Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation.

PURPOSE: We assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. METHODS AND MATERIALS: This single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). RESULTS: Median age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0-22) and median heart mean dose was 8.7 Gy (IQR 4.6-14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. CONCLUSIONS: With modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

Spray fabrication of additive-free electrodes for advanced Lithium-Ion storage technologies.

Polymer binders and carbon conductivity enhancers are inevitably required to make improvements in structural durability and electrochemical performance of lithium-ion battery (LIB) electrodes, although these additive constituents incur weight and volume penalties on the overall battery capacity. Here, additive-free electrode architectures were successfully fabricated over 20 × 20 cm2 electrode areas using a layer-by-layer spray coating approach, with the ultimate goal to boost gravimetric/volumetric electrode capacity and to reduce the total cost of LIB cells. Initially, the binder fraction of spray-coated Li4Ti5O12 (LTO) electrodes was reduced progressively, from 40 to 0 wt%. The electrochemical behavior of electrodes was then re-optimized as a proportion of conductivity enhancers within the binder-free electrode decreased to zero. Further, the otherwise identical spray coating process was applied to manufacture LiFePO4 (LFP) positive electrodes, leading to all-additive-free full-cell LIB configurations with attractive energy density of âˆ¼310 Wh/kg and power performance of âˆ¼1500 W/kg.

Death without progression as an endpoint to describe cardiac radiation effects in locally advanced non-small cell lung cancer.

Background and purpose: Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity. Materials and methods: We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution. Dosimetric parameters to the heart, lung, and ten cardiovascular substructures were extracted. Charlson Comorbidity Index (CCI), excluding NSCLC diagnosis, was used to stratify patients into CCI low (0-2; n = 66), CCI intermediate (3-4; n = 78), and CCI high (≥5; n = 43) groups. Primary endpoint was DWP, modeled with competing risk regression. Secondary endpoints included OS. An external cohort consisted of 140 patients from another institution. Results: Median follow-up was 7.3 years for survivors. Death occurred in 143 patients (76.5 %), including death after progression in 118 (63.1 %) and DWP in 25 (13.4 %). On multivariable analysis, increasing CCI stratum and mean heart dose were associated with DWP. For mean heart dose ≥ 10 Gy vs < 10 Gy, DWP was higher (5-year rate, 16.9 % vs 6.7 %, p = 0.04) and OS worse (median, 22.9 vs 34.1 months, p < 0.001). Ventricle (left, right, and bilateral) and pericardial but not atrial substructure dose were associated with DWP, whereas all three were inversely associated with OS. Cutpoint analysis identified right ventricle mean dose ≥ 5.5 Gy as a predictor of DWP. In the external cohort, we confirmed an association of ventricle, but not atrial, dose with DWP. Conclusion: Cardiovascular substructure dose showed distinct associations with DWP. Future cardiotoxicity studies in NSCLC could consider DWP as an endpoint.

Posterolateral Endoscopic Lumbar Decompression Rotate-to-Retract Technique for Foraminal Disc Herniation: A Technical Report.

BACKGROUND AND STUDY AIM: Foraminal disc herniations present the unique surgical challenge for exiting nerve root retraction and decompression. The aim of current study is to describe an innovative maneuver and evaluate its usefulness for endoscopic decompression of foraminal disc herniations. MATERIAL AND METHODS: A retrospective review was performed including cases of foraminal disc herniations who underwent endoscopic discectomy utilizing the rotate-to-retract technique. Data on patient demographics and improvement in VAS/ODI scores were collected and analyzed statistically. RESULTS: There were ten patients (three male; seven female) in the final analysis. Seven procedures were done at the L4-L5 level, two were done at the L5-S1 level, and one was done at the L3-L4 level. The average VAS scores improved from preoperatively 7.5 to postoperatively 4.4 (p= 0.001). The mean preoperative ODI was 67.8 and improved to 26.6 postoperatively (p< 0.001). None of the cases reported any neurological or dural complication. CONCLUSION: Foraminal disc herniations can be safely and adequately addressed endoscopically with the use of rotate-to-retract technique.

