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Background Literature shows that occurrence of comorbidities in people with severe acquired brain injury (sABI) is a common problem in rehabilitation stay. Consequently, patients could require an increase of interventions for diagnosis and treatment of clinical conditions, with a reduction of the rehabilitative take in charge for both clinical and organizational aspects. Aim The first aim was to evaluate the rate of clinical conditions of sABI patients at admission in rehabilitation and the types of rehabilitative interventions performed in the first week; second objective was to explore the impact of clinical conditions on real rehabilitative take in charge. Design Cross sectional study. Setting Inpatient rehabilitation centers. Population The study included data from 586 sABI patients. Methods Collected data regarded anamnestic information, functional status assessed by means of Glasgow Outcome Scale, Levels of cognitive functioning, Early Rehabilitation Barthel Index, comorbidities at admission and type of rehabilitative interventions carried out in first week of rehabilitation stay. Spearman correlation coefficients were applied to detect possible correlations between the number of treatments in first week and clinical variables; through a multiple regression analysis the effect of patient's characteristics on rehabilitative take in charge was explored. Results Data from the sABI patients: mean age 55.1±17.1 years; etiology of sABI was vascular in 315 patients (53.8%), anoxic in 83 (14.2%), neoplastic in 17 (2.9%), infectious in 15 (2.6%), traumatic in 150 (25.6%); 6 subjects (1%) presented a mixed etiology. Need of cardiorespiratory monitoring, pressure sores, infections or presence of multi drug resistant bacteria were the most frequent comorbidities. Passive mobilization, sitting positioning, arousal/awareness stimulation, evaluation and management of dysphagia were the interventions most frequently carried out in the first week. The regression analysis showed that severe neurological and clinical conditions, acute organ failure, cardio-respiratory instability and paroxysmal sympathetic hyperactivity significantly limit access to rehabilitative sessions. Conclusions In sABI patients clinical comorbidities requiring elevated care assistance are frequent at admission in rehabilitation from acute wards and may interfere with rehabilitative take in charge. Clinical rehabilitation impact The knowledge of clinical complexity of sABI patients may improve their care pathways, promoting early and appropriate transition from acute care to rehabilitation settings.

Aim: We investigated outcomes in patients with advanced non-small-cell lung cancer (NSCLC) and peritoneal involvement. Patients & methods: NSCLC patients with peritoneal carcinomatosis (PC) were included. We evaluated mOS1 (overall survival [OS] from NSCLC diagnosis) and mOS2 (OS from diagnosis of PC). Results: In total, 60 NSCLC patients were diagnosed with PC, 12 (20%) patients had a diagnosis of NSCLC and synchronous PC with a median OS of 9 months. Smokers had a shorter mOS1 and mOS2 compared with never-smokers; EGFR-mutated patients on tyrosine kinase inhibitors had longer mOS1 and mOS2 than EGFR wild-type patients. Conclusion: Metachronous PC is correlated to a short survival, irrespective of treatment line. Never-smokers and EGFR-mutated patients had improved mOS1 and mOS2 when compared with smokers and EGFR wild-type population.

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association.

ALK positivity, despite representing only in a small proportion of patients with non-small-cell lung cancer, is worth researching at diagnosis given the possibility to treat these patients with some targeted ALK inhibitors, which are more potent than chemotherapy. Thanks to understanding the resistance mechanisms, newer and more selective inhibitors are now available in clinical practice. Hence, this disease represents, after EGFR inhibition, a largely effective precision medicine approach. However, there are still some clinical situations in which the targeted drug seems to be ineffective. This review discusses some uncertainty about such a ‘precision medicine application’, focusing on some weaknesses and giving perspectives and suggestions to improve the management of this specific population.

We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1-retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.

Introduction In spite of the progress in the treatment of non-small-cell lung cancer (NSCLC), the majority of patients with advanced disease still receive chemotherapy. Gemcitabine alone or combined with a platinum compound is a valid option. Thrombocytosis is a recognized prognostic factor in lung cancer and an adverse event that may occur during gemcitabine infusion. Methods We retrospectively evaluated all patients with NSCLC treated with first-line gemcitabine-based chemotherapy in two Italian hospitals. We assessed the onset of thrombocytosis within the third cycle of therapy and the relation between thrombocytosis and survival. Results We included 318 patients. Thrombocytosis occurred in 156 patients (49.1%). Median progression-free survival (PFS) was 5.6 months (95% CI, 4.7-6.9 months) in patients who developed thrombocytosis versus 6 months (95% CI, 5.1-7.2 months) in patients without thrombocytosis (p = 0.21). Median overall survival (OS) was 11.2 months (95% CI, 9.8-13.4 months) in patients with thrombocytosis versus 12 months (95% CI, 10.1-14.4 months) in patients without thrombocytosis (p = 0.25). We observed no difference in terms of PFS or OS according to age, sex, stage, chemotherapy (single-agent versus combination chemotherapy) and thrombocytosis. Conclusions Thrombocytosis is neither a prognostic nor a predictive factor for PFS or OS in patients with advanced NSCLC treated with first-line gemcitabine-based chemotherapy.

Immunotherapy is changing the treatment of non-small cell lung cancer (NSCLC). The PD-1 inhibitor nivolumab has demonstrated meaningful results in terms of efficacy with a good safety profile. The novel approach to treating NSCLC using immunotherapy still has unsolved questions and challenging issues. The main doubts regarding the optimal selection of the patient are the role of this drug in first line of treatment, the individualization of the correct methodology of radiologic assessment and efficacy analysis, the best management of immune-mediated adverse events, and how to overcome the immunoresistance. The aim of this review is to analyze literature data on nivolumab in lung cancer with a focus on critical aspects related to the drug in terms of safety, the use in clinical practice, and possible placement in the treatment algorithm.

