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Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET inhibitor after failure of the other is generally not recommended because of cross-resistance mechanisms. We report the case of a patient affected by metastatic RET-rearranged non-small cell lung cancer who experienced long-lasting disease control with pralsetinib. After 13 months from treatment start, the patient developed recurrent drug-related pneumonitis, requiring temporary interruptions and dose reductions and eventually failing to control the disease. Selpercatinib was then started as an off-label treatment, allowing both clinical and radiological intracranial disease control. Selpercatinib was well-tolerated at full dosage, and no pulmonary event occurred. In our case report, after pralsetinib dose reduction due to pulmonary toxicity, the therapeutic switch to selpercatinib allowed the patient to receive a full-dose treatment, eventually restoring disease control. Our case report and a few literature data suggest that switching from pralsetinib to selpercatinib may represent a therapeutic opportunity, especially for patients with brain metastases.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Proteínas Proto-Oncogênicas c-ret , Pirazóis , Piridinas , Humanos , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pneumonia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Pirimidinas , FemininoRESUMO
BACKGROUND: The rehabilitation of paretic stroke patients uses a wide range of intervention programs to improve the function of impaired upper limb. A new rehabilitative approach, called action observation therapy (AOT) is based on the discovery of mirror neurons and has been used to improve the motor functions of adult stroke patients and children with cerebral palsy. Recently, virtual reality (VR) has provided the potential to increase the frequency and effectiveness of rehabilitation treatment by offering challenging and motivating tasks. METHODS: The purpose of the present project is to design a randomized controlled six-month follow-up trial (RCT) to evaluate whether action observation (AO) added to standard VR (AO + VR) is effective in improving upper limb function in patients with stroke, compared with a control treatment consisting of observation of naturalistic scenes (CO) without any action content, followed by VR training (CO + VR). DISCUSSION: AO + VR treatment may provide an addition to the rehabilitative interventions currently available for recovery after stroke and could be utilized within standard sensorimotor training or in individualized tele-rehabilitation. TRIAL REGISTRATION: The trial has been prospectively registered on ClinicalTrials.gov. NCT05163210 . 17 December 2021.
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Neurônios-Espelho , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Realidade Virtual , Adulto , Criança , Humanos , Acidente Vascular Cerebral/terapia , TecnologiaRESUMO
We describe the case of a bilingual patient with persistent symptoms largely, although not fully, consistent with those that are usually reported in Gerstmann's syndrome. Twenty months after a spontaneous primary intracranial hemorrhage, the patient was evaluated with a series of neuropsychological tasks and underwent an MRI investigation based on Diffusion Tensor Imaging probabilistic tractography. The patient suffered from dysgraphia (difficulty in the access to the graphemic representation of letter forms), autotopoagnosia (difficulties in locating body parts on verbal command), right-left confusion (difficulties in localizing right and left side of symmetrical body parts), and number processing/calculation impairments (predominant difficulties on transcoding tasks). Probabilistic tractography revealed a relatively spared superior longitudinal fasciculus and severe damage to the subcortical white matter connecting the angular gyrus with other parietal regions, such as the intraparietal sulcus and the supramarginal gyrus. Within the framework of the contemporary cognitive accounts of Gerstmann's syndrome, the case supports the assumption of an anatomical intraparietal disconnection more than a functional Grundstörung (core impairment).
