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  • 1
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    Role of gastric per-oral endoscopic myotomy (G-POEM) in post-lung transplant patients: a multicenter experience
    Georg Thieme Verlag KG ; 2022
    In:  Endoscopy International Open Vol. 10, No. 06 ( 2022-06), p. E832-E839
    Details
    In: Endoscopy International Open, Georg Thieme Verlag KG, Vol. 10, No. 06 ( 2022-06), p. E832-E839
    Abstract: Background and study aims Gastroparesis post-lung transplant (LTx) can lead to increased risk of gastroesophageal reflux (GER) and accelerated graft dysfunction. We aimed to evaluate the efficacy and safety of gastric per-oral endoscopic myotomy (G-POEM), a promising tool in patients with refractory gastroparesis, for managing refractory gastroparesis and GER in post-LTx patients. Patents and methods This was a multicenter retrospective study on post-LTx patients who underwent G-POEM for management of gastroparesis and GER that were refractory to standard medical therapy. The primary outcome was clinical success post-G-POEM. Secondary outcomes included the rate of post-G-POEM objective esophageal pH exam normalization, rate of gastric emptying scintigraphy (GES) normalization, technical success, and adverse events. Results A total of 20 patients (mean age 54.7 ± 14.1 years, Female 50 %) underwent G-POEM at a median time of 13 months (interquartile range 6.5–13.5) post-LTx. All G-POEM procedures were technically successful. Clinical success was achieved in 17 (85 %) patients during a median follow-up time of 8.9 (IQR: 3–17) months post-G-POEM. Overall GCSI and two of its subscales (bloating and postprandial fullness/early satiety) improved significantly following G-POEM. Two patients (10 %) developed post-procedural AEs (delayed bleeding 1, pyloric stenosis 1, both moderate in severity). Post-G-POEM GES improvement was achieved in 12 of 16 patients (75 %). All 20 patients were on proton pump inhibitors pre-G-POEM, as opposed to five post-G-POEM. Post-G-POEM PH study normalization was noted in nine of 10 patients (90 %) who underwent both pre- and post-G-poem pH testing. Conclusions G-POEM is a promising noninvasive therapeutic tool for management of refractory gastroparesis and GER post-LTx.
    Type of Medium: Online Resource
    ISSN: 2364-3722 , 2196-9736
    URL: Article
    DOI: 10.1055/a-1797-9587
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2022
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  • 2
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    A Low Molecular Weight Heparin Alters the Fetal Coagulation System in the Pregnant Sheep
    Georg Thieme Verlag KG ; 1986
    In:  Thrombosis and Haemostasis Vol. 55, No. 03 ( 1986), p. 342-346
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 55, No. 03 ( 1986), p. 342-346
    Abstract: Standard heparin and a LMWH, CY222 do not cross the placenta nor alter fetal coagulation when injected into the pregnant ewe. We found that another LMWH, Pharmuka-10169 (PK-10169) alters fetal coagulation without crossing the placenta in the pregnant sheep. To characterize this anticoagulant we measured the in vitro and in vivo effects of 125I-PK-10169 in maternal and fetal plasmas following administration of PK-10169 to the mother or fetus. The fetal anticoagulant activity was not neutralizable by protamine sulphate and was attributable to the inhibition of thrombin but not factor Xa. In vitro, the fetal anticoagulant activity had properties similar to dermatan sulphate : both catalyzed the inhibition of thrombin but not factor Xa by sheep plasma; and neither was neutralizable by protamine sulphate. These effects were due to the enhanced neutralization of thrombin by heparin cofactor II. We conclude that PK-10169 does not cross the placenta, but does induce the release of an endogenous dermatan sulphate-like substance which alters fetal coagulation.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1661560
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1986
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  • 3
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    Alpha-2-Macroglobulin Is an Important Progressive Inhibitor of Thrombin in Neonatal and Infant Plasma
    Georg Thieme Verlag KG ; 1989
    In:  Thrombosis and Haemostasis Vol. 62, No. 04 ( 1989), p. 1074-1077
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 62, No. 04 ( 1989), p. 1074-1077
    Abstract: Antithrombin III (ATIII) is the main inhibitor of thrombin in adult plasma; α2-macroglobulin (α2M) and heparin cofactor II (HCII) are of lesser importance. The relative contributions of these inhibitors to the inactivation of thrombin may differ during the neonatal period and infancy, when plasma concentrations of α2M are about twice as high as those of ATIII. We therefore compared the relative importance of these anti-proteases for the inhibition of 125I-thrombin in defibrinated pooled adult and neonatal plasma. Observations were also made in pooled plasma of 6 months old infants. 125I-thrombin-inhibitor complexes were quantitated after SDS-PAGE and autoradiography by scanning densitometry. Thrombin (2.5 NIH U/ml) was inhibited more slowly in neonatal than in adult plasma. However, both plasmas inhibited 88% of the added thrombin by 5 minutes. α2M inhibited consistently a larger fraction of thrombin in neonatal than in adult plasma. Consequently, the ratio of thrombin bound to ATIII over thrombin bound to α2M was significantly lower in neonatal ( 〈 2.5) than in adult plasma ( 〉 4.5; p 〈 0.0001). In infant plasma, this ratio was 〈 2.0. Upon addition of therapeutic amounts of heparin (0.4 U/ml), differences between the contributions of ATIII and α2M to the inhibition of thrombin were no longer apparent, as over 90% of complexed thrombin was bound to ATIII in heparinized plasmas of all age groups. We conclude that α2M is an important progressive inhibitor of thrombin in young infants. This finding may explain why healthy newborns rarely suffer from thrombosis, despite their low plasma ATIII levels.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1647120
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1989
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  • 4
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    Thrombin Generation in Newborn Plasma Is Critically Dependent on the Concentration of Prothrombin
    Georg Thieme Verlag KG ; 1990
    In:  Thrombosis and Haemostasis Vol. 63, No. 01 ( 1990), p. 027-030
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 63, No. 01 ( 1990), p. 027-030
    Abstract: The ability to generate thrombin is decreased and delayed in plasma from the healthy newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity can be produced in neonatal plasma. To test whether this observation can be explained by the low neonatal levels of the contact or vitamin K dependent factors, we measured neonatal thrombin generation after raising the concentration of these factors to adult values. We also determined whether the addition of a variety of blood products to neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled cord plasma from healthy term infants. Added individually, factors VII, IX, X or the contact factors (CF) failed to alter the rate or the total amount of thrombin generated in neonatal plasma. In contrast, the addition of prothrombin increased the total amount of thrombin generated to above adult values in both the APTT and the PT systems but did not alter the rate of thrombin generation. The rate of thrombin generation in cord plasma shortened after a combination of II, IX, X and CF was added to the APTT system or II, VII and X to the PT system. In both systems, the total amount of thrombin generated was linearly related to the initial prothrombin concentration. Each of fresh frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate (in amounts used therapeutically) caused an increase in the total amount of thrombin generated which was related to the increase in prothrombin concentration. Thus, the total amount of thrombin generated in newborn plasma is critically dependent on the prothrombin concentration whereas the rate at which thrombin is generated is dependent on the levels of many other coagulation proteins in combination.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1645680
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1990
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  • 5
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    Antithrombotic Properties of Heparin in a Neonatal Piglet Model of Thrombin-Induced Thrombosis
    Georg Thieme Verlag KG ; 1988
    In:  Thrombosis and Haemostasis Vol. 60, No. 02 ( 1988), p. 289-292
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 60, No. 02 ( 1988), p. 289-292
    Abstract: The relative deficiency of antithrombin III (AT III) in neonatal plasma results in lower recovery of heparin in some assay systems. It is uncertain whether low AT III levels also limit the antithrombotic effects of heparin in this age group. We therefore compared the antithrombotic properties of heparin in mature pigs and newborn piglets, whose coagulation and inhibitor system closely resembles that of the human neonate. Animals were pretreated with saline, 10 or 25 U/kg heparin (n ≥16 per age group and dose). Following an injection of 100 U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Significantly more 125I-fibrinogen was consumed in piglets than in pigs systemically (p 〈 0.0001), as well as within the occluded vein segment (p = 0.0112), largely because heparin was less effective in piglets than in pigs. This neonatal resistance to heparin could not be explained by lower heparin levels in the newborn animals. However, pretreatment with AT III concentrate significantly improved the antithrombotic properties of heparin in this age group (p 〈 0.0001). We conclude that physiologically low AT III levels reduce the efficacy of heparin in neutralizing thrombin activity in newborn piglets. We speculate that AT III deficiency may also limit the antithrombotic properties of heparin in newborn infants with thrombotic disease.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1647046
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1988
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  • 6
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    An Antithrombin III Assay Based on Factor Xa Inhibition Provides a More Reliable Test to Identify Congenital Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition
    Georg Thieme Verlag KG ; 1993
    In:  Thrombosis and Haemostasis Vol. 69, No. 03 ( 1993), p. 231-235
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 69, No. 03 ( 1993), p. 231-235
    Abstract: Objectives: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay. Study design: Cross-sectional study. Patient population: Sixty-seven members of a large family with type 2 AT-III deficiency. Intervention: DNA analysis was used as the reference diagnostic standard for AT-III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-α-thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography. Results: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay. Thrombin inhibition by HC-II likely accounts for the AT-III-IIa assay giving higher values than the AT-III-Xa assay since 1) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and HC-II levels, 2) the mean level of HC-II was significantly higher for individuals who had a positive difference between AT-III-IIa and AT-III-Xa levels compared to those who had a negative difference and 3) there was a significant correlation between the difference in AT-III-IIa and AT-III-Xa levels and the percentage of 125I-α-thrombin complexed to HC-II. Conclusion: The AT-III-Xa assay is a better discriminant between AT-III deficient and AT-III non deficient individuals than the AT-III-IIa assay.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1651586
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1993
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  • 7
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    Comparison of EUS-guided conventional smear and liquid-based cytology in pancreatic lesions: A systematic review and meta-analysis
    Georg Thieme Verlag KG ; 2020
    In:  Endoscopy International Open Vol. 08, No. 11 ( 2020-11), p. E1611-E1622
    Details
    In: Endoscopy International Open, Georg Thieme Verlag KG, Vol. 08, No. 11 ( 2020-11), p. E1611-E1622
    Abstract: Background and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) has limitations of inadequate sampling and false-negative results for malignancy. It has been performed using conventional smear (CS) cytology with rapid on-site evaluation (ROSE) with reasonable diagnostic accuracy. An alternative to ROSE is liquid-based cytology (LBC). Commonly used LBC techniques include precipitation-based (SurePath™) and filtration-based (ThinPrep®, CellPrep®). Data regarding the diagnostic efficacy of LBC compared with CS are limited. Methods Multiple databases were searched through March 2020 to identify studies reporting diagnostic yield of EUS-guided CS and LBC in pancreatic lesions. Pooled diagnostic odds and rates of performance for the cytologic diagnoses of benign, suspicious, and malignant lesions were calculated. Diagnostic efficacy was evaluated by pooled rates of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Nine studies with a total of 1308 patients were included in our final analysis. Pooled diagnostic odds of CS cytology were 1.69 (CI 1.02–2.79) and 0.39 (CI 0.19–0.8) for malignant lesions when compared to filtration-based and precipitation-based LBC techniques, respectively. For CS, precipitation-based and filtration-based LBC, pooled diagnostic accuracy was 79.7 %, 85.2 %, 77.3 %, sensitivity was 79.2 %, 83.6 %, 68.3 %, and specificity was 99.4 %, 99.5 %, 99.5 %, respectively. Conclusions The precipitation-based LBC technique (SurePath™) had superior diagnostic odds for malignant pancreatic lesions compared with CS cytology in the absence of ROSE. It showed superior accuracy and sensitivity, but comparable specificity and PPV. Diagnostic odds of CS cytology in the absence of ROSE were superior to the filtration-based LBC technique (ThinPrep®, Cellprep®) for diagnosing malignant pancreatic lesions.
    Type of Medium: Online Resource
    ISSN: 2364-3722 , 2196-9736
    URL: Article
    DOI: 10.1055/a-1240-0027
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2020
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  • 8
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    Efficacy and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD): A systematic review and meta-analysis of 714 patients
    Georg Thieme Verlag KG ; 2020
    In:  Endoscopy International Open Vol. 08, No. 11 ( 2020-11), p. E1664-E1672
    Details
    In: Endoscopy International Open, Georg Thieme Verlag KG, Vol. 08, No. 11 ( 2020-11), p. E1664-E1672
    Abstract: Background and study aims Endoscopic ultrasound guided pancreatic duct drainage (EUS-PDD) is a minimal-invasive therapeutic option to surgery and in patients with failed endoscopic retrograde pancreatography (ERP). The aim of this review was to quantitatively appraise the clinical outcomes of EUS-PDD by meta-analysis methods. Methods We searched multiple databases from inception through March 2020 to identify studies that reported on EUS-PDD. Pooled rates of technical success, successful drainage of pancreatic duct, clinical success, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95 % prediction interval. Results A total of 22 studies (714 patients) were included. The pooled rate of technical success in EUS-PDD was 84.8 % (95 % CI 79.1–89.2). The pooled rate of successful PD drained by EUS-PDD was 77.5 % (95 % CI 63.1–87.4). The pooled rate of clinical success of EUS-PDD was 89.2 % (95 % CI 82.1–93.7). The pooled rate of all adverse events was 18.1 % (95 % CI 14.2–22.9). On sub-group analysis, the pooled technical success and clinical success of EUS-PDD from Japanese data were considerably superior (91.2 %, 83–95.6 & 92.5 %, 83.9–96.7, respectively). The pooled rate of post EUS-PDD acute pancreatitis was 6.6 % (95 % CI 4.5–9.4), bleeding was 4.1 % (95 % CI 2.7–6.2), perforation and/or pneumoperitoneum was 3.1 % (95 % CI 1.9–5), pancreatic leak and/or pancreatic fluid collection was 2.3 % (95 % CI 1.4–4), and infection was 2.8 % (95 % CI 1.7–4.6). Conclusion EUS-PDD demonstrates high technical success and clinical success rates with acceptable adverse events. Technical success was especially high for anastomotic strictures.
    Type of Medium: Online Resource
    ISSN: 2364-3722 , 2196-9736
    URL: Article
    DOI: 10.1055/a-1236-3350
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2020
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  • 9
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    Peroral endoscopic myotomy (POEM) vs pneumatic dilation (PD) in treatment of achalasia: A meta-analysis of studies with ≥ 12-month follow-up
    Georg Thieme Verlag KG ; 2021
    In:  Endoscopy International Open Vol. 09, No. 07 ( 2021-07), p. E1097-E1107
    Details
    In: Endoscopy International Open, Georg Thieme Verlag KG, Vol. 09, No. 07 ( 2021-07), p. E1097-E1107
    Abstract: Background and study aims Peroral endoscopic myotomy (POEM) is increasingly being used as the preferred treatment option for achalasia. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of POEM versus pneumatic balloon dilation (PD). Methods We performed a comprehensive review of studies that reported clinical outcomes of POEM and PD for the treatment of achalasia. Measured outcomes included clinical success (improvement of symptoms based on a validated scale including an Eckardt score ≤ 3), adverse events, and post-treatment gastroesophageal reflux disease (GERD). Results Sixty-six studies (6268 patients) were included in the final analysis, of which 29 studies (2919 patients) reported on POEM and 33 studies (3050 patients) reported on PD and 4 studies (299 patients) compared POEM versus PD. Clinical success with POEM was superior to PD at 12, 24, and 36 months (92.9 %, vs 76.9 % P = 0.001; 90.6 % vs 74.8 %, P = 0.004; 88.4 % vs 72.2 %, P = 0.006, respectively). POEM was superior to PD in type I, II and III achalasia (92.7 % vs 61 %, P = 0.01; 92.3 % vs 80.3 %, P = 0.01; 92.3 %v 41.9 %, P = 0.01 respectively) Pooled OR of clinical success at 12 and 24 months were significantly higher with POEM (8.97; P = 0.001 & 5.64; P = 0.006). Pooled OR of GERD was significantly higher with POEM (by symptoms: 2.95, P = 0.02 and by endoscopic findings: 6.98, P = 0.001). Rates of esophageal perforation (0.3 % vs 0.6 %, P = 0.8) and significant bleeding (0.4 % vs 0.7 %, P = 0.56) were comparable between POEM and PD groups. Conclusions POEM is more efficacious than PD in the treatment of patients with achalasia during short-term and long-term follow-up, albeit with higher risk of abnormal esophageal acid exposure.
    Type of Medium: Online Resource
    ISSN: 2364-3722 , 2196-9736
    URL: Article
    DOI: 10.1055/a-1483-9406
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2021
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  • 10
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    Inhibition of Thrombin by Antithrombin III and Heparin Cofactor II In Vivo
    Georg Thieme Verlag KG ; 1995
    In:  Thrombosis and Haemostasis Vol. 73, No. 03 ( 1995), p. 405-412
    Details
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 73, No. 03 ( 1995), p. 405-412
    Abstract: The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    URL: Article
    DOI: 10.1055/s-0038-1653789
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1995
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