Epidurographic Findings Following Percutaneous Epidural Adhesiolysis Failed to Correlate with Level of Pain Reduction in Patients with Lumbar Spinal Stenosis.

Background: Spinal stenosis is characterized by narrowing of the spinal canal, with mechanical compression of spinal nerve roots. The latter may cause low back pain and/or leg pain, as well as neurogenic claudication. Epidural steroid injection is commonly used to treat patients with lumbar spinal stenosis (LSS), but percutaneous epidural adhesiolysis has been utilized when symptoms prove refractory. Our goal was to assess the relationship between improvement shown on epidurogram and subjective patient response to adhesiolysis. Methods: For this prospective study, 78 patients with degenerative LSS were enrolled. Each subject underwent magnetic resonance imaging of the lumbar spine, with all therapeutic procedures conducted in the operating room. Two weeks later, a second epidurography was performed. Second epidurography was conducted to assess any change in epidural filling defects. Outcome measures were obtained using the visual analogue scale (VAS) score at two weeks, one month, and three months post-treatment. Results: All of the 78 study participants (mean age = 60.9 years, range = 34-85 years) displayed epidural filling defects at baseline. After percutaneous adhesiolysis, epidurographic filling defects were absent in 73% of patients. In the presence or absence of filling defects, mean VAS scores were 5.2 and 4.5, respectively, at two weeks' follow-up. No significant correlation between postprocedural VAS score and status of filling defects (yes or no) was evident during the three-month follow-up period. Conclusion: In patients with LSS, epidurographic findings following percutaneous epidural adhesiolysis failed to correlate with level of pain reduction achieved.

Efecto de micofenolato mofetilo en la miocardiopatía diabética de ratones db/db / Effect of mycophenolate mofetil on diabetic cardiomyopathy in db/db mice

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Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG.

Modern medicine is founded on the discovery of penicillin and subsequent small molecules that inhibit bacterial peptidoglycan (PG) and cell wall synthesis. However, the discovery of new chemically and mechanistically distinct classes of PG inhibitors has become exceedingly rare, prompting speculation that intracellular enzymes involved in PG precursor synthesis are not 'druggable' targets. Here, we describe a ß-lactam potentiation screen to identify small molecules that augment the activity of ß-lactams against methicillin-resistant Staphylococcus aureus (MRSA) and mechanistically characterize a compound resulting from this screen, which we have named murgocil. We provide extensive genetic, biochemical, and structural modeling data demonstrating both in vitro and in whole cells that murgocil specifically inhibits the intracellular membrane-associated glycosyltransferase, MurG, which synthesizes the lipid II PG substrate that penicillin binding proteins (PBPs) polymerize and cross-link into the cell wall. Further, we demonstrate that the chemical synergy and cidality achieved between murgocil and the ß-lactam imipenem is mediated through MurG dependent localization of PBP2 to the division septum. Collectively, these data validate our approach to rationally identify new target-specific bioactive ß-lactam potentiation agents and demonstrate that murgocil now serves as a highly selective and potent chemical probe to assist our understanding of PG biosynthesis and cell wall biogenesis across Staphylococcal species.

Modulation of adhesion and growth of cardiac myocytes by surface nanotopography.

We have introduced well-defined nanopillar arrays of polyethylene glycol (PEG) as a platform for studying the adhesion and growth of cultured cardiomyocytes. The nanopillar arrays were fabricated by using a simple molding technique involving the placement of a patterned polyurethane acrylate mold on top of a drop-dispensed ultraviolet (UV) curable PEG polymer followed by UV exposure and mold removal. The adhesion and growth of cardiomyocytes turned out be guided by an external nanotopography, which has been characterized in terms of cell morphology and cytoskeletal arrangement. In particular, the nanopillars provided guiding posts to both elongating filopodia and expanding lamellipodia. Interestingly, the 3D growth of cardiomyocytes was mediated by the increased hydrophobicity of the nanostructured PEG substrate, indicating that the cell adhesion and growth is very sensitive to the nanotopography. The precise nanostructures of PEG-based polymer with controlled geometrical features presented in this study not only open opportunities for understanding and tailoring cell adhesion and growth, but could serve as a template for better tissue engineering by controlling cellular activities at the molecular level.