ABSTRACT
Introduction: Simulated training in Pediatric Surgery/Urology is gaining significance due to the following reasons: (a) being a specialty of rare diseases affects individual surgeon's exposure to index cases;(b) subspecialty areas are not universally accessible;and (c) Covid-19 affected elective surgery. Consequently, targeted training, via workshops and simulated models, is necessary. Hypospadias is the index case/operation in Pediatric Urology, requiring a spectrum of dissection and reconstruction skills. It is further challenging to revisit and redo, thus sound initial repair is crucial. To date, there has been no successfully utilizable 3D-printed hypospadias model. We hereby present our experience with silicone 3D-printed high-fidelity hypospadias models. Method(s): Overall, 27 trainees from different countries, under the supervision of 15 instructors, completed the training exercise. They were all given a seminar to show the relevant anatomy and eight key steps of the exercise. Each trainee filled a structured assessment form for the quality of the exercise and resemblance to live surgery. Each exercise was evaluated by a trainer on-site, who supervised the activity and two independent assessors through photographs of the cardinal steps. Result(s): In total, 11 (40.7%) trainees had 1-3 years of specialist training experience, 10 (37%) had 4-6 years, and 6 (22.2%) had beyond. Meanwhile, 2 (7.4%) trainees had no hypospadias experience, 16 (59.2%) assisted in procedures or performed steps, 5 (18.5%) performed whole procedures with guidance, and 4 (14.8%) without guidance. The trainees rated each step from unsatisfactory (1/5) to excellent (5/5) for each of the (1) degloving;(2) urethral marking;(3) incision;(4) tubularization;(5) glanuloplasty;(6) dartos layer preparation;(7) preputioplasty, and (8) skin closure. However, 20 (74%) trainees and 15 (100%) instructors judged the model to resemble the anomaly. Meanwhile, 17 (63%) trainees and 13 (86.6%) instructors rated needle penetrability of the material compared to human tissue >= 3/5. In total, 16 (59%) trainees and 13 (86.6%) instructors rated suture holding >= 3/5. Moreover, 11 (73.3%) and 13 (86.6%) instructors rated sutures' evenness and edge cooptation >= 3/5. Conclusion(s): Majority of instructors found this 3D-model able to mediate transferring skills. Trainees reported adequate skill acquisition.
ABSTRACT
Background: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) 75 years or older, or unfit for intensive chemotherapy. As precision therapy in AML expanded with the addition of venetoclax among others in the therapeutic armamentarium of AML, efficacy and safety reports in ethnic minorities are limited, with a background of well recognized inter-ethnic differences in drug response. Phase III data from VIALE-A, as well as VIALE-C, was limited for the Arab population as no site opened in the Arab world. We herein report our experience on the use of venetoclax with azacitidine in patients with newly diagnosed or relapsed/refractory AML in the Arab population. Methods: Retrospective-single center review on the use of Azacitidine with venetoclax in older patients (aged ≥60 years) with newly diagnosed AML, not eligible for intensive chemotherapy;secondary AML and relapsed or refractory AML. All patients self-identified of Arabic ethnicity. Patients who received previous BCL2-inhibitor therapy were excluded. Patients who received at least one dose of treatment (Azacitidine ≥3 days, >14 days of venetoclax) were included in the intention to treat analysis. Patients typically received azacitidine 75 mg/m2 intravenously for 7 days with oral venetoclax 400 mg daily for induction, with appropriate dose adjustment for concomitant use of azoles. This is followed by the same regimen in consolidation, with adjustment according to response and side effects at the treating physician's discretion. The primary endpoint was overall survival. The secondary endpoints include response rate, safety, and relapse-free survival. Results: Between July 2019, and July 2021, we identified 19 patients;13 (68%) had newly diagnosed AML (ND-AML), and 6 (32%) had relapsed or refractory AML (R/R AML). The median age was 70 years (17-82). In the ND-AML, most patients had an adverse ELN 2017 AML (69%) with 23% having either intermediate or adverse AML (Negative for CBF, NPM1, FLT3-ITD and biCEBPA, but missing NGS data for adverse mutations Tp53/ASXL1 and RUNX1). Only one patient was classified as intermediate-risk AML. The overall response rate in the ND-AML was 77%, with 46% achieving complete remission (CR), and 23% CR with incomplete count recovery (CRi) [Table]. One patient achieved PR after the first cycle (blast 7% by morphology and 1.5% by flow cytometry) and did not have a subsequent bone marrow evaluation, however had a full count recovery. Among the responders in the ND-AML cohort, 4 deaths were noted. One death was related to COVID-19 associated pneumonia, one due to graft failure (at day 42 post Haplo-SCT), one due to septic shock, and one was related to relapse disease. The overall survival and relapse-free survival for ND-AML were 5.6 months for both [Figure]. In the R/R AML, 66% had prior HMA exposure, and all patients did receive high-intensity chemotherapy. The median number of prior treatments was 3 (1-5). the response rate was 80% (4/5), with 60% achieving CR. All patients are still alive with a median follow-up of 7.6 months. One patient had progressive disease. One patient is early to evaluate and was not included in the response analysis [Table]. The 30-day mortality was zero in both ND-AML and R/R AML cohorts. Conclusions: In a majority of adverse risk ND-AML, and in heavily pretreated R/R AML, the response rate and overall survival is comparable to what has been previously reported. Our data support the use of this regimen in older patients with newly diagnosed AML, patients with relapsed or refractory disease, and those with adverse-risk features. This analysis is limited by the small number of patients, and by the lack of ELN 2017 favorable-risk AML. Future prospective and randomized studies are needed to clarify activity and safety in the Arab population, as well as in the high-risk AML subset. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for approximately 25% of all newly diagnosed patients (Swerdlow et. al. IARC, 2017). It is estimated that 40% of patients are refractory to, or relapse after treatment with chemo-immunotherapy (R-CHOP). Salvage therapy with autologous stem-cell transplantation (ASCT) can cure around 40% of those patients, nevertheless, the prognosis is poor for most patients with R/R DLBCL who are relapsed after, or ineligible for ASCT, and in those with suboptimal response to salvage chemotherapy. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate delivering monomethyl auristatin E (MMAE), a microtubule inhibitor. It was granted accelerated approval by the US FDA on June 2019 for treatment of R/R DLBCL after at least two prior therapies, in combination with bendamustine and rituximab. We herein report our experience on the use of polatuzumab in patients with R/R DLBCL. Methods: Retrospective-single center review on the use of polatuzumab vedotin as part of a compassionate program in patients with R/R DLBCL between June 2018 and July 2021. Inclusion criteria for the study were: age ≥ 18 years, R/R DLBCL [both de-novo and transformed lymphoma], 2 or more prior lines of therapy, and treatment with polatuzumab-based therapy for at least 1 cycle. Patients with CNS involvement were excluded. The compassionate use access program provided polatuzumab at a dose of 1.8 mg/kg, administered with or without bendamustine (up to two doses of 90 mg/m2,) and rituximab (375 mg/m2). Treatment was given every 21 days for up to 6 cycles. Results: we identified 3 patients with R/R DLBCL who were treated with polatuzumab-based therapy. The median number of prior therapies was 2 (2 - 5). The median IPI and CNS-IPI score were 2, (1 - 4) and 2, (2 - 5), respectively (Baseline characteristics are summarized in Table). The median number of Pola-BR cycles received was 3 (2 - 6). One patient completed 6 cycles of polatuzumab with bendamustine and rituximab and achieved partial response. The other two patients were taken of treatment at the time of progression on cycles number 1 and 3. Treatment options were limited after polatuzumab-based therapy. The patient who achieved partial response after 6 cycles of Pola-BR maintained that response for 11 months without additional treatment and died due to COVID-19 associated pneumonia. One patient been screened for Glofitamab compassionate use program, and one patient elected to receive no further therapy. Conclusions: Polatuzumab-based treatment in R/R DLBCL is a promising treatment in an otherwise difficult to treat patient population. The compassionate use program provides access in developing countries to an otherwise prohibitively expensive emerging therapeutic armamentarium in R/R DLBCL. [Formula presented] Disclosures: No relevant conflicts of interest to declare.