Impact of Mucinous Histology on the Prognosis of Stage I–III Adenocarcinomas of the Appendix: a Population-Based,Propensity Score-Matched Analysis

Background

Whereas the poor prognosis of signet ring cell adenocarcinomas of the appendix is well known, the significance of mucinous histology remains unclear. The aim of this population-based study was to evaluate if mucinous histology is an independent prognostic factor in appendiceal adenocarcinomas.

Methods

Patients with stage I–III adenocarcinoma of the appendix who underwent surgery between 2004 and 2012 were identified in the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.

Results

Overall, 980 patients with appendix cancer were included, of which 449 (45.8 %) had a mucinous histology. In an unadjusted analysis, the 5-year OS and CSS in patients with a mucinous adenocarcinoma (MC) was 76.8 % (95 % confidence interval (95 %CI): 72.1–81.7 %) and 81.0 % (95 %CI: 76.6–85.6 %), respectively, compared with 70.0 % (95 %CI: 65.1–75.3 %) and 76.2 % (95 %CI: 71.5–81.2 %) in patients with non-mucinous adenocarcinoma (NMC) (P?=?0.082 and P?=?0.368). In multivariable analysis, no impact on survival was observed for OS (HR?=?1.22, 95 %CI: 0.89–1.68, P?=?0.208) and CSS (HR?=?1.21, 95 %CI: 0.84–1.74, P?=?0.296). After propensity score matching, nearly identical survival rates were observed (OS: HR?=?1.03, 95 %CI: 0.71–1.49, P?=?0.881 and CSS: HR?=?1.05, 95 %CI: 0.70–1.59, P?=?0.803).

Conclusions

The present population-based, propensity score matched analysis shows that mucinous histology does not affect survival in stage I–III appendiceal adenocarcinoma patients. Therefore, the same treatment strategies can be applied for patients with NMC and MC of the appendix.

     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to alpha 7 beta 1-integrin deficiency

Integrin-linked kinase (Ilk) is a serine/threonine kinase and an adaptor protein that links integrins to the actin cytoskeleton and to a number of signaling pathways involved in integrin action. We hypothesized that Ilk may act as an important effector of integrins in skeletal muscle, where these receptors provide a critical link between the sarcolemma and the extracellular matrix. Using the cre/lox system, we deleted Ilk from skeletal muscles of mice. The resulting mutants developed a progressive muscular dystrophy with multiple degenerating and regenerating muscle fibers, increased central nuclei, and endomysial fibrosis. These defects were widespread but were most severe near myofascial junctions where Ilk mutants showed displacement of focal adhesion-related proteins, including vinculin, paxillin, focal adhesion kinase, dystrophin, and the alpha 7 beta 1D-integrin subunits. Distal ends of mutant muscle fibers appeared irregular, and there was restructuring of the actin cytoskeleton. These findings resemble those seen in humans and mice lacking the alpha 7-integrin subunit and suggest that Ilk may act as a cytoplasmic effector of alpha 7 beta1-integrin in the pathogenesis of these deficiencies.     

Laterally closed tunnel technique with and without adjunctive photobiomodulation therapy for the management of isolated gingival recession—a randomized controlled assessor-blinded clinical trial

Lasers in Medical Science - The objective of this prospective randomized controlled single-center clinical trial was to prove the efficacy of adjunctive photobiomodulation in improving selected...     

Anti‐inflammatory effects of haptoglobin on LPS‐stimulated macrophages: Role of HMGB1 signaling and implications in chronic wound healing

Nonhealing wounds possess elevated numbers of pro‐inflammatory M1 macrophages, which fail to transition to anti‐inflammatory M2 phenotypes that promote healing. Hemoglobin (Hb) and haptoglobin (Hp) proteins, when complexed (Hb‐Hp), can elicit M2‐like macrophages through the heme oxygenase‐1 (HO‐1) pathway. Despite the fact that nonhealing wounds are chronically inflamed, previous studies have focused on non‐inflammatory systems, and do not thoroughly compare the effects of complexed vs individual proteins. We aimed to investigate the effect of Hb/Hp treatments on macrophage phenotype in an inflammatory, lipopolysaccharide (LPS)‐stimulated environment, similar to chronic wounds. Human M1 macrophages were cultured in vitro and stimulated with LPS. Concurrently, Hp, Hb, or Hb‐Hp complexes were delivered. The next day, 27 proteins related to inflammation were measured in the supernatants. Hp treatment decreased a majority of inflammatory factors, Hb increased many, and Hb‐Hp had intermediate trends, indicating that Hp attenuated overall inflammation to the greatest extent. From this data, Ingenuity Pathway Analysis software identified high motility group box 1 (HMGB1) as a key canonical pathway—strongly down‐regulated from Hp, strongly up‐regulated from Hb, and slightly activated from Hb‐Hp. HMGB1 measurements in macrophage supernatants confirmed this trend. In vivo results in diabetic mice with biopsy punch wounds demonstrated accelerated wound closure with Hp treatment, and delayed wound closure with Hb treatment. This work specifically studied Hb/Hp effects on macrophages in a highly inflammatory environment relevant to chronic wound healing. Results show that Hp—and not Hb‐Hp, which is known to be superior in noninflammatory conditions—reduces inflammation in LPS‐stimulated macrophages, and HMGB1 signaling is also implicated. Overall, Hp treatment on M1 macrophages in vitro reduced the inflammatory secretion profile, and also exhibited benefits in in silico and in vivo wound‐healing models.     

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant – a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO₂/FiO₂ ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.