PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy

Sleep and Breathing -     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Myelographic study of the spinal cord ascent during fetal development

To assess the length of the spinal cord relative to the vertebral column during fetal development, we performed translumbar myelograms on 340 spontaneously aborted fetuses. Of these, 146 were selected for study. There were 76 males and 70 females, with fetal age ranging from 7 to 33 weeks. Significant variation in the level of spinal cord termination was found in fetuses between 12 and 25 weeks gestational age. In fetuses between 25 and 33 weeks gestational age, the cord ended at or above the third lumbar vertebra.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Systematic and random errors in compression testing of trabecular bone

We sought to quantify the systematic and random errors associated with-artifacts in the platens compression test for trabecular bone. Our hypothesis was that while errors may depend on anatomic site, they do not depend on apparent density and therefore have substantial random components. Trabecular bone specimens were first tested nondestructively using newly developed accurate protocols and then were tested again using the platens compression test. Percentage differences in modulus between the techniques (bovine) proximal tibia [n = 18] and humerus [n = 17] and human lumbar spine, [n = 9] were in the range of 4-86%. These differences did not depend on anatomic site (p = 0.21) and were only weakly dependent on apparent density and specimen aspect ratio (r² < 0.10). The mean percentage difference in modulus was 32.6% representing the systematic component of the end-artifact error. Neglecting the minor variations explained by density and specimen size (approximately 10%), an upper bound on the random error from end-artifacts in this experiment was taken as the SD of the modulus difference (±18.2%). Based on a synthesis of data taken from this study and from the literature, we concluded that the systematic underestimation error in the platens compression test can be only approximated and is in the range of 20-40%; the substantial random error (±12.5%) confounds correction, particularly when the sample size is small. These errors should be considered when interpreting results from the platens test, and more accurate testing techniques should be used when such errors are not acceptable.