Risk of Death in Comorbidity Subgroups of Hospitalized COVID-19 Patients Inferred by Routine Laboratory Markers of Systemic Inflammation on Admission: A Retrospective Study.

Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79-0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81-0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammation index (SII), NLR with SII and platelet-to-lymphocyte ratio (PLR) with SII. When analyzing the routine laboratory parameters in the subgroups of comorbidities, the risk of death was associated with a common set of laboratory markers of systemic inflammation. Our results have shown that a panel of several routine laboratory parameters recorded on admission could be helpful for early evaluation of the risk of disease severity and mortality in COVID-19 patients. Inflammatory markers for mortality risk were similar in the subgroups of comorbidities, suggesting the limited effect of confounding factors in predicting COVID-19 mortality at admission.

Evaluation of prognostic significance of hematological profiles after the intensive phase treatment in pulmonary tuberculosis patients from Romania.

We evaluated in this cohort study the predictive ability of 23 peripheral blood parameters and ratios for treatment outcomes after the 2-month intensive phase in patients with PTB. In 63 patients out of 90 that turned culture negative, a significant decrease in white blood cell count, neutrophils, monocyte, hemoglobin, platelet, plateletcrit, erythrocyte sedimentation rate, MLR, NLR, PLR and SII values after anti-TB therapy compared to pretreatment was observed (p <0.001). Logistic regression analysis generated a model of predictors consisting of nine covariates. Spearman's correlation analysis revealed significant positive correlations between NLR with NEU (r = 0.79, p<0.01), SII with NEU (r = 0.846, p<0.01), PLT with SII (r = 0.831, p<0.01), PLT with PCT (r = 0.71, p<0.01) and MPV with P-LCR (r = 0,897, p<0.01) in 63 patients out of 90 that turned culture negative after 2 months of treatment. ROC curve analysis indicated that all areas under the curve (AUC) revealed no statistically significant results, except lymphocyte for culture conversion. In summary, here we observed a set of hematological parameters that declined significantly as the disease was treated in patients that turned culture negative. Despite some limitations, our findings are useful for further studies aiming to identify hematological profiles that could predict the treatment outcome.

Non-Motor Manifestations in Idiopathic Dystonia with Focal Onset - A Pilot Study.

Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project - GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cut-offs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cut-off for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.

Mitochondrial DNA haplogroup K as a contributor to protection against thyroid cancer in a population from southeast Europe.

We aimed to analyze the contribution of mitochondrial DNA (mtDNA) haplogroups of the mtDNA control region to thyroid cancer risk in a population from southeastern Europe consisting of 235 thyroid tumor patients, including 114 patients with thyroid follicular adenoma, 121 patients with papillary thyroid carcinoma, and 419 healthy controls. Binary logistic regression with adjustment for age and gender revealed that mtDNA haplogroup K was significantly associated with a protective role for thyroid cancer in the combined tumor group versus controls. These results indicate a potential role for mtDNA haplogroups as important candidate susceptibility markers for the patients with thyroid nodules.

Genetic affinities among the historical provinces of Romania and Central Europe as revealed by an mtDNA analysis.

BACKGROUND: As a major crossroads between Asia and Europe, Romania has experienced continuous migration and invasion episodes. The precise routes may have been shaped by the topology of the territory and had diverse impacts on the genetic structure of mitochondrial DNA (mtDNA) in historical Romanian provinces. We studied 714 Romanians from all historical provinces, Wallachia, Dobrudja, Moldavia, and Transylvania, by analyzing the mtDNA control region and coding markers to encompass the complete landscape of mtDNA haplogroups. RESULTS: We observed a homogenous distribution of the majority of haplogroups among the Romanian provinces and a clear association with the European populations. A principal component analysis and multidimensional scaling analysis supported the genetic similarity of the Wallachia, Moldavia, and Dobrudja groups with the Balkans, while the Transylvania population was closely related to Central European groups. These findings could be explained by the topology of the Romanian territory, where the Carpathian Arch played an important role in migration patterns. Signals of Asian maternal lineages were observed in all Romanian historical provinces, indicating gene flow along the migration routes through East Asia and Europe. CONCLUSIONS: Our current findings based on the mtDNA analysis of populations in historical provinces of Romania suggest similarity between populations in Transylvania and Central Europe, supported both by the observed clines in haplogroup frequencies for several European and Asian maternal lineages and MDS analyses.

Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. -765G>C PTGS2 polymorphism and NMSC risk.

Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 -765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In BCC and SCC patients with GG genotype, CRP level is significantly increased compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group comparison of CRP levels showed significantly lower CRP levels in patients carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients (p < 0.0001). PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP levels.

A deletion of a novel heat shock gene on the Y chromosome associated with azoospermia.

Deletions of the Y chromosome are a significant cause of spermatogenic failure. Three major deletion intervals have been defined and termed AZFa, AZFb and AZFc. Here, we report an unusual case of a proximal AZFb deletion that includes the Y chromosome palindromic sequence P4 and a novel heat shock factor (HSFY). This deletion neither include the genes EIF1AY, RPS4Y2 nor copies of the RBMY1 genes. The individual presented with idiopathic azoospermia. We propose that deletions of the testis-specific HSFY gene family may be a cause of unexplained cases of idiopathic male infertility. This deletion would not have been detected using current protocols for Y chromosome microdeletion screens, therefore we recommend that current screening protocols be extended to include this region and other palindrome sequences that contain genes expressed specifically in the testis.