Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference?

Due to the limited data on diabetic ketoacidosis and brain edema (DKA/BE) in children/adolescents and the lack of recent data on adults with type 1 diabetes (T1D), we addressed the question of whether neuroinflammation was present in the fatal DKA of adults. We performed immunohistochemistry (IHC) studies on the brains of two young adults with T1D and fatal DKA and compared them with two teenagers with poorly controlled diabetes and fatal DKA. C5b-9, the membrane attack complex (MAC) had significantly greater deposits in the grey and white matter of the teenagers than the young adults (p=0.03). CD59, a MAC assembly inhibitory protein was absent, possibly suppressed by the hyperglycemia in the teenagers but was expressed in the young adults despite comparable average levels of hyperglycemia. The receptor for advanced glycation end products (RAGE) had an average expression in the young adults significantly greater than in the teenagers (p=0.02). The autophagy marker Light Chain 3 (LC3) A/B was the predominant form of programmed cell death (PCD) in the teenage brains. The young adults had high expressions of both LC3A/B and TUNEL, an apoptotic cell marker for DNA fragmentation. BE was present in the newly diagnosed young adult with hyperglycemic hyperosmolar DKA and also in the two teenagers. Our data indicate that significant differences in neuroinflammatory components, initiated by the dysregulation of DKA and interrelated metabolic and immunologic milieu, are likely present in the brains of fatal DKA of teenagers when compared with young adults.

Oestrogen receptor-beta as a potential target for treatment in advanced colorectal cancer: a pilot study.

AIMS: Oestrogen receptor-beta (ER-ß) is expressed in colorectal cancer. Theoretically, ER-ß stimulation could slow down tumour proliferation, and this is supported by preclinical research data. While preparing a Phase II trial for advanced colorectal cancer patients we performed a pilot study with three questions: (i) in what percentage of patients do metastases display strong ER-ß1 expression; (ii) is there any concordance in expression between primary tumours and metastases; and (iii) is the immunohistochemical (IHC) scoring procedure reproducible? METHODS AND RESULTS: Thirty patients were selected, 15 with locoregional lymph node metastases and 15 with either synchronous or metachronous hepatic metastases. All primary tumours and metastases were analysed for immunohistochemical ER-ß1 expression according to a predefined scoring system. The scoring was performed independently by two pathologists in order to calculate the weighted kappa value. Strong ER-ß1 expression was found in four of 15 hepatic metastases and four of 15 lymph node metastases. In 15 of 30 patients, the level of ER-ß1 expression in the metastasis was concordant with that observed in the primary tumour. Weighted kappa values of IHC ER-ß1 expression were satisfactory. CONCLUSIONS: In twenty-five per cent of patients there was strong ER-ß1 expression in metastases, biopsy of which will be considered mandatory for trial inclusion.

Three-dimensional radiological evaluation of secondary alveolar bone grafting in cleft lip and palate patients: a systematic review.

OBJECTIVES: To systematically review the existing literature on the three-dimensional (3D) radiological evaluation of secondary alveolar bone grafting (SABG) in cleft lip and palate (CLP) patients, with specific interest in 3D imaging protocols and assessment methods.  Methods: A comprehensive literature search on PubMed, Embase and the Cochrane Library was conducted. Included publications concerned 3D imaging for evaluation of SABG in CLP patients while articles about primary or tertiary bone grafting or using of two-dimensional images only were excluded. Study quality was evaluated using the Methodological Index for Non-Randomized Studies  or the Cochrane Collaboration tool for assessing risk of bias. RESULTS: The search yielded 1735 citations, of which 38 met the inclusion criteria. We noticed a large variability in imaging protocols and bone graft evaluation methods between studies. Most articles were observational studies with medium to low methodological quality, except for the one randomised clinical trial having a low risk of bias.  Conclusions: There is a lack of prospective, controlled trials based on a consistent imaging protocol with a sufficiently long follow-up period. A pressing need exists for the development of a consistent optimized imaging protocol for diagnosis and follow up of SABG in CLP patients. Although 3D evaluation methods seem to be more precise than two-dimensional methods, we should be careful when comparing the outcomes arising from different 3D measuring techniques.

An optimized imaging protocol for orofacial cleft patients.

The objective was to present an optimized imaging protocol for orofacial cleft (OFC) patients, which might be used as an international recommendation for OFC care programs. The present radiological protocol has been structured by the OFC team of the University Hospitals Leuven based on a combined approach of clinical experience and scientific evidence. The development was based on careful monitoring of the existing needs for radiological diagnosis by the involved disciplines. Needs were revised by expert consensus and radiological optimization. Effective doses were converted to panoramic equivalents (professional conversion) and background radiation (patient conversion). At the age of 6, a panoramic radiograph is taken for the evaluation of dental anomalies. For the preoperative planning of secondary alveolar bone, grafting a low-resolution cone beam computer tomography (CBCT) of a limited field of the maxilla is taken at the age of 7 to 9. At the age of 10, 15, and 20, a low-resolution CBCT of both jaws with the smallest possible field is taken serving as conventional, presurgical, and end of treatment records, respectively. Two-dimensional images are reconstructed out of 3D ones. There are currently no international guidelines concerning the imaging protocol for OFC patients. It is clear that a multidisciplinary approach plays a key role in radiation hygiene. In this article, we presented an optimized imaging protocol for OFC patients based on European guidelines to accomplish the concepts of justification and optimization, which might be used as an international recommendation for OFC care programs.

Delayed diagnosis of angiosarcoma of the spleen: clinically presenting as recurrent haemoperitoneum following embolisation.

Angiosarcoma is a highly aggressive and extremely rare neoplasm of the spleen, with a limited number of reported cases worldwide. We report a case of a 69-year-old man who presented with progressive symptoms of fatigue, abdominal and back pain, anaemia and haemoperitoneum 1 year following embolisation of the spleen for splenic rupture. Additional imaging and colonoscopy with biopsy revealed intra-abdominal fluid and a colonic adenocarcinoma. Diagnostic laparoscopy demonstrated a haemoperitoneum and colon carcinoma, after which splenectomy via laparotomy was performed. Pathology report revealed an angiosarcoma of the spleen with peritoneal tumour deposits. Rupturing of a spleen may be due to an underlying disease. Therefore, the differential diagnosis of splenic rupture should include the possibility of a splenic tumour. The definitive diagnosis and treatment of a splenic angiosarcoma may require splenectomy, although prognosis is poor.

Progressive respiratory distress due to neck mass.

The present report describes the case of an 80-year-old woman who presented at the emergency department with progressive respiratory distress caused by a massive anterior neck mass with tracheal deviation and compression. A CT scan showed diffuse enlargement of the thyroid gland. The patient underwent a left-sided hemithyroidectomy. Pathology unexpectedly revealed a primary thyroid lymphoma. Treatment with prednisone and vincristine was initiated to reduce tumour size and preserve the airway, resulting in rapid volume reduction and airway expansion. Primary thyroid lymphoma is a rare entity that requires adequate diagnosis and rapid initiation of treatment to reduce tumour volume and to prevent airway compromise.