A predictive model for the critical shoulder angle based on a three-dimensional analysis of scapular angular and linear morphometrics.

BACKGROUND: The purpose of this study was to define the features of scapular morphology that are associated with changes in the critical shoulder angle (CSA) by developing the best predictive model for the CSA based on multiple potential explanatory variables, using a completely 3D assessment. METHODS: 3D meshes were created from CT DICOMs using InVesalius (Vers 3.1.1, RTI [Renato Archer Information Technology Centre], Brazil) and Meshmixer (3.4.35, Autodesk Inc., San Rafael, CA). The analysis included 17 potential angular, weighted linear and area measurements. The correlation of the explanatory variables with the CSA was investigated with the Pearson's correlation coefficient. Using multivariable linear regression, the approach for predictive model-building was leave-one-out cross-validation and best subset selection. RESULTS: Fifty-three meshes were analysed. Glenoid inclination (GI) and coronal plane angulation of the acromion (CPAA) [Pearson's r: 0.535; -0.502] correlated best with CSA. The best model (adjusted R-squared value 0.67) for CSA prediction contained 10 explanatory variables including glenoid, scapular spine and acromial factors. CPAA and GI were the most important based on their distribution, estimate of coefficients and loss in predictive power if removed. CONCLUSIONS: The relationship between scapular morphology and CSA is more complex than the concept of it being dictated solely by GI and acromial horizontal offset and includes glenoid, scapular spine and acromial factors of which CPAA and GI are most important. A further investigation in a closely defined cohort with rotator cuff tears is required before drawing any clinical conclusions about the role of surgical modification of scapular morphology. LEVEL OF EVIDENCE: Level 4 retrospective observational cohort study with no comparison group.

Comparing cancer genetic counselling using telegenetics with in-person and telephone appointments: Results of a partially randomised patient-preference pilot study.

INTRODUCTION: Direct-to-patient telegenetics, which uses video conferencing to connect health professionals directly to patients' devices, has been widely adopted during the pandemic. However, limited evidence currently supports its use in cancer genetic counselling. METHODS: Before the pandemic, we conducted a two-arm partially randomised patient-preference pilot trial to evaluate direct-to-patient telegenetics for patients and genetic counsellors. Patients were randomised to a standard care (telephone/in-person) or direct-to-patient telegenetics appointment. Patients completed questionnaires before, during and after appointments measuring: psychological distress, perceived genetic counsellor empathy, telegenetics satisfaction and technical challenges. Genetic counsellor-reported outcomes -measured using purpose-designed questionnaires- included telegenetics satisfaction, therapeutic alliance and time for assessment. Open-ended patient and genetic counsellor questionnaire responses were synthesised using content analysis. RESULTS: Fifty-six patients and seven genetic counsellors participated. Thirteen patients switched appointment type. No significant differences in distress (P = 0.84) were identified between direct-to-patient telegenetics and standard care. Perceived genetic counsellor empathy was high for all appointment types. There was no evidence of differences in reported maximum empathy scores between direct-to-patient telegenetics and standard care [telephone (P = 0.57); in-person (P = 0.44)]. Patients reported high direct-to-patient telegenetics satisfaction despite technical challenges in most appointments (65%). Genetic counsellors were satisfied with direct-to-patient telegenetics and perceived high therapeutic alliance irrespective of appointment type. No significant differences in genetic counsellor time were identified between direct-to-patient telegenetics and standard care [telephone (P > 0.90); in-person (P = 0.35)]. DISCUSSION: Our results suggest that direct-to-patient telegenetics is a satisfactory service delivery model that does not appear to compromise patient-genetic counsellor relationships or increase patient distress. These findings support direct-to-patient telegenetics use in cancer genetic counselling, although larger trials are needed.

Polygenic risk in familial breast cancer: Changing the dynamics of communicating genetic risk.

Hereditary breast cancer is associated with known genetic changes: either variants that affect function in a few rare genes or an ever-increasing number of common genomic risk variants, which combine to produce a cumulative effect, known as a polygenic risk (PR) score. While the clinical validity and utility of PR scores are still being determined, the communication of PR is a new challenge for genetic health professionals. This study investigated how PR scores are discussed in the familial cancer clinic compared with a previous study assessing the communication of monogenic risk (MR) for breast cancer. Sixty-five PR consultations between genetic health professionals and women at familial risk of breast cancer were audiotaped, transcribed, and coded using a methodology adapted from the MR study. Analysis of consultations shows that while there were similarities in communicating MR and PR, the complexity and novelty of the polygenic information influenced the style of counseling used by genetic health professionals toward a teaching model of genetic counseling, rather than a patient-centered approach. In particular, compared to MR consultations, in PR consultations significantly fewer counselees (a) were asked about their reasons for attending genetic counseling; or (b) had their information preferences, decision-making style, medical knowledge, understanding, or concerns checked. In conclusion, it is anticipated that PR scores will become part of standard clinical practice. Thus, it will be important for all genetic health professionals to be appropriately educated so that they can tailor their communication to meet patient needs.

Hemoglobin, Body Mass Index, and Age as Risk Factors for Paclitaxel- and Oxaliplatin-Induced Peripheral Neuropathy.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating adverse effect of neurotoxic cancer treatments including taxanes and platinum agents. Limited knowledge exists of potential prechemotherapy factors associated with CIPN development. Objective: To identify the association of pretreatment blood-based and clinical factors with CIPN persistence in patients who received paclitaxel or oxaliplatin. Design, Setting, and Participants: This cohort study assessed pretreatment blood-based clinical factors and demographic characteristics of 333 patients treated with paclitaxel and oxaliplatin chemotherapy at urban multicenter cancer clinics and academic institutions in Australia between September 2015 and February 2020. Comprehensive neuropathy assessments were undertaken 3 to 12 months posttreatment. Posttreatment CIPN severity was compared with blood-based factors within 30 days prior to commencing chemotherapy. Data were analyzed between March and December 2020. Exposures: Paclitaxel or oxaliplatin chemotherapy. Main Outcomes and Measures: CIPN was measured using composite neurological grading scales, nerve conduction studies, and assessments of fine motor skills (grooved pegboard test), sensory function (grating orientation test and 2-point discrimination), and patient-reported outcomes. Independent samples t tests and Mann-Whitney U tests with post hoc Bonferroni correction were used to compare CIPN between patients according to blood-based factor normative ranges. Linear regression was used to identify blood-based and clinical associations with CIPN development. Results: The study included 333 participants (266 [79.9%] women; median [interquartile range] age, 58 [18] years) who were consecutively recruited and referred (228 treated with paclitaxel, 105 treated with oxaliplatin; 138 [41.4%] with breast cancer, 83 [24.9%] with colorectal cancer). Most participants had grade 1 CIPN or higher (238 [71.5%] participants). Participants with low hemoglobin pretreatment had worse CIPN posttreatment (median [IQR] composite neurological grading scale score, 5 [2-8] vs 4 [1-6]; P = .002; grooved pegboard mean [SD] time, 84.2 [28.7] vs 72.9 [21.1] seconds; P = .002; grating orientation task, 4.8 [2.8] vs 3.9 [1.8] mm; P = .03; 2-point discrimination, 45% vs 28%; P = .01), with no other impairments outside normative ranges associated with CIPN. In the multivariable model, several factors were associated with worse CIPN (F4,315 = 18.6; P < .001; r2 = .19) including for lower hemoglobin (ß = -0.47; 95% CI, -0.73 to -0.21; P < .001), higher body mass index (ß = 0.08; 95% CI, 0.02 to 0.12; P = .007), older age (ß = 0.08; 95% CI, 0.06 to 0.11; P < .001), and female sex (ß = -1.08; 95% CI, -1.76 to -0.16; P = .01). Conclusions and Relevance: The results of this cohort study suggest that participants with low pretreatment hemoglobin, higher body mass index, older age, and female sex were more likely to develop paclitaxel- or oxaliplatin-induced CIPN posttreatment. Future research should investigate prospectively whether these risk factors are associated with a higher incidence of CIPN development.

Motor unit changes in children with symptomatic spinal muscular atrophy treated with nusinersen.

OBJECTIVES: To elucidate the motor unit response to intrathecal nusinersen in children with symptomatic spinal muscular atrophy (SMA) using a novel motor unit number estimation technique. METHODS: MScanFit MUNE studies were sequentially undertaken from the abductor pollicis brevis muscle after stimulation of the median nerve in a prospective cohort of symptomatic children with SMA, undergoing intrathecal treatment with nusinersen at a single neuromuscular centre from June 2017 to August 2019. Electrophysiological measures included compound muscle action potential (CMAP), motor unit number estimation (MUNE), motor unit number contributing to 50%-100% of CMAP (N50) and measures of collateral reinnervation including largest single motor unit potential (LSMUP) and amplitude of the smallest unit contributing to N50 (A50). RESULTS: Twenty children (median age 99 months, range 4-193) were followed for a median of 13.8 (4-33.5) months. Therapeutic intervention was an independent and significant contributor to an increase in CMAP (p = 0.005), MUNE (p = 0.001) and N50 (p = 0.04). The magnitude of this electrophysiological response was increased in children with shorter disease durations (p<0.05). Electrophysiological changes delineated children who were functionally stable from those who attained clinically significant gains in motor function. INTERPRETATION: Nusinersen therapy facilitated functional innervation in SMA through recovery of smaller motor units. Delineation of biomechanisms of therapeutic response may be the first step in identifying potential novel targets for disease modification in this and other motor neuropathies. MScanFit MUNE techniques may have a broader role in establishing biomarkers of therapeutic response in similar adult-onset diseases.

Predicting the outcome of transcatheter mitral valve implantation using image-based computational models.

BACKGROUND: The appropriate placement and size selection of mitral prostheses in transcatheter mitral valve implantation (TMVI) is critical, as encroachment on the left ventricular outflow tract (LVOT) may lead to flow obstruction. Recent advances in computed tomography (CT) can be employed for pre-procedural planning of mitral prosthetic valve placement. This study aims to develop patient-specific computational fluid dynamics models of the left ventricle (LV) in the presence of a mitral valve prosthesis to investigate blood flow and LVOT pressure gradient during systole. METHODS: Patient-specific computational fluid dynamics simulations of TMVI with varied cardiac anatomy and insertion angles were performed (n = 30). Wide-volume full cycle cardiovascular CT images prior to TMVI were used as source anatomical data (n = 6 patients). Blood movement was governed by Navier-Stokes equations and the LV endocardial wall deformation was derived from each patient's CT images. RESULTS: The computed pressure gradients in the presence of the mitral prosthesis compared well with clinically measured gradients. Analysis of the effects of prosthetic valve angulation, aorto-mitral annular angle, ejection fraction, LV size and new LVOT area (neo-LVOT) after TMVI in silico revealed that the neo-LVOT area (p < 0.001) was the most significant factor affecting LVOT pressure gradient. Angulation of the mitral valve can substantially mitigate LVOT gradient. CONCLUSIONS: Computational fluid dynamics simulation is a promising method to aid in pre-TMVI planning and understanding the factors underlying LVOT obstruction.

Field monitoring of plant-growth-promoting rhizobacteria by colony immunoblotting.

Inoculant plant-growth-promoting bacteria are emerging as an important component of sustainable agriculture. There is a need to develop inexpensive methods for enumerating these organisms after their application in the field, to better understand their survival and impacts on yields. Immunoblotting is one potential method to measure viable cells, but the high cost of the conventionally used nylon membranes makes this method prohibitive. In this study, less expensive alternative materials such as filter papers, glossy photo papers, and transparencies for the purpose of colony immunoblotting were evaluated and the best substance was chosen for further studies. Whatman filter paper No. 541 combined with a 0.01 mol·L(-1) H(2)SO(4) rinsing step gave similar results to nylon membranes but <20% of the overall cost of the original colony immunoblotting assay. The application of the modified immunoblot method was tested on nonsterile clay soil samples that were spiked with high numbers (>10(7) CFU·g(-1)) of the plant-growth-promoting bacteria Pseudomonas fluorescens , Azospirillum brasilense , or Rhizobium leguminosarum . The modified protocol allowed the identification and recovery of over 50% of the inoculated cells of all three strains, amidst a background of the native soil microflora. Subsequently, the survival of P. fluorescens was successfully monitored for several months after application to field-grown rice at Jerilderie, New South Wales, Australia, thus validating the procedure.