The role of fulvestrant in endometrial cancer

Introduction: Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms.

Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed. The pharmacokinetic and pharmacodynamic features of selective receptor down-regulators have been also investigated.

Expert opinion: Selective estrogen receptor down-regulators may exhibit clinical efficacy in the treatment of gynecological malignancies due to their pure estrogen receptor antagonist properties. However, up to now data are still limited and some unsolved questions remain. Fulvestrant has poor oral bioavailability and low pharmacodynamic characteristics. Further trials are required to examine new selective estrogen receptor down-regulator agents with better pharmacodynamic and pharmacokinetic profiles.     

Internal carotid artery dissection related to abnormalities of styloid process: is it only a matter of length?

Neurological Sciences - Vascular Eagle syndrome, due to impingement of the extracranial internal carotid artery (ICA) by the styloid process (SP), is an uncommon and not yet widely recognized cause...     

Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome

Introduction

Diagnosing Cushing’s syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion.

Materials and methods

Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test.

Results

Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68–83) and a specificity (SP) of 100 % (95 % CI 83–100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81–93) and a SP of 90 % (95 % CI 68–99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower.

Conclusions

Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

     

Permanent Spacers Are a Reliable Solution for Peri-prosthetic Shoulder Infection: A Systematic Review

HSS Journal ® - Peri-prosthetic shoulder infection (PSI), a highly disabling complication of shoulder arthroplasty, often requires additional surgery and prolonged antibiotic therapy. Of...     

Bone marrow derived stem cells in joint and bone diseases: a concise review

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients’ life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a “reservoir” of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called “stem cell niche” was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.     

Dry Sliding Behavior of an Aluminum Alloy after Innovative Hard Anodizing Treatments

This work evaluates the dry sliding behavior of anodic aluminum oxides (AAO) formed during one traditional hard anodizing treatment (HA) and two golden hard anodizing treatments (named G and GP, respectively) on a EN AW-6060 aluminum alloy. Three different thicknesses of AAO layers were selected: 25, 50, and 100 μm. Prior to wear tests, microstructure and mechanical properties were determined by scanning electron microscopy (VPSEM/EDS), X-ray diffractometry, diffuse reflectance infrared Fourier transform (DRIFT-FTIR) spectroscopy, roughness, microhardness, and scratch tests. Wear tests were carried out by a pin-on-disc tribometer using a steel disc as the counterpart material. The friction coefficient was provided by the equipment. Anodized pins were weighed before and after tests to assess the wear rate. Worn surfaces were analyzed by VPSEM/EDS and DRITF-FTIR. Based on the results, the GP-treated surfaces with a thickness of 50 μm exhibit the lowest friction coefficients and wear rates. In any case, a tribofilm is observed on the wear tracks. During sliding, its detachment leads to delamination of the underlying anodic aluminum oxides and to abrasion of the aluminum substrate. Finally, the best tribological performance of G- and GP-treated surfaces may be related to the existence of a thin Ag-rich film at the coating/aluminum substrate interfaces.     

Thirteen Years of Phleboviruses Circulation in Lombardy,a Northern Italy Region

Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. Toscana phlebovirus (TOSV), Sicilian phlebovirus (SFSV), and Naples phlebovirus (SFNV) are responsible of summer fever, with well-known pathogenic potential for humans ranging from asymptomatic to mild fever, in addition to neuro-invasive infections during summer. Although TOSV, in particular, is a significant and well-known human pathogen, SFVs remain neglected, with many gaps in the relevant knowledge. Sero-epidemiological studies and case reports recently showed a geographical wider distribution than previously considered, although the real incidence of phleboviruses infections in the Mediterranean area is still unknown. Here we retrospectively evaluated the circulation of phleboviruses during summer seasons between 2007 and 2019 in 649 patients showing neurological symptoms using both molecular and serological approaches. We found that 42/649 (6.5%) subjects experienced phlebovirus infection and only 10/42 cases were detected by molecular assays, whereas the other 32/42 were identified using serological approaches, including neutralization assays. During the 2013 summer, an outbreak in the Lombardy region is described because the prevalence of phlebovirus infection reached 37.2% (19/51 subjects). Interestingly, only 5/19 (26.5%) reported traveling in endemic areas. Of note, no cross-neutralization was observed between different strains tested, showing the possibility to be reinfected by newly discovered phlebovirus strains. In conclusion, phlebovirus infections are still inadequately considered by physicians and are generally underestimated. However, based on our results, sandfly fever viruses should be routinely included in diagnostic panels during summer period, including in Northern Italy.     

Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release

Ploidy could be the key to understanding megakaryocyte (MK) biologyand platelet production. Human CD34⁺ cells purified fromumbilical cord blood (CB) and peripheral blood (PB) were investigatedon their capability to give rise, in a serum-free medium containingthrombopoietin, to MKs and platelets. CB-MKs showed reducedpolyploidization and platelet number compared with PB-MKs, but asimilar membrane phenotype. Most CB-MKs showed a 2N content of DNA(~80%) and only 2.6% had 8N, whereas 40% of the PB cells had 8N ormore. Platelets were substantially released in PB culture from day 12;at day 14 the CB-derived MKs were able to release platelets although ata reduced level (~35%), correlating with their reduced size. Adirect correlation was demonstrated by sorting polyploid cells fromPB-MKs and evaluating the platelets released in the supernatant.Furthermore, the study analyzed the expression and distribution ofcyclin D3 and cyclin B1. Cyclin D3 protein was increased in PB incomparison to CB-MKs; in PB culture most cells rapidly became positive,whereas in CB-derived cells cyclin D3 expression was evident only fromday 9 and in a reduced percentage. Cyclin B1 was essentially localizedat the nuclear level in the CB and was expressed during the wholeculture. In PB-MKs, at day 9, a reduction was observed, correlatingwith an advanced ploidy state. The data indicate the inability of the CB-MKs to progress in the endomitotic process and a direct correlation between DNA content and platelet production.