Screening for Bronchoscopic Lung Volume Reduction: Reasons for Not Receiving Interventional Treatment

Background

Evidence for bronchoscopic lung volume reduction (BLVR) is based on phase 2 studies and small randomized controlled trials with in- and exclusion criteria defining a therapeutic window and contraindications. Little is known about the applicability in routine clinical practice.

Aim

Which percentage of patients with severe emphysema referred to a specialized treatment center for BLVR is ultimately suitable for interventional bronchoscopic treatment? What is the relevance of the different contraindications?

Methods

Retrospective evaluation of emphysema patients referred to Asklepios Fachkliniken Munich-Gauting for BLVR between January 2014 and June 2015.

Results

138 patients were referred for evaluation of BLVR. 38 patients (27.5%) underwent BLVR procedures (valves n = 18; coils n = 18; thermal vapor ablation n = 2). 100 patients (72.5%) were deemed not eligible for BLVR based on the following contraindications: 34% emphysema morphology and emphysema-related findings (severe homogeneous emphysema, extensive pleuropulmonary adhesions, postinflammatory scaring with natural volume reduction, giant bullae), 16% active smoking; 9% pulmonary function not within indication range; 8% unexpected CT findings (nodules, cancer, interstitial disease); 8% chronic ventilatory failure; 8% patient refused BLVR; 5% relevant comorbidity; 5% frequent exacerbations, 3% preserved quality of life, 4% other.

Conclusion

BLVR is a therapeutic option for highly selected patients. In our cohort, one in four could be treated. These data highlight the limitations of BLVR under real-life conditions.

     

The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

Sequence Conservation of Glycerophosphodiester Phosphodiesterase among Treponema pallidum Strains

Previous investigations have demonstrated that immunization with Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase significantly protects rabbits from subsequent treponeme challenge. In this report, we show that the glycerophosphodiester phosphodiesterase amino acid sequence is conserved among 12 strains from a total of five pathogenic treponemes. The invariant nature of this immunoprotective antigen makes it an attractive candidate for inclusion in a universal subunit vaccine against T. pallidum infection. In addition, these studies show a silent nucleotide substitution at position 579 of the gpd open reading frame which is consistently observed in the non-T. pallidum subsp. pallidum strains. This sequence alteration introduces a PleI restriction site in the nonsyphilis strains and thus allows genetic differentiation from T. pallidum subsp. pallidum strains.     

The internalization of the IgG2a antigen receptor does not require the association with Ig-α and Ig-β but the activation of protein tyrosine kinases does

The B cell antigen receptor of class IgM is a multimeric protein complex containing the membrane-bound immunoglobulin molecule and a heterodimer of the two B cell-specific transmembrane proteins Ig-α and Ig-β. The B cell antigen receptor fulfills a dual role on the surface of B cells. First, it is a signal transduction complex which can activate protein tyrosine kinases and induce the release of Ca²⁺ ions from intracellular stores. Second, its internalization mediates the specific uptake of bound antigens, which are processed intracellularly and presented as major histocompatibility complex-bound peptides on the cell surface. In case of the IgM antigen receptor, the association with the heterodimer is necessary for expression of large amounts of IgM on the surface. We show here that the IgG2a antigen receptor can be expressed on the surface of myeloma cells in two structurally different forms: either with or without the Ig-α/Ig-β heterodimer. A functional comparison of the two forms of antigen receptors demonstrates that the Ig-α and Ig-β molecules are required for the activation of protein tyrosine kinases after cross-linking of the B cell antigen receptor. In contrast, both forms of IgG2a are equally well internalized. This suggests that Ig-α and Ig-β are essential for signal transduction through the IgG2a antigen receptor, whereas internalization can occur independently of the heterodimer.     

Research participation,trust, and fair compensation among people living with and without HIV in Florida

Florida has the second highest number of newly diagnosed cases of HIV in the United States. Sociodemographic representation that is reflective of the population is essential in developing evidence based interventions to improve HIV outcomes and reduce disparities. Understanding HIV research trial participation, preferences for types of research, and fair compensation for research will further our understanding of someone’s decision to participate in research. The purpose of this analysis was to identify differences in prior research participation, trust, interests in types of research, and fair compensation between people living with HIV and without HIV in North Central Florida. In this sample of 8340 people interviewed in the community about their health concerns and research participation, 156 reported living with HIV. Only 20.5% of people with HIV reported past participation in research, however 94.2% said they were interested in future research participation. While people with HIV were slightly more interested in higher risk/low convenience research, there were no statistically significant differences in preferences for types of research between those with and without HIV. People with HIV reported no difference in the amount they would request for fair compensation ($78.4 USD) compared with those without HIV ($72.2 USD, p?=?0.69). Community members are interested in participating in research, although few had previously participated. Improving our understanding of research study participation will help improve recruitment efforts and draw stronger conclusions regarding the effectiveness of interventions, as well as enhance implementation of these interventions.     

Robotic resection of recurrent pediatric lipoblastoma

This case demonstrates successful resection of a rare, recurrent presacral‐pelvic lipoblastoma in a 19‐year‐old female patient. Because of the anatomical location of the mass and its proximity to vital structures, the robotic approach allowed for both optimal visualization and effective debulking of the mass. Furthermore, with the use of an articulating laparoscopic camera, key visualization of the posterior lateral pelvis was possible. Using a wide breadth of technologies and resources is essential to broadening the surgical armamentarium and achieving resectability in otherwise challenging cases.