Fibrinogen, an abundant plasma glycoprotein, is involved in the final stage of blood coagulation. Decreased fibrinogen levels, which may be caused by mutations, are manifested mainly in bleeding and thrombotic disorders. Clinically relevant mutations of fibrinogen are listed in the Human Fibrinogen Database. For the αC-connector (amino acids Aα240-410, nascent chain numbering), we have extended this database, with detailed descriptions of the clinical manifestations among members of reported families. This includes the specification of bleeding and thrombotic events and results of coagulation assays. Where available, the impact of a mutation on clotting and fibrinolysis is reported. The collected data show that the Human Fibrinogen Database reports considerably fewer missense and synonymous mutations than the general COSMIC and dbSNP databases. Homozygous nonsense or frameshift mutations in the αC-connector are responsible for most clinically relevant symptoms, while heterozygous mutations are often asymptomatic. Symptomatic subjects suffer from bleeding and, less frequently, from thrombotic events. Miscarriages within the first trimester and prolonged wound healing were reported in a few subjects. All mutations inducing thrombotic phenotypes are located at the identical positions within the consensus sequence of the tandem repeats.

• Keywords
• Human Fibrinogen Database, afibrinogenemia, dysfibrinogenemia, fibrinogen, hypodysfibrinogenemia, hypofibrinogenemia, mutations, αC-connector,
• MeSH
• Fibrinogen genetics   MeSH
• Blood Coagulation genetics   MeSH
• Hemorrhage genetics   MeSH
• Humans MeSH
• Mutation genetics   MeSH
• Thrombosis genetics   MeSH
• Blood Coagulation Tests methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Fibrinogen MeSH

Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.

• MeSH
• Afibrinogenemia * epidemiology   genetics   complications   MeSH
• Fibrinogen genetics   MeSH
• Hemostatics * MeSH
• Hemorrhage genetics   MeSH
• Humans MeSH
• Prospective Studies MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fibrinogen MeSH
• Hemostatics * MeSH

The aim of this study was to compare the filling of the pilonidal sinus tract with fibrin sealant (FS) against tract excision and primary closure (PC) as the primary procedure. Details of all patients who underwent treatment for a symptomatic first episode of pilonidal sinus disease between January 2011 and December 2015 were prospectively recorded in a custom database. Patients underwent PC (n=17) or FS (n=17) according to patient preference. Prior surgical treatment and ongoing infection precluded entry. Patients were treated with antibiotics if presenting with infection. Outcomes measured were recurrence, further procedures, outpatient attendances and length of follow-up to resolution. 34 consecutive patients [FS vs. PC: male n=15 vs. 12 p=0.398; mean age 29 (SEM 12) vs. 30 (SEM 15) p=0.849] were included. Treated preoperative infections were similar FS (n=5) vs. PC (n=12) (p=0.038, chi-squared test). FS cohort had more sinuses FS median (range) 2 (1-4) vs. PC 1 (1-3) (p=0.046). Postoperative outcomes: recurrence rate FS (n=5) vs. PC (n=4) (p=0.629); infection rate FS (n=1) vs. PC (n=8) (p=0.045); total number of operations required FS 1 (1-2) vs. PC 1 (1-4) (p=0.19); total number of outpatient attendance FS 2 (1-7) vs. PC 3 (1-16) (p=0.629); follow-up FS 129 days ± 33 vs. PC 136 ± 51 (p=0.914). Fibrin sealant is not inferior to excision followed by primary closure.

• Keywords
• Fibrin glue, Pilonidal disease,
• MeSH
• Adult MeSH
• Fibrin Tissue Adhesive * therapeutic use   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Pilonidal Sinus * surgery   MeSH
• Recurrence MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fibrin Tissue Adhesive * MeSH

PURPOSE: This systematic review and meta-analysis assessed the prognostic value of preoperative blood-based biomarkers in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy. METHODS: PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared cancer-specific survival in UTUC patients with and without pretreatment laboratory abnormalities. Formal meta-analyses were performed for this outcome. RESULTS: The review identified 54 studies with 23,118 patients, of these, 52 studies with 22,513 patients were eligible for the meta-analysis. Several preoperative blood-based biomarkers were significantly associated with cancer-specific survival as follows: neutrophil-lymphocyte ratio (pooled hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.34-2.06), C-reactive protein (pooled HR: 1.17, 95% CI: 1.07-1.29), platelet-lymphocyte ratio (pooled HR: 1.68, 95% CI: 1.30-2.17), white blood cell (pooled HR: 1.58, 95% CI: 1.02-2.46), De Ritis ratio (pooled HR: 2.40, 95% CI: 1.92-2.99), fibrinogen (pooled HR: 2.23, 95% CI: 1.86-2.68), albumin-globulin ratio (pooled HR: 3.00, 95% CI: 1.87-4.84), hemoglobin (pooled HR: 1.51, 95% CI: 1.22-1.87), and estimate glomerular filtration rate (pooled HR: 1.52, 95% CI: 1.19-1.94). The Cochrane's Q test and I2 test revealed significant heterogeneity for neutrophil-lymphocyte ratio, C-reactive protein, white blood cell, hemoglobin, and estimated glomerular filtration rate (P = 0.022; I2 = 50.7%, P = 0.000; I2 = 80.4%, P = 0.000; I2 = 88.3%, P = 0.010; I2 = 62.0%, P = 0.000; I2 = 83.9%, respectively). CONCLUSIONS: Several pretreatment laboratory abnormalities in patients with UTUC were associated with increased risks of cancer-specific mortality. Therefore, blood-based biomarkers may have the potential to serve as prognostic factors to assist patients and physicians in selecting appropriate treatment strategies for UTUC. However, considering the study limitations including heterogeneity and retrospective nature of the primary data, the conclusions should be interpreted with caution.

• Keywords
• Blood-based biomarker, Meta-analysis, Upper tract urothelial carcinoma,
• MeSH
• Carcinoma, Transitional Cell blood   mortality   secondary   MeSH
• Humans MeSH
• Survival Rate MeSH
• Biomarkers, Tumor blood   MeSH
• Kidney Neoplasms blood   mortality   surgery   MeSH
• Ureteral Neoplasms blood   mortality   surgery   MeSH
• Nephroureterectomy * MeSH
• Preoperative Period MeSH
• Prognosis MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

We have retrospectively evaluated a cohort of 144 patients (including 17 pediatric ones) with de novo acute promyelocytic leukemia registered in databases of institutions cooperating within the CELL group (The Czech Leukemia Study Group for Life). The patients were diagnosed according to WHO criteria from 1989 until 2006. The aim was to check how well fared the patients, the majority of whom was not included into clinical trials, in real life. Of 140 evaluable patients, 97 (69.3%) attained complete remission (CR). The projected overall survival (OS) 4 years after diagnosis was 58.9%, and 55.3% at 6 years. In 8 patients (6.0%), no antileukemic therapy at all was given (either they died shortly after admission to the ward or therapy was not feasible due to their clinical status). Of 125 patients with documented commencement of some kind of therapy, 96 (76.8%) achieved CR. Of 102 patients with induction treatment with a combination of anthracycline and tretinoin (ATRA), 84 individuals (82.4%) attained CR (typically, this cohort might have been subjected to clinical trials). This result was better than that of patients treated by chemotherapy only (n = 15; CR 46.7%; P = 0.003) or by ATRA monotherapy (n = 13; CR 62.5%; P = 0.17). Another parameter with a significant impact on attaining CR was the leukocyte (WBC) count at diagnosis: its median values in patients achieving and not achieving CR were 2.1 and 24.0 x 10(9)/l, respectively (P < 0.0001). The WBC counts affected OS as well (P = 0.0001). However, when only patients after attaining CR were evaluated, the initial WBC counts no longer affected OS (P = 0.18). Achieving CR was also influenced by the performance status (PS) 0-1 (P = 0.005), which was in turn closely correlated to WBC counts (P = 0.0006). Additional factors (most likely connected with leukocytosis) influenced attaining CR with borderline statistical significance: e.g. FAB M3v morphology, LDH serum level, fibrinogen level, presence of internal tandem duplication (ITD) of the FLT3 gene (which was strongly associated with leukocytosis and also with the short PML/RARalpha transcript resulting from the bcr3 break in the PML gene). It may be speculated that FLT3-ITD is just one of the possible factors that lead to leukocytosis. The platelet counts at diagnosis had no impact on entering CR. Thus, we have not validated the current PETHEMA risk stratification in distinguishing intertermediate and low risk patients. Our study points to a significant difference of the results obtained in real life and of the results that could be achieved in patients who were fit to enter clinical trials. Among the prognostic factors, the most important one was the WBC count, the PS (which is highly affected by the WBC count), and feasibility of administration of the most potent induction therapy with anthracyclines and ATRA.

• MeSH
• Leukemia, Promyelocytic, Acute drug therapy   genetics   mortality   MeSH
• Child MeSH
• Adult MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Prognosis MeSH
• Recurrence MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH