Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300.

Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy. Trial registration: ClinicalTrials.gov: NCT02625623.

[Endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) in neoplastic Barrett's esophagus or Barrett early cancer is also economically superior to sole radical endoscopic resection]. / Endoskopische Mukosaresektion (EMR) mit nachfolgender Radiofrequenzablation (RFA) bei neoplastischem Barrett-Ösophagus bzw. Barrett-Frühkarzinom ist der alleinigen radikalen endoskopischen Resektion auch ökonomisch überlegen.

INTRODUCTION: Neoplastic changes (mild or high grade intraepithelial neoplasia (L- or HGIEN) or early cancer) in Barrett esophagus are treated with various methods. This study compares clinical-economical aspects of sole stepwise radical endoscopic resection (SRER) against combination treatment with EMR (Endoscopic mucosal resection) and RFA (radiofrequency ablation). MATERIAL AND METHODS: Based on clinical data from a randomized controlled trial 1 we developed an economic model for costs of treatment according to the German Hospital Remuneration System (G-DRG). Our calculating incorporated initial treatment costs and the cost of treating complications (both paid via G-DRG). RESULTS: Medical and economically, the treatment with EMR + RFA advantages over sole SRER treatment 1. The successful complete resection or destruction of neoplastic intestinal metaplastic tissue is similar in both procedures. Acute complications (24 vs. 13 % in SRER EMR + RFA) and late complications (88 vs. 13 % in SRER EMR + RFA) are significantly more likely in sole SRER than in the EMR + RFA. DISCUSSION: While SRER initially appears more cost-effective as a sole therapy, cost levels move significantly above EMR+RFA due to higher complication rates and following procedures costs. Overall, the costs of treatment was €â€Š13 272.11 in the SRER group and €â€Š11 389.33 in the EMR + RFA group. The EMR + RFA group thus achieved a cost advantage of €â€Š1882.78. The study shows that the treatment of neoplastic Barrett esophagus with EMR + RFA is also appropriate in economic terms.

A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203).

BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.

Microbial population dynamics in the faeces of wood-eating loricariid catfishes.

UNLABELLED: Catfishes of the genus Panaque are known for their ability to feed on wood and hence to process cellulose fibres in their digestive systems. The paper industry uses cellulose fibres and thus has an interest in exploiting this property biomimetically: it could be employed as a pretreatment to lessen the energy required by the mechanical production stage of manufacturing nanocellulose fibres. Here, we characterize the diet-associated in situ microbial diversity and population dynamic in the faeces of catfish (Panaque sp.) exposed to consecutive diets of pellet food and then wood. Fish faeces samples were collected and investigated by parallel DNA deep amplicon sequencing of the bacterial 16S rRNA SSU for both diet conditions. The most frequently occurring bacterium in the faeces was Cetobacterium sp. The dominant cellulolytic bacterial genera found in ascending relative abundance were as follows: Aeromonas sp., Flavobacterium sp., Bacteroides sp., Pseudomonas sp. and Cellvibrio sp. Diet-associated changes in the faeces microbiome were noted for Flavobacterium sp. Extensive microbial diversity was found in catfish faeces, evidenced using culture-independent molecular techniques. No significant diet-associated effects on the microbiome in terms of biodiversity were observed in the catfish faeces, but diet-associated changes in the microbial population structure were observed. SIGNIFICANCE AND IMPACT OF THE STUDY: Although catfishes are not classified as true xylivores, inhabiting their faeces are bacteria that may provide a novel source of cellulolytic enzyme. Based on this first microbiology study, the faeces and thus the gastrointestinal microbiome of Panaque catfishes are an unexplored reservoir of microbial extracts with enhanced polysaccharide transforming enzyme activity. The biomimetical exploitation of this cellulolytic activity in the form of novel enzymes or by applying a mixture of cellulolytic micro-organisms could accomplish a pretreatment to the mechanical production process of nanocellulose fibres, thus could reduce the energy consumption costs significantly.

