Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer

Pemetrexed is a new cytotoxic agent that is a standard of care for the second-line treatment of non-small cell lung cancer (NSCLC) and in combination with cisplatin in treatment of malignat pleural mesothelioma. It has been studied in numerous phase II and III trials in combination with different drugs or as single agent. Recently, pemetrexed has been approved in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic NSCLC other than squamous cell histology. The toxicity is acceptable and similar to that of other NSCLC regimens. The postinduction maintenance therapy with pemetrexed is being evaluated in a phase III, double-blind, placebo-controlled study

Ultra-Thin Plasma-Polymerized Functional Coatings for Biosensing: Polyacrylic Acid, Polystyrene and Their Co-Polymer

Recently, many efforts have been done to chemically functionalize sensors surface to achieve selectivity towards diagnostics targets, such as DNA, RNA fragments and protein tumoural biomarkers, through the surface immobilization of the related specific receptor. Especially, some kind of sensors such as microcantilevers (gravimetric sensors) and one-dimensional photonics crystals (optical sensors) able to couple Bloch surface waves are very sensitive. Thus, any kind of surface modifications devoted to functionalize them has to be finely controlled in terms of mass and optical characteristics, such as refractive index, to minimize the perturbation, on the transduced signal, that can affect the response sensitivity towards the detected target species

Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function

New antiangiogenics in non-small cell lung cancer treatment: Vargatef™ (BIBF 1120) and beyond

Lung cancer is the leading cause of mortality worldwide. Non-small cell lung cancer (NSCLC) is a particularly aggressive cancer, the optimum management of which is still being determined. In the metastatic disease, the standard therapy is a platinum-based combination chemotherapy; however, in spite of available treatment options for patients who progress beyond first-line therapy, prognosis remains poor. Angiogenesis is a tightly regulated process which comprises a complex, complementary, and overlapping network. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Antiangiogenic strategy includes: monoclonal antibodies against vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR), small molecule inhibitors of VEGF tyrosine kinase activity, VEGF Trap, and a new class named “vascular disrupting agents,” tested in ongoing clinical trials which will further define their role in the management of NSCLC. BIBF 1120 is an investigational orally administered receptor tyrosine kinase inhibitor that has shown antiangiogenic and antineoplastic activity, inhibiting VEGFR, platelet-derived growth factor receptor, and fibroblast growth factor receptor tyrosine kinases, preventing tumor growth and interfering with the angiogenesis-signaling cascade and overcoming drug resistances

Morphometric Changes of the Corpus Callosum in Congenital Blindness

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12 reduction in the splenium, and a 20 increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness

Impact evaluation of a Critical Pathway for patients with Clostridium difficile infection: a pre-post analysis in a Third Level Referral Center

Background: Clostridium Difficile Infections (CDIs) have been increasing both in incidence and in severity, representing a big public health concern. Aim: The aim of this study was to evaluate the impact of a recently implemented Critical Pathway (CP) focused on patients with CDI in an Italian Teaching Hospital. Methods: The CP implementation consisted of intervention aimed to faster diagnosis and appropriateness in admission and discharge point of care; activation of a multidisciplinary team; staff training; information to patients and caregivers.In a pre-post retrospective observational study, volume, process and outcome indicators were analyzed. Findings: A total of 228 patients (128 in 2013 and 100 in 2016) were included. A decrease in the absolute number of access to the Emergency Department (p = 0.02) and an increase in hospitalization in more appropriate ward (ie gastroenterology ward, p < 0.001) were found. The median hospital length of stay decreased from 20.5 (12.5–31) days in 2013 to 16.5 (7–31) days in 2016 (p = 0.05). With regards to outcome indicators, an increase of discharge to home and a decrease of discharge to long term facilities were showed (p = 0.01 both). Despite a reduction, no statically significant differences in mortality between 2013 and 2016 were revealed by the analysis. Conclusion: In conclusion, we found quality improvement in patient hospital management. Our experience confirms that the implementation of the CP increases the appropriateness in hospital quality of care. Keywords: Patient centeredness, Critical pathways, Clostridium Difficile infection, "Patient centered" analytic

Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain

Abstract Recent evidence points to the gut microbiota as a regulator of brain and behavior, although it remains to be determined if gut bacteria play a role in chronic pain. The endocannabinoid system is implicated in inflammation and chronic pain processing at both the gut and central nervous system (CNS) levels. In the present study, we used low Vitamin D dietary intake in mice and evaluated possible changes in gut microbiota, pain processing and endocannabinoid system signaling. Vitamin D deficiency induced a lower microbial diversity characterized by an increase in Firmicutes and a decrease in Verrucomicrobia and Bacteroidetes. Concurrently, vitamin D deficient mice showed tactile allodynia associated with neuronal hyperexcitability and alterations of endocannabinoid system members (endogenous mediators and their receptors) at the spinal cord level. Changes in endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were also observed in the duodenum and colon. Remarkably, the anti-inflammatory anandamide congener, palmitoylethanolamide, counteracted both the pain behaviour and spinal biochemical changes in vitamin D deficient mice, whilst increasing the levels of Akkermansia, Eubacterium and Enterobacteriaceae, as compared with vehicle-treated mice. Finally, induction of spared nerve injury in normal or vitamin D deficient mice was not accompanied by changes in gut microbiota composition. Our data suggest the existence of a link between Vitamin D deficiency – with related changes in gut bacterial composition – and altered nociception, possibly via molecular mechanisms involving the endocannabinoid and related mediator signaling systems

