Colorectal cancer(CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall...Colorectal cancer(CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent(25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twentythirty per cent(20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and antiEGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases.展开更多
Colorectal cancer(CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. Howe...Colorectal cancer(CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. However, this dynamic infiltration can be influenced by the microenvironment to promote tumor proliferation, survival and metastasis or cancer inhibition. In particular, the cancer microenvironment metabolites can regulate the inflammatory cells to induce a chronic inflammatory response that can be a predisposing condition for CRC retention. In addition, some nutritional components might contribute to a chronic inflammatory condition by regulating various immune and inflammatory pathways. Besides that, diet strongly modulates the gut microbiota composition,which has a key role in maintaining gut homeostasis and is associated with the modulation of host inflammatory and immune responses. Therefore, diet has a fundamental role in CRC initiation, progression and prevention. In particular,functional foods such as probiotics, prebiotics and symbiotics can have a potentially positive effect on health beyond basic nutrition and have antiinflammatory effects. In this review, we discuss the influence of diet on gut microbiota composition, focusing on its role on gut inflammation and immunity.Finally, we describe the potential benefits of using probiotics and prebiotics to modulate the host inflammatory response, as well as its application in CRC prevention and treatment.展开更多
Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels w...Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis （217 males and 59 females; aged 71.2 ±7.8 years） were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value （5.36 mg/dL）. During a median follow up of 31 months （5 to 49 months）, 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events （HR： 1.867, P = 0.014, 95% CI： 1.134-3.074）, The same patients showed a significant increased risk of cancer-related death （HR： 4.335, P = 0.025, 95% CI： 1.204-15.606）. Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.展开更多
Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outco...Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including： psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.展开更多
AIM: To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol. METHODS: Fifty-two patients (22 males, aver...AIM: To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol. METHODS: Fifty-two patients (22 males, average age 55.6 years, range: 25-82 years), studied using a 1.5 Tesla magnetic resonance scanner, were retrospectively analyzed; detection of FLLs was evaluated by considering the number of lesions observed with the following sequences: (1) respiratory-triggered diffusion-weighted single-shot echo-planar (DW SS-EP) sequences; (2) fat-suppressed fast spin-echo (fs-FSE) T2 weighted sequences; (3) steady-state free precession (SSFP) images; and (4) dynamic triphasic gadolinium-enhanced images, acquired with three-dimensional fast spoiled gradient-echo (3D FSPGR). Two radiologists independently reviewed the images: they were blinded to their respective reports. DW SS-EP sequences were compared to fs-FSE, SSFP and dynamic gadolinium-enhanced acquisitions using a t -test. Pairs were compared for the detection of: (1) all FLLs; (2) benign FLLs; (3) malignant FLLs; (4) metastases; and (5) hepatocellular carcinoma (HCC). RESULTS: Interobserver agreement was very good (weighted = 0.926, CI = 0.880-0.971); on the consensus reading, 277 FLLs were detected. In the comparison with fs-FSE, DW SS-EP sequences had a significantly higher score in the detection of all FLLs, benign FLLs, malignant FLLs and metastases; no statistical difference was observed in the detection of hepatocellular carcinoma (HCCs). In the comparison with SSFP sequences, DW SS-EP had significantly higher scores (P < 0.05) in the detection of all lesions, benign lesions, malignant lesions, metastases and HCC. All FLLs were better detected by dynamic 3D FSGR enhanced acquisition, with P = 0.0023 for reader 1 and P = 0.0086 for reader 2 in the comparison with DW SS-EP sequences; with reference to benign FLLs, DW SS-EP showed lower values than 3D FSPGR enhanced acquisition (P < 0.05). No statistical differences were observed in the detection of malign展开更多
Electrical storm(ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator(ICD) therapies in a 24 h period. Mostly, arrhyth...Electrical storm(ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator(ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia(VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.展开更多
The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropa...The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation-involving the activation and proliferation of resident glial cells(astrocytes, Muller cells and microglia) and the release of a plethora of anti-and pro-inflammatory cytokines, chemokines and reactive oxygen species-has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma.展开更多
AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched heal...AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.展开更多
Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role o...Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.展开更多
Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between ac...Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma(HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.展开更多
Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler(TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency(≤ 2 MHz) tr...Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler(TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency(≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage(caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.展开更多
BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation p...BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages 展开更多
With the growing interest in the applications of gold nanoparticles in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. A large number...With the growing interest in the applications of gold nanoparticles in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. A large number of studies carried out over the past few years under a variety of experimental conditions and following different protocols have produced conflicting results, leading to divergent views about the actual safety of gold nanoparticles in human applications. This work is intended to provide an overview of the most recent experimental results and thereby summarize current state-of-the-art. Rather than presenting a comprehensive review of the available literature in this field, which would be impractically broad, we have selected representative examples of both in vivo and in vitro studies, which clearly demonstrate the need for urgent and rigorous standardization of experimental protocols. Despite their significant potential, the safety of gold nanoparticles is highly controversial at this time, and important concerns have been raised that need to be properly addressed. Factors such as shape, size, surface charge, coating, and surface functionalization are expected to influence the interactions of particles with biological systems to a different extent, resulting in different outcomes and influencing the potential of gold nanoparticles for biomedical applications. Moreover, despite continuous attempts to establish a correlation between structure of the particles and their interactions with biological systems, we are still far from elucidating the toxicological profile of gold nanoparticles in an indisputable manner. This review is intended to contribute towards this goal, offering a number of suggestions on how to achieve the systematization of data on the most relevant physico-chemical parameters, which govern and control the toxicity of ~old nanot^articles at cellular and whole-organism levels.展开更多
In this paper, a novel cable-driven parallel robot, CUBE, is introduced for the assistance of patients in rehabilitation exercising of both upper and lower limbs. The system is characterized by a lightweight structure...In this paper, a novel cable-driven parallel robot, CUBE, is introduced for the assistance of patients in rehabilitation exercising of both upper and lower limbs. The system is characterized by a lightweight structure that is easy to set-up and operate, for both clinical and home usage for both pre-determined and customized exercises, with control over the position of the end-effector while locking its rotation around the horizontal axes. Its cable-driven design makes it inherently safe in human/robot interactions also due to the extremely low inertia. While a novel end-effector design makes the device wearable both on the upper and lower limbs without having to disassemble any part of the structure. The design is presented with its kinematic analysis. Then, the manufacturing through 3D?printing and commercial components of a first prototype is reported. Finally, the system is validated through motion tests along simple trajectories and two different spatial exercises.展开更多
Hempseed meal from three dioecious and three monoecious varieties has been evaluated for content and quality of the protein and for the concentration of antinutritional compounds. Hemp seeds were obtained from plants ...Hempseed meal from three dioecious and three monoecious varieties has been evaluated for content and quality of the protein and for the concentration of antinutritional compounds. Hemp seeds were obtained from plants grown in two experimental fields for two consecutive years (2011-2012). For all the varieties, hempseed meal resulted in a rich source of protein (34% mean content) with an amino acid profile extremely rich in arginine and slightly poor in lysine. Differences between dioecious and monoecious varieties were observed in the content of antinutritional compounds. They were more concentrated in monoecious varieties in comparison with those dioecious. The concentration of phytic acid in hempseed meal deserves attention in both groups, being 63 and 75.4 g·kg-1 of dry matter in dioecious and monocieous varieties, respectively. The results show that, besides the recognized value of hemp oil, also the hempseed cake could find application in animal feed as a substitute of other cakes (soybean, rapeseed). From this point of view, the dioecious varieties showing lower contents of antinutritional compounds with respect to the monoecious varieties would be preferred.展开更多
Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis vir...Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are sym...Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.展开更多
文摘Colorectal cancer(CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent(25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twentythirty per cent(20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and antiEGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases.
基金Supported by "The Programma Attuativo Regionale(Toscana)"funded by FAS(now FSC)-MICpROBIMM,the Italian Ministry of University and Research(MIUR)the Foundation ‘Ente Cassa di Risparmio di Firenze’
文摘Colorectal cancer(CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. However, this dynamic infiltration can be influenced by the microenvironment to promote tumor proliferation, survival and metastasis or cancer inhibition. In particular, the cancer microenvironment metabolites can regulate the inflammatory cells to induce a chronic inflammatory response that can be a predisposing condition for CRC retention. In addition, some nutritional components might contribute to a chronic inflammatory condition by regulating various immune and inflammatory pathways. Besides that, diet strongly modulates the gut microbiota composition,which has a key role in maintaining gut homeostasis and is associated with the modulation of host inflammatory and immune responses. Therefore, diet has a fundamental role in CRC initiation, progression and prevention. In particular,functional foods such as probiotics, prebiotics and symbiotics can have a potentially positive effect on health beyond basic nutrition and have antiinflammatory effects. In this review, we discuss the influence of diet on gut microbiota composition, focusing on its role on gut inflammation and immunity.Finally, we describe the potential benefits of using probiotics and prebiotics to modulate the host inflammatory response, as well as its application in CRC prevention and treatment.
文摘Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis （217 males and 59 females; aged 71.2 ±7.8 years） were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value （5.36 mg/dL）. During a median follow up of 31 months （5 to 49 months）, 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events （HR： 1.867, P = 0.014, 95% CI： 1.134-3.074）, The same patients showed a significant increased risk of cancer-related death （HR： 4.335, P = 0.025, 95% CI： 1.204-15.606）. Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.
文摘Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including： psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.
