Circulating KIT D816V mutation-positive non-mast cells in peripheral blood are characteristic of indolent systemic mastocytosis

It is presently accepted that the KIT D816V mutation is detectable in tissues with neoplastic mast cells in most patients with indolent systemic mastocytosis. In this study, neoplastic mast cells were detected in bone marrow, but not in peripheral blood, by flow cytometry in all 25 included cases of indolent systemic mastocytosis. However, the KIT D816V mutation was detected using mutation-specific qPCR in both bone marrow and peripheral blood in all 25 cases, demonstrating for the first time that the KIT D816V mutation is consistently present in non-mast cells in indolent systemic mastocytosis and that these cells are circulating in peripheral blood.     

BMD improvements after operation for primary hyperparathyroidism

Purpose

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables.

Methods

A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed.

Results

The mean age was 60 years (range 19–86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.002), Ca²⁺ (p?<?0.001), and alkaline phosphatase (p?=?0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.005) and Ca²⁺ (p?<?0.001) and inversely associated with plasma creatinine (p?=?0.004) and age (p?=?0.018). Total forearm BMD did not change significantly (?0.2 % (?0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p?<?0.001) and Ca²⁺ (p?=?0.009). In all 91 patients with mild PHPT (plasma Ca²⁺?<?1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (?0.3 % (?0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia.

Conclusions

We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.     

Clinical anatomy of vertebrae in scoliosis: global analysis in four different diseases by multiplanar reconstructive computed tomography

Background contextFew accurate analyses of clinically useful vertebral anatomy have been conducted, and most have focused on thoracic idiopathic scoliosis.PurposeTo evaluate the different anatomic characteristics in scoliosis by disease type and level.Study designObservational cohort study.Patient sampleForty-eight patients with scoliosis were included in this study.Outcome measuresSubjects underwent computed tomography (CT) of the whole spine.MethodsForty-eight patients with scoliosis were included in this study: 15 adolescent idiopathic, 11 cerebral palsy (CP), 10 muscular dystrophy (MD), and 12 congenital (CG) scoliosis patients with similar demographics. Subjects underwent CT of the whole spine, preoperatively. Eight anatomic parameters were measured in multiplanar reconstructive CT images, and statistical analysis was performed to investigate differences.ResultsIn general, values in the anatomic parameters were similar for the four diseases. Each parameter showed the unique change pattern according to the spinal level regardless of curvature shape, direction, or magnitude. In particular, chord length (CL) in MD and CG scoliosis was lower than in adolescent idiopathic scoliosis (AIS) and CP, and pedicle rib unit length was lower in CG scoliosis than in the other diseases (p<.05). Comparisons of convex and concave anatomies in AIS showed that inner pedicle width (PWI) and outer pedicle width (PWO) were wider for convex side, CL, pedicle width, and transverse pedicle angle were greater for concave side (p<.05), and differences were more significant at apices. However, in CP, PWI and PWO were similar between convex and concaves sides (p>.05). Although PWI and PWO were wider for convex sides and CL and pedicle length were greater for concave sides in MD (p<.05), differences were less significant at apices. Particularly, CG scoliosis showed severely deformed anatomy, with differences of seven parameters at apical vertebrae (p<.05).ConclusionClinical anatomies of vertebrae in scoliosis were found to differ significantly at different levels and in terms of convexity and disease type.     

Accuracy of densitometric vertebral fracture assessment when performed by DXA technicians—a cross-sectional,multiobserver study

Summary

Six dual-energy X-ray absorptiometry (DXA) technicians reviewed lateral images of the spine for deformed vertebrae. The images were acquired with a DXA scanner in 235 patients referred for osteoporosis assessment. The outcome was compared to findings on spinal radiographs assessed by two radiologists. Three DXA technicians performed acceptable or better in identifying patients with fractured vertebrae.

Introduction

This is the first study to evaluate the accuracy of vertebral fracture assessment (VFA) when used by DXA technicians as a triage test to select patients with deformed vertebrae for spinal radiographs.

Methods

Lateral single-energy scans and radiographs of the thoracolumbar spine (T4–L4) were acquired in 235 patients aged 65 years or more referred for osteoporosis assessment. Six DXA technicians evaluated lateral scans using dedicated software. The DXA technicians were trained to identify deformed vertebrae, but they did not assess the aetiology of deformity. Two radiologists evaluated the radiographs and their consensus evaluation served as the reference test for vertebral fracture. The main outcome was sensitivity and specificity of the DXA technicians’ identification of patients with one or more grade II–III deformities according to Genant’s classification.

Results

The proportion of patients with one or more grade II–III vertebral fractures was 0.35. Sensitivity ranged from 0.61 to 0.83 and specificity ranged from 0.78 to 0.95 across the DXA technicians. In patients with grade II–III deformities on VFA, the mean probability of one or more grade II–III fractures was 0.74 (range 0.66–0.86). Conversely, in patients without such deformities, the mean probability of grade II–III fractures was 0.14 (range 0.10–0.18). Accuracy was lower for grade I–III deformities for all the DXA technicians.

Conclusion

Three of six DXA technicians achieved acceptable or better accuracy when using VFA to triage patients with grade II–III vertebral deformities for spinal radiographs. Heterogeneity between DXA technicians appears to be due to differences in subjective thresholds. VFA triage by DXA technicians to identify patients with grade II–III fractures is feasible.

     

In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children

P. falciparum-infected red blood cells (IRBC) can adhere to endothelial host receptors through parasite-encoded, clonally variant surface antigens (VSA). The VSA-mediated IRBC adhesion and the acquired VSA-specific antibody response have both been linked to IRBC organ tropism and disease severity. Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM) in older semi-immune children. Establishment of the genetic mechanism underlying changes in VSA expression in response to in vitro selective pressure is now possible because of the availability of the entire genomic sequence of the P. falciparum clone 3D7. As a first step towards direct molecular identification of VSASM-encoding genes in 3D7, we report here a method of enforcing expression of VSASM-like antigens in this parasite clone by a novel selection method using plasma from semi-immune children with low VSAUM-specific, but high VSASM-specific, IgG reactivity. In addition to the resulting increase in VSA-specific IgG recognition, VSASM-expressing 3D7(3D7-Dodowa1) showed reduced adhesion to CD36. Finally, levels of IgG specific for the VSA expressed by 3D7-Dodowa1 were uniformly higher than those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma samples from geographically and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life-threatening P. falciparum malaria.     

Successful Aortic Valve Replacement Surgery in a Patient with Severe Haemophilia a with Low Titre Inhibitor

Acute leukemia, secondary myelodysplasia and paroxysmal nocturnal hemoglobinuria evolving from severe aplastic anemia (AA) following immunosuppressive therapy are well recognized. However, severe AA occurring after complete remission of acute promyelocytic leukemia (APL) has been documented only once in 2009. We report a case of 30-year-old male diagnosed with APL who achieved complete cytogenetic remission with all-trans retinoic acid based induction regimen and developed severe AA few months later during maintenance therapy.     

Characterization of drug-related problems identified by clinical pharmacy staff at Danish hospitals

Background In 2010, a database of drug related problems (DRPs) was implemented to assist clinical pharmacy staff in documenting clinical pharmacy activities locally. A study of quality, reliability and generalisability showed that national analyses of the data could be conducted. Analyses at the national level may help identify and prevent DRPs by performing national interventions. Objective The aim of the study was to explore the DRP characteristics as documented by clinical pharmacy staff at hospital pharmacies in the Danish DRP-database during a 3-year period. Setting Danish hospital pharmacies. Method Data documented in the DRP-database during the initial 3 years after implementation were analyzed retrospectively. The DRP-database contains DRPs reported at hospitals by clinical pharmacy staff. The analyses focused on DRP categories, implementation rates and drugs associated with the DRPs. Main outcome measure Characteristics of DRPs. Results In total, 72,044 DRPs were documented in the DRP-database during the first 3 years of implementation, and the number of documented DRPs increased every year. An overall stable implementation rate of approximately 58 % was identified. The DRPs identified were multi-facetted, however evenly distributed for each of the 3 years. The most frequently identified DRP categories were: “Dose”, followed by “Nonadherence to guidelines” and “Supplement to treatment”. The highest implementation rates were found for the following DRP categories: “Non-adherence to guidelines” (79 %) followed by “Therapeutic duplication” (73 %) and “Dosing time and interval” (70 %). Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The drugs most frequently involved in DRPs were paracetamol (4.6 % of all DRPs), simvastatin (3.0 %), lansoprazole (2.7 %), morphine (2.6 %) and alendronic acid (2.4 %). Conclusions The study found that a national database on DRPs contained multi-facetted DRPs, however evenly distributed for each of the 3 years. Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The study emphasizes the importance of detecting and intervening for DRPs.     

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain,Denmark, 2021/22 influenza season up to 25 March 2022

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2–6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9–84.4) in hospitalised and 64.2% (95% CI: 50.5–74.1) in non-hospitalised children. In non-hospitalised patients aged 7–44 years, VE was 24.8% (95% CI: 12.8–35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.