BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease de...BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.展开更多
The genesis of the Benign Paroxysmal Positional Vertigo(BPPV)seems to be related to some metabolic factors.These factors,such as vitamin D,glucocorticoids,and even thyroid and growth hormones,can affect bone metabolis...The genesis of the Benign Paroxysmal Positional Vertigo(BPPV)seems to be related to some metabolic factors.These factors,such as vitamin D,glucocorticoids,and even thyroid and growth hormones,can affect bone metabolism and the mineralization of otoconia.It also seems to link to factors related to aging or nutritional habits.Besides,since the incidence of BPPV is quantitatively higher in women than in men,female sex steroids could be associated with this process.It could be useful to understand how these factors act in otoconial mineralization if we want to develop treatments aimed at preventing or delaying BPPV recurrences.In this review,we will analyze the role of these metabolic and hormonal factors in otoconial mineralization and in the treatment of BPPV.展开更多
BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–b...BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.展开更多
AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation.METHODS: Two-micrometer thick biops...AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation.METHODS: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation,and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent.RESULTS: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%.CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.展开更多
Bloodborne fibrocytes are cells mobilized from the bone marrow, which express surface antigens commonly ascribed to hematopoietic progenitors and have phenotypic and functional characteristics similar to those of imma...Bloodborne fibrocytes are cells mobilized from the bone marrow, which express surface antigens commonly ascribed to hematopoietic progenitors and have phenotypic and functional characteristics similar to those of immature mesenchymal cells. They exhibit predominant proinflammatory or profibrotic activities at tissue sites, depending on the host＇s response to environmental insults and on the characteristics of the cell infiltrate and cytokine milieu. In patients with allergic asthma, fibrocytes egress from the bone marrow and are recruited into the airways after every allergen exposure and during viral infections. Recruited fibrocytes amplify the inflammatory responses driven by T helper type 2 lymphokines and favor viral replication and further inflammation on respiratory virus infections. Persistently elevated blood fibrocyte counts and persisting airway fibrocytosis are present in patients with chronically undertreated or corticosteroid-insensitive asthma, and are linked to an enhanced risk of adverse outcomes because of the major involvement of fibrocytes in the development of structural abnormalities that lead to chronic airflow obstruction in these patients. Consequently, blood fibrocyte count is an emerging biomarker of asthma control and disease progression and its clinical applicability as a new outcome measure deserves further evaluation in large clinical trials.展开更多
BACKGROUND About 10%-30%of acute pancreatitis remain idiopathic(IAP)even after clinical and imaging tests,including abdominal ultrasound(US),contrast-enhanced computed tomography(CECT)and magnetic resonance cholangiop...BACKGROUND About 10%-30%of acute pancreatitis remain idiopathic(IAP)even after clinical and imaging tests,including abdominal ultrasound(US),contrast-enhanced computed tomography(CECT)and magnetic resonance cholangiopancreatography(MRCP).This is a relevant issue,as up to 20%of patients with IAP have recurrent episodes and 26%of them develop chronic pancreatitis.Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques.AIM To evaluate the diagnostic gain after failure of one or more previous crosssectional exams.METHODS We retrospectively collected data about consecutive patients with AP and at least one negative test between US,CECT and MRCP,who underwent linear EUS between January 2017 and December 2020.We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these crosssectional imaging techniques for the etiologic diagnosis of AP.Types and frequency of EUS diagnosis were also analyzed,and EUS diagnosis was compared with the clinical parameters.After EUS,patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence.RESULTS We enrolled 81 patients(63%males,mean age 61±18,23%with previous cholecystectomy,17%with recurrent pancreatitis).Overall EUS diagnostic yield for AP etiological diagnosis was 79%(20%lithiasis,31%acute on chronic pancreatitis,14%pancreatic solid or cystic lesions,5%pancreas divisum,5%autoimmune pancreatitis,5%ductal abnormalities),while 21%remained idiopathic.US,CECT and MRCP,taken alone or in combination,led to AP etiological diagnosis in 16(20%)patients;among the remaining 65 patients,49(75%)obtained a diagnosis at EUS,with an overall EUS diagnostic gain of 61%.Sixty-eight patients had negative US;among them,EUS allowed etiological diagnosis in 59(87%).Sixty-three patients had a negative CECT;among them,47(74%)obtained diagnosis with EUS.Twenty-four had a negative MRCP;among them,20(83%)had EUS diagnosis.Twenty-one had negative CT+MRCP,of which 17(81%)had EUS diagnosis,with a EUS diagnostic gain of 63%.Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase(154 vs 25,P=0.010),aspartate aminotransferase(95 vs 29,P=0.018),direct bilirubin(1.2 vs 0.6,P=0.015),gammaglutamyl transpeptidase(180 vs 48,P=0.006)and alkaline phosphatase(150 vs 72,P=0.015)Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline(82%vs 21%,P<0.001).During the follow-up,AP recurred in 3 patients,one of which remained idiopathic.CONCLUSION EUS is a good test to define AP etiology.It showed a 63%diagnostic gain over CECT+MRCP.In suitable patients,EUS should always be performed in cases of IAP.Further prospective studies are needed.展开更多
AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in ...AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status(Eastern Cooperative Oncology Group) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion(ILI)], and to stop the out flow(venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration(HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug.RESULTS: Thirty seven ILI were done in 29 cases(31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients(38%) received infusion of melphalan alone, 7(24%) melphalan associated to mitomicin C and 7(24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients(10%) were complete responders and 16(56%) were partial responders; whereas 7 patients(24%) had stable disease, and 3(10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade(I and II) toxicity.CONCLUSION: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.展开更多
Intra-abdominal fibromatosis （IAF） is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age....Intra-abdominal fibromatosis （IAF） is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor （GIST）. This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor ST1571 （imatinib mesylate） has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.展开更多
Background Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the ...Background Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the nor- malization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. Methods We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months cal- cifediol supplementation with a starting dose at first post-operative day of 50 ~tg/die in liquid preparation. Down-titration to 20 Ixg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction （LVEF） and global longitudinal strain （GLS） during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. Results Six months of cal- cifediol supplementation were associated with a significant improvement of both LVEF （＋ 3.94%; 95% CI： -4.0789 to -0.8232; P 〈 0.01） and GLS （＋ 18.56%; Z = -5.895; P 〈 0.0001）. Conclusions Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications.展开更多
Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been...Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been described for the general population. In this observational study we describe the effects of sex and age on AL variables, in a cohort of patients with general anxiety disorders and neuroticism treated with alprazolam during 12 weeks, before and after treatment. Methods: Patients with general (DSM IV) anxiety disorders with >6 in Hamilton scale, AL (>1 Crimmins and Seeman AL modified criteria) and neuroticism >18 (NEO-FFI inventory), were included. All patients completed psychiatric assessment, AL index determination before (−1 week) and after 12 weeks of treatment with alprazolam (0.25 - 1 mg/t.i.d). Allostatic load parameters comprised cardiovascular, metabolic and inflammatory variables. Univariate analysis (two-way ANOVA), Student’s t-test (related variables) and Pearson correlations were determined. Results: Fifty-four patients, 35 females (48.6 ± 11.7 years) and 19 males (44.2 ± 12.8 years) with general anxiety disorder were included;28 patients with Conclusions: In this preliminary analysis we described sex and age differences in psychiatry aspects and AL indexes in patients with general anxiety disorders in the short-term treatment with alprazolam. These considerations remark the need of pondering sex and age differences during the use of drugs for protracted periods.展开更多
In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improvin...In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improving clinical outcomes,the choice of the most effective and safest pathway represents a great challenge.A key point of concern is the anesthetic approach and above all the choice of the locoregional anesthesia combined with general or neuraxial anesthesia.展开更多
AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer.METHODS: We designed a single-arm prospective, multicent...AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer.METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out.RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS).CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation.展开更多
Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resectio...Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored.Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves.Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction,and propose an innovative algorithm.展开更多
BACKGROUND Gastric cancer is an aggressive disease with frequent lymph node(LN)involvement.The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs.This threshold has been the subject of great de...BACKGROUND Gastric cancer is an aggressive disease with frequent lymph node(LN)involvement.The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs.This threshold has been the subject of great debate,not only for the extent of surgery but also for more appropriate staging.The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer(AJCC)staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number.Furthermore,studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastriccancer.AIM To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation.METHODS Eligible patients were identified from the Surveillance,Epidemiology,and End Results database.Those with stage II-III gastric cancer were considered for inclusion.Three groups were compared based on the number of analyzed LNs.They were inadequate LN assessment(ILA,<16 LNs),adequate LN assessment(ALA,16-29 LNs),and optimal LN assessment(OLA,≥30 LNs).The main outcomes were overall survival(OS)and cancer-specific survival.Data were analyzed by the Kaplan-Meier product-limit method,log-rank test,hazard risk,and Cox proportional univariate and multivariate models.Propensity score matching(PSM)was used to compare the ALA and OLA groups.RESULTS The analysis included 11607 patients.Most had advanced T stages(T3=48%;T4=42%).The pathological AJCC stage distribution was IIA=22%,IIB=18%,IIIA=26%,IIIB=22%,and IIIC=12%.The overall sample divided by the study objective included ILA(50%),ALA(35%),and OLA(15%).Median OS was 24 mo for the ILA group,29 mo for the ALA group,and 34 mo for the OLA group(P<0.001).Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group[ALA hazard ratio(HR)=0.84,95%confidence interval(CI):0.79-0.88,P<0.001 and OLA HR=0.73,95%CI:0.68-0.79,P<0.001].The OS outcome was confirmed by multivariate analysis(ALA HR=0.68,95%CI:0.64-0.71,P<0.001 and OLA:HR=0.48,95%CI:0.44-0.52,P<0.001).A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group(OS:OLA median=34 mo vs ALA median=26 mo,P<0.001,which was confirmed by univariate analysis(HR=0.81,95%CI:0.75-0.89,P<0.001)and multivariate analysis:(HR=0.71,95%CI:0.65-0.78,P<0.001).CONCLUSION Proper nodal staging is a critical issue in gastric cancer.Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.展开更多
AIM:To study,in intact male transgenic mice,the effects of three diets based on olive oil and olive oil diet supplemented with lovastatin and orlistat on hepatic lipogenic enzymes expression,considered markers of cell...AIM:To study,in intact male transgenic mice,the effects of three diets based on olive oil and olive oil diet supplemented with lovastatin and orlistat on hepatic lipogenic enzymes expression,considered markers of cell proliferation.METHODS:Forty ApcMin/+mice were randomly divided into 4 groups and fed for 10 wk:olive oil(OO)group,n=10 animals received a diet with olive oil 12%;olive oil plus lovastatin(LOVA)group,n=10 animals received the same diet with olive oil supplemented with lovastatin 5 mg/kg;olive oil plus orlistat(OR)group,n=10 animals fed the diet with olive oil supplemented with orlistat 50 mg/kg and SD group,n=10 animals fed a standard diet.The activity of lipogenic enzymes and their gene expression were evaluated by radiomet-ric and real-time reverse transcription-polymerase chain reaction assay,respectively.RESULTS:After 10 wk of dietary treatment,the body weight was no different among animal groups(21.3±3.1 g for standard group,22.1±3.6 g for OO group,22.0±3.2 g for LOVA group and 20.7±3.4 g for OR group,data expressed as mean±SD),observing a generalized well-being in all animals.All the dietary managed treated groups presented significantly reduced hepatic levels of fatty acid synthase,farnesyl pyrophosphate synthase and 3-hydroxyl-3-methyl-glutaryl CoA reductase activity and gene expression when compared with the mice fed the standard diet.To evaluate cell proliferation in the liver of treated mice,the levels of cyclin E mRNA have been measured,demonstrating a significant reduction of cyclin E gene expression in all treated groups.Evidence of reduced hepatic cell proliferation was present overall in OO group mice.CONCLUSION:We confirm the role of lipogenic enzymes as markers of cell proliferation,suggesting that appropriate dietary management alone or with drugs can be a feasible approach to counteract hepatic cell proliferation in mice.展开更多
AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD3...AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome(Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients who underwent an ASCT for an acute leukemia(n = 20) in the sameperiod were excluded from this analysis. CMV DNA load in the blood has been determined by polymerasechain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.RESULTS: Overall, 36 patients(11%) required a specific antiviral treatment for a symptomatic CMV reactivation(n = 32) or an end-organ disease(n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma(16%) and myeloma patients(8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in Ig G seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplantrelated mortality was significantly higher in patients who experienced a CMV reactivation(8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pretransplant HBc Ig G seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy(P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pretransplant HBc Ig G seropositivity(OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell nonHodgkin's lymphoma(OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBc Ig G seropositivity and a diagnosis of T-cell non-Hodgkin's lymphoma should be considered as independent predictor factors of CMV reactivation.展开更多
BACKGROUND Guidelines recommend to cease inflammatory bowel disease(IBD)biologic therapy during coronavirus disease 2019(COVID-19).AIM To investigate severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibody...BACKGROUND Guidelines recommend to cease inflammatory bowel disease(IBD)biologic therapy during coronavirus disease 2019(COVID-19).AIM To investigate severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibody positivity in an IBD cohort,COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables.METHODS Prospective observational cohort study.IBD patients were tested for SARS-CoV-2 IgG.Data on COVID-19 disease,demographics/therapeutics and clinical features of the IBD population were collected.IgG≥7 was set for SARS-CoV-2 antibody positivity.Throat swab was performed in cases of IgG positivity.Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed.RESULTS In total,103 IBD patients were enrolled.Among them,18.4%had IgG≥7.Multivariate analysis of antibody positivity correlated only with IBD treatment.For IgG≥7,the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine,respectively,vs biologic drugs(P=0.0157 between them).COVID-19 related symptoms were reported in 63%of patients with IgG positivity.All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBDtreatment and body mass index correlated with COVID-19 disease development with symptoms.CONCLUSIONThe IBD population does not have a higher risk of severe COVID-19. The relative risk of havingSARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologictherapy and lastly mesalazine. None of the patients under biologic therapy developed severeCOVID-19.展开更多
Purpose: Anxiety disorders are frequently associated with chronic stress with possible cognitive consequences. The aim of this study was to determine the verbal fluency performance in a cohort of patients with anxiety...Purpose: Anxiety disorders are frequently associated with chronic stress with possible cognitive consequences. The aim of this study was to determine the verbal fluency performance in a cohort of patients with anxiety disorders and allostatic load, treated with alprazolam during 12 weeks. Methods: Patients with GAD (general anxiety disorders, DSM IV), with >6 in Hamilton Anxiety Rating Scale (HAM-A), neuroticism > 18 (NEO-FFI inventory), and normal Mini-Mental State Examination were included. Clinical and Psychiatric examination, Allostatic Load Index and cognitive assessment were analyzed before and after 12 weeks of treatment. The phonemic and semantic verbal fluency tests were determined in all patients. The scoring for each fluency task was determined by counting the number of correct words. The total score from each semantic and phonemic verbal task was analyzed comparing the individual score with normal data controlled by age and sex. Patients with scores > ?2 standard deviation (SD) from normative data were considered impaired. Results: Fifty-four patients completed the semantic verbal fluency test before treatment and fifty patients completed after treatment. According to the z-scores before treatment 7 patients of 54 (12.9%) had verbal fluency impairments. After treatment none patients showed semantic verbal fluency deficits but 3 patients of 50 (6%) showed phonemic impairments. Impaired group was significantly associated with an older age before treatment (p = 0.033) and with a similar tendency but not significant (p = 0.09) after treatment (Student t test). Conclusion: In this study older age factor was associated with verbal fluency impairment in GAD patients. Stratified treatments analyzing age and sex factors, including allostatic load measurements and cognitive assessments may be useful tools to determine the effectiveness and the safety of psychopharmacological treatments.展开更多
BACKGROUND Human immunodeficiency virus(HIV)is a major public health concern,particularly in Africa where HIV rates remain substantial.Pregnant women are at an increased risk of acquiring HIV,which has a significant i...BACKGROUND Human immunodeficiency virus(HIV)is a major public health concern,particularly in Africa where HIV rates remain substantial.Pregnant women are at an increased risk of acquiring HIV,which has a significant impact on both maternal and child health.AIM To review summarizes HIV seroprevalence among pregnant women in Africa.It also identifies regional and clinical characteristics that contribute to study-specific estimates variation.METHODS The study included pregnant women from any African country or region,irrespective of their symptoms,and any study design conducted in any setting.Using electronic literature searches,articles published until February 2023 were reviewed.The quality of the included studies was evaluated.The DerSimonian and Laird random-effects model was applied to determine HIV pooled seroprevalence among pregnant women in Africa.Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity.Heterogeneity was assessed with Cochran's Q test and I2 statistics,and publication bias was assessed with Egger's test.RESULTS A total of 248 studies conducted between 1984 and 2020 were included in the quantitative synthesis(meta-analysis).Out of the total studies,146(58.9%)had a low risk of bias and 102(41.1%)had a moderate risk of bias.No HIV-positive pregnant women died in the included studies.The overall HIV seroprevalence in pregnant women was estimated to be 9.3%[95%confidence interval(CI):8.3-10.3].The subgroup analysis showed statistically significant heterogeneity across subgroups(P<0.001),with the highest seroprevalence observed in Southern Africa(29.4%,95%CI:26.5-32.4)and the lowest seroprevalence observed in Northern Africa(0.7%,95%CI:0.3-1.3).CONCLUSION The review found that HIV seroprevalence among pregnant women in African countries remains significant,particularly in Southern African countries.This review can inform the development of targeted public health interventions to address high HIV seroprevalence in pregnant women in African countries.展开更多
Drug resistance is one of the main challenges in cancer therapy,including in the treatment of female-specific malignancies,which account for more than 60%of cancer cases among women.Therefore,elucidating the underlyin...Drug resistance is one of the main challenges in cancer therapy,including in the treatment of female-specific malignancies,which account for more than 60%of cancer cases among women.Therefore,elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches.Notably,Notch signaling,including either receptors or ligands,has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer.Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts,several studies focused on the Notch-dependent regulation of the cancer stem cell(CSC)subpopulation or the induction of the epithelial-to-mesenchymal transition(EMT),both features implicated in either intrinsic or acquired resistance.Indeed,the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSC-driven drug resistance.Moreover,other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment.Collectively,there is a long way to go before every facet will be fully understood;nevertheless,some small pieces are falling neatly into place.Overall,the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.展开更多
文摘BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.
