Intrarenal resistive index conundrum: systemic atherosclerosis versus renal arteriolosclerosis.

Background: We aimed to evaluate the relationship between biopsy-proven kidney lesions, subclinical markers of atherosclerosis and intrarenal resistive index (RRI) in chronic kidney disease (CKD) patients. Methods: This cross-sectional, single-center study prospectively enrolled 44 consecutive CKD patients (57% male gender, 54.1 (95%CI, 49.7-58.6) years, median eGFR 28.1 (15.0-47.7) mL/min) diagnosed by renal biopsy during 6 months in our clinic. RRI, carotid intima-media thickness (IMT), Kauppila score for abdominal aortic calcification (AACs) were assessed. Traditional and nontraditional atheroscleosis risk factors were also evaluated. Results: Most of the patients had a diagnosis of glomerular nephropathy, with IgA nephropathy and diabetic nephropathy being the most frequent. RRI increased proportionally with CKD stages. Patients with RRI >0.7 (39%) were older, had diabetic and vascular nephropathies more frequently, higher mean arterial blood pressure, increased systemic atherosclerosis burden (IMT and AACs), higher percentage of global glomerulosclerois, GBM thickness, arteriolosclerosis and interstitial fibrosis/tubular atrophy. RRI directly correlated with age (rs = 0.55, p < 0.001) and with all the studied atherosclerosis markers (clinical atherosclerosis score rs = 0.50, p = 0.02; AACs rs = 0.50, p < 0.01; IMT rs = 0.34, p = 0.02). Also, global glomerulosclerosis (rs = 0.31, p = 0.03) and interstitial fibrosis/tubular atrophy (rs = 0.35, p = 0.01) were directly correlated with RRI. In multivariable adjusted binomial logistic regression models, only arteriolosclerosis was retained as independent predictor of RRI >0.7. Conclusion: The analysis of RRI may be useful in the evaluation of the general vascular condition of the patient with CKD, supplying information about both microvascular and macrovascular impairment. Moreover, RRI correlates well with renal histopathologic characteristics, particularly with arteriolosclerosis.

Osteosarcoma Arising as a Secondary Malignancy following Treatment for Hematologic Cancer: A Report of 33 Affected Patients from the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: Osteosarcoma may arise as a secondary cancer following leukemias or lymphomas. We intended to increase the knowledge about such rare events. PATIENTS AND METHODS: We searched the Cooperative Osteosarcoma Study Group's database for individuals who developed their osteosarcoma following a previous hematological malignancy. The presentation and treatment of both malignancies was investigated, and additional neoplasms were noted. Outcomes after osteosarcoma were analyzed and potential prognostic factors were searched for. RESULTS: A total of 33 eligible patients were identified (male: 23, female: 10; median age: 12.9 years at diagnosis of hematological cancer; 20 lymphomas, 13 leukemias). A cancer predisposition syndrome was evident in one patient only. The hematological cancers had been treated by radiotherapy in 28 (1 unknown) and chemotherapy in 26 cases, including bone-marrow transplantation in 9. The secondary bone sarcomas (high-grade central 27, periosteal 2, extra-osseous 2, undifferentiated pleomorphic sarcoma of bone 2) arose after a median lag-time of 9.4 years, when patients were a median of 19.1 years old. Tumors were considered radiation-related in 26 cases (1 unknown). Osteosarcoma-sites were in the extremities (19), trunk (12), or head and neck (2). Metastases at diagnosis affected eight patients. Information on osteosarcoma therapy was available for 31 cases. All of these received chemotherapy. Local therapy involved surgery in 27 patients, with a good response reported for 9/18 eligible patients. Local radiotherapy was given to three patients. The median follow-up was 3.9 (0.3-12.0) years after bone tumor diagnosis. During this period, 21 patients had developed events as defined, and 15 had died, resulting in 5-year event-free and overall survival rates of 40% (standard error: 9%) and 56% (10%), respectively. There were multiple instances of additional neoplasms. Several factors were found to be of prognostic value (p < 0.05) for event-free (osteosarcoma site in the extremities) or overall (achievement of a surgical osteosarcoma-remission, receiving chemotherapy for the hematologic malignancy) survival. CONCLUSIONS: We were able to prove radiation therapy for hematological malignancies to be the predominant risk factor for later osteosarcomas. A resulting overrepresentation of axial and a tendency towards additional neoplasms affects prognosis. Still, selected patients may become long-term survivors with appropriate therapies, which is an argument against therapeutic negligence.

Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies.

The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.