Pharmacogenetics of the local thrombolysis in patients with deep vein thrombosis

Thrombophilia, the state of increased tendency for blood clotting, is considered the disorder of a complex etiology, caused by both environmental and genetic factors. As gene variants predisposing to thrombophilia and influencing the increased risk of vein thrombosis might influence response to local thrombolysis, the aim of the work was to characterize the pharmacogenetic conditions for local streptokinase treatment in patients with a deep vein thrombosis (DVT) of lower extremities based on the following polymorphism analyses: G1691A polymorphism of factor V (FV), G20210A polymorphism of prothrombin (PT), A4250G (Thr312Ala) polymorphism of fibrinogen-alpha (FGA), G(-455)A polymorphism of fibrinogen-beta (FGB), 4G/5G polymorphism of plasminogen activator inhibitor type 1(PAI-1) and insertion/deletion (I/D) polymorphism of tissue plasminogen activator (t-PA). The study included 40 DVT patients who underwent a local thrombolytic treatment within 14-day period from diagnosis. Full recanalization was achieved in 20 subjects (50%) [group R(+)], whereas incomplete or total lack of recanalization was identified in the remaining 20 patients [group R(-)]. No major complications of thrombolytic treatment occurred in the studied group. In the case of prothrombin gene all individuals carried homozygous wild type genotype (GG). Prevalence of the genotypes and alleles of the remaining five polymorphisms did not differ significantly between the groups R(+) and R(-). Neither sex nor age, smoking or time period from diagnosis to introduction of the thrombolytic treatment significantly influenced treatment efficacy. The results of the study suggest that a local thrombolysis with streptokinase introduced within two week period from the diagnosis is a safe and efficient method of treatment for deep vein thrombosis of lower extremities. However, size of the group is insufficient to clearly determine the association between investigated polymorphisms and efficacy of local treatment with streptokinase.     

Przedtransplantacyjne czynniki ryzyka reaktywacji zakażenia wirusem cytomegalii po przeszczepieniach allogenicznych komórek hematopoetycznych u dzieci i młodych dorosłych

BackgroundCytomegalovirus (CMV) reactivation remains one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT).MethodsAn analysis of the pre-transplant risk factors of CMV reactivation was performed in 98 patients aged 0.5–22 years (median 10.5) undergoing allogeneic HSCT. CMV reactivation was tested by assessing viral load using PCR method. Following factors were analyzed: type of conditioning, graft source, donor type, use of T-depletion and CMV-serostatus of the donor and recipient. Each factor was assigned from 0 to 2 points. Based on total score for each patient, CMV reactivation risk scale was developed, and two groups with low (LR) and high (HR) risk were determined.ResultsCMV reactivation was seen in 25 patients (24.5%). The significant risk factors for CMV reactivation were: CMV-positive recipient (p<0.001), unrelated donor (p<0.002), use of ATG (p<0.002) and PBSC (p<0,01). In the HR group the incidence of reactivation CMV was significantly higher than in LR group (47.8% vs. 5.4%, p<0.001).ConclusionsCMV seropositivity of the recipient was an independent predictor factor of CMV reactivation. The use of risk point scale of CMV reactivation allows for identification of patients with the higher risk of CMV reactivation.     

New anatomical data on the growing C4 vertebra and its three ossification centers in human fetuses

Purpose

Detailed knowledge on the normative growth of the spine is of great relevance in the prenatal diagnosis of its abnormalities. The present study was conducted to compile age-specific reference data for vertebra C4 and its three ossification centers in human fetuses.

Materials and methods

With the use of CT (Biograph mCT), digital image analysis (Osirix 3.9) and statistical analysis (Wilcoxon signed-rank test, Kolmogorov–Smirnov test, Levene’s test, Student’s t test, one-way ANOVA, post hoc RIR Tukey test, linear and nonlinear regression analysis), the normative growth of vertebra C4 and its three ossification centers in 55 spontaneously aborted human fetuses (27 males, 28 females) aged 17–30 weeks was examined.

Results

Significant differences in neither sex nor laterality were found. The height and transverse and sagittal diameters of the C4 vertebral body increased logarithmically as: y = ?3.866 + 2.225 × ln(Age) ± 0.238 (R ² = 0.69), y = ?7.077 + 3.547 × ln(Age) ± 0.356 (R ² = 0.72) and y = ?3.886 + 2.272 × ln(Age) ± 0.222 (R ² = 0.73), respectively. The C4 vertebral body grew linearly in cross-sectional area as y = ?7.205 + 0.812 × Age ± 1.668 (R ² = 0.76) and four-degree polynomially in volume as y = 14.108 + 0.00007 × Age⁴ ± 6.289 (R ² = 0.83). The transverse and sagittal diameters, cross-sectional area and volume of the ossification center of the C4 vertebral body generated the following functions: y = ?8.836 + 3.708 × ln(Age) ± 0.334 (R ² = 0.76), y = ?7.748 + 3.240 × ln(Age) ± 0.237 (R ² = 0.83), y = ?4.690 + 0.437 × Age ± 1.172 (R ² = 0.63) and y = ?5.917 + 0.582 × Age ± 1.157 (R ² = 0.77), respectively. The ossification center-to-vertebral body volume ratio gradually declined with age. On the right and left, the neural ossification centers showed the following growth: y = ?19.601 + 8.018 × ln(Age) ± 0.369 (R ² = 0.92) and y = ?15.804 + 6.912 × ln(Age) ± 0.471 (R ² = 0.85) for length, y = ?5.806 + 2.587 × ln(Age) ± 0.146 (R ² = 0.88) and y = ?5.621 + 2.519 × ln(Age) ± 0.146 (R ² = 0.88) for width, y = ?9.188 + 0.856 × Age ± 2.174 (R ² = 0.67) and y = ?7.570 + 0.768 × Age ± 2.200 (R ² = 0.60) for cross-sectional area, and y = ?13.802 + 1.222 × Age ± 1.872 (R ² = 0.84) and y = ?11.038 + 1.061 × Age ± 1.964 (R ² = 0.80) for volume, respectively.

Conclusions

The morphometric parameters of vertebra C4 and its three ossification centers show no sex differences. The C4 vertebral body increases logarithmically in height and both sagittal and transverse diameters, linearly in cross-sectional area, and four-degree polynomially in volume. The three ossification centers of vertebra C4 grow logarithmically in both transverse and sagittal diameters, and linearly in both cross-sectional area and volume. The age-specific reference intervals for evolving vertebra C4 may be useful in the prenatal diagnosis of congenital spinal defects.     

High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland

IntroductionThe incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases.Material and methodsFour hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China).ResultsIn the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively.ConclusionsIn this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.     

Outcomes of physical therapy in patients with temporomandibular disorder: a retrospective review

Temporomandibular disorder (TMD) encompasses a spectrum of disorders that are associated with pain in the temporomandibular joint (TMJ) and surrounding musculature. Current research shows that conservative physical therapy is beneficial in the management of the disorder. This study further explores if physical therapy is an effective approach to treating patients with TMJ disorders. Our objectives were to determine the effect of conservative physical therapy interventions on pain, maximal mouth opening, and TMJ disability index for patients with TMD. Medical records from 2013-2018 were retrospectively reviewed to identify patients and obtain demographic, baseline, and short-term outcomes of maximal mouth opening (MMO), pain, and temporomandibular disability index (TDI). A total of 100 patients were included. Significant changes were noted in MMO, pain rating, and TDI from initial evaluation to discharge from physical therapy. Sex, age, and weight did not affect the outcomes. There was also no correlation between the number of visits attended and change in MMO. Patients treated conservatively did show improvements in short term outcomes (MMO, pain rating, and TDI). These changes were statistically significant, indicating that conservative therapy may be a beneficial treatment option for patients with TMJ dysfunction. Future studies assessing the long-term outcomes of TMJ patients treated conservatively would determine if this treatment is beneficial in the long-term. In addition, researching the effectiveness of specific interventions for TMJ patients, and if certain TMJ disorders are more responsive to conservative care than others would be valuable in providing information on the effectiveness of conservative treatment in this patient population.     

