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1.
Clin Ter ; 173(2): 121-127, 2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35385034

ABSTRACT

Background: The use of anthracyclines in metastatic breast cancer (MBC) is limited by cumulative dose-dependent cardiotoxicity mostly in elderly women with comorbidities. The aim of this observational retrospective study was to evaluate the efficacy of non-pegylated liposomal doxorubicin (Myocet®) and cyclophosphamide in elderly women as HER2 negative first-line MBC treatment. Methods: 84 elderly women >70 years of age (median age 78 years) with MBC HER2 negative were enrolled. Performance Status in 58 patients was ECOG-0 and in 26 patients was ECOG-1. Results: The drug was well tolerated, with overall response rates were >40%, median overall survival was 16.2 months (95%CI:14.6-18.8) and median progression free survival was 5.8 months (95%CI:4.4-8.6). Hematologic toxicity with neutropenia was the most frequent adverse event, but the treatment was well tolerated maintained a manageable cardiotoxicity. Conclusion: Non-pegylated liposomal doxorubicin may represent a valid therapeutic option in first-line for elderly patients with HER/2 negative MBC improving survival, anti-tumor response rate and de-creases cardiotoxicity.


Subject(s)
Breast Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cardiotoxicity/drug therapy , Cardiotoxicity/etiology , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , Humans , Polyethylene Glycols/adverse effects , Retrospective Studies , Treatment Outcome
2.
Peptides ; 150: 170729, 2022 04.
Article in English | MEDLINE | ID: mdl-34958850

ABSTRACT

Substance P (SP), a product of the tachykinin 1 (Tac1) gene, is expressed in many hypothalamic neurons. Its wake-promoting potential could be mediated through histaminergic (HA) neurons of the tuberomamillary nucleus (TMN), where functional expression of neurokinin receptors (NKRs) waits to be characterized. As in the process of nociception in the peripheral nervous system (PNS) capsaicin-receptor (transient potential vanilloid 1: TRPV1) signalling is amplified by local release of histamine and SP, we tested the involvement of tachykinins in the capsaicin-induced long-lasting enhancement (LLEcaps) of HA neurons firing by investigating selective neurokinin receptor ligands in the hypothalamic mouse brain slice preparation using patch-clamp recordings in cell-attached mode combined with single-cell RT-PCR. We report that the majority of HA neurons respond to SP (EC50 3 nM), express the SP precursor tachykinin 1 (Tac1) gene and at least one of the neurokinin receptors. Responses to selective agonists of three known neurokinin receptors were sensitive to corresponding antagonists. LLEcaps was significantly impaired by the neurokinin receptor antagonists, indicating that in hypothalamus, as in the PNS, release of tachykinins downstream to TRPV1 activation is able to boost the release of histamine. The excitatory action of SP on histaminergic neurons adds another pathway to the noradrenergic and orexinergic ones to synergistically enhance cortical arousal. We show NK1R to play a prominent role on HA neurons and thus the control of wakefulness.


Subject(s)
Capsaicin , Histamine , Animals , Capsaicin/metabolism , Capsaicin/pharmacology , Mice , Neurons/metabolism , Receptors, Neurokinin-1/genetics , Receptors, Neurokinin-1/metabolism , Receptors, Neurokinin-2/metabolism , Receptors, Tachykinin/genetics , Receptors, Tachykinin/metabolism , Substance P/metabolism , Tachykinins/metabolism
3.
J Healthc Eng ; 2021: 5579232, 2021.
Article in English | MEDLINE | ID: mdl-34840699

ABSTRACT

Elastography is a noninvasive imaging technique that provides information on soft tissue stiffness. Young's modulus is typically used to characterize soft tissues' response to the applied force, as soft tissues are often considered linear elastic, isotropic, and quasi-incompressible materials. This approximation is reasonable for small strains, but soft tissues undergo large deformations also for small values of force and exhibit nonlinear elastic behavior. Outside the linear regime, the elastic modulus is dependent on the strain level and is different for any kind of tissue. The aim of this study was to characterize, ex vivo, the mechanical response of two different mice muscles to an external force. A system for transverse force-controlled uniaxial compression enabled obtaining the stress-strain (σ-ε) curve of the samples. The strain-dependent Young's modulus (SYM) model was adopted to reproduce muscle compression behavior and to predict the elastic modulus for large deformations. After that, a recursive linear model was employed to identify the initial linear region of the σ-ε curve. Results showed that both muscle types exhibited a strain hardening effect and that the SYM model provided good fitting of the entire σ-ε curves. The application of the recursive linear model allowed capturing the initial linear region in which the approximation of these tissues as linear elastic materials is reasonable. The residual analysis displayed that even if the SYM model better summarizes the muscle behavior on the entire region, the linear model is more precise when considering only the initial part of the σ-ε curve.