Knowledge, attitudes and practices related to the COVID-19 outbreak among Romanian adults with cancer: a cross-sectional national survey.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic outbreak forced cancer care providers to face different challenges in terms of prevention and treatment management due to specific precautions implemented for oncological patients. We aimed to describe the level of knowledge, attitude and practices (KAP) among cancer patients, with the purpose to provide an image of the impact of COVID-19 and evaluate the effectiveness of pandemic response measures. PATIENTS AND METHODS: We developed a cross-sectional multicentric study that targeted adults with active cancer during the COVID-19 outbreak, aiming to describe KAP related to COVID-19 among Romanian oncological patients. A questionnaire investigating 64 items on KAP related to the novel coronavirus was designed and applied in seven Romanian hospitals. The group of participants consisted of 1585 oncological patients who completed the questionnaire during the outbreak (April-May 2020). RESULTS: Only 172 patients (10.8%) had very good knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection symptoms, treatment options and incubation period. Only 44.3% of patients identified diarrhoea as a sign of COVID-19. About one-third of patients (32.6%) declared that they are 'very worried' about getting infected with the novel coronavirus. More than two-thirds of participants (68%) considered that having cancer represents an additional risk for infection with SARS-CoV-2, but 27.8% would rather not vaccinate against SARS-CoV-2 should a vaccine be available. A small percentage (8.8%) believed that the risk of infection justifies delaying/stopping oncological treatment until after the pandemic. Around half of the participants (55.5%) declared being compliant with all the protective measures against coronavirus infection listed in the questionnaire. CONCLUSION: Romanian oncological patients have a less than expected knowledge about SARS-CoV-2, appropriate prevention behaviours, with limited trust in their efficacy, optimistic attitudes towards COVID-19 and low level of trust in information sources. Good COVID-19 knowledge was associated with appropriate practices towards COVID-19 and optimistic attitudes.

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Molecular Profiling of EGFR Status to Identify Skin Toxicity in Colorectal Cancer: A Clinicopathological Review.

Colorectal cancer (CRC) represents an important health problem, being the third most common type of cancer. In Romania, the CRC incidence has doubled over the years. Both environmental factors and genetic susceptibility are very important for the pathogenesis of CRC. The epidermal growth factor receptor (EGFR) plays an extremely important role in CRC tumorigenesis. Overexpression or dysregulation of EGFR pathway molecules are frequently associated with tumor aggressiveness and patient response to treatment. Based on these considerations, EGFR became one of the first targets of molecular therapies used in CRC. At present, cetuximab and panitumumab are considered to be essential in the treatment of patients with metastatic colorectal cancer expressing the KRAS wild-type gene and EGFR. The main adverse effect for both cetuximab and panitumumab is skin toxicity, present in approximately 80% of patients. The risk of secondary infections, in particular of bacterial infections, is also increased. Cases of staphylococcal infection associated with skin peeling, cellulite, erysipelas, and even Staphylococcus sepsis, were reported. For a long time cutaneous toxicity has been a positive predictor in the efficacy of anti-EGFR treatment, but compliance with treatment and the quality of life of patients with metastatic CRC decreases in the presence of these skin reactions. That is why we emphasize the necessity and importance of using a modern method (molecular analysis of gene polymorphisms possibly supplemented by targeted confocal laser endomicroscopy) to identify a molecular diagnosis, in order to foresee and prevent the appearance of skin reactions and to manage skin toxicity.

[Procalcitonin as a tool for the assessment of successful therapy of severe sepsis : An analysis using clinical routine data]. / Procalcitonin als Instrument zur Erfolgsmessung der Therapie einer schweren Sepsis : Eine Untersuchung mit klinischen Routinedaten.

INTRODUCTION: Procalcitonin (PCT) is a well-evaluated biomarker for the detection of severe bacterial infections and monitoring effectiveness of antibiotic therapy. This study aims to evaluate the usefulness of PCT in a clinical routine setting. MATERIALS AND METHODS: Of 358,763 clinical cases from 7 German hospitals in 2012 and 2013, 3854 cases had an ICD-10 code representing sepsis. A total of 1778 cases had pathologic PCT and one episode of infection. Of those, 671 showed a series of measures that was suitable to assess treatment success using PCT reduction. Propensity score matching was used to create two comparable groups with 211 patients in each group. RESULTS: The group with PCT reduction within 12 days showed a highly significant better proportion of survival (146/211 vs. 17/211; p < 0.0001). The odds ratio for death according to PCT reduction vs. nonreduction is 25.64 (p < 0.0001; 95 % CI: 14.49-45.45). PCT was normalized after an average of 6.2 days. DISCUSSION: The difference in survival implicates that PCT reduction is a suitable surrogate parameter to indicate successful antimicrobial therapy. Successful antibiotic therapy is a proven predictor for survival in sepsis. This study also showed concordant results in the group of patients with sepsis after abdominal surgery. Results from subgroup analyses confirm the initial findings. PCT reduction was used as surrogate for therapy success, as the antimicrobial therapy was not electronically available. CONCLUSION: PCT reduction is a strong predictor for survival. However, the data show that overall use of PCT to monitor sepsis therapy is not yet routinely established. Hospitals should establish algorithms for sepsis treatment that include PCT for the assessment of adequacy and the monitoring of success of the antimicrobial therapy.

The Effect of Season and Weather on Orthopaedic Trauma: Consult Volume Is Significantly Correlated with Daily Weather.

INTRODUCTION: On-call orthopedic clinicians have long speculated that daily consult volume is closely correlated with weather. While prior studies have demonstrated a relationship between weather and certain fracture types, the effect of weather on total orthopaedic consult volume has not yet been examined. The aim of this study was to investigate this relationship. METHODS: We retrospectively reviewed orthopaedic consult data from 405 consecutive days at an urban, level one trauma center. The number, mechanism of injury, and type of consult were collected, along with daily weather data (temperature, wind, and precipitation). Statistical analysis was then performed to determine the relationship between weather and orthopaedic trauma consults. RESULTS: A total of 4543 consults were received during the study period. There was a significant difference in total number of consults between months of the year (p<0.001). A post hoc analysis revealed that this was due to increased volume in the summer months relative to the winter months (i.e., August 13.7 consults/day; January 9.3 consults/day). Average daily temperature and consult volume were also positively correlated (p<0.001, r= 0.30). While there was no significant association between precipitation and total consult volume, when there was over 0.25 inches of rain, there were less penetrating trauma (p=0.034) and motorcycle collision consults (p=0.013). CONCLUSION: Weather parameters, specifically average temperature and precipitation, were found to be associated with daily orthopedic consult type and volume. Additionally, consult volume varies significantly between months of the year. Because trauma centers are often resource scarce, this is an important relationship to understand for proper resource allocation.

Correlations between CD34 Immunolabelled Blood Vessels and CD34 mRNA Expression in Colorectal Cancer.

PURPOSE: This study aims to determine the correlation between microvessel density of CD34 immunolabelled blood vessels and CD34 mRNA gene expression in colorectal cancer tissue. MATERIAL/METHODS: Standard immunohistochemistry and gene expression was perform on samples collected from 76 patients with colorectal cancer in order to determinate the number of CD34 immunolabelled blood vessels and the relative quantity of CD34 mRNA. RESULTS: For the study group, the mean CD34 immunolabelled microvascular density (MVD) was of 307/mm2, and the mean CD34 gene expression value for colon cancer was 2.303. The low p value (<0.001) of the Spearman correlation test showed a significant direct correlation between CD34 MVD and CD34 gene expression for the entire study group. CONCLUSIONS: CD34 gene`s expression can be looked at as a prognostic factor in colorectal cancer.

Hepatitis C Infection in Hemodialysis Patients.

Three centuries after the identification of hepatitis C virus (HCV), specialized literature has outlined the epidemiology, viral kinetics and clinical manifestations of this infection. A major cause of morbidity-mortality in patients with renal transplantation and in hemodialysis patients is HCV infection. In high seroprevalence countries, internal accounts are not uniform. The European trend is to decrease the incidence and prevalence of HCV in hemodialysis patients. In Europe, the prevalence of HCV infection among hemodialysis patients tends to be higher than that of the general population, but it is variable by region. Some studies indicate a decrease in incidence in parallel with prevalence in dialysis centers over the last 10 years, while others maintain a high incidence. In some countries, as is the case with Romania, both prevalence and incidence remain high, with the major route of transmission being nosocomial, probably due to limited resources for a rapidly growing dialyzed population. Some authors recommend more isolation measures to be taken in centers with high prevalence of infection.

Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study.

The temporal development of autoantibodies was studied in 1,353 offspring of parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring had islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detected thereafter were likely to represent a true de novo production, since prevalences were the same for offspring from mothers and fathers with diabetes, antibodies detected at 9 months were almost always confirmed in the 2-year sample and were associated with an increased likelihood of having or developing other antibodies. By 2 years of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody. IAAs were detected most frequently, and few had autoantibodies in the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional antibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk.

GADIA2-combi determination as first-line screening for improved prediction of type 1 diabetes in relatives.

A new radiobinding assay for the simultaneous detection of antibodies to GAD and the tyrosine phosphatase IA2 has been recently described in patients with newly diagnosed type 1 diabetes. Here we assessed sensitivity and predictive value of this GADIA2-combi test in first-degree relatives of type 1 diabetic patients compared with islet cell antibody (ICA) and insulin autoantibody (IAA) screening. Of 1,606 relatives, 77 (4.8%) had elevated GADIA2-combi titers above the 99th percentile of 105 nondiabetic control subjects, and results were confirmed by testing these samples for GAD antibody (GADA) and tyrosine phosphatase IA2 antibody (IA2A) in the single antibody test (29 GADA+/IA2A+, 44 GADA+/IA2A-, and 4 IA2A+/GADA-). A further 9 of 1,606 relatives had detectable ICA (1) or IAA (8), but they were negative in the GADIA2-combi assay as well as in the single test for GADA or IA2A. Twenty-four relatives progressed to IDDM within a median follow-up time of 5.6 years (range 0.5-8.2). The sensitivity of antibody determination in relatives with progression to IDDM was 92% for the GADIA2-combi assay, 96% for the combined testing of IAA and GADIA2-combi antibodies, and 83, 67, 67, and 79%, respectively, for GADA, IA2A, IAA, or ICA testing alone. The cumulative life-table risk of antibody-positive relatives was related to GADIA2-combi titers (5-year risk: >50 U, 51% [95% CI 30-73]; >10 to 50 U, 12% [1-24]; <10 U, 0.17% [0-0.5]; P=0.0001) and on the presence of IA2A in addition to GADA (5-year risk: GADA+/IA2A+, 47% [25-68]; GADA+/IA2A-, 15% [2-28]; P=0.006). In those with detectable antibodies, risk was not associated with age (<15 vs. >15 years) or relation to proband (offspring, sibling, parent). Relatives with GADIA2-combi antibodies >10 U and the additional presence of IAA had a slightly higher diabetes risk than relatives without IAA (5-year: IAA+, 46% [23-68]; IAA-, 19% [6-32]; P=0.07). Furthermore, low first-phase insulin release after intravenous glucose tolerance test was associated with risk in relatives with GADIA2-combi antibodies (P=0.01). These results indicate that the GADIA2-combi test is a valuable marker for first-line screening and risk assessment of type 1 diabetes in relatives. It can be used for venous as well as capillary blood samples.

Costs of hepatitis C.

OBJECTIVE: To estimate the direct and indirect costs of the hepatitis C virus (HCV) in the United States in 1997. DESIGN: Aggregation and analysis of national data sets collected by the National Center for Health Statistics, the Health Care Financing Administration, and other government bureaus and private firms. To estimate costs, we used the human capital method, which decomposes costs into direct categories, such as medical expenses, and indirect categories, such as lost earnings and lost home production. We consider HCV that results in chronic liver disease separate from HCV that results in primary liver cancer. RESULTS: We estimate $5.46 billion as the cost of HCV in 1997. Costs are split as follows: 33% for direct and 67% for indirect costs. Hepatitis C virus that results in chronic liver disease contributes roughly 92% of the costs, and HCV that results in primary liver cancer contributes the remaining 8%. The total estimate of $5.46 billion is conservative, because we ignore costs associated with pain and suffering and the value of care rendered by family members. CONCLUSIONS: To our knowledge, only one estimate of the annual costs of HCV in the 1990s has appeared in the literature, $0.6 billion. However, that estimate was not supported by an explanation of the methods. Our estimate, which relies on detailed methods, is nearly 10 times the original estimate. Our estimate of $5.46 billion is on a par with the cost of asthma ($5.8 billion [1994]).

No major association of breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB Study.

OBJECTIVE: Environmental factors have been suggested to play an important role in the pathogenesis of type 1 diabetes. The aim of this study was to assess the influence of breast-feeding, vaccinations, and childhood viral diseases on the initiation of islet autoimmunity in early childhood. RESEARCH DESIGN AND METHODS: Data were prospectively collected from questionnaires obtained at birth, at 9 months of age, and at 2 years of age in 823 offspring from parents with type 1 diabetes. By 2 years of age, 31 offspring had islet antibodies, and 10 developed overt diabetes by the time of follow-up. RESULTS: In offspring from mothers with type 1 diabetes, duration of exclusive and total breast-feeding did not differ between islet antibody-positive and -negative children, regardless of HLA genotype, and breast-feeding of 3 months or longer was not associated with protection from antibody development or diabetes onset. In offspring from diabetic fathers, non-statistically significant reductions in exclusive and total breast-feeding times were observed in the antibody-positive cohort. Neither type nor quantity of vaccinations (including Bacille Calmette-Guerin vaccine; haemophilus influenzae vaccine; diphtheria, tetanus, and pertussis vaccine; tick-born encephalitis vaccine; or measles, mumps, and rubella vaccine) were associated with the development of islet antibodies and diabetes. Measles, mumps, and rubella were not reported in children with islet antibodies or diabetes. CONCLUSIONS: This study showed no evidence that proposed environmental factors affect islet antibody development in the first 2 years of life in offspring from parents with type 1 diabetes.

The value of serum and tissular expression of CA 125 antigen, in evaluation of the response to second line chemotherapy for the relapsed ovarian carcinoma.

PURPOSE: The purpose of this study is to compare the predicted value of the blood levels variations of CA 125 antigen and the imunohistochemical expression of CA 125, with imagistic criteria (The Response Evaluation Criteran in Solid Tumor--RECIST) regarding the survival estimation of female patients with relapsed ovarian carcinoma which undergo to second line chemotherapy. MATERIAL AND METHOD: We included in this study 40 female patients diagnosed with ovarian carcinoma in the Oncology Clinic of the Emergency County Hospital Craiova, in a period of two years (from 2000 to 2002), which have fulfilled the following criteria: ovarian carcinoma IC-IV stage, according to FIGO system, first line treatment represented by the association between paclitaxel and a platinum salt, refractory or recurrent disease, indications for beginning the second line chemotherapy represented by topotecan or paclitaxel and carboplatin. The serial CA 125 antigen was determined in all patients before starting the chemotherapy and after each two sequences of chemotherapy, and the imunohistochemical expression of CA 125 was evaluated from surgery extracts before the second line chemotherapy (11 cases). The imagistic evaluation of the treatment response was done after 4 sequences of chemotherapy. RESULTS: All patients had measurable disease according to RECIST criteria and had high values (at least double) of the CA 125 antigen blood level at the time of diagnosis. The imunohistochemically expression of CA 125 was correlated in most cases with the blood level of CA 125. The evaluation criterion of the CA 125 antigen has been shown to be more efficient in estimation the survival rate compared with the RECIST system. In a various analysis, which included numerous potential prognostic factors, only the variation of blood levels of these antigen and the free disease interval from the finalization of the first line chemotherapy have been identified as predictive factors of survival, while the other variables, including the RECIST criteria, had no impact on the prognosis regarding the survival. CONCLUSIONS: The response evaluation criteria based on the blood levels variations of CA 125 antigen are a better instrument for the estimation of the compared prognosis with the RECIST criteria, for patients on second line chemotherapy for relapsed ovarian carcinoma.

Autophagy and Neovascularization in Colorectal Cancer.

PURPOSE: This study aims to determinate the microvessel density at the base of the tumor, as well in tumor's mass, in order to determinate the number of neovascularization vessels (marked with CD105) in comparison with presence or absence of autophagy puncta. MATERIAL/METHODS: Standard immunohistochemistry was performed on 38 samples of colorectal adenocarcinoma, in order to determinate the presence of autophagy and neovascularization blood vessels with the help of LC3, CD34, CD31 and CD105 antibodies. RESULTS: The autophagy process was observed in the cancerous cells and was noted as present in both regions of interest from the tumor. The mean number of blood vessels market with CD105 is higher in tumor mass then at its base, p value of the Student t test being highly significant (p<0.0001). CONCLUSIONS: The presence of autophagy puncta was notice in every case, both in the mass of the tumor and at its base. Microvascular density of new-grown blood vessels is higher in the mass of the tumor compared with the base of the tumor.

Exposures and health effects from inorganic agricultural dusts.

Most studies of respiratory disease from dust exposure in the agricultural workplace have focused on allergic diseases caused by inorganic dusts, specifically occupational asthma and hypersensitivity pneumonitis. Exposures to inorganic (mineral) dusts among farmers and farm workers may be substantial. Such exposures are most frequent in dry-climate farming regions. In such locations farming activities that perturb the soil (e.g., plowing, tilling) commonly result in exposures to farm operators of 1-5 mg/m(3) respirable dust and >= 20 mg/m(3) total dust. The composition of inorganic dust in agriculture generally reflects the soil composition. Crystalline silica may represent up to 20% of particles, and silicates represent up to 80%. These very high concentrations of inorganic dust are likely to explain some of the increase in chronic bronchitis reported in many studies of farmers. Pulmonary fibrosis (mixed dust pneumoconiosis) has been reported in agricultural workers, and dust samples from the lungs in these cases reflect the composition of agricultural soils, strongly suggesting an etiologic role for inorganic agricultural dusts. However, the prevalence and clinical severity of these cases are unknown, and many exposures are to mixed organic and inorganic dusts. Epidemiologic studies of farmers in diverse geographic settings also have observed an increase in chronic obstructive pulmonary disease morbidity and mortality. It is plausible that agricultural exposure to inorganic dusts is causally associated with chronic bronchitis, interstitial fibrosis, and chronic obstructive pulmonary disease, but the independent contribution of mineral dusts beyond the effects of organic dusts remains to be determined.

Distribution of particulate matter and tissue remodeling in the human lung.

We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H(2)O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter.