Centralization of Biliary Atresia: Has Germany Learned Its Lessons?

2021 ◽  
Author(s):  
Omid Madadi-Sanjani ◽  
David Fortmann ◽  
Udo Rolle ◽  
Burkhard Rodeck ◽  
Ekkehard Sturm ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Data Transfer ◽  
Previous Analysis ◽  
Outcome Data ◽  
Free Survival ◽  
Change In Practice ◽  
Native Liver ◽  
Survival With Native Liver ◽  
Pediatric Liver Transplant

Abstract Introduction The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. Materials and Methods In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. Result Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001–2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001–2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001–2005 [p = 0.5]). Compared with the 2001–2005 analysis, all criteria showed improvement but the differences are statistically not significant. Conclusion Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.

scholarly journals Adjuvant Therapy with Budesonide Post-Kasai Reduces the Need for Liver Transplantation in Biliary Atresia

2021 ◽  
Vol 10 (24) ◽  
pp. 5758
Author(s):  
Joachim F. Kuebler ◽  
Omid Madadi-Sanjani ◽  
Eva D. Pfister ◽  
Ulrich Baumann ◽  
David Fortmann ◽  
...  
Keyword(s):  
Side Effects ◽  
Adjuvant Therapy ◽  
Biliary Atresia ◽  
Experimental Therapy ◽  
Control Group ◽  
Multicenter Observational Study ◽  
Kasai Procedure ◽  
Native Liver ◽  
Survival With Native Liver

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis gave rise to experimental therapy using budesonide as an adjuvant BA treatment. Ninety-five BA patients prospectively received a budesonide 2 mg/dose rectal foam daily for three months (SG). A case-matched control group (CG: 81) was retrospectively recruited. The outcome measures were survival with native liver (SNL), determined at six months and two years after the Kasai procedure. The follow-up rate was 100%. At six months, SNL was statistically not different but became so after two years (SG: 54%; CG: 32%; p < 0.001). No steroid-related side effects were observed, except for eight patients with finally caught-up growth retardation. This study demonstrates for the first time a significantly longer survival with native liver in patients with BA after adjuvant therapy. However, indication, dosage, and duration of any budesonide application is not given in neonates with BA. Hence, we suggest extending the postoperative use of budesonide in a multicenter observational study with a clearly defined follow-up protocol, particularly in terms of potentially underestimated side effects.

Outcomes after Emergency Admission with a Diabetic Foot Attack Indicate a High Rate of Healing and Limb Salvage But Increased Mortality: 18-Month Follow-up Study

2020 ◽  
Author(s):  
Erika Vainieri ◽  
Raju Ahluwalia ◽  
Hani Slim ◽  
Daina Walton ◽  
Chris Manu ◽  
...  
Keyword(s):  
Limb Salvage ◽  
Diabetic Foot ◽  
Emergency Admission ◽  
Arterial Disease ◽  
Major Amputation ◽  
Outcome Data ◽  
High Rate ◽  
Free Survival ◽  
Peripheral Arterial

Abstract Aim The diabetic foot attack (DFA) is perhaps the most devastating form of diabetic foot infection, presenting with rapidly progressive skin and tissue necrosis, threatening both limb and life. However, clinical outcome data in this specific group of patients are not available. Methods Analysis of 106 consecutive patients who underwent emergency hospitalisation for DFA (TEXAS Grade 3B or 3D and Infectious Diseases Society of America (IDSA) Class 4 criteria). Outcomes evaluated were: 1) Healing 2) major amputation 3) death 4) not healed. The first outcome reached in one of these four categories over the follow-up period (18.4±3.6 months) was considered. We also estimated amputation free survival. Results Overall, 57.5% (n=61) healed, 5.6% (n=6) underwent major amputation, 23.5% (n=25) died without healing and 13.2% (n=14) were alive without healing. Predictive factors associated with outcomes were: Healing (age<60, p=0.0017; no Peripheral arterial disease (PAD) p= 0.002; not on dialysis p=0.006); major amputation (CRP>100 mg/L, p=0.001; gram+ve organisms, p=0.0013; dialysis, p= 0.001), and for death (age>60, p= 0.0001; gram+ve organisms p=0.004; presence of PAD, p=0.0032; CRP, p=0.034). The major amputation free survival was 71% during the first 12 months from admission, however it had reduced to 55.4% by the end of the follow-up period. Conclusions In a unique population of hospitalised individuals with DFA, we report excellent healing and limb salvage rates using a dedicated protocol in a multidisciplinary setting. An additional novel finding was the concerning observation that such an admission was associated with high 18-month mortality, almost all of which was after discharge from hospital.

scholarly journals Predictors of Successful Kasai Portoenterostomy and Survival with Native Liver at 2 Years in Infants with Biliary Atresia

2019 ◽  
Vol 9 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Ruchika Kumar ◽  
Bikrant B. Lal ◽  
Vikrant Sood ◽  
Rajeev Khanna ◽  
Senthil Kumar ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Kasai Portoenterostomy ◽  
Native Liver ◽  
Survival With Native Liver

P1031The impact of the duration of atrial fibrillation persistence for arrhythmia free survival in patients undergoing catheter ablation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Furukawa ◽  
T Yamada ◽  
T Morita ◽  
S Tamaki ◽  
M Kawasaki ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Outcome Data ◽  
Free Survival ◽  
Group 4 ◽  
Kaplan Meier ◽  
Group 3 ◽  
Group 2 ◽  
Af Recurrence ◽  
Group 1

Abstract Background Catheter ablation (CA) for atrial fibrillation (AF) is a curable treatment option. However, AF recurrence after CA remains an important problem. Although the success rate has been improved after catheter ablation (CA) in patients with paroxysmal AF (PAF), outcome data after CA for persistent AF (PeAF) are highly variable. Previous studies showed the PeAF is one of independent predictors for AF recurrence in comparison to PAF. However, there are little information available on the prognostic significance of AF duration after CA for AF. The aim of this study is to evaluate the impact of AF duration on long-term outcomes of AF ablation in patients with PeAF compared with PAF. Methods We enrolled 778 consecutive patients, who were referred our institution between August 2015 and December 2017 for undergoing the first time CA for AF. We divided 5 groups (Group 1; PAF (n=442), Group 2; PeAF duration ≤6 months (n=198), Group 3; PeAF duration of 6 months to 2 years (n=87), Group 4; PeAF duration of 2–5 years (n=30) and Group 5; PeAF duration ≥5 years (n=21)). All patients followed up for at least 1 year. Outcome data on recurrence of AF after ablation were collected. Results There were no significant differences in baseline clinical characteristics before CA among 5 groups, except for the prevalence of congestive heart failure, left atrial diameter and left ventricular ejection fraction. During a mean follow-up period of 511±298 days, 217 patients had AF recurrence. Kaplan-Meier analysis revealed that AF recurrence was significantly higher in group 2 compared to group 1 (31% vs 20%, p=0.002) and in group 4 compared to group 3 (83% vs 30%, p<0.0001). However, AF recurrence was no significantly differences between groups 2 and 3 (31% vs 30%, p=0.76) and between groups 4 and 5 (83% vs 81%, p=0.45). Of 217 patients with AF recurrence, 154 patients had undergone multiple procedures. After last procedures, during a mean follow-up period of 546±279 days, 61 patients had AF recurrence. Kaplan-Meier analysis revealed that AF recurrence was significantly higher in group 2 compared to group 1 (10% vs 3%, P=0.0005) and in group 4 compared with group 3 (35% vs 10%, p=0.0001). However, AF recurrence was no significantly difference between groups 2 and 3 (10% vs 10%, p=0.91) and between groups 4 and 5 (47% vs 35%, p=0.47). AF Free Survival Curve Conclusion Although patients with PeAF within 2 years had significantly higher AF recurrence compared to PAF, AF ablation might still be a good contributor as the first line approach to improve outcomes in patient with PeAF within 2 years.

scholarly journals Follow-up Analysis of Ixazomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Routine Clinical Practice

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2716-2716
Author(s):  
Jiri Minarik ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
Tomas Jelinek ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Previous Analysis ◽  
Progression Free Survival ◽  
Routine Clinical Practice ◽  
Toxicity Profile ◽  
Advisory Committees ◽  
Free Survival ◽  
Significant Difference

Abstract Background: The addition of ixazomib to the doublet lenalidomide and dexamethasone (RD) in relapsed and refractory multiple myeloma (RRMM) has shown significant benefit in progression free survival (PFS) in the TOURMALINE-MM1 study. Several real-world data including our previous analysis confirmed that the combination IRD is feasible and with fair outcomes even outside the clinical trial. Here we report an updated analysis which is aimed at overall survival (OS) and the PFS2 interval which is defined as the time from the date of treatment initiation to the date of first documentation of progressive disease after initiation of further anti-myeloma treatment or death from any cause. Methods: We analyzed a cohort of 344 patients with RRMM, 127 being treated by IRD and 217 by RD combination. The group characteristics and study design are described elsewhere. 1 The median follow-up of the whole cohort was 28.5 months. The primary endpoint was OS, OS in patients with relapse 1-3, progression free survival (PFS), and PFS2. Secondary endpoints were response rates and toxicity profile. For statistical analysis we used Fisher's exact test or Mann-Whitney U test. Survival measures were assessed using the Kaplan-Meier methodology, and statistical significance was assessed using the log-rank test at a significance level of α = 0.05 (all tests two-sided). Results: The outcomes of OS in the whole cohort were already published before, with significantly longer median OS in the IRD vs RD cohort (mOS 36.6 months vs 26.0 months, p = 0.008).1 In the follow-up analysis, the medians were slightly improved, maintaining a significant difference (mOS 40.9 vs 27.1 months, p = 0.001). In patients treated within relapse 1-3, the results outcomes were even more pronounced (mOS 51.7 vs 27.8 months, p ˂ 0.001). The median PFS was also better in the IRD cohort (mPFS 17.5 vs 12.5 months, p = 0.013) but the results did not substantially differ from our previous analysis. The median PFS2 in the IRD vs RD cohort was significantly longer in the IRD cohort (mPFS2 29.8 vs 21.6 months, p = 0.016). The subsequent therapy included mostly pomalidomide (27.5% vs 30.8%), bortezomib (28.8% vs 28.2%) or thalidomide (10.0% vs 16.2%). Monoclonal antibodies (daratumumab, isatuximab) were more frequently used after IRD combination (21.3% vs 4.3%). The response rates in the IRD vs RD cohort were similar as in our primary analysis: overall response rate (ORR) 73.0% vs 66.8%, with significant difference in very good partial response and better (VGPR+) 38.1% vs 26.3%. The toxicity profile did not reveal any additional safety concerns. Majority of grade 3+ toxicities included hematological toxicity (anemia, neutropenia, thrombocytopenia) and infections, with similar distribution in the cohorts. Conclusion: The treatment of RRMM using the full oral IRD regimen in routine clinical practice is easy, safe and with significantly improved outcomes in comparison to RD doublet. Our follow-up analysis confirmed the impact on OS in patients in the whole cohort including relapse 1-3. The median PFS2 was also longer in the IRD cohort, possibly affected by more frequent use of monoclonal antibodies in the next treatment. With support of AZV 17-29343A, NV18-03-00500, MH CZ - DRO (FNOl, 00098892), IGA-LF-2021-001. 1) Minarik J, Pika T, Radocha J. et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer 2021; 21: https://doi.org/10.1186/s12885-020-07732-1 Disclosures Minarik: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Hajek: Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Prognosis of Biliary Atresia After 2-year Survival With Native Liver

2018 ◽  
Vol 67 (6) ◽  
pp. 689-694 ◽  
Author(s):  
Mauri Witt ◽  
Daan B.E. van Wessel ◽  
Ruben H.J. de Kleine ◽  
Janneke L.M. Bruggink ◽  
Jan B.F. Hulscher ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Native Liver ◽  
Survival With Native Liver

Prognostic factors indicating survival with native liver after Kasai procedure for biliary atresia

2017 ◽  
Vol 33 (10) ◽  
pp. 1047-1052 ◽  
Author(s):  
Juma Obayashi ◽  
Kohei Kawaguchi ◽  
Shutaro Manabe ◽  
Hideki Nagae ◽  
Munechika Wakisaka ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Biliary Atresia ◽  
Kasai Procedure ◽  
Native Liver ◽  
Survival With Native Liver

The validity of progression-free survival (PFS) 2 as a surrogate endpoint for overall survival (OS) in randomized controlled trials (RCTs) of advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1516-1516
Author(s):  
Rachel Woodford ◽  
Deborah Zhou ◽  
Peey-Sei Kok ◽  
Sally Lord ◽  
Ian Marschner ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Outcome Data ◽  
Survival Times ◽  
Free Survival ◽  
Hazard Ratios ◽  
Investigational Agents ◽  
Tumor Types

1516 Background: OS is the gold-standard endpoint for treatment efficacy in oncology RCTs. However, prolonged follow-up is required to obtain mature data, which impedes regulatory approval of potentially beneficial therapies. Furthermore, increasing therapeutic options including cross over to investigational agents at disease progression often confound OS findings. PFS-2, defined as time from randomization to progression on second-line therapy, has been proposed as a potential surrogate endpoint for OS. Using a meta-analytic approach, we aimed to assess the association between OS and PFS-2, and its validity compared with other surrogate endpoints. Methods: We performed an electronic literature search to identify RCTs of systemic therapies that reported PFS-2 as a pre-specified endpoint with defined follow up protocols. Articles were screened for eligibility and outcome data were extracted. Correlations in the relative treatment difference between treatment arms for OS vs PFS-2, PFS-1, and objective response rate (ORR) were assessed as the comparison of hazard ratios (HR) and odds ratio (OR) respectively. Results: 38 eligible RCTs comprising of 44 analysis units, with 19,031 patients across 8 unique tumor types were identified. The majority received targeted therapies (72.2%), followed by immunotherapy (IO; 26.3%). The correlations of HR-OS/HR-PFS-2, HR-OS/HR-PFS-1 and HR-OS/OR-ORR were r = 0.67 (95% CI 0.08-0.69), r = 0.12 (95% CI 0.00-0.13) and r = 0.21 (95% CI 0.00-0.33) respectively. Correlations between OS with surrogates was assessed in different subgroups according to post-progression survival times (SPP), types of treatment agents and rate of subsequent therapy after progression (table). Conclusions: Across diverse tumors and therapies, treatment effect on PFS-2 has modest to strong correlation with OS, but poor correlations were observed between OS-PFS-1 and OS-ORR respectively. Across all subgroups, PFS-2 performs consistently better than traditional surrogates of PFS-1 and ORR, validating and providing support for use in future RCTs.[Table: see text]

37. Predictors of successful kasai-portoenterostomy and survival with native liver at 2 years in infants with biliary atresia

2018 ◽  
Vol 8 ◽  
pp. S119
Author(s):  
Ruchika Kumar ◽  
Bikrant Bihari Lal ◽  
Vikrant Sood ◽  
Rajeev Khanna ◽  
Senthil Kumar ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Kasai Portoenterostomy ◽  
Native Liver ◽  
Survival With Native Liver

Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16274-e16274
Author(s):  
Andrew Peter Dean ◽  
Fiona Mulligan ◽  
Geena Kelly ◽  
Emma Shaughnessy ◽  
Kate Wilson
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Cyclic Peptide ◽  
Day Treatment ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Metastatic Pancreatic Cancer ◽  
Free Survival ◽  
Phase 2 Trial

e16274 Background: In our phase I trial of the first-in-class agent CEND-1 with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer, we reported a preliminary overall RR of 59% in 29 patients across 3 institutions. Our site enrolled 19 of these patients and we present updated outcome data from this institution. CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. Methods: We reviewed our updated outcome data from the first in human CEND-1 trial in pancreatic cancer. Patients received a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Data was analysed to determine response rate, progression free survival and ongoing benefit. Results: Of the 19 patients that were enrolled at this institution; 13 (69%) showed partial response, 5 (26) % had stable disease, and 1 (3.4%) had progressive disease. Median progression free survival for this cohort was 8.8 months. 4 patients (21%) remain on the trial without disease progression to date. Median treatment duration for these patients is 20 months (range 17.1 – 24.6 months). Adverse events were as previously described¹ with no new significant events or toxicities. Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial with notable progression free survival. No new safety signals or adverse events have been detected with this prolonged follow-up. The randomised phase 2 trial of this combination will be proceeding later this year. Clinical trial information: ACTRN12618000804280.

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