Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 164
Filter
1.
ESMO Open ; 9(6): 103591, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38878324

ABSTRACT

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.


Subject(s)
Lung Neoplasms , Neuroendocrine Tumors , Humans , Lung Neoplasms/pathology , Lung Neoplasms/classification , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/classification , Female , Ki-67 Antigen/metabolism , Male , Biomarkers, Tumor/metabolism , Middle Aged , World Health Organization , Histones/metabolism , Aged , Prognosis , Deep Learning
2.
ESMO Open ; 8(5): 101628, 2023 10.
Article in English | MEDLINE | ID: mdl-37713929

ABSTRACT

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Laboratories , Retrospective Studies , Pandemics , Mutation , ErbB Receptors/genetics , Europe
3.
ESMO Open ; 6(1): 100024, 2021 02.
Article in English | MEDLINE | ID: mdl-33399086

ABSTRACT

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.


Subject(s)
COVID-19/prevention & control , Clinical Laboratory Services/statistics & numerical data , Pathology, Clinical/statistics & numerical data , Pathology, Molecular/statistics & numerical data , Surveys and Questionnaires , Thoracic Diseases/diagnosis , Biological Specimen Banks/organization & administration , Biological Specimen Banks/statistics & numerical data , COVID-19/epidemiology , COVID-19/virology , Clinical Laboratory Services/trends , Containment of Biohazards/statistics & numerical data , Disease Outbreaks , Europe/epidemiology , Forecasting , Humans , Pandemics , Pathology, Clinical/methods , Pathology, Clinical/trends , Pathology, Molecular/methods , Pathology, Molecular/trends , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Specimen Handling/methods , Specimen Handling/statistics & numerical data , Thoracic Diseases/therapy
4.
Eur J Cancer ; 135: 221-229, 2020 08.
Article in English | MEDLINE | ID: mdl-32610210

ABSTRACT

BACKGROUND: Radiotherapy is a standard of care for locally advanced stage III N2 non-small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival. PATIENTS AND METHODS: We retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival. RESULTS: High density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99-3.78]) and DFS (p = 0.003, HR = 2.42 [1.31-4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11-3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98-3.74]) and PFS (p = 0.03, HR = 1.83 [1.03-3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1-49%) was associated with a higher survival in the PORT. CONCLUSIONS: Intra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy , Forkhead Transcription Factors/analysis , Lung Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/analysis , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy/adverse effects , Chemoradiotherapy/mortality , Chemoradiotherapy, Adjuvant , Female , Humans , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Time Factors , Treatment Outcome , Tumor Microenvironment
5.
Biochim Biophys Acta Mol Basis Dis ; 1865(11): 165516, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31362041

ABSTRACT

Loss of galactose-1 phosphate uridylyltransferase (GALT) activity in humans results in Classic Galactosemia, and the GalT-deficient (GalT-/-) mouse mimics the patient condition. GalT-/- ovaries display elevated endoplasmic reticulum (ER) stress marker, BiP, and downregulated canonical phosphatidylinositol 3-kinase (Pi3k)/protein kinase B (Akt) growth/pro-survival signaling. Numbers of primordial follicles are reduced in the mutants, recapitulating the accelerated ovarian aging seen in human patients. We previously found that oral administration of the compound Salubrinal (an eIF2α phosphatase inhibitor), resulted in reduction of ovarian BiP expression, rescued Pi3k/Akt signaling, and a doubling of primordial follicles in GalT-/- adults. Here, we further characterized galactosemic stress in GalT-/- mice versus wild-type (WT) controls, and examined whether Salubrinal treatment improved broader reproductive parameters. We assessed the expression levels of factors of the unfolded protein response (UPR), and found that BiP, phospho-Perk, and phospho-eIF2α were all elevated in GalT-/- ovaries. However, neither IKK activation (NFκB pathway) nor alternative Xbp1 splicing downstream of ER membrane protein Ire1α activation was induced, suggesting an Xbp1-independent UPR in galactosemic stress. Moreover, Salubrinal treatment significantly increased the number of ovulated eggs in mutant animals after gonadotrophic superovulation. Salubrinal treatment also normalized estrus cycle stage lengths and resulted in significantly larger litter sizes than vehicle-treated mutants. Overall, we show that Salubrinal protects against galactosemia-induced primordial follicle loss in a fashion that includes suppressing the de-phosphorylation of eIF2α, and that intervention in this way significantly improves and extends ovarian function, fertility, and fecundity.


Subject(s)
Cinnamates/therapeutic use , Eukaryotic Initiation Factor-2/metabolism , Galactosemias/complications , Infertility, Female/drug therapy , Infertility, Female/etiology , Thiourea/analogs & derivatives , Animals , Cinnamates/pharmacology , Disease Models, Animal , Female , Fertility/drug effects , Galactosemias/metabolism , Infertility, Female/metabolism , Mice , Ovary/drug effects , Ovary/metabolism , Phosphorylation/drug effects , Thiourea/pharmacology , Thiourea/therapeutic use , Unfolded Protein Response/drug effects
6.
J Geophys Res Atmos ; 124(2): 530-543, 2019 Jan 27.
Article in English | MEDLINE | ID: mdl-31080699

ABSTRACT

Mid-Missouri experienced up to 2 min 40 s of totality at around solar noon during the total eclipse of 2017. We conducted the Mid-Missouri Eclipse Meteorology Experiment to examine land-atmosphere interactions during the eclipse. Here, research examining the eclipse responses in three contrasting ecosystems (forest, prairie, and soybeans) is described. There was variable cloudiness around first and fourth contacts (i.e., the start and end of partial solar obscuration) at the forest and prairie; however, solar irradiance (K ↓) signals during the eclipse were relatively clean. Unfortunately, the eclipse forcing at the soybean field was contaminated by convective activity, which decreased K ↓ beginning about an hour before first contact and exposed the field to cold outflow ~30 min before second contact. Turbulence was suppressed during the eclipse at all sites; however, there was also an amplified signal at the soybean field during the passage of a gust front. The standard deviations of the horizontal and vertical wind velocities and friction velocities decreased by ~75% at the forest (aerodynamically rough), and ~60% at the prairie (aerodynamically smooth). The eddy fluxes of energy were highly coherent with the solar forcing with the latent and sensible heat fluxes approaching 0 W/m2 and changing in direction, respectively. For the prairie site, we estimated a canopy-scale time constant for the surface conductance light response of 10 min. Although the eclipse imparted large forcings on surface energy balances, the air temperature response was relatively muted (1.5-2.5 °C decrease) due to the absence of topographic effects and the relatively moist land and atmosphere.

7.
Transplant Proc ; 51(1): 136-139, 2019.
Article in English | MEDLINE | ID: mdl-30655148

ABSTRACT

BACKGROUND: Although optimization of immunosuppressive schemes in renal transplantation have minimized acute posttransplant complications, long-term outcomes are still not optimal and most of the chronic graft damage is drug-related. Therefore, to define the best long-term maintenance immunosuppressive regimen is of major importance in renal transplantation. To assess this objective, we undertook a large, multicenter cohort study in Italy. METHODS: We retrospectively analyzed data of 5635 patients (enrolled from 1983 to 2012) and we assessed the impact of 3 major immunosuppressive regimens (calcineurin inhibitors+antimetabolites+corticosteroids [CNI+ANT+CS] vs CNI+mammalian target-of-rapamycin (mTOR) inhibitors+CS [CNI+mTOR-I+CS] vs CNI+CS) on long-term clinical outcomes by employing several statistical algorithms. RESULTS: The overall difference in the incidence of outcome over time was not statistically different within the first 5 years of follow-up (P = .13); however, it became significant at 10 years and 20 years (P < .01), with the CNI+CS group showing the lowest cumulative incidence of outcome. Compared with the CNI+ANT+CS group, the CNI+mTOR-I+CS group patients had a significantly higher risk of outcome (hazard ratio [HR], 1.30; P = .024); the difference remained significant and even increased in magnitude after adjustment for potential confounders (HR, 1.38; P = .006). Similarly, patients in the CNI+CS group had a significantly higher risk of the outcome (HR, 1.64; P < .001). CONCLUSION: Our data confirm that CNI+ANT+CS is the "gold standard" therapy in renal transplantation, but, whenever required, the introduction of mTOR-Is instead of ANT may not dramatically modify major clinical outcomes. The use of mTOR-I could be a valuable pharmacologic tool to minimize CNI complications and insure adequate immunosuppression.