Subject(s)
Elasticity Imaging Techniques , Animals , Elastic Modulus , Elasticity , Mechanical Phenomena , Mice , Muscles
4.
Eur Rev Med Pharmacol Sci ; 25(16): 5310-5317, 2021 08.
Article in English | MEDLINE | ID: mdl-34486707

ABSTRACT

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.


Subject(s)
Antiemetics/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Colorectal Neoplasms/drug therapy , Palonosetron/therapeutic use , Pyridines/therapeutic use , Aged , Antiemetics/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , COVID-19 , Female , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Humans , Irinotecan/administration & dosage , Irinotecan/therapeutic use , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Male , Middle Aged , Nausea/prevention & control , Oxaliplatin/administration & dosage , Oxaliplatin/therapeutic use , Palonosetron/administration & dosage , Pandemics , Prospective Studies , Pyridines/administration & dosage , Vomiting/prevention & control
5.
Eur Rev Med Pharmacol Sci ; 24(24): 12727-12734, 2020 12.
Article in English | MEDLINE | ID: mdl-33378020

ABSTRACT

OBJECTIVE: Eribulin mesylate (Halaven®) is a non-taxane inhibitor of microtubule indicated as monotherapy in patients with metastatic breast cancer (MBC), which progresses after anthracycline and taxanes therapy. In this retrospective observational study, we want to evaluate the efficacy of Eribulin in elderly women with MBC pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: 40 elderly patients > 70 years of age were enrolled, and the median age was 76 years (range 70-82). Overall survival (OS), Progression Free Survival (PFS), Objective Response Rate (ORR) were primary endpoints, tolerability, carcinoembryonic antigen levels 15.3 (Ca 15.3), before and after treatment, and Quality of Life (QoL) were secondary endpoints. RESULTS: Eribulin treatment was well tolerated, produced a good level of disease control, a manageable toxicity profile and a significant impact on QoL. Median OS was 12.8 months and median PFS was 3.2 months. A significant correlation was observed between reduction of Ca 15.3 and PFS with a value of 0.59 (p = 0.002). CONCLUSIONS: Despite a limited number of patients and a modest manageable toxicity, Eribulin is a chemotherapy treatment that has showed to be an effective and well-tolerated therapeutic option in elderly patients with MBC. Further analysis should focus on the elderly patients in our setting of study.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Furans/therapeutic use , Ketones/therapeutic use , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Drug Tolerance , Female , Humans , Quality of Life
6.
Eur Phys J Plus ; 135(10): 861, 2020.
Article in English | MEDLINE | ID: mdl-33134007

ABSTRACT

The simplest delay differential equation describing the dynamics of non-lethal infectious diseases in a fixed-size population is extended to include the incubation period, as an additional delay parameter. It is observed that these types of deterministic models consist of one delay differential equation, whereas standard SIR and SEIR models consist of two and three ordinary differential equations, respectively. The extended model presents interesting peculiarities as, for example, initial oscillatory patterns in the curve counting the infectious individuals. A comparison of the doubly delayed differential equation with the standard SEIR model is made. It is argued that self-sustained oscillations, which are intrinsic properties of models with time delay, have to be taken into account in designing optimal epidemic containment strategies.

