Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls

alexandrossfakianakis shared this article with you from Inoreader Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls via Pediatric Blood & Cancer Abstract Background There is growing interest among pediatric institutions for implementing iodine-131 (I-131) meta-iodobenzylguanidine (MIBG) therapy for treating children with high-risk neuroblastoma. Due to regulations on the medical use of radioactive material (RAM), and the complexity and safety risks associated with the procedure, a multidisciplinary team involving radiation therapy/safety experts is required. Here, we describe methods for implementing pediatric I-131 MIBG therapy and evaluate our program's robustness via failure modes and effects analysis (FMEA). Methods We formed a multidisciplinary team, involving pediatric oncology, radiation oncology, and radiation safety staff. To evaluate the robustness of the therapy workflow and quantitatively assess potential safety risks, an FMEA was performed. Failure modes were scored (1–10) for their risk of occurrence (O), severity (S), and being undetected (D). Risk priority number (RPN) was calculated from a product of these scores and used to identify high-risk failure modes. Results A total of 176 failure modes were identified and scored. The majority (94%) of failure modes scored low (RPN <100). The highest risk failure modes were related to training and to drug-infusion procedures, with the highest S scores being (a) caregivers did not understand radiation safety training (O = 5.5, S = 7, D = 5.5, RPN = 212); (b) infusion training of staff was inadequate (O = 5, S = 8, D = 5, RPN = 200); and (c) air in intravenous lines/not monitoring for air in lines (O = 4.5, S = 8, D = 5, RPN = 180). Conclusion Through use of FMEA methodology, we successfully identified multiple potential points of failure that have allowed us to proactively mitigate risks when implementing a pediatric MIBG program. View on Web

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Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study

alexandrossfakianakis shared this article with you from Inoreader Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study via The Laryngoscope This serves as the seminal work from the prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity Surgery (POUCHS) Collaborative. Of the 250 persons enrolled, 85% had a Zenker diverticula (ZD), 9% had evidence of cricopharyngeus muscle dysfunction (CPMD) without diverticula and 4% had a Killian Jamieson diverticula (KJD). Patients with isolated CPMD appear to be more symptomatic than persons with ZD or KJD. Objective To describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula. Methodology Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient-reported outcome measures (e.g., Eating Assessment Tool [EAT-10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance. Results A total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty-two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction-type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT-10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT-10 scores compared to the other diagnostic groups (p = 0.03). Conclusion ZD is the most common, followed by CPMD without diverticula, KJD, and traction-type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD. Level of Evidence Level 4 Laryngoscope, 2022 View on Web

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Identity-by-descent analysis of CMTX3 links three families through a common founder

alexandrossfakianakis shared this article with you from Inoreader Identity-by-descent analysis of CMTX3 links three families through a common founder via Journal of Human Genetics - Issue - nature.com science feeds View on Web

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Evaluation of Physicochemical Properties, Pharmacokinetics, Biodistribution, Toxicity, and Contrast-Enhanced Cancer MRI of a Cancer-Targeting Contrast Agent, MT218

alexandrossfakianakis shared this article with you from Inoreader Evaluation of Physicochemical Properties, Pharmacokinetics, Biodistribution, Toxicity, and Contrast-Enhanced Cancer MRI of a Cancer-Targeting Contrast Agent, MT218 via Investigative Radiology - Current Issue Objectives Preclinical assessments were performed according to the US Food and Drug Administration guidelines to determine the physicochemical properties, pharmacokinetics, clearance, safety, and tumor-specific magnetic resonance (MR) imaging of MT218, a peptidic gadolinium-based MR imaging agent targeting to extradomain B fibronectin for MR molecular imaging of aggressive tumors. Materials and Methods Relaxivity, chelation stability, binding affinity, safety-related target profiling, and effects on CYP450 enzymes and transporters were evaluated in vitro. Magnetic resonance imaging was performed with rats bearing prostate cancer xenografts, immunocompetent mice bearing murine pancreatic cancer allografts, and mice bearing lung cancer xenografts at different doses of MT218. Pharmacological effects on cardiovascular, respiratory, and central nervous systems were determined in rats and conscious beagle dogs. Pharmacokinetics were tested in rats and dogs. Biodistribution and excretion were studied in rats. Single and repeated dosing toxicity was evaluated in rats and dogs. In vitro and in vivo genotoxicity, in vitro hemolysis, and anaphylactic reactivity were also performed. Results At 1.4 T, the r1 and r2 relaxivities of MT218 were 5.43 and 7.40 mM−1 s−1 in pure water, 6.58 and 8.87 mM−1 s−1 in phosphate-buffered saline, and 6.54 and 8.70 mM−1 s−1 in aqueous solution of human serum albumin, respectively. The binding affinity of MT218 to extradomain B fragment is 3.45 μM. MT218 exhibited no dissociation of the Gd(III) chelates under physiological conditions. The peptide degradation half-life (t1/2) of MT218 was 1.63, 5.85, and 2.63 hours in rat, dog, and human plasma, respectively. It had little effect on CYP450 enzymes and transporters. MT218 produced up to 7-fold increase of contrast-to-noise ratios in the extradomain B fibronectin–rich tumors with a dose of 0.04 mmol/kg for at least 30 minutes. MT218 had little pharmacological effect on central nervous, cardiovascular, or respiratory systems. MT218 had a mean plasma elimination half-life (t1/2) of 0.31 and 0.89 hours in rats and dogs at 0.1 mmol/kg, respectively. No detectable Gd deposition was observed in the brain at 6 hours postinjection of MT218 at 0.1 mmol/kg in rats. MT218 was not mutagenic and had no mortality or morbidity in the rats or dogs up to 1.39 and 0.70 mmol/kg/d, respectively. The no observed adverse effect level of MT218 in Sprague-Dawley rats was 1.39 mmol/kg for single dosing and 0.46 mmol/kg/d for repeated dosing. The no observed adverse effect level in dogs was 0.07 mmol/kg/d. MT218 exhibited no genotoxicity, hemolysis, and anaphylactic reactivity. Conclusion The preclinical assessments showed that the targeted contrast agent MT218 has high r1 and r2 relaxivities, satisfactory physicochemical properties, pharmacokinetic, and safety profiles and produces effective tumor enhancement in multiple cancer types in rats and mice at reduced doses. View on Web

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The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape and vaccine effectivity

alexandrossfakianakis shared this article with you from Inoreader The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape and vaccine effectivity via Journal of Medical Virology ABSTRACT As of November 2021, several SARS-CoV-2 variants appeared and became dominant epidemic strains in many countries, including five VOCs (Alpha (1), Beta (2), Gamma (3), Delta (4) and Omicron (5) defined by the World Health Organization (WHO) during the COVID-19 pandemic. As of August 2022, Omicron is classified into five main lineages, BA.1, BA.2 (6), BA.3, BA.4, BA.5 (7) and some sub-lineages (BA.1.1, BA.2.12.1, BA.2.11, BA.2.75, BA.4.6) (https://www.gisaid.org/). Compared to the previous VOCs (Alpha, Beta, Gamma, and Delta), all the Omicron lineages have the most highly mutations in the spike protein, and with 50 mutations accumulated throughout the genome. Early data indicated that Omicron BA.2 sub-lineage had higher infectivity and more immune escape than the early wild-type (WT) strain, the previous VOCs, and BA.1 (8, 9, 10). Recently, global surveillance data suggest a higher transmissibility of BA.4/BA.5 than BA.1, BA.1.1 and BA.2, and BA.4/BA.5 is becoming dominant strain in many countries globally (7, 11). This article is protected by copyright. All rights reserved. View on Web

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Voriconazole‐induced severe skin allergy and neurological adverse event in a liver failure patient: A case report

alexandrossfakianakis shared this article with you from Inoreader Voriconazole‐induced severe skin allergy and neurological adverse event in a liver failure patient: A case report via Journal of Clinical Pharmacy and Therapeutics Severe allergy and neurological adverse events were appeared on the 19th day, which was the next day after voriconazole injection. The adverse events were alleviated after voriconazole withdraw for 1 week. VCZ: voriconazole, 0.4 g on the 18th day, followed by 0.2 g once daily, ALP: alprazolam, 0.2 g, per night, PT: piperacillin-tazobactam, 2.5 g every 12 h, IC: Imipenem cilastatin, 0.5 g every 8 hours, ENT: entecavir, 0.5 mg once daily, ADE: ademetionine, 0.25 g once daily, VAN: Vancomycin, 1 g every 12 h. Abstract What Is Known and Objective Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. Case Summary A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. What Is New and Conclusion To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration. View on Web

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Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties

alexandrossfakianakis shared this article with you from Inoreader Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties via Annals of Surgery - Most Popular Articles Introduction: The 6-hour threshold to revascularization of an ischemic limb is ubiquitous in the trauma literature, however, contemporary evidence suggests that this threshold should be less. This study aims to characterize the relationship between the duration of limb ischemia and successful limb salvage following lower extremity arterial trauma. Methods: This is a cohort study of the United States and UK military service members injured while serving in Iraq or Afghanistan between 2003 and 2013. Consecutive patients who sustained iliac, femoral, or popliteal artery injuries, and underwent surgery to attempt revascularization, were included. The association between limb outcome and the duration of limb ischemia was assessed using the Kaplan-Meier method. Results: One hundred twenty-two patients (129 limbs) who sustained iliac (2.3%), femoral (56.6%), and popliteal (41.1%) arterial injuries were included. Overall, 87 limbs (67.4%) were successfully salvaged. The probability of limb salvage was 86.0% when ischemia was ≤1 hour; 68.3% when between 1 and 3 hours; 56.3% when between 3 and 6 hours; and 6.7% when >6 hours (P View on Web

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