Improvement of myocardial contractility with leadless endocardial single-lead atrial sensing ventricular pacing in patients with prolonged PQ interval.

Micra AV represents a leadless endocardial pacing system able to detect atrial contractions providing atrioventricular synchrony. A reduction of myocardial contractility may be detected in case of first-degree atrioventricular block (AVB). In six patients with first-degree AVB (PQ interval ≥220 msec) was evaluated the left ventricle global longitudinal strain (LV GLS) by speckle tracking (ST) echocardiography during single-lead atrial sensing ventricular pacing (VDD) stimulation as compared with spontaneous rhythm (SR), 24-48 h after Micra AV implantation.

Successful uniportal thoracoscopic removal of a new generation implantable loop recorder accidentally migrated into the left pleural cavity and concomitant re-implantation: A case report.

Introduction: With the spread of the use of implantable loop recorders (ILRs) by cardiologists for outpatient cardiac monitoring, intrathoracic migration represents a rare but possible complication occurring after the placement of these devices. Very few cases of ILRs intrathoracic migration into the pleural cavity have been reported, followed in even fewer cases by surgical removal of the devices, but in none re-implantation was performed.

Presentation Of Case: We report the first case of a patient with a new generation ILR accidentally migrated into the postero-inferior costophrenic recess of the left pleural cavity, successfully removed by uniportal video-assisted thoracic surgery (VATS) and submitted to re-implantation of a new ILR in the same operating session.

Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis.

Purpose: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED.

Importance of clinical suspicion and multidisciplinary management for early diagnosis of a cardiac laminopathy patient: A case report.

Background: Laminopathies are rare diseases, whose cardiac manifestations are heterogeneous and, especially in their initial stage, similar to those of more common conditions, such as ischemic heart disease. Early diagnosis is essential, as these conditions can first manifest themselves with sudden cardiac death. Electrical complications usually appear before structural complications; therefore, it is important to take into consideration these rare genetic disorders for the differential diagnosis of brady and tachyarrhythmias, even when left ventricle systolic function is still preserved.

A sulfonyl fluoride derivative inhibits EGFR by covalent modification of the catalytic lysine.

The emergence of the C797S mutation in EGFR is a frequent mechanism of resistance to osimertinib in the treatment of non-small cell lung cancer (NSCLC). In the present work, we report the design, synthesis and biochemical characterization of UPR1444 (compound 11), a new sulfonyl fluoride derivative which potently and irreversibly inhibits EGFR through the formation of a sulfonamide bond with the catalytic residue Lys745. Enzymatic assays show that compound 11 displayed an inhibitory activity on EGFR comparable to that of osimertinib, and it resulted more selective than the sulfonyl fluoride probe XO44, recently reported to inhibit a significant part of the kinome.

Chemical modification of NSC12 leads to a specific FGF-trap with antitumor activity in multiple myeloma.

Inhibition of FGF/FGFR signaling is a promising strategy for the treatment of malignances dependent from FGF stimulation, including multiple myeloma (MM). The steroidal derivative NSC12 (compound 1) is a pan-FGF trap endowed with antitumor activity in vivo. Chemical modifications of compound 1 were explored to investigate structure-activity relationships, focusing on the role of the bis(trifluoromethyl)1,3-propanediol chain, the stereochemistry at C20 and functionalization of C3 position.

15-year follow-up of MoM 36-mm THA: clinical, laboratory, and radiological (CT and MRI) prospective assessment.

Introduction: There is limited knowledge of the long-term results of metal-on-metal total hip arthroplasty (MoM THA), particularly concerning adverse local tissue reaction (ALTR), Co/Cr ions level and revision rate. Even if MoM bearing surfaces are no longer used, long-term data could help in defining the course and best management for these patients. The purpose of this study is to investigate the clinical outcomes, describe radiological findings including CT metal artefact reduction algorithm for orthopaedic implants (O-MAR) and MRI multi acquisition variable resonance image combination (MAVRIC) in 36-mm MoM THA.

Halting the FGF/FGFR axis leads to antitumor activity in Waldenström macroglobulinemia by silencing MYD88.

The human fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) axis deregulation is largely involved in supporting the pathogenesis of hematologic malignancies, including Waldenström macroglobulinemia (WM). WM is still an incurable disease, and patients succumb because of disease progression. Therefore, novel therapeutics designed to specifically target deregulated signaling pathways in WM are required.

Expanding the Arsenal of FGFR Inhibitors: A Novel Chloroacetamide Derivative as a New Irreversible Agent With Anti-proliferative Activity Against FGFR1-Amplified Lung Cancer Cell Lines.

Fibroblast Growth Factor Receptors (FGFR1-4) have a critical role in the progression of several human cancers, including Squamous Non-Small-Cell Lung Cancer (SQCLC). Both non-selective and selective reversible FGFR inhibitors are under clinical investigation for the treatment of patients with tumors harboring FGFR alterations. Despite their potential efficacy, the clinical development of these drugs has encountered several challenges, including toxicity, and the appearance of drug resistance.

Balancing reactivity and antitumor activity: heteroarylthioacetamide derivatives as potent and time-dependent inhibitors of EGFR.

Second- and third-generation inhibitors of EGFR possess an acrylamide group which alkylates Cys797, allowing to overcome resistance due to insurgence of T790M mutation. Less reactive warheads, yet capable to bind the target cysteine, may be useful to design newer and safer inhibitors. In the present work, we synthesized a 2-chloro-N-(4-(phenylamino)quinazolin-6-yl)acetamide (8) derivative as a prototype of EGFR inhibitor potentially able to react with Cys797 by nucleophilic substitution.

Synthesis, Structural Elucidation, and Biological Evaluation of NSC12, an Orally Available Fibroblast Growth Factor (FGF) Ligand Trap for the Treatment of FGF-Dependent Lung Tumors.

NSC12 is an orally available pan-FGF trap able to inhibit FGF2/FGFR interaction and endowed with promising antitumor activity. It was identified by virtual screening from a NCI small molecule library, but no data were available about its synthesis, stereochemistry, and physicochemical properties. We report here a synthetic route that allowed us to characterize and unambiguously identify the structure of the active compound by a combination of NMR spectroscopy and in silico conformational analysis.