SARS-CoV-2 Igg seroprevalence in IBD patients treated with biologics: first vs. second pandemic wave in a prospective study.

OBJECTIVE: In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave. PATIENTS AND METHODS: From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1. INCLUSION CRITERIA: age ≥ 18 years; diagnosis of IBD; follow-up; written consent. EXCLUSION CRITERIA: SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used. RESULTS: IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p<0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1). CONCLUSIONS: During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.

Multiple hepatic and brain abscesses caused by Parvimonas micra: A case report and literature review.

Gram-positive anaerobic cocci (GPAC) are responsible for 30% of anaerobic infections. Parvimonas micra is an emergent pathogen that is part of the oral and gastrointestinal commensal flora, and its role in several infection processes has recently emerged thanks to the improvement of diagnostic techniques. P. micra bacteraemia is reported in immunocompromised patients and is often complicated by abscesses. Here, we present a case study of multiple hepatic and brain abscesses caused by P. micra bacteraemia in a patient with complicated diverticulitis.

Low prevalence of SARS-CoV-2 infection in inflammatory bowel disease.

OBJECTIVE: Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated. PATIENTS AND METHODS: In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients. RESULTS: Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p<0.0001]. CONCLUSIONS: The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

Hepatic follicular lymphoma in an old patient with Crohn's disease: a rare case and review of the literature.

OBJECTIVE: Crohn's Disease (CD) has been associated with non-Hodgkin lymphoma. Follicular Lymphoma (FL) limited to the liver is extremely rare, accounting for 1% to 4.4% of all Primary Hepatic Lymphoma (PHL). CASE PRESENTATION: In 2018, an 85-years old male patient with post-operative recurrence of ileal CD referred rare episodes of fever and mild diffuse abdominal pain. Since cholecystectomy in 2001, clinical history was characterized by recurrent episodes of cholangitis and common bile duct stones. In 2018, ultrasonography and MRI showed a solid focal hepatic lesion (FHL)(4.5 cm x 2.5 cm) in the IV hepatic segment. The radiographic aspect of the lesion was unusual. Initially, focal nodular hyperplasia was suspected. Clinical history of cholangitis and radiological findings subsequently suggested a diagnosis of Hepatic Abscess (HA). A progressive enlargement of the FHL (7.3 cm x 5.8 cm) despite antibiotic treatments, led to perform a liver biopsy. Histological and immunophenotypical analysis of the FHL (7.5 cm x 5.4 cm) enabled a final diagnosis of FL. The "in situ" hybridization for Epstein-Barr virus (EBER) was negative. No additional lesions related to FL were initially detected, thus suggesting a very rare case of PHL in an old patient with CD never treated with thiopurines. CONCLUSIONS: This case report highlights the need to consider a rare diagnosis of FL of the liver in patients showing a challenging focal hepatic lesion of unknown origin.

Agreement between different versions of MNA.

UNLABELLED: Malnutrition occurs frequently in the elderly with important clinical and functional consequences. Moreover, the treatment of malnutrition in the elderly may be effective if clinical and nutritional interventions are performed in the early stages. Therefore the early identification of the risk of malnutrition using validated and handy tools plays a pivotal role in terms of clinical outcome. Mini Nutritional Assessment (MNA) was validated for this purpose since many years but it is still ongoing the debate over whether the use of different items in certain clinical conditions can be effective without affecting the validity of the nutritional status evaluation. The aim of this study was to assess the agreement between different versions of MNA in the evaluation of nutritional risk in elderly subjects. METHODS: 522 subjects, 345 women and 177 men, were recruited from nursing homes or were free living in three different regions in Italy. All subjects underwent a multidimensional geriatric evaluation, addressed especially to nutritional status. We compared three different versions of MNA: the "original" version; a "proportional" MNA (MNA- P) in which the total MNA score was replaced by the ratio between the maximum score that each subject could obtain without including the body mass index (BMI) and the total original MNA score; and a third version in which calf circumference (CC) and mid- upper arm circumference (MAC) were used instead of BMI. RESULTS: According to the original MNA, a high prevalence of malnutrition was found out in both genders (26% of women and 16.3% of men); both the versions of MNA, in which BMI was not considered, showed a good predictive value compared to original MNA. In particular, the MNA- P. showed an overall efficiency equal to 89,1% with specificity and positive predictive value respectively equal to 97.5% and 95.2%. MNA- CC- MAC showed even better results in terms of overall efficiency (91.4%), sensitivity (81.1%), specificity (97.1%), positive and negative predictive values (94.2% and 94.4%, respectively). CONCLUSION: The different versions of MNA gave similar results in the classifications of subjects and in comparison with nutritional and biochemical parameters. Moreover MNA versions that did not considered BMI seem to be more effective in singling out subjects with risk factors related to malnutrition (disability, reduced strength and calf circumference, anaemia).

Malnutrition in elderly: social and economic determinants.

UNLABELLED: Malnutrition occurs frequently in the frailest groups of the population, especially in people who are on a low income and elderly subjects, overall if they are institutionalized. The aim of this study was to assess the prevalence of malnutrition in a sample of elderly people living in different settings and to identify the determinants of malnutrition. METHODS: A total of 718 subjects, 472 females (F) and 246 males (M), were recruited from nursing homes or were free living in three different regions in Italy. Nutritional status, depression, social, functional and cognitive status, were evaluated. RESULTS: According to the Mini Nutritional Assessment (MNA), a high prevalence of malnutrition was found out in both genders: 26% of F and 16.3% of M were classified as being malnourished (MNA<17); 40.9% of F and 35% of M were at risk of malnutrition (MNA 17-23,5). The prevalence of malnutrition was significantly higher in NH subjects in both sexes. Moreover, a relationship was shown between malnutrition and inability to shop, prepare and cook meals because of a low income, distance from markets or supermarkets as well as impossibility to drive the car or to use public transportation. This study confirms the necessity to routinely perform nutritional status evaluation in elderly subjects, to carry out training courses for health workers (doctors, nurses, psychologists, dietitians), to implement nutritional education of the geriatric population, to develop tools and guidelines for health workers and caregivers, to identify and reduce clinical, functional, social or economic risk factors for malnutrition.

The efficacy and tolerability of a sunitinib 3-week administration schedule in metastatic renal cell carcinoma patients: report of three cases.

Sunitinib, an orally multitargeted tyrosine kinase inhibitor and standard first-line treatment for metastatic renal cell carcinoma, is usually administered on a 6-week schedule. Toxicities reported with this drug are usually of moderate grade, which results in good treatment tolerability and patients' compliance. However, in some cases high-grade or prolonged toxicities require temporary treatment interruption or dose adjustment, possibly resulting in reduced treatment efficacy. We describe three cases of metastatic renal cell carcinoma patients (a 53-year-old male, a 70-year-old woman, and a 65-year-old woman) who received a shortened 3-week sunitinib administration schedule, 2 weeks daily administration followed by 1 week of rest (2/1) due to toxicities developed on the classic 6-week schedule, which would have required a temporary treatment interruption or a dose reduction. Treatment was generally well tolerated with manageable toxicities. A 3-week administration schedule of sunitinib may represent a valid alternative for managing toxicity while maintaining the planned dose intensity over a 6-weeks period of time. Sunitinib may thus be administered using a flexible dosing schedule to meet individual patient needs, achieving better tolerability and maintaining significant response to treatment.

Predicting the outcome of long-term care by clinical and functional indices: the role of nutritional status.