Subject(s)
Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adrenal Cortex Hormones/therapeutic use , Antimetabolites/therapeutic use , Calcineurin Inhibitors/therapeutic use , Cohort Studies , Female , Humans , Italy , Kidney/drug effects , Male , Middle Aged , Retrospective Studies , TOR Serine-Threonine Kinases/antagonists & inhibitors
8.
Funct Neurol ; 33(3): 131-136, 2018.
Article in English | MEDLINE | ID: mdl-30457965

ABSTRACT

Stroke patients have reduced balance and postural control that limits their activities of daily living and participation in social life. Recently, many exergaming systems based on video-biofeedback have been developed for balance training in neurological conditions, however their efficacy remains to be proven. The aim of this study was to investigate the effects on balance skills and patient compliance of biofeedback training based on inertial measurement units and exergaming in subacute stroke. The enrolled subjects were randomized into two groups: subjects allocated to the experimental group performed 10 sessions of biofeedback balance training using inertial sensors, whereas subjects allocated to the control group performed 10 sessions of conventional balance training. All subjects were assessed at T0 (pre-treatment), T1 (posttreatment) and T2 (1-month follow-up). The Berg Balance Scale, Rivermead Mobility Index and modified Barthel Index were used to assess balance, mobility and global disability, respectively. To assess the severity of the stroke and its effects on the patient we used the National Institutes of Health Stroke Scale and the Canadian Neurological Scale. Finally, a static force platform evaluating stabilometric parameters was used to assess balance skills. Fifteen subjects with subacute stroke (4F; age 57.80 ± 13.7) completed the experimental protocol. The analysis showed a significant improvement in balance skills and in the overall clinical outcomes in the experimental group compared with the control group; the experimental group also showed better compliance with the training. The biofeedback system of the device used in this study probably enhances neuroplasticity mechanisms of postural and balance skills in subacute stroke patients.


Subject(s)
Biofeedback, Psychology , Brain Ischemia/complications , Exercise Therapy/methods , Patient Compliance , Postural Balance , Stroke Rehabilitation/methods , Stroke/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , Motor Skills , Pilot Projects , Stroke/complications , Treatment Outcome
9.
Rev Pneumol Clin ; 74(5): 339-350, 2018 Oct.
Article in French | MEDLINE | ID: mdl-30337201

ABSTRACT

Immune checkpoint inhibitors (ICI), targeting the PD1/PD-L1 axis has shown their efficacy in lung cancer but only in a restricted population of patients, thus it is mandatory to identify biomarkers predicting the clinical benefit. In this article we will describe and analyzed biomarkers already published, from protein, to RNA and at last DNA markers, discussing each markers feasibility and interest. In the future, combined analysis of several markers will probably be proposed, particularly with the increasing complexity of therapy schema with molecules association.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/immunology , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy/methods , Lung Neoplasms/therapy , Programmed Cell Death 1 Receptor/immunology , Antibodies, Monoclonal/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/diagnosis , Humans , Lung Neoplasms/diagnosis , Predictive Value of Tests , Prognosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Treatment Outcome
10.
Rev Pneumol Clin ; 74(5): 327-338, 2018 Oct.
Article in French | MEDLINE | ID: mdl-30343945

ABSTRACT

Lung cancer is the leading cause of cancer deaths in France, with about 30,000 deaths per year. The overwhelming majority (90 %) are tobacco-related. The prognosis is dark but great therapeutic advances have been made with the development of targeted therapies first and then immunotherapy afterwards. These medications are conditioned to the expression of biomarkers that require specific tools in routine to measure them. We will detail in this chapter several techniques of anatomopathology, cytogenetics and molecular biology necessary for the detection of biomarkers in lung cancers, and their applications in thoracic oncology in 2018.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/diagnosis , Cytogenetic Analysis/methods , High-Throughput Nucleotide Sequencing/methods , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Chromatin Immunoprecipitation/methods , Cytogenetic Analysis/trends , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Sequence Analysis, DNA/methods , Translocation, Genetic
11.
Rev Pneumol Clin ; 74(5): 351-358, 2018 Oct.
Article in French | MEDLINE | ID: mdl-30316650

ABSTRACT

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent. STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea. PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied. CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.


Subject(s)
Lung Neoplasms/surgery , Mesothelioma/surgery , Pleural Neoplasms/surgery , Thoracic Surgical Procedures/methods , Chemotherapy, Adjuvant , Combined Modality Therapy , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Mesothelioma/diagnosis , Mesothelioma/drug therapy , Mesothelioma/radiotherapy , Mesothelioma, Malignant , Pleural Neoplasms/diagnosis , Pleural Neoplasms/drug therapy , Pleural Neoplasms/radiotherapy , Pneumonectomy , Radiotherapy, Adjuvant , Thoracoscopy , Treatment Outcome
12.
Cancer Radiother ; 22(6-7): 688-693, 2018 Oct.
Article in French | MEDLINE | ID: mdl-30131267

ABSTRACT

Recent therapeutic advances in non-small cell lung cancer allow a better understanding of the interactions between the tumour and its direct immune environment. The identification of new immune biomarkers integrating both cell subpopulations and their interactions is a real issue in oncology. New techniques of tissue analysis, particularly multiplex immunohistochemistry, consisting of a labelling of several antigens of interest by immunofluorescence on the same slide, provide a better understanding of the tumour environment. Integration of these modalities of analysis to the therapeutic decision is promising, because it allows an increased characterization of each tumour, particularly interesting with radiotherapy and immunotherapy. This article describes the potential of these assays in locally advanced non-small cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Tumor Microenvironment/immunology , Humans , Immunohistochemistry , Neoplasm Staging
13.
J Neurol ; 265(7): 1676-1683, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29777361

ABSTRACT

INTRODUCTION: Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated. METHODS: 126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled. Participants underwent a deep neurological examination by two blinded to the treatment raters, and a blood sampling to assess plasmatic immunosuppressant level and nephrological function tests. Tremor and cerebellar signs were scored according to the Fahn-Tolosa-Marin and the SARA scale. Parkinsonism was excluded applying the UPDRS (part III). RESULTS: Tremor was more common and severe in the Tacrolimus group, similar to impairment in ADL. Regardless of treatment, tremor involved both upper and lower limbs and was activated by action, but in about 50% of cases presented in action and rest condition. Plasmatic level of Tacrolimus was higher in patients with tremor than in those without, while cholesterol was significantly lower. Cerebellar and neuropathic signs were overall mild and were not significantly different across the three groups comparing patients with and without tremor. CONCLUSIONS: Non-Calcineurin inhibitors such as Sirolimus have the lowest propensity to induce tremor and with a milder severity, while Calcineurin inhibitors, especially Tacrolimus, the highest, and regardless of the formulation. Plasmatic concentration of Tacrolimus was higher in tremulous patients; further research needs to validate the role of cholesterol plasmatic concentration in predicting the occurrence of tremor in patients on Tacrolimus.


Subject(s)
Calcineurin Inhibitors/adverse effects , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Postoperative Complications/physiopathology , Tremor/chemically induced , Adult , Aged , Aged, 80 and over , Blood Cells/pathology , Female , Hematocrit/methods , Hemoglobins/metabolism , Humans , Italy , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Statistics, Nonparametric
14.
Funct Neurol ; 33(4): 200-205, 2018.
Article in English | MEDLINE | ID: mdl-30663966

ABSTRACT

Even after rehabilitation, post stroke patients remain disabled. The Post Stroke Checklist (PSC) was developed to highlight unmet needs of community-dwelling stroke patients. The present study set out to validate Post Soft Care-App, designed to administer the PSC using smartphones and tablets, in order to monitor unmet needs in chronic patients. Fifty-three patients and fifteen physiotherapists were enrolled. The therapists administered the PSC to patients using the app, and then completed a structured questionnaire on its usability and utility. The Post Soft Care-App highlighted the following unmet needs: increased spasticity (56.6%), reduced independence in activities of daily living (47.2%), reduced mobility (45.3%), absence of secondary prevention (45.3%). Therapists positively evaluated Post Soft Care-App as useful, practical, quick to complete (96.2%), and effective in helping improve communication with patients (75.5%). The Post Soft Care-App can be considered a valid assessment tool for helping therapists to monitor functional outcomes in chronic patients.


