Peri-procedural thromboprophylaxis in the prevention of DVT in varicose vein interventions: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to determine the role of thromboprophylaxis in the prevention of venous thromboembolism in patients undergoing varicose vein interventions. METHODS: PUBMED, EMBASE and Web of Science were searched for comparative studies of patients undergoing varicose vein interventions and received either thromboprophylaxis or no thromboprophylaxis. Data were collected on the number of thrombotic events including deep vein thrombosis (DVT), pulmonary embolism (PE) and endothermal heat-induced thrombosis (EHIT) as well as bleeding events. The primary outcomes for the meta-analysis were the risk of all thrombotic events, risk of DVT and risk of bleeding. Pooled risk ratios were calculated using random effects modelling. RESULTS: Eight studies (6479 participants) were included. The use of thromboprophylaxis reduces the risk of all thrombotic events (Pooled risk ratio = 0.63, 95% Confidence interval [CI], 0.04-10.43) and the risk of DVT (Pooled risk ratio = 0.59, 95% CI, 0.08-4.60) with no increased risk of bleeding (Pooled risk ratio = 0.66, 95% CI, 0.06-7.21]. Rivaroxaban has similar efficacy in the prevention of DVT compared to Fondaparinux in patients undergoing endovenous ablation of varicose veins (Pooled risk ratio = 0.68, 95% CI, 0.06-7.41). An extended course of thromboprophylaxis reduces the risk of developing DVT compared to a short course (Pooled risk ratio = 1.40, 95% CI, 0.44-4.46). However, the two studies reporting on the duration of thromboprophylaxis did not stratify patients according to their risk of developing venous thromboembolism. CONCLUSION: The use of thromboprophylaxis in patients undergoing varicose vein interventions reduces the risk of venous thromboembolism with no significant increase in the risk of bleeding. However, the included studies were underpowered with high to moderate risk of bias. Therefore, more randomised controlled trials with a large sample size are needed in order to provide high quality evidence for clinical practice.

Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study.

BACKGROUND: The chemokine CXCL12 and its two receptors (CXCR4 and CXCR7) are involved in inflammation and hematopoietic cell trafficking. This study was designed to investigate molecular docking interactions of four popular cardiovascular-active natural compounds; curcumin, resveratrol, quercetin, and eucalyptol; with these receptors and to predict their drug-like properties. We hypothesize that these compounds can modify CXCL12/CXCR4/CXCR7 pathway offering benefits for coronary artery disease patients. METHODS: Docking analyses were carried and characterized by Molecular Environment (MOE) software. Protein Data Bank ( http://www.rcsb.org/ ) has been retrieved from protein structure generation and crystal structures of CXCR4 and CXCR7 receptors (PDB code = 3ODU and 6K3F). The active sites of these receptors were evaluated and extracted from full protein and molecular docking protocol was done for compounds against them. The presented parameters included docking scores, ligand binding efficiency, and hydrogen bonding. The pharmacokinetic/toxic properties (ADME/T) were calculated using SwissADME, ProTox-II, and Pred-hERG softwares to predict drug-like properties of the compounds. The thermochemical and molecular orbital analysis, and molecular dynamics simulations were also done. RESULTS: All compounds showed efficient interactions with the CXCR4 and CXCR7 receptors. The docking scores toward proteins 3ODU of CXCR4 and 6K3F of CXCR7 were - 7.71 and - 7.17 for curcumin, - 5.97 and - 6.03 for quercetin, - 5.68 and - 5.49 for trans-resveratrol, and - 4.88 and - 4.70 for (1 s,4 s)-eucalyptol respectively indicating that all compounds, except quercetin, have more interactions with CXCR4 than with CXCR7. The structurally and functionally important residues in the interactive sites of docked CXCR4-complex and CXCR7-complex were identified. The ADME analysis showed that the compounds have drug-like properties. Only (1 s,4 s)-Eucalyptol has potential weak cardiotoxicity. The results of thermochemical and molecular orbital analysis and molecular dynamics simulation validated outcomes of molecular docking study. CONCLUSIONS: Curcumin showed the top binding interaction against active sites of CXCR4 and CXCR7 receptors, with the best safety profile, followed by quercetin, resveratrol, and eucalyptol. All compounds demonstrated drug-like properties. Eucalyptol has promising potential because it can be used by inhalation or skin massage. To our knowledge, this is the first attempt to find binding interactions of these natural agents with CXCR4 and CXCR7 receptors and to predict their druggability.

Development and Validation of an Arabic Version of the Drug Abuse Screening Test-10 (DAST-10) among Saudi Drug Abusers.

The Drug Abuse Screening Test-10 (DAST-10) is a valid and reliable screening tool for drug use-related problems, however there is no Arabic version. To our knowledge, this is the first study to develop and validate an Arabic DAST-10 version. Saudi young adults participated in the study as two groups; drug users (n=360) recruited from Alamal Complex for Mental Health, Jeddah, and drug non-users (n=100). Three measures were used: (1) Demographic and drug use description questionnaire, (2) Arabic DAST-10 version, and (3) Urine analysis for drug use. The developed Arabic DAST-10 version demonstrated adequate internal consistency. High correlations were shown between its scores and the two standard measures (urine analysis and self-reporting question) indicating good criterion validity. Sensitivity and specificity values were between 91.5 - 99.7% and 57 - 92.5% with different DAST-10 cutoff values. An optimal performance at a cutoff score of 3 or more was most likely to significantly identify drug users. Discriminant analysis showed that more than 90% of cases were correctly classified. Distribution of participants in categories of DAST-10 scores according to degree of problems was reasonable. It is concluded that the developed Arabic DAST-10 version is a reliable and valid screening tool for drug use-related problems in Arabic speakers.

Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia.

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands. Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation. Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD). Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families.

Protective effect of 6-paradol in acetic acid-induced ulcerative colitis in rats.

BACKGROUND: Ulcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-α activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory cells, leading to ulceration and haemorrhage through cytotoxic reactive oxygen species. 6-Paradol, a dietary component in several plants belonging to the Zingiberaceae family, has shown anti-inflammatory and antioxidant activities. Current study evaluates the effect of 6-paradol in amelioration of ulcerative colitis in rats for the first time. METHODS: 6-Paradol (95% purity) was obtained from seeds of Aframomum melegueta. Rats were divided randomly into six groups (n = 8). Group one was administered normal saline; group two was treated with the vehicle only; group three, sulfasalazine 500 mg/kg; and groups four, five, and six, were given 6-paradol (50, 100, 200, respectively) mg/kg orally through gastric gavage for 7 days. Colitis was induced on 4th day by intrarectal administration of 2 ml acetic acid (3%), approximately 3 cm from anal verge. On 8th day, rats were sacrificed, and distal one-third of the colon extending proximally up to 4 cm from anal orifice was taken for biochemical and gross examination. Two centimetres of injured mucosal portion was taken for histopathological investigations. SPSS (ver.26) was used for statistical analysis. RESULTS: Colonic and serum glutathione (GSH) levels decreased, while colonic and serum malondialdehyde (MDA), colonic myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6), serum tumour necrosis factor-α (TNF-α) levels, and colon weight to length ratio were increased significantly in the colitis untreated group compared to normal control. Treatment with 6-paradol considerably improved all these parameters, especially at a dose of 200 mg/kg (p < 0.001), revealing non-significant differences with sulfasalazine 500 mg/kg and normal control (p = 0.998). Sulfasalazine and 6-paradol in a dose dependent manner also markedly reversed mucosal oedema, atrophy and inflammation, cryptic damage, haemorrhage, and ulceration. There were non-significant differences between low and medium doses and between medium and high doses of 6-paradol for IL-6 and serum MDA levels. CONCLUSION: 6-Paradol demonstrated protection against acetic acid-induced ulcerative colitis, probably by anti-inflammatory and antioxidant actions.

A systematic review and meta-analysis of comparative studies comparing nonthermal versus thermal endovenous ablation in superficial venous incompetence.

OBJECTIVE: Endovenous thermal ablation (TA) offers an effective initial treatment option for superficial venous incompetence of the lower limb. These techniques offer lower complication rates with similar efficacy to traditional open surgery. In recent years, nonthermal ablation (NTA) in the form of mechanochemical ablation and cyanoacrylate vein ablation has been suggested to further reduce perioperative morbidity. This study aimed to compare the use of both thermal and nonthermal endovenous ablative techniques in the management of superficial venous incompetence. METHODS: A search of online databases including MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane database was last performed in January 2019. Comparative studies comparing NTA with TA were included. The primary outcome was technical success. Secondary outcomes included operative pain, complications, modification of disease severity, and quality of life. RESULTS: Six studies describing the outcomes of 1236 participants and 1256 truncal ablations were included for analysis. Follow-up ranged from 6 weeks to 36 months. With regard to overall technical success, 458 of 483 (94.8%) receiving NTA and 521 of 553 (94.2%) undergoing TA had successful truncal ablation on follow-up ultrasound imaging at the study end point (pooled risk ratio, 1.01; 95% confidence interval [CI], 0.99-1.04). Subgroup analysis identified no difference in success between groups during immediate, 6-month, 12-month, or >12-month follow-up periods. Postprocedural pain was generally lower in those undergoing NTA with a mean difference of -18.11 (95% CI, -36.7 to 0.48). Techniques experienced significatly lower rates of ecchymosis (risk ratio, 0.43; 95% CI, 0.23-0.78), with no difference identified with regard to rates of paresthesia, phlebitis, and skin pigmentation. Further assessment of quality of life (mean difference, -0.27; 95% CI, -0.57 to 0.04) and Venous Clinical Severity Score (-0.52; 95% CI, -1.05 to 0.01) revealed no difference between groups. Included data were deemed of moderate methodologic quality. CONCLUSIONS: Nonthermal techniques are as effective as standard TA in the first year and, in some studies, may be associated with less procedural pain. These data suggest that NTA offers an alternative and safe means to treat superficial venous disease. There is, however, a need for further powered trials with larger numbers of patients and longer follow-up to definitively examine this hypothesis.

Effect of genetic polymorphisms in SREBF-SCAP pathway on therapeutic response to rosuvastatin in Saudi metabolic syndrome patients.

AIM: Genetic variants contribute to statins' therapeutic variability. SREBF-SCAP pathway is a key player in lipid homeostasis. Hence, effect of SREBF-SCAP polymorphisms on therapeutic response was studied. PATIENTS & METHODS: Metabolic syndrome patients of either sex were prescribed rosuvastatin 10 mg for 24 weeks. Clinical, anthropometric and lipid measurements were done before and after treatment. Genotyping was done by pyrosequencing. RESULTS & CONCLUSION: No associations of SCAP and SREBF-1a genotypes with baseline lipids but significant associations with lipid reductions were observed. Significant effect of SCAP (GG; B = -8.16, p = 0.001); SREBF-1a (GG; B = -7.47, p = 0.001) and SREBF-1a (-delG; B = -7.42, p = 0.001) was observed on total cholesterol reduction. Additive trend was found between SCAP genotypes and lipid reductions. A total of 88% responders have SCAP 'G' allele (p = 0.001). Patients carrying SCAP (GG) and SREBF-1a (GG and -delG) have 9.5-, 8.6- and 14.6-times more likelihood of being responders (p < 0.05). 'G' allele in SCAP and SREBF-1a is significant predictor of rosuvastatin response.

Cystic fibrosis: current therapeutic targets and future approaches.

OBJECTIVES: Study of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use. METHODS: Extensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics. KEY FINDINGS: Cystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Some improvement is observed by the corrector drugs. Other promising approaches are gene therapy, targeting of cellular interactomes, and newer drugs for symptomatic improvement. CONCLUSIONS: The treatment has a long way to go as most of the existing therapeutics is for older children. Other limiting factors include mutation class, genetic profile, drug interactions, adverse effects, and cost. Novel approaches like gene transfer/gene editing, disease modeling and search for alternative targets are warranted.

Immobilization and characterization of inulinase from Ulocladium atrum on nonwoven fabrics.

Ulocladium atrum inulinase was immobilized on different composite membranes composed of chitosan/nonwoven fabrics. Km values of free and immobilized U. atrum inulinase on different composite membranes were calculated. The enzyme had optimum pH at 5.6 for free and immobilized U. atrum inulinase on polyester nonwoven fabric coated with 3 percent chitosan solution (PPNWF3), but optimum pH was 5 for immobilized U. atrum inulinase on polyester and polypropylene nonwoven fabrics coated with 1 percent chitosan solution. The enzyme had optimum temperature at 40 degree C for immobilized enzyme on each of polyester and polypropylene composite membranes coated with 1 percent chitosan, while it was 50 degree C for free and immobilized enzyme on polypropylene nonwoven fabric coated with 3 percent chitosan solution. Free U. atrum inulinase was stable at 40 degree C but thermal stability of the immobilized enzyme was detected up to 60 degree C. Reusability of immobilized enzyme was from 38 to 42 cycles of reuse; after this, the immobilized enzyme lost its activity completely. In conclusion, immobilized U. atrum inulinase was considerably more stable than the free enzyme, and could be stored for extended periods.

Effect of sequential versus standard Helicobacter pylori eradication therapy on the associated iron deficiency anemia in children.

OBJECTIVES: Helicobacter pylori infection may be associated with low iron stores and iron deficiency anemia. Eradication of infection by the standard 10-day therapy (a proton pump inhibitor [PPI], clarithromycin and amoxicillin; each given orally, twice daily) is decreasing. The sequential 10-day therapy (a PPI and amoxicillin; each given orally twice daily for 5 days; followed by a PPI, clarithromycin and tinidazole; each given orally twice daily for another 5 days) may achieve higher eradication rates. This study was designed to investigate, which eradication regimen; sequential or standard; more effectively improves the associated iron status and iron deficiency in children. MATERIALS AND METHODS: Children (12-15 years) with H. pylori active infection (positive H. pylori immunoglobulin G and urea breath test [UBT]) were subjected to measurement of serum ferritin and then randomized into two groups to receive standard and sequential eradication therapy. Six weeks after completing therapy, UBT was performed to check eradication and serum ferritin was measured to estimate affection by therapy. Statistical Package for Social Sciences (SPSS, IBM, NY, USA) was used for analysis. RESULTS: H. pylori eradication rates of sequential versus standard therapy were non-significantly different. Serum ferritin non-significantly differed between the two therapy groups and in the same group before and after treatment. CONCLUSIONS: There is no significant difference in H. pylori eradication rates between sequential and standard therapies in children. Moreover, no significant relationship was found between eradication therapy and serum ferritin. Further studies enrolling more markers of iron deficiency are required to precisely assess this relationship.

Delayed presentation of a traumatic brachial artery pseudoaneurysm.

Delayed presentation of a brachial artery pseudoaneurysm following penetrating trauma is infrequently reported. We report the case of a 23-year-old male who presented three months following a penetrating trauma to his antecubital fossa with a sudden exacerbation of swelling and tenderness of his elbow. Doppler ultrasound and computed tomography arteriography confirmed the presence of a large pseudoaneurysm. Surgical reconstruction was performed using the long saphenous vein as an interposition vein graft, restoring normal arterial circulation.

The management of mycotic femoral pseudoaneurysms in intravenous drug abusers.

Mycotic femoral pseudoaneurysms, particularly in the drug-abusing population, pose a difficult problem to the vascular surgeon. Management ranges from ligation with debridement to extra-anatomical bypass. This study reviewed the management of mycotic femoral pseudoaneurysms presenting in intravenous drug abusers to an inner city tertiary referral center. Between 2001 and 2006, 11 cases presenting in nine patients were treated. The mean age was 30.7 years with a male-to-female ratio of 1:2. Eight patients had a positive viral status for the human immunodeficiency virus and/or hepatitis C. Two patients re-presented with a contralateral pseudoaneurysm. A combination of groin pain and swelling was the most common presentation. Two patients presented with significant hemorrhage. The diagnosis was confirmed by ultrasound in the majority of cases. Nine cases were managed with arterial ligation and debridement of the necrotic tissue. The two remaining cases were managed with ultrasound-guided thrombin injection and arterial puncture closure. On follow-up, one patient required a below-knee amputation following reinjection into the postoperative wound site. One further patient underwent a fifth metatarsal amputation due to ischemia. Ligation and debridement are well tolerated in the majority of drug-abusing patients diagnosed with mycotic femoral pseudoaneurysms.