7.
J Healthc Eng ; 2020: 8851964, 2020.
Article in English | MEDLINE | ID: mdl-32832048

ABSTRACT

Currently, surgeons in operating rooms are forced to focus their attention both on the patient's body and on flat low-quality surgical monitors, in order to get all the information needed to successfully complete surgeries. The way the data are displayed leads to disturbances of the surgeon's visuals, which may affect his performances, besides the fact that other members of the surgical team do not have proper visual tools able to aid him. The idea underlying this paper is to exploit mixed reality to support surgeons during surgical procedures. In particular, the proposed experimental setup, employed in the operating room, is based on an architecture that put together the Microsoft HoloLens, a Digital Imaging and Communications in Medicine (DICOM) player and a mixed reality visualization tool (i.e., Spectator View) developed by using the Mixed Reality Toolkit in Unity with Windows 10 SDK. The suggested approach enables visual information on the patient's body as well as information on the results of medical screenings to be visualized on the surgeon's headsets. Additionally, the architecture enables any data and details to be shared by the team members or by external users during surgical operations. The paper analyses in detail advantages and drawbacks that the surgeons have found when they wore the Microsoft HoloLens headset during all the ten open abdomen surgeries conducted at the IRCCS Hospital "Giovanni Paolo II" in the city of Bari (Italy). A survey based on Likert scale demonstrates how the use of the suggested tools can increase the execution speed by allowing multitasking procedures, i.e., by checking medical images at high resolution without leaving the operating table and the patient. On the other hand, the survey also reveals an increase in the physical stress and reduced comfort due to the weight of the Microsoft HoloLens device, along with drawbacks due to the battery autonomy. Additionally, the survey seems to encourage the use of DICOM Viewer and Spectator View both for surgical education and for improving surgery outcomes. Note that the real use of the conceived platform in the operating room represents a remarkable feature of this paper, since most if not all the studies conducted so far in literature exploit mixed reality only in simulated environments and not in real operating rooms. In conclusion, the study clearly highlights that, despite the challenges required in the forthcoming years to improve the current technology, mixed reality represents a promising technique that will soon enter the operating rooms to support surgeons during surgical procedures in many hospitals across the world.


Subject(s)
Abdomen/surgery , Augmented Reality , Imaging, Three-Dimensional/methods , Operating Rooms , Surgery, Computer-Assisted/methods , Electronics , Equipment Design , General Surgery , Humans , Italy , Software , User-Computer Interface
8.
Curr Oncol ; 27(2): e75-e80, 2020 04.
Article in English | MEDLINE | ID: mdl-32489255

ABSTRACT

Background: Nivolumab is an anti-PD-1 antibody that restores the antitumour immune function of T cells, blocking the binding of PD-1 with its ligand PD-L1. PD-1 is expressed on T cells and interacts with PD-L1 on tumour cells. The PD-1-PD-L1 link inhibits T cell activation. In metastatic melanoma, PD-1-PD-L1 binding plays a critical role, and the advent of the immune checkpoint inhibitor nivolumab has delivered new and effective treatment options with proven clinical benefit. In the present study, we evaluated the efficacy of nivolumab in elderly patients with metastatic melanoma. Methods: The study enrolled 55 elderly patients (75 years of age and older) with a diagnosis of metastatic melanoma. Primary endpoints of the study were progression-free survival (pfs) and the objective response rate; secondary endpoints were overall survival, reduction in serum lactate dehydrogenase (ldh) from before to after treatment, and tolerability. Results: Nivolumab was well tolerated and resulted in good disease control, with a manageable toxicity profile and significant clinical benefit. The duration of pfs was 5.1 months (95% confidence interval: 3.5 months to 6.8 months). A significant correlation was observed between reduction in serum ldh and pfs: 0.60 (95% confidence interval: 0.28 to 0.86; p = 0.002). Conclusions: Nivolumab is an immunotherapy treatment that has proved to be an effective and well-tolerated therapeutic option in elderly patients with metastatic melanoma.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Immunotherapy/methods , Melanoma/drug therapy , Nivolumab/therapeutic use , Quality of Life/psychology , Aged , Antineoplastic Agents, Immunological/pharmacology , Female , Humans , Male , Neoplasm Metastasis , Nivolumab/pharmacology
10.
Eur J Surg Oncol ; 46(9): 1683-1688, 2020 09.
Article in English | MEDLINE | ID: mdl-32220542

ABSTRACT

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.


Subject(s)
Anastomotic Leak/epidemiology , Colectomy/methods , Colon, Transverse/surgery , Colonic Neoplasms/surgery , Length of Stay/statistics & numerical data , Surgical Wound Infection/epidemiology , Aged , Aged, 80 and over , Colon, Transverse/pathology , Colonic Neoplasms/pathology , Disease-Free Survival , Female , Humans , Italy/epidemiology , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/epidemiology , Retrospective Studies , Survival Rate , Time Factors
11.
J Assist Reprod Genet ; 36(11): 2297, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31631238

ABSTRACT

The original article unfortunately contained a mistake. The names of the collaborators were captured as authors of the article.

12.
J Assist Reprod Genet ; 36(11): 2287-2295, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31463873

ABSTRACT

PURPOSE: To estimate the contribution of cryopreservation to the cumulative live birth rate (CLBR) after law modification in Italy in the era of vitrification and freeze-all. METHODS: The Italian National Registry performed a cycle-based data collection. Nine Italian IVF clinics were involved incorporating a total of 10,260 fresh cycles performed between January 2015 and April 2016 resulting in 9273 oocyte retrievals and 3266 subsequent warming cycles from the same oocyte retrievals performed up to December 2016. Mean female age was 37 ± 4.3 years. Primary outcome measure was CLBR per oocyte retrieval. Confounding factors were tested in multivariate regression analysis, and the relative impact of cryopreservation to the CLBR in different patient categories was calculated. RESULTS: CLBR per oocyte retrieval was 32.6%, 26.5%, 18.7%, 13.0%, and 5.5% for women younger than 36, aged 36-39, 40-41, and older than 41 years, respectively. The total relative contribution of oocyte/embryo cryopreservation was 40.6% (95% CI 38.41-42.75). An association between maternal age, number of oocytes retrieved, fertilization rate, cryopreservation, and cumulative live birth was shown. When adjusted for confounders, a 2.3-fold increase was observed in the chance of live birth when cryopreservation was performed (OR 2.3; 95% CI 1.99-2.56). In high responder patients (> 15 oocytes retrieved) where freeze-all was applied in 67.6% of cycles to avoid the risk of hyper stimulation syndrome, the relative contribution of vitrification to the CLBR was 80.6%. CONCLUSIONS: Cryopreservation is essential in IVF and should always be available to patients to optimize success rates. Multicentric, cycle-based data analyses are crucial to provide infertile couples, clinicians, and regulatory bodies with accurate information on IVF effectiveness including fresh and cryopreserved cycles.

13.
Funct Neurol ; 34(1): 35-43, 2019.
Article in English | MEDLINE | ID: mdl-31172938

ABSTRACT

This study aimed to evaluate the efficacy of low-tech augmentative and alternative communication (AAC) aids in improving quality of life (QoL) and mood disorders, as well as the psychosocial impact of assistive devices, in 10 patients affected by amyotrophic lateral sclerosis (ALS) in the early stage of the disease, when speech difficulties appear. The AACtraining (AAC-T) study lasted around six months and comprised two phases of three months each: AAC-intervention (AAC-I) followed by AAC-familiarization (AAC-F). All the patients were assessed at the beginning (T0) and at the end (T1) of AAC-I, as well as at the end of AAC-F (T2). During the AAC-I phase, we applied a three-phase AAC intervention model to evaluate intelligibility of language, participation patterns, communication needs and adaptation to the AAC tools. All the patients showed a gradual and significant improvement, especially in acceptance of the AAC aids, mood and QoL. Moreover, a reduction of caregiver burden was noted. Our study has demonstrated the utility of the AAC aids also in the early stages of the disease in patients with ALS presenting with dysarthria. In our opinion, AAC-T may act as a bridge between the initial and later phases of the disease, when patients need to use high-tech aids, including an eye-tracking communication device. In conclusion, in this study we highlighted how early AAC-T in patients with ALS may be a valuable tool to demonstrate how specific strategies and low-technology aids can improve QoL of these patients and their caregivers, also decreasing stress and depression.


