Forensic DNA databases in Western Balkan region: retrospectives, perspectives, and initiatives

The European Network of Forensic Science Institutes (ENFSI) recommended the establishment of forensic DNA databases and specific implementation and management legislations for all EU/ENFSI members. Therefore, forensic institutions from Bosnia and Herzegovina, Serbia, Montenegro, and Macedonia launched a wide set of activities to support these recommendations. To assess the current state, a regional expert team completed detailed screening and investigation of the existing forensic DNA data repositories and associated legislation in these countries. The scope also included relevant concurrent projects and a wide spectrum of different activities in relation to forensics DNA use. The state of forensic DNA analysis was also determined in the neighboring Slovenia and Croatia, which already have functional national DNA databases. There is a need for a 'regional supplement' to the current documentation and standards pertaining to forensic application of DNA databases, which should include regional-specific preliminary aims and recommendations.     

Immunohistochemical validation of multiple phospho-specific epitopes for estrogen receptor α (ERα) in tissue microarrays of ERα positive human breast carcinomas

Estrogen receptor α (ERα) activity is regulated by phosphorylation at several sites. Recently several antibodies specific for individual phosphorylated sites within ERα have became available. Such antibodies potentially provide invaluable tools to gain insight into the relevance in vivo of phosphorylated ERα in human breast tumors. However, validation of these antibodies for immunohistochemistry in particular is necessary in the first instance. In this study we have investigated the usefulness of several antibodies generated to specific phosphorylated sites within ERα for immunohistochemistry of formalin-fixed, paraffin-embedded human breast cancer biopsy samples. As well, these data demonstrate for the first time, the detection of multiple phosphorylated ERα forms in breast cancer (P-S104/106-ERα, P-S118-ERα, P-S167-ERα, P-S282-ERα, P-S294-ERα, P-T311-ERα, and P-S559-ERα) suggesting the possibility that profiling of phosphorylated ERα isoforms might be useful in selecting subgroups of breast cancer patients that would benefit from endocrine therapy.     

Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia

Abstract Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated lucatumumab in a phase I clinical trial in chronic lymphocytic leukemia (CLL). Twenty-six patients with relapsed CLL were enrolled on five different dose cohorts administered weekly for 4 weeks. The maximally tolerated dose (MTD) of lucatumumab was 3.0 mg/kg. Four patients at doses of 4.5 mg/kg and 6.0 mg/kg experienced grade 3 or 4 asymptomatic elevated amylase and lipase levels. Of the 26 patients enrolled, 17 patients had stable disease (mean duration of 76 days, range 29-504 days) and one patient had a nodular partial response for 230 days. Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts. At the MTD, the median half-life of lucatumumab was 50 h following the first infusion, and 124 h following the fourth infusion. In summary, lucatumumab had acceptable tolerability, pharmacokinetics that supported chronic dosing and pharmacodynamic target antagonism at doses of 3.0 mg/kg, but demonstrated minimal single-agent activity. Future efforts with lucatumumab in CLL should focus on combination-based therapy.     

Diagnostic accuracy and complication rates of percutaneous CT-guided coaxial needle biopsy of pulmonary lesions

PURPOSEThe aim of this retrospective study was to evaluate and compare diagnostic accuracy and complication rates of percutaneous computed tomography (CT)-guided biopsies of pulmonary lesions 10–35 mm, 35–50 mm, and >50 mm, using the coaxial biopsy technique.METHODSOver a 4-year period, 235 lung biopsies were performed using the coaxial biopsy technique with 18G semi-automated true-cut needle. There were 163 (69.4%) male and 72 (30.6%) female patients, with a mean age of 64.01±9.18 years (18–85 years). The mean lesion size was 59.6±29.3 mm. The lesions were stratified into three groups according to size: lesions <35 mm (n=42, 17.9%), lesions 35–50 mm (n=53, 22.5%), and lesions >50 mm (n=140, 59.6%). Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for all biopsies, and for each group separately, as well as the incidence of complications.RESULTSThe overall diagnostic accuracy was 95.4%, with 95.52% sensitivity, 100% specificity, 100% PPV, and 47.37% NPV. For lesions <35 mm, diagnostic accuracy, sensitivity, and PPV were 100%. The lowest diagnostic accuracy was 93.9% in lesions >50 mm, with 93.65% sensitivity, 100% specificity, 100% PPV, and 42.86% NPV. An adequate sample was obtained in 219 core biopsies (93.2%), while 16 biopsies (6.8%) were nondiagnostic due to necrosis (4.25%) and insufficient biopsy material (2.55%). The most frequent complication was minor pneumothorax, which was seen at a rate of 19.1%; pneumothorax requiring chest tube placement occurred in 3 patients (1.3%).CONCLUSIONDiagnostic accuracy decreased with increasing lesion size. On the other hand, complication rates were higher in smaller lesions, more distanced from the pleura.

Computed tomography (CT)-guided percutaneous needle biopsy is a well-established method in the diagnostic algorithm of various pulmonary lesions, with two types of biopsy techniques employed, fine-needle aspiration biopsy (FNAB) and core biopsy (CB). Both techniques yield high diagnostic accuracy for carcinomas, from 89% in FNAB to 98% in CB (1). Coaxial biopsy technique has a reported overall diagnostic accuracy for both malignant and benign lesions ranging from 82.6% to 95% (2–4).Besides the needle type, other factors such as lesion size, nature of the lesion, experience and skills of interventional radiologist influence the diagnostic accuracy. Lesion size ≥1 cm is reported as a significant risk factor decreasing diagnostic accuracy, but in published data lesions >5 cm and even ≥3.1 cm, are also identified as factors that decrease the diagnostic accuracy mainly due to the higher rates of necrosis (4, 5).The most frequent complication in lung biopsy is pneumothorax, with the reported pooled rate 25.3% for CB and 18.8% for FNAB (6).The aim of this retrospective single-center study was to determine diagnostic accuracy and complication rates of percutaneous CT-guided coaxial lung biopsies of pulmonary lesions stratified by lesion size into <35 mm, 30–50 mm, and >50 mm lesions, as well as to identify the relevant risk factors.     

Lung involvement in systemic connective tissue diseases

BACGROUND/AIM: Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems.Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. METHODS: In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. RESULTS: Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). CONCLUSION: Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.