Prenatal Features of MIRAGE Syndrome-Case Report and Review of the Literature.

MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor sterile alpha domain containing 9 (SAMD9) located on the arm of chromosome 7 (7q21.2). The syndrome is rare and is usually diagnosed in newborns and children with myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, hence the acronym MIRAGE. The aims of this paper are (1) to present fetal ultrasound features in a case where MIRAGE syndrome was diagnosed prenatally and (2) to review the existing literature records on prenatal manifestations of MIRAGE syndrome. In our case, the fetus had severe early fetal growth restriction (FGR) with normal Doppler studies, atypical genitalia, oligohydramnios, and hyperechogenic bowel at the routine mid-gestation anomaly scan. Amniocentesis excluded infections and numeric or structural chromosomal abnormalities while whole exome sequencing (WES) of the fetal genetic material identified the specific mutation. Targeted testing in parents was negative, suggesting the "de novo" mutation in the fetus. We could not identify other specific case reports in the literature on the prenatal diagnosis of MIRAGE syndrome. In cases reported in the literature where the diagnosis of MIRAGE syndrome was achieved postnatally, there are mentions related to the marked FGR on prenatal ultrasound. Severe early-onset FGR with no other apparent cause seems to be a central prenatal feature in these babies, and WES should be offered, especially if there are other structural abnormalities. Prenatal diagnosis of MIRAGE syndrome is possible, allowing for reproductive choices, improved counseling of parents, and better preparation of neonatal care.

Platelet-Rich Plasma in Dermatology: New Insights on the Cellular Mechanism of Skin Repair and Regeneration.

The skin's recognised functions may undergo physiological alterations due to ageing, manifesting as varying degrees of facial wrinkles, diminished tautness, density, and volume. Additionally, these functions can be disrupted (patho)physiologically through various physical and chemical injuries, including surgical trauma, accidents, or chronic conditions like ulcers associated with diabetes mellitus, venous insufficiency, or obesity. Advancements in therapeutic interventions that boost the skin's innate regenerative abilities could significantly enhance patient care protocols. The application of Platelet-Rich Plasma (PRP) is widely recognized for its aesthetic and functional benefits to the skin. Yet, the endorsement of PRP's advantages often borders on the dogmatic, with its efficacy commonly ascribed solely to the activation of fibroblasts by the factors contained within platelet granules. PRP therapy is a cornerstone of regenerative medicine which involves the autologous delivery of conditioned plasma enriched by platelets. This is achieved by centrifugation, removing erythrocytes while retaining platelets and their granules. Despite its widespread use, the precise sequences of cellular activation, the specific cellular players, and the molecular machinery that drive PRP-facilitated healing are still enigmatic. There is still a paucity of definitive and robust studies elucidating these mechanisms. In recent years, telocytes (TCs)-a unique dermal cell population-have shown promising potential for tissue regeneration in various organs, including the dermis. TCs' participation in neo-angiogenesis, akin to that attributed to PRP, and their role in tissue remodelling and repair processes within the interstitia of several organs (including the dermis), offer intriguing insights. Their potential to contribute to, or possibly orchestrate, the skin regeneration process following PRP treatment has elicited considerable interest. Therefore, pursuing a comprehensive understanding of the cellular and molecular mechanisms at work, particularly those involving TCs, their temporal involvement in structural recovery following injury, and the interconnected biological events in skin wound healing and regeneration represents a compelling field of study.

Diagnostic Value of Artificial Intelligence-Assisted Endoscopic Ultrasound for Pancreatic Cancer: A Systematic Review and Meta-Analysis.

We performed a meta-analysis of published data to investigate the diagnostic value of artificial intelligence for pancreatic cancer. Systematic research was conducted in the following databases: PubMed, Embase, and Web of Science to identify relevant studies up to October 2021. We extracted or calculated the number of true positives, false positives true negatives, and false negatives from the selected publications. In total, 10 studies, featuring 1871 patients, met our inclusion criteria. The risk of bias in the included studies was assessed using the QUADAS-2 tool. R and RevMan 5.4.1 software were used for calculations and statistical analysis. The studies included in the meta-analysis did not show an overall heterogeneity (I2 = 0%), and no significant differences were found from the subgroup analysis. The pooled diagnostic sensitivity and specificity were 0.92 (95% CI, 0.89-0.95) and 0.9 (95% CI, 0.83-0.94), respectively. The area under the summary receiver operating characteristics curve was 0.95, and the diagnostic odds ratio was 128.9 (95% CI, 71.2-233.8), indicating very good diagnostic accuracy for the detection of pancreatic cancer. Based on these promising preliminary results and further testing on a larger dataset, artificial intelligence-assisted endoscopic ultrasound could become an important tool for the computer-aided diagnosis of pancreatic cancer.

