Metachronous primary uterine cancer surgically resected during crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of nonsmall-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral smallmolecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slowgrowing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out

Frontal lobe metabolic alterations in autism spectrum disorder: a 1H-magnetic resonance spectroscopy study.

Recently, neuroimaging studies were performed using 1H-magnetic resonance spectroscopy (1H-MRS), revealing a quantitative alteration of neurochemicals (such as neurotransmitters and metabolites) in several brain regions of patients with autism spectrum disorder (ASD). The involvement of the frontal lobe in the neurobiology of ASD has long been documented in the literature. Therefore, the aim of this study was to analyze the alterations of N-acetylaspartate/creatine (NAA/Cr) and choline/Cr (Cho/Cr) ratios in the frontal lobe subcortical white matter (WM) in ASD patients, in order to reveal any alteration of metabolites that might be the expression of specific clinical features of the disorder

Exposure of Seeds to ELF MF. Effects on Germination and Growth. Preliminary Results

Seeds of Eruca sativa and Lactuga sativa were exposed to 75 Hz Magnetic Field at 15 and 150 G. Some seeds were plunged into the water during exposure to magnetic fields. Then seeds were placed in germinator and seed germination rate and seedling excretion rate were measured

SUBACUTE STENT THROMBOSIS AND STRESS-INDUCED CARDIOMYOPATHY: TRIGGER OR CONSEQUENCE?

Stress-induced cardiomyopathy or Takotsubo cardiomyopathy (TCM) is a unique syndrome, characterized by transient left ventricular (LV) apical ballooning without significant coronary arteries stenosis, affecting mainly menopausal women. We present the case of a 70 year old woman with subacute stent thrombosis (ST) at the level of the right coronary artery and transient apical ballooning with normal flow of left and circumflex coronary arteries. TCM is frequently associated with emotional stress, but to date no case of ST triggering TCM have been reported

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study

Background Dupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings. Objective This study aimed to identify predictive clinical and demographic factors affecting patient selection for dose spacing or treatment withdrawal due to satisfactory response. Materials and methods This retrospective study included adult patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Descriptive statistics were performed to analyze demographic and clinical variables. Logistic regression models were used to identify predictor variables. Results A total of 818 adult patients with moderate-to-severe AD was included in the study and 12% (97/818) of them performed dose spacing to 3–4 weeks or treatment withdrawal (8%, 67/818). The presence of non-cutaneous atopic manifestations (OR = 1.59, 95%CI = 1.06–2.38, p = 0.024), prurigo nodularis phenotype (OR = 4.5, 95%CI = 1.87–10.9, p = 0.001) and the age at treatment initiation (OR = 1.82, 95%CI = 1.12–2.94, p = 0.015) were confirmed as the strongest predictors of dose spacing or treatment withdrawal while maintaining dupilumab effectiveness. Conclusion Our findings contribute to define the patient profile that could maintain the therapeutic response after dose spacing or treatment withdrawal

Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non–Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation sequencing (NGS). The response to crizotinib of treated patients was recorded. RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. They showed coexistent split signals pattern, with mean percentage of 15.4%, and 5′ deletions pattern, with mean percentage 31.7%. Two cases had also gene amplification pattern. In three cases (42.8 %), the polysomy was observed. The NGS assay confirmed IHC results. In these patients, the treatment with crizotinib was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice

Pathological Complete Response to Neoadjuvant Chemoimmunotherapy for Early Triple-Negative Breast Cancer: An Updated Meta-Analysis

Immune checkpoint inhibitors (ICIs) have made a breakthrough in the systemic treatment for metastatic triple-negative breast cancer (TNBC) patients. However, results of phase II and III clinical trials assessing ICIs plus chemotherapy as neoadjuvant treatment were controversial and conflicting. We performed a meta-analysis aimed at assessing the Odds Ratio (OR) of the pathological complete response (pCR) rate in trials assessing neoadjuvant chemoimmunotherapy in TNBC. According to our results, the use of neoadjuvant chemoimmunotherapy was associated with higher pCR (OR 1.95; 95% Confidence Intervals, 1.27–2.99). In addition, we highlighted that this benefit was observed regardless of PD-L1 status since the analysis reported a statistically significant and clinically meaningful benefit in both PD-L1 positive and PD-L1 negative patients. These findings further support the exploration of the role of ICIs plus chemotherapy in early-stage TNBC, given the potentially meaningful clinical impact of these agents. Further studies aimed at more deeply investigating this emerging topic in breast cancer immunotherapy are warranted

BESIDE \u2013BEhavioral integrated System for diagnosis, support and monItoring of neuro-Degenerative diseasEs

Il progetto di ricerca industriale e sviluppo sperimentale denominato BESIDE intende applicare tecniche di intelligenza artificiale per l\u2019analisi di pattern motori (Gait Analysis) e comportamentali di individui affetti da malattie neurodegenerative. In particolare, il progetto intende individuare i sensori pi\uf9 idonei e sviluppare un complesso sistema di sorveglianza IoT in grado di fornire evidenze specifiche agli staff medici inerenti i comportamenti e le evoluzioni del decadimento fisico del paziente anche quando lo stesso non \ue8 sotto diretta osservazione