15 results on '"Assi Z"'
Search Results
2. The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat
- Author
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Sukhotnik, I., Shahar, Y. Ben, Pollak, Y., Dorfman, T., Shefer, H. Kreizman, Assi, Z. E., Mor-Vaknin, N., and Coran, A. G.
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- 2017
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3. Investigations of the Thermally Induced Hydrogen Release of NaBh4, Nh3Bh3and Their Geopolymer Composites
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Assi, Z., primary, Schomborg, L., additional, and Rüscher, C. H., additional
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- 2017
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4. NH3 BH3 and NaBH4 Enclosed in Geopolymers and Zeolites
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Rüscher, C. H., primary, Schomborg, L., additional, Assi, Z., additional, and Buhl, J. C., additional
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- 2016
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5. The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat.
- Author
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Sukhotnik, I., Shahar, Y. Ben, Pollak, Y., Dorfman, T., Shefer, H. Kreizman, Assi, Z. E., Mor-Vaknin, N., and Coran, A. G.
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INTESTINAL disease treatment ,EPITHELIAL cells ,SURGICAL excision ,INTESTINAL surgery ,CYTOPLASMIC filaments ,LABORATORY rats ,SMALL intestine surgery ,ANIMAL experimentation ,APOPTOSIS ,BIOLOGICAL models ,CELL physiology ,CYTOPLASM ,CYTOSKELETAL proteins ,DIGESTIVE organ surgery ,GENES ,IMMUNOHISTOCHEMISTRY ,SMALL intestine ,POLYMERASE chain reaction ,PROTEINS ,RATS ,RNA ,WESTERN immunoblotting ,REVERSE transcriptase polymerase chain reaction ,SHORT bowel syndrome - Abstract
Purpose: Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS).Materials and Methods: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry.Results: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-β, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals).Conclusions: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation. [ABSTRACT FROM AUTHOR]- Published
- 2018
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6. INVESTIGATIONS OF THE THERMALLY INDUCED HYDROGEN RELEASE OF NaBH4, NH3BH3 AND THEIR GEOPOLYMER COMPOSITES.
- Author
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Assi, Z., Schomborg, L., and Rüscher, C. H.
- Subjects
POLYMERIC composites ,HYDROGEN storage ,HYDROGEN ,POLYMERS ,INFRARED absorption - Abstract
Some new applications in geopolymer research concerning hosting hydrogen storage materials have been reported recently. According to this, sodium boronhydride (SB = NaBH
4 ) and ammoniaborane (AB = NH3 BH3 ) could be re-crystallized within a geopolymer (G). In this study an investigation of the thermally induced hydrogen release reactions and destruction products of these new materials in comparison to the behavior of SB and AB were carried out at temperatures up to 400°C. New results are obtained in TG/DTA and temperature dependent infrared absorption (TIR) experiments, where the different materials were diluted in KBr and pressed in pellets. The melting of AB is observed at the same temperature of 115-118°C for AB and AB-G in DTA and TIR experiments. Hydrogen release could be followed using the reduction reaction of NaNO3 added in the pressed pellet starting from about 110°C for AB and AB-G and with a maximum at 120°C in accordance with the first exothermic maximum in DTA. The formation of BH4 - anions indicating the formation of DADB ([(NH3 )2 BH2 ]BH4 ]) and NH2 of PAB (poly-aminoborane) are observed at about 110 and 120°C for AB-G and AB, respectively. SB-G shows a temperature shift from about 250 to 300°C in the reaction with oxygen depending on being dried by evacuating previous to the temperature treatment or not. A similar effect is observed for SB, as well, but with a shift of only 10°C. The TIR method conducted on SB using NaNO3 indicates an initial hydrogen release between 200 and 300°C and a more pronounced effect between 300 and 400°C. An increase in NaBO2 could be detected above 300°C. Indications of a possible transient state could be seen at about 1575 cm-1 in the IR absorption spectra between 200 and 300°C. [ABSTRACT FROM AUTHOR]- Published
- 2016
7. Esophageal Atresia with Tracheoesophageal Fistula Is Associated with Consanguinity.
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Nassar R, Hougui O, Zerem M, Omary M, Assi Z, Ling G, and Yerushalmi B
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- Humans, Retrospective Studies, Female, Male, Israel epidemiology, Incidence, Infant, Newborn, Arabs, Risk Factors, Esophageal Atresia epidemiology, Tracheoesophageal Fistula epidemiology, Consanguinity, Jews statistics & numerical data
- Abstract
Objective: To examine the association between nonsyndromic esophageal atresia with tracheoesophageal fistula (EA-TEF) and consanguinity., Study Design: A retrospective study comparing the incidence of EA-TEF between a low-consanguineous Jewish population and a high-consanguineous Bedouin population. All patients were treated at Soroka University Medical Center, the only tertiary medical center in southern Israel., Results: From 2000 to 2022, 579 130 children were born in southern Israel, and 386 915 (66.8%) were Jewish, and 192 215 were Bedouin Muslims. A total of 96 patients were diagnosed with EA-TEF; 83 of them were nonsyndromic. The incidence of EA-TEF was 1.66 cases per 10 000 live births and was statistically higher among the Bedouin population (3 vs 0.95 cases per 10 000 live births; P < .001). The consanguinity rate among the Bedouin group was higher compared with the Jewish (67.8% vs 0%; P < .001). There were no differences in other risk factors., Conclusions: The incidence of EA-TEF is higher among the Bedouin population that lives in the same geographic region and has the same medical access as the Jewish population, proposing consanguinity as a risk factor for EA-TEF., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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8. Orchiopexy: one procedure, two diagnoses - different male infertility outcomes.
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Newman NH, Farber I, Lunenfeld E, Zeadna A, Vardi IH, and Assi Z
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- Humans, Male, Retrospective Studies, Adult, Spermatic Cord Torsion surgery, Spermatic Cord Torsion diagnosis, Child, Adolescent, Treatment Outcome, Semen Analysis, Young Adult, Child, Preschool, Jews, Arabs, Israel epidemiology, Orchiopexy, Cryptorchidism surgery, Cryptorchidism diagnosis, Infertility, Male surgery, Infertility, Male etiology, Infertility, Male diagnosis, Sperm Count
- Abstract
Abstract: Infertility, affecting one in six couples, is often related to the male partner's congenital and/or environmental conditions or complications postsurgery. This retrospective study examines the link between orchiopexy for undescended testicles (UDT) and testicular torsion (TT) in childhood and adult fertility as assessed through sperm analysis. The study involved the analysis of semen samples from 7743 patients collected at Soroka University Medical Center (Beer Sheva, Israel) between January 2009 and December 2017. Patients were classified into two groups based on sperm concentration: those with concentrations below 5 × 10 6 sperm per ml (AS group) and those above (MN group). Medical records and surgical histories were reviewed, categorizing orchiopexies by surgical approach. Among 140 individuals who had undergone pediatric surgery, 83 (59.3%) were placed in the MN group and 57 (40.7%) in the AS group. A higher likelihood of being in the MN group was observed in Jewish compared to Arab patients (75.9% vs 24.1%, P = 0.006). In cases of childhood UDT, 45 (78.9%) patients exhibited sperm concentrations below 5 × 10 6 sperm per ml ( P < 0.001), and 66 (76.7%) had undergone unilateral and 18 (20.9%) bilateral orchiopexy. Bilateral orchiopexy was significantly associated with lower sperm concentration, total motility, and progressive motility than unilateral cases ( P = 0.014, P = 0.001, and P = 0.031, respectively). Multivariate analysis identified UDT as a weak risk factor for low sperm concentration (odds ratio [OR]: 2.712, P = 0.078), with bilateral UDT further increasing this risk (OR: 6.314, P = 0.012). Jewish ethnicity and TT diagnosis were associated with a reduced risk of sperm concentrations below 5 × 10 6 sperm per ml. The findings indicate that initial diagnosis, surgical approach, and ethnicity markedly influence male fertility outcomes following pediatric orchiopexy., (Copyright © 2024 Copyright: ©The Author(s)(2024).)
