21 research outputs found
Erratum to: Lung Tissue Damage Caused by Heat Accumulation from Adjacent Laser Application: Surgical Implications (Thoracic and Cardiovascular Surgeon (2014) DOI: 10.1055/s-0034-1389086)
No full textIt has been brought to the Publisher's attention that the author names "Filippo Lococo" and "Alfredo Cesario" were not listed correctly in the above-mentioned article, published on eFirst on September 5, 2014. DOI of the original article is DOI: 10.1055/s-0034-1389086. The names should be read as "Filippo Lococo" and "Alfredo Cesario" in place of "Lococo Filippo" and "Cesario Alfredo."
Pharmacological Stimulation of Nicotinamide Phosphoribosyltransferase with P7c3-A20 as a Protective Strategy for Paclitaxel-Induced Peripheral Neuropathy
No full textImprovements in anticancer pharmacotherapy over the past 40 years have led to a steady increase in the number of cancer survivors worldwide. The clinical effectiveness of anticancer agents like the microtubule-stabilizing agent, paclitaxel, ultimately led to their adoption into standard of care regimens for most cancers. What makes these drugs so effective is how they bind to their respective targets to disrupt fundamental cellular processes. For example, by binding to β-tubulin, paclitaxel induces polymerization and stabilization of cellular microtubules, leading to impairments in cellular functions like mitosis and intracellular transport. While an ingenious approach to kill cancer cells, microtubules are ubiquitous in all cell types. Consequently, paclitaxel has a burdensome side effect profile due to its effects on noncancerous cells. The most prevalent nonhematologic side effect is chemotherapy-induced peripheral neuropathy, which arises due to paclitaxel-induced damage to peripheral afferent sensory neurons. Cancer patients with peripheral neuropathy often develop debilitating neuropathic pain and numbness that diminish everyday quality of life. Symptoms intensify as treatment progresses and can persist for months and years beyond treatment. There is no effective treatment or prevention for chemotherapy-induced peripheral neuropathy. Instead, patients must dose de-escalate or discontinue life-saving chemotherapy, which subsequently worsens cancer prognosis. Thus, there is a compelling need to identify novel therapeutic options to prevent or treat chemotherapy-induced peripheral neuropathy so to improve both anticancer treatment and patient quality of life. The goal of this dissertation is to evaluate the neuroprotective efficacy of a first-in-class stimulator of nicotinamide phosphoribosyltransferase, P7C3-A20, against paclitaxel-induced peripheral neurotoxicity. Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme in the salvage pathway for nicotinamide adenine dinucleotide, an indispensable redox biomolecule that drives energy production. We first developed an aggressive model of paclitaxel-induced peripheral neuropathy in adult male rats. Treatment with a near maximally-tolerated dose of paclitaxel produced significant, but recoverable weight loss and leukopenia. Paclitaxel-treated rats exhibited differentially altered nociceptive thresholds to noxious stimuli, including the development of persistent allodynia to mechanical and cold stimulation as well as transient hyposensitivity to heat stimulation. Toxicity associated with paclitaxel treatment required that 25% of the rats be removed from the study. Histological analysis determined that paclitaxel triggered degeneration of intraepidermal nerve fibers and up-regulated expression of activating transcription factor 3 in nuclei of neuron cell bodies residing in the lumbar dorsal root ganglia. Remarkably, daily treatment with P7C3-A20 prevented mechanical allodynia and heat hypoalgesia, and reduced the cold allodynia associated with paclitaxel treatment. P7C3-A20 also prevented intraepidermal nerve fiber degeneration and partially decreased activating transcription factor 3 expression in lumbar dorsal root ganglia neurons. A randomized, double-blind trial determined that P7C3-A20, and another analogue, P7C3-S321, dose-dependently decreased paclitaxel-induced neuropathic pain and intraepidermal nerve fiber loss. Furthermore, P7C3-A20 improved indices of general health and prevented premature death that normally arose because of overt toxicity caused by paclitaxel. P7C3-A20 displayed superior neuroprotective efficacy, while an inhibitor of poly(adenosine diphosphate-ribose) polymerase was completely ineffective. P7C3-A20 stimulated nicotinamide adenine dinucleotide production in vitro following induction of damage with either hydrogen