Subject(s)
Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/psychology , Caregivers/psychology , Communication Aids for Disabled/psychology , Quality of Life/psychology , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/physiopathology , Caregivers/trends , Communication Aids for Disabled/trends , Female , Humans , Male , Middle Aged , Pilot Projects
14.
Eur Rev Med Pharmacol Sci ; 22(23): 8227-8236, 2018 12.
Article in English | MEDLINE | ID: mdl-30556862

ABSTRACT

OBJECTIVE: To evaluate the prognostic value of 18F-FDG PET/CT in terms of survival in patients with locally advanced rectal cancer (LARC) who had undergone surgery preceded by neoadjuvant chemoradiotherapy (nCRT). Moreover, the existence of correlation between Overall Survival (OS) and Disease Free Survival (DFS) with pathological staging ((y)pTNM and TRG) was evaluated. PATIENTS AND METHODS: A total of 58 patients with biopsy-proven of LARC were included. All patients underwent conventional diagnostic/staging procedures to characterize the rectal lesion. The first whole-body 18F-FDG PET/CT was performed 1 week before the beginning of nCRT (baseline scan). The second 18F-FDG PET/CT was scheduled at 5-6 weeks from nCRT completion (post-nCRT scan). Survival was evaluated in 3 different restaging classification systems, based on focusing only on primary lesion (TRG), loco-regional evaluation (ypTNM) and whole-body 18F-FDG PET/CT evaluation (VRA). RESULTS: Among the 58 patients at the end of the observation, 46/58 patients (79.3%) were alive and 12/58 (20.7%) were dead. This work demonstrated a higher percentage of patients with TRG complete response (39.7%) compared to literature (24.6%), with longer Overall Survival (OS) and Disease Free Survival (DFS) in responders even if without statistically significant differences. CONCLUSIONS: The present study highlights the predictive and prognostic potential role of 18F-FDG PET/CT in assisting physicians on personalized decision in the selective risk-adapted treatment strategy, and to schedule the correct follow-up approach.


Subject(s)
Chemoradiotherapy, Adjuvant , Fluorodeoxyglucose F18/administration & dosage , Neoadjuvant Therapy , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/administration & dosage , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant/adverse effects , Chemoradiotherapy, Adjuvant/mortality , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/mortality , Neoplasm Staging , Predictive Value of Tests , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Time Factors , Whole Body Imaging
15.
Funct Neurol ; 33(4): 213-216, 2018.
Article in English | MEDLINE | ID: mdl-30663968

ABSTRACT

Post-stroke apathy is considered to be one of the clinical consequences of lesions affecting the structures of the prefrontal cortex, basal ganglia, thalamus and limbic system. However, there is no current consensus on the treatment of post-stroke apathy, which mainly depends on the underlying etiology and comorbidities. A 62-year-old man, affected by hemorrhagic stroke in the left thalamus, presented with mood depression, anhedonia, hyporexia and marked apathy. The patient underwent clinical evaluation before and after receiving two different pharmacological therapies: escitalopram and bupropion. Only after treatment with the latter drug did the patient show changes: high motivation and willingness to pursue activities, greater interest in the external environment and social life activities, and an overall reduction of apathy. On the basis of our observations in this case, we hypothesize that the thalamic lesion resulted in disconnection of the fronto-striatal-thalamic circuits, and that loss of the dopaminergic striatal innervation caused the patient's apathetic state. The resolution of the apathetic disorder may be attributable to the action of the dopaminergic drug bupropion on the mesocortical pathway.


Subject(s)
Antidepressive Agents, Second-Generation/pharmacology , Apathy/drug effects , Bupropion/pharmacology , Stroke , Thalamus , Antidepressive Agents, Second-Generation/administration & dosage , Bupropion/administration & dosage , Humans , Male , Middle Aged , Stroke/complications , Stroke/pathology , Stroke/physiopathology , Thalamus/drug effects , Thalamus/pathology , Thalamus/physiopathology
16.
Neuropediatrics ; 49(2): 150-153, 2018 04.
Article in English | MEDLINE | ID: mdl-29284168

ABSTRACT

Neuronal ceroid lipofuscinoses represent a heterogeneous group of early onset neurodegenerative disorders that are characterized by progressive cognitive and motor function decline, visual loss, and epilepsy. The age of onset has been historically used for the phenotypic classification of this group of disorders, but their molecular genetic delineation has now enabled a better characterization, demonstrating significant genetic heterogeneity even among individuals with a similar phenotype. The rare Congenital Neuronal Ceroid Lipofuscinosis (CLN10) caused by mutations in the CTSD gene encoding for cathepsin D is associated with a dramatic presentation with onset before or around birth. We report on a female born to consanguineous parents who presented at birth with severe neonatal encephalopathy with massive cerebral and cerebellar shrinking on magnetic resonance imaging. Whole exome sequencing with targeted bioinformatic analysis of a panel of genes associated with prenatal/perinatal onset of neurodegenerative disease was performed and revealed the presence of a novel homozygous in-frame deletion in CTSD. Additional functional studies further confirmed the pathogenic character of this variant and established the diagnosis of CLN10 in the patient.


Subject(s)
Cathepsin D/genetics , Mutation/genetics , Neuronal Ceroid-Lipofuscinoses/genetics , Brain Stem/diagnostic imaging , Cerebellum/diagnostic imaging , Female , Humans , Infant , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Neuronal Ceroid-Lipofuscinoses/diagnostic imaging
17.
Br J Surg ; 105(3): 159-167, 2018 02.
Article in English | MEDLINE | ID: mdl-29091259

ABSTRACT

BACKGROUND: Several associations between microsatellite instability (MSI) and other clinicopathological factors have been reported in gastric cancer, but the results have been ambiguous. This systematic review and meta-analysis investigated the relationship between MSI and overall survival and clinicopathological characteristics of patients with gastric cancer. METHODS: A systematic literature search of the PubMed, Cochrane and Ovid databases until 31 January 2016 was performed in accordance with the PRISMA statement. The articles were screened independently according to PICO (population, intervention, comparator, outcome) eligibility criteria. All eligible articles were evaluated independently by two reviewers for risk of bias according to the Quality In Prognosis Study tool. RESULTS: Overall, 48 studies with a total of 18 612 patients were included. MSI was found in 9·2 per cent of patients (1718 of 18 612), and was associated with female sex (odds ratio (OR) 1·57, 95 per cent c.i. 1·31 to 1·89; P < 0·001), older age (OR 1·58, 2·20 to 1·13; P < 0·001), intestinal Laurén histological type (OR 2·23, 1·94 to 2·57; P < 0·001), mid/lower gastric location (OR 0·38, 0·32 to 0·44; P < 0·001), lack of lymph node metastases (OR 0·70, 0·57 to 0·86, P < 0·001) and TNM stage I-II (OR 1·77, 1·47 to 2·13; P < 0·001). The pooled hazard ratio for overall survival of patients with MSI versus those with non-MSI gastric cancer from 21 studies was 0·69 (95 per cent c.i. 0·56 to 0·86; P < 0·001). CONCLUSION: MSI in gastric cancer was associated with good overall survival, reflected in several favourable clinicopathological tumour characteristics.


Subject(s)
Microsatellite Instability , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Genetic Markers , Humans , Odds Ratio , Prognosis
18.
Eur J Surg Oncol ; 43(8): 1472-1480, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28571778

ABSTRACT

AIM: To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. METHODS: Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. RESULTS: Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months. Twenty-two relapses were observed, 91.6% at a distant site. The mean time to recurrence was of 35.3 months. On univariate analysis, the use of adjuvant chemotherapy correlated with better OS exclusively in ypT0N + patients and not in ypT0N0. Univariate and multivariate analyses documented nodal positivity as the only prognostic factor correlated with a worse OS. CONCLUSION: Recurrences were mostly diagnosed at a distant site and within the third year of follow-up. Nodal positivity was the only variable independently correlated with a worse OS. Univariate analysis documented a benefit for the use of adjuvant chemotherapy treatment exclusively in ypT0N + rectal cancers.


Subject(s)
Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Italy , Lymphatic Metastasis , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Rectal Neoplasms/pathology , Retrospective Studies , Spain , Survival Analysis , Treatment Outcome
19.
Acta Otorhinolaryngol Ital ; 37(5): 410-415, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28530257

ABSTRACT

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.


Subject(s)
Models, Theoretical , Nasal Obstruction/diagnosis , Nasal Obstruction/surgery , Preoperative Care , Adult , Humans
20.
J Genet Couns ; 26(5): 999-1007, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28283917

ABSTRACT

Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.


Subject(s)
Anxiety/psychology , Breast Neoplasms/psychology , Genetic Counseling/psychology , Genetic Predisposition to Disease/psychology , Ovarian Neoplasms/psychology , Adult , Breast Neoplasms/genetics , Female , Humans , Middle Aged , Mutation , Ovarian Neoplasms/genetics , Perception , Risk Factors , Stress, Psychological/psychology
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