Although heart metastases are uncommon and generally a sign of disseminated disease, they are up to 40 times more frequent than primary cancers of the heart, and typically arise from melanoma or primary mediastinal cancer, but also from lymphoma, breast cancer, esophageal cancer, and leukemia. They are usually asymptomatic and found only at autopsy. Symptomatic patients generally die within a few weeks of diagnosis and usual treatments are chemotherapy, radiotherapy, or both. Surgical resection is recommended only for a single lesion, which is rare. We describe a 49-year-old man treated for squamous cell cancer of the esophagus in whom a single asymptomatic left heart metastasis was discovered incidentally during follow-up. The lesion was debulked surgically and multimodal treatment followed. The patient survived 1 year after diagnosis with good performance status during which time no other lesion was discovered. Cardiac metastasis is challenging and necessitates skilled multidisciplinary management to maximize the clinical outcome.

10.2217/fon.15.159 © 2015 Future Medicine Ltd Lung cancer is a neoplasm characterized by uncontrolled growth, intrinsic antiblastic resistance and a high frequency of heterogeneity. These characteristics have led to a huge effort by clinicians for many years to perform clinical trials with experimental drugs, unfortunately without any real impact on survival outcomes. More recently many steps have been taken toward developing a deeper understanding of biological and genetic aspects of lung cancer, especially in non-small-cell lung cancers (NSCLCs). Nowadays, thanks to these discoveries, clinicians employ the term ‘precision medicine’ to define a biological drug with a great impact against diseases characterized by a genetic driver mutation. In the last few years, the knowledge about the targeted agents, such as the EGF receptor (EGFR) and ALK inhibitors, have led to the most impressive results increasing median overall survival beyond 24 months [1,2]. On the other hand, in the ‘nononcogene addicted’ population the maintenance strategy with pemetrexed allows a median overall survival of almost 18 months [3]. The molecular knowledge of lung cancer, along with properly employed targeted agents in oncogene addicted tumors and the maintenance strategy are the cornerstones that offer our patients more possibilities to live longer, with a better quality of life, as a result increasing the hope to receive several therapeutic lines after the first treatment attempt. Unfortunately, these improvements are more theoretical than applicable to daily clinical practice. In fact, despite a higher number of patients suitable for third-line therapies, the quantity and quality of a vailable drugs in this setting is poor. Actually, in many countries erlotinib is the only drug approved as third-line therapy. However, the population studied in the pivotal BR21 study [4] is probably not representative of a real practice patients population. It should be kept in mind that erlotinib was compared with best supportive care in a population not eligible for chemotherapy. Unfortunately, many trials published after the BR21 study did not manage to understand the real impact of a third-line therapy on clinical outcomes. In particular, the recently published DELTA trial tried to understand the role of docetaxel compared with erlotinib in an EGFR unselected pretreated population in second and third line. However, the study was not powered to observe a statistical COMMENTARY

BACKGROUND: Apoptosis plays an important role in regulating spermatogenesis. However, the biological significance of apoptosis in ejaculated sperm is not yet clear. This study set out to investigate how apoptosis correlates with semen quality and the presence of seminal leukocytes. METHODS: Fifty-seven semen samples from the male partners of infertile couples were classified as normal or abnormal according to World Health Organization guidelines. Flow cytometry was used to evaluate sperm populations and seminal leukocytes. Preliminary flow cytometry analysis using 6-carboxyfluoresceindiacetate (6-CFDA), which identifies live cells, and propidium iodide (PI), which stains only dead cells, was performed in order to pinpoint the sperm region accurately. Having thus gated the sperm population, bivariate Annexin V/PI analysis was then carried out in order to measure the percentage of apoptotic and necrotic sperm and the apoptotic index (the ratio between apoptotic:live sperm). Leukocytes were counted by the standard peroxidase test and by flow cytometry using monoclonal antibody (mAb) anti-CD45 or anti-CD53. RESULTS: No significant differences in the apoptotic index and the percentage of live and apoptotic sperm were detected between the subjects with normal and abnormal semen. A significant inverse correlation between sperm concentration and the apoptotic index was observed only in the normal sperm group. There was no correlation between the concentration of leukocytes, detected either by peroxidase or by mAb anti-CD45 or anti-CD53, either with the percentage of apoptotic sperm or with the apoptotic index. In contrast, the ratio between CD45 positive leukocytes and sperm showed a significant correlation with the apoptotic index. A weaker correlation was found when leukocytes were counted by peroxidase, while no correlation was observed using mAb anti-CD53. CONCLUSIONS: Sperm apoptosis did not seem to be correlated with semen quality. In the absence of genito-urinary infection, one of the main functions of seminal leukocytes is probably to provide for the removal of apoptotic sperm.

We developed a rapid, sensitive and robust high risk human papillomavirus (HR HPV) detection protocol based on direct in situ PCR technology and fluorochrome-modified nucleotides on cytologic specimens (cell smears) and on HPV infected tissues (CIN III). Reproducible results on both cytologic specimens and paraffin-embedded tissues were obtained, providing a powerful tool for clinical investigation on HR HPV infection. Quantitative PCR performed on the same tissue sections adjacent to those used for in situ techniques allowed us to establish the sensitivity of our methods, able to detect rare copies (about 15 in our paraffin-embedded tissues) of HPV.