UNLABELLED: In elderly subjects, past researches have already underlined the role of nutritional status as a basic factor able to influence the prognosis either in acute wards or in rehabilitation and long-term care settings. Aim of the study is that of retrospectively verify, through a multivariate analysis, the factors able to condition mortality in long-term care, paying particular attention to the nutritional status. METHODS: The survey included 513 patients aged more than 65 years admitted to a long-term care unit during a three years period. Exitus within the first three months of hospitalization was considered the outcome variable, while baseline functional, cognitive, clinical and nutritional status were considered the independent variables eventually related to mortality. RESULTS: The univariate analysis found that some variables were significantly correlated with the outcome: comorbidity, ADL, cognitive status, pressure sores, albumin, transferrin, CRP, mucoprotein, cholesterol, cholinesterase, MAMC and MNA. The predictive value of the block model of the logistic regression analysis was 77.9% (specificity = 85.3%, sensitivity = 63.9%). With the forward stepwise analysis only MNA, cholinesterase, CRP and mucoprotein were considered in the final model. In this case the predictive value of the model was 79.3% (specificity = 84.6%, sensitivity = 69.46%).

Validation study on avermectine residues in foodstuffs.

Avermectines are antiparasitic agents widely used as veterinary drugs for food producing animals. The European Community, due to their side effects, limited the use of these molecules establishing maximum residue limits (MRLs) in some foods. A validated qualitative and quantitative high performance liquid chromatography method with fluorescence detection (HPLC-FL) is presented for the simultaneous determination of ivermectin (IVM), abemectin (ABA), moxidectin (MOX), eprinomectin (EPR), doramectin (DOR) and emamectin (EMA) in foodstuffs (muscle, eggs and milk). Samples were extracted with acetonitrile, purified with liquid-liquid extraction (LLE), and analysed by HLPC-FL previous derivatization with trifluoroacetic anhydride (TFAA) in presence of 1-methyl-imidazole (MI) and acetic acid. To date, the presented method is the first validated for the matrix eggs, and in accordance with the requirements set by Commission Decision 2002/657/EC. Recoveries of the methods, calculated spiking the samples in the range 5.0-100.0 µg kg(-1), were 64-83% for muscle, 65-89% for milk and 63-84% for eggs. The precision (CV) ranged between 9.2 and 17.1% for muscle, 9.9 and 16.6% for milk and from 9.4 to 17.4% for eggs. Linearity for the six analytes was calculated from 5.0 to 200.0 µg kg(-1). The main advantages of the presented method are its rapidity, the specificity, the good precision and recovery that make it very suitable to the detection and determination of avermectines.

[Malnutrition in the elderly: clinical features, psychological and social determinants. Preliminary results]. / La malnutrizione in età geriatrica: caratteristiche cliniche e determinanti psico-sociali (MEG). Risultati preliminari.

In industrialized Countries malnutrition is a very frequent condition in frail groups of the population, people with low income and elderly subjects above all if institutionalized. The aim of the study is to: analyse the prevalence of malnutrition in a sample of elderly people located in different geographical areas in Italy; identify the psychological, social, economic, environmental, cultural and demographic determinants of malnutrition. The prevalence of malnutrition (estimated through the MNA) is high in both sexes (28% of F and 21.9% of M. Age, institutionalisation, health status, autonomy status, cognitive status and education level are some of the factors that correlate with the presence of malnutrition. Loneliness and poverty seem to have a negative impact on nutritional status but further data are needed to confirm this hypothesis. The data collected confirm the need to activate services dedicated to assess the nutritional status of elderly people, to implement campaigns in particular on food education for the elderly population, to set tools and guide lines for caregivers.

Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient.

BACKGROUND: The activity of sunitinib, a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activities, has been explored in several solid malignancies such as breast, lung, prostate and pancreatic cancer. Currently it is approved for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Non-small cell lung cancer usually presents at an advanced or metastatic stage at diagnosis. Treatment options are limited for this disease, therefore symptom palliation and patient's quality of life are primary objectives of therapy. CASE REPORT: We describe the case of a patient (male, 67 years old) with heavily pre-treated metastatic non-small cell lung carcinoma who received sunitinib according to the following 3-week schedule: 50 mg daily for 2 weeks followed by a 1-week rest. The patient completed six months of therapy achieving a major disease response without high-grade toxicities. CONCLUSION: In this case, sunitinib shows promising single-agent activity in pretreated non-small cell lung cancer, with a good toxicity profile and flexible administration schedule.

