The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Overcoming barriers to opioid-induced constipation management in cancer patients.

PURPOSE: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients. METHODS: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus. RESULTS: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification. CONCLUSIONS: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.

Potential control of the infective stage of Taenia pisiformis using Bacillus thuringiensis GP526 strain.

The GP526 strain of Bacillus thuringiensis has been referred as an in vitro helminthicide on various stages of Dipylidium caninum and Centrocestus formosanus. Our study addresses the in vitro ovicidal activity of GP526 strain spore-crystal complex on Taenia pisiformis eggs, evaluating induced damage microscopically. The eggs exposed to the total extract containing spores and crystals show damage after 24 hours, with loss of integrity on the eggshell, and an ovicidal activity of 33% at 1mg/ml. The destruction of the embryophore was observed after 120 h with a 72% of ovicidal activity at 1 mg/ml. The LC50 was 609.6 µg/ml, dose that causes a 50% of lethality on the hexacanth embryo, altering the oncosphere membrane. The spore-crystal proteins were extracted, and the protein profile was obtained by electrophoresis, finding a major band of 100 kDa suggestive of an S-layer protein, since an S-layer was immunodetected in both, spores and extracted proteins. The protein fraction containing the S-layer protein presents adhesion to the T. pisiformis eggs, and 0.4 mg/ml of the protein induces a lethality of 21.08% at 24 h. The characterization of molecular mechanisms of ovicidal activity will be an important contribution, so the characterization of the proteins that make up the extract of the GP526 strain, would be useful to support the biological potential for control of this cestodiasis and other parasitosis. B. thuringiensis is shown as a potent helminthicide on eggs, with useful potential for biological control of this cestodiasis.

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review.

OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. METHODS: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. RESULTS: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. CONCLUSION: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.

Incidence of COVID-19 in outpatients with cancer receiving active treatment in the context of a pandemic: An Andalusian cohort study.

BACKGROUND: Leading scientific societies have recommended delaying and/or suspending active cancer treatment during the COVID-19 pandemic. Nevertheless, data on this novel infection in patients with a diagnosis of cancer receiving active treatment are scarce and it is unknown if these recommendations could have repercussions on future progress of the disease. The main objective of this study is to learn the COVID-19 incidence rate in outpatients with cancer receiving active treatment. METHODS: This work is a retrospective cohort study that included all patients with a diagnosis of cancer who received active cancer treatment in two Andalusian hospitals between February 26 and May 13, 2020. Variables regarding the patient, tumor, and development of COVID-19 were collected. A descriptive analysis was performed and the cumulative incidence of COVID-19 in these patients was evaluated. RESULTS: A total of 673 patients were included. The median age was 62 years. There was a low rate of comorbidity and 12.1% had an ECOG >2. Breast cancer was the most common cancer (41%), followed by colorectal and lung cancer. Stage IV cancer was reported in 52.7% of patients. The most common treatment was chemotherapy (53.9%). Treatment was delayed or suspended in 6% of patients. Only three patients developed COVID-19. The cumulative incidence was 0.44% and one person died due to infection. CONCLUSIONS: In the present retrospective cohort study we found a low incidence of COVID-19 infection in patients with cancer receiving active treatment in an outpatient setting. The sociodemographic factors of Andalusia may explain why these results differ from those presented by other colleagues in Spain, but raise questions about whether universal recommendations may put the benefits of antineoplastic therapy at risk.

Effects of Taenia Pisiformis Infection and Obesity on Clinical Parameters, Organometry and Fat Distribution in Male Rabbits.

Taenia pisiformis infection causes important economic loss in farms. It is suggested that obesity has a major impact on infection and reproduction. We addressed the impact of T. pisiformis infection in normal and obese rabbits to evaluate its effect on parameters important in behavior and reproduction. T. pisiformis infection in obese rabbits decreased body weight. In the obese-infected rabbits, eosinophils and heterophiles were increased 23% by the infection (P ≤ 0.05). T. pisiformis decreased cholesterol by 13% in normal weight infected rabbits and 10% in obese group (P ≤ 0.05), while triglyceride and VLDL were increased by 23% and 45% in the non-infected obese group (P ≤ 0.05). The infection increased serum cortisol levels only in normal weight rabbits (P ≤ 0.05). Liver weight was 20% higher in obese and obese-infected rabbits (P ≤ 0.05). Testicular weight in obese-infected was 46% higher than normal weight (P ≤ 0.0001) and 20% more than the obese-non-infected (P ≤ 0.0001). Furthermore, the infection reduced the weight of submandibular glands in infected and obese-infected rabbits (P ≤ 0.05), body fat increased 10% in the obese-infected than in the obese, and infected group was 35% over the normal weight non-infected (P ≤ 0.01). Our results show that T. pisiformis alters metabolic characteristics in rabbits, which can impact on the production and welfare of animals.

Nematicidal and ovicidal activity of Bacillus thuringiensis against the zoonotic nematode Ancylostoma caninum.

Ancylostoma caninum is a gastrointestinal parasite that affect dogs and humans, considered a worldwide public health problem. The control of these parasitosis is increasingly difficult due to the development of multi-drug resistance. Bacillus thuringiensis is an insecticidal, spore forming bacterium, often species specific. The strain GP526 of B. thuringiensis has toxic effect on the cestode Dipylidium caninum and the trematode Centrocestus formosanus, both of them zoonotic parasites. The high degrees of specificity and environment safe make B. thuringiensis suitable for use against pathogen parasites, especially those resistant to synthetic chemical insecticides. The objective of the current work was to evaluate the in vitro effect of B. thuringiensis on Ancylostoma caninum. Spore-crystal mixture of the strains was co-incubated with 120 adult nematodes (males, non-pregnant females and pregnant females) or with 4800 eggs. GP526 showed a nematicidal effect with an LT50 of 35.8 h and an LC50 of 60 µg/ml. It also showed an ovicidal effect with an LC50 of 94.9 µg/ml. Histological analyses showed detachment of the cuticle and of the uterus in adult females, and vacuolization with destruction of the eggs. The effects of GP526 strain were comparable to those of albendazole, allowing us to propose GP526 for A. caninum control, in both, the adult stage at a gastrointestinal level, and in egg stage in the environment. In addition, GP526 can be proposed as a potential broad spectrum antiparasitic drug.

Influence of the interaction between cysticercosis and obesity on rabbit behavior and productive parameters.

Parasites induce behavioral changes in the host and obesity is a health problem affecting different animal species. Cysticercosis caused by Taenia pisiformis affects some behavior of rabbits and reproductive behavior of does. Rabbits do not escape from metabolic disorders, being long-live animals useful in breeding, research and companion animals. Here, we addressed the interaction between parasitosis and obesity, and studied how these conditions or the comorbidity affect behavioral and productive parameters in bucks infected with 3000 T. pisiformis eggs. We found that the chronic infection reduced locomotor activity by 28.5% in obese, 18.5% in infected and 47% in obese-infected group (comorbid). The exploratory activity reduced by 42% in obese, 48% in infected and 68% in comorbid rabbits (P ≤ 0.001). Chinning was not affected by obesity, while infection decreased it by 25%. Behavioral reproductive parameters like response time, the mount latency and number of ejaculates were affected by infection and obesity. Furthermore, obesity seems to increase the parasite load promoting the formation of liver granulomas (16% granulomas compared with normal weight), with a higher number of cysticerci in obese animals (86% more than normal weight). Infection decreases body weight, body mass index and the zoometric index BW/LV in obese and normal weight rabbits. In conclusion, infection with T. pisiformis altered behavioral and productive parameters, and obesity magnifies the impact caused by the infection. Also, obesity leads to major susceptibility to infection with T. pisiformis.

Allergic sensitization increases the amount of extracellular ATP hydrolyzed by guinea pig leukocytes.

Increased levels of ATP have been found in the bronchoalveolar lavage of patients with asthma, and subjects with this disease, but not healthy subjects, develop bronchospasm after nebulization with ATP. Because the main mechanism for controlling the noxious effects of extracellular ATP is its enzymatic hydrolysis, we hypothesized that allergic sensitization is accompanied by a decreased functioning of such hydrolysis. In the present study, peripheral blood leukocytes from sensitized and non-sensitized guinea pigs were used for determining the extracellular metabolism (as assessed by inorganic phosphate production) of ATP, ADP, AMP, or adenosine, and for detecting possible changes in the expression (qPCR and Western blot) of major ectonucleotidases (NTPDase1, NTPDase3, and NPP1) and purinoceptors (P2X1, P2X7, P2Y4, and P2Y6). Contrary to our hypothesis, we found that leukocytes from allergic animals produced higher amounts of inorganic phosphate after stimulation with ATP and ADP, as compared with leukocytes from non-sensitized animals. Although at first glance, this result suggested that sensitization caused higher efficiency of ectonucleotidases, their mRNA and protein expressions were unaffected. On the other hand, after sensitization, we found a significant increase in the protein expression of P2X7 and P2Y4, two purinoceptors known to be responsible for ATP release after activation. We concluded that allergic sensitization increased the amount of ATP hydrolyzed by ectonucleotidases, the latter probably not due to the enhanced efficiency of its enzymatic breakdown, but rather due to an increased release of endogenous ATP or other nucleotides, partly mediated by enhanced expression or P2X7 and P2Y4 receptors.

Nutritional risk and malnutrition rates at diagnosis of cancer in patients treated in outpatient settings: Early intervention protocol.

OBJECTIVES: Malnutrition is frequent in patients with cancer and is associated with a higher rate of morbidity and mortality. However, a significant number of patients at nutritional risk remain undetected due to the lack of a routine screening procedure during diagnosis. Costa del Sol Hospital in Marbella (Málaga), Spain has implemented a protocol for outpatients with cancer aimed at identifying and treating malnutrition at an early stage. The aim of this study was to determine the prevalence of nutritional risk and the rate of malnutrition when cancer is diagnosed. METHODS: We conducted a complete assessment of the nutritional status of patients with cancer of the upper digestive tract (esophagus, stomach, pancreas, or biliary tract) or head and neck cancer. Using the Nutriscore tool at the first oncology consultation, a screening for nutritional risk was performed for patients with other solid tumors. When nutritional risk was detected, a complete nutritional assessment was conducted. RESULTS: Of 295 consecutive patients, 21.4% were found to be at nutritional risk (Nutriscore ≥5). After complete assessment, a moderate degree of malnutrition was observed in 76% and severe malnutrition in 12%. Among patients with colorectal cancer or tumors of gynecologic origin, only 7.5% presented nutritional risk, but 52.8% presented cachexia. CONCLUSION: The high rate of malnutrition observed and the identification of cachexia at an early stage highlight the importance of obtaining early identification of patients at risk to improve the efficacy of nutritional interventions.

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8-8.1). The median PFS was 5.3 months (95% CI 3.2-7.3), and OS was 9.7 months (95% CI 7.6-11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0-1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00-€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0-1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

Behavioral and hormonal changes associated with the infective dose in experimental taeniasis in golden hamsters (Mesocricetus auratus).

INTRODUCTION: It has been reported that behavioral changes relate to infection in different parasitoses. However, the relation between the extent of the behavioral changes and the magnitude of the infection has been scarcely studied. The aim of this study was to evaluate the relationship between different doses of infection and the behavioral changes induced in the experimental Taenia pisiformis taeniasis in golden hamsters. METHODS: Groups of nine hamsters were infected with three or six T. pisiformis metacestodes. The locomotor activity was quantified daily in an open field test during the 21 days after infection; anxiety test was performed in an elevated plus-maze with a dark/light area at 7, 14 and 21 days post-infection, and serum cortisol levels were determined by radioimmunoassay before infection and at day 22 after infection. RESULTS: The challenge itself induced modifications on behavior and cortisol levels in hamsters, with or without successful infection (taenia development). Animals challenged with three metacestodes induced a decrease in locomotor activity and an increase in anxiety in infected animals. A higher and earlier decrease in locomotor activity and increased anxiety levels were observed in hamsters challenged with six cysticerci, which were accompanied by higher levels of sera cortisol at the end of the experiment. At necropsy, 44-55% of hamster became infected with an efficiency of implantation of 22-26%, challenged with three or six cysticerci respectively. CONCLUSION: The challenge of hamsters with metacestodes, promote behavioral changes in an extent dependent on the magnitude of the challenge, disregarding the effectiveness of the infection.

[Respiratory day hospital care for immunocompetent adult patients with community-acquired pneumonia]. / Hospitalización diurna como modelo de atención de salud en pacientes adultos inmunocompetentes con neumonía adquirida en la comunidad.

BACKGROUND: Day hospitals can reduce health care costs without increasing the risks of patients with lower respiratory tract infection. AIM: To report the experience of a respiratory day hospital care delivered to adult patients with community-acquired pneumonia (CAP) in a public hospital. MATERIAL AND METHODS: During the fall and winter of 2011 and 2012, adult patients with CAP of intermediate risk categories were assessed in the emergency room, their severity was stratified according to confusion, respiratory rate, blood pressure, 65 years of age or older (CRB-65) score and the Chilean CAP Clinical Guidelines, and were admitted to the respiratory day hospital. RESULTS: One hundred seventeen patients aged 67 ± 16 years, (62% females) with CAP were attended in the respiratory day hospital. Ninety percent had comorbidities, especially chronic obstructive pulmonary disease in 58%, heart disease in 32%, diabetes in 16% and asthma in 13%. Their most important risk factors were age over 65 years in 60%, comorbidities in 88%, failure of antibiotic treatment in 17%, loss of autonomy in 21%, vital sign abnormalities in 60%, mental confusion in 5%, multilobar CAP in 23%, pleural effusion in 15%, hypoxemia in 41% and a serum urea nitrogen over 30 mg/dL in 16%. Patients stayed an average of seven days in the day hospital with oxygen, hydration, chest physiotherapy and third-generation cephalosporins (89%) associated with quinolones (52%) or macrolides (4%). Thirteen patients required noninvasive ventilation, eight patients were hospitalized because of clinical deterioration and three died in hospital. CONCLUSIONS: Day hospital care reduced hospital admission rates of patients with lower respiratory tract infections.

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 µg/mL) compared with those with PAPA syndrome (116 ± 74 µg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD. METHODS: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups. RESULTS: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05). CONCLUSIONS: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects. VIRTUAL SLIDES: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160.

Anakinra: new therapeutic approach in children with Familial Mediterranean Fever resistant to colchicine.

Familial Mediterranean fever (FMF), a recessively inherited autoinflammatory disorder, is the prototype of a group of disorders termed systemic autoinflammatory diseases. Such diseases are characterized by seemingly unprovoked episodes of inflammation without evidence of high-titer autoantibodies or antigen-specific T cell. Repeated bouts of inflammation may lead to systemic AA protein deposition, making FMF a potentially fatal disease. Pyrin, the protein mutated in FMF, regulates caspase-1 activation and consequently IL-1beta production. Although colchicine is the standard prophylactic therapy for attacks and amyloid deposition, some patients fail to respond or cannot tolerate its side effects. Anticytokine therapies have shown promise in the treatment of autoinflammatory disorders in children. We report on the use of the recombinant interleukin 1 receptor antagonist anakinra in one child with therapy-resistant FMF. The patient experienced immediate, sustained resolution of symptoms and laboratory markers of inflammation, and also, possibly, a reduced long-term risk of AA amyloidosis.

Efficacy of bosentan in treatment of unresponsive cutaneous ulceration in disabling pansclerotic morphea in children.

Disabling pansclerotic morphea (PM) of childhood is a rare and debilitating variant of localized scleroderma. We describe a 4-year-old girl with rapid progression of deep cutaneous fibrosis extending into the muscle fascia with disabling joint contractures of the hips, knees, ankles, and fingers and recalcitrant ischemic ulcerations. Within the first months of therapy with dual oral endothelin receptor antagonist bosentan (31.25 mg qd for 4 weeks [DOSAGE ERROR CORRECTED], then 31.25 mg bid) limb ulcers improved, with resolution of the widespread sclerotic skin lesions. Joint mobility improved, and a substantial decrease of skin thickness was noted. No side effects were noted. In the context of other data in scleroderma, bosentan may be a promising option in the treatment of PM.