Analysis of IGF and IGFBP as Prognostic Serum Biomarkers for Adrenocortical Carcinoma

Background

Adrenocortical carcinoma (ACC) lacks diagnostic and prognostic biomarkers to guide treatment. A consistently dysregulated pathway in ACC is the IGF signaling pathway, specifically overexpression of IGF2, IGF-I-receptor, and IGFBP2. The objective of this study was to perform a comprehensive analysis of serum IGF and IGFBP levels and to determine their utility as diagnostic and prognostic biomarkers in ACC.

Methods

Preoperative serum samples from 53 patients who underwent surgery for adrenocortical adenomas, 3 patients who underwent initial surgery for ACC, 16 patients who underwent reoperative surgery for ACC, and 5 healthy volunteer controls were analyzed. The serum concentration of IGF1, IGF2, IGFBP1, IGFBP2, and IGFBP3 was determined by enzyme-linked immunosorbent assay.

Results

No difference in the levels of IGF2 (p = .231) and IGFBP2 (p = .511) was observed between patients with ACC, benign adrenocortical tumors, and healthy volunteers. IGF1, IGFBP1, and IGFBP3 levels were not detected. High IGFBP2 levels were associated with better overall survival (OS) (p = .001) and showed a trend toward better abdominal progression-free (APFS) survival (p = .070) in patients with ACC. A subanalysis of patients undergoing reoperation for recurrent ACC showed better OS with high levels of IGFBP2 (p = .003) and a trend toward better APFS (p = .107). There was no significant difference in IGF2 and IGFBP2 levels by extent of disease.

Conclusions

IGF2 and IGFBP2 are not elevated in the serum of patients with ACC compared with patients with benign neoplasms and healthy volunteers. Elevated serum IGFBP2 is associated with better survival in patients with ACC and those undergoing reoperative surgery for recurrent ACC.     

Cryopyrin‐associated periodic fever syndrome in children: A case‐based review

Cryopyrin‐associated periodic fever syndrome (CAPS) represents an increasingly recognized disease group entity, with varied presentations. CAPS includes 3 clinical entities, namely, familial cold‐induced autoinflammatory syndrome (FCAS; MIM #120100), Muckle‐Wells syndrome (MWS; MIM #191900) and chronic inflammatory neurologic cutaneous and articular syndrome (CINCA; MIM #607115); which share several overlapping clinical features. These patients often present with early‐onset episodes of fever and rash, and variable systemic signs and symptoms, making it a great mimicker of other systemic autoimmune diseases. The episodes are transient and related to exposure to cold temperature and worsen in the winter season. We hereby present a case presenting with recurrent seasonal fever and rash, diagnosed as FCAS/ MWS overlap based on clinical signs and symptoms and positive testing for NLRP3 gene mutation. We also discuss the clinical presentation and complications of CAPS, chiefly FCAS and MWS, along with the previously described pediatric cases of CAPS. We tried to review the complexities of management of such patients, including the genetic diagnosis and the role of biological therapy. Based on the review of the literature, given the evident broad spectrum of symptoms and signs, use of next‐generation sequencing can help in prompt diagnosis and early initiation of biological agents, which may play a great role in reducing the complications that these patients may experience in the long run.     

Graphene tailored by Fe3O4 nanoparticles: low-adhesive and durable superhydrophobic coatings

This study reports stable superhydrophobic Fe₃O₄/graphene hybrid coatings prepared by spin coating of the Fe₃O₄/graphene/PDMS mixed solution on titanium substrates. By tailoring graphene sheets with Fe₃O₄ nanoparticles, the superhydrophobicity of graphene platelets was largely enhanced with a water contact angle of 164° and sliding angle <2°. Fe₃O₄ nanoparticles interact with FLG sheets via Fe–O–C covalent link, to form a graphene micro-sheet pinned strongly by nano-sized Fe₃O₄. The newly-formed micro/nano-structured sheets interact with each other via strong dipole–dipole attractions among Fe₃O₄ nanoparticles, confirmed by the blue shifts of G band observed in Raman spectra. The strongly interactive micro/nano-structured sheets are responsible for the improvement of both the surface hydrophobicity and the durability towards water impacting. The obtained hybrid coatings possess excellent durability in various environments, such as acidic and basic aqueous solutions, simulating ocean water. And also the coatings can retain their stable superhydrophobicity in Cassie–Baxter state even after annealing at 250 °C or refrigerating at −39 °C for 10 h. We employed an AFM to probe nanoscale adhesion forces to examine further the ability of the as-prepared coatings to resist the initial formation of water layers which reflects the ability to prevent the water spreading. The most superhydrophobic and durable hybrid coating with 1.8 g Fe₃O₄, shows the smallest adhesion force, as expected, indicating this surface possesses the weakest initial water adhesive strength. The resulting low-adhesive superhydrophobic coating shows a good self-cleaning ability. This fabrication of low-adhesive and durable superhydrophobic Fe₃O₄/FLG hybrid coatings advances a better understanding of the physics of wetting and yield a prospective candidate for various practical applications, such as self-cleaning, microfluidic devices, etc.

Strongly interactive graphene micro-sheets tailored by Fe₃O₄ nanoparticles exhibit low-adhesive and durable superhydrophobicity.     

Acquired (post-angioplasty) coronary ventricular fistula draining into left ventricle aneurysm

Coronary artery fistula is a rare condition where a fistulous communication exists between the coronary artery and a cardiac chamber or vein. Mostly they are of congenital origin, but rarely may be acquired due to trauma, post cardiac surgery or angioplasty, or very rarely, because of coronary aneurysm rupture. Ours is an interesting case of a post-coronary artery bypass graft surgery status with a fistula in second obtuse marginal branch of left circumflex coronary artery draining into left ventricle aneurysm. We explore possible causes including erosion of the thin aneurysmal wall into coronary lumen. Given the history of previous surgical revascularization, it may be a contained rupture and the possibility of pulsatile effect of the obtuse marginal branch eroding into the thin wall aneurysm is considered.     

Third molar maturity index (I3M) assessment according to different geographical zones: a large multi-ethnic study sample

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I_3M) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I_3ML and I_3MR) and the combination of both sides (I_3ML_I_3MR) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I_3ML; I_3MR; I_3ML_I_3MR, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I_3ML for male African people (91%) and the higher specificity (Sp) of all the parameters (I_3ML; I_3MR; I_3ML_I_3MR) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice.

     

Surgical Management of Cystic Duct Stump Stone or Gall Bladder Remnant Stone

Retained calculi in the cystic duct or gall bladder remnant can present as a post-cholecystectomy problem. Increased suspicion is necessary to diagnose this condition in a symptomatic post-cholecystectomy patient. Ultrasonography usually detects this condition, but magnetic resonance cholangiopancreatography is the test of choice for diagnosis as well as for surgical planning. Laparoscopic re-excision of the stump in most cases is feasible and safe. It is increasingly becoming the treatment of choice.     

Ferulic Acid: therapeutic potential through its antioxidant property

There has been considerable public and scientific interest in the use of phytochemicals derived from dietary components to combat human diseases. They are naturally occurring substances found in plants. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants. It exhibits a wide range of therapeutic effects against various diseases like cancer, diabetes, cardiovascular and neurodegenerative. A wide spectrum of beneficial activity for human health has been advocated for this phenolic compound, at least in part, because of its strong antioxidant activity. FA, a phenolic compound is a strong membrane antioxidant and known to positively affect human health. FA is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation. It effectively scavenges superoxide anion radical and inhibits the lipid peroxidation. It possesses antioxidant property by virtue of its phenolic hydroxyl group in its structure. The hydroxy and phenoxy groups of FA donate electrons to quench the free radicals. The phenolic radical in turn forms a quinone methide intermediate, which is excreted via the bile. The past few decades have been devoted to intense research on antioxidant property of FA. So, the present review deals with the mechanism of antioxidant property of FA and its possible role in therapeutic usage against various diseases.     

Kinetic analysis of FDG in rat liver: Effect of dietary intervention on arterial and portal vein input

IntroductionDietary conditions may affect liver [¹⁸F]FDG kinetics due to arterial and portal vein (PV) input. The purpose of this study was to evaluate kinetic models of [¹⁸F]FDG metabolism under a wide range of dietary interventions taking into account variations in arterial (HA) and portal vein (PV) input.MethodsThe study consisted of three groups of rats maintained under different diet interventions: 12 h fasted, 24 h fasted and those fed with high fructose diet. [¹⁵O]H₂O PET imaging was used to characterize liver flow contribution from HA and PV to the liver's dual input function (DIF). [¹⁸F]FDG PET imaging was used to characterize liver metabolism. Differences in [¹⁸F]FDG kinetics in HA, PV and liver under different diet interventions were investigated. An arterial to PV Transfer Function (TF) was optimized in all three dietary states to noninvasively estimate PV activity. Finally, two compartment 3-parameter (2C3P), two compartment 4-parameter (2C4P), two compartment 5-parameter (2C5P), and three compartment 5-parameter (3C5P) models were evaluated and compared to describe the kinetics of [¹⁸F]FDG in the liver across diet interventions. Sensitivity of the compartmental models to ratios of HA to PV flow fractions was further investigated.ResultsDifferences were found in HA and PV [¹⁸F]FDG kinetics across 12 h fasted, 24 h fasted and high fructose fed diet interventions. A two exponential TF model was able to estimate portal activity in all the three diet interventions. Statistical analysis suggests that a 2C3P model configuration was adequate to describe the kinetics of [¹⁸F]FDG in the liver under wide ranging dietary interventions. The net influx of [¹⁸F]FDG was lowest in the 12 h fasted group, followed by 24 h fasted group, and high fructose diet.ConclusionsA TF was optimized to non-invasively estimate PV time activity curve in different dietary states. Several kinetic models were assessed and a 2C3P model was sufficient to describe [¹⁸F]FDG liver kinetics despite differences in HA and PV kinetics across wide ranging dietary interventions. The observations have broader implications for the quantification of liver metabolism in metabolic disorders and cancer, among others.