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1.
IJID Reg ; 12: 100404, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39188886

ABSTRACT

Objectives: Ixodes ricinus is under-recognized in Europe. This study aimed to determine the seroprevalence and spatial distribution of tick-borne encephalitis (TBE) virus (TBEV) in areas close to endemic regions in Northern Italy. Methods: A multicenter study was conducted on a random sample of the general population afferent to hospitals in Veneto, Lombardy, and Piedmont with a pre-determined sample size of 1500 participants. The presence of TBEV-neutralizing antibodies was determined for sera positive to the TBE-specific immunoglobulin G test in a centralized laboratory. Results: Out of 1537 samples analyzed (790 from Lombardy, 394 from Veneto, 353 from Piedmont), 39 (2.5%) were immunoglobulin G TBEV-positive. The frequency of positive cases was similar amid the regions (24-3.0% Lombardy, 10-2.5% Veneto, and 5-1.4% Piedmont; P = 0.27). The seropositivity rates were 3.6% in subjects aged over 50 years, 2.0% in those aged 30-50 years, and 1.5% in subjects aged under 30 years (P = 0.10). Two of them (one from Veneto and one from Lombardy) were confirmed by TBEV neutralization test (prevalence 130 per 100,000). One lived close to an endemic area (Treviso); the other spent time in an endemic region (Friuli) and did not remember experiencing tick bites. Conclusions: The results from this study highlight the need for raising awareness among the population and health care workers to limit the risk of TBE infection.

2.
Front Oncol ; 12: 989713, 2022.
Article in English | MEDLINE | ID: mdl-36313660

ABSTRACT

Background: Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutive patients admitted at SCOC from 2018 to 2021 in terms of appropriateness, process, and outcome indicators. Here, we report further analysis in the same group of 753 patients, evaluating other parameters and the correlation between symptom intensity, gender, age, and survival. Methods: SCOC data were retrieved from a prospectively maintained database. Results: Among the patients, 42.2% were women, and the median age was 68 years, with 46.7% of patients aged ≥70 years. The most prevalent disease type was gastrointestinal cancer (75.2%), and 90.9% of the patients had metastatic disease. The median score for the distress thermometer was 4; the vast majority of the patients (98.6%) reported physical problems, and 69.4% presented emotional issues. Younger women demonstrated a significantly greater median distress than other patients (p=0.0018). Almost all symptoms had a higher prevalence on the 0-3 Edmonton Symptom Assessment Scale (ESAS) score, except for fatigue. About 43.8% of the patients received systemic anticancer treatment (SAT) in the last 60 days of life, 15.0% of whom received SAT in the last month and 3.1% in the last 2 weeks. For some symptoms, women frequently had more ESAS >3. Pain and nausea were significantly less reported by older patients compared with younger adults. Men had a lower risk of having MUST score ≥ 2 (p=0.0311). Men and older patients showed a lower prognosis awareness (p=0.0011 and p=0.0049, respectively). Older patients received less SAT within the last 30 days of life (p=0.0006) and had death risk decreased by 20.0%. Conclusion: Our study identified two subgroups of patients with advanced cancer who require special attention and support due to important symptoms' burden detected by Patient Reported Outcome Measures tests: women and younger adults. These categories of patients require special attention and should be provided early access at SCOC. The role of an oncologist remains crucial to intercept all patients in need of early palliative care and balancing trade-offs of anticancer treatment in advanced metastatic disease.

