher-order cellular structures. They play an essential role in lowering levels of fasting blood sugar, hemoglobin A1c, and C-peptide, and in treating microvascular complications associated with T1D. However, some of the disadvantages of its use in clinical practice are limited to its method of collection, proliferation rate, cell activity with age, and the risk of tumour formation identified in some studies. Large-scale studies are required to discover the mechanism of action of MSCs after administration as well as the optimal route, dose, and timing to maximize the benefits to patients. This article focuses primarily on the role of MSCs in the treatment of T1D and compares the feasibility, benefits, and drawbacks of MSCs in the treatment of T1D.

Therapeutic Efficacy of Botulinum Toxin in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a unilateral, paroxysmal, sharp, shooting, or jabbing pain that occurs in the trigeminal nerve divisions, including the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. Typically, an episode is triggered by anything touching the face or teeth. TN is a clinical diagnosis with no specific diagnostic test; it is determined by the patient's medical history and pain description. Imaging is necessary to exclude secondary causes. The precise reason for TN is uncertain, but it is commonly believed to result from vascular compression of the trigeminal nerve root, typically near its origin in the pons. There are numerous surgical and medical treatment options available. The most frequently applied medical treatment therapies are carbamazepine and oxcarbazepine. Surgical alternatives are reserved for patients who do not respond to medical treatment. Botulinum toxin A (BTX-A) has emerged as a novel and promising alternative to surgery for individuals whose pain is unresponsive to medication. Multiple studies have established the safety and usefulness of BTX-A in treating TN, with the most significant benefits occurring between six weeks and three months after the surgery. This article reviews various studies published in the last 10 years regarding the therapeutic use of BTX-A in TN. These studies include various observational, clinical, pilot, and animal studies.

Ethnical Disparities in Response to Edaravone in Patients With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disease characterized by the weakness of voluntary muscles due to the loss of motor neurons. Symptoms ultimately culminate in the form of respiratory failure due to the involvement of the diaphragm. Unfortunately, there is no known cure for this disease. Hence, supportive therapy is the only available option in most terminal cases. However, Riluzole and Edaravone (EDA) are the only two known drugs approved by the U.S. Food and Drug Administration (FDA) for treating this condition. In 2017, EDA was approved for the treatment of ALS. It is hypothesized that Riluzole and EDA work via a mechanism involving antioxidants, which nullifies the oxidative stress believed to be involved in ALS. However, most studies in several countries have found a wide range of disparities in the efficacy of this drug. In this review, we aim to summarize the differences in results from epidemiological studies across 10 different countries and hypothesize the potential causes of these differences.