Challenges in Utilization of Osteoporosis Healthcare Services during COVID-19 Pandemic in Romania - a Nationwide Population Study.

Objectives: This study compares the utilization of osteoporosis and osteoporosis complication healthcare services before and during the COVID-19 pandemic in Romania. Methods:The descriptive nationwide population study has used secondary data collected from the national health information system. We have calculated and compared the procedures performed for osteoporosis diagnosis and screening, standardized incidence and hospitalization rate for osteoporosis and osteoporosis fractures before and during the COVID-19 pandemic. Results:A 37.84% reduction in the number of DXA scans performed in 2020 have been observed, decreasing from 30,698 in 2019 to 12,064 in 2020. The standardized incidence for osteoporosis was 212.97 cases/100.000 person-years in 2018, 234 cases/100,000 person-years in 2019, and 185.97 cases/100,000 person-years in 2020. The hospitalization rates for osteoporosis have decreased by 68% compared with 2019 and the continuous hospitalization rate for osteoporotic fracture by 48% compared with 2019. Conclusions:The COVID-19 pandemic affected the utilization of healthcare services for osteoporosis management, posing a threat due to a magnified effect on osteoporotic fracture burden. More efforts are further needed to progress and re-engage with osteoporotic fracture prevention in our country and to develop and shape an optimal implementation of prevention and management strategies for all level of health care in Romania.

FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation.

Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.

Activity of vancomycin release from bioinspired coatings of hydroxyapatite or TiO2 nanotubes.

Herein we investigate the efficiency of various biomimetic coatings for localized drug delivery, using vancomycin as key therapeutic drug, which is a widely used antibiotic for the treatment of strong infections caused by positive Gram bacteria. We evaluate classical hydroxyapatite and biomimetic hydroxyapatite-collagen coatings obtained by electrochemical deposition as well as TiO2 nanotubes arrays obtained by electrochemical anodization. Surface morphology, compositional and structural data confirm the incorporation of vancomycin into the layers and drug release profiles for vancomycin evaluate their release ability. Namely, hydroxyapatite coatings lead to a ≈92% vancomycin release after 30h and hydroxyapatite-collagen to 85%, while the TiO2 nanotubes layers lead to 78% release. The antibacterial effect of such drug loaded coatings is evaluated against S. aureus (Gram-positive bacteria). Our study shows that the vancomycin incorporated hydroxyapatite coatings lead to a faster release, while the nanotubular coatings may lead to longer time release and additionally both types of coatings ensure a good antibacterial inhibition.

TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms - a multicentric study on 529 patients.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.

2016 WHO Clinical Molecular and Pathological Criteria for Classification and Staging of Myeloproliferative Neoplasms (MPN) Caused by MPN Driver Mutations in the JAK2, MPL and CALR Genes in the Context of New 2016 WHO Classification: Prognostic and Therapeutic Implications.

The 2016 WHO-CMP classification proposal defines a broad spectrum of JAK2 V617F mutated MPN phenotypes: normocellular ET, hypercellular ET due to increased erythropoiesis (prodromal PV), hypercellular ET with megakaryocytic-granulocytic myeloproliferation and splenomegaly (EMGM or masked PV), erythrocythemic PV, early and overt classical PV, advanced PV with MF and post-PV MF. ET heterozygous for the JAK2 V617F mutation is associated with low JAK2 mutation load and normal life expectance. PV patients are hetero-homozygous versus homozygous for the JAK2 V617F mutation in their early versus advanced stages with increasing JAK2 mutation load from less than 50% to 100% and increase of MPN disease burden during life long follow-up in terms of symptomatic splenomegaly, constitutional symptoms, bone marrow hypercellularity and secondary MF. Pretreatment bone marrow biopsy in prefibrotic MPNs is of diagnostic and prognostic importance. JAK2 exon 12 mutated MPN is a distinct benign early stage PV. CALR mutated hypercellular thrombocythemia show distinct PMGM bone marrow characteristics of clustered larged immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei, which are not seen in JAK2 mutated ET and PV. MPL mutated normocellular thrombocythemia is featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei without features of PV in blood and bone marrow. Myeloproliferative disease burden in each of the JAK2, CALR and MPL MPNs is best reflected by the degree of anemia, splenomegaly, mutation allele burden, bone marrow cellularity and myelofibrosis.

Epidemiological data from the registry of patients with myelodysplastic syndrome in a single hospital center of Romania.

We present the first Romanian study on the epidemiological characteristics of MDS, based on the data existing in Fundeni Clinical Institute, Hematological Department, Bucharest. The files at diagnosis of the adult patients with primary MDS admitted during the period 1982-2005, recorded in the registration forms provided by the MDS Foundation (USA), represented the primary database. This study indicates an increase in the number of new MDS cases over the period of time investigated. Also, a 10 years lower median age of the patients, a noticeable proportion of young patients and a low proportion of patients >or=81 years have been found, which situates our findings in the middle between the Eastern and Western epidemiological reported data on MDS.

Hypolipemiant besides antileukemic effect of imatinib mesylate.

The use of imatinib mesylate (IM) (Gleevec, Novartis) in chronic myeloid leukemia (CML) and other neoplastic disorders is in a dramatic increase, inducing long-standing survival. Therefore, the interest in the associated events with this treatment is more and more manifest. We describe a case of CML in which, at the usual antileukemic dose, IM induced a rapid and persistent normalization of the levels of serum cholesterol, triglycerides, low- and high-density lipoproteins and glucose. In the present case report we confirm other observations on the hypolipemiant and antidiabetic effects, concomitant with that antileukemic, of IM.

Laparoscopic splenectomy can induce significant improvement in hypoplastic myelodysplastic syndrome.

A 20 years old male patient was diagnosed as hypoplastic myelodysplastic syndrome (hMDS) - refractory cytopenia with multilineage dysplasia in November 2002. He received packed blood cells, methylprednisolon and dexamethason but no persistent improvement and even worsening of the thrombocytopenia and the appearance of neutropenia were registered. Laparoscopic splenectomy has been performed in January 2003, when the platelets were approximately 15000/mm3, without intraoperative incidents. After splenectomy, no other therapy or transfusions have been applied and a slow but continuous improvement of the peripheral blood counts up to normal values has been noted. In the bone marrow, a notable increase of cellular density was registered after more than three years from splenectomy, with the persistence of the other morphological dysplastic features.