Subject(s)
Activities of Daily Living , Mobile Applications/standards , Muscle Spasticity , Needs Assessment , Outcome Assessment, Health Care/methods , Physical Therapists , Secondary Prevention , Stroke Rehabilitation , Stroke , Aged , Aged, 80 and over , Chronic Disease , Female , Humans , Male , Middle Aged , Muscle Spasticity/diagnosis , Muscle Spasticity/etiology , Muscle Spasticity/physiopathology , Muscle Spasticity/therapy , Needs Assessment/standards , Outcome Assessment, Health Care/standards , Stroke/complications , Stroke/diagnosis , Stroke/physiopathology , Stroke/therapy
15.
Neurol Sci ; 39(1): 135-139, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29086123

ABSTRACT

The needs of community-dwelling stroke patients are often not fully addressed. The Global Stroke Community Advisory Panel had developed the Post Stroke Checklist (PSC) with the aim of standardizing long-term stroke assessment and consequently care of patients. PSC has been validated for UK and Singapore, and an Italian version has been proposed. The aim of this study is to assess the needs of community-dwelling Italian stroke patients using an online version of PSC. Secondary aim is to assess utility of PSC for patients and clinicians. The PSC was administered to a sample of 64 patients with stroke in Italy by general practioners. PSC is a questionnaire formed by 11 questions, each one covering a domain identified as important for patients' health. After administration of PSC, patient and clinician satisfaction with the PSC was assessed by a specific questionnaire. The PSC identified specific problems for patients related to a worsening from the last examination not evaluated by any specialist. The online PSC highlighted problems related to mood, (in 50% of sample), mobility (53.1%), spasticity (42.2%), and pain (37.5%). Both patients and clinicians provided good results about the utility of online PSC. The PSC was confirmed to be a useful tool for identifying the needs of community-dwelling patients with stroke. Particular attention should be deserved to problems related to mood, mobility, and hence participation to social life, pain, and spasticity. For taking into account these aspects, the online PSC can be a useful portable tool for clinicians.


Subject(s)
Checklist/standards , Primary Health Care/standards , Stroke Rehabilitation/standards , Stroke/diagnosis , Aged , Female , Humans , Italy , Male , Middle Aged , Needs Assessment , Patient Satisfaction
16.
Transplant Proc ; 49(4): 674-676, 2017 May.
Article in English | MEDLINE | ID: mdl-28457369

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) after liver transplantation (LT) is a frequent and serious complication. The incidence of AKI requiring continuous renal replacement therapy (CRRT) ranges from 10% to 30%. Kidney Disease: Improving Global Outcomes guidelines indicate the use of citrate as a locoregional anticoagulant drug for CRRT regardless of the patient's hemorrhagic risk. Despite this indication, however, the use of citrate is still under debate in patients with liver failure and/or LT owing to the potential risk of plasmatic citrate accumulation due to reduced liver clearance. The aim of this study was to evaluate the safety and efficacy of citrate as a locoregional anticoagulation drug in CRRT for AKI after LT. METHODS: A retrospective analysis was performed in patients with AKI after liver transplantation who were treated with CRRT using citrate as local anticoagulant. Five patients were enrolled from January to December 2015. RESULTS: No patients showed complications related to citrate (metabolic acidosis, hyperlactatemia, hypercalcemia, or hypernatremia). All treatments with heparin were stopped owing to circuit clotting. Treatments with citrate was interrupted where it was no longer needed or when other examinations had to be made. None were stopped because of circuit coagulation. CONCLUSIONS: At our center, 5 patients have been successfully treated with the use of CRRT with citrate for AKI during the post-LT course. Our results, though on a small series of patients, provide evidence that CRRT with citrate can be a safe and promising treatment for AKI after LT.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Anticoagulants/therapeutic use , Citric Acid/therapeutic use , Liver Transplantation/adverse effects , Renal Replacement Therapy/methods , Blood Coagulation/drug effects , Female , Humans , Male , Middle Aged , Retrospective Studies
17.
Adv Protein Chem Struct Biol ; 107: 191-222, 2017.
Article in English | MEDLINE | ID: mdl-28215224

ABSTRACT

ZNF224 is a member of the Kruppel-associated box zinc finger proteins (KRAB-ZFPs) family. It was originally identified as a transcriptional repressor involved in gene-specific silencing through the recruitment of the corepressor KAP1, chromatin-modifying activities, and the arginine methyltransferase PRMT5 on the promoter of its target genes. Recent findings indicate that ZNF224 can behave both as a tumor suppressor or an oncogene in different human cancers. The transcriptional regulatory properties of ZNF224 in these systems appear to be complex and influenced by specific sets of interactors. ZNF224 can also act as a transcription cofactor for other DNA-binding proteins. A role for ZNF224 in transcriptional activation has also emerged. Here, we review the state of the literature supporting both roles of ZNF224 in cancer. We also examine the functional activity of ZNF224 as a transcription factor and the influence of protein partners on its dual behavior. Increasing information on the mechanism through which ZNF224 can operate could lead to the identification of agents capable of modulating ZNF224 function, thus potentially paving the way to new therapeutic strategies for treatment of cancer.


Subject(s)
Neoplasms/physiopathology , Repressor Proteins/physiology , Humans , Protein Binding , Repressor Proteins/drug effects , Repressor Proteins/metabolism
18.
Pathologica ; 109(4): 401-404, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29449733

ABSTRACT

Mediastinal tumors are heterogeneous and the diagnosis depends on their location in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and thymoma. The clinical and radiological aspects are often not sufficient to orient the diagnosis and biopsy is necessary to confirmed it. Here, we present a rare case of an anterior mediastinal mass incidentally detected in a 63 years old man during assessment for asthma. The lesion was presumptively diagnosed as a thymic epithelial tumor based on location and radiological characteristics. Surgical biopsy revealed a primary dedifferentiated mediastinal liposarcoma with multiple lung metastases.


Subject(s)
Liposarcoma/diagnostic imaging , Mediastinal Neoplasms/diagnostic imaging , Neoplasms, Glandular and Epithelial/diagnostic imaging , Thymus Neoplasms/diagnostic imaging , Biopsy , Humans , Liposarcoma/pathology , Liposarcoma/surgery , Male , Mediastinal Neoplasms/pathology , Mediastinal Neoplasms/surgery , Mediastinum/pathology , Mediastinum/surgery , Middle Aged , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery , Tomography, X-Ray Computed
19.
J Wound Care ; 25(2): 104, 106-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26878303

ABSTRACT

Chest wall defects are an unusual complication of burn injury, generally seen after high-voltage electrical burns. Here we report the case of a 57-year-old man who developed costal chondritis and osteomyelitis 23 months after flame injury, which covered 50% of the total body surface area. Management included the resection of two ribs and coverage with an omental flap, overlaid by a split-thickness skin graft during the same surgical procedure. Declaration of interest: The authors have no conflict of interest to declare.


Subject(s)
Burns/complications , Cutaneous Fistula/etiology , Cutaneous Fistula/therapy , Osteomyelitis/etiology , Osteomyelitis/therapy , Tietze's Syndrome/etiology , Tietze's Syndrome/therapy , Humans , Male , Middle Aged , Skin Transplantation , Surgical Flaps , Thoracic Wall/injuries , Treatment Outcome , Wound Healing
20.
Diagn Interv Imaging ; 97(3): 347-53, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26542536

ABSTRACT

OBJECTIVE: To identify computed tomography (CT) predictors of malignancy, from a retrospective study of preoperative CT scans of patients with solitary fibrous tumors (SFT) of the pleura. PATIENTS AND METHODS: The CT scans of 56 patients with histopathologically confirmed SFT (33 women and 23 men; mean age, 60years) who underwent surgery between December 2004 and November 2012 were retrospectively analyzed by three radiologists working in consensus, blinded to the final histological diagnosis. RESULTS: SFT was asymptomatic and incidentally discovered in 22 patients (45.8%). Resection specimen analysis (R0 resection in all cases) revealed that 23 tumors (41%) were malignant. The CT features, which significantly differed between malignant and benign SFTs were tumor size (P=0.002) with a discriminative threshold value of 10cm, tumor heterogeneity before (P=0.02) and after (P=0.03) intravenous administration of iodinated contrast material, presence of intratumoral hydric attenuation areas (P=0.01), pleural effusion (P=0.01), measurable intratumoral vessels (P=0.02), hypervascularization with visible intratumoral vessels and/or marked enhancement (P=0.001). Presence of intratumoral calcifications (P=0.2) and maximum post-contrast enhancement value (P=0.6) were not significantly different between the two groups. CONCLUSION: A size greater than or equal to 10cm, hypervascularization, attenuation heterogeneity and association with pleural effusion are individual variables that suggest malignant SFT on CT.


Subject(s)
Solitary Fibrous Tumor, Pleural/diagnostic imaging , Solitary Fibrous Tumor, Pleural/pathology , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pleural Neoplasms/pathology , Predictive Value of Tests , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL