Reliability of measurements performed on two dimensional and three dimensional computed tomography in glenoid assessment for instability

Purpose

The main purpose of this study is to establish which of two methods is more reliable in glenoid assessment for instability in pre-operative planning. Accordingly, we have studied the intra- and inter-observer reliability of glenoid parameters with the use of two-dimensional (2D) and three-dimensional (3D) reconstructed computed tomography (CT) images.

Methods

One hundred glenoids were measured with the use of 2D-CT and 3D-CT (in 3D orientation) by two independent observers (one experienced and one inexperienced). Measurements were repeated after one week for 30 randomly selected glenoids.

Results

The intra-class correlation coefficient (ICC) for inter-observer reliability was significantly greater for 3D-CT (0.811 to 0.915) than for 2D-CT (0.523 to 0.925). All intra-observer reliability values for 3D-CT were near perfect (0.835 to 0.997), while those for 2D-CT were less reliable (0.704 to 0.960). A dependent t-test showed that, for both observers, almost all glenoid parameters (except R and d) differed significantly (p?<?0.05) between 2D and 3D measurement methods.

Conclusions

Therefore, it can be concluded that 3D glenoid reconstructions are more reliable for glenoid bone loss assessment than 2D-CT. The results suggest that quantifying a glenoid defect with the use of 2D image only—even if performed by an experienced orthopaedic surgeon—is prone to errors. Differences in measurements between and within observers can be explained by plane setting and identifying glenoid rim in 2D-CT. Accordingly, we recommend that glenoid measurements should be performed in 3D orientation using 3D reconstruction obtained from CT images for pre-operative assessments, which are crucial for surgical planning.

     

Ethical and human rights concerns of Connecticut nurses: survey and implications for the profession

A survey of a random sample of Connecticut registered nurses' experiences with issues of ethics and human rights found a strong focus on protecting patient rights and dignity, adequacy of staffing patterns, informed consent, and respecting advance directives. Ethics committees were commonly available but were infrequently used. Participants reported high levels of ethics education but also desired more such education. The character of the issues is consistent with other studies and largely reflects conflicts over which nurses do not have independent control. Consideration is given to issues of nurses' moral agency in health care organizations.     

A Phase II Study of Telisotuzumab Vedotin in Patients With c–MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K,NCT03574753)

IntroductionLung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET–positive squamous cell carcinoma (SCC).Patients and MethodsPatients with previously treated SCC with c-MET–positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment.ResultsForty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1).ConclusionTelisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.     

Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success

Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.     

First example of anti-Kx in a person with the McLeod phenotype and without chronic granulomatous disease

BACKGROUND: Kx is lacking in the RBCs of patients with the McLeod syndrome. This condition is sometimes associated with chronic granulomatous disease (CGD). If given allogeneic RBCs, CGD patients with the McLeod phenotype may produce anti-Kx and anti-Km, and only phenotypically matched McLeod blood would be compatible. McLeod phenotype persons without CGD have made anti-Km but not anti-Kx (2 examples), and thus both McLeod and K(O) blood would be compatible. CASE REPORT: RBCs from a transfused patient with the McLeod phenotype but not with CGD (non-CGD McLeod) were typed for the Kell blood group antigens, and the plasma was analyzed for the presence of antibody by agglutination. The molecular basis was determined by analyzing for XK protein on RBC membranes by Western immunoblotting, by sequencing the XK gene, and by RFLP. RESULTS: The RBCs did not react with anti-Kx + anti-Km and showed weakening of Kell system antigens. The patient's plasma reacted moderately (2+) with RBCs of common Kell type and strongly (4+) with K(O) RBCs and RBCs of common Kell type treated with dithiothreitol, and did not react with McLeod RBCs. XK protein was absent from the RBC membranes. The XK gene had a point mutation in the donor splice site of intron 1 (G>C). CONCLUSION: This is the first report describing the molecular alteration in a non-CGD McLeod patient who has made anti-Kx. The immune response of people with the McLeod phenotype can vary, and K(O) blood may not always be compatible.     

Mutations that diminish expression of Kell surface protein and lead to the Kmod RBC phenotype

BACKGROUND: Kmod is an inherited rare RBC phenotype characterized by weak but detectable expression of high-incidence Kell antigens. STUDY DESIGN AND METHODS: The 19 exons and the intron-exon regions of the KEL gene from four unrelated Kmod individuals were sequenced and compared to wild-type KEL. To study the mechanisms by which the mutations result in depression of Kell antigens, mutant and wild-type Kell proteins were expressed in 293T cells and the amounts of protein present on the cell surface were determined. RESULTS: The following point mutations were identified: Kmod-1, homozygous 1208G>A, S363N; Kmod-2, heterozygous, 1208G>A, S363N and 2150 A>G, Y677C; Kmod-3 (previously classified as KEL:-13), heterozygous 1106T>C, L329P and 1716G>A, W532Stop; Kmod-4, heterozygous, 2227G>A, G703R and a silent 1839C>T mutation. In transfected 293T cells, fewer G703R and L329P mutant Kell proteins were transported to the cell surface compared with wild-type Kell protein, and there was no detectable Y677C mutant Kell protein. Previously, it was shown that that S363N Kell protein was not detected on the cell surface. CONCLUSION: Different point mutations, causing amino acid substitutions and presumably altering protein conformation, inhibit transport of the mutant Kell proteins to the cell surface. The different mutations leading to the Kmod phenotype explain why anti-Ku made by persons with the Kmod phenotype are not mutually compatible.     

Long‐term benzodiazepine use: Problems for the criminal justice system

Benzodiazepines (BZs) were introduced into clinical practice in the 1960's. The major indications for their use are to treat anxiety, as sedative‐hypnotics, anti‐convulsants, muscle relaxants and pre‐anaesthetics. They replaced barbiturate tranquillisers and hypnotics which have significant and well‐documented dependence and overdose risks (Dupont & Saylor, 1991). Initially the BZs were thought not to induce dependence, to be of low overdose risk and to be relatively free of adverse side‐effects. However, during the 1970's it became apparent that these drugs do have quite serious adverse effects, especially in the elderly fluergens, 1993), and that dependence and withdrawal symptoms are not uncommon. Regular use of BZs, at normally prescribed doses, can lead to dependence in patients who do not abuse either BZs or other drugs (Owen & Tyrer, 1983). Dependence can develop in as little as 6–8 weeks' continuous administration (Lader & Petursson, 1983), and may persist for many months (Ashton, 1984). Symptoms include anxiety, insomnia, depression, aches and pains, muscle spasm, gastrointestinal disorders, and increased sensitivity to light sound & touch (Petursson & Lader, 1981; Ashton, 1984). At the same time the problems of drug interactions, whereby polydrug users add BZs to their drug cocktails, have brought them to the attention of the criminal justice system. This paper will review the mechanisms of action and patterns of use of BZs in Australia. The major adverse effects of BZs, on psychomotor skills and memory, in addition to the less common paradoxical effects on aggressive behaviour, will be discussed. The wide‐spread, long‐term use of these drugs, at least by certain groups, has consequences for the criminal justice system.