<Superscript>99m</Superscript>Tc-Tetrofosmin brain SPECT in the assessment of meningiomas—correlation with histological grade and proliferation index

Meningiomas account for about 30% of all intracranial tumors. Evaluation of their proliferation rate is useful for assessing their biological behavior. We evaluated prospectively whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake in meningiomas correlates with cellular proliferative activity and with tumor grade. We prospectively studied 18 meningioma cases. Brain single-photon emission computed tomography (SPECT) by (99m)Tc-TF was performed within a week prior to surgical excision. In the excised tumor specimens we assessed Ki-67 antigen expression. 14 of 18 patients had benign meningiomas, while the remaining four had anaplastic meningiomas. A significant correlation was found between both (99m)Tc-TF uptake and tumor grade (r = 0.722, P = 0.001) and between (99m)Tc-TF uptake and Ki-67 expression (r = 0.930, P < 0.001). There was a significant correlation between the intensity of tracer uptake and tumor recurrence at 1 year postoperative (r = 0.574, P = 0.02). This pilot study implies that (99m)Tc-TF brain SPECT could prove useful in differentiating benign from anaplastic meningiomas and is a potential indicator of their proliferative activity.     

The prognostic inhomogeneity of colorectal carcinomas Stage III: a proposal for subdivision of Stage III.

BACKGROUND: The prognosis of patients with Stage III colorectal carcinoma seems to be inhomogeneous. Therefore a subdivision of Stage III was performed. METHODS: Data from 850 patients of the Erlangen Registry of Colo-Rectal Carcinomas and 603 patients of the Study Group Colo-Rectal Carcinoma (SGCRC) with Stage III colorectal carcinoma were analyzed. Three different subdivisions of Stage III were performed according to pT, pN, and pTpN. Observed 5-year survival rates for all possible substages were calculated according to Kaplan-Meier. To compare the predictive value of several possible substages, Brier-Score and receiver operator charcteristics (ROC) analysis were applied. RESULTS: The subdivision according to pT (pT1,2pN1,2 versus pT3 pN1,2 versus pT4 pN1,2) as well as the subdivision according to pN (any pT pN1 vs. any pT pN2) resulted in significant differences of observed 5-year survival rates. However, subdivision according to pT and pN (pT1,2 pN1 vs. pT3,4pN1 and pT1,2pN2 vs. pT3,4 pN2) was found to be superior. The three substages, IIIA, IIIB, and IIIC, identified 10%, 50%, and 40% of the patients with observed 5-year survival rates of 80%, 60%, and 30%, respectively. Using Brier-Score and ROC analysis an increase in predictive power was found, especially for the patients of the Erlangen Registry, but less clearly for SGCRC patients. CONCLUSION: Subdivision of Stage III colorectal carcinoma into three substages according to the pT and pN categories resulted in subgroups which differed significantly in prognosis. This may be important for comparing treatment results, especially in adjuvant treatment and patient care evaluation studies.     

Cost consequences of induced abortion as an attributable risk for preterm birth and impact on informed consent

OBJECTIVE: To investigate the human and monetary cost consequences of preterm delivery as related to induced abortion (IA), with its impact on informed consent and medical malpractice. STUDY DESIGN: A review of the literature in English was performed to assess the effect of IA on preterm delivery rates from 24 to 31 6/7 weeks to assess the risk for preterm birth attributable to IA. After calculating preterm birth risk, the increased initial neonatal hospital costs and cerebral palsy (CP) risks related to IA were calculated. RESULTS: IA increased the early preterm delivery rate by 31.5%, with a yearly increase in initial neonatal hospital costs related to IA of > $1.2 billion. The yearly human cost includes 22,917 excess early preterm births (EPB) (< 32 weeks) and 1096 excess CP cases in very-low-birth-weight newborns, <1500 g. CONCLUSION: IA contributes to significantly increased neonatal health costs by causing 31.5% of EPB. Providers of obstetric care and abortion should be aware of the risk of preterm birth attributable to induced abortion, with its significant increase in initial neonatal hospital costs and CP cases.     

Study of Optimal Perimetric Testing In Children (OPTIC): developing consensus and setting research priorities for perimetry in the management of children with glaucoma

BackgroundPerimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research.MethodsExperts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish ‘agreement’. Divergence of opinions was investigated and resolved where possible through further iterations.Results7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75–7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally.Panel members highlighted the importance of informing decisions based upon individual circumstances—from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing.ConclusionsThere is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals’ lifetime, highlighting the need for further research.Subject terms: Paediatrics, Glaucoma     

Association of HLA-DQ Heterodimer Residues −18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial–Type 1

OBJECTIVEThe purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).RESEARCH DESIGN AND METHODSNext-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial–Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.RESULTSThe opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio [HR] 1.36; P = 2.01 ∗ 10⁻³) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue −18β in the signal peptide and β57 in the β-chain to form six motifs. DQ*VA was associated with faster (HR 1.49; P = 6.36 ∗ 10⁻⁴) and DQ*AD with slower (HR 0.64; P = 0.020) progression to diabetes onset. VA/VA, representing DQA1*03:01-B1*03:02 (DQ8/8), had a greater HR of 1.98 (P = 2.80 ∗ 10⁻³). The DQ*VA motif was associated with both islet cell antibodies (P = 0.023) and insulin autoantibodies (IAAs) (P = 3.34 ∗ 10⁻³), while the DQ*AD motif was associated with a decreased IAA frequency (P = 0.015). Subjects with DQ*VA and DQ*AD experienced, respectively, increasing and decreasing trends of HbA_1c levels throughout the follow-up.CONCLUSIONSHLA-DQ structural motifs appear to modulate progression from islet autoimmunity to diabetes among at-risk relatives with islet autoantibodies. Residue −18β within the signal peptide may be related to levels of protein synthesis and β57 to stability of the peptide-DQab trimolecular complex.     

ATM mutations in patients with hereditary pancreatic cancer

Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. SIGNIFICANCE: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes.