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Lung cancer presents significant therapeutic challenges, motivating the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms, encompassing apoptosis, autophagy, and programmed necrosis, are pivotal in lung cancer pathogenesis and the treatment response. Dysregulation of these pathways contributes to tumor progression and therapy resistance. Immunonutrition, employing specific nutrients to modulate immune function, and metabolic reprogramming, a hallmark of cancer cells, offer promising avenues for intervention. Nutritional interventions, such as omega-3 fatty acids, exert modulatory effects on PCD pathways in cancer cells, while targeting metabolic pathways implicated in apoptosis regulation represents a compelling therapeutic approach. Clinical evidence supports the role of immunonutritional interventions, including omega-3 fatty acids, in augmenting PCD and enhancing treatment outcomes in patients with lung cancer. Furthermore, synthetic analogs of natural compounds, such as resveratrol, demonstrate promising anticancer properties by modulating apoptotic signaling pathways. This review underscores the convergence of immunonutrition, metabolism, and PCD pathways in lung cancer biology, emphasizing the potential for therapeutic exploration in this complex disease. Further elucidation of the specific molecular mechanisms governing these interactions is imperative for translating these findings into clinical practice and improving lung cancer management.

Aim: To describe a term newborn with acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem involvement including seizures associated to ischemic lesions in the brain., Background: Coronavirus disease 2019 (COVID-19) is predominantly a respiratory infection, but it may affect many other systems. Most pediatric COVID-19 cases range from asymptomatic to mild-moderate disease. There are no specific clinical signs described for neonatal COVID-19 infections. In children, severe central nervous system compromise has been rarely reported., Case Description: We describe a 17-day-old newborn who acquired a SARS-CoV-2 infection in a family meeting that was admitted for fever, seizures and lethargy and in whom consumption coagulopathy, ischemic lesions in the brain and cardiac involvement were documented., Conclusions: SARS-CoV-2 neonatal infection can be associated with multi-organic involvement. In our patient, significant central nervous system compromise associated to ischemic lesions and laboratory findings of consumption coagulopathy were found., Clinical Significance: Although neonatal SARS-CoV-2 infections are infrequent, they can be associated with multi-organic involvement. Neonatologists and pediatricians should be aware of this unusual way of presentation of COVID-19 in newborn infants., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Adenoids, tubal tonsil, palatine tonsil, and lingual tonsil are immunological organs included in the Waldeyer's ring, the basic function of which is the antibody production to common environmental antigens. Adenoidal hypertrophy (AH) is a major medical issue in children, and adenoidectomy is still the most used treatment worldwide. The response of adenoids to allergens is a good model to evaluate their immunological function. This report assessed the immunological changes in adenoid tissues from children with allergic rhinitis (AR) undergoing sublingual immunotherapy (SLIT)., Methods: Adenoid samples from 16 children (seven males, nine females, mean age 7.12 years) with AH and clinical indication to adenoidectomy were collected. Of them, five children were not allergic and 11 had house dust mite and grass pollen-induced AR. Among allergic children, in four AR was treated by antihistamines while in seven AR was treated by high-dose SLIT during 4-6 months. The evaluation addressed the T helper 1 (Th1), Th2, and Th3 cells by performing a PCR array on mRNA extracted from adenoid samples., Results: In non-allergic children, a typical Th1 pattern was found. SLIT induced a strong down-regulation of genes involved in Th2 and Th1 activation and function. In particular, in SLIT-treated allergic children IL-4, CCR2, CCR3, and PTGDR2 (Th2 related genes) and CD28, IL-2, and INHA (Th1 related genes) expression was reduced, compared with children treated with antihistamines., Conclusions: These preliminary findings warrant investigation in trials including larger numbers of patients, but indicate that hypertrophic adenoids of allergic children have the typical response to the specific allergen administered by SLIT. This should suggest that one should reconsider the immunological role of adenoids.

Purpose: Uveal melanoma (UM) was a fatal malignancy in 40% to 50% of cases. The aim of this study is to evaluate the independent contributions of chromosome 1, 3, 6, and 8 abnormalities for prognostication of metastasis, and to define multichromosome copy number aberration (CNA) signatures that can be used to evaluate risk., Methods: A series of 320 UM were analyzed for chromosome 1, 3, 6, and 8 abnormalities using whole genome single-nucleotide polymorphism arrays. Results for changes in six chromosomal regions were analyzed using univariate and multivariate Cox proportional hazard modeling to identify significant predictors of metastasis and CNA signatures., Results: Univariate Cox analysis indicated that losses of chromosome 3, 1p, 6q, and 8p and gain of 8q, as well as sex, source of tumor tissue (fine-needle aspiration biopsy [FNAB] compared with tumor from an enucleated eye), tumor basal diameter and height, and ciliary body involvement were all significant predictors of poor metastatic outcome. In the multivariate analysis, loss of chromosome 3 and 8p remained significant after adjusting for the effects of all other variables, as did sex, tissue source, and basal diameter. Multivariate analysis of the joint effects of changes in the six chromosomal regions showed that six signatures, including chromosome 3-loss, 1p-loss, 8p-loss, and/or 8q-gain had hazard ratios (HR) ranging from 7.90 to 37.25., Conclusions: In UM, tumor size and location, tissue source, and sex were all significantly associated with increased metastasis. In addition, chromosome 3-loss and 8p-loss were found to be independent predictors of poor metastatic outcome and CNA signatures were identified that can add a specific HR value for classification of risk categories.

The purpose of this investigation was to analyse incidents discovered in our radiation therapy department by means of human factor analysis and classification system (HFAC S). We adapted the original framework of the HFAC S and apply it to the analysis of incidents discovered in our radiotherapy department during a five-year period. Results showed that recurrent causal factors of incidents were attention failures and distracted/overconfidence behaviour as well as loss of situational awareness and mental fatigue. In our radiation therapy department the HFAC S allowed to highlight recurrent errors causal factors. Consequently we defined corrections factors for operators behaviour and implemented an operational protocol which improve operators attitude.

Esthesioneuroblastoma is a rare tumour arising from the olfactory epithelium of the nasal vault which frequently invades the cranial base and orbit. Esthesioneuroblastoma has a bimodal age distribution between 11 and 20 years and between 51 and 60 years. Esthesioneuroblastoma accounts for approximately 1-5% of intranasal cancers. The case is reported of a 79-year-old female patient with a Kadish stage C tumour with a one-year history of headache, nasal obstruction, anosmia, rhinorrhoea and epistaxis. Aim of this study is to analyse the natural history, treatment and prognosis of this tumour, based on a review of the literature.

Purpose: The aim of this study was to evaluate the survival of patients with "glioblastoma multiforme", to analyse the prognostic factors influencing the survival rate and to review recent results in the literature., Materials and Methods: Seventy five patients underwent radiation treatment between May 1998 and April 2003. Among the factors under investigation we ascertained that sex, chemotherapy, conformal treatment, surgery, and the choice of the irradiation area (whole brain or only the involved field) did not influence the survival in a statistically significant manner., Results: Whereas age and total dose were the 95% statistically significant variables. Hazard ratio of patients older than 58 years compared to younger patients was 1.69. The death risk was 69% in older than younger patients. A greater irradiation dose improved the survival with an increase of the median survival days. The total dose lower than 6000 cGy caused an increase of 81.8% in the death risk. The median survival from the diagnosis to the death was 14.7 months (446 days) and 1-, 2- and 3- year survival rate was 69.3%, 38.4%, and 14.7% respectively., Conclusions: The current medical literature and our experience attests that the use of temozolomide improves the survival of these patients.

The phenomenon known as one-trial tolerance (OTT) to the anxiolytic effects of benzodiazepines observed in rats submitted to the elevated plus-maze test (EPM) is considered to be due to the emergence of phobic states across the test/retest sessions. Antinociception is a usual component of the defense reaction. Until now, no study has examined antinociception and OTT together in freely behaving rats in the EPM. This work is a new approach looking at the sensorimotor gatings underlying OTT through the examination of the changes in reactivity to noxious stimuli during OTT development. We used the tail-flick test to assess the reactivity of rats to noxious stimulus during the effects of midazolam in test/retest sessions using two types of EPM, one with opaque (standard EPM) and another one with transparent walls (modified EPM). The authors had previously shown that this modified test caused an overall stressful situation more related to anxiety while the standard test coursed with a mixture of anxiety and high fear levels. In both plus mazes, the study was conducted in two experiments: (i) midazolam before the first trial, and (ii) midazolam before the second trial. In each experimental condition the effects of midazolam were tested under two doses (0.5 and 1.0 mg/kg) against a control group that received injections of saline. The anxiolytic effects of midazolam were more pronounced in animals tested in the modified EPM than in the standard EPM. Stressful stimuli present in both types of maze were able to elicit one-trial tolerance to midazolam on re-exposure. However, anxiolytic-insensitive behaviors in the first and the reduction in exploratory activity in the second trial are more pronounced in the standard EPM indicating that this test is more prone to transfer fear-related states across trials than the modified maze test. Antinociception is not present upon the re-exposure of rats to the EPM. These findings show that animals tested in the modified EPM showed higher sensitivity to the anxiolytic effects of midazolam than the standard EPM. Antinociception was not a concomitant of the shift in the emotional state present in the retest sessions of the EPM. These results are in agreement with the premises that repeated stressful experience leads to anxiolytic-insensitive fear state different from anxiety.

It has been suggested that antinociception is part of the animal's defensive reaction to threatening situations. Chemical or electrical stimulation of the ventrolateral portion of the periaqueductal gray (vlPAG) produces both defensive freezing behavior and antinociception, supporting the view that the vlPAG is a critical structure in the coordination of the defensive reaction. The present study indicated that electrical stimulation of the vlPAG, at a current intensity sufficient to induce defensive freezing, caused a decrease in reactivity to a phasic escapable noxious stimulus (as measured in the tail-flick test) and to a tonic, inescapable noxious stimulus (as measured in the formalin test). These antinociceptive effects were reversed by microinjections of the opioid antagonist naltrexone or the specific 5-HT2A receptor antagonist ketanserin into the stimulation sites. These results suggest that (a) activation of neural circuits of the vlPAG, responsible for the production of freezing behavior, reduces the reactivity to nociceptive stimuli (as evaluated by the tail-flick and formalin tests) and that (b) opioid- and 5-HT2A-mediated mechanisms are called into action for regulating the antinociceptive response that accompanies the freezing behavior induced by vlPAG stimulation.

Purpose: Chemotherapy and concurrent irradiation, intended to cure, are presently standard treatments for non metastatic, unresectable oesophageal cancer. The results of the combined therapy are superior to those of radiotherapy alone, attaining 25-35% 2-year survival rates. However these results mainly refer to stage I and II tumours as most of the available literature has focussed on these groups. The aim of our report is to present our experience with Stage III and IV patients., Material and Methods: Sixty-four Stage III and IV oesophageal cancer patients were referred to our Departments from January 1, 1990 to December 31, 1996. Diagnosis was obtained through oesophagoscopy and biopsy, stage was assessed by physical examination, chest CT scan, bronchoscopy, barium X-ray examination, upper abdomen ultrasonography and bone nuclide scan. Thirty-four patients, with no signs of blood-born metastases and in satisfactory medical conditions (i.e. age not exceeding 70 years, weight loss not exceeding 10% of body weight, normal serum values of BUN and creatinine, no other severe disease), were submitted to concurrent chemo-radiotherapy. The case features were as follows: histology of squamous cell carcinoma in 32 cases, of adenocarcinoma in 2; tumour in the upper third of the oesophagus in 11 (32.5%), in the middle third in 18 (53%), in the lower third in 5 (14.5%); male/female ratio 29/5, age 48-68 years (mean 56), Karnofsky performance status of 60% or higher. On referral, 18 out of 34 (53%) had a weight loss more than 5% of body weight and 22 (64.5%) had dysphagia. Twenty-one had Stage III (61.75%) and 13 stage IV (38.25%) cancer, with metastasis limited to the supraclavicular or coeliac nodes, which could be included in the radiation volume. In all cases chemotherapy consisted of 5-Fluoruracil (administered in a continuous i.v. infusion, from day 1 to 5, with a 750-1.000 mg/n.sq daily dose) and Cisplatin (75-100 mg/n.sq on the first day, or 20 mg/n.sq for 5 consecutive daily doses, administered by i.v. bolus). Three to 5 cycles were administered, one every 21 days. Irradiation started with the first cycle of chemotherapy in 5 patients, with the second or third cycle in 29. At least two cycles of chemotherapy were administered during the course of radiation. Radiotherapy was performed with 4 to 18 MeV linear accelerator X-rays, or telecobalt, through opposite anterior and posterior treatment portals or more complex field arrangements. The doses were in the range of 44-66 Gy, with fractionation of 5x180-200 cGy weekly sessions. After treatment, periodic follow-up controls were carried out in all cases. Thorough restaging was performed only in selected cases, thus a systematic evaluation of objective responses was not possible. Data on improvement of swallowing were always available, however, and the early therapeutic results were analysed accordingly. Toxicity was recorded according to the WHO parameters. Two-year survival after conclusion of the treatment was calculated according to Kaplan and Maier. Survival was analysed (log-rank test) according to stage, Performance Status, oesophagectomy and body weight loss., Results: After treatment, subjective symptomatic relief occurred in 17 of the 22 patients presenting dysphagia (77.5%). Acute toxicity (Grade III or IV WHO) of the treatment accounted for 47% of hematologic adverse effects, 40% of mucositis, 20.5% of vomiting or diarrhoea not responding to drug treatment. Treatment delays of more than one week, due to toxicity, occurred in 23.5%. Moreover, we observed 20.5% of mild cardiotoxicity and 6% of mild nephrotoxicity. No symptomatic lung fibrosis was observed. No death could be related to toxicity. Overall 2 year survival was 13%, with a median value of 10 months. Survival analysis, according to stage, showed 2 year values of 24% in Stage III and 0% in Stage IV (p=0.09). No significant difference was related to Performance Status and weight loss. Six patients showed a remarkable improvement in symptoms and general conditions after treatment, and were restaged with oesophagoscopy, thoracic CT scan and bronchoscopy, which evidenced resectable residual tumors, and they were then operated. Although histologic examination showed tumour in all the resected specimens, 2 patients survived more than two years (33.5% survival, median 14 months). Due to the small number of operated patients, no attempt was made to assess the significance of this result, in comparison with the other cases., Discussion and Conclusions: Many Stage III and IV patients, selected for an aggressive chemo-radiation approach on the grounds of satisfactory medical conditions, can obtain relief of dysphagia. Toxicity can be severe, but is rarely life-threatening. Some cases, without extrathoracic spread of the tumor can achieve long term survival (in our experience 24% 2-year survival in Stage III, in our experience which favourably compares with the results obtained by other authors). Whether surgery may improve the therapeutic results of chemo-radiotherapy in patients whose tumour has become resectable, is an issue that cannot be satisfactorily addressed on the basis of our experience, nor are the results from the available literature exhaustive to this regard.