peroxide or paclitaxel, but not under normal conditions. Additionally, P7C3-A20 in vivo stimulated nicotinamide adenine dinucleotide recovery in the hindpaw and sciatic nerve of rats treated with paclitaxel. FK866 blocked P7C3-A20-mediated nicotinamide adenine dinucleotide production in vitro and the neuroprotective effects on peripheral nociceptive neurons in vivo. Although treatment with either nicotinamide or a subthreshold dose of P7C3-A20 alone was ineffective, the combination produced neuroprotection against paclitaxel that was equivalent to that of a maximal dose of P7C3-A20. We also investigated the effects of P7C3-A20 on cancer cell proliferation and on the anticancer efficacy of paclitaxel. Only MDA-MB-231 breast cancer cells demonstrated a slight increase in proliferation by P7C3-A20, but enhanced growth of implanted MDA-MB-231 tumor xenografts was not observed. Furthermore, P7C3-A20 did not diminish the antiproliferative effects of paclitaxel, despite preventing the development of mechanical allodynia in the tumored mice. In conclusion, these studies discovered robust neuroprotective efficacy of P7C3-A20 against paclitaxel -induced peripheral neurotoxicity, likely through the enhancement of nicotinamide phosphoribosyltransferase-mediated recovery of nicotinamide adenine dinucleotide. Based on these results, clinical investigation of P7C3-A20 as a potential treatment option for chemotherapy-induced peripheral neuropathy may be warranted
Dataset and analysis of automated and manual methods to differentiate wide QRS complex tachycardiasDataverse
No full textThe differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia (SWCT) via 12-lead ECG (electrocardiogram) interpretation is a crucial yet demanding clinical task. Decades of research have been dedicated to simplifying and improving this differentiation via manual algorithms. Despite such research, the effectiveness of such algorithms still remains limited, primarily due to reliance on user expertise. To combat this limitation, automated algorithms have been created that show promise as alternatives to manual ECG interpretation. However, direct comparison of the methods’ diagnostic performances has not been undertaken. A recent publication (LoCoco et al., 2024) compared the diagnostic performance between traditional manual ECG interpretation approaches (i.e. Brugada, Vereckei aVR, and VT Score) to novel automated wide QRS complex tachycardia differentiation algorithms (i.e. WCT Formula I, WCT Formula II, VT Prediction Model, Solo Model, and Paired Model). Two electrophysiologists independently applied the 3 manual WCT differentiation approaches to 213 ECGs. Simultaneously, computerized data from the same paired WCT with baseline ECGs were processed by the 5 automated WCT differentiation algorithms. Following these analyses, the diagnostic performance of automated algorithms was compared with manual ECG interpretation approaches. In this article, a summary of data components relating to diagnostic performance of the methods tested is presented
Author response: Pharmacological augmentation of nicotinamide phosphoribosyltransferase (NAMPT) protects against paclitaxel-induced peripheral neuropathy
No full textASO Author Reflections: The Number of Involved Structures is a Promising Prognostic Factor in Thymic Epithelial Tumors
No full textOn the Art of the Saiva Temple Banteay Srei: Its Stylistic Position in the Art History of Cambodia
No full textIn March this year, on his way back from a research trip to India, the author had an opportunity of visiting Banteay Srei, a Śaiva temple situated alone in a jungle 21km. northeast of Angkor Thom. Though small in scale this temple is significant in the classical period of Cambodian art history as the place where a unique type of art was developed. After the publication of the monograph “Le temple d’Īçvarapura” in 1926 there have been reconstruction of the original buildings of the temple and discovery of previously unknown sources of information, and studies on the age and style of Banteay Srei art have seen progress. But it is surprise to find a recently published book (written in English) on Indian art and architecture still including statements on the temple which are based upon out-of-date chronology. The author therefore introduces herein to Japanese students, through his own observation as well as through reference to previous studies by French scholars, the outline of the unique art at Banteay Srei illustrated by photographs taken by himself, focusing his discussion on the position which Banteay Srei art holds in ihe history of Cambodian art.
The central and most important buildings of Banteay Srei were formerly considered, based upon the interpretation of numerous inscriptions that had been dicsovered, to have been constructed (or reconstructed) in 1304 A. D., but studies on other important inscriptions discovered thereafter have led to the theory, which is now generally accepted, that the temple was founded in 967 A. D. and that its buildings were all finished by about 1000 A. D. However, as is suggested by the fact that Banteay Srei art was once misunderstood by a certain scholar to be a “Lococo phase” of the last part of the classical period, it gives, at a glance, an impression of stylistic floridness; it should therefore be carefully studied whether the above-mentioned dating is applicable, from a stylistic point of view, to all fields of its architecture, ornamentation and sculpture.
French scholars—of whom M. H. Parmentier on architecture, Mme G. de Coral Rémusat on ornamentation as well as on the style of Banteay Srei art in general, and M. J. Boisselier on the stylistic analysis of sculpture, are worth special mention- have achieved notable progress in detailed analysis of the various styles of Khmer art, and they universally agree that the style of Banteay Srei should be dated to the late tenth century. The present author, in support of their theory, discusses that Banteay Srei art contains much of stylistic tradition carried on from ninth-century art, and is rich especially in “archaisant” elements; and he emphasizes that it does not show any tendency for “degeneration” of style indicative of the last period of classical age, but in stead is full of fresh, vivid effect; and that it reveals a new creation of artistic representation.
After discussing on the disposition of the buildings and on the motifs and style of their brilliant decoration, the author gives descriptions of the bas-reliefs illustrating stories, the relief images of gods and goddesses (dvārapāla and devatā) and the full-sculptured images. He emphasizes especially the fascinating harmonious portrayal of the goddesses (devatā), and the unique new style of Banteay Srei art represented by it.
The author takes this opportunity to express his sincerest gratitude to M. Louis Content and M. Henry Dufour of the Conservation who kindly guided him at his visit to Banteay Srei as well as to the sites in and around Angkor Thom.journal articl
Impact of High‐Grade Patterns in Early‐Stage Lung Adenocarcinoma: A Multicentric Analysis
No full textObjective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a signifcantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas.
Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Diferences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-highgrade and high-grade patterns.
Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a signifcant better prognosis compared to T1a-b-c with high-grade pattern (p=0.020), but the latter had similar OS compared to T2a (p=0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a signifcantly better DFS compared to
those with high-grade patterns (p=0.034), and it was similar to T2a (p=0.839). Multivariable analysis confrms the role of T descriptor according to high-grade pattern both for OS (p=0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p=0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confrmed after the propensity score matching analysis.
Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors
Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study
No full textOBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008).CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern
Abstract P3-12-06: Subpopulations of peripheral sensory neurons are differentially sensitive to the microtubule-targeting agent, paclitaxel
No full textMayo Clinic VT calculator: A practical tool for accurate wide complex tachycardia differentiation
No full textAbstract The discrimination of ventricular tachycardia (VT) versus supraventricular wide complex tachycardia (SWCT) via 12‐lead electrocardiogram (ECG) is crucial for achieving appropriate, high‐quality, and cost‐effective care in patients presenting with wide QRS complex tachycardia (WCT). Decades of rigorous research have brought forth an expanding arsenal of applicable manual algorithm methods for differentiating WCTs. However, these algorithms are limited by their heavy reliance on the ECG interpreter for their proper execution. Herein, we introduce the Mayo Clinic ventricular tachycardia calculator (MC‐VTcalc) as a novel generalizable, accurate, and easy‐to‐use means to estimate VT probability independent of ECG interpreter competency. The MC‐VTcalc, through the use of web‐based and mobile device platforms, only requires the entry of computerized measurements (i.e., QRS duration, QRS axis, and T‐wave axis) that are routinely displayed on standard 12‐lead ECG recordings
