LC-MS/MS analysis of 2-aminothiazoline-4-carboxylic acid as a forensic biomarker for cyanide poisoning

AIM: To demonstrate the potential of using 2-aminothiazoline-4-carboxylic acid(ATCA) as a novel biomarker/forensic biomarker for cyanide poisoning. METHODS: A sensitive method was developed and employed for the identification and quantification of ATCA in biological samples, where the sample extraction and clean up were achieved by solid phase extraction(SPE). After optimization of SPE procedures, ATCA was analyzed by high performance liquid chromatographytandem mass spectrometry. ATCA levels following the administration of different doses of potassium cyanide(KCN) to mice were measured and compared to endogenous ATCA levels in order to study the significance of using ATCA as a biomarker for cyanide poisoning.RESULTS: A custom made analytical method was established for a new(mice) model when animals were exposed to increasing KCN doses. The application of this method provided important new information on ATCA as a potential cyanide biomarker. ATCA concentration in mice plasma samples were increased from 189 ± 28 ng/mL(n = 3) to 413 ± 66 ng/mL(n = 3) following a 10 mg/kg body weight dose of KCN introduced subcutaneously. The sensitivity of this analytical method proved to be a tool for measuring endogenous level of ATCA in mice organs as follows: 1.2 ± 0.1 μg/g for kidney samples, 1.6 ± 0.1 μg/g for brain samples, 1.8 ± 0.2 μg/g for lung samples, 2.9 ± 0.1 μg/g for heart samples, and 3.6 ± 0.9 μg/g for liver samples. CONCLUSION: This finding suggests that ATCA has the potential to serve as a plasma biomarker / forensic biomarker for cyanide poisoning.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA were based on the following parameters:branching,vessel caliber and area of adjacent capillary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44%)remained unchanged,six IRMAs(13%)progressed with enlargement or development of new IRMAs and five IRMAs(11%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMA(63%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The difference in rank order between the two groups was statistically significant(p=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stabilit,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.

Morphological changes in intraretinal microvascular abnormalities after anti-VEGF therapy visualized on optical coherence tomography angiography

Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naive diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA was based on the following parameters:branching,vessel aliber and area of adjacent capllary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31.1%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44.4%)remained unchanged,6 IRMAs(13.3%)progressed with enlargement or development of new IRMAs and 5 IRMAs(11.1%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMAs(63.0%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The dfference in rank order between the two groups was statistically significant(P=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stability,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as wellas the response to anti-VEGF treatment.

Do more mature preterm babies with surgical necrotizing enterocolitis predominantly develop the colonic disease?

Background The primary aim was to scrutinize our hypothesis:“Do more mature preterm(MMP)babies with surgical necrotizing enterocolitis(NEC)predominantly develop the colonic disease and are different in their response and behaviour in comparison to exceedingly preterm(EP)babies?”Secondary outcomes were to define time taken in developing NEC,time from diagnosis to laparotomy,requirement of parenteral nutrition(PN),and ventilatory support.Methods We defined MMP babies as≥30 weeks of gestation and EP babies as≤29 weeks+6 days of gestation.Inclusion criteria were all babies<37 weeks with NEC requiring surgery(called surgical NEC group).Data were collected retrospectively and analyzed using QuickCalcs.Results Of the total,41%(97/234)of babies underwent laparotomy between 2010 and 2019.Totally,81%were EP and 19%were MMP babies.Pure colonic involvement was seen in 9%of EP babies in comparison to 56%in the MMP babies(p=0.0001).Involvement of only the small bowel was seen in two-thirds of EP babies in comparison to only one-third in MMP babies(p=0.01).EP cohort required PN for 82 days(median)in comparison to 17 days(median)in the MMP cohort(p=0.001).Ventilation requirement in the EP group versus the MMP group was 24 vs 9 days(median),respectively(p=0.0006).Conclusions MMP babies predominantly developed colonic disease,whereas EP babies predominantly developed small bowel disease.EP babies required a longer duration of PN and ventilation support.This study opens a new area of research to differentiate pathogenesis and maturation patterns of the small and large bowels in babies with NEC.