Immune tolerance via FCR001 cell therapy compared with maintenance immunosuppression for kidney transplantation: Real-world evidence analysis of safety and efficacy.

While kidney transplantation (KTx) has traditionally required lifelong immunosuppression, an investigational stem cell therapy, FCR001, has been demonstrated to induce tolerance and eliminate the need for immunosuppression through the establishment of persistent mixed chimerism in a phase 2 clinical study. Real-world evidence (RWE) methods were employed to compare the safety and efficacy of non-myeloablative conditioning with FCR001 with standard of care [SOC] immunosuppression in a retrospective single-center analysis of outcomes among propensity score matched living-donor KTx receiving SOC (n = 144) or FCR001 (n = 36). Among the FCR001 recipients, 26 (72%) developed persistent chimerism allowing durable elimination of all immunosuppression. There was no significant difference in the composite primary endpoint (biopsy-proven acute rejection [BPAR], graft loss, or death) at 60 months (FCR001 27.8%, n = 10 and SOC 28.5%, n = 41; p = .9). FCR001 recipients demonstrated superior kidney function at 5 years (estimated glomerular filtration rate [eGFR] [mean ± standard deviation]: 64.1 ± 15.3) compared to SOC (51.7 ± 18.8; p = .02). At 5 years, FCR001 recipients experienced fewer complications including new-onset diabetes post-transplant, although two patients developed graft versus host disease. In conclusion, RWE demonstrated that KTx combined with non-myeloablative conditioning and FCR001 resulting in superior kidney function without increasing the risk of rejection, graft loss, or death among patients off immunosuppression.

Characterizing turbulence profile layers through celestial single-source observations.

Future spacecraft missions aim to communicate with the Earth using near-infrared lasers. The possible bit rate of free-space optical communication (FSOC) is orders of magnitude greater when compared to current radio frequency transmissions. The challenge of ground-space FSOC is that atmospheric turbulence perturbs optical wavefront propagation. These wavefront aberrations can be measured using a Shack-Hartmann wavefront sensor (SHWFS). A ground-based adaptive optics (AO) system can mitigate these aberrations along the optical path by translating wavefront measurements into deformable mirror commands. However, errors result from atmospheric turbulence continuously evolving, and there are unavoidable delays during AO wavefront correction. The length of an acceptable delay is referred to as the coherence time-a parameter dependent on the strength of turbulence profile layers and their corresponding wind-driven velocity. This study introduces a novel technique, to the best of our knowledge, for using SHWFS single-source observations, e.g., the downlink signal from a geostationary satellite, to measure the strength and velocity of turbulence profile layers. This work builds upon previous research and demonstrates that single-source observations can disentangle turbulence profile layers through studying the cross-covariance of temporally offset SHWFS centroid measurements. Simulated data are used to verify that the technique can recover the coherence time. The expected and measured results have a correlation coefficient of 0.95.

Aseptic presentation of interventricular septal abscess with progressive heart block: a case report.

BACKGROUND: Infective endocarditis can progress to an intracardiac abscess in 20% to 30% of cases, with interventricular septal abscess (IVSA) being one of the rare complications usually presenting with sepsis. We present a case of IVSA presenting with a new-onset second-degree heart block, which rapidly progressed to a complete heart block. CASE PRESENTATION: A 80-year-old Caucasian female with a past medical history of hypertension and hyperlipidemia presented with exertional chest pain, lightheadedness, and shortness of breath with telemetry and electrocardiogram revealing persistent Mobitz type II second degree atrioventricular block. The rest of the vitals were normal. As she was being planned for a pacemaker placement, she spiked a temperature of 103F. Blood cultures grew methicillin-sensitive Staphylococcus aureus, and appropriate antibiotics were initiated. Transthoracic echocardiogram was grossly normal. However, transesophageal echocardiogram revealed a heterogeneous extension of an echodensity from the aortic root, along the aorto-mitral cushion and into the interventricular septum, indicating an interventricular septal abscess. Her course was complicated by altered mental status, with computed tomography of the brain revealing hypodense regions in the left lentiform nucleus and anterior caudate nucleus representing acute/subacute stroke. Surgery was deferred as she was deemed a poor candidate. She succumbed to her illness on day 6 of hospitalization. CONCLUSION: Intracardiac abscesses should be considered a possible initial differential in patients with progressive heart block despite aseptic presentation and no risk factors.

Association of atrial fibrillation burden with in-hospital outcomes in patients with Takotsubo cardiomyopathy.

BACKGROUND: The effects of atrial fibrillation (AF) and its burden on in-hospital mortality in patients with Takotsubo cardiomyopathy (TCM) are unclear. Here, we examined the effect of AF and paroxysmal AF on in-hospital outcomes in patients with TCM. METHODS: We used ICD-10 codes to retrospectively identify patients with a primary diagnosis of TCM in the National Inpatient Sample database 2016-2018. We compared in-hospital outcomes in TCM patients with and without AF before and after propensity score matching. The effect of AF burden on outcomes was assessed in patients with paroxysmal AF and no AF. RESULTS: Of the 4,733 patients with a primary diagnosis of TCM, 650 (13.7%) had AF, and 4,083 (86.3%) did not. Of TCM patients with AF, 368 (56.6%) had paroxysmal AF. In-hospital mortality was higher in patients with AF before (3.4% vs 1.2%, P <  0.001) and after propensity matching (3.4% vs 1.7%, P = 0.021) but did not differ between the paroxysmal AF and the no AF groups (P = 0.205). In the matched cohorts, both AF and paroxysmal AF groups were associated with a higher rate of cardiogenic shock (AF, P < 0.001; paroxysmal AF, P < 0.001), ventricular arrhythmia (AF, P = 0.002; paroxysmal AF, P = 0.02), acute kidney injury (AF, P = 0.007; paroxysmal AF, P = 0.008), and acute respiratory failure (AF, P < 0.001; paroxysmal AF, P < 0.001) compared with the no AF group. CONCLUSIONS: Although AF was associated with increased in-hospital mortality, paroxysmal AF did not affect in-hospital mortality, suggesting a higher AF burden is associated with worse clinical outcome in patients with TCM.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. However, only 80% of patients benefit from initial CBA. There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) decreases the recurrence of AF postablation, particularly in nonparoxysmal AF undergoing radiofrequency ablation. The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia (AA) following CBA for paroxysmal AF. AIM: To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF. METHODS: We followed 103 patients (age 60.6 ± 9.1 years, 29% women) with paroxysmal AF undergoing CBA 1-year post procedure. Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring. A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence. RESULTS: After a 1-year follow-up, 19 (18.4%) participants developed recurrence of AA. Use of ACEI or ARB therapy was noted in the study population. Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (P = 0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA (P = 0.2173). CONCLUSION: In our study population, preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Presence of a left common pulmonary vein and pulmonary vein anatomical characteristics as predictors of outcome following cryoballoon ablation for paroxysmal atrial fibrillation.

PURPOSE: Pulmonary vein (PV) isolation using cryoballoon ablation (CBA) is a common therapy for patients with drug-refractory paroxysmal atrial fibrillation (PAF). However, initial CBA is successful in only 70-80% of patients. The role of an atypical left common PV (LCPV) and PV anatomical indices on CBA outcomes remains unclear. METHODS: We followed 80 patients (age 60.7 ± 9.7, 31 % women) with PAF undergoing CBA for 1-year post-procedure for the development of recurrent atrial arrhythmias (AA). Recurrence was assessed by documented AA on EKG or any form of long-term cardiac rhythm monitoring. The presence of an LCPV and individual PV diameters were evaluated using cardiac CT. Based on the maximum and minimum PV ostial diameters, the eccentricity index (EI), ovality index (OI), and PV ostial area (PVA) were calculated for all the veins. A multivariable Cox-proportional hazard model assessed whether the presence of an LCPV or PV anatomic indices (EI, OI, and PVA) predicted recurrence of AA following CBA. RESULTS: After 1-year follow-up, 19 (23.7%) participants developed recurrence of AA. On multivariable regression, the presence of an LCPV did not predict the recurrence of AA (p = 0.38). Among the PV anatomical indices, on univariate analysis, only the area of the left inferior PV showed a trend towards predicting recurrence, though this result was not significant on multivariate analysis (p = 0.09). CONCLUSIONS: In patients with PAF, neither the presence of an LCPV nor individual PV anatomical indices predicted recurrence of AA following CBA.

Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death. However, the selection of patients for implanted cardioverter-defibrillators (ICDs), as well as programming of the ICD, is unclear. OBJECTIVES: The objective of this study was to identify predictors, characteristics, and treatment of ventricular arrhythmias in patients with ARVC. METHODS: The Multidisciplinary Study of Right Ventricular Cardiomyopathy established the North American ARVC Registry and enrolled patients with a diagnosis of ARVC. Patients were followed prospectively. RESULTS: Of 137 patients enrolled, 108 received ICDs. Forty-eight patients had 502 sustained episodes of ventricular arrhythmias, including 489 that were monomorphic and 13 that were polymorphic. In the patients with ICDs, independent predictors of ventricular arrhythmias in follow-up included spontaneous sustained ventricular arrhythmias before ICD implantation and T-wave inversions inferiorly. The only independent predictor for life-threatening arrhythmias, defined as sustained ventricular tachycardia (VT) ≥240 beats/min or ventricular fibrillation, was a younger age at enrollment. Anti-tachycardia pacing (ATP), independent of the cycle length of the VT, was successful in terminating 92% of VT episodes. CONCLUSIONS: In the North American ARVC Registry, the majority of ventricular arrhythmias in follow-up are monomorphic. Risk factors for ventricular arrhythmias were spontaneous ventricular arrhythmias before enrollment and a younger age at ICD implantation. ATP is highly successful in terminating VT, and all ICDs should be programmed for ATP, even for rapid VT.