Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.     

Possibilities in diagnostic laparoscopy of acute appendicitis

Results of diagnostic laparoscopy in acute appendicitis suspects are presented. Laparoscopy allowed examination of the appendix in 96.5% cases, to make final diagnosis in 92.5% and to avoid surgery in 31.2% cases. Larger application of diagnostic laparoscopy in patients suspected of acute appendicitis will reduce significantly rate of diagnostic mistakes, complications and unwarranted appendectomies.     

Diagnostic significance of ferritin assay in peritoneal fluid and gastric juice

Ferritin was assayed by immunoradiometrical procedure in peritoneal fluid (26 patients with various ovarian pathologies) and gastric juice (18 patients with stomach cancer and 28 cases of gastric ulcer disease). It was found that diagnostic significance of ferritin measurements in peritoneal fluid in ovarian pathology is compromised by inflammation. Therefore, this marker cannot be used to differentiate between malignant and benign ovarian tumor. Single measurements of ferritin for detecting stomach ulcers were also diagnostically irrelevant since the data for stomach cancer and gastric ulcer exacerbation showed no significant difference.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.     

Algorithm of cardiopulmonary resuscitation in a cardiological hospital

Recent comments and amendments to routine algorithm of P. Safar's cardiopulmonary resuscitation, known as the ABCD principle, are critically analyzed. The primary mechanisms of thanatogenesis in sudden death in the majority of cases are not respiratory problems (requiring ABCD algorithm), but cardiac rhythm disorders. Based on their studies and practical and training experience, the authors suggest a new algorithm of cardiopulmonary resuscitation: UNIVERSAL, with the following steps: precordial stroke, indirect massage of the heart, forced ventilation of the lungs, venipuncture, electrocardiography, defibrillation by electric pulse therapy, electrocardiostimulation, and injections of adrenalin, atropine, and lidocaine. Introduction of this algorithm decreased hospital mortality of acute coronary patients, increased the rate of reanimation of suddenly dead patients, and reduced the incidence of iatrogenic complications of resuscitation.     

Atypical methods of surgical arrest of profuse gastric hemorrhage

The methods for arrest of profuse gastric hemorrhage in difficult situations aimed at life salvage of a patient, prevention of the postoperative complications are suggested. Knowledge of the non-conventional methods for arrest of hemorrhage will be of an essential help to a practical physician.     

Crystalline and amorphous forms of SiO2 in the lungs of patients with silicosis

Lung samples of dead patients with silicosis (9 persons) and those without silicosis were compared. The obtained results showed that there was no significant difference in the content of crystalline and amorphous forms of SiO2 in the control group and the dust-exposed group. Because of elevated content of SiO2 amorphous form total SiO2 concentrations were higher in the lungs of patients with silicosis than in the control group, but the content of the crystalline form didn't differ significantly. The samples were analyzed on the basis of the technique used with slight modifications for the determination of SiO2 crystalline form in industrial dust. Before the analysis was carried out the conditions for primary sample treatment were standardized. It was also shown that the mass of ashed lungs constituted 0.8 +/- 0.2% of the damp mass and 2.4 +/- 0.7% of the dry one.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.