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Quantum noise is currently limiting efficient quantum information processing and computation, impacting on the fidelity and reliability of quantum states. In this work, we consider the tasks of reconstructing and classifying quantum states corrupted by the action of an unknown noisy channel using classical feed-forward neural networks. By framing reconstruction as a regression problem, we show how such an approach can be used to recover with fidelities exceeding 99% the noiseless density matrices of quantum states of up to three qubits undergoing noisy evolution, and we test its performance with both single-qubit (bit-flip, phase-flip, depolarizing, and amplitude damping) and two-qubit quantum channels (correlated amplitude damping). Furthermore, a critical aspect of our investigation involves also a comprehensive comparison between mean squared error and infidelity as loss functions. Our findings reveal that these two metrics yield comparable results in the context of state reconstruction. Moreover, we also consider the task of distinguishing between different quantum noisy channels, and show how a neural network-based classifier is able to solve such a classification problem with perfect accuracy.

Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.

Background: The farnesyltransferase inhibitor SCH66336, in combination with other receptor tyrosine kinase inhibitors, inhibits the growth of non-small-cell lung cancer (NSCLC) cells. We examined whether SCH66336 inhibits angiogenesis of aerodigestive tract cancer cells. Methods: Antiangiogenic activities of SCH66336 against NSCLC, head and neck squamous cell carcinoma (HNSCC), and endothelial cells were examined with cell proliferation, capillary tube formation, and chick aorta (under hypoxic, normoxic, insulin-like growth factor I (IGF)--stimulated, and unstimulated conditions); reverse transcription--polymerase chain reaction; and western blot analyses. The specific roles of the ubiquitin-mediated proteasome machinery, mitogen-activated protein kinase (MAPK) and Akt pathways, and heat shock protein 90 (Hsp90) in the SCH66336-mediated degradation of hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) were assessed with ubiquitin inhibitors and adenoviral vectors that express constitutively active MAP kinase kinase (MEK)1, constitutively active Akt, or Hsp90. Results: SCH66336 showed antiangiogenic activities and decreased the expression of vascular endothelial cell growth factor (VEGF) and HIF-1[alpha] in hypoxic, IGF-stimulated, and unstimulated aerodigestive tract cancer and endothelial cells. SCH66336 reduced the half-life of the HIF-1[alpha] protein, and ubiquitin inhibitors protected the hypoxia- or IGF-stimulated HIF-1[alpha] protein from SCH66336-mediated degradation. SCH66336 inhibited the interaction between HIF-1[alpha] and Hsp90. The overexpression of Hsp90, but not constitutive Akt or constitutive MEK, restored HIF-1[alpha] expression in IGF-stimulated or hypoxic cells but not in unstimulated cells. Conclusions: SCH66336 appears to inhibit angiogenic activities of NSCLC and HNSCC cells by decreasing hypoxia- or IGF-stimulated HIF-1[alpha] expression and to inhibit VEGF production by inhibiting the interaction between HIF-1[alpha] and Hsp90, resulting in the proteasomal degradation of HIF-1[alpha].

Objective: Exploring the association between frailty and mortality in a cohort of patients with COVID-19 respiratory insufficiency treated with continuous positive airway pressure. Methods: Frailty was measured using a Frailty Index (FI) created by using the baseline assessment data on comorbidities and body mass index and baseline blood test results (including pH, lactate dehydrogenase, renal and liver function, inflammatory indexes and anemia). FI > 0.25 identified frail individuals. Results: Among the 159 included individuals (81% men, median age of 68) frailty was detected in 69% of the patients (median FI score 0.3 ± 0.08). Frailty was associated to an increased mortality (adjusted HR 1.99, 95% CI 1.02–3.88, p= 0.04). Conclusions: Frailty is highly prevalent among patients with COVID-19, predicts poorer outcomes independently of age. A personalization of care balancing the risk and benefit of treatments (especially the invasive ones) in such complex patients is pivotal.

The aim of this study was to evaluate, through a meta-analysis, the predictability of Regenerative Endodontic therapies with antibiotic pastes and calcium hydroxide [Ca(OH)2], related to four variables as follows: root dentin wall thickening, apical closure, apical repair and root lengthening.

As professionals working with individuals who misuse addictive substances, we sometimes are asked to evaluate someone who suffers from both a potential substance misuse problem and a chronic pain disorder. [...]

ABSTRACTIntroduction: Cancer immunotherapies with monoclonal antibodies (mAbs) against immune checkpoints (i.e. CTLA-4 and PD-1/PD-L1) have revolutionized antineoplastic treatments. Immune checkpoint inhibitors (ICIs) approved for cancer immunotherapy are mAbs anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab, and cemiplimab), and anti-PD-L1 (atezolizumab, avelumab, and durvalumab). Treatment with ICIs can be associated with immune-related adverse events (irAEs), including an increased risk of developing myocarditis. These findings are compatible with the observation that, CTLA-4, PD-1, and PD-L1 pathways play a central role in the modulation of autoimmunity.Areas covered: In this paper, we start from examining the pathogenesis of cardiovascular adverse events from ICIs, and then we focus on risk factors and strategies to prevent and manage this cardiotoxicity.Expert opinion: There is a growing need for a multidisciplinary approach of ICI-associated cardiotoxicity, involving oncologists, cardiologists, and immunologists. Prevention and effective management of ICIs cardiotoxicity starts with an in-depth screening and surveillance strategies of high-risk patients, in order to improve early detection and appropriate management in a personalized approach.

Inadvertent perioperative hypothermia is a frequent problem associated with surgical patients which can have significant consequences during surgery and in the immediate postoperative period. We compared 35 randomised patients using over vs. under body forced air heating. There were no statistically significant differences between some demographic and surgical parameters such as: age, weight, height, body mass index, length of anaesthesia and operation. Statistically significant differences were found between the patient’s admission to the operating room and 30 minutes and the end of the procedure on the under body patients group. This study analyses a uniform population of patients (Foot and Ankle Surgery) previously not studied and supports the use of under body blankets.

Blocking angiogenesis represents a fundamental process in Colorectal Cancer (CRC) treatment. VEGF (vascular endothelial growth factor) pathway is implicated in various processes that regulate tumor vascularization and proliferation. In the last years, great efforts have been made thanks to the discovery of targeted drugs that block VEGF and its receptors conferring a benefit in a variety of tumors, including CRC. To date, four drugs have been approved for the treatment of metastatic CRC (mCRC): bevacizumab, aflibercept, ramucirumab and regorafenib. Unfortunately, patients relapse due to the appearance of resistance. The VEGF family, its role in the angiogenesis and complex heterogeneity of mechanisms that escape tumor blockade are not completely understood and there is a lack of biomarkers of response to anti-angiogenic drugs. We describe the principal mechanisms of resistance to anti-VEGF therapy and discuss potential biomarkers to be investigated in the near future.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Tyrosine kinase inhibitors (TKIs) of the EGF receptor (EGFR) have provided a significant improvement in the disease outcome of nonsmall cell lung cancer (NSCLC). Unfortunately, resistance to these agents frequently occurs, and it is often related to the activation of the Hedgehog (Hh) and MET signaling cascades driving the epithelial-to-mesenchymal transition (EMT). Because the concomitant inhibition of both Hh and MET pathways restores the sensitivity to anti-EGFR drugs, here we aimed at discovering the first compounds that block simultaneously MET and SMO. By using an “in silico drug repurposing” approach and by validating our predictions both in vitro and in vivo, we identified a set of compounds with the desired dual inhibitory activity and enhanced antiproliferative activity on EGFR TKI-resistant NSCLC. The identification of the known MET TKIs, glesatinib and foretinib, as negative modulators of the Hh pathway, widens their application in the context of NSCLC.

