Reticulated platelets and immature platelet fraction: Clinical applications and method limitations

So-called \u201creticulated\u201d or \u201cimmature platelets,\u201d which are newly released into the circulation, are more reactive than mature platelets, contain more RNA, and can be counted using flow cytometry after staining with thiazole orange or using some fully automated hematology analyzers, albeit with numerical disagreement. This review provides an overview of the state of the art of available technology for measuring immature or reticulated platelets (RP) with preanalytical (time stability, biological variation), analytical (methods, imprecision), and postanalytical (reference range) limitations. We also analyzed the clinical conditions in which immature/RP can be considered a diagnostic or prognostic tool (ie, differential diagnosis of thrombocytopenia, recovery after bone marrow or stem cell transplantation, risk assessment in cardiovascular diseases, response to antiplatelet drugs). They might also be of clinical utility in other settings but with lower evidence. The lack of a specific reference method and universal control material, as well as dependency of results on the measurement technique used, calls for different reference intervals and compromises comparison between clinical studies carried out using different analytical methods. To obviate lack of agreement between methods, more specific RNA dyes are necessary and the impact of the platelet size on the fluorescence signal defined. In the harmonization age, also in nomenclature field, a new definition instead of \u201creticulated\u201d or \u201cimmature\u201d platelets would be useful, and \u201cyoung platelets\u201d might be a more appropriate definition taking into account both the age and the functionality of this platelet fraction

Extra-osseous Ewing sarcoma of the thyroid gland mimicking lymphoma recurrence: a case report

Extra-osseous Ewing sarcomas/peripheral primitive neuroectodermal tumors (EOES/pPNETs) are high-grade malignant tumors found in various organs, such as the lung, skin, intestine, kidney and female genital tract; however, to the best of our knowledge, only two cases have previously been identified in the thyroid gland. We describe a case of primary EOES/PNET of the thyroid gland in a 66-year-old man with a previous history of large B cell lymphoma. During a routine follow-up examination, the patient underwent an ultrasound cervical scan showing a solid nodule of the left thyroid lobe. The fine-needle aspiration biopsy of the nodule suggested a neuroendocrine tumor. Histological and immunohistochemical examination of the surgical specimen supported a diagnosis of EOES/PNET, which was further confirmed by the demonstration of EWSR1 gene translocation by means of fluorescent in situ hybridization and by the detection of glycogen particles and neurosecretory granules by means of electron microscopy. Total body computed tomography and magnetic resonance imaging excluded the involvement of other sites, and therefore a diagnosis of primary EOES/PNET of the thyroid gland was made.This paper also discusses the main differential diagnoses, including lymphoma recurrence, other small round cell tumors (primary or metastatic), and a thyroid localization of an EWS/PNET from another organ

Prognostic Value of QFR Measured Immediately After Successful Stent Implantation: The International Multicenter Prospective HAWKEYE Study

The aim of this study was to investigate the potential role of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) measurements to predict clinical outcomes in patients with successful PCI

Epidermal growth factor receptor gene analysis with a highly sensitive molecular assay in routine cytologic specimens of lung adenocarcinoma

Epidermal growth factor receptor (EGFR) gene mutational analysis is critical for guiding the treatment of lung adenocarcinoma. In everyday clinical practice, EGFR testing is frequently centralized in referral laboratories that may receive paucicellular cytologic specimens, often fixed in various ways. We conducted a search for EGFR mutations in 108 cytologic samples of lung adenocarcinoma from different hospitals using the TheraScreen EGFR29 kit. These samples included 80 (74.1%) fine-needle aspirations, 13 (12%) pleural/ascitic fluids, 13 (12%) bronchial washings, and 2 bronchial brushings. The samples were fixed in ethanol (n = 79), Duboscq-Brasil (n = 18) or formalin (n = 10); 1 was unfixed. Ninety-two (85.2%) were amplified, 16 (14.8%) were not. Mutations were detected in 22 (23.9%) of 92 amplified samples, 9 containing less than 200 cancer cells, and 4 with less than 50% cancer cells. DNA was amplified in 12 of 18 Duboscq-Brasil-fixed samples. These findings indicate that cytologic specimens are adequate for EGFR testing when a highly sensitive assay is used, even if they are paucicellular or not optimally fixed

Mutation analysis of KRAS in primary colorectal cancer and matched metastases by means of highly sensitivity molecular assay.

Mutation analysis of KRAS is needed before starting treatment with anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (CRC). In most of the cases, testing is performed on primary tumors, assuming that KRAS mutation status does not change in metastasis although correlation studies gave conflicting results. We evaluated the KRAS status concordance rate between primary tumors and related metastasis using a highly sensitive molecular assay. Forty-five primary tumors and related metastases from patients with CRC (28/45 male-62.2% and 17/45 female-37.8%; mean age 66.4 years) were analyzed by using TheraScreen: KRAS mutational kit. Metastatic samples were collected from lymph nodes (8/45-17.8%) and visceral sites (37/45-82.2%); 23 were synchronous (49%) and 22 were metachronous (51%), obtained after a mean of 30.8 months after the first diagnosis of CRC. Twenty-eight patients had KRAS mutations in both primary CRC and related metastases (62.2%). No differences in type and frequency of mutations were identified, despite different metastatic sites and time of onset of metastatic disease. Our results indicate that the mutation status of KRAS is the same in primary CRC and metastasis, suggesting that in clinical practice, KRAS testing can be performed on both tumor tissues when using a highly sensitive molecular assay

Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma.

BACKGROUND: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies. METHODS: After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing. RESULTS: Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552). CONCLUSIONS: Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials

Eranshahr: Uomo, ambiente e società nell’Iran arsacide e sasanide. Testimonianze scritte, cultura materiale e società da Arsace a Yazdegard III

L’arco temporale che si pone a cavallo tra due transizioni politiche di notevole importanza, la prima tra la dinastia dei Seleucidi e quella degli Arsacidi, la seconda tra la dinastia dei Sasanidi e il califfato islamico, costituisce un contesto cruciale per la messa in pratica di diversi approcci metodologici volti alla comprensione delle relazioni tra uomo, potere politico e territorio nell’Iran tra III sec. a.C. e VII d.C. In tale quadro si è scelto di focalizzare l’attenzione su tre aree nodali dell’Iran antico: le regioni storiche dell’Elimaide (Khuzestan), della Persia (Pars) e della Media (Mad e Pahlaw). Le regioni prese in considerazione, pur caratterizzate da notevoli differenze, furono al centro delle trasformazioni del periodo e forniscono informazioni utili per la ricostruzione di specifiche dinamiche storico-culturali