Do we truly see what we think we see? The role of cognitive bias in pathological interpretation

In the histomorphological grading of prostate carcinoma, pathologists have regularly assigned comparable scores for the architectural Gleason and the now‐obsolete nuclear World Health Organization (WHO) grading systems. Although both systems demonstrate good correspondence between grade and survival, they are based on fundamentally different biological criteria. We tested the hypothesis that this apparent concurrence between the two grading systems originates from an interpretation bias in the minds of diagnostic pathologists, rather than reflecting a biological reality. Three pathologists graded 178 prostatectomy specimens, assigning Gleason and WHO scores on glass slides and on digital images of nuclei isolated out of their architectural context. The results were analysed with respect to interdependencies among the grading systems, to tumour recurrence (PSA relapse > 0.1 ng/ml at 48 months) and robust nuclear morphometry, as assessed by computer‐assisted image analysis. WHO and Gleason grades were strongly correlated (r = 0.82) and demonstrated identical prognostic power. However, WHO grades correlated poorly with nuclear morphology (r = 0.19). Grading of nuclei isolated out of their architectural context significantly improved accuracy for nuclear morphology (r = 0.55), but the prognostic power was virtually lost. In conclusion, the architectural organization of a tumour, which the pathologist cannot avoid noticing during initial slide viewing at low magnification, unwittingly influences the subsequent nuclear grade assignment. In our study, the prognostic power of the WHO grading system was dependent on visual assessment of tumour growth pattern. We demonstrate for the first time the influence a cognitive bias can have in the generation of an error in diagnostic pathology and highlight a considerable problem in histopathological tumour grading. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development

Split hand/split foot malformation (SHFM) is a heterogeneous limb developmental disorder, characterized by missing digits and fusion of remaining digits. An autosomal dominant form of this disorder (SHFM1) has been mapped to 7q21.3-q22.1 on the basis of SHFM-associated chromosomal rearrangements. Utilizing a YAC contig across this region, we have defined a critical interval of 1.5 Mb by the analysis of six interstitial deletion patients and mapped the translocation breakpoints of seven ectrodactyly patients within the interval. To delineate the basic molecular defect underlying SHFM, we have searched for candidate genes in a 500 kb region containing five of the translocation breakpoints. Three genes were identified, two genes of the Distal-less (dii) homeobox gene family, DLX5 and DLX6 and a novel gene, which we named DSS1. DSS1 is predicted to encode a highly acidic polypeptide with no significant similarity to any known proteins but 100% amino acid sequence identify with its murine homolog (Dss1). Using RNA in situ hybridization analysis, we detected a tissue-specific expression profile for Dss1 in limb bud, craniofacial primordia and skin. A deficiency in expression of Dss1, DLX5 and/or DLX6 during development may explain the SHFM phenotypes.      

Proposed new target height equations for use in Australian growth clinics

Equations for target height estimation designed for easy use in the Australian growth clinics are presented that are based on the standard deviation score method of Hermanussen and Cole. These equations are superior to the commonly used corrected midparental height method as they account for assortative mating and regression to the mean. Simulations using different mating types were performed to compare different methods of target height estimation. While the equations relate directly to growth charts used in Australia, it is noted that neither account for the secular increase in height observed from generation to generation.     

When the heart kills the liver: acute liver failure in congestive heart failure

Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases.Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach.As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST), bilirubin, and international normalized ratio (INR) did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI) was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m² vs. 1.6 L/min/m², p = 0.04). Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock.In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.     

人工全膝关节置换修复晚期膝关节病变的短期随访

背景：在最近的数十年,人工全膝关节置换被广泛地应用于晚期膝关节病变,如骨关节炎、类风湿关节炎和创伤性骨关节炎等疾病的治疗。全膝关节置换过程中的截骨方法、软组织平衡以及假体旋转定位一直是争论和探讨的问题。 目的：探讨晚期膝关节病变行全膝关节置换的修复效果。 方法：采用人工全膝关节置换修复31例(31膝)晚期膝关节病变,其中骨关节炎26例26膝,类风湿关节炎5例5膝。所有病例均伴有不同程度屈曲挛缩畸形,最大屈曲畸形角度均小于25°。分别对患者在置换前和置换后进行膝关节美国特种外科医院评分,所有31膝均使用固定平台后稳定型人工全膝关节假体。 结果与结论：置换后无早期感染,无假体脱位并发症发生。置换后关节疼痛症状明显缓解、屈曲和内翻畸形均得到明显改善。置换后X射线片显示假体位置良好,下肢力线良好。所有患者均获随访,随访时间6-12个月。膝关节美国特种外科医院评分置换前为(46.4±5.3)分,置换后6个月为(84.6±10.5)分,优良率为84%。提示人工全膝关节置换修复晚期膝关节病变效果确切,但操作较复杂,技术要求精确。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

Progressive multifocal leukoencephalopathy in patients with AIDS: appearance on MR images

Progressive multifocal leukoencephalopathy (PML) is an uncommon demyelinating disease that occurs in immunocompromised patients. The authors evaluated magnetic resonance (MR) images of 10 patients with pathologically proved PML and clinically diagnosed acquired immunodeficiency syndrome (AIDS) to determine the MR characteristics of this disorder. All patients had asymmetric cerebral involvement. Lesions were distributed throughout the brain, including the brain stem and basal ganglia. White matter was affected in all 10 patients; gray matter was also involved in five. In one patient the lesion enlarged and crossed the corpus callosum and contained focal hemorrhage. The authors conclude that, contrary to reported findings on computed tomographic scans, PML in patients with AIDS has a variable appearance on MR images and has many characteristics that differ from those previously thought to be typical on imaging studies.