2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors

Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target molecules might be a promising therapeutic strategy against the symptoms associated with NP. 2-pentadecyl-2-oxazoline (PEA-OXA) is a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders. The molecular mechanisms by which PEA-OXA exerts its effects are, however, only partially known. In the current study, we show that PEA-OXA, besides being an alpha2 adrenergic receptor antagonist, also acts as a modulator at histamine H3 receptors, and report data on its effects on sensory, affective and cognitive symptoms associated with the spared nerve injury (SNI) model of neuropathic pain in mice. Treatment for 14&nbsp;days with PEA-OXA after the onset of the symptoms associated with neuropathic pain resulted in the following effects: (i) allodynia was decreased; (ii) affective/cognitive impairment associated with SNI (depression, spatial, and working memories) was counteracted; (iii) long-term potentiation in vivo in the lateral entorhinal cortex-dentate gyrus (perforant pathway, LPP) was ameliorated, (iv) hippocampal glutamate, GABA, histamine, norepinephrine and dopamine level alterations after peripheral nerve injury were reversed, (v) expression level of the TH positive neurons in the Locus Coeruleus were normalized. Thus, a 16-day treatment with PEA-OXA alleviates the sensory, emotional, cognitive, electrophysiological and neurochemical alterations associated with SNI-induced neuropathic pain

Activity of the EGFR-HER2 dual inhibitor afatinib in EGFR-mutant lung cancer patients with acquired resistance to reversible EGFR tyrosine kinase inhibitors

Background: The purpose of this study was to evaluate the efficacy of afatinib in EGFR-mutant metastatic NSCLC patients with acquired resistance to erlotinib or gefitinib. Materials and methods: We retrospectively analyzed the outcome of patients with EGFR-mutant advanced NSCLC treated with afatinib after failure of chemotherapy and EGFR TKIs. Results: A total of 96 individuals were included in the study. According to EGFR status, most patients (n = 63; 65.6%) harbored a deletion in exon 19, and de novo T790M mutation was detected in 2 cases (T790M and exon 19). Twenty-four (25%) patients underwent repeated biopsy immediately before starting afatinib and secondary T790M was detected in 8 (33%) samples. Among the 86 patients evaluable for efficacy, response rate was 11.6%, with a median progression free-survival (PFS) and overall survival (OS) of 3.9 and 7.3 months, respectively. No significant difference in PFS and OS was observed according to type of last therapy received before afatinib, type of EGFR mutation or adherence to Jackman criteria, and patients benefiting from afatinib therapy had longer PFS and OS (P &lt; .001). Outcome results for repeated biopsy patients were similar to the whole population, with no evidence of response in T790M-positive patients. All patients were evaluable for toxicity, and 81% experienced an AE of any grade, with grade 3 to 4 AEs, mainly diarrhea and skin toxicity, occurring in 19 (20%) patients. Conclusion: Our results showed that afatinib has only modest efficacy in a real life population of EGFR mutant NSCLC patients with acquired resistance to erlotinib or gefitinib

Italian Consensus Statement on Patient Engagement in Chronic Care: Process and Outcomes

Patient engagement has been recognized as a key priority in chronic care. However,scholars agree that guidelines are needed to ensure effective patient engagement strategies. Tothis end, a Consensus Conference process was promoted with the following methodological steps:(1) extensive literature review about patient engagement initiatives in chronic care; (2) a stakeholderssurvey to collect best practices and (3) workshops with experts. On the basis of the informationcollected, a consensus statement was drafted, revised, and finalized by a panel of select renownedexperts. These experts agreed in defining engagement as an eco-systemic concept involving multipleactors all of which contribute to influence patients\u2019 willingness and ability to engage in chronic care.Moreover, experts recommended, whenever possible, to adopt standardized instruments to assess engagement levels and related unmet needs. Then, experts strongly advised appropriate trainings for healthcare professionals about patient engagement strategies. Furthermore, the importance of promoting healthcare professionals\u2019 wellbeing has been advocated. Family caregivers, as well as patients\u2019 organizations - should be trained and engaged to increase the effectiveness of interventions dedicated to patients. Finally, experts agreed that digital technologies should be considered as acrucial enhancer for patient engagement in chronic car