Diffusion tensor magnetic resonance imaging in the gradingof liver fibrosis associated with congenital ductal plate malformations

Purpose: Liver biopsy is still the standard method for the diagnosis of ductal plate malformations (DPM). However, it is an invasive tool. Magnetic resonance imaging (MRI) has shown its accuracy in the diagnosis of this pathology. Herein, a study was conducted to elucidate the role of diffusion MRI parameters in predicting the degree of hepatic fibrosis. Material and methods: This prospective study included 29 patients with DPM and 20 healthy controls. Both groups underwent diffusion tensor magnetic resonance imaging (DT-MRI), and its parameters were compared between patients and controls, and then they were correlated with the degree of liver fibrosis in the patient group. Results: All patients with DPM, whatever its type, expressed a significantly lower hepatic apparent diffusion coefficient (ADC) compared to controls. However, fractional anisotropy (FA) showed no significant difference between them. The ADC value of 1.65 × 10-3 mm2/s had sensitivity and specificity of 82.1% and 90%, respectively, in differentiating DPM patients from healthy controls. It was evident that patients with higher fibrosis grades had significantly lower hepatic ADC, indicating a negative correlation between ADC and the grade of hepatic fibrosis; rs = -0.901, p < 0.001. Conclusions: DT-MRI showed good efficacy in the diagnosis of congenital DPM. Moreover, ADC could be applied to monitor the degree of liver fibrosis rather than the invasive liver biopsy. No significant correlation was noted between the FA and the grades of liver fibrosis

PEGylated liposomes : immunological responses

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Sister Mary Joseph's nodule: A case of umbilical cutaneous metastasis with signet ring cell histology

The metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph′s nodule". It is a rare clinical sign indicating advanced, metastasizing intraabdominal cancer. We report a 50-year-old man who developed metastatic skin cancer in the form of semicircular indurated plaque on top of which was a firm mobile rounded nodule at the umbilical area. Histopathological examination demonstrated diastase-resistant periodic acid-Schiff and mucicarmine positive signet ring cells, suggesting gastric carcinoma. Immunohistochemical staining showed that these cells were positive for cytokeratins and epithelial membrane antigen, suggesting epithelial origin

A novel fibrillin-1 mutation in an Egyptian Marfan family : a proband showing nephrotic syndrome due to focal segmental glomerulosclerosis

Marfan syndrome (MFS), the founding member of connective tissue disorder, is an autosomal dominant disease; it is caused by a deficiency of the microfibrillar protein fibrillin-1 (FBN1) and characterized by involvement of three main systems; skeletal, ocular, and cardiovascular. More than one thousand mutations in FBN1 gene on chromosome 15 were found to cause MFS. Nephrotic syndrome (NS) had been described in very few patients with MFS being attributed to membranoproliferative glomerulonephritis secondary to infective endocarditis. Focal segmental glomerulosclerosis (FSGS) had been reported in NS in conjunction with MFS without confirming the diagnosis by mutational analysis of FBN1. We hereby present an Egyptian family with MFS documented at the molecular level; it showed a male proband with NS secondary to FSGS, unfortunately, we failed to make any causal link between FBN dysfunction and FSGS. In this context, we review the spectrum of renal involvements occurring in MFS patients

Schimke immune-osseous dysplasia: A case report

Schimke immune-osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondylo-epiphyseal dysplasia (SED), progressive renal insufficiency beginning as steroid-resistant nephrotic syndrome (SRNS) and defective cellular immunity. This article reports a case from Egypt with a mild form of SIOD. A 14.5-year-old male patient presented with disproportionate short stature, SRNS (focal and segmental glomerulosclerosis), laboratory evidence of cellular immune deficiency and radiologic characteristics of SED. He died at the age of 16.5 years with bone marrow failure and severe pneumonia. To the best of our knowledge, this is the first case of SIOD to be reported from Egypt

Synthesis and Characterization of New Dihydronaphthalene Candidates as Potent Cytotoxic Agents against MCF-7 Human Cancer Cells

In the present work, a new series of dihydronaphthalene derivatives were synthesized starting with 6-methoxy-1-tetralone 1, and the corresponding hydrazine derivative 2. Reaction of compound 2 with aryl isothiocyanates produced thiosemicarbazides 3a-d, which were reacted with ethyl chloroacetate to give thiazolidinone derivatives 4a-d. Pyrano thiazolecarbonitrile derivatives 5a-f were prepared by heating a mixture of compounds 4a or 4c, aryl aldehydes, and malononitrile utilizing distilled water in the presence of catalytic amount of potassium hydrogen phthalate. Also, treatment of 4a with DMF-DMA under solvent-free conditions gave enaminone derivative 6, which condensed with ethyl acetoacetate or acetylacetone or malononitrile or cyanothioacetamide to give compounds 7-10, respectively. Finally, reaction of the enaminone 6 with 2-aminoimidazol or 2-aminothiazol in the presence of glacial acetic acid produced derivatives 11 and 12, respectively. Cytotoxic evaluation of eleven compounds, against MCF-7 (human breast adenocarcinoma) cell lines, was estimated. Results revealed that five of the examined compounds 5a, 5d, 5e, 10, and 3d showed potent cytotoxic activities recording, IC50 values; 0.93±0.02, 1.76±0.04, 2.36±0.06, 2.83±0.07, and 3.73±0.09 μM, respectively, which were more potent than the reference used (Saturosporin, IC506.08±0.15 μM). The new products were also examined towards normal epithelial breast cells (MCF10A). All of them showed very good safety profile with different degrees and were safer than the reference drug used. Compound 5a was the most effective against MCF-7 cells and was less toxic than Saturosporin by about 18.45-folds towards MCF01A normal cells. All the new compounds were fully characterized by the different spectral and analytical tools. Herein, detailed syntheses, spectroscopic, and biological data are reported