INSULIN AUTOIMMUNE SYNDROME IN A YOUNG CAUCASIAN WOMAN.

A young Caucasian woman presents several episodes of severe fasting hypoglycemia. Fasting lab tests revealed: glycemia 28 mg/dL, insulinemia 143.3 µU/mL, insulin antibodies above 100 U/mL, leading to the diagnosis of insulin autoimmune syndrome. Due to lack of clinical improvement after 2 months, prednisone was started at 0.5 mg/kg/day, and then tapered by 5 mg every 5 days. Three weeks after discontinuing corticotherapy, the patient had no more severe fasting hypoglycemia, but occasionally postprandial mild hypoglycemia. Fasting lab tests showed: glycemia 83 mg/dL, insulinemia 58.6 µU/mL. At 5 hours during oral glucose tolerance test glycemia was 33 mg/dL, insulinemia 152.9 µU/mL.

[2+2] Cycloadditions with an Iron Carbene: A Critical Step in Enyne Metathesis.

Ruthenium carbenes, famously used in olefin metathesis, have impacted numerous research areas, ranging from synthesis to materials and biology. Although in the same group as ruthenium, iron carbenes showing similar reaction patterns have not been reported. Such targets are of high interest because the use of a sustainable metal would lead to a decreased cost, toxicity, and environmental impact of the corresponding compounds. Herein, we report the synthesis of an iron carbene complex, [{PC(sp2)P}Fe(N2)(PMe3)] ([PC(sp2)P] = (bis[2-(di-isopropylphosphino)phenyl]methylene), which is capable of performing [2+2] cycloaddition reactions in the presence of alkynes. Specifically, η3-vinyl carbenes are formed stoichiometrically through a [2+2] cycloaddition between the alkyne and the metal carbene. Additional reactivity of the η3-vinyl carbenes with alkynes yields a second insertion product containing a new iron carbene moiety.

Polymeric Carriers Designed for Encapsulation of Essential Oils with Biological Activity.

The article reviews the possibilities of encapsulating essential oils EOs, due to their multiple benefits, controlled release, and in order to protect them from environmental conditions. Thus, we present the natural polymers and the synthetic macromolecular chains that are commonly used as networks for embedding EOs, owing to their biodegradability and biocompatibility, interdependent encapsulation methods, and potential applicability of bioactive blend structures. The possibilities of using artificial intelligence to evaluate the bioactivity of EOs-in direct correlation with their chemical constitutions and structures, in order to avoid complex laboratory analyses, to save money and time, and to enhance the final consistency of the products-are also presented.

Clonal Hematopoiesis and Liquid Biopsy in Gastrointestinal Cancers.

The use of blood liquid biopsy is increasingly being incorporated into the clinical setting of gastrointestinal cancers care. Clonal hematopoiesis (CH) occurs naturally as a result of the accumulation of somatic mutations and the clonal proliferation of hematopoietic stem cells with normal aging. The identification of CH-mutations has been described as a source of biological noise in blood liquid biopsy. Incorrect interpretation of CH events as cancer related can have a direct impact on cancer diagnosis and treatment. This review summarizes the current understanding of CH as a form of biological noise in blood liquid biopsy and the reported clinical significance of CH in patients with GI cancers.

Retinal Hemorrhages During Examination for Retinopathy of Prematurity: A Form of Ocular Decompression Retinopathy.

Purpose: Posterior segment hemorrhage occurring during or shortly after examination (PSHE) for retinopathy of prematurity (ROP) is a very rare complication. We present a case of and review the literature on PSHE during ROP examination to better characterize this complication. Methods: A case report is presented, followed by a review of similar cases in the literature. Results: An infant undergoing laser photocoagulation for ROP rapidly developed diffuse intraretinal hemorrhages in his right eye during the laser and after a Valsalva event while he was intubated under general anesthesia. The hemorrhages resolved within 1 week. This presentation was similar to those in previously reported cases. Conclusions: PSHE in ROP usually consists of multiple, diffuse, intraretinal hemorrhages that occur within minutes of ROP examination and resolve within a few weeks without any other ocular findings or sequelae. PSHE seems to represent a form of ocular decompression retinopathy.

Alterations of heart rate variability and turbulence in female patients with hyperthyroidism of various severities.

OBJECTIVE: The objective of the this study is to document the existence of statistically significant differences between parameters of heart rate variability (HRV) and heart rate turbulence (HRT), determined in women with overt hyperthyroidism (hT), compared to controls and to highlight their correlations with the level of thyroid hormones and the incidence of arrhythmias. METHODS: We studied the HRV in time and frequency domain, and the HRT in a group of 113 women with overt hT, without other cardiovascular risk factors or comorbidities, admitted to the endocrinology clinic of our hospital, between 2012 and 2016. Depending on the severity and duration of hT and levels of thyroid hormones, the patients were assigned to three groups: mild and moderate forms, severe hT with thyrotoxicosis and persistent cases with a relapse of hT. We performed 24 h Holter monitoring in all patients. RESULTS: HRV parameters in time domain (TD) were significantly depressed in patients comparing to controls. All patients had abnormal, positive values of turbulence onset (TO) with significant statistically differences (P < 0.0001) comparing to controls. Although positive, the values of turbulence slope (TS) decreased according to the severity of hT. CONCLUSION: Patients with hT had depressed values of HRV parameters in TD, correlated with the severity of the thyroid disease and with the incidence of arrhythmias. All patients presented pathological values of TO. TS values were positive, but lower compared to controls.

Oxidation reactions of a nucleophilic palladium carbene: mono and bi-radical carbenes.

Palladium(ii) cationic carbene radical and neutral bi-radical complexes were synthesized from a previously reported Pd(ii) carbene in the presence of one and two electron oxidants. When [{PC(sp2)P}tBuPd(PMe3)] (1, [PC(sp2)P]tBu = (bis[2-(di-iso-propylphosphino)-4-tertbutylphenyl]methylene)) was treated with [Cp2Fe][X] (X = BArF4, ArF = 3,5-(CF3)2C6H3, or PF6), the corresponding radical cationic complexes [{PC˙(sp2)P}tBuPd(PMe3)][X] (2: X = BArF4, 3: PF6) were isolated and characterized. Magnetic moment measurements and EPR spectroscopy indicated the presence of a ligand centered unpaired electron. In the presence of two electron oxidants such as 1,8-naphthylene disulfide or 9,10-anthracenedione, 1 converts to [{PC˙(sp2)P}tBuPdS(C10H6)SPd{PC˙(sp2)P}tBu] (4) or [{PC˙(sp2)P}tBuPdO(C14H10)OPd{PC˙(sp2)P}tBu] (5), respectively. Single crystal X-ray diffraction and EPR spectroscopy confirmed the bi-radical nature of 4 and 5.

Inflammatory-Driven Angiogenesis in Bone Augmentation with Bovine Hydroxyapatite, B-Tricalcium Phosphate, and Bioglasses: A Comparative Study.

INTRODUCTION: The clinical use of bioactive materials for bone augmentation has remained a challenge because of predictability and effectiveness concerns, as well as increased costs. The purpose of this study was to analyse the ability to integrate bone substitutes by evaluating the immunohistochemical expression of the platelet endothelial cell adhesion molecules, vascular endothelial growth factor, collagen IV, laminin, and osteonectin, in the vicinity of bone grafts, enabling tissue revascularization and appearance of bone lamellae. There is a lack of in vivo studies of inflammatory-driven angiogenesis in bone engineering using various grafts. METHODS: The study was performed in animal experimental model on the standardized monocortical defects in the tibia of 20 New Zealand rabbits. The defects were augmented with three types of bone substituents. The used bone substituents were beta-tricalcium phosphate, bovine hydroxyapatite, and bioactive glasses. After a period of 6 months, bone fragments were harvested for histopathologic examination. Endothelial cell analysis was done by analysing vascularization with PECAM/CD31 and VEGF and fibrosis with collagen IV, laminin, and osteonectin stains. Statistical analysis was realized by descriptive analysis which was completed with the kurtosis and skewness as well as the Kruskal-Wallis and Mann-Whitney statistical tests. RESULTS: The discoveries show that the amount of bone that is formed around beta-tricalcium phosphate and bovine hydroxyapatite is clearly superior to the bioactive glasses. Both the lumen diameter and the number of vessels were slightly increased in favor of beta-tricalcium phosphate. CONCLUSION: We can conclude that bone substitutes as bovine bone and beta-tricalcium phosphate have significant increased angiogenesis (and subsequent improved osteogenesis) compared to the bioactive glass. In our study, significant angiogenesis is linked with a greater tissue formation, indicating that in bone engineering with the allografts we used, inflammation has more benefic effects, the catabolic action being exceeded by the tissue formation.

NON-INVASIVE ASSESSMENT OF LIVER STEATOSIS AND FIBROSIS USING TRANSIENT ELASTOGRAPHY AND CONTROLLED ATTENUATION PARAMETER IN TYPE 2 DIABETES PATIENTS.

CONTEXT: Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. OBJECTIVE: To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. DESIGN: This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital "Pius Brinzeu" Timisoara. SUBJECTS AND METHODS: We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. RESULTS: The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). CONCLUSIONS: Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Formation of Palladium η2 -Bound Chalcogenoketones across a Pd+ -C- Bond.

A series of chalcogen analogues encompassing a ketone and chalcogenoketones [{PC(=E)P}Pd(PMe3 )] (E=O, S, Se, Te) was generated from a nucleophilic palladium carbene compound, [{PC(sp2 )P}Pd(PMe3 )] ([PC(sp3 )HP]=bis[2-(diisopropylphosphino)-phenyl]methyl, iPr2 P-C6 H4 -CH-C6 H4 -PiPr2 ). The thio-, seleno-, and telluroketone were all synthesized by means of an atom transfer from the respective chalcogens. The ketone analogue, however, required the use of nitrobenzene or nitrosobenzene as the oxygen-atom transfer agent.

NI(ii) phosphine and phosphide complexes supported by a PNP-pyrrole pincer ligand.

The reaction between [(PNpyrP)NiCl] (1, PNpyrP = 2,5-bis((di-iso-propylphosphino)-methyl)-1H-pyrrolide) and TlPF6 in the presence of a monodentate phosphine ligand led to cationic nickel phosphine and phosphite complexes, [(PNpyrP)Ni(PHPh2)][PF6] (2), [(PNpyrP)Ni(PMe3)][PF6] (3), and [(PNpyrP)Ni{P(OMe)3}][PF6] (4). Compound 2 can be deprotonated resulting in the generation of a terminal phosphido complex, [(PNpyrP)Ni(PPh2)] (5). When 3 is subjected to a base, a methyl proton of PMe3 is abstracted to afford [(PNpyrP)Ni(CH2PMe2)] (6), containing a methylene bridge between Ni and the external phosphine. Compounds 2-6 were characterized by single crystal X-ray diffraction in addition to multi-nuclear NMR spectroscopy and elemental analysis.

Iron pyrrole-based PNP pincer ligand complexes as catalyst precursors.

The structure of a pincer ligand consists of a backbone and two `arms' which typically contain a P or N atom. They are tridentate ligands that coordinate to a metal center in a meridional configuration. A series of three iron complexes containing the pyrrole-based PNP pincer ligand 2,5-bis[(diisopropylphosphanyl)methyl]pyrrolide (PNpyrP) has been synthesized. These complexes are possible precursors to new iron catalysts. {2,5-Bis[(diisopropylphosphanyl)methyl]pyrrolido-κ3P,N,P'}carbonylchlorido(trimethylphosphane-κP)iron(II), [Fe(C18H34NP2)Cl(C3H9P)(CO)] or [Fe(PNpyrP)Cl(PMe3)(CO)], (I), has a slightly distorted octahedral geometry, with the Cl and CO ligands occupying the apical positions. {2,5-Bis[(diisopropylphosphanyl)methyl]pyrrolido-κ3P,N,P'}chlorido(pyridine-κN)iron(II), [Fe(C18H34NP2)Cl(C5H5N)] or [Fe(PNpyrP)Cl(py)] (py is pyridine), (II), is a five-coordinate square-pyramidal complex, with the pyridine ligand in the apical position. {2,5-Bis[(diisopropylphosphanyl)methyl]pyrrolido-κ3P,N,P'}dicarbonylchloridoiron(II), [Fe(C18H34NP2)Cl(CO)2] or [Fe(PNpyrP)Cl(CO)2], (III), is structurally similar to (I), but with the PMe3 ligand replaced by a second carbonyl ligand from the reaction of (II) with CO. The two carbonyl ligands are in a cis configuration, and there is positional disorder of the chloride and trans carbonyl ligands.

Potential risks of using cement-augmented screws for spinal fusion in patients with low bone quality.

BACKGROUND CONTEXT: Dramatic increases in the average life expectancy have led to increases in the variety of degenerative changes and deformities observed in the aging spine. The elderly population can present challenges for spine surgeons, not only because of increased comorbidities, but also because of the quality of their bones. Pedicle screws are the implants used most commonly in spinal surgery for fixation, but their efficacy depends directly on bone quality. Although polymethyl methacrylate (PMMA)-augmented screws represent an alternative for patients with osteoporotic vertebrae, their use has raised some concerns because of the possible association between cement leakages (CLs) and other morbidities. PURPOSE: To analyze potential complications related to the use of cement-augmented screws for spinal fusion and to investigate the effectiveness of using these screws in the treatment of patients with low bone quality. STUDY DESIGN: A retrospective single-center study. PATIENT SAMPLE: This study included 313 consecutive patients who underwent spinal fusion using a total of 1,780 cement-augmented screws. METHODS AND OUTCOME MEASURES: We analyzed potential complications related to the use of cement-augmented screws, including CL, vascular injury, infection, screw extraction problems, revision surgery, and instrument failure. There are no financial conflicts of interest to report. RESULTS: A total of 1,043 vertebrae were instrumented. Cement leakage was observed in 650 vertebrae (62.3%). There were no major clinical complications related to CL, but two patients (0.6%) had radicular pain related to CL at the S1 foramina. Of the 13 patients (4.1%) who developed deep infections requiring surgical debridement, two with chronic infections had possible spondylitis that required instrument removal. All patients responded well to antibiotic therapy. Revision surgery was performed in 56 patients (17.9%), most of whom had long construction. A total of 180 screws were removed as a result of revision. There were no problems with screw extraction. CONCLUSIONS: These results demonstrate the efficacy and safety of cement-augmented screws for the treatment of patients with low bone mineral density.

Budd-chiari syndrome causing acute liver failure: A multicenter case series.

Budd-Chiari syndrome (BCS) is a rare disease resulting from obstruction of the hepatic venous outflow tract that typically presents with abdominal pain, jaundice, and ascites without frank liver failure. However, BCS may also evolve more rapidly to acute liver failure (ALF). In this study, we describe the clinical features, treatment, and outcomes of ALF due to BCS and compare our results with those in the published literature. Twenty of the 2344 patients enrolled in the Acute Liver Failure Study Group (ALFSG) registry since 1998 presented with a clinical diagnosis of BCS. An additional 19 patients of ALF-BCS in the English language literature were reviewed and compared with the ALFSG cases. Most ALF-BCS patients were white (84%) and female (84%) in their fourth decade. A hypercoagulable state was noted in 63% of patients. BCS was diagnosed by Doppler ultrasonography or abdominal computed tomography in all patients. Liver biopsies (n = 6) all had evidence of severe pericentral necrosis. Treatments used included most commonly anticoagulation (71%), but also transjugular intrahepatic portosystemic shunt (TIPS; 37%) and orthotopic liver transplantation (37%). In-hospital mortality was approximately 60%. In conclusion, BCS is a rare cause of ALF and mandates prompt diagnosis and management for successful outcomes. Once the diagnosis is confirmed, prompt anticoagulation is recommended in conjunction with evaluation for malignancy or thrombophilic disorder. Mortality may have improved in recent years with use of TIPS and/or orthotopic liver transplantation compared with prior published reports. Liver Transplantation 23 135-142 2017 AASLD.

Poor outcomes despite aspirin or statin use in high-risk patients with retinal vein occlusion.

PURPOSE: Since atherosclerosis contributes to the pathophysiology of retinal vein occlusion (RVO), we aimed to assess the effects of aspirin and statins on the visual outcomes of RVO in high-risk patients, whom we define to have hypertension and open-angle glaucoma prior to RVO. METHODS: We conducted a retrospective case-control study of adults diagnosed with RVO between 2006 and 2014. To evaluate for a preventive effect of these medications, we compared the prevalence of aspirin or statin use (either separately or concomitantly) among high-risk patients who developed RVO and among those who did not during at least 2 years of follow-up. To evaluate for a therapeutic effect, we then compared the final follow-up visual acuity (VA) of high-risk RVO patients who had and who had not been taking a statin prior to the RVO. RESULTS: We analyzed 43 eyes [23 central RVOs (CRVOs), 16 branch RVOs (BRVOs), and 4 hemi-RVOs (HRVOs)] from 42 high-risk patients, along with 129 high-risk controls. There was no significant difference (p = 0.47) in aspirin exposure between the control (60%) and RVO (67%) groups, and the increased statin exposure among controls (72% vs. 53% for the cases; p = 0.03) paralleled their higher prevalence of hyperlipidemia. The non-statin and statin RVO groups each had a mean VA of 20/800 at a mean 30 and 43 months of follow-up, respectively. CONCLUSIONS: No preventive benefit of aspirin or statins, and no therapeutic benefit of statins, was found for RVO in high-risk patients. High-risk RVO patients suffer substantially worse outcomes than those reported in other studies not limited to such patients.