Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks. METHODS: We analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level. RESULTS: We found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our finding may help understand networks related to a more "isolated" epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.

The changing scenario of 1st line therapy in non-oncogene addicted NSCLCs in the era of immunotherapy.

During the last two decades front-line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) has profoundly changed moving from the old "one size fits all" concept to a "histology-based" approach and then, for a small subgroup of patients to a "molecularly-selected" one. The development of immune checkpoint inhibitors and the unprecedented results reported in 2nd/3rd line prompted the evaluation of these novel therapeutic agents in chemotherapy-naïve patients either alone or in combination with platinum-based chemotherapy. Several randomized trials are evaluating the impact of immune-checkpoint inhibitors in 1st line and some of them have yet produced preliminary evidence of efficacy. However, still a long way to go and several questions are still unanswered, including proper patients selection, optimal sequential/combinatorial use of these agents, appropriate treatment duration, and finally the identification of predictive biomarkers. The aim of this paper is to provide a comprehensive overview on the growing role of immune checkpoint inhibitors in the upfront treatment of advanced non-oncogene addicted NSCLC either as single agent or in combination with other agents.

Deoxygenation of waste cooking oil and non-edible oil for the production of liquid hydrocarbon biofuels.

Deoxygenation of waste cooking vegetable oil and Jatropha curcas oil under nitrogen atmosphere was performed in batch and semi-batch experiments using CaO and treated hydrotalcite (MG70) as catalysts at 400 °C. In batch conditions a single liquid fraction (with yields greater than 80 wt.%) was produced containing a high proportion of hydrocarbons (83%). In semi-batch conditions two liquid fractions (separated by a distillation step) were obtained: a light fraction and an intermediate fraction containing amounts of hydrocarbons between 72-80% and 85-88% respectively. In order to assess the possible use of the liquid products as alternative fuels a complete chemical characterization and measurement of their properties were carried out.

Post-transplant Lymphoproliferative Disorders: A Rare Case of Primary Pericardial Involvement Epstein-Barr Virus-Correlated in Heart Transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) are considered a fatal consequence of immunosuppression. We report a case of a 52-year-old patient, who underwent a cardiac transplantation and presented undefined recurrent episodes of pleuropericardial effusions without lymphoadenomegaly at chest radiographs and computed tomography. Histopathological analysis of the bioptic pericardium showed a specific chronic inflammation. Monitoring endomyocardial biopsies (EMBs) showed only 1 episodes of greater than grade 2R acute cellular rejection requiring immunosuppressive treatment, mild vasculitis in 2 subsequently EMBs while constantly negative for antibody-mediated rejection or infection. Only a post-mortem examination demonstrated the presence of an aggressive acute non-Epstein-Barr virus (EBV)-related proliferative disorder with unusual primitive localization into the pericardium and with coronary epicardial and intramyocardial necrotizing vasculitis and superimposed occlusive and subocclusive thrombosis. Recurrence of unexplained early pleuropericardial effusion and mild intramyocardial vasculitis should raise the suspicion of PTLD requiring reduction of immunosuppression, even in the setting of negative intramyocardial cellular infiltrate and tissue EBV-negative molecular assessment.

HLA-DRB1 typing by micro-bead array assay identifies the origin of early lymphoproliferative disorder in a heart transplant recipient.

We report the case of a 68-year-old woman who underwent heart transplantation for hypertrophic cardiomyopathy. Two months after the transplant she developed mild fever and dyspnea with a marked drop in left ventricle ejection fraction of 31%. Coronary angiography was negative for cardiac allograft vasculopathy. Endomyocardial biopsy revealed ischemic damage with no evidence of acute cellular rejection, antibody-mediated rejection or viral myocarditis. A neoplastic process was suspected even though full-body computerized tomography was negative for malignancy. The patient died 4 months after transplantation. The autopsy showed acute antero-septal myocardial infarction due to a nodular epicardial EBV-related posttransplant lymphoproliferative disorder (PTLD) infiltrating the left anterior descending coronary artery with occlusive neoplastic thrombosis. We highlight two major aspects of this case: (1) the unusual occurrence of early PTLD involving the cardiac allograft and causing a fatal outcome, (2) the application of an immunological technique for HLA-DRB1 typing to posttransplant paraffin-embedded autopsy material to identify the recipient origin of this early malignancy, thus excluding a possible donor-transmitted neoplasm.

A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

Tumour proliferation, angiogenesis, and ploidy status in human colon cancer.

AIMS: Tumour angiogenesis is essential for carcinogenesis and facilitates the process of tumour development and metastasis. Vascular endothelial growth factor (VEGF) is a well characterised angiogenetic factor and is known to play a crucial role in new vessel development. To gain further insight into the effects of microvessel density and VEGF expression in colon cancer, their relation with tumour proliferation, ploidy status, and p53 expression was investigated in colon cancer. METHODS: Tissue samples of 50 archived colon cancers were analysed by immunohistochemistry for VEGF, p53, and the endothelial cell marker, von Willebrand factor (VWF), using specific antibodies. The same samples were re-cut for flow cytometric studies to obtain S phase fraction (SPF) and ploidy status. RESULTS: A positive significant correlation was found between SPF and angiogenesis. The median microvessel count in high SPF tumours was significantly higher than in low SPF ones. No association was found between VEGF expression and SPF. A positive correlation was found between ploidy status and p53 expression and microvessel count. Furthermore, a positive correlation was established between DNA ploidy, VEGF expression, and microvessel count. CONCLUSION: This study provides evidence that in colon cancer, tumour growth may be stimulated by vascular supply, and the lack of a correlation between tumour cell proliferation and VEGF expression indicates that these two parameters may be regulated by separate mechanisms. Furthermore, the positive correlation between microvessel density, VEGF expression, and ploidy status provides more evidence that genetic alterations are involved in tumour angiogenesis.

[Prevention and treatment of mucositis from cytotoxic chemotherapy]. / Prevenzione e trattamento della mucosite da chemioterapici antiblastici.

The administration of several chemotherapeutic regimens could be conditioned by the onset of mucositis. The characteristic lesions of the mucositis affect whole buccal mucosa. That derives from rapid turnover of the oropharyngeal epithelial surfaces. The mucosa can suffer from direct damage of antiblastic drugs or be susceptible of microbic infections. Moreover, other factors correlated to the patients as age, nutritional status, tumor type, oral hygiene and neutrophil count. Up to date, there is not a standard therapy for the cure or mucositis prevention. Some formalities can be employed in order to reduce chemo-induced damage: 1) altering the distribution and the excretion of drugs on the mucosa; 2) stimulating the basal cells of the mucosa; 3) trying to modify the infectious or inflammatory risks. The effective oral care, dietary changes and the use of protective topical and the careful use of topical and systemic anesthetic drugs are the cornerstones of mucositis care.

[Effectiveness and side effects of the treatment with propafenone and flecainide for recent-onset atrial fibrillation]. / Efficacia ed effetti collaterali del trattamento con propafenone e flecainide della fibrillazione atriale di recente insorgenza.

BACKGROUND: The authors report their experience in recent-onset atrial fibrillation treated with intravenous flecainide and propafenone, in comparison with the placebo group. METHODS: We randomized 352 (138 in the flecainide group, 164 in the propafenone group and 50 in the control group) consecutive patients (167 males, 185 females, mean age 59 +/- 12 years) with recent-onset atrial fibrillation. The electrocardiogram of all patients was monitored for at least 24 hours. RESULTS: The restoration of sinus rhythm occurred in 72.5, 80.4, 86.2 and 89.8% of patients in the flecainide group; in 54.3, 68.3, 75 and 92.1% in the propafenone group; in 22.2, 27.8, 35.2 and 46.3% in the control group, at 1, 3, 6 and 24 hours respectively. The occurrence of side effects was the same in all treatment groups, and occurred in about 10% of patients in the flecainide and propafenone groups, and in 4% in the control group. In our study population the treatment of recent-onset atrial fibrillation with flecainide was faster in converting the arrhythmia to sinus rhythm (p < 0.005 at 1 hour, p < 0.05 at 3 hours, p = 0.05 at 6 hours). However within 24 hours the efficacy of either flecainide or propafenone was the same (p = NS at 24 hours). CONCLUSIONS: Side effects were similar in both treatment groups. In particular malignant arrhythmias did not occur in the treatment groups and in the control group.

