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

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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

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Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma

alexandrossfakianakis shared this article with you from Inoreader Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma via Pediatric Blood & Cancer Abstract Background In recent years, many research groups have attempted to identify a subgroup of "ultra-high risk" patients within the high-risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I-meta-iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high-risk patients with NB. Methods The established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single-center retrospective study of high-risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters. Results Twenty-eight high-risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of "full" cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, p = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event-free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046). Conclusion In this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event-free survival in high-risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used. View on Web

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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

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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

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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

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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

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Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients

alexandrossfakianakis shared this article with you from Inoreader Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients via Journal of Clinical Pharmacy and Therapeutics Bodyweight and combination with SSRIs are related to bleeding adverse reaction of aspirin. Patients weighted less than 60 kg will be at a higher risk of adverse bleeding events. Abstract What is Known and Objectives Bleeding is the most common adverse reaction to aspirin and can lead to drug discontinuation or even be life-threatening in the secondary prevention of stroke or transient ischemic attack. The aim of this study was to evaluate risk factors for bleeding adverse reaction of aspirin in ischemic stroke or transient ischemic attack. Methods This retrospective analysis included patients treated with aspirin (100 mg) as a secondary prevention for ischemic stroke or transient ischemic attack. The bleeding events that occurred during the first year were collected, including gastrointestinal, skin, nasal cavity, gum, and urinary tract bleeding events. Then, univariate and multivariate logistic regression analyses were used to identify independent factors associated with bleeding events of aspirin. Results and Discussion A total of 578 patients were enrolled in this study, and 58 patients developed bleeding during the first year of secondary prevention. Body weight and combination with selective serotonin reuptake inhibitors were found to be significant risk factors for overall bleeding (p = 0.025 and 0.012). Body weight below 60 kg was a risk factor for overall bleeding and gastrointestinal bleeding events. What is new and conclusion Patients weighing less than 60 kg were at increased risk of bleeding with 100 mg aspirin for secondary prevention of cerebral infarction transient ischemic attack. View on Web

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Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia

alexandrossfakianakis shared this article with you from Inoreader Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia via Journal of Clinical Pharmacy and Therapeutics This study retrospectively evaluated the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) who were refractory to regular treatment in a real-world setting. We found that a significant decrease in serum ferritin (SF) and an improvement in haematologic parameters, organ function and even overall survival (OS) can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. Abstract What is known and objective Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) often need transfusions, which may accelerate iron overload. The aim of this study was to evaluate the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk MDS and AA who were refractory to regular treatment in a real-world setting. Methods Patient data were recorded, and dose–effect relationships of DFX were calculated after the first 6 months. Total annual exposure to DFX was calculated after 12 months and expressed as the accumulated exposure time at a dosage of 20 mg/kg/day. Results and discussion Sixty-one patients with low-risk MDS and 51 with AA were enrolled. The minimum dosage of DFX needed for a significant serum ferritin (SF) decrease was 20 mg/kg/day at 6 months, and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/day by 12 months for patients with low-risk MDS. For patients with AA, the minimum dosage was 10 mg/kg/day at 6 months, and the minimum accumulation had to reach 3 months at 20 mg/kg/day by 12 months. With the same exposure, significant improvements in haematological parameters were also observed in AA. Lower liver enzymes compared with baseline were observed. Gastrointestinal disorders and elevated serum creatinine were the most common side effects. Higher exposure to DFX correlated with longer overall survival (OS). What is new and conclusion A significant decrease in SF and an improvement in haematologic parameters, organ function and even OS can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. View on Web

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Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post‐transplant BK and CMV infection

alexandrossfakianakis shared this article with you from Inoreader Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post‐transplant BK and CMV infection via Transplant Infectious Disease Abstract Background kidney transplantation from HCV-viremic donors to uninfected recipients is associated with excellent short-term outcomes. However, HCV viremia might be associated with an increased risk for post-transplant viral complications. Methods We designed a retrospective study of HCV-negative kidney-only transplant recipients between 2018 and 2020. Recipients were grouped into group 1; HCV-negative donors, and group 2; HCV-viremic donors. Patients were matched 1:1 using propensity score. Primary objectives were to compare the incidence of CMV viremia ≥ 200 ml/IU, and BK viremia ≥1000 copies/ml between the groups. Secondary outcomes included group comparison of CMV disease, BK viremia ≥10,000 copies/ml, and one year patient and allograft survival. Results The study included 634 patients in group 1, and 71 patients in group 2. 65 pairs of patients were matched. Incidence of CMV viremia (33.3% vs 40.0%, p = 0.4675), and BK viremia (15.9% vs 27.7%, P = 0.1353) did not differ significantly between groups in the matched cohort. Incidence of CMV disease (81.0% Vs 76.9%; p = 1.000), and BK viremia ≥10,000 copies/ml (9.5% vs 16.9%, p = 0.2987) were comparable between groups. There was no difference in the one-year patient or allograft survival between groups. Conclusion kidney transplant from HCV-viremic donors is not associated with increased risk for BK or CMV viremia. This article is protected by copyright. All rights reserved View on Web

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