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. To date, standard MPM therapy is still limited to surgery, radiotherapy, and chemotherapy, including pemetrexed and platinum compounds. The main mechanisms of platinum resistance are associated with DNA repair pathways. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) are important components of the DNA repair, considered as prognostic and predictive biomarkers in various cancer types. The main goal of the present study was to investigate the ERCC1 and RRM1 expression and their potential impact on outcome in this tumor. A series of 73 MPM, mainly treated with a platin-based regimen, was collected and the immunohistochemistry tests were performed to assess ERCC1 and RRM1 expression. In addition, a multiplex immunohistochemistry has been validated to detect simultaneously the 2 proteins on the same slide. In our series, 36 of 73 cases showed ERCC1 expression and 55 of 73 showed RRM1 expression. The double immunohistochemical staining showed the coexpression of ERCC1/RRM1 in 34 of 73 cases. A significant association between ERCC1 and RRM1 expression was observed in our series (P<0.05). Patients with ERCC1/RRM1 coexpression experienced shorter median overall survival (6.6 vs. 13.8 mo, log-rank=7688; P=0.006). Our results suggest that the coexpression of ERCC1/RRM1 could define a group of MPM patients with the worst prognosis who should need likely alternative treatment. In conclusion, we propose the putative usefulness of ERCC1/RRM1 coexpression as prognostic biomarkers for overall survival in MPM.

Osimertinib showed great clinical efficacy for activated-EGFR NCLC patient treatment. The aim of this work was to test the efficacy of a complete EGFR-inhibition by osimertinib plus the monoclonal antibody cetuximab or the MEK1/2-inhibitor selumetinib in EGFR-mutated NCLC in vivo models.

Thanks for another great issue of Handguns. Patrick Sweeney is one of my favorite authors, but his comment in the 'Ammo Shelf' article may not be exactly accurate. He considers [...]

Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED.

Introduction:In recent times, there has been much interest in the development of pharmacological kinase inhibitors that treat NSCLC. Furthermore, treatment options have been guided by the development of a wide panel of synthetic small molecule kinase inhibitors. Most of the molecules developed belong to the type I class of inhibitors that target the ATP-binding site in its active conformation. The high sequence similarity in the ATP-binding site among members of the kinase families often results in low selectivity and additional toxicities. Also, second mutations in the ATP-binding site, such as threonine to methionine at position 790, have been described as a mechanism of resistance to ATP-competitive kinase inhibitors. For these reasons, alternative drug development approaches targeting sites other than the ATP cleft are being pursued. The class III or allosteric inhibitors, which bind outside the ATP-binding site, have been shown to negatively modulate kinase activity.Areas covered:In this review, the authors discuss the most well-characterised allosteric inhibitors that have reached clinical development in NSCLC.Expert opinion:Great progress has made in developing inhibitors with entirely new modes of action. That being said, it is important to highlight that despite their apparent simplicity, biochemical assays will remain at the core of drug discovery activities to better explore these new opportunities.

A number of successful systemic therapies are available for the treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Resistance to either chemotherapy and targeted agents limits the effectiveness of current cancer therapies, including those used to treat metastatic colorectal cancer (mCRC) which is one of the leading causes of cancer-related death worldwide. Resistance to therapeutic drugs can be already present at diagnosis or it can develop after treatment. These two forms of resistance are respectively called intrinsic and acquired. The identification of mechanisms of drug resistance may highlight new biomarkers useful to predict the clinical outcome or the likely responsiveness to pharmacological treatment of those metastatic CRC patients who cannot benefit from current therapeutic regimen. Moreover, the recognition of panels of biomarkers may suggest new strategies to overcome resistance by rational drug design and combination treatment. In this review, we describe molecular mechanisms of resistance to chemotherapies and targeted agents that may be relevant to colorectal cancer and the possible strategies to overcome the resistance.

SUMMARY Lung cancers harboring mutations in the EGFRrespond to EGF receptor-tyrosine kinase inhibitor, which at present represent the most appropriate treatment for EGFRmutation-positive advanced non-small-cell lung cancer. Unfortunately drug resistance invariably emerges with different known mechanisms, including the EGFRT790M mutation, METgene amplification, EGFRamplification, mutations in the PIK3CAgene, mutations in the HER2gene, IGF1Ramplification, transformation of non-small-cell lung cancer into small-cell lung cancer and moreover epithelial-to-mesenchymal transition. Various strategies to manage secondary resistance have been explored and in this review we will analyze scientific data in support of these different strategies to assess the most adequate to use in relation to the progression disease.

Introduction: Metformin is a widely used antidiabetic drug, which also displays significant growth inhibitory and proapoptotic effects in several cancer models, including lung cancer, alone or in combination with chemotherapeutic drugs.Areas covered: The role of metformin as a chemopreventive drug in lung cancer is still an object of debate as epidemiological studies have shown contrasting results. More preclinical data support its role as an adjuvant drug in the treatment of lung cancer, in combination with chemotherapy or targeted molecular drugs, although the complete mechanism of action of metformin is still unclear, and potentially may exert unexpected effects with contradictory clinical implications.Expert opinion: Future perspective studies are required in nonsmall-cell lung cancer (NSCLC) patients to better investigate the effect of metformin action on the RAS/RAF/MAPK pathway and the best context in which to use metformin in combination with molecularly targeted agents.

Introduction:Targeted agents have dramatically improved and enriched the therapeutical choices for patients with metastatic colorectal cancer (mCRC). By better understanding the role of the angiogenic pathway in colorectal cancer (CRC), new therapies have been developed. Bevacizumab, the first anti-angiogenetic agent approved for the treatment of mCRC provide a proof of concept since it has improved the progression-free survival and overall survival when combined with cytotoxic chemotherapy.Areas covered:This review is focused on the most recent findings on the VEGF signaling pathway and new therapeutic drugs explored in clinical trials.Expert opinion:Despite the advantage offered by bevacizumab, the median overall survival of mCRC patient exceeds 21 months; thus, investigational efforts are needed. Several antiangiogenic agents for the treatment of mCRC are being tested in preclinical and clinical Phase I/II trials. Unfortunately a discrete number of Phase III trials produced negative results. Recently aflibercept and regorafenib, two new antiangiogenic drugs, have been approved as the new-targeted agents for the treatment of mCRC, according to the positive findings from the VELOUR and the CORRECT studies. In order to maximize clinical impact it will be important to validate predictive biomarkers and best combination treatments to offer for mCRC patients; further research and intense investigation is still required.

The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non–small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here.

Introduction:Treatment of colorectal cancer (CRC) has changed dramatically over the past decade, mainly due to the advent of molecularly targeted agents. In particular, an improved understanding of the role of the angiogenesis pathway in CRC has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic CRC (mCRC) and at present is the only antiangiogenesis agent approved for the treatment of this cancer.Areas covered:In this review, the authors outline the most recent data on the VEGF signaling pathway and on new therapeutic reagents that target it, provide insight into their mechanisms, and describe results from recent clinical trials.Expert opinion:In the new decade of ‘modern therapy', an increasing number of antiangiogenic agents for the treatment of mCRC are being tested in preclinical models, and dozens of studies on these drugs are ongoing. Presently, eight novel antiangiogenic agents are in Phase III trials and a wide range of other candidates are being tested in Phase I/II trials. Given the preliminary positive results of two recent Phase III trials, aflibercept and regorafenib, probably, will be new-targeted agents approved for the treatment of mCRC. Furthermore, the list of potentially approved agents seems to increase in the next years and to maximize their potential clinical impact, is critically important to introduce efficient molecular diagnostic methodologies into the drug development process to indentify the subset of patients who would benefit most from their use.

The prognosis of patients with pancreatic cancer is extremely poor, and current systemic therapies provide marginal survival benefits for treated patients. The era of targeted therapies has offered a new avenue to search for potentially more effective strategies. Epidermal growth factor receptor (EGFR) is a member of the erbB/human epidermal growth factor receptor family of tyrosine kinases, which includes erbB2/HER2, erbB3/HER3 and erbB4/HER4. Epidermal growth factor receptor overexpression may be detected in up to 90 of pancreatic tumors. Two pharmacologic approaches have been successfully used to inhibit epidermal growth factor receptor function in cancer treatment: neutralizing monoclonal antibodies and small molecule tyrosine inhibitors. The randomized trials studying the addition of EGFR targeted agents to gemcitabine compared with gemcitabine alone have been disappointing, although results with the EGFR tyrosine kinase inhibitor erlotinib were statistically significant but clinically of marginal benefit. In this article, we review the epidermal growth factor receptor signaling network in pancreatic cancer, the strategies to increase the effectiveness of epidermal growth factor receptor inhibitors, and the clinical trials of these inhibitors in pancreatic cancer.

Our goal was to determine the role of vascular endothelial growth factor (VEGF) in diagnosing of pleural effusion (PE) in order to select patients deserving of more aggressive procedures. Seventy-nine consecutive patients with undiagnosed unilateral PE were enrolled. Pleural VEGF levels, measured using enzyme-linked immunosorbent assay (ELISA), were correlated to etiology of PEs and other markers (protein, lactic dehydrogenase, amylase, glucose). The median level of VEGF in exudates (n=65) was significantly higher than that in transudates (P=0.0001) and among exudates, it was significantly higher in malignant (n=49) than that in benign exudates (P=0.005). No significant differences were observed between malignant effusions due to lung cancer (n=11) and other malignant effusions [mesothelioma (n=13) and/or extra-thoracic cancer]. Among all variables evaluated, logistic regression found that only VEGF was significantly correlated with the presence of malignant disease (P=0.002). Analysis of the receiver operating characterists (ROC) curves showed that the areas under the curve of VEGF were significantly larger than that of amylase (P=0.02), glucose (P=0.01), lactic dehydrogenase (P=0.001) and protein (P=0.01). VEGF increased the diagnostic rate of cytological examination by 24%. VEGF may represent a helpful adjunct to conventional diagnostic tools in ruling out malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Cetuximab and panitumumab have been approved for the treatment of metastatic colorectal cancer when used alone or in combination with irinotecan. Although EGFR is expressed in most metastatic colorectal tumors, only a subset of patients derive clinical benefit from treatment with EGFR inhibitors. The experimental and clinical evidence supporting the use ofKRAStesting for selecting patients for treatment with anti-EGFR monoclonal antibodies is discussed.

In the current clinical trial summary, we present a randomized phase II trial of pemetrexed or RAD001 as second-line treatment of elderly patients with advanced non–small-cell lung cancer. The molecular and clinical rationale is reviewed. The primary endpoint is progression-free survival, and secondary endpoints include objective tumor response rates, disease control rates, safety, tolerability, and overall survival. Based on the statistical design, the investigators plan to enroll 92 elderly patients, 46 per arm.

In the last decades the epidermal growth factor receptor (EGFR), which is frequently expressed in a variety of epithelial tumors, has been a major target of molecular anticancer therapy.

Novel therapeutic approaches targeting signaling pathways involved in cell proliferation, apoptosis, angiogenesis and metastasis have been under clinical development. Of many potential targets in adult solid tumors, the epidermal growth factor receptor (EGFR) has been the most extensively studied since its over-expression has been observed in several common solid tumors. However, the insurgence for resistance to drugs targeting the EGF-receptor has been described. The understanding of the mechanisms which are responsible of resistance to EGFR inhibitors could lead to the development of improved strategies to integrate anti-EGFR therapies. In this review, we will describe the latest new strategies developed to optimize the therapeutic effects of EGFR inhibitors, by exploring combinations with other molecular targeted approaches including other erbB family member inhibitors, drugs with different structure and mechanism of action, other tumor cell-directed signal transduction inhibitors, anti-angiogenic treatment modalities, and the use of broad spectrum EGFR tyrosine kinase inhibitors.

The epidermal growth factor receptor (EGFR) is a cell membrane receptor that plays a key role in cancer development and in the progression of many human malignancies, including non-small-cell lung cancer (NSCLC). EGFR-dependent signaling is involved in cancer cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Targeting the EGFR is a valuable molecular approach in cancer therapy. This receptor is overexpressed in up to 80% of NSCLC cases. Thus, several molecules inhibiting this critical biologic pathway have been synthesized and tested as a single agent or in combination with other anticancer modalities in a wide of clinical trials, including reversible and irreversible small tyrosine kinase inhibitors, such as gefitinib and erlotinib, dual vascular endothelial growth factor receptor EGFR tyrosine kinase inhibitors, such as vandetanib (ZD-6474), and monoclonal antibodies, such as cetuximab, which have shown promising activity in patients with NSCLC. This review focuses on the preclinical and clinical results available with EGFR inhibitors in the treatment of NSCLC patients.

Over the last decade, the concept of targeted biological therapy for the treatment of cancer has emerged. However, a better understanding of these targets and their role in tumor cells and in the surrounding stromal cells is required. Two interesting biological targets are the epidermal growth factor receptor (EGFR) and the vascular endothelia growth factor (VEGF) and its receptors. A number of agents that target these pathways have been described. Many of these are currently in clinical trials and a few have recently been approved by the regulatory authorities in USA and in the European Union. The molecular pathways involved in the proliferation of cancer cells and in tumor-related angiogenesis are very complex and the interference with only a single step of these pathways may often reveal an insufficient therapeutic approach. Moreover, cancer cells have an inherent ability to harness different growth factor signaling pathways for growth advantage and cell survival, a process that may even be facilitated by the use of selective targeted agents. Because of these escape mechanisms, monotherapy with selective targeted agents is unlikely to be a fully effective cancer treatment. For these reasons, targeting different pathways is an attractive and effective therapeutic strategy with a strong rationale for investigating this approach in the clinic. This review focuses on the preclinical rationale of combining targeted agents such as EGFR and VEGF inhibitors in the treatment of cancer and on the clinical trials that have emerged from these studies.

Farnesyl transferase inhibitors (FTIs) are anticancer agents that were designed to block the post-translational attachment of the prenyl moiety to C-terminal cysteine residue of Ras and thus inactivate it. Because Ras plays an important role in tumour progression and the ras mutation is one of the most frequent aberrations in cancer, FTIs have been expected to exert excellent therapeutic activities. Phase I and II clinical trials confirmed relevant antitumour activity and low toxicity; however, no improvement in overall survival has been reported in Phase III trials. The exact mechanism of action of this class of agents is currently unknown. Increasing lines of evidence indicate that the cytotoxic actions of FTIs are not due to the inhibition of Ras proteins exclusively, but to the modulation of other targets, including RhoB, the centromere-binding proteins and other proteins that have not yet been identified. This review describes the pharmacological and clinical data as well as mechanisms of action of FTIs, especially lonafarnib (SCH-66336), a non-peptidomimetic inhibitor that has shown anticancer activity.

To the authors' knowledge, little is known to date regarding the prognostic relevance of measuring serum levels of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, in patients with colon carcinoma who undergo surgery. Preoperative and postoperative VEGF serum levels were determined by enzyme-linked immunoadsorbent assay in 81 patients with colon carcinoma who were undergoing surgery. Fifty healthy individuals served to define normal VEGF serum levels. Preoperative VEGF serum levels were significantly higher in the group of patients with colon carcinoma (mean, 504.1 pg/mL ± 223 pg/mL; range, 285–1390 pg/mL; 95% confidence interval [95%CI], 49 pg/mL) compared with the control group (mean, 78.1 pg/mL ± 22 pg/mL; range, 40–110 pg/mL; 95%CI, 4.3 pg/mL; P &lt; 0.001). Multiple regression analysis demonstrated a significant correlation (r) between preoperative VEGF serum levels and age (r = − 0.275; P = 0.013), Dukes stage (r = 0.488; P &lt; 0.001), and carcinoembryonic antigen (CEA) levels (r = 0.285; P &lt; 0.018). No significant correlation was found between preoperative VEGF serum levels and disease site, patient gender, tumor size, tumor grade, or performance status. Moreover, preoperative VEGF serum levels were significantly lower in patients who underwent curative surgery compared with patients who underwent noncurative surgery (443 pg/mL ± 117 pg/mL vs. 821 ± 353 pg/mL, respectively; P &lt; 0.0001). Logistic regression analysis selected preoperative VEGF and CEA serum levels as the only good prognostic indicators of curative and noncurative surgery (P &lt; 0.001; relative risk, 2.98 and 2.03, respectively). Furthermore, VEGF serum levels dropped significantly after surgery, with a further downward trend until the 30th postoperative day (P &lt; 0.001). Stepwise regression analysis selected preoperative VEGF serum level as the only variable associated significantly with the prediction of both disease-specific survival and disease-free survival (P = 0.001). Preoperative serum VEGF levels may be useful for predicting outcome in patients with colon carcinoma who undergo surgery. Cancer 2004;100:270–8. © 2003 American Cancer Society.

Interleukin-8 (IL-8) is a pleiotropic cytokine that has also been shown to exert effects relevant to cancer growth and progression. Cancer progression is believed to be contributed to by the ability of this cytokine to promote angiogenesis and mitogenic effects. As IL-8 production at the tumor site may determine elevated serum levels of this cytokine because of hematogenous leakage, it is conceivable that patients with high IL-8 serum levels may have tumors actively producing this cytokine. The aim of this study was, therefore, to assess IL-8 serum levels in 60 non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and to correlate them with prognosis. IL-8 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, IL-8 serum levels were shown to be significantly increased in stage IV patients compared with stage III patients. When basal IL-8 serum levels in cancer patients were analyzed according to response to chemotherapy, responders were shown to have significantly lower IL-8 serum levels than nonresponders. On univariate analysis, the IL-8 serum level was included among the variables capable of affecting both overall survival (OS) and time to treatment failure (TTF). However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-8 serum levels. In conclusion, this study showed that IL-8 serum levels were elevated in advanced NSCLC patients and correlated with both OS and TTF, but they were shown not to be an independent prognostic factor.

The effects of silicone oil and perfluorocarbon liquids used in retinal reattachment surgery were studied in vitrousing rat retinal cultures seeded on microporous inserts. These inserts allow the cell layer to be in contact with the material to be tested on the apical side and with the nutrient medium on the basal side. The materials tested were silicone oil, the perfluorocarbons perfluorophenanthrene and perfluoroctane, and hydroxypropylmethylcellulose. Perfluorophenanthrene, the heaviest of the compounds, induced a very precocious detachment of the cell layer. All the other tested biomaterials were compatible with cell survival and did not alter the structural organization of the retinal cultures, as revealed by scanning electron microscopy. By immunocytochemical techniques we evaluated the cell composition and the differentiation state of each of the cultures. In both control and treated samples, neuronal cells were well preserved. The expression of microtubule−asso ciated protein 2, a marker of differentiated neuronal cytoskeleton, was not affected. Amacrine neurons, immunolabeled for γaminobutyric acid, still were detectable after treatment. Synapses, marked by immunoreactivity for synapthophysin, were equally preserved. Vimentinpositive glial cells did not show modifications. The apoptotic rate, as determined by the terminal transferasemediated dUTP–biotin nick endlabeling assay, was similar in treated and control samples. The results confirm that the use of biomaterials with a specific gravity close to intraocular fluids is compatible with retinal cell survival and differentiation in vitro. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 548–555, 2002

The Thoracic Centers International COVID-19 Collaboration (TERAVOLT) registry found ∼ 30% mortality in patients with thoracic malignancies during the initial COVID surges. Data from South Africa suggested a decrease in severity and mortality with the Omicron wave. Our objective was to assess mortality of patients with thoracic malignancies with the Omicron-predominant wave, and efficacy of vaccination.

Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.

Flunarizine (10 mg/day for 60 days) was given to eight postmenopausal women with common migraine. Plasma LH pulsatility fluctuation, peripheral concentrations of prolactin (PRL), cortisol, β-endorphin (β-EP), β-lipotropin (β-LPH) and Pain Total Index (PTI) were evaluated before and after treatment. PTI was significantly reduced by flunarizine, which did not affect β-LPH, β-EP and cortisol plasma levels. On the contrary, both PRL values and amplitude, and length of LH pulses had increased at the end of treatment. Flunarizine reduced head pain in postmenopausal women. However, the enhancement of both PRL and LH release indicates that this calcium antagonist might interfere with the dopaminergic tonus.

The optimal placement of a tracheal tube following percutaneous dilator tracheostomy is technically demanding in patients with tracheal stents. We report a successful technique of tracheostomy tube placement with PercuTwist in an intubated patient with a tracheal stent for malignant stenosis. The endotracheal tube was replaced with a laryngeal mask, a 9.0-mm tracheostomy tube was inserted into the trachea over a PercuTwist percutaneous dilator and through the tracheal stent under video-bronchoscopic vision. The PercuTwist technique kept the lumen of trachea, a laryngeal mask enabled adequate ventilation, and a video-bronchoscope guided the prompt insertion of the tracheostomy tube through the stent.