Real‐world experience in treating pediatric relapsed/refractory or therapy‐related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium

alexandrossfakianakis shared this article with you from Inoreader Real‐world experience in treating pediatric relapsed/refractory or therapy‐related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium via Pediatric Blood & Cancer Abstract Current therapies for relapsed/refractory (R/R) pediatric myeloid neoplasms are inadequately effective. Real-world data (RWD) can improve care by augmenting traditional studies and include individuals not eligible for clinical trials. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium recently completed T2016-003, a phase 1 study of decitabine, vorinostat, fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in R/R acute myeloid leukemia (AML), which added epigenetic drugs to a cytotoxic backbone. We report results of RWD from six centers that treated 28 pediatric patients (26 with AML, two with other myeloid neoplasms) identically to the TACL study but who were not enrolled. This allowed unique analyses and the ability to compare data with the 35 TACL study patients. The overall response rate (ORR) (complete response [CR] plus CR with incomplete count recovery) among 26 RWD evaluable patients was 65%. The ORR of 13 patients with re lapsed AML with epigenetic alterations was 69% (T2016-003 + RWD: 68%, n = 25), of eight patients with refractory AML was 38% (T2016-003 + RWD: 41%, n = 17) and of five patients with therapy-related AML (t-AML) was 80% (T2016-003 + RWD: 75%, n = 8). The mean number of Grade 3/4 toxicities experienced by the T2016-003-eligible RWD population (n = 22) (one per patient-cycle) was not meaningfully different than those (n = 6) who would have been TACL study-ineligible secondary to comorbidities (two per patient-cycle). Overall, this therapy was well tolerated and effective in pediatric patients with R/R myeloid neoplasms, particularly those with epigenetic alterations, t-AML, and refractory disease. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A sensitive and inexpensive HRM‐based testing algorithm for diagnosis of TAM and myeloid leukemia of Down syndrome

alexandrossfakianakis shared this article with you from Inoreader A sensitive and inexpensive HRM‐based testing algorithm for diagnosis of TAM and myeloid leukemia of Down syndrome via Pediatric Blood & Cancer ABSTRACT Patients with Down syndrome (DS) are commonly affected by a pre-leukemic disorder known as transient abnormal myelopoiesis (TAM). This condition usually undergoes spontaneous remission within the first two months after birth, however in children under 5, 20 – 30% of cases evolve to myeloid leukemia of DS (ML-DS). TAM and ML-DS are caused by co-operation between trisomy 21 and acquired mutations in the GATA1 gene. Currently, only NGS-based methodologies are sufficiently sensitive for diagnosis in samples with small GATA1 mutant clones (≤ 10% blasts). Alternatively, this article presents research on a new, fast, sensitive and inexpensive HRM-based diagnostic approach that allows the detection of most cases of GATA1 mutations, including silent TAM. The algorithm first uses flow cytometry for blast count, followed by high resolution melting (HRM) and Sanger sequencing to search for mutations on exons 2 and 3 of GATA1. We analyzed 138 samples of DS patie nts: 110 of asymptomatic neonates, 10 suspected of having TAM, and 18 suspected of having ML-DS. Our algorithm enabled the identification of 33 mutant samples, among them 5 cases of silent TAM (5/110) and 7 cases of ML-DS (7/18) with blast count ≤ 10%, in which GATA1 alterations were easily detected by HRM. Depending on the type of genetic variation and its location, our methodology reached sensitivity similar to that obtained by NGS (0.3%) at a considerably reduced time and cost thus making it accessible worldwide. This article is protected by copyright. All rights reserved View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metastatic rhabdomyosarcoma: evidence of the impact of radiotherapy on survival. A retrospective single‐center experience

alexandrossfakianakis shared this article with you from Inoreader Metastatic rhabdomyosarcoma: evidence of the impact of radiotherapy on survival. A retrospective single‐center experience via Pediatric Blood & Cancer Abstract Background The prognosis for patients with metastatic rhabdomyosarcoma (RMS) remains largely unsatisfactory despite the adoption of intensive multimodal therapy. To assess the role of different treatments adopted over the years, we retrospectively analyzed a cohort of patients <21 years old with metastatic RMS, treated from 1990 to 2020 at a referral center for pediatric sarcomas. Methods Patients were treated using a multimodal approach that included surgery, radiotherapy and chemotherapy (both high-dose chemotherapy and maintenance therapy in some cases). The type of radiotherapy administered was categorized as: radical (to all sites of disease); partial (to at least one, but not all sites of disease); or none. A landmark analysis was used to examine the impact of radiotherapy on survival, i.e. patients who had an event before day 221 were excluded from the analysis. Results The series included 80 patients. Event-free survival (EFS) and overall survival (OS) rates at 5 years were 17.3% and 21.3%, respectively. Survival was significantly associated with radiotherapy to metastatic sites, and with the radiotherapy category. In particular, 5-year EFS and OS rates were 70.6% and 76.0% for patients given radical radiotherapy, and 4.8% and 10.7%, respectively, for those given partial radiotherapy or none. Using the Cox multivariable analysis, OS correlated significantly with radiotherapy category. Conclusions While confirming the poor overall outcome of patients with metastatic RMS, this study identified radiotherapy – when given to all sites of disease (including metastases) - as the main variable influencing survival. This article is protected by copyright. All rights reserved View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

High‐frequency temperature monitoring at home using a wearable device: A case series of early fever detection and antibiotic administration for febrile neutropenia with bacteremia

alexandrossfakianakis shared this article with you from Inoreader High‐frequency temperature monitoring at home using a wearable device: A case series of early fever detection and antibiotic administration for febrile neutropenia with bacteremia via Pediatric Blood & Cancer Abstract We present a case series of three febrile episodes in neutropenic pediatric cancer patients who wore a Food and Drug Administration approved high-frequency temperature monitoring (HFTM) wearable device (WD) at home. The WD detected fever events when temperature monitoring by thermometer did not detect fever or was not feasible to perform. Two of the episodes were associated with bloodstream infections and the WD detected fevers 5 and 12 h prior to fevers detected by thermometer, triggering earlier medical evaluation and more prompt administration of antibiotics. These observations provide a basis for future investigation of home-based HFTM to improve infection-related outcomes in pediatric oncology. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diabetes and Cancer – optimising glycaemic control

alexandrossfakianakis shared this article with you from Inoreader Diabetes and Cancer – optimising glycaemic control via Journal of Human Nutrition and Dietetics Abstract Diabetes and cancer are both common and increasingly prevalent conditions, but emerging epidemiological evidence confirms that the risk of developing a number of common cancers is increased in those with type 2 diabetes. The risk of cancer in type 1 diabetes is less clearly defined, and therefore this review will focus on type 2 diabetes. Emerging evidence also supports an influence of diabetes on outcomes of cancer treatment. However, this relationship is bi-directional, with cancer and its treatment impacting on glucose control, whilst there is also emerging evidence that diabetes care can deteriorate after a cancer diagnosis (summarised in Figure 1). Despite these clear links there is a lack of evidence to guide clinicians in how to manage patients with diabetes during their cancer treatment. Although recent UK guidelines have started to address this, with the development of guidance for the management of hyperglycaemia in cancer, there is a clear n eed for wider guidance on the management of multi-morbidity during cancer, including diabetes and obesity, to incorporate nutritional management We have therefore undertaken a narrative review of the evidence of links between type 2 diabetes and cancer incidence and outcomes, and discuss the challenges to diabetes care during cancer treatment. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preoperative hemoglobin A1c and perioperative blood glucose in patients with diabetes mellitus undergoing spinal cord stimulation surgery: a literature review of surgical site infection risk

alexandrossfakianakis shared this article with you from Inoreader Preoperative hemoglobin A1c and perioperative blood glucose in patients with diabetes mellitus undergoing spinal cord stimulation surgery: a literature review of surgical site infection risk via Pain Practice Abstract Aims The aim of our study was to review the surgical literature regarding the relationship between hemoglobin A1c (HbA1c), diagnosis of diabetes mellitus (DM), and risk of post-operative surgical site infection (SSI). Methods A librarian-assisted literature search was performed with two goals: 1) identify surgical publications related to SSI and HbA1c values, and 2) identify publications reporting infection risk with DM in spinal cord stimulation (SCS), intrathecal drug delivery systems (IDDS), and cardiovascular implantable electronic device (CIED) implantation surgeries. Published guidelines on perioperative management of DM are reviewed. Results We identified 30 studies reporting SSI and HbA1c values. The literature review indicated that for many surgical procedures elevated HbA1c is not correlated to rate of SSI. We identified 16 studies reporting infection rates within DM cohorts following SCS, IDDS, and CIED implantation surgeries. The data reviewed did not indicate DM as an independent risk factor for SSI. Conclusion Preoperative HbA1c levels in patients with a history of DM is not a singularly sufficient tool to estimate risk of perioperative infection in SCS implantation surgery. Published guidelines on perioperative management of DM do not suggest a specific HbA1c above which surgery should be delayed; intentional perioperative glycemic control is recommended. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Systematic review and meta‐analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer

alexandrossfakianakis shared this article with you from Inoreader Systematic review and meta‐analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer via Pain Practice Abstract Introduction Celiac plexus neurolysis (CPN) has been developed as adjunctive therapy to medical management (MM) of abdominal pain associated with unresectable pancreatic cancer. We aimed to conduct a systematic review and meta-analysis to obtain updated and more accurate evidence on the efficacy of additional types of CPN, including endoscopic ultrasound-guided CPN (EUS-CPN). Methods On March 16, 2021, we performed searches of PubMed, Web of Science, and CENTRAL for original randomized controlled trials (RCTs). We defined the primary outcome as a standardized pain intensity score with a range of 0-10, and evaluated the mean difference between the CPN+MM and MM groups at 4, 8, and 12 weeks after the initiation of treatment. We used a random-effects model to synthesize the mean differences across RCTs. Results We selected 10 RCTs involving 646 individuals. The synthesized mean difference in the pain intensity score between the CPN+MM and MM groups was -0.58 (95% confidence interval [CI]: -1.09 to -0.07) (P = 0.034) in favor of CPN+MM at 4 weeks, -0.46 (95%CI: -1.00 to 0.08) (P = 0.081) at 8 weeks, and -1.35 (95%CI: -3.61 to 0.92) (P = 0.17) at 12 weeks. Conclusions This updated meta-analysis of CPN demonstrates its efficacy for managing abdominal pain at 4 weeks. Although there are various limitations, when abdominal pain in patients with unresectable pancreatic cancer is poorly controlled with MM alone, CPN should be an option even if the duration of effect is short-lived, taking into account the absence of serious adverse events. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Increased local concentrations of growth factors from leucocyte‐ and platelet‐rich fibrin do not translate into improved alveolar ridge preservation: an intraindividual mechanistic randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Increased local concentrations of growth factors from leucocyte‐ and platelet‐rich fibrin do not translate into improved alveolar ridge preservation: an intraindividual mechanistic randomized controlled trial via Journal of Clinical Periodontology Abstract Aims Leucocyte- and platelet-rich fibrin (L-PRF) has been tested for enhancing alveolar ridge preservation (ARP), but little is known about the local release profile of growth factors (GF) and the clinical equipoise related to its efficacy remains. This study compared the patterns of GF release, early soft tissue healing and alveolar ridge resorption following unassisted healing and L-PRF application in non-molar extraction sockets. Materials and Methods Atraumatic tooth extraction of two hopeless teeth per patient was followed by unassisted healing or L-PRF placement to fill the socket in 18 systemically healthy, nonsmoking subjects. This intraindividual trial was powered to assess changes in horizontal alveolar ridge dimensions 1 mm below the crest of alveolar bone. GF concentrations in wound fluid were assessed with a multiplex assay at 6, 24, 72 and 168 hours. Early healing was evaluated with the wound-healing index and changes in soft tissue volumes on serial digital scans. Hard tissue changes were measured on superimposed CBCT images after 5 months of healing. Results L-PRF resulted in higher GF concentrations in WF as compared to the control, but no differences in release patterns or time of peak were observed. No intergroup differences in early healing parameters were observed. Alveolar bone resorption was observed in both groups. No significant intergroup differences were observed in hard tissue healing 1, 3 or 5 mm apical to the original bone crest, or in ability to digitally plan a prosthetically guided implant with or without bone augmentation. Conclusions L-PRF increased the GF concentrations in wound fluid of extraction sockets without shifting the pattern observed in unassisted healing, while the increased delivery did not translate into clinical benefits in early wound healing or ARP. The current findings question the assumption that increased local concentrations of GF by L-PRF translate into improved clinical outcomes. Additional definitive studies are needed to establish the benefits of L-PRF in ARP. (clinicaltrials.gov NCT03985033) View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws

alexandrossfakianakis shared this article with you from Inoreader When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws via Epidemiology - Published Ahead-of-Print Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world thr eats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effects of Naloxone Access Laws on opioid overdose rates. Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world threats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effec ts of Naloxone Access Laws on opioid overdose rates. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of platelet‐rich fibrin and connective tissue graft in papilla reconstruction

alexandrossfakianakis shared this article with you from Inoreader Efficacy of platelet‐rich fibrin and connective tissue graft in papilla reconstruction via Journal of Esthetic and Restorative Dentistry Abstract Purpose To evaluate efficacy of platelet-rich fibrin (PRF) or connective tissue graft (CTG) in papilla reconstruction (PR) with the semilunar incision (SI) technique. Materials and Methods The analysis consisted of 55 sites (27 CTG and 28 PRF) from 20 patients who underwent PR with either PRF or CTG placed in the maxillary anterior region with SI technique. Baseline (BL) and follow-up (T1, first month, T3, third month, T6, sixth month) clinical data including periodontal evaluations (gingival index (GI), plaque index (PI), pocket depth (PD), keratinized tissue width (KTW), gingival recession), papilla-associated recordings (alveolar crest-interdental contact point [AC-IC], alveolar crest-papilla tip [AC-PT], papilla tip-interdental contact point [PT-IC], papilla height loss [PHL], interdental tissue stroke [ITS] and papilla presence index [PPI]) and patient satisfaction were analyzed. Results CTG provided better PR outcomes. GI, PI, and PD showed a slight increase at T1 and then, turned to their BL levels. The other periodontal parameters showed significant improvement after both treatment modalities. No inter-group difference was found except for KTW, which was in favor of CTG. Conclusion Based on the results, CTG is recommended over PRF in PR treatment due to its superior outcomes with less recurrence risk. Clinical Significance Connective tissue graft provides superior results than platelet-rich fibrin in papilla reconstruction with the semilunar incision technique. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.