Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis

Cryptococcus neoformans is an opportunistic fungal pathogen preferentially causing disease in immunocompromised individuals such as organ-transplant-recipients, patients receiving immunosuppressive medications or, in particular, individuals suffering from HIV infection. Numerous studies clearly indicated that the control of C. neoformans infections is strongly dependent on a prototypic type 1 immune response and classical macrophage activation, whereas type 2-biased immunity and alternative activation of macrophages has been rather implicated in disease progression and detrimental outcomes. However, little is known about regulatory pathways modulating and balancing immune responses during early phases of pulmonary cryptococcosis. Here, we analyzed the role of group 2 innate lymphoid cells (ILC2s) for the control of C. neoformans infection. Using an intranasal infection model with a highly virulent C. neoformans strain, we found that ILC2 numbers were strongly increased in C. neoformans-infected lungs along with induction of a type 2 response. Mice lacking ILC2s due to conditional deficiency of the transcription factor RAR-related orphan receptor alpha (Rora) displayed a massive downregulation of features of type 2 immunity as reflected by reduced levels of the type 2 signature cytokines IL-4, IL-5, and IL-13 at 14 days post-infection. Moreover, ILC2 deficiency was accompanied with increased type 1 immunity and classical macrophage activation, while the pulmonary numbers of eosinophils and alternatively activated macrophages were reduced in these mice. Importantly, this shift in pulmonary macrophage polarization in ILC2-deficient mice correlated with improved fungal control and prolonged survival of infected mice. Conversely, adoptive transfer of ILC2s was associated with a type 2 bias associated with less efficient anti-fungal immunity in lungs of recipient mice. Collectively, our date indicate a non-redundant role of ILC2 in orchestrating myeloid anti-cryptococcal immune responses toward a disease exacerbating phenotype

Do cleft lip and palate patients opt for secondary corrective surgery of upper lip and nose, frequently?

Purpose This prospective study was aimed at assessing cleft lip and palate (CLP) patients’ opinions and attitudes towards their upper lip and nose and the number of secondary corrective surgical interventions electively undertaken to upper lip and nose that were carried out during a 2 year follow-up period. Materials and methods During a 2 year follow-up period CLP outpatients were recruited for the study who attended follow-up examinations at a cleft lip and palate craniofacial center and received a recommendation for secondary corrective facial surgery. The participants filled in a questionnaire that included questions regarding the patients’ opinions and attitudes towards appearance of lip and nose and need for secondary corrective facial surgery. During an additional interval of 2 years the rate of patients who underwent secondary corrective surgery to lip and nose was documented. Results Out of 362 CLP patients 37 (mean age 13.6 ± 7.6 years) received a recommendation for secondary corrective surgery to upper lip and/or nose. 22 patients (mean age 12.6 ± 6.3 years) filled in the questionnaire (response rate of 62.1%). The satisfaction with the overall facial appearance following the first corrective operation was statistically significantly better than the satisfaction with the nose (p = .016). The satisfaction with facial symmetry (5.6 ± 2.0) did not differ statistically significantly from the overall satisfaction with the facial appearance (6.2 ± 1.8; p = .093). Significantly fewer patients (n = 9) opted for corrective surgery compared to the number of patients who got the recommendation to have secondary corrective surgery done (n = 22, p < .0005). Conclusions The findings of the present study may reflect a high overall patient satisfaction with the primary treatment outcome following surgery for CLP. Perceived patient need for secondary operation for the lip/nose may be as low as 5%

Do cleft lip and palate patients opt for secondary corrective surgery of upper lip and nose, frequently?

Purpose: This prospective study was aimed at assessing cleft lip and palate (CLP) patients’ opinions and attitudes towards their upper lip and nose and the number of secondary corrective surgical interventions electively undertaken to upper lip and nose that were carried out during a 2 year follow-up period. Materials and methods: During a 2 year follow-up period CLP outpatients were recruited for the study who attended follow-up examinations at a cleft lip and palate craniofacial center and received a recommendation for secondary corrective facial surgery. The participants filled in a questionnaire that included questions regarding the patients’ opinions and attitudes towards appearance of lip and nose and need for secondary corrective facial surgery. During an additional interval of 2 years the rate of patients who underwent secondary corrective surgery to lip and nose was documented. Results: Out of 362 CLP patients 37 (mean age 13.6 +/- 7.6 years) received a recommendation for secondary corrective surgery to upper lip and/or nose. 22 patients (mean age 12.6 +/- 6.3 years) filled in the questionnaire (response rate of 62.1%). The satisfaction with the overall facial appearance following the first corrective operation was statistically significantly better than the satisfaction with the nose (p = .016). The satisfaction with facial symmetry (5.6 +/- 2.0) did not differ statistically significantly from the overall satisfaction with the facial appearance (6.2 +/- 1.8; p = .093). Significantly fewer patients (n = 9) opted for corrective surgery compared to the number of patients who got the recommendation to have secondary corrective surgery done (n = 22, p &lt; .0005). Conclusions: The findings of the present study may reflect a high overall patient satisfaction with the primary treatment outcome following surgery for CLP. Perceived patient need for secondary operation for the lip/nose may be as low as 5%

Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration