Early Outcome of Multisystem Inflammatory Syndrome in Neonates Diagnosed following Prenatal Maternal COVID-19 Infection: A Three-Case Series.

BACKGROUND: The aim of this case series report is to evaluate the characteristics of multisystem inflammatory syndrome (MIS) in neonates following prenatal maternal COVID-19 infection. METHODS: We present a case series of three newborns (≤28 days of age) diagnosed with MIS due to the vertical transmission of SARS-CoV2 infection and admitted from 1 January 2021 to 1 June 2023. The inclusion criteria were negative RT-PCR-SARS-CoV-2 test in infants, initial negative IgM-SARS-CoV-2 in infants followed by the emergence of positive IgG-SARS-CoV-2 antibodies in infants and maternal COVID-19 infection in the third trimester of pregnancy. Patients enrolled in this case series were admitted due to acute febrile illnesses. RESULTS: All three cases occurred in patients born at a mean gestational age of 39 weeks and who were appropriate for gestational age. The mean age at admission was 18.3 days. Fibrinogen (>400 mg/dL) and ferritin (>120 mg/dL) were elevated above the upper normal limit. Elevated levels of myocardial biomarkers (D-dimers, N-terminal pro b-type natriuretic peptide troponin T and creatine phosphokinase myocardial band) were recorded, with normal heart function evaluated using echocardiography. All three patients were treated with antibiotics; one received intravenous immunoglobulin. A 4-week follow-up was completed in two patients when their myocardial biomarkers and ferritin were still elevated but lower compared with previous examinations. D-dimers levels were normalized in 2/3 patients. CONCLUSIONS: Subclinical myocarditis was diagnosed as an early outcome in infants with MIS diagnosed postnatally due to the vertical transmission of SARS-CoV2 infection and may represent a new challenge for pediatricians in the pandemic era.

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study.

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.

Trends of Lipophilic, Antioxidant and Hematological Parameters Associated with Conventional and Electronic Smoking Habits in Middle-Age Romanians.

It is known that cigarette smoking is correlated with medical associated inquires. New electronic cigarettes are intensively advertised as an alternative to conventional smoking, but only a few studies demonstrate their harmful potential. A cross-sectional study was designed using 150 subjects from Brasov (Romania), divided into three groups: non-smokers (NS = 58), conventional cigarettes smokers (CS = 58) and electronic cigarettes users (ECS = 34). The aim of this study was to determine levels of some plasma lipophilic and hematological components, and the total antioxidant status that could be associated with the smoking status of the subjects. Serum low density lipoproteins (LDL) cholesterol increased significantly for ECS participants versus NS group (18.9% difference) (p < 0.05). Also, the CS group is characterized by an increase of serum LDL cholesterol (7.9% difference vs. NS), but with no significant statistical difference. The variation of median values of serum very low density lipoproteins (VLDL) was in order NS < ECS < CS, with statistical difference between NS and CS groups (34.6% difference; p = 0.023). When comparing the antioxidant status of the three groups, significant differences (p < 0.05) were obtained between NS vs. CS and NS vs. ECS. Similar behavior was identified for CS and ECS. Statistically significant changes (p < 0.0001) for both vitamin A and vitamin E were identified in the blood of NS vs. CS and NS vs. ECS, and also when comparing vitamin A in the blood of the CS group versus the ECS group (p < 0.05). When all groups were compared, the difference in the white blood cell (WBC) was (p = 0.008). A slight increase in the red blood cell (RBC) count was observed, but with no statistical difference between groups. These results indicated that conventional cigarette and e-cigarette usage promotes the production of excess reactive oxygen species, involving different pathways, different antioxidants and bioactive molecules.

Body burden of organohalogenated pollutants and polycyclic aromatic hydrocarbons in Romanian population: Influence of age, gender, body mass index, and habitat.

Persistent organochlorine pollutants (POPs) are highly lipophilic and resistant to degradation, hence these substances are commonly found in the environment even decades after their prohibition. The aim of the present study was to determine human serum concentrations of POPs and polycyclic aromatic hydrocarbons (PAHs) in the Romanian population, investigating the role of demographic variables on the body burden of such chemicals. A cross-sectional study including a total of 121 subjects from Brasov (Transylvania region) was designed. The concentration of 62 chemicals, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (BDEs) and PAHs, was measured by gas chromatography-mass spectrometry (GC-MS) in the serum of the participants. p,p'-DDE and ß-HCH were detected in 100% and 62% of the series (median values = 2.1 and 0.5 µg/L); PCB-153 was detected in 77.7% of the subjects and PCB-28 showed the highest median concentration (0.5 µg/L); BDE-47 was detected at a low concentration in 11.6% of the individuals; phenanthrene and naphthalene were present in 98.3% and 38.8% of the serum samples (median values = 0.9 and 6.5 µg/L, respectively). Age was the main determinant of the total body burden of OCPs and PCBs. A positive correlation was observed between p,p'-DDE and age (Spearman Rho = 0.312, P < 0.0001), suggesting the prevalence of higher levels of pollutants at older ages. The present results showed a significant decrease in serum levels of p,p'-DDE and HCH in Romania -a country which has traditionally reported higher values than other Eastern European countries- as well as low levels of PCBs and BDEs. The presence of PAHs suggests an unknown source of exposure that deserves further investigation.

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.

Double transformation of a hematopoietic malignancy and severe associated thrombopathy. Case presentation and review of the literature.

We present the case of a patient with a double transformation during the evolution of chronic hematopoietic malignancy - JAK2 positive chronic myeloproliferative neoplasm; the first transformation had occurred previous to the presentation in our Department, but the second transformation was observed in evolution and it was into a rapidly evolving disease, followed by survival of less than one month. We underline the very poor prognosis -- overall survival of 2.5 years from initial presentation -- a much reduced survival for a chronic myeloproliferative neoplasm, probably due also to multiple associated pathology. Also, the other interesting element of the case is related to the dysfunctional platelets -- hemorrhagic complication at increased platelet count, respectively thrombosis at platelet count under 20000/mmc.

Chronic myeloid leukemia--from the National to the European Registry--limited experience of a single center.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the diagnosis is confirmed by detection of a genetic marker: Philadelphia (Ph) chromosome in almost 90% of cases. Some of Ph1 negative patients, nevertheless, test positive for the abnormal gene, or the abnormal protein associated with this chromosome, when more sensitive studies, such as PCR or FISH are used and nowadays the diagnosis of CML is based, not only on cytogenetic, but also on molecular analysis. The better understanding of the CML biology provided by the latest researches requires a deeper knowledge about the epidemiologic data in each geographic area, so the compiling of a National and/or European Registry for CML patients, that represents one of the aims of this study, became a stringent matter in our days; it can offer valuable data concerning the real incidence of this disease in Romania and can provide the basics for establishing long-term budgetary strategies.