Safety and Immunogenicity of V114 in Preterm Infants: A Pooled Analysis of Four Phase Three Studies.

BACKGROUND: Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in PCV13 plus 2 unique serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 pediatric phase 3 studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. METHODS: Healthy preterm infants were randomized 1:1 to receive V114/PCV13 in the 4 studies. Safety was evaluated as the proportion of participants with adverse events (AEs) following receipt of PCV. Serotype-specific antipneumococcal immunoglobulin G (IgG) geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were measured at 30 days postdose 3, pretoddler dose and 30 days postdose 4. RESULTS: V114 and PCV13 were administered to 174 and 180 participants, respectively. Mean gestational age was 35.4 weeks (range: 27 - <37 weeks). Proportions of participants with AEs were comparable between vaccination groups; most AEs experienced were of short duration (≤3 days) and mild-to-moderate intensity. V114-elicited IgG geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days postdose 3 and postdose 4. CONCLUSIONS: In preterm infants, V114 was well tolerated and induced comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to serotypes 22F and 33F. Results support the use of V114 in preterm infants.

Influence of Ion Nitriding on Microstructure and Properties of Haynes 282 Nickel Superalloy Specimens Produced Using DMLS Technique.

The paper investigates the influence of the ion-nitriding process on the microstructure, corrosion resistance, and tensile strength at elevated temperatures of Haynes 282 nickel superalloy specimens produced by the Direct Metal Laser Sintering (DMLS) technique. The study was performed for two conditions, i.e., as-built by DMLS method and as-built by DMLS method + covered by a layer containing CrN + Cr2N phases. An analysis of the surface morphology revealed that the ion-nitriding process significantly affects the physical and chemical phenomena occurring on the specimen's surface. The XRD measurement of the specimens showed that preparing them with the DMLS method as well as following a nitriding process produced residual tensile stresses. Based on the measurement of the nanohardness distribution through the layer approximatively of 7 µm in width and the superalloys substrate, the results of the nanohardness showed the maximum values of 27 GPa and 13.5 GPa for the nitrided layer and the substrate, respectively. The surface protection from the nitrided layer proved a positive effect on the corrosion resistance of the DMLS specimens in the solution of 0.1 M Na2SO4 + 0.1 M NaCl at room temperature. The results of the tensile tests at 750 °C showed that the ion-nitriding process did not significantly affect the elevated-temperature tensile strength of the superalloy specimens produced with the DMLS technique.

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1).

BACKGROUND: V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines. METHODS: V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. RESULTS: 1184 healthy infants 42-90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 µg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa-HBV-IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa-HBV-IPV/Hib and anti-rotavirus IgA geometric mean titers. CONCLUSIONS: After a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31.

Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2).

BACKGROUND: This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F. METHODS: Healthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F. RESULTS: 1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 µg/mL (lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose. Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates. CONCLUSION: A two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.

Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS).

Background: Lebrikizumab is a monoclonal antibody that modulates activity of interleukin-13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled asthma despite standard-of-care treatment. Methods: Adolescents (aged 12-17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%-90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks. Results: Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio [RR] 0.49 [95% CI 0.28-0.83]; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 [95% CI 0.35-1.03]; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/µl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 [95% CI 0.21-0.89]; 37.5 mg: 0.42 [95% CI 0.19-0.93]). Treatment-emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred. Conclusion: Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results. Clinical trial registration: NCT01875003 (www.ClinicalTrials.gov).

Improving the Properties of Composite Titanium Nitride Layers on the AZ91D Magnesium Alloy Using Hydrothermal Treatment.

Coating magnesium alloys with nitride surface layers is a prospective way of improving their intrinsically poor surface properties; in particular, their tribological and corrosion resistance. These layers are usually produced using PVD methods using magnetron sputtering or arc evaporation. Even though the thus-produced layers significantly increase the wear resistance of the alloys, their effects on corrosion resistance are unsatisfactory because of the poor tightness, characteristic of PVD-produced products. Tightness acquires crucial significance when the substrate is a highly-active magnesium alloy, hence our idea to tighten the layers by subjecting them to a post-deposition chemical-hydrothermal-type treatment. This paper presents the results of our experiments with a new hybrid surface engineering method, using a final tightening pressure hydrothermal gas treatment in overheated steam of the composite titanium nitride layers PVD, produced on AZ91D magnesium alloy. The proposed method resulted in an outstanding improvement of the performance properties, in particular resistance to corrosion and wear, yielding values that exceed those exhibited by commercially anodized alloys and austenitic stainless 316L steel. The developed hybrid method produces new, high-performance corrosion and wear resistant, lightweight magnesium base materials, suitable for heavy duty applications.

Hybrid a-CNH+TiO2+TiN-type surface layers produced on NiTi shape memory alloy for cardiovascular applications.

AIM: The goal was to improve the properties of NiTi shape memory alloy to make it suitable for cardiac applications. For this purpose, a hybrid a-CNH+TiO2+TiN-type surface layer was produced on NiTi alloy and characterized. MATERIALS & METHODS: The NiTi alloy subjected to hybrid process combining low-temperature oxynitriding under glow discharge conditions and radio frequency chemical vapor deposition process was examined for microstructure, surface topography, corrosion resistance, wettability and surface-free energy, Ni ion release and platelets adhesion, aggregation and activation. RESULTS: The hybrid surface layers showed slightly increased surface roughness, better corrosion resistance, a more hydrophobic nature, decreased surface free energy, smaller release of nickel ions and reduced platelets activation. CONCLUSION: The produced layers could expand the range of NiTi medical applications.

Hydrostatic Extrusion and Nano-Hardness of Nanocrystalline Grade 2 Titanium.

The structure and corrosion resistance of Grade 2 titanium subjected to the hydroextrusion processes were examined. The microstructure was characterized using optical microscopy and transmission electron microscopy. The corrosion resistance was determined using the impedance and potentiodynamic methods, in 0.1 M H2SO4 solutions and an acidified 0.1 M NaCl solution with a pH of 4.2, at ambient temperature. Nanohardness tests were performed under a load of 100 mN. It has been demonstrated that the hydroextrusion method makes it possible to obtain relatively homogeneous nanocrystalline titanium Grade 2 with an increased hardness, the elastic modulus almost unchanged with respect to that of the initial structure and a lower corrosion resistance.

[Patient with haemoptysis, dyspnoea, fever and lung infiltration]. / Chory z krwiopluciem, dusznoscia , stanami goraczkowymi i naciekiem w plucach.

In this study we presented the case of 55 years old man who was admitted to the Dept. of Lung Diseases and Tuberculosis in Zabrze with haemoptysis, dyspnoea, fever and lung infiltration. Initially the neoplastic disease was diagnosed. From the information gathered from the patient's family it was stated that the patient has been taking acenocoumarol for a considerably long time without any professional supervision. In this study we emphasize the importance of motivating and informing patients about the purposefulness of control examinations while using this kind of drugs.

[Diagnostic difficulties in diffuse pulmonary infiltrations]. / Trudnosci diagnostyczne zmian rozsianych w plucach.

We described a case of 26-year-old woman, with the history of cough and exercise dyspnoea. Chest X-ray and HRCT examination showed diffuse interstitial infiltration. Histopathological examination of supraclavicular lymph nodes and lung tissue obtained by transbronchial biopsy revealed metastatic adenocarcinoma. Despite several examinations, including gastroscopy- the primary site of cancer was not established. Rapid progression of the disease led to death. Post-mortem examination revealed diffuse gastric carcinoma as the primary neoplasm.

[Invasive pulmonary aspergillosis as a complication of prolonged antibiotic therapy]. / Aspergiloza inwazyjna pluc jako powiklanie dlugotrwalej antybiotykoterapii.

In this study we present the case of 53 year old woman hospitalized in the Department of Lung Diseases and Tuberculosis in Zabrze, Silesian Medical University in Katowice, due to chronic cough and infiltration in the chest radiogram. Prior to the admission, the patient received long-lasting antibiotic ambulatory treatment leveled at laryngobronchitis. After admission the patient underwent bronchofiberoscopy during which a sample for mycological examination of bronchoalveolar lavage was taken. The result of the examination made possible to give the diagnosis--invasive pulmonary aspergillosis. Proper antifungal treatment was used and in consequence considerable improvement in both clinical and radiological state was achieved. Invasive pulmonary aspergillosis is mostly diagnosed in immunocompromised patients. The patient described in this case had none risk factors. Based on that particular case we may state a hypothesis that a prolonged antibiotic therapy is an important risk factor of invasive pulmonary aspergillosis incidence.

[Mucoepidermoid carcinoma of the lung--case reports]. / Rak sluzowo-nablonkowy oskrzela--opis przypadków.

Two patients, a young woman and a young man, with mucoepidermoid carcinoma of the lung, who were diagnosed at the Department of Phthisiopneumonology in Zabrze Silesian Medical University in Katowice are described. The principal method of diagnostics in the presented cases were bronchofiberoscopy followed by the histopathological examination of the lesions. There are no cases of massive bleeding as the side effect of this procedures described. This type of carcinoma of the lung is mostly found in young patients, usually without any risk factors of lung cancer, what confirms the rule, that all pulmonological symptoms of unknown origin should be verified by bronchoscopy, because other methods of diagnostics, including TC of chest-like in our patient, may be false-negative. The method of choice in the treatment of mucoepidermoid carcinoma is surgery. One should avoid a through bronchoscope resection, as it may be only partial. Metastases, mostly found in the local lymph nodes, are rarely described.

[Survey of bronchoscopy in the Pulmonology Centers of the Upper Silesian region in 2002. Part I. Doctor and patient]. / Bronchoskopia w oddzialach chorób pluc w Województwie Slaskim w 2002 roku: wyniki badania ankietowego. Czesc I--Lekarz i Pacjent.

The aim of the study is to present the up-to-date data concerning bronchoscopy in the Silesian region in the year 2002. The study was performed as a survey. The survey was mailed to all the 18 pulmonological centres in the silesian region. Questions included in the survey, were divided into three groups: Doctor, Patient, Performance. This article, which is the first part of the analysis, presents data concerning doctors and patients. We conclude, on the ground of the collected data, that there are differences in performing bronchoscopy in the analysed centres. It may result from the fact, that the practice is often guided by personal experience and some drugs and diagnostic procedures are not equally available. It seems to be necessary to perform prospective clinical studies in order to indicate the optimal procedures in bronchoscopy.

[Survey of bronchoscopy in the Pulmonology Centers of the Upper Silesian region in 2002. Part II. Performance]. / Bronchoskopia w oddzialach chorób pluc w województwie slaskim w 2002 roku: wyniki badania ankietowego. Czesc II--Wykonywanie badania.

The aim of the study is to present the up-to-date data concerning bronchoscopy in the Silesian region in the year 2002. The study was performed as a survey. The survey was mailed to all the 18 pulmonological centres in the silesian region. The questions included in the survey, were divided into three groups: Doctor, Patient, Performance. This article, which is the second part of the analysis, presents data concerning the Performance. We conclude, on the ground of the collected data, that there are differences in performing bronchoscopy in the analysed centres. It may result from the fact, that the practice is often guided by personal experience and some drugs and diagnostic procedures are not equally available. It seems to be necessary to perform prospective clinical studies in order to indicate the optimal procedures in bronchoscopy. One should also recommend to work up up-to-date instructions for the postgraduate training in the fields of bronchology.

[Broncho-alveolar lavage cells are the most significant reservoir of human cytomegalovirus genome]. / Komórki z popluczyn oskrzelowo-pecherzykowych (BAL) istotnym rezerwuarem genomu ludzkiego wirusa cytomegalii.

The aim of the study is to estimate human cytomegalovirus DNA copy number in different compartments (BAL cells, blood leukocytes, serum) in patients with idiopathic pulmonary fibrosis (IPF). There were 16 patients (mean age 40.87 +/-10.97; 9 males, 7 females) with newly diagnosed and so far not treated IPF included in the study. The diagnosis of IPF was confirmed by typical HRCT findings and/or lung biopsy histopathological examination (result of the biopsy: "usual interstitial pneumonia"). There were also 16 adult volunteers (mean age 36.75 +/- 6.43; 12 males, 4 females) included in the study as a control group. Using the real-time quantitative polymerase chain reaction the HCMV DNA copy number was estimated. The prevalence of HCMV DNA positive subjects in the IPF group (75%) was higher, but did not differ significantly from the control group (69%). The HCMV DNA copy number in 1 million BAL cells was significantly higher comparing to blood leukocytes, both in IPF and control group (log10 = 2.7 vs. 1.2 for IPF and 2.8 vs. 0.9 for control, respectively). Higher mean HCMV DNA copy number was observed in IPF patients comparing to control group (log10 = 3.2 for IPF and 2.0 for control) in 1 mL of blood serum. We concluded that the lungs play an important role in human cytomegalovirus latency and infection reactivation and thus could be a cofactor modulating the course of IPF in humans. The contribution of HCMV infection in IPF patients should be taken into account during immunosuppression therapy planning.

[Chronic obstructive pulmonary disease in inhabitants of Zabrze]. / Przewlekla obturacyjna choroba pluc u mieszkanców miasta Zabrza.

In 2001 a modified MRC questionnaire and spirometry were performed in the inhabitants of Zabrze (Poland). Two hundred and thirty-nine men and 320 women aged 19-69 years were studied. Forty percent of men and 23% of women were smokers. In men but not in women a decline in smoking habit was observed as compared with previous studies in Zabrze carried out in the eighties. More men (32%) than women (19%) gave up smoking. The prevalence of chronic productive cough was closely related to smoking habit. Dyspnea and wheezing were also related to smoking but less strongly than productive cough. The prevalence of COPD (diagnosed according to GOLD criteria) was 10.2%. COPD was more common in smokers than in non-smokers, especially among men (19% and 2% respectively). Persistent productive cough, wheezing and advanced dyspnoea as well as intensive smoking (more than 40 pack years) were strongly connected with the prevalence of COPD. COPD was previously diagnosed in more than 50% of subjects identified as having COPD in this study. Almost 80% of subjects with COPD were not given any treatment in the past year.