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Síndrome de Gerstmann , Imagem de Tensor de Difusão , Síndrome de Gerstmann/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Lobo Parietal/diagnóstico por imagemRESUMO
PURPOSE: To determine whether half of the approved dose of gadobenate dimeglumine (MultiHance) is as effective as a full dose of gadoterate meglumine (Dotarem) for qualitative and quantitative cerebral blood volume (CBV) perfusion evaluation at 3T in patients with brain gliomas. MATERIALS AND METHODS: We enrolled 65 adult patients in an interindividual comparative study. Patients were randomized to one of two study arms: 33 patients received 0.1 mmol/kg body weight (bw) of gadoterate, 32 patients received 0.05 mmol/kg bw of gadobenate. The patients underwent identical examinations at 3T. Arterial input function (AIF), tissue function (TF), and the maximum tumor CBV (CBV_T) were obtained from each patient. The quality of the CBV maps were independently reviewed by two neuroradiologists blinded to the administered contrast agent. RESULTS: The administration of a half dose of gadobenate led to a roughly 40% reduction in signal drop compared to that achieved with a full dose of gadoterate (P values for AIF and TF maximum and integral were <0.01); quantitative and qualitative assessment of CBV maps revealed no difference between contrast agents (P values for CBV_T of high- and low-grade gliomas, image quality evaluation were 0.87, 0.48, >0.65, respectively) CONCLUSION: The CBV maps obtained with a half dose gadobenate (0.05 mmol/kg bw) are of comparable diagnostic quality as the corresponding images acquired with a full dose of gadoterate (0.1 mmol/kg bw). LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:500-506.
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Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Meglumina/análogos & derivados , Compostos Organometálicos/administração & dosagem , Adulto , Neoplasias Encefálicas/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Meglumina/administração & dosagem , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Percutaneous radiofrequency ablation (PRFA) of renal malignancies is currently a therapeutic option for patients who are not able to undergo surgery. Some authors consider PRFA as the therapeutic standard in the treatment of renal neoplasms in non-operable patients due to comorbid conditions and in patients with mild-moderate renal failure, to preserve residual renal functionality. The use of PRFA has become more and more widespread due to a rise in the incidental detection of renal cell carcinomas with the ever-increasing use of Imaging for the study of abdominal diseases. Clinical studies indicate that RF ablation is an effective therapy with a low level of risk of complications, which provides good results in selected patients over short and medium term periods of time, however up to now few long-term studies have been carried out which can confirm the effectiveness of PRFA.
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Carcinoma de Células Renais/cirurgia , Ablação por Cateter/métodos , Neoplasias Renais/cirurgia , Biópsia , Humanos , Imagem por Ressonância Magnética Intervencionista , Nefrectomia , Complicações Pós-Operatórias , Ondas de Rádio , Radiografia IntervencionistaRESUMO
Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.
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Paralisia Cerebral , Hemiplegia , Criança , Humanos , Hemiplegia/diagnóstico por imagem , Hemiplegia/complicações , Encéfalo , Paralisia Cerebral/patologia , Imageamento por Ressonância Magnética/métodos , Movimento , MãosRESUMO
BACKGROUND: Action observation treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by their subsequent repetition. The standard version of AOT consists in the observation/imitation of a typically developed individual, which is proposed as model (TDM-AOT). AIM: This study aims to compare the effectiveness of AOT based on a pathological ameliorative model (PAM-AOT) versus TDM-AOT in improving upper limb ability in children with unilateral cerebral palsy (UCP). DESIGN: The study consists in a prospective randomized controlled, evaluator-blinded trial (RCT), with two active arms, designed to evaluate the effectiveness of AOT based on pathological model (PAM-AOT) as compared to a standard AOT based on TDM (TDM-AOT). SETTING: The 3-week AOT program was administered in a clinical setting. For some patients, the treatment was delivered at participant's home with the remote support of the physiotherapist (tele-rehabilitation). POPULATION: Twenty-six children with UCP (mean age 10.5±3.09 years; 14 females) participated in the study, with the experimental group observing a pathological model and the control group observing a typically developed model. METHODS: Motor assessments included unimanual and bimanual ability measures conducted at T0 (baseline, before the treatment), T1 (3 weeks after T0), T2 (8-12 weeks after treatment) and T3 (24-28 weeks after treatment); a subset of 16 patients also underwent fMRI motor assessment. Generalized Estimating Equations models were used for statistical analysis. RESULTS: Both groups showed significant improvement in bimanual function (GEE, Wald 106.16; P<0.001) at T1 (P<0.001), T2 (P<0.001), and T3 (P<0.001). Noteworthy, the experimental group showed greater improvement than the control group immediately after treatment (P<0.013). Both groups exhibited similar improvement in unimanual ability (GEE, Wald 25.49; P<0.001). The fMRI assessments revealed increased activation of ventral premotor cortex after treatment in the experimental compared with control group (GEE, Wald 6.26; P<0.012). CONCLUSIONS: Overall, this study highlights the effectiveness of PAM-AOT in achieving short-term improvement of upper limb ability in children with UCP. CLINICAL REHABILITATION IMPACT: These findings have significant implications for rehabilitative interventions based on AOT in hemiplegic children, by proposing a non-traditional approach focused on the most functional improvement achievable by imitating a pathological model.
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PURPOSE: To report our experience with a case of a very atypical clinical onset of multiple sclerosis in a young boy during a COVID-19 infection. CASE REPORT: A 16-year-old boy was referred to our ophthalmology clinic with a complete isolated bilateral horizontal gaze palsy. The condition had onset suddenly 2 weeks prior and he had no associated symptoms, as well as no significant medical history. His corrected visual acuity was 0.0 logMAR in both eyes. While hospitalized, he was found infected with COVID-19. Subsequent brain MRI showed multiple lesions typical of a yet undiagnosed MS, as well as an active pontine plaque which was highly probable the cause of the horizontal gaze palsy. High-dose steroid treatment was initiated 1 week later, after the patient exhibited negative COVID-19 test results. CONCLUSION: Clinical manifestations of MS are rarely seen in male teenagers and only a few cases of isolated bilateral horizontal gaze palsy have been reported as the initial manifestation, but never during concomitant COVID-19 infection. We presume that the presence of COVID-19 may have been a neuroinflammatory trigger of underlying MS.
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COVID-19 , Esclerose Múltipla , Estrabismo , Adolescente , Humanos , Masculino , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Imageamento por Ressonância Magnética/métodos , Paralisia/complicaçõesRESUMO
BACKGROUND: Intravenous thrombolysis and endovascular reperfusion represent nowadays the standard treatment for acute ischemic stroke. However, ineffective reperfusion may occur, representing a major negative prognostic factor on clinical outcome. Extracranial-intracranial (EC-IC) bypass revascularization procedure in an acute setting appears as a promising tool to increase reperfusion rates and improve clinical outcome in a highly selected population refractory or ineligible for standard reperfusion therapies. METHODS: The Extracranial-Intracranial Revascularization for Acute Stroke - Parma (EIRASP) study is an observational, prospective, single-center, study (protocol 203/2020/OSS/AOUPR). Patients admitted for an acute ischemic anterior circulation stroke due to large vessels occlusion and refractory or ineligible for standard reperfusion therapies will be submitted to an extracranial-intracranial bypass revascularization procedure when fulfilling all clinical and radiological inclusion criteria. The primary outcome will be the functional outcome (modified Rankin Scale and NIHSS score) at 3 months after the surgical procedure. Secondary outcome will include the evaluation of clinical and surgical complications rates, quantitative monitoring of perfusion parameters, and further functional and survival rates. RESULTS: Despite promising data regarding the feasibility and the favorable outcome of urgent EC-IC bypass revascularization procedure in selected patients suffering an acute ischemic stroke are emerging in literature, no studies to date have prospectively explored the real potential of this technique. CONCLUSIONS: The EIRASP study aims to provide further and stronger methodological evidence of the benefit of urgent EC-IC bypass revascularization procedure in acute ischemic stroke.
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Revascularização Cerebral , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Revascularização Cerebral/métodos , Procedimentos Endovasculares/efeitos adversos , AVC Isquêmico/complicações , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Estudos Observacionais como AssuntoRESUMO
Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32, which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell-derived (iPSC-derived) retinal models. Our data showed that TBC1D32 was expressed during retinal development and that it played an important role in retinal pigment epithelium (RPE) differentiation. Furthermore, we identified a role for TBC1D32 in ciliogenesis of the RPE. We demonstrated elongated ciliary defects that resulted in disrupted apical tight junctions, loss of functionality (delayed retinoid cycling and altered secretion balance), and the onset of an epithelial-mesenchymal transition-like phenotype. Last, our results suggested photoreceptor differentiation defects, including connecting cilium anomalies, that resulted in impaired trafficking to the outer segment in cones and rods in TBC1D32 iPSC-derived retinal organoids. Overall, our data highlight a critical role for TBC1D32 in the retina and demonstrate that TBC1D32 mutations lead to RP. We thus identify TBC1D32 as an IRD-causative gene.
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Células-Tronco Pluripotentes Induzidas , Degeneração Retiniana , Retinose Pigmentar , Humanos , Retina , Retinose Pigmentar/genética , Degeneração Retiniana/genética , Epitélio Pigmentado da Retina , Proteínas Adaptadoras de Transdução de SinalRESUMO
BACKGROUND: Posterior reversible encephalopathy (PRES) is a rare syndrome characterized by headache, confusion, seizures, visual changes and white matter edema at radiological imaging. Its pathophysiology is not clarified and different causes, including uncontrolled hypertension, eclampsia, chemotherapy and hypomagnesemia have been suggested. CASE REPORT: A woman affected by stage IV breast cancer with lower extremity deep vein thrombosis treated with low-molecular-weight-heparin, currently in therapy with Palbociclib/Fulvestrant (antiCDK4 and 6/estrogen receptor antagonist) but previously treated with several other chemotherapy lines (including VEGF inhibitor bevacizumab), was admitted to our Internal Medicine department because of ascites and abdominal pain. She was treated with diuretics (and paracentesis). Recently (six-month earlier) a pan-encephalic radiotherapy was done because of brain and skull metastasis. Among blood tests, low serum levels of hypomagnesemia were observed. She developed PRES that rapidly progressed to lethargy, unresponsiveness till coma without changes in blood pressure. Magnetic Resonance Imaging study showed bilateral parieto-occipital edema and a thrombosis of left transverse and sigmoid sinuses. Anti-edema therapy, intravenous supplementation of magnesium and decoagulation were started, with complete and rapid recovery (within 18 hours) of clinical and radiologic changes. CONCLUSIONS: PRES diagnosis was based on the rapid clinical recovery after antiedema treatment and magnesium supplementation. Low magnesium level related to both diuretic and Fulvestrant/Palbociclib therapies and recent radiotherapy can represent potential mechanisms favouring PRES development. The previous bevacizumab treatment may also be involved as a PRES predisposing factor. The concomitant occurrence of cerebral thrombosis can have precipitated the clinical situation.
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Antineoplásicos/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Deficiência de Magnésio/complicações , Síndrome da Leucoencefalopatia Posterior/etiologia , Antineoplásicos/uso terapêutico , Feminino , HumanosRESUMO
Thromboembolic events are frequent in patients with cancer, commonly involving the venous and pulmonary circulation. The arterial system is rarely implicated in embolism and, when involved, a cardiogenic origin should always be excluded. In the present study, a case of a patient who developed multiple embolic events concomitantly with the diagnosis of locally-advanced non-small cell lung cancer with high expression levels of programmed death-ligand 1 (PD-L1) in >50% of tumor cells is reported. A cardiac defect interpreted as a patent foramen ovale required low molecular weight heparin administration. Despite the anti-coagulant therapy, before first-line anticancer treatment with pembrolizumab immunotherapy could be administered due to high PD-L1 expression levels, a new hospitalization was required due to the onset of novel ischemic manifestation. New transthoracic and transesophageal echocardiography revealed a previously misdiagnosed vegetation of the mitral valve that caused systemic embolization. The lack of any sign of infection led to the diagnosis of a non-bacterial thrombotic endocarditis (NBTE), whose embolic sprouting gave rise to the widespread ischemic events. No active anticancer treatment was feasible due to the rapid progression of the disease. NBTE can evolve quickly, eventually preventing any chance of treatment targeting the primary cause, which in the present study was lung cancer. If NBTE can be correctly diagnosed sooner then there may be the potential for anticancer therapy that does not worsen the hypercoagulability state, thus improving cancer-associated survival.
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Jugular foramen (JF) metastasis is rare and often presents as JF syndrome. A 73-year-old male complained of left-sided mastoid pain that irradiated to the neck since the past 3 months. Onset of facial nerve (FN) palsy and persistence of the symptomatology despite corticosteroid therapy demanded radiologic evaluation. Computed tomography and magnetic resonance imaging showed a wide osteolytic lesion of the left JF with involvement of the third segment of the FN. The patient underwent transmastoid incisional biopsy. Histopathological examination showed an adenocarcinoma that was suggested to be of respiratory origin. A primary pulmonary lesion and metastasis to other sits were detected. The patient died 1 month after the initiation of the chemotherapy. Persistent mastoid pain and progressive FN palsy must be considered indicative of JF malignant lesions. Despite early diagnosis, secondary lesions of the JF are characterized by a poor prognosis; however, accurate diagnosis may avoid unnecessary aggressive surgery.
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Doenças dos Nervos Cranianos/diagnóstico , Forâmen Jugular/patologia , Neoplasias Pulmonares/patologia , Neoplasias da Base do Crânio/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias da Base do Crânio/secundárioRESUMO
Background: Motor Imagery (MI) refers to mental simulation of a motor action without producing any overt movement. Previous studies showed that children with Unilateral Cerebral Palsy (UCP) are impaired in implicit MI, as demonstrated by the performance of Hand Laterality Judgment tasks. The aim of this study was to examine the specificity of explicit MI deficits in UCP children. Methods: A group of UCP children (n = 10; aged 9-14) performed a mental chronometry task consisting in grasping an object and placing it into a container, or in imagining to perform the same action. As control, a group of typically developing (TD) children, matched by age, performed the same task. Movement durations for executed and imagined trials were recorded. A subgroup of 7 UCP children and 10 TD children also underwent a session of functional MRI to examine the activation of parieto-frontal areas typically associated to MI processes, during the imagination of reaching-grasping actions performed with the paretic hand. Results: Behavioral results revealed the existence of a correlation between executed and imagined movement durations both in TD and UCP groups. Moreover, the regression analysis in TD children showed that higher scores in mental chronometry tasks were positively correlated to increased bilateral activation of the intraparietal sulcus (IPS), superior parietal lobule (SPL), and dorsal premotor (PMd) cortex. A similar analysis revealed in the UCP group a positive correlation between a higher score in the mental chronometry task and bilateral activations of IPS, and to activation of contralesional, right PMd, and putamen during imagination of grasping movements. Conclusions: These results provide new insights on the relationship between MI capacity and motor deficits in UCP children, suggesting the possibility of the use of explicit MI training to improve patient's upper limb motor functions.
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INTRODUCTION: Treatment paradigms for EGFR-mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of EGFR T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status. PATIENTS AND METHODS: In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation. RESULTS: Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib. CONCLUSIONS: Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stress the opportunity of its administration in the case of CNS failure of first-line EGFR inhibition, even in the absence of T790M proof.
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Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Mutação/genética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Sistema Nervoso Central/patologia , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSE: In this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis. PATIENTS AND METHODS: COPD cases were selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis. RESULTS: The frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio [OR] 4.05, 95% confidence interval [CI]: 2.2-7.4) and increasing pack-years (OR 1.01, 95% CI: 1-1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10-1.25) and male (OR 8.58, 95% CI: 1.58-68.9). CONCLUSION: There was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.