3.
Cancers (Basel) ; 14(10)2022 May 23.
Article in English | MEDLINE | ID: mdl-35626172

ABSTRACT

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients' characteristics and SCOC outcomes through internal procedure indicators. Data were retrieved from the SCOC prospectively maintained database. There were 753 eligible patients. The median age was 68 years; primary tumor sites were gastrointestinal (75.2%), genitourinary (15.0%) and other sites (9.8%). Predominant symptoms were psychological issues (69.4%), appetite loss (67.5%) and pain (65.9%). Dyspnea was reported in 53 patients (7%) in the referral form, while it was detected in 226 patients (34.2%) during SCOC visits (p < 0.0001). Median survival of patients after the SCOC visit was 7.3 months. Survival estimates by the referring oncologist were significantly different from the actual survival. Psychological intervention was deemed necessary and undertaken in 34.6% of patients, and nutritional support was undertaken in 37.9% of patients. Activation of palliative care services was prompted for 77.7% of patients. Out of 357 patients whose place of death is known, 69.2% died at home, in hospice or residential care. With regard to indicators' assessment, the threshold was reached for 9 out of 11 parameters (81.8%) requested by the procedure. This study confirmed the importance of close collaboration between oncologists and palliative care teams in responding properly to cancer patients' needs. The introduction of a procedure with indicators allowed punctual assessment of a team's performance.

4.
J Clin Med ; 10(24)2021 Dec 12.
Article in English | MEDLINE | ID: mdl-34945108

ABSTRACT

(1) Background: Data on different steroid compounds for the treatment of hospitalized COVID-19 (coronavirus disease 2019) patients are still limited. The aim of this study was to compare COVID-19 patients admitted to non-intensive units and treated with methylprednisolone or dexamethasone. (2) Methods: This was a single-center retrospective study that included consecutive patients with COVID-19 hospitalized in medical wards during the second wave of the pandemic. Thirty-day mortality and the need for intensive or semi-intensive care were the main clinical outcomes analyzed in patients receiving methylprednisolone (60 mg/day) compared with dexamethasone (6 mg/day). Secondary outcomes included complication rates, length of hospital stay, and time to viral clearance. (3) Results: Two-hundred-forty-six patients were included in the analysis, 110 treated with dexamethasone and 136 with methylprednisolone. No statistically significant differences were found between the two groups of patients regarding 30-day mortality (OR 1.35, CI95% 0.71-2.56, p = 0.351) and the need for intensive or semi-intensive care (OR 1.94, CI95% 0.81-4.66, p = 0.136). The complication rates, length of hospital stay, and time to viral clearance did not significantly differ between the two groups. (4) Conclusions: In patients hospitalized for COVID-19 in non-intensive units, the choice of different steroid compounds, such as dexamethasone or methylprednisolone, did not affect the main clinical outcomes.

5.
Pain Pract ; 2019 Mar 27.
Article in English | MEDLINE | ID: mdl-30917409

ABSTRACT

BACKGROUND: Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic. METHODS: We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale. RESULTS: Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation >5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response. CONCLUSIONS: OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

6.
J Geriatr Oncol ; 10(4): 637-642, 2019 07.
Article in English | MEDLINE | ID: mdl-30686679

ABSTRACT

BACKGROUND: Pain is a common symptom among patients with cancer, yet pain prevalence and management in older cancer pts. are poorly known. METHODS: Patients aged ≥70 years referred to Istituto Oncologico Veneto IRCCS from January 2011 to December 2013 were evaluated with Comprehensive Geriatric Assessment (CGA). Pain was assessed by means of short form of McGill Pain Questionnaire (MPQ-sf), Brief Pain Inventory (BPI-sf), and numerical rating scale (NRS). Pts with completed CGA, no severe cognitive impairment and completed pain assessment were enrolled. RESULTS: Enrolled patients were 745; 51% male, median age 76 years, median ECOG Performance Status (PS) 1. Frail patients at CGA were 45.2%. Patients with pain were 266 (35.7%). Mean Average Pain Intensity (API) was significantly higher among females, patients fit at CGA, with advanced disease, poorer PS and more comorbidity. Pain was detected by the oncologist in 20.4% of cases and deemed cancer-related in 54.8%. Gender, PS, status of disease, stage, function disability, mood, cognitive functioning and frailty were significantly associated with reporting of pain. At BPI, moderate-severe pain was found in 81 patients. The degree of agreement between API and pain intensity evaluated by physician was minimal. Patients on pain medications were 184, with 113 patients reporting rates of pain relief ≥50%. CONCLUSION: About one third of older patients with cancer report pain, which is not cancer-related in about half of cases. Female gender, fitness at CGA, advanced stage, poorer PS, higher number of comorbidities and primary site were associated with significant differences in pain reporting.


Subject(s)
Cancer Pain/epidemiology , Frailty/epidemiology , Neoplasms/epidemiology , Affect , Aged , Aged, 80 and over , Analgesics, Opioid/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cancer Pain/drug therapy , Cancer Pain/physiopathology , Cancer Pain/psychology , Cognition , Female , Geriatric Assessment , Humans , Italy/epidemiology , Linear Models , Logistic Models , Male , Neoplasms/pathology , Neoplasms/physiopathology , Neoplasms/psychology , Pain/drug therapy , Pain/epidemiology , Pain/physiopathology , Pain/psychology , Pain Measurement , Prospective Studies , Sex Factors
7.
Support Care Cancer ; 27(7): 2425-2434, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30357555

ABSTRACT

PURPOSE: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. METHODS: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. RESULTS: The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC. CONCLUSIONS: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01996540).


Subject(s)
Hospice and Palliative Care Nursing/methods , Palliative Care/methods , Quality of Life/psychology , Stomach Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Stomach Neoplasms/pathology
9.
Eur J Cancer ; 69: 110-118, 2016 12.
Article in English | MEDLINE | ID: mdl-27821313

ABSTRACT

AIM: Early palliative care (EPC) in oncology has shown sparse evidence of a positive impact on patient outcomes, quality of care outcomes and costs. PATIENTS AND METHODS: Data for this secondary analysis were taken from a trial of 207 outpatients with metastatic pancreatic cancer randomly assigned to receive standard cancer care plus on-demand EPC (standard arm) or standard cancer care plus systematic EPC (interventional arm). After 20 months' follow-up, 149 (80%) had died. Outcome measures were frequency, type and timing of chemotherapy administration, use of resources, place of death and overall survival. RESULTS: Some indices of end-of-life (EoL) aggressiveness had a favourable impact from systematic EPC. Interventional arm patients showed higher use of hospice services: a significantly longer median and mean period of hospice care (P = 0.025 for both indexes) and a significantly higher median and mean number of hospice admissions (both P < 0.010). In the experimental arm, chemotherapy was performed in the last 30 days of life in a significantly inferior rate with respect to control arm: 18.7% versus 27.8% (adjusted P = 0.036). Other non-significant differences were seen in favour of experimental arm. CONCLUSIONS: Systematic EPC showed a significant impact on some indicators of EoL treatment aggressiveness. These data, reinforced by multiple non-significant differences in most of the other items, suggest that quality of care is improved by this approach. This study is registered on ClinicalTrials.gov (NCT01996540).


Subject(s)
Antineoplastic Agents/therapeutic use , Hospice Care/statistics & numerical data , Palliative Care/methods , Pancreatic Neoplasms/therapy , Quality of Health Care , Quality of Life , Terminal Care/standards , Adult , Aged , Aged, 80 and over , Delivery of Health Care/methods , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Pancreatic Neoplasms/pathology , Time Factors
10.
Pharmacogenomics ; 12(1): 15-25, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21174619

ABSTRACT

AIM: A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose. MATERIALS & METHODS: The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age. RESULTS: The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25-45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series. CONCLUSION: The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Cytochrome P-450 Enzyme System/genetics , Mixed Function Oxygenases/genetics , Polymorphism, Genetic , Warfarin/administration & dosage , Adult , Aged , Aged, 80 and over , Algorithms , Blood Coagulation/drug effects , Blood Coagulation/genetics , Cytochrome P-450 CYP2C9 , Cytochrome P450 Family 4 , Dose-Response Relationship, Drug , Female , Humans , Italy , Male , Middle Aged , Pharmacogenetics , Precision Medicine , Retrospective Studies , Vitamin K Epoxide Reductases , Warfarin/adverse effects , Warfarin/pharmacokinetics , Warfarin/therapeutic use
11.
Clin Chim Acta ; 402(1-2): 54-60, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19135434

ABSTRACT

BACKGROUND: The combined evaluation of serum pepsinogens A (PGA) and C (PGC), gastrin-17 (G17) and anti-H. pylori antibodies (anti-H. pylori)(GastroPanel) has recently been proposed as a useful aid for investigating H. pylori-associated gastric mucosal inflammation. Our aim was to evaluate whether GastroPanel can correctly classify children who need or not endoscopy (EGD). METHODS: GastroPanel was performed in 554 consecutive children subjected to EGD. RESULTS: PGC and anti-H. pylori were sensitive (82.5% and 73.1%) and specific (58.1% and 84.0%) indices of H. pylori infection. Antral H. pylori colonization density, inflammation and activity grades were correlated with PGC. PGC and G17 were significantly higher in children with celiac disease (14.9+/-0.88 microg/L and 5.6+/-0.79 pmol/L) than in controls (8.5+/-0.38 microg/L and 2.4+/-0.24 pmol/L). The best cut-offs to distinguish H. pylori infected children from controls were 7.45 microg/L for PGC, 4.2 pmol/L for G17, 18 U for anti-H. pylori and 25 microg/L for PGA. With these cut-offs, GastroPanel had a NPV of 89.6% and a PPV of 66.8%. CONCLUSIONS: A negative GastroPanel result in children with upper abdominal non alarm symptoms, should allow the paediatrician to reasonably rule out the presence of major gastro-duodenal diseases and therefore avoid EGD.


Subject(s)
Antibodies, Bacterial/blood , Gastrins/blood , Gastrointestinal Diseases/diagnosis , Pepsinogen A/blood , Pepsinogen C/blood , Adolescent , Celiac Disease/diagnosis , Child , Child, Preschool , Endoscopy, Gastrointestinal , Female , Gastric Mucosa/microbiology , Gastritis/diagnosis , Gastritis/microbiology , Gastrointestinal Diseases/microbiology , Helicobacter Infections/complications , Helicobacter pylori/immunology , Humans , Infant , Logistic Models , Male , Sensitivity and Specificity
12.
Clin Chem ; 55(1): 150-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18988751

ABSTRACT

BACKGROUND: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker. METHODS: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12-84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs. RESULTS: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children <2 years old without total IgA deficiency, AGA IgG II and tTG IgA performed equally well (sensitivity 96.4% and specificity 100%). AGA IgA II, AGA IgG II, and tTG IgA concentrations diminished significantly (P < 0.0001) after 1 year of a gluten-free diet, reaching values below the cutoff in 87%, 70%, and 51% of cases, respectively. CONCLUSIONS: The best available index for diagnosing CD in children was tTG IgA. In infants <2 years old, AGA IgG II performed as well as tTG IgA in cases without total IgA deficiency and allowed detection of CD when total IgA was <0.06 g/L. Gluten-free diet monitoring can be achieved using any of the studied serum markers.


Subject(s)
Antibodies/blood , Celiac Disease/blood , Celiac Disease/diagnosis , Gliadin/blood , Peptides/blood , Adolescent , Antibodies/immunology , Biomarkers/blood , Celiac Disease/immunology , Child , Child, Preschool , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Gliadin/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Male , Peptides/immunology , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
13.
Gastroenterology ; 135(1): 91-9, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18474244

ABSTRACT

BACKGROUND & AIMS: The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease. METHODS: We studied 203 H pylori-infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction. RESULTS: cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98-27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41-125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19-5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained. CONCLUSIONS: We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Gastritis/microbiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Adolescent , Adult , Aged , Alleles , Female , Gastritis/epidemiology , Gastritis/pathology , Genotype , Helicobacter Infections/epidemiology , Helicobacter Infections/pathology , Helicobacter pylori/pathogenicity , Humans , Male , Middle Aged , Multivariate Analysis , Peptic Ulcer/epidemiology , Peptic Ulcer/microbiology , Peptic Ulcer/pathology , Polymorphism, Genetic , Retrospective Studies , Risk Factors , Stomach/microbiology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Virulence
14.
Clin Chim Acta ; 389(1-2): 139-45, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18179773

ABSTRACT

BACKGROUND: The Th2 cytokine IL-4 might limit H. pylori associated gastric inflammation and favour H. pylori clearance. The aim of the study was to verify whether IL-4 -588C>T SNP, or two SNPs of the gene coding the alpha chain of IL-4 receptor (IL-4RA Ex5+14A>G, IL-4RA Ex11+828A>G) considered singly or as haplotypes, are correlated with H. pylori virulence genes or H. pylori associated diseases. METHODS: We studied 144 patients with non-cardia gastric cancer (NCGC)(41/50 with present or past H. pylori infection), 75 with duodenal ulcer (DU)(66 H. pylori infected) and 171 with gastritis (CG)(107 H. pylori infected). cagA gene was present in 24/28 NCGC, 45/59 DU and 56/107 CG. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. IL-4RA haplotypes frequencies were estimated using Arlequin software. Neither the SNPs nor the IL-4RA haplotype correlated with disease diagnosis, H. pylori infection, degree of mucosal inflammation or intestinal metaplasia. IL-4 -588T allele (OR=3.69, 95% CI:1.34-10.16) and IL-4RA GA haplotype (p<0.05) enhanced the risk for cagA positive infections. IL-4RA GA haplotype correlated with IL-4 protein levels in H. pylori infected gastric mucosa. CONCLUSIONS: IL-4 and IL-4RA gene polymorphisms concur in selecting the H. pylori infecting strain, probably influencing the IL-4 signalling pathway.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Haplotypes , Helicobacter Infections/genetics , Interleukin-4 Receptor alpha Subunit/genetics , Interleukin-4/genetics , Polymorphism, Genetic , Adult , Aged , Female , Helicobacter Infections/diagnosis , Humans , Male , Middle Aged
15.
J Gastrointest Surg ; 11(11): 1506-14; discussion 1514, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17846855

ABSTRACT

Several bacterial and host-related factors concur in causing Helicobacter pylori eradication failure. We ascertained the role of bacterial virulence genes (cagA, vacA), clarithromycin resistance [Cla(R), 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-gamma+874A>T, TNF-alpha-1031T>C, TNF-alpha-857C>T, TNF-alpha-376G>A, TNF-alpha-308G>A, TNF-alpha-238G>A, IL-10-1082A>G, IL-10-819C>T, IL-10-592C>A, IL-12A+6686G>A, IL-12B+15485A>C. Two groups of H. pylori-infected and H. pylori-treated patients were retrospectively identified: 45 not eradicated and 57 eradicated. Treatment failure was significantly correlated with Cla(R) (all resistant strains in non-eradicated patients); with TNF-alpha-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering Cla(S)-infected patients only, logistic regression analysis (eradication = dependent; TNF-alpha-238, IL12B + 15485 genotypes, IL10 ATA/ATA as present or absent, antral gastritis grade = covariates) confirmed as significantly correlated with eradication antral gastritis grade only (Exp(B) = 6.48; 95% CI, 1.2-35.01). In conclusion, the bacterial determinant causing triple therapy failure is clarithromycin resistant, being virulence genes not involved. The host related factors that favor eradication are those linked to inflammation: a higher inflammatory infiltrate in the mucosa, possibly favored by genotypes able to down regulate the anti-inflammatory cytokine response, enhance the chance of eradication success.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clarithromycin/pharmacology , Helicobacter Infections/drug therapy , Helicobacter pylori , Adolescent , Adult , Aged , Antigens, Bacterial/genetics , Aryl Hydrocarbon Hydroxylases/genetics , Bacterial Proteins/genetics , Child , Child, Preschool , Cytochrome P-450 CYP2C19 , Drug Resistance, Microbial , Drug Therapy, Combination , Female , Gastric Mucosa , Gene Frequency , Helicobacter Infections/genetics , Humans , Interleukin-10/genetics , Male , Middle Aged , Mixed Function Oxygenases/genetics , Pharmacogenetics , Point Mutation , Polymorphism, Genetic , Treatment Outcome , Tumor Necrosis Factor-alpha/genetics , Virulence
16.
Clin Chim Acta ; 381(1): 50-5, 2007 May.
Article in English | MEDLINE | ID: mdl-17397816

ABSTRACT

This work focuses on the main DNA repair pathways, highlighting their role in gastrointestinal carcinogenesis and the role of mitochondrial DNA (mtDNA), mutations being described in several tumor types, including those of the gastrointestinal tract. The mismatch repair (MMR) system is inherently altered in patients with hereditary non-polyposis colorectal cancer, and plays a role in carcinogenesis in a subset of sporadic colorectal, gastric and esophageal cancers. Alterations in homologous recombination (HR) and non-homologous end-joining (NHEJ) also contribute to the development of pancreatic cancer. Gene polymorphisms of some X-ray cross-complementing (XRCCs), cofactor proteins involved in the base excision repair pathway, have been investigated in relation to gastric, colorectal and pancreatic cancer. Yet only one polymorphism, XRCC1 Arg194Trp, appears to be involved in smoking-related cancers and in early onset pancreatic cancer. Although evidence in the literature indicates that mtDNA somatic mutations play a role in gastric and colorectal carcinogenesis, no sound conclusions have yet been drawn regarding this issue in pancreatic cancer, although an mtDNA variant at 16519 is believed to worsen the outcome of pancreatic cancer patients, possibly because it is involved in altering cellular metabolism.


Subject(s)
DNA Repair/drug effects , DNA, Mitochondrial/genetics , Gastrointestinal Neoplasms/genetics , Mutation/physiology , Signal Transduction/drug effects , Animals , DNA Mismatch Repair , Gastrointestinal Neoplasms/pathology , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology
17.
J Pediatr Gastroenterol Nutr ; 43(5): 613-8, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17130737

ABSTRACT

OBJECTIVES: Anti-tissue transglutaminase antibody (anti-tTG) determination using second-generation (human antigen) enzyme-linked immunoassays (ELISAs) is a very accurate test to diagnose celiac disease (CD). In this study, we compared 2 second-generation ELISAs (Celikey tTG; Pharmacia Diagnostics GmbH & Co, Freiburg, Germany, and QuantaLite; Inova Diagnostics, San Diego, CA) and antiendomysial antibodies (EMAs) with a new indirect chemiluminescence immunoassay (LIAISON tTG; DiaSorin S.p.A., Saluggia, Italy) in diagnosing and monitoring CD in children. PATIENTS AND METHODS: Antiendomysial antibodies, anti-tTGs and total immunoglobulin A were measured in the sera of 103 control children, 101 children with histologically proven CD and 31 CD children on gluten-free diet (GFD). RESULTS: Anti-tissue transglutaminase antibody mean levels were significantly higher in CD with respect to control or GFD children. The sensitivity value of EMAs, LIAISON tTG, Celikey tTG and QuantaLite in diagnosing CD was 97.7%, 97.0%, 94.1% and 98.0%, respectively, and the corresponding specificity values were 91.1%, 98.1%, 97.1% and 96.1%, respectively. The degree of mucosal destruction (Marsh criteria) was correlated with EMA semiquantification (P < 0.01) and with the circulating levels of anti-tTGs measured using LIAISON (P < 0.05) or QuantaLite (P < 0.01). Twenty-six CD children were followed up from 5 to 25 months after GFD. The circulating levels of anti-tTGs measured with any of the 3 assays significantly dropped after GFD. CONCLUSIONS: Anti-tissue transglutaminase antibody determination with second-generation ELISAs is as effective as EMAs for CD diagnosis. The novel chemiluminescent method described in the present paper for the detection of anti-tTGs in the diagnosis of CD had the highest sensitivity and specificity values. The anti-tTG test correlates with the degree of mucosal destruction and is suitable for verifying patient compliance to dietary treatment.


Subject(s)
Autoantibodies/analysis , Celiac Disease/immunology , Immunoglobulin A/analysis , Luminescent Measurements , Transglutaminases/immunology , Adolescent , Celiac Disease/diagnosis , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Sensitivity and Specificity
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