CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Hip Displacement in Cerebral Palsy: The Role of Surveillance

IntroductionHip displacement is common in cerebral palsy (CP) and is related to the severity of neurological and functional impairment. It is a silent, but progressive disease, and can result in significant morbidity and decreased quality of life, if left untreated. The pathophysiology of hip displacement in CP is a combination of hip flexor-adductor muscle spasticity, abductor muscle weakness, and delayed weight-bearing, resulting in proximal femoral deformities and progressive acetabular dysplasia. Due to a lack of symptoms in the early stages of hip displacement, the diagnosis is easily missed. Awareness of this condition and regular surveillance by clinical examination and serial radiographs of the hips are the key to early diagnosis and treatment.Hip surveillance programmesSeveral population-based studies from around the world have demonstrated that universal hip surveillance in children with CP allows early detection of hip displacement and appropriate early intervention, with a resultant decrease in painful dislocations. Global hip surveillance models are based upon the patients’ age, functional level determined by the Gross Motor Function Classification system (GMFCS), gait classification, standardized clinical exam, and radiographic indices such as the migration percentage (MP), as critical indicators of progressive hip displacement.ConclusionDespite 25 years of evidence showing the efficacy of established hip surveillance programmes, there is poor awareness among healthcare professionals in India about the importance of regular hip surveillance in children with CP. There is a need for professional organizations to develop evidence-based guidelines for hip surveillance which are relevant to the Indian context.     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Noise characterization of “effective quiet” areas on a U.S. Navy aircraft carrier

The purpose of this investigation was to characterize noise levels in spaces designated as “effective quiet” areas on a U.S. Navy aircraft carrier. Noise dosimetry samples were collected in 15 designated spaces, representing 15 noise measurements, while at-sea during airwing carrier qualifications. Equivalent sound level (L_eq) measurements were collected during flight operations (L_{eq (flt ops)}), non-flight operations (L_{eq (non-flt ops)}), and over 24-hr periods (L_{eq (24-hr)}). These data were compared to the 70 dBA American Conference of Governmental Industrial Hygienists (ACGIH^®) Threshold Limit Value (TLV^®) for “effective quiet” areas intended for temporary threshold shift recovery when personnel live and work in a potentially noise hazardous environment for periods greater than 24?hr. The monitored areas were selected based on personnel occupancy/use during off-duty time periods. Areas were classified by either (1) leisure areas that included mess (eating areas), gyms, lounges, an internet cafe, and the fantail social area or (2) berthing (sleeping) areas. The L_eq measurements in decibels “A” weighted (dBA) were compared to determine significant differences between L_{eq (flt ops)}, L_{eq (non-flt ops)}, and L_{eq (24-hr)} and were compared between leisure area and berthing area. Measured noise levels according to time period ranged as follows: (1) L_{eq (24-hr)}: 70.8–105.4 dBA; (2) L_{eq (flt ops)}: 70–101.2 dBA; and (3) L_{eq (non-flt ops)}: 39.4–104.6 dBA. All area measurements over the 24-hr period and during flight operations and 46.7% of the areas during the non-flight operation time period exceeded the “effective quiet” 70 dBA ACGIH TLV. Mean L_eqs were 15 dBA higher during flight operations compared to non-flight operations in “effective quiet” areas (p?=?0.001). The L_eqs in leisure areas were significantly higher than berthing areas by approximately 21 dBA during non-flight operation periods (p?=?0.001). Results suggest noise levels in “effective quiet” areas frequented by aircraft carrier personnel during off-duty hours when at-sea may inhibit auditory recovery from occupational noise exposures that occur on-duty.