Three-dimensional assessment of palatal area changes after posterior crossbite correction with tooth-borne and tooth bone–borne rapid maxillary expansion: A randomized controlled trial with 5-year follow-up

ObjectivesTo assess and compare the three-dimensional treatment changes in palatal surface area and volume using either tooth-borne (TB) or tooth bone–borne (TBB) rapid maxillary expanders and to evaluate the long-term effects of the two devices and the incidence of the relapse between the groups.Materials and MethodsA total of 52 consecutive patients who met the eligibility criteria were recruited and allocated to either the TB group, mean age 9.3 years (standard deviation [SD], 1.3), or the TBB group, mean age 9.5 years (SD, 1.2). Study casts were taken before, directly after, 1 year after, and 5 years after expansion. Study casts were digitized, superimposed, and evaluated. Participants were randomly allocated in blocks of different sizes using the concealed allocation principle in a 1:1 ratio.ResultsChanges in palatal volume, palatal surface area, and palatal projection area within and between the groups up to 5 years after expansion followed the same pattern and did not show any statistically significant differences between the groups. Relapse was seen in 15% of the patients. It seemed that open-bite and a Class III growth pattern could be assumed as prognosis-deteriorating factors in regard to stability of the treatment.ConclusionsThere were no significant differences between the TB and TBB groups in palatal volume, palatal shell area, or palatal projection area directly after expansion or at 1 year and 5 years after expansion, which implies that the two devices gave rise to the same immediate and long-term outcomes.     

【In Press】Lyme Borrelia as the etiological factor in three cases of primary inflammatory choriocapillaropathies

Letter to the editor     

Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression

Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor β (TGF-β) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-β1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3 that are permissive for SARS-CoV-2. The inhibition of ALK5 by incubation with SB431542 revealed a dose-dependent downregulation of both basal and TGF-β1 induced furin expression. Furthermore, we demonstrate that the ALK5 inhibitors SB431542 and Vactosertib negatively affect the proteolytic processing of the SARS-CoV-2 Spike protein and significantly reduce spike-mediated cell–cell fusion. This correlated with an inhibitory effect of ALK5 inhibition on the production of infectious SARS-CoV-2. Altogether, our study shows that interference with ALK5 signaling attenuates SARS-CoV-2 infectivity and cell–cell spread via downregulation of furin which is most pronounced upon TGF-β stimulation. Since a TGF-β dominated cytokine storm is a hallmark of severe COVID-19, ALK5 inhibitors undergoing clinical trials might represent a potential therapy option for COVID-19.     

Secondary biogenic amine deficiencies: genetic etiology,therapeutic interventions,and clinical effects

neurogenetics - Monoamine neurotransmitter disorders present predominantly with neurologic features, including dystonic or dyskinetic cerebral palsy and movement disorders. Genetic conditions that...     

The prognostic role of diabetes mellitus type 2 in the setting of hepatocellular carcinoma: a systematic review and meta-analysis

AimTo evaluate the effect of diabetes mellitus type 2 (T2DM) on the outcomes after treatment of hepatocellular carcinoma (HCC).MethodsPubMed and Cochrane Central Register of Controlled Trials Databases were systematically searched. Three HCC clinical outcomes were explored: death, progressive disease after locoregional therapies, and recurrence. Sub-analysis was performed according to the use of potentially curative (resection, transplantation, termo-ablation) or non-curative therapies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare the pooled data between T2DM and non-T2DM groups.ResultsA total of 27 studies were analyzed. Overall, 85.2% of articles were from Asia. T2MD was associated with an increased risk of death (OR 3.60; 95%CI 2.18-5.95; P < 0.001), irrespective of the treatment approach: curative (OR 1.30 95%CI 1.09-1.54; P = 0.003) or non-curative (OR 1.05; 95%CI 1.00-1.10; P = 0.045), increased HCC recurrence (OR 1.30; 95%CI 1.03-1.63; P = 0.03), and increased disease progressiveness (OR 1.24; 95%CI 1.09-1.41; P = 0.001).ConclusionsCurrent data provide strong evidence that T2DM unfavorably affects HCC progression and recurrence, and patients'' survival after treatment, irrespective of the approach used.

The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) is increasing (1,2) as the result of the globally increased prevalence of NALFD, which is estimated to be about 25% (3). NAFLD patients have a two- to three-fold increase in the risk of developing diabetes mellitus type 2 (T2DM), and the risk is even higher in those with more severe hepatic disease and fibrosis (4-6). On the other hand, patients with T2DM have a higher prevalence of non-alcoholic steatohepatitis (NASH), liver fibrosis, and end-stage liver disease (7).Several studies have documented the relation between T2DM and the incidence of different cancer types, while the data on the relationship between T2DM and increased risk of incident HCC seem especially robust and clinically reliable (8-10). Observational studies suggest higher mortality of patients developing HCC in the presence of T2DM (11,12). On the other hand, data from meta-analyses suggest that both the risk and prognosis of patients with HCC and diabetes might be influenced by the type of anti-diabetic treatment, where metformin, unlike sulphonylurea, potentially protects against cancer and leads to better prognosis in case of cancer development (13,14).The underlying mechanisms linking T2DM and HCC are still under scientific scrutiny. However, the interconnections between metabolic derangements characteristic for T2DM, obesity, and NAFLD suggest that insulin resistance on the hepatic and systemic level and the release of pro-inflammatory cytokines, vasoactive factors, and pro-oxidant molecules are potentially implicated in the development and progression of HCC.With the intent to gain a better insight into this issue, we performed a meta-analysis to evaluate the effect of T2DM on poor outcomes after HCC treatment. To explore several different clinical settings, three outcomes of interest were investigated: death, progressive disease after locoregional therapies, and recurrence. Moreover, sub-analyses were performed according to the use of potentially curative (resection, transplantation, termo-ablation) or non-curative therapies.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Validation of low-cost models for minimal invasive surgery training of congenital diaphragmatic hernia and esophageal atresia

BackgroundMinimal invasive surgery (MIS) is increasingly used for the correction of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). It is important to master these complex procedures, preferably preclinically, to avoid complications. The aim of this study was to validate recently developed models to train these MIS procedures preclinically.MethodsTwo low cost, reproducible models (one for CDH and one for EA) were validated during several pediatric surgical conferences and training sessions (January 2017–December 2018), used in either the LaparoscopyBoxx or EoSim simulator. Participants used one or both models and completed a questionnaire regarding their opinion on realism (face validity) and didactic value (content validity), rated on a five-point-Likert scale.ResultsOf all 60 participants enrolled, 44 evaluated the EA model. All items were evaluated as significantly better than neutral, with means ranging from 3.7 to 4.1 (p < 0.001). The CDH model was evaluated by 48 participants. All items scored significantly better than neutral (means 3.5–3.9, p < 0.001), with exception of the haptics of the simulated diaphragm (mean 3.3, p = 0.054). Both models were considered a potent training tool (means 3.9).ConclusionThese readily available and low budget models are considered a valid and potent training tool by both experts and target group participants.Type of studyProspective study.Level of evidenceLevel II.     

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus (T1DM). Fear of hypoglycemia (FoH) is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity (e.g., cardiometabolic health, improved body composition, cardiovascular fitness, quality of life). Technological advances, improved insulin regimens, and a better understanding of the physiology of various types of exercise could help ameliorate FoH. This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.