Sigurnost rada u anatomskom laboratoriju s formalinom i inovativno praćenje procjene profesionalne izloženosti formaldehidu

This review is directed at preventive health professionals, anatomic pathologists and technicians to focus their attention on the rapidly growing field of safe formalin practices. An updated overview of the most recent improvements in preventive measures versus formaldehyde (FA) in the anatomic pathology laboratories (APL) is provided. The occupational hygienist role and the required knowledge for a modern and clear occupational exposure assessment are described. Real-time, in-continuous, commercial analyzers for repeated FA exposure assessment are considered to evaluate technical changes in air monitoring programs, introduced to mitigate FA emissions, in compliance with the adopted limit values. To better choose the adequate instrumentation, the main features of each FA monitoring instrument recently introduced on the market are listed. Moreover, the main features of the modern workflow setting in APL are summarized. A computer-based scientific and non-scientific reports search by key-words was performed on PubMed, Web of Science, Google Scholar and Google Patents databases, querying the following topics: i) grossing workstation for ergonomic layout, ii) commercially available direct reading tools to measure formalin, iii) real-time, in-continuous FA monitoring instruments for sale. This review represents a useful tool to summarize the technical requirements and expert know-how necessary to minimize FA emissions and produce an exhaustive FA assessment in the APL.Ovaj pregled usmjeren je na preventivne zdravstvene radnike, anatomske patologe i tehničare kako bi svoju pozornost usredotočili na brzo rastuće područje sigurnih formalinskih praksi. Ažurirani pregled nudi najnovija poboljšanja preventivnih mjera u odnosu na formaldehid (FA) u laboratorijima za anatomsku patologiju (APL). Opisana je uloga higijeničara na radu i potrebna znanja za modernu i jasnu procjenu izloženosti na radu. Komercijalni analizatori u stvarnom vremenu za kontinuiranu procjenu izloženosti FA razmatraju se za procjenu tehničkih promjena u programima praćenja zraka, uvedenim radi ublažavanja emisija FA, u skladu s prihvaćenim graničnim vrijednostima. Kako bi se bolje odabrala odgovarajuća instrumentacija, navedene su glavne značajke svakog instrumenta za praćenje FA koji je nedavno predstavljen na tržištu. Štoviše, sažete su glavne značajke suvremenih postavki tijeka rada u APL-u. Računalno zasnovano pretraživanje znanstvenih i neznanstvenih izvješća po ključnim riječima provedeno je u bazama podataka PubMed, Web of Science, Google Scholar i Google Patents, s težištem na sljedeće teme: i) prikupljanje radnih stanica za ergonomski raspored, ii) komercijalno dostupni alati za izravno očitanje mjerenja formalina, iii) instrumenti za kontinuirano praćenje FA u stvarnom vremenu u prodaji. Ovaj pregled predstavlja koristan alat za sažimanje tehničkih zahtjeva i stručnog znanja potrebnog za minimiziranje emisija FA i izradu iscrpne procjene FA u APL-u

Integrated FDG-PET/CT imaging is useful in the apporach to carcinoid tumors of the lung

Background. Carcinoids enter the differential diagnosis of the solitary pulmonary nodule. Bronchial carcinoids have been traditionally considered as FDG-PET negative but recent studies have found an higher sensitivity of integrated FDG-PET/CT for the detection of these neoplasms. The purpose of this study was to investigate the value of integrated FDG-PET/CT for the evaluation of SPN suspected to be carcinoids. Methods. All patients with pathologically proven bronchial carcinoids who had FDG-PET/CT scans between 2006 and 2012 have been retrospectively reviewed. PET/CT was performed with the same scanner and the same technique for all patients. The following data were retrieved: age, sex CT findings (side, location, size, shape, margins), SUVmax, type of operation, pathological findings (size and number of mitoses). Regarding PET findings, only SUVmax was considered, whereas the visual assessment was not undertaken. Carcinoids were defined as typical and atypical and as central and peripheral. The long-term follow-up was also recorded. The SUVmax was compared with the other clinical, radiological and pathological variables to find any significant difference or correlation. Results. Twenty-five patients were retrieved, 24 typical and one atypical carcinoid, 21 peripheral and 4 central lesions. The mean diameter on CT-scan was 25.3mm and the clinical size correlated well with the pathological size. Fifty-six percent of the tumors were ovoid and 68% had smooth margins. The mean SUVmax was 3.6 (range 1.4-12.9). All the lesions were completely resected. The regression analysis showed a direct correlation between the SUVmax and the tumor size (p=0.004). No further correlations were found between the SUVmax and the other variables. None of the patients had recurrent disease or died during the follow-up. Conclusions. Our study showed that FDG-PET/CT might be a useful tool in the evaluation of SPNs suspected to be bronchial carcinoids. When a solitary pulmonary nodule shows an ovoid/round shape and smooth margins on the CT scan and demonstrates an FDG uptake higher than that of the normal lung and with a SUVmax value >1-1.5, a carcinoid should be suspected. If benign lesions can be presumably excluded, surgical resection or at least a biopsy of the lesion is recommended

Tuneable peptide cross-linked nanogels for enzyme-triggered protein delivery

Many diseases are associated with the dysregulated activity of enzymes, such as matrix metalloproteinases (MMPs). This dysregulation can be leveraged in drug delivery to achieve disease- or site-specific cargo release. Self-assembled polymeric nanoparticles are versatile drug carrier materials due to the accessible diversity of polymer chemistry. However, efficient loading of sensitive cargo, such as proteins, and introducing functional enzyme-responsive behaviour remain challenging. Herein, peptide-crosslinked, temperature-sensitive nanogels for protein delivery were designed to respond to MMP-7, which is overexpressed in many pathologies including cancer and inflammatory diseases. The incorporation of N-cyclopropylacrylamide (NCPAM) into N-isopropylacrylamide (NIPAM)-based copolymers enabled us to tune the polymer lower critical solution temperature from 33 to 44 °C, allowing the encapsulation of protein cargo and nanogel-crosslinking at slightly elevated temperatures. This approach resulted in nanogels that were held together by MMP-sensitive peptides for enzyme-specific protein delivery. We employed a combination of cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle neutron scattering (SANS), and fluorescence correlation spectroscopy (FCS) to precisely decipher the morphology, self-assembly mechanism, enzyme-responsiveness, and model protein loading/release properties of our nanogel platform. Simple variation of the peptide linker sequence and combining multiple different crosslinkers will enable us to adjust our platform to target specific diseases in the future

Enantioselective Synthesis of Spiro[indolizidine-1,3 '-oxindoles]

A three-step procedure for the enantioselective synthesis of spiro[indolizidine-1,3'-oxindoles], consisting of a stereoselective cyclocondensation reaction between (S)-tryptophanol and a prochiral or racemic 5-oxoester, bromination of the resulting oxazolopiperidone lactam, and a final stereoselective spirocyclization, is reported

The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis

AbstractIt is well established that some patients with diffuse large B-cell lymphoma (DLBCL) and the negative end of treatment PET-CT (EOT-PET-CT) will relapse, while a proportion with positive upt..

Clinical, histopathological and molecular features of dedifferentiated melanomas:An EORTC Melanoma Group Retrospective Analysis

PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.</p

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Enzyme and temperature dual-responsive polymer nanostructures towards the treatment of osteoarthritis

Many diseases are associated with increased enzyme activities. Osteoarthritis (OA) is such an example where the over-expression of proteolytic enzymes leads to the erosion of the articular cartilage. These changes in the enzymatic environment offer inspiration for the design of smart drug delivery systems with triggered response to disease-specific conditions. In this context, self-assembled polymeric nanoparticles have come into focus due to their adaptable chemistry enabling the introduction of stimuli-responsive motifs to achieve triggered nanoparticle assembly and cargo release. Here, peptide-crosslinked, thermoresponsive polymer nanostructures cleavable by disease-associated enzymes are developed. More specifically, libraries of thermo-responsive N-isopropylacrylamide (NIPAM)- and N-cyclopropylacrylamide (NCPAM)-based triblock copolymers able to self-assemble across a range of temperatures were synthesized by controlled reversible addition-fragmentation chain-transfer (RAFT) polymerization. Two of the developed block copolymers were selected to be used for the construction of the enzyme-triggered delivery platform. By using copper-catalyzed click chemistry, these nanostructures were cross-linked with various peptide substrates sensitive to specific proteases. This approach confers improved system stability and controlled drug release kinetics. The morphology of both purely self-assembled and cross-linked nanostructures was investigated in detail by small angle neutron scattering (SANS) and cryogenic transmission electron microscopy (cryo-TEM). Further, loading capability towards multiple model cargos was demonstrated and enzyme-triggered release of a selected model protein was studied using fluorescence correlation spectroscopy (FCS). By accurate choice of the peptide cross-linker, nanoparticle degradation was achieved with various enzymes including MMP-13, which is the major enzyme causing cartilage degradation in OA. Finally, nanoparticle-cell interactions were studied using human OA chondrocytes and the synthesized copolymers / cross-linked nanoparticles did not reveal any cytotoxicity. Based on their fine control over the assembly temperature, chemical versatility, loading capabilities, enzyme-responsive properties and biocompatibility, these peptide cross-linked nanostructures are promising candidates as smart delivery systems for various diseases, including OA, where certain enzymes are over-expressed.Open Acces