Analytical and Clinical Validation of a Non-Ristocetin Based VWF Assay on 2 Automated Analyzers in a Large Reference Laboratory.

BACKGROUND: Historically, von Willebrand factor (VWF) activity assays utilized ristocetin despite limitations including poor limits of detection and high imprecision. Newer VWF activity assays such as the INNOVANCE® VWF Ac assay, however, do not rely on ristocetin to measure platelet-dependent VWF function. The purpose of this study was to evaluate the analytical and clinical performance of the Siemens Healthineers INNOVANCE VWF Ac Assay on the Siemens BCS® XP and the Sysmex® CS-2500 systems in a large reference laboratory setting. METHODS: Performance indicators for the INNOVANCE VWF Ac assay were the limit of quantitation (LoQ), precision, and method comparison. Method comparison studies were performed using remnant plasma patient samples from routine coagulation tests and analyzed using both the INNOVANCE VWF Ac assay and the Siemens Healthineers ristocetin-dependent BC von Willebrand Reagent. RESULTS: Evaluation of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems demonstrated good precision and a lower LoQ compared to the BC von Willebrand Reagent. Method comparisons support the use of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems to measure platelet-dependent VWF function. The INNOVANCE VWF Ac assay was able to further assist in von Willebrand disease classification in 6/7 (86%) samples when the result was below the LoQ for the BC von Willebrand Reagent (ristocetin cofactor activity). CONCLUSIONS: These data are consistent with the 2021 American Society of Hematology/International Society on Thrombosis and Haemostasis/National Hemophilia Foundation/World Federation of Hemophilia von Willebrand disease guidelines that suggest using newer assays such as the INNOVANCE VWF Ac assay in place of ristocetin cofactor activity assays.

Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.

Scatter Radiation Distribution to Radiographers, Nearby Patients and Caretakers during Portable and Pediatric Radiography Examinations.

Scatter radiation from portable and pediatric X-rays could pose a risk to radiographers, nearby patients, and caretakers. We aim to evaluate the spatial scatter radiation distribution to the radiographers, nearby patients, and caretakers during common projections in portable and pediatric X-rays. We evaluated the three-dimensional scatter dose profiles of four and three commonly used portable and pediatric X-ray projections, respectively, by anthropomorphic phantoms and scatter probes. For portable X-ray, the AP abdomen had the highest scatter radiation dose recorded. Radiographer scatter radiation doses were 177 ± 8 nGy (longest cord extension) and 14 ± 0 nGy (hiding behind the portable X-ray machine). Nearby patient scatter radiation doses were 3323 ± 28 nGy (40 cm bed distance), 1785 ± 50 nGy (80 cm bed distance), and 580 ± 42 nGy (160 cm bed distance). The AP chest and abdomen had the highest scatter radiation dose in pediatric X-rays. Caretaker scatter radiation doses were 33 ± 1 nGy (50 cm height) and 659 ± 7 nGy (140 cm height). Although the estimated lens doses were all within safe levels, the use of shielding and caution on dose estimation by inverse square law is suggested to achieve the ALARA principle and dose optimization.

Hemoglobin Alpha Chain Variant Zara Associated With Familial Asymptomatic Hypoxemia.

Numerous hemoglobin (Hb) gene mutations have been identified, leading to a spectrum of phenotypes ranging from asymptomatic carrier states to complicated hemolytic anemias. We report a rare case of asymptomatic hypoxemia in a father and his teenage daughter both of whom were found to be carriers of Hb gene variant Zara. Workup for alternative cardiovascular causes of hypoxemia was unremarkable. Further sequencing of the alpha globin locus showed both individuals to be heterozygous for the Hb Zara c.274C>A (p.Leu92Ile) variant of unknown significance in the alpha2-globin gene. This is the first documented association of this Hb variant with familial asymptomatic hypoxemia, highlighting the importance of evaluating for hemoglobinopathies in patients with reduced oxygen saturation.

Current State of Pediatric Reference Intervals and the Importance of Correctly Describing the Biochemistry of Child Development: A Review.

Importance: Appropriately established pediatric reference intervals are critical to the clinical decision-making process and should reflect the physiologic changes that occur during healthy child development. Reference intervals used in pediatric care today remain highly inconsistent across a broad range of common clinical biomarkers. Observations: This narrative review assesses biomarker-specific pediatric reference intervals and their clinical utility with respect to the underlying biological changes occurring during development. Pediatric reference intervals from PubMed-indexed articles published from January 2015 to April 2021, commercial laboratory websites, study cohorts, and pediatric reference interval books were all examined. Although large numbers of pediatric reference intervals are published for some biomarkers, very few are used by clinical and commercial laboratories. The patterns, extent, and timing of biomarker changes are highly variable, particularly during developmental stages with rapid physiologic changes. However, many pediatric reference intervals do not capture these changes and thus do not accurately reflect the underlying biochemistry of development, resulting in significant inconsistencies between reference intervals. Conclusions and Relevance: There is a need to correctly describe the biochemistry of child development as well as to identify strategies to develop accurate and consistent pediatric reference intervals for improved pediatric care.

The role of chalcogen vacancies for atomic defect emission in MoS2.

For two-dimensional (2D) layered semiconductors, control over atomic defects and understanding of their electronic and optical functionality represent major challenges towards developing a mature semiconductor technology using such materials. Here, we correlate generation, optical spectroscopy, atomic resolution imaging, and ab initio theory of chalcogen vacancies in monolayer MoS2. Chalcogen vacancies are selectively generated by in-vacuo annealing, but also focused ion beam exposure. The defect generation rate, atomic imaging and the optical signatures support this claim. We discriminate the narrow linewidth photoluminescence signatures of vacancies, resulting predominantly from localized defect orbitals, from broad luminescence features in the same spectral range, resulting from adsorbates. Vacancies can be patterned with a precision below 10 nm by ion beams, show single photon emission, and open the possibility for advanced defect engineering of 2D semiconductors at the ultimate scale.

Use of therapeutic plasma exchange for pediatric neurological diseases.

Therapeutic plasma exchange is used to treat neurological diseases in the pediatric population. Since its first use in pediatric patients with hepatic coma in the form of manual whole blood exchange, therapeutic plasma exchange has been increasingly used to treat these disorders of the nervous system. This expansion is a result of improved techniques and apheresis instruments suitable for small children, as well as the recognition of its applicability to many diseases in the pediatric population. This review provides a historical overview of the use of therapeutic apheresis in children and highlights the most common applications for therapeutic plasma exchange to treat neurological disorders in children.

Electrically driven photon emission from individual atomic defects in monolayer WS2.

Quantum dot-like single-photon sources in transition metal dichalcogenides (TMDs) exhibit appealing quantum optical properties but lack a well-defined atomic structure and are subject to large spectral variability. Here, we demonstrate electrically stimulated photon emission from individual atomic defects in monolayer WS2 and directly correlate the emission with the local atomic and electronic structure. Radiative transitions are locally excited by sequential inelastic electron tunneling from a metallic tip into selected discrete defect states in the WS2 bandgap. Coupling to the optical far field is mediated by tip plasmons, which transduce the excess energy into a single photon. The applied tip-sample voltage determines the transition energy. Atomically resolved emission maps of individual point defects closely resemble electronic defect orbitals, the final states of the optical transitions. Inelastic charge carrier injection into localized defect states of two-dimensional materials provides a powerful platform for electrically driven, broadly tunable, atomic-scale single-photon sources.

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.

BACKGROUND: Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. STUDY DESIGN AND METHODS: We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. RESULTS: After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. CONCLUSION: In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.