The Diagnostic Process of Spinal Post-Traumatic Deformity: An Expert Survey of 7 Cases, Consensus on Clinical Relevance Does Exist

STUDY DESIGN: Survey of cases. OBJECTIVE: To evaluate the opinion of experts in the diagnostic process of clinically relevant Spinal Post-traumatic Deformity (SPTD). SUMMARY OF BACKGROUND DATA: SPTD is a potential complication of spine trauma that can cause decreased function and quality of life impairment. The question of when SPTD becomes clinically relevant is yet to be resolved. METHODS: The survey of 7 cases was sent to 31 experts. The case presentation was medical history, diagnostic assessment, evaluation of diagnostic assessment, diagnosis, and treatment options. Means, ranges, percentages of participants, and descriptive statistics were calculated. RESULTS: Seventeen spinal surgeons reviewed the presented cases. The items\u27 fracture type and complaints were rated by the participants as more important, but no agreement existed on the items of medical history. In patients with possible SPTD in the cervical spine (C) area, participants requested a conventional radiograph (CR) (76%-83%), a flexion/extension CR (61%-71%), a computed tomography (CT)-scan (76%-89%), and a magnetic resonance (MR)-scan (89%-94%). In thoracolumbar spine (ThL) cases, full spine CR (89%-100%), CT scan (72%-94%), and MR scan (65%-94%) were requested most often. There was a consensus on 5 out of 7 cases with clinically relevant SPTD (82%-100%). When consensus existed on the diagnosis of SPTD, there was a consensus on the case being compensated or decompensated and being symptomatic or asymptomatic. CONCLUSIONS: There was strong agreement in 5 out of 7 cases on the presence of the diagnosis of clinically relevant SPTD. Among spine experts, there is a strong consensus to use CT scan and MR scan, a cervical CR for C-cases, and a full spine CR for ThL-cases. The lack of agreement on items of the medical history suggests that a Delphi study can help us reach a consensus on the essential items of clinically relevant SPTD. LEVEL OF EVIDENCE: Level V

Comprehensive Peripheral Blood Immunoprofiling Reveals Five Immunotypes With Immunotherapy Response Characteristics in Patients With Cancer

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient\u27s immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling

Easy method to simplify “freehand” subaxial cervical pedicle screw insertion

Study Design: Technical note. Objectives: The objective of this study is to check out safety and rationality of standardized and fast tricks to select trajectory of subaxial cervical pedicle screw (SCPS) insertion, based on simple angles to bony landmarks. Materials and Methods: Stage 1 – Computed tomography (CT)-morphometric analysis of C3–C7 vertebrae of ten patients with cervical degenerative diseases. Stage 2 – SCPS insertion in 6 cadavers, according to the developed technique (59 pedicle screws). Stage 3 – SCPS insertion in 6 patients, according to the developed technique (32 pedicle screws). Results: CT-morphometric analysis showed that the average length of C3–C7 pedicle channels was 32 mm, the average angle between a pedicle axis and an axis of contralateral lamina - 180°, the average angle between a pedicle axis and plane of a posterior surface of a lateral mass amounted to 90° and the coordinates of an optimal entry point – 2 mm from a lateral edge and 2 mm from an upper edge of the lateral mass posterior surface. During the cadaveric study, 39 screws had a satisfactory position (66.1%), 7 screws permissible (11.9%), and 13 screws unacceptable (22%). During the clinical study, 26 screws (81.25%) had satisfactory position, 4 (12.5%) had permissible position, and 2 (6.25%) unacceptable position. Conclusion: Developed and clinically approved a method for simplicity SCPS insertion is relatively safe and cheap. No doubt, it requires further investigation, but the results of primary analysis allow us to recommend it to wide practical application

Binding of Coagulation Factor XIII Zymogen to Activated Platelet Subpopulations: Roles of Integrin alpha (IIb) beta (3) and Fibrinogen

International audienceFactor XIIIa (fXIIIa) is a transglutaminase that plays a crucial role in fibrin clot stabilization and regulation of fibrinolysis. It is known to bind to procoagulant platelets. In contrast, the zymogen fXIII interaction with platelets is not well characterized. We investigated the interaction of zymogen fXIII with activated platelet subpopulations. Confocal microscopy and flow cytometry using fluorescently labelled factors and antibodies. Phosphatidylserine (PS)-positive activated platelets bound 700 to 800 molecules/cell of fXIII at 100nM, while both PS-negative activated platelets and resting platelets bound 200 to 400 molecules/cell. The binding was reversible, calcium-independent and linear within the fXIII concentration range of up to 1,000 nM. fXIII predominantly bound to the caps of procoagulant platelets and co-localized with fibrinogen. Exogenous fibrinogen promoted fXIII binding by activated PS-negative platelets; this effect was abolished by the integrin alpha IIb beta 3 antagonist monafram. The fXIII binding was 1.5- to 3-fold decreased for platelets from four patients with grey platelet syndrome, and was variable for platelets from six patients with Glanzmann's thrombasthenia. Strong platelet stimulation, fibrinogen and alpha IIb beta 3 play essential roles in fXIII binding, without any of them fXIII does not bind to platelets. The preferential binding in the cap-like structures might be important for increasing local fXIII concentration in platelet thrombi

The GAGA factor regulatory network: Identification of GAGA factor associated proteins

<div><p>The Drosophila GAGA factor (GAF) has an extraordinarily diverse set of functions that include the activation and silencing of gene expression, nucleosome organization and remodeling, higher order chromosome architecture and mitosis. One hypothesis that could account for these diverse activities is that GAF is able to interact with partners that have specific and dedicated functions. To test this possibility we used affinity purification coupled with high throughput mass spectrometry to identify GAF associated partners. Consistent with this hypothesis the GAF interacting network includes a large collection of factors and complexes that have been implicated in many different aspects of gene activity, chromosome structure and function. Moreover, we show that GAF interactions with a small subset of partners is direct; however for many others the interactions could be indirect, and depend upon intermediates that serve to diversify the functional capabilities of the GAF protein.</p></div

Y2H analysis of GAF direct C2H2-type Zinc Finger domain partners.

<p>(A) The test of ability of proteins with C2H2-type Zinc Finger domains to interact with GAF in the yeast two-hybrid assay. (B) Identification of the GAF domain that mediates interactions with the 3 interacting Zinc Finger proteins. The GAF deletion variants tested are indicated: 1–131 aa BTB GAF domain; 1–316 aa and 1–389 aa GAF fragments lacking or including the C2H2-type ZnF domain. Other designations are as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173602#pone.0173602.g002" target="_blank">Fig 2</a>.</p

GAF associated TrxG/PcG factors.

<p>GAF associated TrxG/PcG factors.</p

GAF associated ATP-dependent chromatin remodelers.

<p>GAF associated ATP-dependent chromatin remodelers.</p

Y2H analysis of GAF direct BTB/POZ domain partners.

<p>(A) The structure of GAF protein. The N-terminal BTB/POZ, a central C2H2-type zinc finger and several alternative glutamine rich (Q) C-terminal domains are indicated. The 1–131 aa GAF was used in Y2H analysis as BTB/POZ containing fragment. (B) The test of ability of the BTB/POZ proteins to interact with GAF in yeast two-hybrid assay. The data on the left lists the peptide count of tested proteins in the GAF immunoaffinity purified samples. The two-hybrid assay was performed with full length 519 aa GAF isoform or with BTB/POZ GAF containing fragment (1–131 aa indicated in the scheme above) fused to GAL4 binding domain (BD). The BTB/POZ domain of each protein in this group was fused with GAL4 activation domain (AD). Three types of selective media was used: lacking tryptophan, leucine, and histidine in the presence of 1mM or 5 mM 3-aminotriazole (3-AT) (-3+3-AT) and lacking tryptophan, leucine, histidine and adenine (-4). The +++ (strong), ++ (middle), + (weak), indicates the extent of growth that was detected at day 2, day 4 or day 7 respectively.</p