Coeliac trunk and its anatomic variations : a cadaveric study

Background: Coeliac trunk (CT) is the first major visceral branch of the abdominal aorta. The aim of this work was to present the CT division pattern and its anatomical variants in a sample of Polish population. Materials and methods: Coeliac trunk dissection was performed in 50 adult cadavers in the Department of Anatomy, Jagiellonian University Medical College. Cadavers of Polish subjects were included. Cadavers with previous upper abdominal surgery, abdominal trauma, disease process that distorted arterial anatomy or signs of putrefaction were excluded. CT variations, accessory vessels, and vertebral level of origin were described. CT patterns were reported according to the Adachi classification. This study was reviewed and approved by the local Ethics Committee. Results: Coeliac trunk consisting of the left gastric, common hepatic and splenic artery (type 1 according to the Adachi classification) was found in 82% of cadavers. The true tripod was found in 20% and the false one in 80%. Additional vessels were also found: greater pancreatic from the splenic artery and left inferior phrenic from the left gastric artery, which accounted for 2% sections. Type 2 according to the Adachi classification (i.e. the hepatosplenic trunk) was found in 16% of the sections. Other types of CT were not observed. The level of origin was found to be at the inter-vertebral disc between T12 and L1 in all of the cases. Conclusions: Based on the analysis of the sectional material of the Department of Anatomy, it was found that the typical visceral segmental division is approximate to that observed by Adachi in its classification, whereas the second type of CT was twice as frequent and no other, less frequent types were found

Postępowanie w chorobie Cushinga — od testu diagnostycznego do leczenia

Choroba Cushinga jest spowodowana przez gruczolaka przysadki, produkującego hormon adrenokortykotropowy (ACTH) i jest najczęstszą przyczyną endogennego hiperkortyzolizmu. W przypadku podejrzenia zespołu Cushinga zalecane testy przesiewowe to test hamowania 1 mg deksametazonu, test hamowania małymi dawkami deksametazonu albo badanie nocnego kortyzolu w ślinie. Jeżeli wynik testu przesiewowego jest 2-krotnie dodatni, pacjent powinien być skierowany do specjalisty–endokrynologa, a stwierdzenie w warunkach szpitalnych podwyższonego stężenia kortyzol w surowicy o północy i brak hamowania kortyzolu małymi dawkami deksametazonu potwierdza hiperkortyzolemię. Następnie należy oznaczyć stężenie ACTH we krwi o 9. rano i jeżeli jest podwyższone należy wykonać MR przysadki. Test stymulacji CRH (hormonem uwalniającym hormon kortykotropowy) pomaga odróżnić przysadkowy od ektopowego ACTH-zależnego zespół Cushinga, ale „złotym standardem” pozostaje cewnikowanie zatok skalistych w celu pobrania krwi do oznaczeń ACTH. Operacyjne usunięcie gruczolaka przysadki przez zatokę klinową jest leczeniem pierwszego rzutu w chorobie Cushinga i może być powtórzone jeżeli będzie nieskuteczne. Leczeniem drugiego rzutu są radioterapia przysadki, obustronne usunięcie nadnerczy i leczenie farmakologiczne. Radioterapia przysadki jest bardzo skuteczna, ale pełny efekt leczniczy uzyskujemy po kilku latach. Obustronne usuniecie nadnerczy jest nadal stosowane u ciężko chorych pacjentów, którzy nie tolerują leczenia farmakologicznego. Najbardziej skuteczne leki hamujące syntezę steroidów nadnerczowych to metyrapon, ketokonazol, mitotan i etomidat. Leczenie farmakologiczne stosuje się podczas przygotowania do operacji, kiedy operacja jest nieskuteczna albo w czasie oczekiwania na skutki radioterapii. Kabergolina i pasireotyd obniżają stężenie ACTH, ale są skuteczne odpowiednio tylko w 30% i 25%. Pacjenci z chorobą Cushinga powinni być leczeni w specjalistycznych ośrodkach endokrynologicznych, ponieważ współpraca wielodyscyplinarnego zespołu specjalistów (endokrynologów, neurochirurgów, onkologów i radiologów) decyduje o powodzeniu leczenia

Rathke's Cleft Cyst Abscess with a Very Unusual Course

Infected Rathke's cleft cysts (RCC) are extremely rare with only a few published cases. We report the case of a 31-year-old man who presented with headaches, visual disturbance, and hypopituitarism secondary to an infected RCC with extension of abscesses along the optic tract. Magnetic resonance imaging showed ring enhancing cystic lesions within an expanded sella with suprasellar and intraparenchymal extension. The radiological appearance suggested a high-grade optic glioma, but an endoscopic transsphenoidal biopsy revealed frank pus in the pituitary fossa, which subsequently grew Staphylococcus aureus . Pathological examination of the cyst wall showed an inflamed RCC. Following a prolonged course of intravenous antibiotics, the infection resolved and vision improved. RCC abscesses are rare and the intracranial extension of the infection in our case makes it unique

Fucosylated AGP glycopeptides as biomarkers of HNF1A-Maturity onset diabetes of the young

Aims: We previously demonstrated that antennary fucosylated N-glycans on plasma proteins are regulated by HNF1A and can identify cases of Maturity-Onset Diabetes of the Young caused by HNF1A variants (HNF1A-MODY). Based on literature data, we further postulated that N-glycans with best diagnostic value mostly originate from alpha-1-acid glycoprotein (AGP). In this study we analyzed fucosylation of AGP in subjects with HNF1A-MODY and other types of diabetes aiming to evaluate its diagnostic potential. Methods: A recently developed LC-MS method for AGP N-glycopeptide analysis was utilized in two independent cohorts: a) 466 subjects with different diabetes subtypes to test the fucosylation differences, b) 98 selected individuals to test the discriminative potential for pathogenic HNF1A variants. Results: Our results showed significant reduction in AGP fucosylation associated to HNF1A-MODY when compared to other diabetes subtypes. Additionally, ROC curve analysis confirmed significant discriminatory potential of individual fucosylated AGP glycopeptides, where the best performing glycopeptide had an AUC of 0.94 (95% CI 0.90–0.99). Conclusions: A glycopeptide based diagnostic tool would be beneficial for patient stratification by providing information about the functionality of HNF1A. It could assist the interpretation of DNA sequencing results and be a useful addition to the differential diagnostic process.publishedVersio

Effect of COVID-19 on the clinical course of diabetic ketoacidosis (DKA) in people with type 1 and type 2 diabetes

Objective COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA. Design Retrospective cohort study. Methods All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected. Results A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups. Conclusion COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9–60.0) vs 31.4 mmol/L (28.0–39.1) vs 24 mmol/L (20.2–33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results

Plasma fucosylated glycans and C-reactive protein as biomarkers of HNF1A-MODY in young adult–onset nonautoimmune diabetes

OBJECTIVE Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the commonest type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and hs-CRP are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes. RESEARCH DESIGN AND METHODS We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed. RESULTS We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L). CONCLUSIONS Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele

Assessment and translation of novel biomarkers for diagnosis of maturity onset diabetes of the young due to HNF1A variants

HNF1A-MODY is the most common form of monogenic diabetes, but due to low awareness among clinicians and limited availability of genetic testing in many countries, the majority of cases are misdiagnosed as type 1 or type 2 diabetes. In clinical practice, it is apparent that some young adults with non-autoimmune diabetes share several features of MODY and type 2 diabetes. Hence, I aimed to understand the range of genetic variation in HNF1A in this group and whether we could use biomarkers to help identify those with HNF1A alleles likely to be influencing their diabetes status. I performed HNF1A sequencing in 1058 subjects with non-autoimmune diabetes diagnosed below 45 years of age and identified 26 rare non-synonymous HNF1A alleles in 30 probands and 8 relatives. A systematic assessment assigned a likely damaging functional effect to 50% of these HNF1A alleles. The assessment of HNF1A alleles and their experimental characterisation unveiled the complexity of the genotype-phenotype relationship and continuity of the functional spectrum of HNF1A alleles from benign through likely benign, likely damaging to damaging effect. To clarify the performance of C-reactive protein (CRP) and N-glycan profile as biomarkers of HNF1A-MODY, I evaluated them in the above unselected sample of individuals who also underwent HNF1A sequencing. I have shown that 3-antennary fucosylated N-glycans and CRP were significantly lower in subjects with likely damaging HNF1A alleles in this group when compared to participants without HNF1A variants. Both biomarkers distinguished individuals with likely damaging HNF1A alleles from those without HNF1A variants with a C-statistic of 0.82-0.92. Plasma levels of these biomarkers negatively correlated with the predicted pathogenicity of HNF1A alleles. The expression of several steroidogenesis enzymes had been reported to be reduced in the liver cells of Hnf1a knock-out mice. Hence, I assessed the urinary steroid profile in individuals with HNF1A-MODY and age- and BMI-matched non-diabetic subjects and those with type 2 diabetes. The activity of 11β-hydroxysteroid dehydrogenase type 2 was reduced and the activity of 5β-steroid reductase increased in individuals with HNF1A-MODY. Their performance in selecting subjects with HNF1A-MODY was inferior to that of CRP and 3-antenary fucosylated glycans. In summary, my thesis has shown the complexity of the interpretation of genetic variation which is crucial for an accurate diagnosis and the assessment of potential biomarkers for genetic disease. Careful evaluation of the functional effect of HNF1A alleles identified on sequencing informs diagnosis in individuals with early-onset diabetes. Furthermore, the combination of functional assessment and clinical phenotype can guide management in those without canonical monogenic phenotypes found to have variant HNF1A alleles.</p