Non-invasive ventilation and clinical outcomes in cystic fibrosis: Findings from the UK CF registry

BackgroundNon-invasive ventilation (NIV) for respiratory failure and airway clearance is an established intervention in cystic fibrosis (CF), but its therapeutic benefit on lung function and survival remains under-investigated.MethodsUsing data from the UK CF Registry between 2007 and 2015, we explored the patterns of NIV use, and assessed changes in mean percent predicted FEV₁ (ppFEV₁) prior to and after NIV use, and the survival of patients on NIV.ResultsAmong 11,079 patients, 1107 had at least one record of NIV treatment. Incidence and prevalence of NIV was lower in children and followed non-linear temporal patterns. Adjusting for other risk factors, ppFEV₁ rose by 0.70 (95%CI: -0.83, 2.24) after first NIV use in children. In adults with a low ppFEV₁ (<40%) at initiation of treatment, NIV increased mean ppFEV₁ by 2.60 (95% CI: 0.93, 4.27). Our analysis showed that NIV initiation is associated with an increased risk of death/transplant in both children (HR = 2.47; 95%CI: 1.20–5.08) and adults (HR = 1.96; 95% CI: 1.63–2.36) but effect was attenuated in children with low ppFEV₁ (<40%).ConclusionsNIV usage in CF improves spirometric values but does not benefit survival. Further studies are required to better understand survival outcomes and ultimately improve NIV outcomes in CF.     

Super-resolution Ultrasound Imaging

The majority of exchanges of oxygen and nutrients are performed around vessels smaller than 100 μm, allowing cells to thrive everywhere in the body. Pathologies such as cancer, diabetes and arteriosclerosis can profoundly alter the microvasculature. Unfortunately, medical imaging modalities only provide indirect observation at this scale. Inspired by optical microscopy, ultrasound localization microscopy has bypassed the classic compromise between penetration and resolution in ultrasonic imaging. By localization of individual injected microbubbles and tracking of their displacement with a subwavelength resolution, vascular and velocity maps can be produced at the scale of the micrometer. Super-resolution ultrasound has also been performed through signal fluctuations with the same type of contrast agents, or through switching on and off nano-sized phase-change contrast agents. These techniques are now being applied pre-clinically and clinically for imaging of the microvasculature of the brain, kidney, skin, tumors and lymph nodes.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Strain shielding for cemented hip implants

BackgroundLong-term survival of hip implants is of increasing relevance due to the rising life expectancy. The biomechanical effect of strain shielding as a result of implant insertion may lead to bone resorption, thus increasing risk for implant loosening and periprosthetic fractures. Patient-specific quantification of strain shielding could assist orthopedic surgeons in choosing the biomechanically most appropriate prosthesis.MethodsValidated quantitative CT-based finite element models of five femurs in intact and implanted states were considered to propose a systematic algorithm for strain shielding quantification. Three different strain measures were investigated and the most appropriate measure for strain shielding quantification is recommended. It is used to demonstrate a practical femur-specific implant selection among three common designs.FindingsStrain shielding measures demonstrated similar trends in all Gruen zones except zone 1, where the volumetric strain measure differed from von-Mises and maximum principal strains. The volumetric strain measure is in better agreement with clinical bone resorption records. It is also consistent with the biological mechanism of bone remodeling so it is recommended for strain shielding quantification. Applying the strain shielding algorithm on three different implants for a specific femur suggests that the collared design is preferable. Such quantitative biomechanical input is valuable for practical patient specific implant selection.InterpretationVolumetric strain should be considered for strain shielding examination. The presented methodology may potentially enable patient-specific pre-operative strain shielding evaluation so to minimize strain shielding. It should be further used in a longitudinal study so to correlate between strain shielding predictions and clinical bone resorption.