Post-mortem radiology in fetal and neonatal death: the diagnostic value of post-mortem MRI versus autopsy regarding non-cardiac thoracic and abdominal abnormalities.

AIM: To compare the diagnostic value and accuracy of post-mortem magnetic resonance imaging (PMMRI) and autopsy for non-cardiac thoracic and abdominal abnormalities in fetal death. MATERIALS AND METHODS: This single-institution retrospective study included all consecutive cases of fetal and perinatal death between January 2015 and December 2021 for which PMMRI followed by autopsy was conducted. These cases comprised fetuses at >18 weeks of gestation and preterm and term neonates who lived for <24 h. All PMMRI and autopsy reports were re-assessed and scored for seven non-cardiac thoracic and 52 abdominal abnormalities, and concordance between autopsy and PMMRI findings was determined as the primary outcome. RESULTS: Eighty cases were included in this study. Fetal loss was caused by termination of pregnancy in 80% of cases. Further, the mean gestational age was 166 days (23 weeks and 5 days, range 126-283 days). The concordance between PMMRI and autopsy for non-cardiac thoracic and abdominal abnormalities was 83.1% (95% confidence interval [CI] 71.3-83.3) and 76.3% (95% CI 65.8-84.2%), respectively, with a substantial and moderate strength of agreement (Cohen's kappa = 0.63 and 0.51 respectively). CONCLUSION: PMMRI exhibited good overall diagnostic value for non-cardiac thoracic and abdominal abnormalities, specifically large structural abnormalities. PMMRI may offer parents and physicians a valuable addition to autopsy for the detection of non-cardiac thoracic and abdominal abnormalities, or even an alternative option when parents do not consent to autopsy.

Biochemical Effects on the Liver of 1 Month of Alcohol Abstinence in Moderate Alcohol Consumers.

SHORT SUMMARY: : In this study in healthy moderate alcohol consumers, we observe that one month of alcohol abstinence results in decreased gamma-glutamyl transferase levels, which return to baseline levels after resumption of alcohol consumption.

Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. CONCLUSION: Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post-mortem magnetic resonance imaging can be complementary thereof.

Disclosure of cardiac variants of uncertain significance results in an exome cohort.

This study examined the impact of disclosing subclassifications of genetic variants of uncertain significance (VUS) on behavioral intentions. We studied return of VUS results to 79 individuals with a cardiomyopathy-associated VUS, subclassified into VUS-high or VUS-low. Primary outcomes were perceived risk (absolute and comparative), perceived severity, perceived value of information, self-efficacy, decision regret, and behavioral intentions to share results and change behaviors. There was no significant difference between the 2 subclasses in overall behavioral intentions (t = 0.023, P = .982) and each of the individual items on the behavioral intentions scale; absolute (t = -1.138, P = .259) or comparative (t = -0.463, P = .645) risk perceptions; perceived value of information (t = 0.582, P = .563) and self-efficacy (t = -0.733, P = .466). Decision regret was significantly different (t = 2.148, P = .035), with VUS-low (mean = 17.24, SD = 16.08) reporting greater regret. Combining the subclasses, perceived value of information was the strongest predictor of behavioral intentions (ß = 0.524, P < .001). Participants generally understood the meaning of a genetic VUS result classification and reported satisfaction with result disclosure. No differences in behavioral intentions were found, but differences in decision regret suggest participants distinguish subclasses of VUS results. The perceived value of VUS may motivate recipients to pursue health-related behaviors.

Radiological imaging of teratological fetuses: what can we learn?

OBJECTIVES: To determine the advantages of radiological imaging of a collection of full-term teratological fetuses in order to increase their scientific and educational value. BACKGROUND : Anatomical museums around the world exhibit full-term teratological fetuses. Unfortunately, these museums are regularly considered as "morbid cabinets". Detailed dysmorphological information concerning the exhibited specimens is often lacking. Moreover, fetuses with severe and complex congenital anomalies are frequently diagnosed incompletely, incorrectly or not at all. METHODS: In order to verify diagnoses and to enrich their educational and scientific value, we imaged 41 out of the 72 teratological specimens present in the collection of our Anatomy and Pathology Museum in Nijmegen (The Netherlands) by means of magnetic resonance imaging (MRI) and computed tomography (CT). Additionally, contemporary dysmorphological insights and 3D models are implemented in the teratology education of medical students and residents. CONCLUSIONS: Full-term teratological fetuses have become increasingly rare and deserve a prominent place in every anatomical museum; they are suitable for contemporary teratological research and education. Modern radiological techniques markedly enhance their scientific and didactic value. TEACHING POINTS: • To explore the scientific and educational potential of institutionalised teratological collections • To understand the additional value of radiological imaging in diagnosing teratological specimens • To learn about the specific settings of MRI parameters when scanning fixed specimens • To recognise specific internal dysmorphology in several congenital anomalies.

PUGS: A novel scale to assess perceptions of uncertainties in genome sequencing.

Expectations of results from genome sequencing by end users are influenced by perceptions of uncertainty. This study aimed to assess uncertainties about sequencing by developing, evaluating, and implementing a novel scale. The Perceptions of Uncertainties in Genome Sequencing (PUGS) scale comprised ten items to assess uncertainties within three domains: clinical, affective, and evaluative. Participants (n=535) from the ClinSeq® NIH sequencing study completed a baseline survey that included the PUGS; responses (mean = 3.4/5, SD=0.58) suggested modest perceptions of certainty. A confirmatory factor analysis identified factor loadings that led to elimination of two items. A revised eight-item PUGS scale was used to test correlations with perceived ambiguity (r = -0.303, p < 0.001), attitudinal ambivalence (r = -0.111, p = 0.011), and ambiguity aversion (r = -0.093, p = 0.033). Results support nomological validity. A correlation with the MICRA uncertainty subscale was found among 175 cohort participants who had received results (r = -0.335, p < 0.001). Convergent and discriminant validity were also satisfied in a second sample of 208 parents from the HudsonAlpha CSER Project who completed the PUGS (mean = 3.4/5, SD = 0.72), and configural invariance was supported across the two datasets. As such, the PUGS is a promising scale for evaluating perceived uncertainties in genome sequencing, which can inform interventions to help patients form realistic expectations of these uncertainties.

MR angiography of the lower extremities with a moving-bed infusion-tracking technique.

PURPOSE: To assess the value of MR angiography (MRA) with automatic table movement in a consecutive series of patients with peripheral arterial disease. METHODS: Seventy-two patients underwent both conventional angiography (CA) and MRA for peripheral arterial occlusive disease. Both techniques were scored in a masked way. Consensus scoring for CA was compared with MRA scoring per observer. If there was a discrepancy in scoring of a segment on MRA and CA, the images were reviewed and a consensus arrived at. RESULTS: Observer A found 7.4% and observer B found 6.5% of the segments could not be analyzed on MRA. Observer A scored 11.4% dissimilar on MRA and CA, observer B 15.2%. In the aortoiliac arteries, this was mainly caused by stents and overestimation of stenoses; in the crural arteries it resulted from underestimation of the stenoses on MRA. Overall sensitivity and specificity for the aortoiliac, femoropopliteal and crural vessels were respectively 90% and 91%, 90% and 96%, 59% and 96% for observer A, and 85% and 91%, 84% and 89%, 68% and 85% for observer B. CONCLUSION: Although MRA of the lower extremities is a promising technique, improvements still need to be made. In particular, MRA below the knee is suboptimal for clinical use.

Communicating breast cancer risks to women using different formats.

Using a pre-post test design with a baseline, laboratory, and a 6-month follow-up, we communicated women's objective breast cancer risks, based on the Gail Model, using two formats: (a) range of risks (e.g., risk of breast cancer can be as low as 1% and as high as 5%); and (b) as a point estimate (e.g., your risk of breast cancer is 3%). We examined how these presentations individually and jointly affected women's perceived lifetime breast cancer risks. Overall, providing risk estimates either as a range of risks or as a point estimate lowered women's perceived lifetime risks compared with women who did not get information presented this way shortly after receipt of this information relative to baseline. At the 6-month follow-up, perceptions of lifetime risks generally returned to their baseline values. Overall, women viewed their risk feedback, whether presented as a point estimate or as a range of risks, as equally credible, trustworthy, accurate, and personally relevant. These results suggest that women evaluate risk feedback containing either point estimates or range of risks as equally acceptable. Both formats lead to short-term reductions in perceived risk (i.e., greater accuracy).

Objective standards are not enough: affective, self-evaluative, and behavioral responses to social comparison information.

Three studies examined affective, self-evaluative, and behavioral responses to objective and social comparison information. In the first study, 437 male and female college undergraduates imagined they had a 30% or 60% risk of experiencing a negative event and that the average person's risk was higher or lower. All types of responses were sensitive to relative but not absolute risk. In the second study, 60 male and female college undergraduates learned that they scored 40% or 60% on a task and that this score was above or below average. Subsequent behaviors whose outcomes depended largely on objective ability still reflected attention to relative standing. This effect of comparative feedback was shown to be mediated by changes in self-evaluation. A third, follow-up study demonstrated that attention to comparative feedback (in the context of objective information) hinges on its desirability. Implications for social comparison theory are discussed.

Psychosocial barriers to health promotion in an American Indian population.

Northern Plains Indians (N = 200) completed the Indian Specific Health Risk Appraisal and measures assessing beliefs about risk factors and personal risk. Participants rated personal risk optimistically, judged their risk factor standing as superior to that of their peers, and neglected to consider risk factor standing when appraising personal risk. Moreover, participants were often not improving their standing on risk factors they considered relevant to their health. Such biases in health beliefs may prevent health interventions from being successful.

Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.

We previously demonstrated that the putative oncogene AKT2 is amplified and overexpressed in some human ovarian carcinomas. We have now identified amplification of AKT2 in approximately 10% of pancreatic carcinomas (2 of 18 cell lines and 1 of 10 primary tumor specimens). The two cell lines with altered AKT2 (PANC1 and ASPC1) exhibited 30-fold and 50-fold amplification of AKT2, respectively, and highly elevated levels of AKT2 RNA and protein. PANC1 cells were transfected with antisense AKT2, and several clones were established after G418 selection. The expression of AKT2 protein in these clones was greatly decreased by the antisense RNA. Furthermore, tumorigenicity in nude mice was markedly reduced in PANC1 cells expressing antisense AKT2 RNA. To examine further whether overexpression of AKT2 plays a significant role in pancreatic tumorigenesis, PANC1 cells and ASPC1 cells, as well as pancreatic carcinoma cells that do not overexpress AKT2 (COLO 357), were transfected with antisense AKT2, and their growth and invasiveness were characterized by a rat tracheal xenotransplant assay. ASPC1 and PANC1 cells expressing antisense AKT2 RNA remained confined to the tracheal lumen, whereas the respective parental cells invaded the tracheal wall. In contrast, no difference was seen in the growth pattern between parental and antisense-treated COLO 357 cells. These data suggest that overexpression of AKT2 contributes to the malignant phenotype of a subset of human ductal pancreatic cancers.

High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas.

Malignant mesotheliomas (MMs) are aggressive tumors that develop most frequently in the pleura of patients exposed to asbestos. In contrast to many other cancers, relatively few molecular alterations have been described in MMs. The most frequent numerical cytogenetic abnormality in MMs is loss of chromosome 22. The neurofibromatosis type 2 gene (NF2) is a tumor suppressor gene assigned to chromosome 22q which plays an important role in the development of familial and spontaneous tumors of neuroectodermal origin. Although MMs have a different histogenic derivation, the frequent abnormalities of chromosome 22 warranted an investigation of the NF2 gene in these tumors. Both cDNAs from 15 MM cell lines and genomic DNAs from 7 matched primary tumors were analyzed for mutations within the NF2 coding region. NF2 mutations predicting either interstitial in-frame deletions or truncation of the NF2-encoded protein (merlin) were detected in eight cell lines (53%), six of which were confirmed in primary tumor DNAs. In two samples that showed NF2 gene transcript alterations, no genomic DNA mutations were detected, suggesting that aberrant splicing may constitute an additional mechanism for merlin inactivation. These findings implicate NF2 in the oncogenesis of primary MMs and provide evidence that this gene can be involved in the development of tumors other than nervous system neoplasms characteristic of the NF2 disorder. In addition, unlike NF2-related tumors, MM derives from the mesoderm; malignancies of this origin have not previously been associated with frequent alterations of the NF2 gene.

Resistance of personal risk perceptions to debiasing interventions.

The tendency to believe that one's own risk is less than that of others may reduce interest in health-protective behaviors. This article describes 4 attempts to reduce such optimistic biases. In Study 1, New Jersey residents (N = 222) were provided with lists of risk factors for several health problems. This manipulation was strengthened in Study 2 by presenting risk factors in such a way that participants (164 undergraduates) might see their own standing as inferior to that of others. In Study 3, risk factors were presented one at a time, and participants (190 undergraduates) incorporated them into a mental image of a high-risk individual. Finally, 374 undergraduates in Study 4 generated lists of personal attributes that they believed increased their risk. Optimistic biases were found in each study, but none of the manipulations reduced these biases consistently. In contrast, conditions using opposite manipulations often exacerbated the biases.

p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma.

To determine whether p16 is altered in human malignant mesothelioma (MM), molecular analysis of multiple 9p loci was performed on 40 cell lines and 23 primary tumors from 42 MM patients. We identified homozygous deletions of p16 in 34 (85%) cell lines and a point mutation in 1 line. Down-regulation of p16 was observed in 4 of the remaining cell lines, 1 of which displayed a DNA rearrangement of p16. Homozygous deletions of p16 were identified in 5 of 23 (22%) primary tumors; no mutations or rearrangements were found in these specimens. Four cell lines displayed a single homozygous deletion proximal to or distal to p16; 4 others had 2 nonoverlapping deletions, one involving p16 and the other involving a region proximal to this locus. These data indicate that alterations of p16 are a common occurrence in MM cell lines and, to a lesser extent, in primary tumors. Furthermore, deletions of 9p21-p22 outside of the p16 locus may reflect the involvement of other putative tumor suppressor genes that could also contribute to the pathogenesis of some MMs.

A simple office spirometer for the pediatrician.

A comparative study of a new, simple, pneumatic, direct-recording office spirometer versus a long-accepted, water-sealed, water-filled spirometer was performed on 103 patients ranging from four to 20 years of age. Good correlation between the two spirometers was seen through a wide range of values for forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced expiratory flow during 25% to 75% of forced vital capacity and FEV1/FVC.