Tetracycline residues in royal jelly and honey by liquid chromatography tandem mass spectrometry: validation study according to Commission Decision 2002/657/EC.

A specific, sensitive and robust liquid chromatography tandem mass spectrometry method for determining oxytetracycline, tetracycline, chlortetracycline and doxycycline in royal jelly and honey samples is presented. Extraction of drug residues was performed by ammonium acetate buffer as extractant followed by a clean-up with metal chelate affinity chromatography and solid-phase extraction. Tetracycline analysis was performed using liquid chromatography-electrospray ionisation-tandem mass spectrometry. The presented method is the first validated for royal jelly and in accordance with the requirements set by Commission Decision 2002/657/EC. Recoveries of the methods, calculated spiking the samples at 5.0, 10.0, 20.0 and 30.0 µg kg(-1), were 79% to 90% for honey and 77% to 90% for royal jelly. The intra-day precision (RSD) ranged between 8.1% and 15.0% for honey and from 9.1% to 16.3% for royal jelly, while inter-day precision values were from 10.2% to 17.6% and from 10.6% to 18.4% respectively for honey and royal jelly. Linearity for the four analytes was calculated from 5.0 to 50.0 µg kg(-1). The decision limits (CCα) ranged from 6.2 to 6.4 µg kg(-1) and from 6.1 to 6.5 µg kg(-1) for honey and royal jelly, respectively. Detection capabilities values (CCß) ranged between 7.2 and 7.7 µg kg(-1) and from 7.3 to 7.9 µg kg(-1) respectively for honey and royal jelly. The developed method is currently in use for confirmation of the official control analysis of honey and royal jelly samples.

Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.

Use of serum biomarkers in a diagnostic test for irritable bowel syndrome.

BACKGROUND: Currently, no single serum biomarker can reliably differentiate irritable bowel syndrome (IBS) from other functional gastrointestinal disorders or organic diseases of the gastrointestinal tract. AIM: To develop and validate a diagnostic test using serum biomarkers to detect IBS. METHODS: Ten serum biomarkers were selected from a potential panel of 140 for their ability to differentiate IBS from non-IBS disease in blood samples from patients with IBS, other gastrointestinal disorders and healthy volunteers. A predictive modelling tool was developed to assess patterns and relationships among the 10 serum biomarkers that best differentiated IBS patients from healthy controls and patients with non-IBS gastrointestinal disease. This model was tested in a different cohort of patients and healthy controls (n = 516) to determine the predictive accuracy of differentiating IBS from non-IBS. RESULTS: The sensitivity and specificity of the 10-biomarker algorithm for differentiating IBS from non-IBS was 50% and 88% respectively. The positive predictive value was 81%, and the negative predictive value was 64% at 50% IBS prevalence in the validation cohort. Overall accuracy was 70%. CONCLUSIONS: Assessing serum biomarker patterns can differentiate IBS from non-IBS with reasonable sensitivity and specificity. Assessing serum biomarkers in an overall diagnostic strategy may allow earlier diagnosis and treatment for patients with IBS.

Postoperative chemotherapy in resected gastric cancer: results of a single center experience.

Gastric cancer remains a major health problem despite its decline in incidence in Western countries. Although radical surgery represents the primary curative option for gastric cancer patients, most of them relapse and die due to their disease despite an R0 resection. At present the routine use of postoperative adjuvant therapy to reduce disease recurrence is still considered an investigational approach. Out of a total of 275 patients (stage IB through IV M0 AJCC/UICC) who underwent surgery for gastric cancer at our Surgery Unit between 1993 and 2001, 156 were eligible for adjuvant chemotherapy, of whom only 52 accepted to undergo this treatment. This group of patients was retrospectively compared with a control group (1:2) and overall survival was assessed using hazard ratio and Kaplan-Meier estimates. Five-year survival was 40% in the chemotherapy group and 37.8% in the group which underwent surgery alone. Indeed, chemotherapy did not reduce the risk of death (HR 0.87, 95% CI = 0.57-1.34, p=0.54). Serosal involvement and the invasion of more than 6 lymph nodes were the main independent prognostic factors identified by multivariate analysis. The current study did not show a clear advantage of chemotherapy over surgery alone. However, our results can help to define strategies for future clinical trials with the use of new regimens based on more effective and less toxic drugs.

Deregulation of the mitochondrial apoptotic machinery and development of molecular targeted drugs in acute myeloid leukemia.

Apoptosis plays a key role in the control of rapidly renewing tissues, such as the hematopoietic system and leukemia cells invariably have abnormalities in one or more apoptotic pathways, determining a survival advantage of these cells and the development of drug resistance. These defects are also frequently associated with a low rate of response to standard chemotherapy and with a poor survival in acute myeloid leukemia (AML). The major form of apoptosis proceeds through the mitochondrial pathway, with the mitochondrial outer membrane permeabilization, leading to the release of proteins normally found in the space between the inner and outer mitochondrial membranes (cytochrome C, AIF and others). Higher levels of anti-apoptosis proteins bcl-2, bcl-x(L), Mcl-1 block permeabilization of the membrane and are reported in AML patients presenting a poor outcome. On the contrary, activated pro-apoptotic bax or bad proteins allow this permeabilization and are correlated to a good prognosis in AML. Defects in the mitochondrial pathway induce multidrug-resistance and confer important prognostic information in AML. High ratios of bcl-2 to bax protein confer a poor prognosis with decreased rates of complete remission and overall survival. The prognostic information from the ratio of the proteins is greater than bcl-2 levels alone. Recently, we confirmed the impressive impact of the bax/bcl-2 ratio, determined by flow cytometry, on AML prognosis (complete remission and overall survival) in 255 AML patients. Bcl-2 down regulation might lower the apoptotic threshold of leukemic cells and, through this mechanism, favor response to chemotherapy. Phase II studies of oblimersen (antisense Bcl-2), cytarabine and daunorubicin or oblimersen plus gentuzumab, a cytotoxic antibody directed against CD33+ cells in relapsed AMLs, showed promising results. Defects in apoptosome proteins, such as APAF-1, are frequent in AML and treatment with 5-aza-2'-deoxycytidine, a specific inhibitor of DNA methylation, restored APAF-1 expression in leukemic cells. In conclusion, targeted therapies that are designed to induce apoptosis in leukemic cells, are the most promising anti-leukemia strategies. The elucidation of the apoptotic machinery and of its defects in AML lays the basis for developing new drugs able to trigger apoptosis and overcome therapy resistance.

Wearable microwave radiometers for remote fire detection: System-on-Chip (SoC) design and proof of the concept.

The paper reports the present status of the project aimed at the realization of a wearable low-cost low-power System-on-Chip (SoC) 13-GHz passive microwave radiometer in CMOS 90 nm technology. This sensor has been thought to be inserted into the firemen jacket in order to help them in the detection of a hidden fire behind a door or a wall, especially where the IR technology fail. With respect of the prior art, the SoC is further developed and a proof of the concept is provided by means of a discrete-component prototype.

Wearable system-on-a-chip radiometer for remote temperature sensing and its application to the safeguard of emergency operators.

The remote sensing and the detection of events that may represent a danger for human beings have become more and more important thanks to the latest advances of the technology. A microwave radiometer is a sensor capable to detect a fire or an abnormal increase of the internal temperature of the human body (hyperthermia), or an onset of a cancer, or even meteorological phenomena (forest fires, pollution release, ice formation on road pavement). In this paper, the overview of a wearable low-cost low-power system-on-a-chip (SoaC) 13 GHz passive microwave radiometer in CMOS 90 nm technology is presented. In particular, we focused on its application to the fire detection for civil safeguard. In detail, this sensor has been thought to be inserted into the fireman jacket in order to help the fireman in the detection of a hidden fire behind a door or a wall. The simulation results obtained by Ptolemy system simulation have confirmed the feasibility of such a SoaC microwave radiometer in a low-cost standard silicon technology for temperature remote sensing and, in particular, for its application to the safeguard of emergency operators.

Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study.

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.