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- 2024
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9. Performance of Echinococcosis Serology is Associated with Disease Endemicity, Hydatid Cyst Location, Eosinophilia, Imaging Finding, and Treatment.
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Shmueli M, Van Buren J, Sagi O, Grupel D, Sheves A, Assi Z, and Ben-Shimol S
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- Humans, Child, Retrospective Studies, Male, Female, Adolescent, Enzyme-Linked Immunosorbent Assay, Serologic Tests methods, Child, Preschool, Animals, Echinococcosis epidemiology, Echinococcosis diagnosis, Eosinophilia epidemiology, Endemic Diseases, Sensitivity and Specificity
- Abstract
Background: We aimed to assess echinococcosis serology performance for diagnosing cystic echinococcosis (CE) in children living in CE-endemic vs. non-endemic populations, and in different clinical settings., Methods: A retrospective cohort study, assessing children with ELISA test for echinococcosis, 2005-2021. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated comparing CE-endemic vs. non-endemic populations, cases with/without eosinophilia, and cases with/without CE-suggestive imaging findings. Additionally, we examined the association between serology titers/levels (values) and clinical characteristics., Results: Of 273 cases, 66 (24%) were confirmed as CE. Overall, 97% of CE were in Bedouin children, and the pre-test probability was 28% vs. 9% (p < 0.001) in CE-endemic vs. non-endemic population, respectively. Sensitivity was higher in hepatic than extra-hepatic CE (74% vs. 47%). Overall specificity was 86%. PPVs were higher in CE-endemic population compared to non-endemic (66% vs. 22%), while NPVs were higher in non-endemic population (100% vs. 87%). Eosinophilia was associated with lower specificity (73% vs. 94%) and PPV (47% vs. 78%). Typical imaging was associated with higher specificity (94% vs. 82%) and PPV (91% vs. 11%), while NPVs were lower in typical imaging cases (77% vs. 98%). Higher titer levels (above median) were associated with typical imaging (76% vs. 49%), higher PPV (79% vs. 43%), albendazole treatment (100% vs. 56%), surgery (60% vs. 19%), and new imaging finding (75% vs. 0%)., Conclusions: Echinococcosis serology performance was impacted by disease endemicity, and by various clinical characteristics. These findings may assist physicians in the interpretation of echinococcosis serology results., (© 2023. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)
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- 2024
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10. Albendazole Monotherapy for Pediatric Cystic Echinococcosis: A Case Series.
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Shmueli M, Elamour S, Sagi O, Grupel D, Assi Z, and Ben-Shimol S
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- Humans, Child, Albendazole therapeutic use, Albendazole adverse effects, Retrospective Studies, Echinococcosis drug therapy, Cysts chemically induced, Cysts drug therapy, Echinococcosis, Hepatic drug therapy
- Abstract
Background: Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with albendazole monotherapy., Methods: A retrospective case series, 2005-2021, assessing factors leading to albendazole monotherapy, demographic, clinical, duration of treatment and follow-up, and outcome (changes in cyst size and side effects) characteristics., Results: Overall, we identified 18 patients with 31 cysts; liver: 68% (n = 21), lungs: 29% (n = 9), and kidney: 3% (n = 1). Mean cyst size was 4.5 ± 2.6 cm. Reasons for administrating albendazole monotherapy were small (< 4 cm) cyst size (56%), difficulty to operate (33%) and comorbidity (22%). Duration of treatment (range 1-32 months) was 1, 2-3, 4-6 and > 6 months in 28% (n = 5), 39% (n = 7), 17% (n = 3) and 17% (n = 3) of children, respectively. Duration of follow up (range 1-87 months) was 1, 2-3, 4-6 and > 6 months in 11% (n = 2), 11% (n = 2), 17% (n = 3) and 61% (n = 11) of children, respectively. Overall, 83% (n = 15) of patients experienced lack of cyst growth, and 72% (n = 13) experienced reduction in cyst size, while 44% (n = 8) experienced reduction larger than 50%. Full resolution was noted in 22% (n = 4) of patients. In three cases (17%) treatment failure was recorded: one (6%) recurrence, and two cases (11%) of cyst growth. Neutropenia was recorded in two patients (11%), and liver enzymes elevation was recorded in six patients (33%)., Conclusions: Albendazole monotherapy may be an adequate treatment for selected cases of CE disease in children, especially in CE with small, hepatic cysts., (© 2023. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)
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- 2023
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11. Treatment of Cystic Echinococcosis in Children: A Single Center Experience.
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Sheves A, Fuxman Y, Gazer B, Shmueli M, Van Buren J, Ben-Shimol S, and Assi Z
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- Humans, Child, Albendazole therapeutic use, Retrospective Studies, Anthelmintics therapeutic use, Echinococcosis drug therapy, Cysts drug therapy
- Abstract
Background: Cystic echinococcosis (CE) treatment is complicated, relying on cysts characteristics, host factors and possible treatment adverse events. We assessed childhood CE treatment characteristics., Methods: A retrospective cohort study, 2005-2021, which presents our experience with treating children with CE. We compared therapeutic interventions use in association with the location, size and number of cysts. Additionally, we assessed complications rate following those interventions., Results: Sixty six children had CE; 97% were Bedouins. Overall, 183 cysts were identified in 74 organs: liver (n = 47, 64%), lungs (n = 23, 31%), brain, para-ovarian, kidney and peritoneum (other-grouped, n = 4, 5%). Mean ± Standard deviation largest cyst size (per patient) was 6.6 ± 3.2 cm. Treatment with albendazole was administered to 94% of CE, while albendazole monotherapy was used in 27% (n = 18, including 4 cases with extra-hepatic cysts). Surgical interventions included drainage/puncture, aspiration, injection and reaspiration (PAIR; n = 20), mainly performed in hepatic-CE (40% vs. 4% in pulmonary-CE, and 0% in other-CE), excision and drainage (n = 34) and complete excision (n = 10), mainly done in other-CE (50% vs. 26% and 4% in pulmonary-CE and hepatic-CE, respectively). Larger cyst size was associated with complete excision compared with albendazole monotherapy. The number of cysts was not associated with the chosen intervention. Fever was recorded following 39% of surgical interventions. Local surgical complications were relatively rare., Conclusions: Cysts location and size affected treatment choice among CE patients. Procedures with drainage had relatively higher rate of complications, including recurrence. Albendazole monotherapy may be a viable therapeutic option in selected CE cases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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12. Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis.
- Author
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Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, Jaff MR, Razavi MK, Kindzelski AL, Bashir R, Patel P, Sharafuddin M, Sichlau MJ, Saad WE, Assi Z, Hofmann LV, Kennedy M, and Vedantham S
- Subjects
- Acute Disease, Adult, Anticoagulants administration & dosage, Female, Humans, Male, Middle Aged, Postthrombotic Syndrome etiology, Anticoagulants adverse effects, Endovascular Procedures adverse effects, Femoral Vein surgery, Iliac Vein surgery, Mechanical Thrombolysis adverse effects, Postthrombotic Syndrome epidemiology
- Abstract
Background: The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) previously reported that pharmacomechanical catheter-directed thrombolysis (PCDT) did not prevent postthrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis. In the current analysis, we examine the effect of PCDT in ATTRACT patients with iliofemoral deep vein thrombosis., Methods: Within a large multicenter randomized trial, 391 patients with acute deep vein thrombosis involving the iliac or common femoral veins were randomized to PCDT with anticoagulation versus anticoagulation alone (No-PCDT) and were followed for 24 months to compare short-term and long-term outcomes., Results: Between 6 and 24 months, there was no difference in the occurrence of PTS (Villalta scale ≥5 or ulcer: 49% PCDT versus 51% No-PCDT; risk ratio, 0.95; 95% CI, 0.78-1.15; P=0.59). PCDT led to reduced PTS severity as shown by lower mean Villalta and Venous Clinical Severity Scores ( P<0.01 for comparisons at 6, 12, 18, and 24 months), and fewer patients with moderate-or-severe PTS (Villalta scale ≥10 or ulcer: 18% versus 28%; risk ratio, 0.65; 95% CI, 0.45-0.94; P=0.021) or severe PTS (Villalta scale ≥15 or ulcer: 8.7% versus 15%; risk ratio, 0.57; 95% CI, 0.32-1.01; P=0.048; and Venous Clinical Severity Score ≥8: 6.6% versus 14%; risk ratio, 0.46; 95% CI, 0.24-0.87; P=0.013). From baseline, PCDT led to greater reduction in leg pain and swelling ( P<0.01 for comparisons at 10 and 30 days) and greater improvement in venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life unit difference 5.6 through 24 months, P=0.029), but no difference in generic quality of life ( P>0.2 for comparisons of SF-36 mental and physical component summary scores through 24 months). In patients having PCDT versus No-PCDT, major bleeding within 10 days occurred in 1.5% versus 0.5% ( P=0.32), and recurrent venous thromboembolism over 24 months was observed in 13% versus 9.2% ( P=0.21)., Conclusions: In patients with acute iliofemoral deep vein thrombosis, PCDT did not influence the occurrence of PTS or recurrent venous thromboembolism. However, PCDT significantly reduced early leg symptoms and, over 24 months, reduced PTS severity scores, reduced the proportion of patients who developed moderate-or-severe PTS, and resulted in greater improvement in venous disease-specific quality of life., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00790335.
- Published
- 2019
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13. The contemporary hybrid operative procedure for incapacitating post-thrombotic iliofemoral and vena caval obstruction improves procedural outcomes.
- Author
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Comerota AJ, Lurie F, and Assi Z
- Subjects
- Adolescent, Adult, Aged, Anticoagulants therapeutic use, Chronic Disease, Combined Modality Therapy, Female, Humans, Iliac Vein diagnostic imaging, Iliac Vein physiopathology, Male, Middle Aged, Postoperative Complications therapy, Postthrombotic Syndrome diagnostic imaging, Postthrombotic Syndrome physiopathology, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Vascular Patency, Vena Cava, Inferior diagnostic imaging, Vena Cava, Inferior physiopathology, Young Adult, Blood Vessel Prosthesis Implantation adverse effects, Blood Vessel Prosthesis Implantation instrumentation, Endovascular Procedures adverse effects, Endovascular Procedures instrumentation, Iliac Vein surgery, Postthrombotic Syndrome surgery, Vena Cava, Inferior surgery
- Abstract
Objective: Chronic, post-thrombotic iliofemoral and inferior vena caval obstruction is associated with debilitating morbidity. Venoplasty and stenting are often successful; however, in the presence of a diseased or occluded common femoral vein (CFV), failure is common. A hybrid operative procedure of open surgical CFV endovenectomy and endoluminal recanalization or bypass of the obstructed iliofemoral and vena caval segments has been developed and modified. The purpose of this report was to assess the technical evolution of this procedure on operative complications., Methods: Thirty-one patients undergoing CFV endovenectomy and proximal ipsilateral endoluminal reconstruction (iliac, inferior vena caval) or contralateral outflow were analyzed. The initial techniques of patient management were compared with the present contemporary techniques, evaluating procedural complications and failures. The contemporary procedure evolved to include routine axial imaging, preoperative venography through the popliteal vein, preoperative passage of a guidewire or catheter into the patent vena cava, placement of an ipsilateral popliteal vein sheath for intraoperative and postoperative anticoagulation, routine patch closure, routine arteriovenous fistulas, routine completion intravascular ultrasound, and long-term anticoagulation with warfarin to a target international normalized ratio of 3.0 to 4.0. Procedure-related complications were compared between the initial and contemporary techniques., Results: Of 17 patients treated with the early techniques, 15 (88%) had major complications: 5 iliofemoral thromboses, 4 major wound bleeds, 4 wound infections, and 2 CFV stenoses requiring reintervention. One iliac vein rupture treated with a stent graft thrombosed. Of 14 patients treated with the contemporary techniques, 2 (14%; P = .006) had major complications: 1 bleed and 1 infected seroma. One intraoperative iliac vein rupture, treated with a second stent relining the first, remains patent., Conclusions: Contemporary hybrid operative techniques for incapacitating post-thrombotic iliofemoral and vena caval obstruction increase procedural success and reduce complications compared with the initial approach. The contemporary techniques are recommended for patients undergoing hybrid operative management of post-thrombotic iliofemoral and vena caval occlusion involving the CFV., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2019
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14. Which melanoma patient carries a BRAF-mutation? A comparison of predictive models.
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Eigentler T, Assi Z, Hassel JC, Heinzerling L, Starz H, Berneburg M, Bauer J, and Garbe C
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- Adult, Aged, DNA Mutational Analysis methods, Female, Humans, Logistic Models, Male, Melanoma diagnosis, Middle Aged, Nomograms, Regression Analysis, Sensitivity and Specificity, Skin Neoplasms diagnosis, Statistics as Topic methods, Melanoma genetics, Mutation, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms genetics
- Abstract
Background: In patients with advanced melanoma the detection of BRAF mutations is considered mandatory before the initiation of an expensive treatment with BRAF/MEK inhibitors. Sometimes it is difficult to perform such an analysis if archival tumor tissue is not available and fresh tissue has to be collected., Results: 514 of 1170 patients (44%) carried a BRAF mutation. All models revealed age and histological subtype of melanoma as the two major predictive variables. Accuracy ranged from 0.65-0.71, being best in the random forest model. Sensitivity ranged 0.76-0.84, again best in the random forest model. Specificity was low in all models ranging 0.51-0.55., Methods: We collected the clinical data and mutational status of 1170 patients with advanced melanoma and established three different predictive models (binary logistic regression, classification and regression trees, and random forest) to forecast the BRAF status., Conclusions: Up to date statistical models are not able to predict BRAF mutations in an acceptable accuracy. The analysis of the mutational status by sequencing or immunohistochemistry must still be considered as standard of care., Competing Interests: TKE has received personal fees for participating in advisory boards and lectures from BMS, Amgen, MSD, and Roche. JH has received personal fees for participating in advisory boards and lectures from BMS, Amgen, MSD, Novartis and Roche. LH reports personal fees and other from GSK, BMS, Roche during conduct of the study. CG has received honoraria from Amgen, BMS, GlaxoSmithKline, MSD, Novartis, Roche, Philogen and LEO Pharma, and received research grants from Roche, BMS and GlaxoSmithKline. The other authors reported no conflicts of interest.
- Published
- 2016
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15. Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma.
- Author
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Zimmer L, Eigentler TK, Kiecker F, Simon J, Utikal J, Mohr P, Berking C, Kämpgen E, Dippel E, Stadler R, Hauschild A, Fluck M, Terheyden P, Rompel R, Loquai C, Assi Z, Garbe C, and Schadendorf D
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Female, Humans, Ipilimumab, Kaplan-Meier Estimate, Male, Melanoma mortality, Middle Aged, Remission Induction, Skin Neoplasms mortality, Treatment Outcome, Melanoma, Cutaneous Malignant, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Melanoma drug therapy, Skin Neoplasms drug therapy
- Abstract
Background: Ipilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma., Patients and Methods: We undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months., Results: 103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %, 14 % and 27 %, respectively. Median OS was 6.8 months (95 % CI 5.3-9.9) for cutaneous, 9.6 months (95 % CI 1.6-11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %, 17 % and 11 %, respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %), none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %), including 20 grade 3-4 events (19 %). No new and unexpected safety findings were noted., Conclusions: Ipilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines., Trial Registration: Clinical Trials.gov NCT01355120.
- Published
- 2015
- Full Text
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