Tangential View and Intraoperative Three-Dimensional Fluoroscopy for the Detection of Screw-Misplacements in Volar Plating of Distal Radius Fractures

Background: Volar locking plate fixation has become the gold standard in the treatment of unstable distal radius fractures. Juxta-articular screws should be placed as close as possible to the subchondral zone, in an optimized length to buttress the articular surface and address the contralateral cortical bone. On the other hand, intra-articular screw misplacements will promote osteoarthritis, while the penetration of the contralateral bone surface may result in tendon irritations and ruptures. The intraoperative control of fracture reduction and implant positioning is limited in the common postero-anterior and true lateral two-dimensional (2D)-fluoroscopic views. Therefore, additional 2D-fluoroscopic views in different projections and intraoperative three-dimensional (3D) fluoroscopy were recently reported. Nevertheless, their utility has issued controversies. Objectives: The following questions should be answered in this study; 1) Are the additional tangential view and the intraoperative 3D fluoroscopy useful in the clinical routine to detect persistent fracture dislocations and screw misplacements, to prevent revision surgery? 2) Which is the most dangerous plate hole for screw misplacement? Patients and Methods: A total of 48 patients (36 females and 13 males) with 49 unstable distal radius fractures (22 x 23 A; 2 x 23 B, and 25 x 23 C) were treated with a 2.4 mm variable angle LCP Two-Column volar distal radius plate (Synthes GmbH, Oberdorf, Switzerland) during a 10-month period. After final fixation, according to the manufactures' technique guide and control of implant placement in the two common perpendicular 2D-fluoroscopic images (postero-anterior and true lateral), an additional tangential view and intraoperative 3D fluoroscopic scan were performed to control the anatomic fracture reduction and screw placements. Intraoperative revision rates due to screw misplacements (intra-articular or overlength) were evaluated. Additionally, the number of surgeons, time and radiation-exposure, for each step of the operating procedure, were recorded. Results: In the standard 2D-fluoroscopic views (postero-anterior and true lateral projection), 22 screw misplacements of 232 inserted screws were not detected. Based on the additional tangential view, 12 screws were exchanged, followed by further 10 screws after performing the 3D fluoroscopic scan. The most lateral screw position had the highest risk for screw misplacement (accounting for 45.5% of all exchanged screws). The mean number of images for the tangential view was 3 ± 2.5 images. The mean surgical time was extended by 10.02 ± 3.82 minutes for the 3D fluoroscopic scan. An additional radiation exposure of 4.4 ± 4.5seconds, with a dose area product of 39.2 ± 14.5 cGy/cm2 were necessary for the tangential view and 54.4 ± 20.9 seconds with a dose area product of 2.1 ± 2.2 cGy/cm2, for the 3D fluoroscopic scan. Conclusions: We recommend the additional 2D-fluoroscopic tangential view for detection of screw misplacements caused by overlength, with penetration on the dorsal cortical surface of the distal radius, predominantly observed for the most lateral screw position. The use of intraoperative 3D fluoroscopy did not become accepted in our clinical routine, due to the technical demanding and time consuming procedure, with a limited image quality so far

Students' and lecturers' perspectives on the implementation of online learning in medical education due to COVID-19 in Germany: a cross-sectional pilot study

BackgroundDuring the coronavirus disease 2019 (COVID-19) crisis, many things changed in universities around the world. In-person learning was not possible. Instead, courses were offered in digital form. The sudden change posed enormous challenges to universities, students, and teachers. The aim of this study was to investigate the disadvantages as well as the advantages and opportunities of digital learning.ObjectiveThis study investigated the evaluation of an elective module by medical students and teachers in the traditional in-person and virtual teaching forms during the COVID-19 pandemic.MethodsUsing the elective module “Sports Medicine,” which includes both lectures and practical units, the opinions of the medical students about conventional teaching compared to digital instruction were evaluated. In the winter semester of 2019/2020, all classes were taught face-to-face but had to be switched to virtual teaching in the summer semester of 2020 on an ad hoc basis due to the pandemic. The students were asked to answer questions on general conditions, participant behavior, instructor evaluation, skill acquisition, topic selection, and overall evaluation after both forms of teaching. Likewise, the lecturers of both courses were queried in semiqualitative interviews about the same topics. Descriptive data analysis was performed to process the data.ResultsThe students perceived digital teaching to be superior in most subareas compared to in-person teaching in terms of framework, instructor evaluation, skill acquisition, topic selection, and overall rating. Medical students seemed to feel better with digital teaching in most areas of evaluation. The lecturers found the new form of teaching rather unsettling and criticized the lack of verbal and especially nonverbal communication as well as the short preparation time for the new challenge. The instructors were uncomfortable with some aspects of the virtual teaching format.ConclusionIn the wake of the COVID-19 pandemic, medical schools should rapidly digitize their teaching offerings and support faculty members in their computer-based competence with continuing education opportunities and time resources

Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists

OBJECTIVE: To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. MATERIALS AND METHODS: We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables. RESULTS: In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564). DISCUSSION: We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. CONCLUSIONS: Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts

A selected ion flow tube study of the ion-molecule reactions of monochloroethene, trichloroethene and tetrachloroethene

Data for the rate coefficients and product cations of the reactions of a large number of atomic and small molecular cations with monochloroethene, trichloroethene and tetrachloroethene in a selected ion flow tube at 298 K are reported. The recombination energy of the ions range from 6.27 eV (H$_3$O$^+$) through to 21.56 eV (Ne$^+$). Collisional rate coefficients are calculated by modified average dipole orientation theory and compared with experimental values. Thermochemistry and mass balance predict the most feasible neutral products. Together with previously reported results for the three isomers of dichloroethene (J. Phys. Chem. A., 2006, 110, 5760), the fragment ion branching ratios have been compared with those from threshold photoelectron photoion coincidence spectroscopy over the photon energy range 9-22 eV to determine the importance or otherwise of long-range charge transfer. For ions with recombination energy in excess of the ionisation energy of the chloroethene, charge transfer is energetically allowed. The similarity of the branching ratios from the two experiments suggest that long-range charge transfer is dominant. For ions with recombination energy less than the ionisation energy, charge transfer is not allowed; chemical reaction can only occur following formation of an ion-molecule complex, where steric effects are more significant. The products that are now formed and their percentage yield is a complex interplay between the number and position of the chlorine atoms with respect to the C=C bond, where inductive and conjugation effects can be important

Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment

Bone marrow transplantation offers great promise for treating a number of disease states. However, the widespread application of this approach is dependent upon the development of less toxic methods to establish chimerism and avoid graft-versus-host disease (GVHD). CD8+/TCR− facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. In the present studies, we have identified the main subpopulation of FCs as plasmacytoid precursor dendritic cells (p-preDCs). FCs and p-preDCs share many phenotypic, morphological, and functional features: both produce IFN-α and TNF-α, both are activated by toll-like receptor (TLR)-9 ligand (CpG ODN) stimulation, and both expand and mature after Flt3 ligand (FL) treatment. FL-mobilized FCs, most of which express a preDC phenotype, significantly enhance engraftment of HSCs and induce donor-specific tolerance to skin allografts. However, p-preDCs alone or p-preDCs from the FC population facilitate HSC engraftment less efficiently than total FCs. Moreover, FCs depleted of preDCs completely fail to facilitate HSC engraftment. These results are the first to define a direct functional role for p-preDCs in HSC engraftment, and also suggest that p-preDCs need to be in a certain state of maturation/activation to be fully functional

Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies.

BACKGROUND: Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. METHODS AND RESULTS: Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique NOTCH1 mutations, including 3 de novo amino acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of NOTCH1-positive probands and affected family members. In leukocyte-derived RNA from subjects harboring NOTCH1 extracellular domain mutations, we observed significant reduction of NOTCH1 expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized NOTCH1 missense constructs also revealed significant reduction in gene expression. Mutant NOTCH1 expression was associated with downregulation of the Notch target genes HEY1 and HES1, indicating that NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway. CONCLUSIONS: These findings highlight a key role for NOTCH1 across a range of developmental anomalies that include cardiac defects and implicate NOTCH1 haploinsufficiency as a likely molecular mechanism for this group of disorders

Holoprosencephaly–polydactyly/pseudotrisomy 13: a presentation of two new cases and a review of the literature

Patients with a combination of holoprosencephaly and polydactyly, but with apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly–polydactyly syndrome (HPS), also termed pseudotrisomy 13. However, the criteria for HPS have been controversial since the advent of the diagnostic term, and a clear understanding of the condition lacks definitive delineation. We review the historical and current perspectives on the condition and analyze findings in 40 patients with apparent HPS, including cases from the literature and two previously unreported patients. Overall, our analysis suggests previously unrecognized trends in patients diagnosed with HPS. Specifically, there appears to be a higher prevalence of visceral anomalies, most significantly cardiac and genitourinary, but also with increased gastrointestinal, pulmonary, adrenal, skeletal, and renal abnormalities, in patients with HPS. Although these visceral anomalies may not be essential for the identification of HPS, clinicians should be aware of the presence of such characteristics in these patients to optimize management and help establish etiologies