TCT-100 Real-World Experience and Outcomes of Protected Versus Unprotected Left Main Percutaneous Coronary Intervention: Insights From the VA CART Program

Background: Outcomes of protected left main (PLM) and unprotected left main (ULM) percutaneous coronary intervention (PCI) are not well defined in contemporary U.S. practice. Previous studies of real-world data have shown worse in-hospital outcomes of ULM PCI compared with randomized trial data. We used a large national registry to characterize real-world practice and outcomes of left main PCI. Methods: Data were collected from the Veteran Affairs (VA) Clinical Assessment Reporting and Tracking (CART) Program for patients undergoing left main PCI between 2009 and 2019. PLM PCI was defined by the presence of at least 1 functioning bypass graft, and ULM PCI was defined as patients with no bypass grafting. Temporal trends, patient and procedure characteristics, anatomic complexity, and clinical complexity were assessed. A 1-to-1 propensity-matched analysis was performed using common comorbidities and clinical variables. One-year outcome analyses were conducted for major adverse cardiovascular events (MACE), all-cause mortality, rehospitalization for myocardial infarction (MI) and revascularization. Results: Of 4,351 patients undergoing left main PCI, 2,800 were PLM PCI and 1,551 were ULM PCI, of which 1,335 PLM and ULM PCI were included in the propensity matched cohort. Patients undergoing ULM PCI were older, more likely to present with acute coronary syndrome (ACS) and had a higher clinical complexity. In the propensity-matched cohort, there was no difference in age, rate of ACS presentation, burden of comorbidities, or left ventricular ejection fraction. There were no differences in in-hospital adverse events between the 2 groups. At 12 months, MACE occurred more frequently with ULM PCI compared with PLM PCI (25% [334] vs 20% [270]; P = 0.004), and all-cause mortality was also higher (18% [239] vs 14% [185]; P = 0.005). There was no difference in rehospitalization for MI, stroke, or revascularization at 12 months. Conclusion: In the VA Healthcare System, patients undergoing ULM PCI were older and more clinically complex than those undergoing PLM PCI. In the propensity-matched cohort, patients undergoing PLM PCI had better 12 outcomes than those undergoing ULM PCI, but there was a high rate of mortality and MACE at 1 year in both groups, despite a relatively low rate of MI or revascularization

INITIAL EXPERIENCE WITH LITHOTRIPSY FOR MITRAL BALLOON VALVULOPLASTY

Background: Mitral annular calcification (MAC) causes degeneration of the mitral valve function. Since these patients are poor surgical candidates, options are limited to percutaneous solutions. Use of balloon lithotripsy (BL) to augment mitral balloon valvuloplasty (MBV) is a novel technique for treatment of MAC-related mitral stenosis (MS). Methods: Single-center retrospective review of 35 consecutive MBV for MAC cases at Henry Ford from 3/2013 to 4/2021. Outcome variables are reported as median and interquartile ranges (IQR). Chi-squared and Wilcoxon-signed rank tests were used to compare categorical and continuous variables respectively using 95% confidence intervals for statistical significance. Procedural success was defined as a final mitral valve area ≥1.5 cm2 or ≥50% reduction in gradient. Results: Of 35 MBV cases done for MAC, 5 utilized lithotripsy balloons to augment valvuloplasty results (Table). Mean baseline gradients were similar and right ventricular systolic pressures trended higher for BL cases. Cases utilizing lithotripsy were longer and utilized more fluoroscopy time but the final invasive gradient trended lower (non-BL 7mmHg [4, 9] vs. BL 1 mmHg [0,5] p=0.113), therefore, higher rates of procedural success were seen (non-BL 47% vs. BL 80%, p=0.2). Survival analysis was hampered due to loss of follow-up in the BL group. Conclusion: BL appears to augment immediate valvuloplasty results. Further studies regarding the durable impact of balloon lithotripsy on MBV are warranted

SURVIVAL OF PATIENTS WITH RHEUMATIC AND NON-RHEUMATIC MITRAL VALVE STENOSIS AFTER VALVULOPLASTY

Background: Non-rheumatic (NR) mitral stenosis (MS) due to mitral annular calcification (MAC) presents in elderly patients and is difficult to treat due elevated surgical risk. In search for alternative treatments, mitral balloon valvuloplasty (MBV) has been performed in non-rheumatic mitral stenosis but no outcomes have been described in this cohort. Methods: Single center retrospective review of 85 consecutive MBV cases at Henry Ford from 3/2013 to 4/2021. Clinical and procedural outcome variables are reported as median and interquartile ranges (IQR). Kaplan-Meier method was used to estimate survival. Chi-squared and Wilcoxon-signed rank tests were used to compare categorical and continuous variables respectively using 95% confidence intervals for statistical significance. Results: Of 85 MBV cases, 50 and 35 were performed for rheumatic (R) and NR MS respectively. NR patients tended to be older and were more likely to have hypertension, diabetes, coronary artery disease, chronic kidney disease, aortic valve procedures. Rates of ≥moderate-severe mitral regurgitation (MR) (R 18% vs. NR 12% p=0.4) and procedure success (R 57% vs NR 42.9% p=0.2) were similar. Median follow up for the entire cohort was 0.5 yrs [0.1, 2.1]. Survival was significantly better for rheumatic cases (Figure). Conclusion: Survival of NR MS post-valvuloplasty is significantly attenuated as compared to those with R MS. Larger prospective studies are necessary in understanding optimal bridging therapies for patients with MAC

Substance P autocrine signaling contributes to persistent HER2 activation that drives malignant progression and drug resistance in breast cancer.

ERBB receptor transmodulation by heterologous G-protein-coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2(+) primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle