Multiple malignancies in a child with de novo TP53 mutation

The authors present the case of an 8.5-year-old boy diagnosed with embryonal rhabdomyosarcoma of the infratemporal fossa at 21 months old. Five years later he developed an osteosarcoma of the tibia, for which he was treated with standard chemotherapy and resection. Soon after completing this treatment, ptosis of the right eye developed. A mass in the cavernous sinus was found, interpreted as an osteogenic metastatsis, although a third primary tumor could not be ruled out. Molecular genetic investigation revealed a de novo germline TP53 mutation, and heralded an aggressive clinical progression of multiple malignancies in a child.     

The high risk of obstructive sleep apnea--an independent risk factor of erectile dysfunction in ST-segment elevation myocardial infarction patients

IntroductionSleep-related breathing disorders are highly prevalent in patients with established cardiovascular disease. Obstructive sleep apnea (OSA) is associated with several cardiovascular conditions such as hypertension, ischemic heart disease, arrhythmias, and erectile dysfunction (ED).AimThe aim of this prospective study was to investigate the prevalence of ED in ST-segment elevation myocardial infarction (STEMI) patients at high risk of OSA, and to evaluate the leading factors that increase the risk of ED.MethodsWe prospectively studied 90 consecutive male STEMI patients.Main Outcome MeasuresA risk of OSA was assessed using the Berlin questionnaire (BQ) and Epworth Sleepiness Scale (ESS). Erectile function was assessed using the International Index of Erectile Function (IIEF).ResultsThirty-two (35.6%) patients were at high risk of OSA. Patients were at high risk of OSA who on admission had significantly higher mean ESS score, and abnormal BQ, higher incidence of hypertension, and higher body mass index. They were also found to have significantly higher mean C-reactive protein level and higher incidence of ED. The mean IIEF score was significantly lower in patients at high risk of OSA (16.2 ± 5.4 vs. 20.5 ± 6.4; P = 0.004). In the multiple logistic regression analysis, high risk of OSA was strong and an independent risk factor of ED in STEMI patients (odds ratio 55.71, 95% confidence interval 3.36–923.81; P = 0.005).ConclusionED was highly prevalent in STEMI patients at high risk of OSA. High risk of OSA was strong, independent risk factor for developing ED. Szymanski FM, Filipiak KJ, Hrynkiewicz-Szymanska A, Grabowski M, Dabrowska-Kugacka A, and Opolski G. The high risk of obstructive sleep apnea—An independent risk factor of erectile dysfunction in ST-segment elevation myocardial infarction patients.     

Novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type‐2 diabetes mellitus: In vitro studies against yeast α‐ and β‐glucosidase and in silico molecular modeling

A range of novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds ( 4a–i ) were synthesized in good to excellent yields (63–92%). The enzyme inhibitory potentials of these compounds were investigated against α‐ and β‐glucosidases because these enzymes play a crucial role in treating type‐2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC₅₀ 38.22 ± 0.12 μM), compounds 4i (IC₅₀ 25.49 ± 0.67 μM), 4f (IC₅₀ 28.91 ± 0.43 μM), 4h (IC₅₀ 30.66 ± 0.52 μM), and 4e (IC₅₀ 35.01 ± 0.45 μM) delivered better inhibition against α‐glucosidase and were quite inactive/completely inactive against β‐glucosidase. The structure–activity relationship of these compounds was developed and elaborated with the help of molecular docking studies.     

Acid Ceramidase Upregulation in Prostate Cancer Cells Confers Resistance to Radiation: AC Inhibition, a Potential Radiosensitizer

Radiation resistance in a subset of prostate tumors remains a challenge to prostate cancer radiotherapy. The current study on the effects of radiation on prostate cancer cells reveals that radiation programs an unpredicted resistance mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated limited changes of ceramide levels while elevating levels of sphingosine and sphingosine-1-phosphate. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Conversely, AC overexpression further decreased sensitivity to radiation. We also observed that radiation-induced AC upregulation was sufficient to create cross-resistance to chemotherapy as demonstrated by decreased sensitivity to Taxol and C₆ ceramide compared to controls. Lower levels of caspase 3/7 activity were detected in cells pretreated with radiation, also indicating increased resistance. Finally, utilization of the small molecule AC inhibitor, LCL385, sensitized PPC-1 cells to radiation and significantly decreased tumor xenograft growth. These data suggest a new mechanism of cancer cell resistance to radiation, through upregulation of AC that is, in part, mediated by application of the therapy itself. An improved understanding of radiotherapy and the application of combination therapy achieved in this study offer new opportunities for the modulation of radiation effects in the treatment of cancer.     

Dietary intake of heterocyclic amines and cancers of the esophagus and gastric cardia.

The results of two epidemiological studies suggest that high intake of heterocyclic amines, which are formed on the surface of meats cooked at high temperatures, might be associated with increased risk of esophageal or cardia cancers. Our aim was to further investigate heterocyclic amine intake and risk of these cancers. We examined data from a nationwide, population-based, case-control study of risk factors for adenocarcinoma of the esophagus and gastric cardia and squamous cell carcinoma of the esophagus in Sweden, with 185, 258, and 165 cases, respectively, and 815 controls. Heterocyclic amine intake was estimated based on the frequency of consumption and degree of surface browning of commonly fried meats, and the consumption of pan juices. Statistically nonsignificant 50-70% higher risks of esophageal squamous cell carcinoma were observed among individuals in the highest quartile levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, and 2-amino-1methyl-6-phenylimidazo[4,5-b]pyridine relative to those in the lowest. Dose-risk trends were evident. Subjects reporting high intake of all three heterocyclic amines had an odds ratio of 2.4 (95% confidence interval, 1.2-4.8) relative to those with low intake of all three substances. In contrast, no association was found with risk of adenocarcinoma of the esophagus or gastric cardia. Heterocyclic amine intake might be associated with an increase in risk of squamous cell carcinoma of the esophagus. Given the dearth of epidemiological data regarding these cancers and the lack of established biological mechanisms, confirmatory data are needed.     

Automated static perimetry in myopes with peripapillary crescents--Part II

Central visual fields were investigated by automated static perimetry, using programs 30-2 and 30-1 of the Humphrey Field Analyzer (HFA), in a group of healthy myopic individuals with peripapillary crescents and tigroid fundus changes only. Results were compared with 'non-myopic' and 'myopic subjects without crescents' control groups. The sample comprised 122 young, healthy volunteers between the ages of 18.5 and 35.4 years, free from any ocular or systemic disease, with refractive errors ranging from +4.00 to −25.75 D. Linear regression results are presented and may be useful in predicting the global indices mean deviation (MD) and mean sensitivity (MS), given either the axial length of ocular refraction, for medium and high myopes. Analysis of the HFA printouts revealed significantly depressed locations in all subject groups. However, locations identified at the 2, 1 and 0.5% probability levels were observed more frequently and more commonly in the myopes with peripapillary crescents than in the control groups. In this non-glaucomatous sample, four myopes had a borderline glaucoma hemifield test and two fell outside normal limits of this test. The superior hemifield, particularly the upper temporal quadrant, appeared to be most affected. Enlargement of the blind spot occurred in some subjects. Several possible explanations are suggested for the visual field sensitivity reduction in myopia.     

Post-Contrast Acute Kidney Injury in Patients with Various Stages of Chronic Kidney Disease—Is Fear Justified?

Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We analyzed all computed tomographies performed in our clinic in 2019, including data about the patient and the procedure. In each case, we recorded the parameters of kidney function (serum creatinine concentration and eGFR) in four time intervals: before the test, immediately after the test, 14–28 days after the test, and over 28 days after the test. Patients who did not have a follow-up after computed tomography were excluded. After reviewing 706 CT scans performed in 2019, we included 284 patients undergoing contrast-enhanced CT and 67 non-enhanced CT in the final analysis. On this basis, we created two comparable groups in terms of age, gender, the severity of chronic kidney disease, and the number of comorbidities. We found that AKI was more common in the non-enhanced CT population (25.4% vs. 17.9%). In terms of our experience, it seems that PC-AKI is not a great risk for patients, even those with chronic kidney disease. Consequently, the fear of using contrast agents is not justified.