文摘AIM: To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol. METHODS: Fifty-two patients (22 males, average age 55.6 years, range: 25-82 years), studied using a 1.5 Tesla magnetic resonance scanner, were retrospectively analyzed; detection of FLLs was evaluated by considering the number of lesions observed with the following sequences: (1) respiratory-triggered diffusion-weighted single-shot echo-planar (DW SS-EP) sequences; (2) fat-suppressed fast spin-echo (fs-FSE) T2 weighted sequences; (3) steady-state free precession (SSFP) images; and (4) dynamic triphasic gadolinium-enhanced images, acquired with three-dimensional fast spoiled gradient-echo (3D FSPGR). Two radiologists independently reviewed the images: they were blinded to their respective reports. DW SS-EP sequences were compared to fs-FSE, SSFP and dynamic gadolinium-enhanced acquisitions using a t -test. Pairs were compared for the detection of: (1) all FLLs; (2) benign FLLs; (3) malignant FLLs; (4) metastases; and (5) hepatocellular carcinoma (HCC). RESULTS: Interobserver agreement was very good (weighted = 0.926, CI = 0.880-0.971); on the consensus reading, 277 FLLs were detected. In the comparison with fs-FSE, DW SS-EP sequences had a significantly higher score in the detection of all FLLs, benign FLLs, malignant FLLs and metastases; no statistical difference was observed in the detection of hepatocellular carcinoma (HCCs). In the comparison with SSFP sequences, DW SS-EP had significantly higher scores (P < 0.05) in the detection of all lesions, benign lesions, malignant lesions, metastases and HCC. All FLLs were better detected by dynamic 3D FSGR enhanced acquisition, with P = 0.0023 for reader 1 and P = 0.0086 for reader 2 in the comparison with DW SS-EP sequences; with reference to benign FLLs, DW SS-EP showed lower values than 3D FSPGR enhanced acquisition (P < 0.05). No statistical differences were observed in the detection of malign
文摘Electrical storm(ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator(ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia(VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.
文摘The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation-involving the activation and proliferation of resident glial cells(astrocytes, Muller cells and microglia) and the release of a plethora of anti-and pro-inflammatory cytokines, chemokines and reactive oxygen species-has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma.
文摘AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.
基金Supported by The Italian Ministry for Education,University and Research to Paolo Calabrò,NO.FIRB RBFR12W5V5
文摘Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.
文摘Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma(HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.
文摘Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler(TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency(≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage(caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.
基金Supported by Italian Society for Celiac Disease and Foundation for Celicac Disease,No.007_FC_2016Regione Toscana(The Programma Attuativo Regionale Toscana funded by FAS),No.MICp ROBIMM
文摘BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages
文摘With the growing interest in the applications of gold nanoparticles in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. A large number of studies carried out over the past few years under a variety of experimental conditions and following different protocols have produced conflicting results, leading to divergent views about the actual safety of gold nanoparticles in human applications. This work is intended to provide an overview of the most recent experimental results and thereby summarize current state-of-the-art. Rather than presenting a comprehensive review of the available literature in this field, which would be impractically broad, we have selected representative examples of both in vivo and in vitro studies, which clearly demonstrate the need for urgent and rigorous standardization of experimental protocols. Despite their significant potential, the safety of gold nanoparticles is highly controversial at this time, and important concerns have been raised that need to be properly addressed. Factors such as shape, size, surface charge, coating, and surface functionalization are expected to influence the interactions of particles with biological systems to a different extent, resulting in different outcomes and influencing the potential of gold nanoparticles for biomedical applications. Moreover, despite continuous attempts to establish a correlation between structure of the particles and their interactions with biological systems, we are still far from elucidating the toxicological profile of gold nanoparticles in an indisputable manner. This review is intended to contribute towards this goal, offering a number of suggestions on how to achieve the systematization of data on the most relevant physico-chemical parameters, which govern and control the toxicity of ~old nanot^articles at cellular and whole-organism levels.
文摘In this paper, a novel cable-driven parallel robot, CUBE, is introduced for the assistance of patients in rehabilitation exercising of both upper and lower limbs. The system is characterized by a lightweight structure that is easy to set-up and operate, for both clinical and home usage for both pre-determined and customized exercises, with control over the position of the end-effector while locking its rotation around the horizontal axes. Its cable-driven design makes it inherently safe in human/robot interactions also due to the extremely low inertia. While a novel end-effector design makes the device wearable both on the upper and lower limbs without having to disassemble any part of the structure. The design is presented with its kinematic analysis. Then, the manufacturing through 3D?printing and commercial components of a first prototype is reported. Finally, the system is validated through motion tests along simple trajectories and two different spatial exercises.
文摘Hempseed meal from three dioecious and three monoecious varieties has been evaluated for content and quality of the protein and for the concentration of antinutritional compounds. Hemp seeds were obtained from plants grown in two experimental fields for two consecutive years (2011-2012). For all the varieties, hempseed meal resulted in a rich source of protein (34% mean content) with an amino acid profile extremely rich in arginine and slightly poor in lysine. Differences between dioecious and monoecious varieties were observed in the content of antinutritional compounds. They were more concentrated in monoecious varieties in comparison with those dioecious. The concentration of phytic acid in hempseed meal deserves attention in both groups, being 63 and 75.4 g·kg-1 of dry matter in dioecious and monocieous varieties, respectively. The results show that, besides the recognized value of hemp oil, also the hempseed cake could find application in animal feed as a substitute of other cakes (soybean, rapeseed). From this point of view, the dioecious varieties showing lower contents of antinutritional compounds with respect to the monoecious varieties would be preferred.
文摘Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
文摘Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.