Cisapride and dexamethasone in the prevention of delayed emesis after cisplatin administration.

Management of delayed emesis (DE) remains unsatisfactory, and only 50% of the patients achieve complete protection. Cisapride is a strong prokinetic gastrointestinal drug that could have a role in the prevention of DE. We enrolled 31 adult naive outpatients who were scheduled to receive cisplatin chemotherapy at doses of > or = 75 mg/m2. All patients received the same prophylactic treatment for acute emesis (20 mg dexamethasone and 8 mg ondansetron i.v.) and, as preventive therapy for DE, oral cisapride, 10 mg every 8 h on days 2-4, combined with dexamethasone i.m., 8 mg twice daily on days 2 and 3, and 4 mg twice daily on day 4. All patients were evaluable for activity. Complete protection from acute vomiting was 80.7%, from nausea 71% and from nausea/vomiting 64.5%. The overall protection from DE (days 2-4) was 74.1% for vomiting, 64.5% for nausea and 58% for nausea/vomiting. In our study the combination of cisapride and dexamethasone was effective, giving 58% of complete protection from DE, and it is therefore worthy of further studies.

Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study.

AIMS AND BACKGROUND: The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease. METHODS: From April 1999 to June 2000, we enrolled 11 chemotherapy-naïve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks. RESULTS: Four partial responses, 1 regression of disease (objective response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity. CONCLUSIONS: We consider the combination promising and worthy of further studies.

Reoperations for acute prosthetic thrombosis and pannus: an assessment of rates, relationship and risk.

OBJECTIVE: Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is dependant on valve design, materials and host-related interface. While pannus is common to both biologic and mechanical valves, acute prosthetic thrombosis is mostly a complication of mechanical valves; therefore we investigated to find rates and risk of these obstructive complications. METHODS: Between 1/1/70 and 31/12/97, 2680 patients received at least one mechanical prosthesis in the aortic or mitral or tricuspid position and a total of 3014 operations were performed. Follow-up included 18523 years and was 98% complete. Incidence rates, Kaplan-Meier estimates, modeling of the hazard and multivariate analysis in the hazard domain were used in the analysis. RESULTS: Overall survival was 76%, 64%, 51%, 38.5% and 29% at 5, 10, 15, 20 and 25 years, respectively. It was significantly better in aortic than in mitral than in double prosthesis. 290 patients received a single reoperation, 37 a second, six a third and one a fourth reoperation. Two-hundred and fifty-one of these reoperations were exclusively due to malfunction of mechanical prosthesis, nine to malfunction of both mechanic and biologic prostheses. Most frequent reoperative indications was dehiscence (133), pannus (48) and thrombosis (29). The linearized rate of reoperations for pannus was 0.24%/patient per year, for valvular thrombosis 0.15%/patient per year. The shape of the thrombotic hazard was constant (at random) and the relative risk 12 times higher for tricuspid prosthesis, seven times higher for mitral prosthesis. Multivariate analysis controlling for prosthetic position, age, sex and prosthetic size, showed a 67% risk reduction with larger prosthesis (>27 mm), a 69% risk reduction with the Sorin tilting disk prosthesis and an 83% risk reduction with the bileaflet prosthesis. Pannus hazard shows a delayed exponential rise and was two times higher in tricuspid and three times higher in mitral position. Multivariate analysis showed a 50% risk reduction with larger prosthesis, an 11 times higher hazard of old (caged-disk, caged ball) prosthesis and a three times higher hazard of Lillehei-Kaster prosthesis. Reoperation for thrombosis has a 62% perioperative (30 days) survival compared to 92% survival of pannus reoperation. CONCLUSIONS: Mechanical valves have a low incidence of reoperation, mostly for prosthetic dehiscence. Pannus development is the next frequent complication increasing with time since implant, therefore in this series it was related to old valvular models and tilting disk prosthesis, with longer follow-up. Acute thrombosis occurs significantly earlier than pannus formation. Despite shorter follow-up we are therefore confident that bileaflet prostheses are less prone to this complication and pannus is a rare early etiologic factor. Thrombosis has very high operative risk as compared to pannus, justifying the present trend to thrombolysate selected cases.

Combined epirubicin and interleukin-2 regimen in the treatment of malignant mesothelioma: a multicenter phase II study of the Italian Group on Rare Tumors.

The Italian Group on Rare Tumors undertook a phase II study of a combination of epirubicin and interleukin-2 in 21 chemotherapy-naive patients with malignant mesothelioma. All patients had bidimensionally measurable disease at CT scan. Treatment included Intravenous administration of epirubicin at a dose of 110 mg/m2 i.v. on day 1, and interleukin-2 at a dose of 9 MU subcutaneously from day 8 to day 12 and from day 15 to day 19. Cycles were repeated every three weeks, up to six times in the absence of progressive disease. Treatment response was evaluated after two cycles of therapy. Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months, respectively. Toxicity was relevant and caused treatment discontinuation in many patients. These results do not support the use of such a combination in the management of malignant mesothelioma.

Isolated rectal relapse in non Hodgkin lymphoma patient.

The authors report on case of isolated rectal relapse of non Hodgkin lymphoma after complete remission with chemotherapy. They analyse diagnostic and therapeutic aspects, on the grounds of literature data and personal experience.

Defibrotide in the prevention of venous irritation by vinorelbine administration.

BACKGROUND: Vinorelbine is active in a variety of malignancies. The most common side effects are leukopenia and granulocytopenia, moreover Vinorelbine is a vescicant and venous irritant, the incidence of the latter being 10-26% in patients who received VNB as a 20-30 minute peripheral infusion. To prevent venous toxicity we have carried out a study in order to evaluate the efficacy of Defibrotide in this issue. MATERIALS AND METHODS: 41 patients were enrolled in the study, the experimental schedule was: Defibrotide 400 mg on 250 cc of normal saline iv, after 15 minutes of infusion, we delivered quick, brief and repeated pulses of Vinorelbine through the plastic tube followed by remaining Defibrotide: For grading venous irritation we used the scale by Rittenberg et al. RESULTS: A total of 360 infusion were delivered, the incidence of any venous irritation was 5% and maximum grade 2. No severe toxicity was recorded. CONCLUSION: These data show that Defibrotide might serve as a therapeutic drug to prevent vascular toxicity by Vinorelbine.

VP16, epirubicin and procarbazine in the treatment of advanced non-small-cell lung cancer.

We report the results obtained in the treatment of 52 advanced non-small-cell lung cancer patients with the combination chemotherapy VP16 (120 mg/m2 i.v., days 1-2-3), epirubicin (50 mg/m2 i.v., day 1) and procarbazine (100 mg/m2 p.o., days 1 through 8). The courses were repeated every 21 days. No patient had been pretreated. A median of 5 courses was administered. Partial response was obtained in 33% and no change in 21% of patients. Median remission time was 6.5 months, and median survival of responders was 10 months. The best response rate and median survival were obtained in the lowest grade performance status patients and in locally advanced disease patients. Major chemotherapy related toxicities were grade 1-2 leukopenia and grade 2-3 alopecia.