ABSTRACT
BACKGROUND: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted). RESULTS: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study. CONCLUSIONS: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF. TRIAL REGISTRATION: NCT02803580.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Idiopathic Pulmonary Fibrosis/physiopathology , Vital Capacity/physiology , Aged , Disease Progression , Female , Follow-Up Studies , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Male , Prognosis , Prospective Studies , Time FactorsABSTRACT
OBJECTIVE: The Silva invasion pattern-based classification system stratifies endocervical adenocarcinomas (ECAs) into 3 categories corresponding to risk of metastasis and recurrence, but has only been evaluated for HPV-associated ECAs of usual type. We examined whether the Silva system is applicable to all endocervical adenocarcinomas, especially those not associated with HPV. METHODS: Complete slide sets from 341 surgical specimens of ECA were collected from 7 institutions worldwide. All specimens were associated with clinical records covering at least 5â¯years of follow-up. Tumors were classified as HPV-associated (HPVA) or not (NHPVA) by both morphology and detection of HPV using in situ hybridization. Recurrence and survival were analyzed by multivariate Mantel-Haenszel methods. RESULTS: Most specimens (292; 85.6%) were HPVA, while 49 (14.3%) were NHPVA. All NHPVAs were Silva pattern C, while 76.0% of HPVAs were pattern C, 14.7% pattern A, and 9.3% pattern B. Including both HPVAs and NHPVAs, lymphovascular invasion (LVI) was detected in 0% of pattern A, 18.5% of pattern B and 62.6% of pattern C cases (pâ¯<â¯0.001). None of the pattern A or B cases were associated with lymph node metastases (LNM), in contrast to pattern C cases (21.8%). Among patients with Silva pattern C ECA, those with HPVA tumors had a lower recurrence rate and better survival than those with NHPVA; however, when adjusted for stage at diagnosis, the difference in recurrence and mortality was small and not statistically significant. CONCLUSIONS: Application of the Silva system is only relevant in HPVA cervical adenocarcinoma.
Subject(s)
Adenocarcinoma/pathology , Lymphatic Metastasis/immunology , Papillomaviridae/pathogenicity , Papillomavirus Infections/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/mortality , Female , Humans , Neoplasm Recurrence, Local , Risk Factors , Survival Rate , Uterine Cervical Neoplasms/mortalityABSTRACT
BACKGROUND: Healthcare utilization data are increasingly used for chronic disease surveillance. Nevertheless, no standard criteria for estimating prevalence of high-impact diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are available. In this study an algorithm for recognizing COPD/asthma cases from HCU data is developed and implemented in the HCU databases of the Italian Lombardy Region (about 10 million residents). The impact of diagnostic misclassification for reliably estimating prevalence was also assessed. METHODS: Disease-specificdrug codes, hospital discharges together with co-payment exemptions when available, and a combination of them according with patient's age, were used to create the proposed algorithm. Identified cases were considered for prevalence estimation. An external validation study was also performed in order to evaluate systematic uncertainty of prevalence estimates. RESULTS: Raw prevalence of COPD and asthma in 2010 was 3.6 and 3.3% respectively. According to external validation, sensitivity values were 53% for COPD and 39% for asthma. Adjusted prevalence estimates were respectively 6.8 and 8.5% for COPD (among person aged 40 years or older) and asthma (among person aged 40 years or younger). CONCLUSIONS: COPD and asthma prevalence may be estimated from HCU data, albeit with high systematic uncertainty. Validation is recommended in this setting.
Subject(s)
Asthma/epidemiology , Databases, Factual , Pulmonary Disease, Chronic Obstructive/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Child , Child, Preschool , Chronic Disease , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Middle Aged , Sensitivity and Specificity , Uncertainty , Young AdultABSTRACT
INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6â min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.
Subject(s)
Bronchiectasis/diagnosis , Severity of Illness Index , Aged , Bronchiectasis/mortality , Bronchiectasis/physiopathology , Disease Progression , Europe/epidemiology , Female , Follow-Up Studies , Forced Expiratory Volume/physiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Quality of Life , Risk Assessment/methodsABSTRACT
BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.
Subject(s)
Idiopathic Pulmonary Fibrosis/drug therapy , Pyridones/administration & dosage , Vital Capacity/drug effects , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Disease Progression , Female , Humans , Idiopathic Pulmonary Fibrosis/epidemiology , Idiopathic Pulmonary Fibrosis/physiopathology , Incidence , Italy/epidemiology , Male , Retrospective Studies , Treatment OutcomeABSTRACT
Gastrointestinal stromal tumors (GISTs) represent a distinct subset of mesenchymal tumours of the gastrointestinal tract. They are more common in the stomach and small intestine, and are characterized by the proliferation of spindle or epithelioid cells and by the expression of CD117. Extra-gastrointestinal stromal tumors are rare and only 13 cases of pancreatic GISTs have been reported in the literature, only 1 of which presented as a cystic lesion. Mutational analysis of KIT and Platelet derived growth factor receptor-α genes was performed only in two out of the 13 cases. We report 3 cases of cystic GISTs of the pancreas, radiologically mimicking a cystoadenocarcinoma. Routine histopathology and molecular characterization of the tumours have been performed. In two of them, molecular analysis showed unusual genetic alterations (the internal repeat of codon 502 and 503 in exon 9 of the KIT gene and the KIT exon 9 single nucleotide substitution c.1427G⟩T). Pancreatic GIST should be included in the differential diagnosis of both cystic and solid masses of the pancreas. The diagnosis should be accomplished by a combination of radiology, histology, immunohistochemistry and molecular biology. The evaluation of CD117 expression and the sequence analysis of KIT and Platelet derived growth factor receptor-α gene is mandatory for therapy.
Subject(s)
Cystadenocarcinoma/diagnosis , Gastrointestinal Stromal Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Adult , Aged , DNA Mutational Analysis , Diagnosis, Differential , Female , Gastrointestinal Stromal Tumors/genetics , Gene Deletion , Humans , Immunohistochemistry , Male , Middle Aged , Pancreatic Neoplasms/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-kit/geneticsABSTRACT
We assessed the prevalence of interstitial lung disease (ILD) in a cohort of smokers included in a lung cancer screening trial. Two observers independently reviewed, for the presence of findings consistent with ILD, the computed tomography (CT) examinations of 692 heavy smokers recruited by the Multicentric Italian Lung Detection (MILD) trial. Four CT patterns were considered: usual interstitial pneumonia (UIP), other chronic interstitial pneumonia (OCIP), respiratory bronchiolitis (RB) and indeterminate. Subsequently, the evolution of ILD in those subjects who had undergone a repeat CT examination after 3 yrs was assessed. The UIP pattern and the OCIP pattern were identified in two (0.3%) out of 692 and 26 (3.8%) out of 692 patients, respectively; 109 (15.7%) out of 692 patients showed CT abnormalities consistent with RB, while an indeterminate CT pattern was reported in 21 out of 692 (3%) patients. Age, male sex and current smoking status were factors associated with the presence of OCIP and UIP (combined) pattern, although the relationship did not attain statistical significance. A progression of the disease was observed in three (25%) out of 12 subjects with OCIP who underwent repeat CT after 3 yrs. Thin-section CT features of ILD, probably representing smoking-related ILD, are not uncommon in a lung cancer screening population and should not be overlooked.
Subject(s)
Bronchiolitis/epidemiology , Early Detection of Cancer , Idiopathic Pulmonary Fibrosis/epidemiology , Lung Diseases, Interstitial/epidemiology , Lung Neoplasms/epidemiology , Smoking/epidemiology , Aged , Bronchiolitis/diagnostic imaging , Chronic Disease , Cohort Studies , Disease Progression , Female , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Italy/epidemiology , Lung Diseases, Interstitial/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Multicenter Studies as Topic , Prevalence , Radiography , Randomized Controlled Trials as Topic , Respiratory Function Tests , Retrospective StudiesABSTRACT
Bronchoalveolar lavage (BAL) has only a limited role in diagnosis of idiopathic pulmonary fibrosis (IPF). A finding of raised neutrophils (>5%) and eosinophils (>2%) is characteristic but not diagnostic of IPF. BAL cell count does not clearly differentiate between fibrotic non-specific interstitial pneumonia and IPF either diagnostically or prognostically. BAL in IPF should be considered in all patients with suspected infection, malignancy or acute exacerbations. In such cases, it may be diagnostic. Because of few and conflicting results BAL fluid analysis has very little clinical relevance determining prognosis and response to treatment in IPF.
Subject(s)
Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage , Idiopathic Pulmonary Fibrosis/pathology , Eosinophils , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Lymphocytes , Neutrophils , PrognosisABSTRACT
Granulomas are a frequent challenge for pathologists, which can be identified both in histological and cytological material in a number of conditions. With regard to interstitial lung diseases, granulomas can be associated with infection (e.g. mycobacterial), immunological conditions (e.g. hypersensitivity pneumonitis), or may be idiopathic (e.g. sarcoidosis). Considering morphology, features that should be identified are the presence of necrosis, the cohesiveness and coalescence of granulomas, the presence of fibrosis and the amount and quality of the associated inflammatory infiltrate. The most interesting approach to granulomatous lung disease is indeed represented by their pattern of distribution within the secondary lobule; in fact, granulomas can be distributed along lymphatic routes (e.g. sarcoidosis), randomly (miliary infections, e.g. mycobacterial and fungal infections), or along the airways (hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia and sometimes infections). We propose a combined radiological-histopathological approach for defining the morphological features and anatomic localization of granulomatous ILDs. In addition, a detailed review of their clinical features is provided, together with a description of the main procedures used to obtain respiratory samples for pathology and microbiology studies in these patients.
Subject(s)
Granuloma/diagnosis , Lung Diseases, Interstitial/diagnosis , Lung/pathology , Fibrosis , Granuloma/diagnostic imaging , Granuloma/etiology , Humans , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Necrosis , Radiography, Thoracic , Sarcoidosis, Pulmonary/pathologyABSTRACT
After the first outbreak identified in Mexico in late March 2009, influenza A sustained by a modified H1N1 virus ("swine flu") rapidly spread to all continents. This article describes the first Italian case of life-threatening ARDS associated with H1N1 infection, treated with extracorporeal respiratory assistance (venovenous extracorporeal membrane oxygenation [ECMO]). A 24-year-old, previously healthy man was admitted to the Intensive Care Unit (ICU) of the local hospital for rapidly progressive respiratory failure with refractory impairment of gas exchange unresponsive to rescue therapies (recruitment manoeuvres, pronation and nitric oxide inhalation). An extracorporeal respiratory assistance (venovenous ECMO) was performed. It allowed a correction of the respiratory acidosis and made possible the transportation of the patient to the ICU (approximately 150 km from the first hospital). A nasal swab tested positive for H1N1 infection and treatment with oseltamivir was started. The chest computed tomography scan showed bilateral massive, patchy consolidation of lung parenchyma; lab tests showed leukopenia, elevated CPK levels and renal failure. The patient required high dosages of norepinephrine for septic shock and continuous renal replacement therapy. The clinical course was complicated by Pseudomonas aeruginosa superinfection, treated with intravenous and aerosolised colistin. ECMO was withheld after 15 days, while recovery of renal and respiratory function was slower. The patient was discharged from the ICU 34 days after admission. In this case, ECMO was life-saving and made the inter-hospital transfer of the patient possible.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human/complications , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Humans , Male , Young AdultABSTRACT
The respiratory system may be involved in all systemic vasculitides (SV), although with a variable frequency. Lung disease is a very common and important feature of the antineutrophil cytoplasmic antibodies (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). In WG, almost all patients have either upper airway or lower respiratory tract disease. Solitary or multiple nodules and masses are the most common findings on chest radiograph. Asthma is a cardinal symptom of CSS, often preceded by allergic rhinitis, frequently complicated by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar infiltrates are the most common radiographic findings. In MPA, diffuse alveolar hemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation of the respiratory involvement, clinically expressing with hemoptysis, respiratory distress and anemia. However, DAH may be subclinical and has to be suspected when chest radiograph demonstrates new unexplained bilateral alveolar infiltrates, in the face of falling hemoglobin levels. In giant cell arteritis, the most frequent respiratory symptom is cough, usually non-productive, persistent, and responsive to corticosteroids. In Takayasu arteritis, pulmonary involvement is frequently subclinical and detectable by non-invasive techniques. Pulmonary involvement is rare in polyarteritis nodosa, Kawasaki disease, Henoch-Schönlein purpura and cryoglobulinemic vasculitis. In conclusion, the involvement of the respiratory system is a very common and important feature of AASV, whereas is less frequent in other SV. It comprises a wide spectrum of clinical features and radiological findings, and may have a prognostic significance. The assessment of the respiratory system should be included in the work-up of all patients with SV, especially of those with AASV.
Subject(s)
Lung Diseases/etiology , Vasculitis/complications , Antibodies, Antineutrophil Cytoplasmic/analysis , Antibodies, Antineutrophil Cytoplasmic/immunology , Antibodies, Antineutrophil Cytoplasmic/physiology , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/pathology , Churg-Strauss Syndrome/physiopathology , Giant Cell Arteritis/complications , Giant Cell Arteritis/pathology , Giant Cell Arteritis/physiopathology , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/pathology , Granulomatosis with Polyangiitis/physiopathology , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/physiopathology , Lung Diseases/diagnostic imaging , Lung Diseases/pathology , Lung Diseases/physiopathology , Radiography , Takayasu Arteritis/complications , Takayasu Arteritis/pathology , Takayasu Arteritis/physiopathology , Vasculitis/classification , Vasculitis/immunology , Vasculitis/pathology , Vasculitis/physiopathologyABSTRACT
BACKGROUND: Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus (HCV) infection after liver transplantation. PATIENTS/METHODS: HCV-infected cirrhotic patients randomised to tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1 mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3 months. RESULTS: Twenty-seven patients (MT) and 29 (TT)--median follow up 661 days (range, 1-1603). Rejection episodes (protocol/further biopsies) within first 3 months and use of empirical treatment were evaluated. New rejection was diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with 19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46 (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%), with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal dysfunction, retransplantation, and death were not significantly different. CONCLUSION: Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected liver transplant recipients.
Subject(s)
Graft Rejection/prevention & control , Hepatitis C/therapy , Immunosuppressive Agents/therapeutic use , Liver Cirrhosis/therapy , Liver Transplantation , Tacrolimus/therapeutic use , Adult , Aged , Azathioprine/therapeutic use , Drug Therapy, Combination , Female , Hepatitis C/complications , Humans , Liver Cirrhosis/virology , Liver Transplantation/immunology , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Prednisolone/therapeutic use , Secondary Prevention , Survival Analysis , Time Factors , Transplantation, Homologous , Treatment OutcomeABSTRACT
Pneumonia is common in those patients placed in intensive care units, especially in mechanically ventilated patients. The high mortality rate of ventilator-associated pneumonia requires a rapid initiation of the appropriate antibiotic treatment. Patients who do not respond to initial antibiotic regimens could have the additional benefit of the use of invasive techniques such as bronchoalveolar lavage. Moreover, BAL is of clinical use to identify several non-infectious pulmonary conditions that may mimic pneumonia in these patients. Such conditions include pulmonary haemorrhages, acute eosinophilic pneumonia, malignancy, drug-induced toxicity, adult respiratory distress syndrome and cardiogenic pulmonary oedema. It is important to distinguish these conditions from pneumonia because the management and prognosis of these entities is quite different.
Subject(s)
Bronchoalveolar Lavage/methods , Intensive Care Units , Pneumonia, Bacterial/diagnosis , Humans , Microbiological Techniques , Pneumonia, Bacterial/etiology , Pneumonia, Bacterial/microbiology , Pulmonary VentilationABSTRACT
BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.
Subject(s)
Asthma/drug therapy , Cysteine/metabolism , Dinoprost/analogs & derivatives , F2-Isoprostanes/metabolism , Leukotrienes/metabolism , Adolescent , Asthma/diagnosis , Asthma/physiopathology , Biomarkers/analysis , Breath Tests , Child , Female , Forced Expiratory Volume/physiology , Glucocorticoids/therapeutic use , Humans , Male , Nitric Oxide/metabolism , Peak Expiratory Flow Rate/physiology , Prednisone/therapeutic useABSTRACT
BACKGROUND: Despite more recent technical advances, single detector spiral computed tomography is still the most widely used imaging technique for the detection and staging of pancreatic adenocarcinoma. Many reports have recently focused on single detector spiral computed tomography imaging findings indicative of unresectability AIM: To evaluate the ability of single detector spiral computed tomography in the pre-operative staging of ductal adenocarcinoma of the pancreas in selecting surgically resectable versus unresectable cases, considering different parameters (vascular and local infiltration, liver metastases, lymphadenopathy, and peritoneal carcinomatosis). PATIENTS AND METHODS: A total of 100 patients diagnosed with ductal adenocarcinoma of the pancreas, pathologically verified, and examined with single detector spiral computed tomography were considered. Of these, 63 underwent surgery; 37 were excluded (imaging evidence of unresectability in biopsy-proven adenocarcinomas). Single detector spiral computed tomography studies, performed at the time of surgery, were retrospectively reviewed by two radiologists. The final results were reached by consensus, without being aware of the operation. All prospective clinical readings were also considered, and tabulated. RESULTS: In the patients undergoing surgery, 44 proved to be unresectable and 19 resectable. Considering the above-mentioned parameters, the prospective assessment of resectability demonstrated a rather low sensitivity (68%), with high specificity (95%). Accordingly, a high positive predictive value (97%) was achieved, while the negative predictive value was 56%. After the retrospective evaluation, the value of sensitivity increased (84%) to the expense of the specificity (84%). Moreover, a positive predictive value of 92.5%, and a negative predictive value of 69.5% were obtained. CONCLUSIONS: The demonstration of many signs of unresectability of pancreatic ductal adenocarcinoma reported in the literature yields a better sensitivity in the diagnosis, but unfortunately, is associated with an inevitable reduction in specificity.
Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Tomography, Spiral Computed , Female , Humans , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
Previous studies on the effect of seasonal exposure to the sensitizing antigen on T-cell cytokine pattern from atopic subjects evaluated T-cell cytokine production by titration in the serum or culture supernatants. The purpose of this study was to determine the seasonal variations of T-cell cytokine pattern from atopic subjects at the single-cell level. We examined the interleukin-4 (IL-4) and interferon-gamma expression in peripheral blood CD4 + and CD8 + T cells from 11 subjects with grass-pollen-sensitive allergy before and during the 1999 grass pollen season using a flow cytometric method of intracellular cytokine detection. Eight healthy volunteers served as the control group. Flow cytometric analysis of peripheral blood lymphocytes showed no seasonal variations of IL-4- and interferon-gamma-producing T cells in atopic subjects. However, there was a decreased percentage of IL-4-producing cells among peripheral blood CD4+ and CD8+ T cells from the atopic subjects both during and outside the pollen season in comparison to the controLs. We did not find seasonal variations of T-cell cytokine pattern in peripheral blood from atopic subjects. However, we observed a decreased percentage of IL-4-producing T cells in peripheral blood from these subjects in comparison to healthy controls. These data add to the view of a continuous migration of T helper 2 (TH2) cells from the blood to the tissues of primary allergen exposure.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Respiratory Hypersensitivity/blood , Respiratory Hypersensitivity/immunology , Adult , Female , Humans , Male , SeasonsABSTRACT
Nitrosothiols (RS-NOs) are formed by interaction of nitric oxide (NO) with glutathione and may limit the detrimental effect of NO. Because NO generation is increased in airway inflammation, we have measured RS-NOs in exhaled breath condensate in patients with asthma, cystic fibrosis, or chronic obstructive pulmonary disease (COPD). We also measured exhaled NO and nitrite (NO(2-)) in the same subjects. RS-NOs were detectable in exhaled breath condensate of all subjects. RS-NOs were higher in subjects with severe asthma (0.81 +/- 0.06 microM) when compared with normal control subjects (0.11 +/- 0.02 microM, p < 0.01) and with subjects with mild asthma (0.08 +/- 0.01 microM, p < 0.01). Elevated RS-NOs values were also found in patients with cystic fibrosis (0.35 +/- 0.07 microM, p < 0.01), in those with COPD (0.24 +/- 0.04 microM, p < 0.01) and in smokers (0.46 +/- 0.09 microM, p < 0.01). In current smokers there was a correlation (r = 0.8, p < 0.05) between RS-NOs values and smoking history (pack/year). We also found elevated concentrations of NO(2-) in patients with severe asthma, cystic fibrosis, or COPD, but not in smokers or patients with mild asthma. This suggests that exhaled NO(2-) is less sensitive than exhaled RS-NOs. This study has shown that RS-NOs are detectable in exhaled breath condensate of healthy subjects and are increased in patients with inflammatory airway diseases. As RS-NOs concentrations in exhaled breath condensate vary in the different airway diseases and increase with the severity of asthma, their measurement may have clinical relevance as a noninvasive biomarker of nitrosative stress.
Subject(s)
Asthma/physiopathology , Cystic Fibrosis/physiopathology , Lung Diseases, Obstructive/physiopathology , Mercaptoethanol , Nitroso Compounds/metabolism , S-Nitrosothiols , Smoking/physiopathology , Adult , Aged , Biomarkers/analysis , Breath Tests , Female , Humans , Inflammation/physiopathology , Male , Middle Aged , Nitric Oxide/metabolism , Nitroso Compounds/analysis , Probability , Prognosis , Reference Values , Respiratory Function Tests , Sensitivity and Specificity , Severity of Illness Index , Statistics, NonparametricABSTRACT
A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF-PETs) has been generated by microsatellite analysis of DNA from 16 frozen cases, each probed with 394 markers. Two subgroups of NF-PETs were found. Seven cases showed frequent, large allelic deletions [loss of heterozygosity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas nine cases showed a small number of random losses with a FAL of 0.15. Designated high or low FAL, respectively, these genetic phenotypes showed correlation with the ploidy status: high-FAL tumors were aneuploid, low-FAL were diploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of cases had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH. The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as well as from that of functional-PETs. Moreover, whereas deletions involving chromosome 11 also are a feature of functional-PETs, the involvement of chromosome 6q is characteristic of NF-PETs. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent factor adding prognostic information to that furnished by the proliferative index measured by Ki-67 immunohistochemistry.