Treatment of heart failure: guidelines compared to clinical practice

Last decade brought great development in the treatment of patients with heart failure (HF). General use of angiotensin-converting-enzyme inhibitors (ACE-I) in patients with asymptomatic left ventricular dysfunction or with HF significantly reduced morbidity and mortality. The aim of this study was to assess how the specialists from Cardiology Department and Gastroenterology Department think that heart failure should be managed, how they implement their knowledge and if it is consistent with the recommendation of European Society of Cardiology (ESC) and whether differences exists in practice between specialists. In the first phase the specialists, cardiologists and diabetologists, answered the questions about the management of different stages of HF. In second phase we analysed medical documentation of 345 patients aged between 38 and 98 years, hospitalised in Cardiology and Gastroenterology Departments from October 2000 to February 2002 by reason of coronary artery disease, hypertension and dilated cardiomyopathy. In the third phase we compared the knowledge of heart failure management from questionnaire and its implementation, the compliance with ESC recommendation and finally whether differences in clinical practice exist between cardiologist and diabetologists. RESULTS: ACE-I were prescribed in all NYHA classes of HF. In over 50% patients in II NYHA class to 94% in IV NYHA class in Cardiology Department. Differences between the Departments in prescribing of ACE-I were observed. Beta-blockers (BB) were used with the same frequency in all NYHA classes, more often in Cardiology Department. Frequency of the administration of digoxin, diuretics, aldosterone receptor blocker was increasing starting with II NYHA class. The highest compliance between declarations from questionnaire and clinical practice concerned the use of BB and ACE-I combination.     

Risk of thromboembolic complications in patients with permanent atrial fibrillation undergoing cardioverter-defibrillator implantation

BACKGROUND: Cardioversion of atrial fibrillation (AF) carries the risk of thromboembolic complications and, therefore, anticoagulation therapy is routinely administered before and after this procedure. In patients with permanent AF who undergo implantation of cardioverter-defibrillator (ICD), anticoagulants are usually withdrawn during the perioperative period. However, in some patients sinus rhythm may be restored during defibrillation threshold (DFT) testing which potentially may increase the risk of thromboembolic complications. AIM: To assess the frequency of sinus rhythm restoration during ICD implantation in patients with permanent AF and the rate of both thromboembolic events and local bleeding complications which may occur due to temporary withdrawal of anticoagulation therapy and its re-initiation early after the procedure. METHODS: Permanent AF was present in 23 (12%) of 193 patients selected for ICD implantation. All patients received prolonged oral anticoagulation according to the generally accepted standards. Anticoagulation therapy was stopped few days before the procedure and replaced by low molecular weight heparin which was administered up to 24 hours before ICD implantation and re-initiated 12-24 hours afterwards. RESULTS: During DFT testing sinus rhythm was restored in 5 (21.7%) patients with AF. Clinical and DFT characteristics were similar in those who were converted to sinus rhythm and those who remained in AF. No thromboembolic events were noted in either group. Local haematoma at the site of ICD implantation occurred in two (8%) patients. CONCLUSIONS: Sinus rhythm was restored in 21.7% of patients with permanent AF who underwent ICD implantation. Temporary withdrawal of anticoagulation therapy did not increase the risk of thromboembolic complications, however, its early re-initiation after implantation resulted in an increase in local bleeding complication rate.     

Prenatal Sonographic Diagnosis of Premature Constriction of the Fetal Ductus Arteriosus After Maternal Self‐Medication With Benzydamine Hydrochloride

We report 3 cases of prenatal diagnosis of premature constriction of the ductus arteriosus after maternal benzydamine hydrochloride therapy (3‐mg lozenges) in third‐trimester pregnancies. In each case, fetal echocardiography revealed a dilated, hypocontractile right ventricle with severe tricuspid regurgitation and constriction of the ductus arteriosus. Although the effect of indomethacin and other nonsteroidal anti‐inflammatory drugs on prenatal ductal constriction is well known, readily available over‐the‐counter nonsteroidal anti‐inflammatory drugs such as benzydamine can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.