NeRN -- Learning Neural Representations for Neural Networks

Neural Representations have recently been shown to effectively reconstruct a wide range of signals from 3D meshes and shapes to images and videos. We show that, when adapted correctly, neural representations can be used to directly represent the weights of a pre-trained convolutional neural network, resulting in a Neural Representation for Neural Networks (NeRN). Inspired by coordinate inputs of previous neural representation methods, we assign a coordinate to each convolutional kernel in our network based on its position in the architecture, and optimize a predictor network to map coordinates to their corresponding weights. Similarly to the spatial smoothness of visual scenes, we show that incorporating a smoothness constraint over the original network's weights aids NeRN towards a better reconstruction. In addition, since slight perturbations in pre-trained model weights can result in a considerable accuracy loss, we employ techniques from the field of knowledge distillation to stabilize the learning process. We demonstrate the effectiveness of NeRN in reconstructing widely used architectures on CIFAR-10, CIFAR-100, and ImageNet. Finally, we present two applications using NeRN, demonstrating the capabilities of the learned representations

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study

BackgroundAs indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults.MethodsA retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (>= 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR).ResultsWe identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged >= 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (P-interaction threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults.ConclusionIn this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted

Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1-4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5-8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89+/-16% and 94+/-9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.NTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE

Left atrial size predicts long-term outcome after balloon mitral valvuloplasty

Background: The treatment of choice for severe rheumatic mitral stenosis is balloon mitral valvuloplasty (BMV). Numerous predictors of immediate and long-term procedural success have been described. The aims of this study were to describe our experience with BMV over the last decade and to evaluate predictors of long-term event-free survival.  Methods: Medical records were retrospectively analyzed of patients who underwent BMV between 2009 and 2021. The primary outcome was a composite endpoint of all-cause mortality, mitral valve replacement (MVR), and repeat BMV. Long-term event-free survival was estimated using the Kaplan-Meier curves. Logistic regression was used to create a multivariate model to assess pre-procedural predictors of the primary outcome. Results: A total of 96 patients underwent BMV during the study period. The primary outcome occurred in 36 patients during 12-year follow-up: 1 (1%) patient underwent re-BMV, 28 (29%) had MVR, and 8 (8%) died. Overall event-free survival was 62% at 12 years. On multivariate analysis, pre-procedural left atrial volume index (LAVI) > 80 mL/m2 had a significant independent influence on event-free survival, as did previous mitral valve procedure and systolic pulmonary arterial pressure above 50 mmHg. Conclusion: Despite being a relatively low-volume center, excellent short and long-term results were demonstrated, with event-free survival rates consistent with previous studies from high-volume centers. LAVI independently predicted long-term event-free survival

Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis

Background: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled ‘low-flow low-gradient aortic stenosis (AS)’, there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. Methods: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). Results: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AV area ≤ 1 cm2). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. Conclusions: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment

Transcatheter edge-to-edge mitral valve repair in patients with acute decompensated heart failure due to severe mitral regurgitation

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has been established as a therapy for severe symptomatic mitral regurgitation (MR) in stable patients, and it has recently emerged as a reasonable option for acutely ill patients. The aim of this study was to evaluate the safety and efficacy of TEER in hospitalized patients with acute decompensated heart failure (ADHF) and severe MR that was deemed to play a major role in their deterioration. Methods: We included 31 patients who underwent emergent TEER for MR ≥ 3+ from 2012 to 2022 at Sheba Medical Center. Outcomes included procedural safety, procedural success, all-cause mortality, heart failure readmission, and functional improvement. Outcomes were evaluated at 3 months and at 1 year. Data were obtained retrospectively by chart review. Results: Implantation of a TEER device was achieved in 97% of patients, and reduction in MR severity of at least two grades and final MR ≤ 2+ at discharge was achieved in 74%. No intra-procedural mortality or life-threatening complications were noted. Mortality at 30 days was 23%. No excess mortality occurred beyond 6 months, with a total mortality of 41%. At 1 year all survivors had MR ≤ 2+, all were free of heart failure hospitalizations, and 88% were at New York Heart Association class ≤ II. Conclusions: Mitral valve TEER for patients with ADHF and significant MR is safe, feasible, and achieves substantial reduction in MR severity. Despite high early mortality, procedural success is associated with good long-term clinical outcomes for patients surviving longer than 6 months