文摘The genesis of the Benign Paroxysmal Positional Vertigo(BPPV)seems to be related to some metabolic factors.These factors,such as vitamin D,glucocorticoids,and even thyroid and growth hormones,can affect bone metabolism and the mineralization of otoconia.It also seems to link to factors related to aging or nutritional habits.Besides,since the incidence of BPPV is quantitatively higher in women than in men,female sex steroids could be associated with this process.It could be useful to understand how these factors act in otoconial mineralization if we want to develop treatments aimed at preventing or delaying BPPV recurrences.In this review,we will analyze the role of these metabolic and hormonal factors in otoconial mineralization and in the treatment of BPPV.
基金the Nazarbayev University Faculty Development Competitive Research Grant 2020-2022,No.240919FD3912.
文摘BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.
基金Supported by the "Michele Rodriguez" Foundation, Institute for Quantitative Measures in Medicine, Milan, Italy
文摘AIM: To introduce a computer-aided morphometric method for quantifying the necro-inflammatory phase in liver biopsy specimens using fractal geometry and Delaunay's triangulation.METHODS: Two-micrometer thick biopsy sections taken from 78 chronic hepatitis C virus-infected patients were immunohistochemically treated to identify the inflammatory cells. An automatic computer-aided image analysis system was used to define the inflammatory cell network defined on the basis of Delaunay's triangulation,and the inflammatory cells were geometrically classified as forming a cluster (an aggregation of a minimum of three cells) or as being irregularly distributed within the tissue. The phase of inflammatory activity was estimated using Hurst's exponent.RESULTS: The proposed automatic method was rapid and objective. It could not only provide rigorous results expressed by scalar numbers, but also allow the state of the whole organ to be represented by Hurst's exponent with an error of no more than 12%.CONCLUSION: The availability of rigorous metrical measures and the reasonable representativeness of the status of the organ as a whole raise the question as to whether the indication for hepatic biopsy should be revised by establishing clear rules concerning the contraindications suggested by its invasiveness and subjective interpretation.
文摘Bloodborne fibrocytes are cells mobilized from the bone marrow, which express surface antigens commonly ascribed to hematopoietic progenitors and have phenotypic and functional characteristics similar to those of immature mesenchymal cells. They exhibit predominant proinflammatory or profibrotic activities at tissue sites, depending on the host＇s response to environmental insults and on the characteristics of the cell infiltrate and cytokine milieu. In patients with allergic asthma, fibrocytes egress from the bone marrow and are recruited into the airways after every allergen exposure and during viral infections. Recruited fibrocytes amplify the inflammatory responses driven by T helper type 2 lymphokines and favor viral replication and further inflammation on respiratory virus infections. Persistently elevated blood fibrocyte counts and persisting airway fibrocytosis are present in patients with chronically undertreated or corticosteroid-insensitive asthma, and are linked to an enhanced risk of adverse outcomes because of the major involvement of fibrocytes in the development of structural abnormalities that lead to chronic airflow obstruction in these patients. Consequently, blood fibrocyte count is an emerging biomarker of asthma control and disease progression and its clinical applicability as a new outcome measure deserves further evaluation in large clinical trials.
文摘BACKGROUND About 10%-30%of acute pancreatitis remain idiopathic(IAP)even after clinical and imaging tests,including abdominal ultrasound(US),contrast-enhanced computed tomography(CECT)and magnetic resonance cholangiopancreatography(MRCP).This is a relevant issue,as up to 20%of patients with IAP have recurrent episodes and 26%of them develop chronic pancreatitis.Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques.AIM To evaluate the diagnostic gain after failure of one or more previous crosssectional exams.METHODS We retrospectively collected data about consecutive patients with AP and at least one negative test between US,CECT and MRCP,who underwent linear EUS between January 2017 and December 2020.We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these crosssectional imaging techniques for the etiologic diagnosis of AP.Types and frequency of EUS diagnosis were also analyzed,and EUS diagnosis was compared with the clinical parameters.After EUS,patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence.RESULTS We enrolled 81 patients(63%males,mean age 61±18,23%with previous cholecystectomy,17%with recurrent pancreatitis).Overall EUS diagnostic yield for AP etiological diagnosis was 79%(20%lithiasis,31%acute on chronic pancreatitis,14%pancreatic solid or cystic lesions,5%pancreas divisum,5%autoimmune pancreatitis,5%ductal abnormalities),while 21%remained idiopathic.US,CECT and MRCP,taken alone or in combination,led to AP etiological diagnosis in 16(20%)patients;among the remaining 65 patients,49(75%)obtained a diagnosis at EUS,with an overall EUS diagnostic gain of 61%.Sixty-eight patients had negative US;among them,EUS allowed etiological diagnosis in 59(87%).Sixty-three patients had a negative CECT;among them,47(74%)obtained diagnosis with EUS.Twenty-four had a negative MRCP;among them,20(83%)had EUS diagnosis.Twenty-one had negative CT+MRCP,of which 17(81%)had EUS diagnosis,with a EUS diagnostic gain of 63%.Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase(154 vs 25,P=0.010),aspartate aminotransferase(95 vs 29,P=0.018),direct bilirubin(1.2 vs 0.6,P=0.015),gammaglutamyl transpeptidase(180 vs 48,P=0.006)and alkaline phosphatase(150 vs 72,P=0.015)Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline(82%vs 21%,P<0.001).During the follow-up,AP recurred in 3 patients,one of which remained idiopathic.CONCLUSION EUS is a good test to define AP etiology.It showed a 63%diagnostic gain over CECT+MRCP.In suitable patients,EUS should always be performed in cases of IAP.Further prospective studies are needed.
文摘AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status(Eastern Cooperative Oncology Group) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion(ILI)], and to stop the out flow(venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration(HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug.RESULTS: Thirty seven ILI were done in 29 cases(31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients(38%) received infusion of melphalan alone, 7(24%) melphalan associated to mitomicin C and 7(24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients(10%) were complete responders and 16(56%) were partial responders; whereas 7 patients(24%) had stable disease, and 3(10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade(I and II) toxicity.CONCLUSION: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.
文摘Intra-abdominal fibromatosis （IAF） is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor （GIST）. This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor ST1571 （imatinib mesylate） has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.
文摘Background Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the nor- malization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. Methods We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months cal- cifediol supplementation with a starting dose at first post-operative day of 50 ~tg/die in liquid preparation. Down-titration to 20 Ixg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction （LVEF） and global longitudinal strain （GLS） during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. Results Six months of cal- cifediol supplementation were associated with a significant improvement of both LVEF （＋ 3.94%; 95% CI： -4.0789 to -0.8232; P 〈 0.01） and GLS （＋ 18.56%; Z = -5.895; P 〈 0.0001）. Conclusions Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications.
文摘Introduction: Allostatic load (AL) index proposes indicators for the functioning of the main potentially stress-affected systems. Sex differences in stress response and stress-related diseases susceptibility have been described for the general population. In this observational study we describe the effects of sex and age on AL variables, in a cohort of patients with general anxiety disorders and neuroticism treated with alprazolam during 12 weeks, before and after treatment. Methods: Patients with general (DSM IV) anxiety disorders with >6 in Hamilton scale, AL (>1 Crimmins and Seeman AL modified criteria) and neuroticism >18 (NEO-FFI inventory), were included. All patients completed psychiatric assessment, AL index determination before (−1 week) and after 12 weeks of treatment with alprazolam (0.25 - 1 mg/t.i.d). Allostatic load parameters comprised cardiovascular, metabolic and inflammatory variables. Univariate analysis (two-way ANOVA), Student’s t-test (related variables) and Pearson correlations were determined. Results: Fifty-four patients, 35 females (48.6 ± 11.7 years) and 19 males (44.2 ± 12.8 years) with general anxiety disorder were included;28 patients with Conclusions: In this preliminary analysis we described sex and age differences in psychiatry aspects and AL indexes in patients with general anxiety disorders in the short-term treatment with alprazolam. These considerations remark the need of pondering sex and age differences during the use of drugs for protracted periods.
文摘In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improving clinical outcomes,the choice of the most effective and safest pathway represents a great challenge.A key point of concern is the anesthetic approach and above all the choice of the locoregional anesthesia combined with general or neuraxial anesthesia.
基金Supported by A Grant of the National Ministry of Health and the Italian Association for Cancer Research (AIRC)An AIRC fellowship to Vaccaro V
文摘AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer.METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out.RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS).CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation.
文摘Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored.Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves.Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction,and propose an innovative algorithm.
文摘BACKGROUND Gastric cancer is an aggressive disease with frequent lymph node(LN)involvement.The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs.This threshold has been the subject of great debate,not only for the extent of surgery but also for more appropriate staging.The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer(AJCC)staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number.Furthermore,studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastriccancer.AIM To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation.METHODS Eligible patients were identified from the Surveillance,Epidemiology,and End Results database.Those with stage II-III gastric cancer were considered for inclusion.Three groups were compared based on the number of analyzed LNs.They were inadequate LN assessment(ILA,<16 LNs),adequate LN assessment(ALA,16-29 LNs),and optimal LN assessment(OLA,≥30 LNs).The main outcomes were overall survival(OS)and cancer-specific survival.Data were analyzed by the Kaplan-Meier product-limit method,log-rank test,hazard risk,and Cox proportional univariate and multivariate models.Propensity score matching(PSM)was used to compare the ALA and OLA groups.RESULTS The analysis included 11607 patients.Most had advanced T stages(T3=48%;T4=42%).The pathological AJCC stage distribution was IIA=22%,IIB=18%,IIIA=26%,IIIB=22%,and IIIC=12%.The overall sample divided by the study objective included ILA(50%),ALA(35%),and OLA(15%).Median OS was 24 mo for the ILA group,29 mo for the ALA group,and 34 mo for the OLA group(P<0.001).Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group[ALA hazard ratio(HR)=0.84,95%confidence interval(CI):0.79-0.88,P<0.001 and OLA HR=0.73,95%CI:0.68-0.79,P<0.001].The OS outcome was confirmed by multivariate analysis(ALA HR=0.68,95%CI:0.64-0.71,P<0.001 and OLA:HR=0.48,95%CI:0.44-0.52,P<0.001).A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group(OS:OLA median=34 mo vs ALA median=26 mo,P<0.001,which was confirmed by univariate analysis(HR=0.81,95%CI:0.75-0.89,P<0.001)and multivariate analysis:(HR=0.71,95%CI:0.65-0.78,P<0.001).CONCLUSION Proper nodal staging is a critical issue in gastric cancer.Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.
文摘AIM:To study,in intact male transgenic mice,the effects of three diets based on olive oil and olive oil diet supplemented with lovastatin and orlistat on hepatic lipogenic enzymes expression,considered markers of cell proliferation.METHODS:Forty ApcMin/+mice were randomly divided into 4 groups and fed for 10 wk:olive oil(OO)group,n=10 animals received a diet with olive oil 12%;olive oil plus lovastatin(LOVA)group,n=10 animals received the same diet with olive oil supplemented with lovastatin 5 mg/kg;olive oil plus orlistat(OR)group,n=10 animals fed the diet with olive oil supplemented with orlistat 50 mg/kg and SD group,n=10 animals fed a standard diet.The activity of lipogenic enzymes and their gene expression were evaluated by radiomet-ric and real-time reverse transcription-polymerase chain reaction assay,respectively.RESULTS:After 10 wk of dietary treatment,the body weight was no different among animal groups(21.3±3.1 g for standard group,22.1±3.6 g for OO group,22.0±3.2 g for LOVA group and 20.7±3.4 g for OR group,data expressed as mean±SD),observing a generalized well-being in all animals.All the dietary managed treated groups presented significantly reduced hepatic levels of fatty acid synthase,farnesyl pyrophosphate synthase and 3-hydroxyl-3-methyl-glutaryl CoA reductase activity and gene expression when compared with the mice fed the standard diet.To evaluate cell proliferation in the liver of treated mice,the levels of cyclin E mRNA have been measured,demonstrating a significant reduction of cyclin E gene expression in all treated groups.Evidence of reduced hepatic cell proliferation was present overall in OO group mice.CONCLUSION:We confirm the role of lipogenic enzymes as markers of cell proliferation,suggesting that appropriate dietary management alone or with drugs can be a feasible approach to counteract hepatic cell proliferation in mice.
文摘AIM: To determine the incidence of and the risk factors for cytomegalovirus(CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation(ASCT).METHODS: A total of 327 consecutive non CD34+ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome(Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients who underwent an ASCT for an acute leukemia(n = 20) in the sameperiod were excluded from this analysis. CMV DNA load in the blood has been determined by polymerasechain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.RESULTS: Overall, 36 patients(11%) required a specific antiviral treatment for a symptomatic CMV reactivation(n = 32) or an end-organ disease(n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma(16%) and myeloma patients(8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in Ig G seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplantrelated mortality was significantly higher in patients who experienced a CMV reactivation(8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pretransplant HBc Ig G seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy(P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pretransplant HBc Ig G seropositivity(OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell nonHodgkin's lymphoma(OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBc Ig G seropositivity and a diagnosis of T-cell non-Hodgkin's lymphoma should be considered as independent predictor factors of CMV reactivation.
文摘BACKGROUND Guidelines recommend to cease inflammatory bowel disease(IBD)biologic therapy during coronavirus disease 2019(COVID-19).AIM To investigate severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)antibody positivity in an IBD cohort,COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables.METHODS Prospective observational cohort study.IBD patients were tested for SARS-CoV-2 IgG.Data on COVID-19 disease,demographics/therapeutics and clinical features of the IBD population were collected.IgG≥7 was set for SARS-CoV-2 antibody positivity.Throat swab was performed in cases of IgG positivity.Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed.RESULTS In total,103 IBD patients were enrolled.Among them,18.4%had IgG≥7.Multivariate analysis of antibody positivity correlated only with IBD treatment.For IgG≥7,the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine,respectively,vs biologic drugs(P=0.0157 between them).COVID-19 related symptoms were reported in 63%of patients with IgG positivity.All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBDtreatment and body mass index correlated with COVID-19 disease development with symptoms.CONCLUSIONThe IBD population does not have a higher risk of severe COVID-19. The relative risk of havingSARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologictherapy and lastly mesalazine. None of the patients under biologic therapy developed severeCOVID-19.
文摘Purpose: Anxiety disorders are frequently associated with chronic stress with possible cognitive consequences. The aim of this study was to determine the verbal fluency performance in a cohort of patients with anxiety disorders and allostatic load, treated with alprazolam during 12 weeks. Methods: Patients with GAD (general anxiety disorders, DSM IV), with >6 in Hamilton Anxiety Rating Scale (HAM-A), neuroticism > 18 (NEO-FFI inventory), and normal Mini-Mental State Examination were included. Clinical and Psychiatric examination, Allostatic Load Index and cognitive assessment were analyzed before and after 12 weeks of treatment. The phonemic and semantic verbal fluency tests were determined in all patients. The scoring for each fluency task was determined by counting the number of correct words. The total score from each semantic and phonemic verbal task was analyzed comparing the individual score with normal data controlled by age and sex. Patients with scores > ?2 standard deviation (SD) from normative data were considered impaired. Results: Fifty-four patients completed the semantic verbal fluency test before treatment and fifty patients completed after treatment. According to the z-scores before treatment 7 patients of 54 (12.9%) had verbal fluency impairments. After treatment none patients showed semantic verbal fluency deficits but 3 patients of 50 (6%) showed phonemic impairments. Impaired group was significantly associated with an older age before treatment (p = 0.033) and with a similar tendency but not significant (p = 0.09) after treatment (Student t test). Conclusion: In this study older age factor was associated with verbal fluency impairment in GAD patients. Stratified treatments analyzing age and sex factors, including allostatic load measurements and cognitive assessments may be useful tools to determine the effectiveness and the safety of psychopharmacological treatments.
文摘BACKGROUND Human immunodeficiency virus(HIV)is a major public health concern,particularly in Africa where HIV rates remain substantial.Pregnant women are at an increased risk of acquiring HIV,which has a significant impact on both maternal and child health.AIM To review summarizes HIV seroprevalence among pregnant women in Africa.It also identifies regional and clinical characteristics that contribute to study-specific estimates variation.METHODS The study included pregnant women from any African country or region,irrespective of their symptoms,and any study design conducted in any setting.Using electronic literature searches,articles published until February 2023 were reviewed.The quality of the included studies was evaluated.The DerSimonian and Laird random-effects model was applied to determine HIV pooled seroprevalence among pregnant women in Africa.Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity.Heterogeneity was assessed with Cochran's Q test and I2 statistics,and publication bias was assessed with Egger's test.RESULTS A total of 248 studies conducted between 1984 and 2020 were included in the quantitative synthesis(meta-analysis).Out of the total studies,146(58.9%)had a low risk of bias and 102(41.1%)had a moderate risk of bias.No HIV-positive pregnant women died in the included studies.The overall HIV seroprevalence in pregnant women was estimated to be 9.3%[95%confidence interval(CI):8.3-10.3].The subgroup analysis showed statistically significant heterogeneity across subgroups(P<0.001),with the highest seroprevalence observed in Southern Africa(29.4%,95%CI:26.5-32.4)and the lowest seroprevalence observed in Northern Africa(0.7%,95%CI:0.3-1.3).CONCLUSION The review found that HIV seroprevalence among pregnant women in African countries remains significant,particularly in Southern African countries.This review can inform the development of targeted public health interventions to address high HIV seroprevalence in pregnant women in African countries.
基金Maria V.Giuli was supported by a AIRC fellowship for Italy.
文摘Drug resistance is one of the main challenges in cancer therapy,including in the treatment of female-specific malignancies,which account for more than 60%of cancer cases among women.Therefore,elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches.Notably,Notch signaling,including either receptors or ligands,has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer.Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts,several studies focused on the Notch-dependent regulation of the cancer stem cell(CSC)subpopulation or the induction of the epithelial-to-mesenchymal transition(EMT),both features implicated in either intrinsic or acquired resistance.Indeed,the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSC-driven drug resistance.Moreover,other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment.Collectively,there is a long way to go before every facet will be fully understood;nevertheless,some small pieces are falling neatly into place.Overall,the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.
