PE MIMICS: a structured approach for the emergency radiologist in the evaluation of chest pain.

Chest pain is a common reason for presentation to the emergency department. In many cases, a CTPA or CT thoracic aorta is performed during work up to assess for pulmonary embolism and aortic pathology, critical diagnoses that can be difficult to out rule clinically. However, the causes of chest pain are myriad. It is therefore crucial for the interpreting radiologist to be cognizant of other potential etiologies when interpreting these studies. The purpose of this pictorial essay is to highlight the causes of non-PE or aortic-related chest pain and provide radiologists with a structured approach to interpreting these studies, ensuring a comprehensive search strategy so that important pathologies are not missed.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). CONCLUSIONS: Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

A description of sleep behaviour in healthy late pregnancy, and the accuracy of self-reports.

BACKGROUND: The importance of maternal sleep and its contribution to maternal and fetal health during pregnancy is increasingly being recognised. However, the ability to accurately recall sleep practices during pregnancy has been questioned. The aim of this study is to test the accuracy of recall of normal sleep practices in late pregnancy. METHODS: Thirty healthy women between 35 and 38 weeks of gestation underwent level III respiratory polysomnography (PSG) with infrared digital video recordings in their own homes. Data regarding sleep positions, number of times getting out of bed during the night and respiratory measures were collected. A sleep questionnaire was administered the morning after the recorded sleep. Continuous data were assessed using Spearman's Rho and Bland-Altman. Cohen's Kappa was used to assess recall in the categorical variables. RESULTS: Two-thirds of participants went to sleep on their left side. There was good agreement in sleep onset position between video and questionnaire data (Kappa 0.52), however the there was poor agreement on position on wakening (Kappa 0.24). The number of times getting out of bed during the night was accurately recalled (Kappa 0.65). Twenty five out of 30 participants snored as recorded by PSG. Questionnaire data was inaccurate for this measure. Bland-Altman plots demonstrated acceptable agreement between video and questionnaire data for estimated sleep duration, but not the time taken to fall asleep (sleep latency). One participant had mild obstructive sleep apnoea and another probable high upper airways resistance. CONCLUSIONS: Sleep onset position, sleep duration and the number of times getting out of bed during the night were accurately recalled, but sleep latency and sleep position on waking were not. This study identifies the sleep variables that can be accurately obtained by questionnaire and those that cannot.

An Integrated theory of false insights and beliefs under psychedelics.

Psychedelics are recognised for their potential to re-orient beliefs. We propose a model of how psychedelics can, in some cases, lead to false insights and thus false beliefs. We first review experimental work on laboratory-based false insights and false memories. We then connect this to insights and belief formation under psychedelics using the active inference framework. We propose that subjective and brain-based alterations caused by psychedelics increases the quantity and subjective intensity of insights and thence beliefs, including false ones. We offer directions for future research in minimising the risk of false and potentially harmful beliefs arising from psychedelics. Ultimately, knowing how psychedelics may facilitate false insights and beliefs is crucial if we are to optimally leverage their therapeutic potential.

Extra-abdominal desmoid tumours: a review of the literature.

Extra-abdominal desmoid lesions, otherwise known as aggressive fibromatosis, are slow-growing benign lesions which may be encountered in clinical practice. Recent controversies exist regarding their optimal treatment. Given their benign nature, is major debulking surgery justified, or is it worth administering chemotherapy for a disease process which unusually defies common teaching and responds to such medications? We present a literature review of this particular pathology discussing the aetiology, clinical presentation, and various current controversies in the treatment options.

Do psychedelics change beliefs?

Renewed interest in psychedelics has reignited the debate about whether and how they change human beliefs. In both the clinical and social-cognitive domains, psychedelic consumption may be accompanied by profound, and sometimes lasting, belief changes. We review these changes and their possible underlying mechanisms. Rather than inducing de novo beliefs, we argue psychedelics may instead change the impact of affect and of others' suggestions on how beliefs are imputed. Critically, we find that baseline beliefs (in the possible effects of psychedelics, for example) might color the acute effects of psychedelics as well as longer-term changes. If we are to harness the apparent potential of psychedelics in the clinic and for human flourishing more generally, these possibilities must be addressed empirically.

Change from transrectal to transperineal ultrasound-guided prostate biopsy under local anaesthetic eliminates sepsis as a complication.

Transrectal ultrasound-guided (TRUS) biopsy of the prostate is associated with increased risk of post-procedural sepsis with associated morbidity, mortality, re-admission to hospital, and increased healthcare costs. In the study institution, active surveillance of post-procedural infection complications is performed by clinical nurse specialists for prostate cancer under the guidance of the infection prevention and control team. To protect hospital services for acute medical admissions related to the coronavirus disease 2019 (COVID-19) pandemic, TRUS biopsy services were reduced nationally, with exceptions only for those patients at high risk of prostate cancer. In the study institution, this change prompted a complete move to transperineal (TP) prostate biopsy performed in outpatients under local anaesthetic. TP biopsies eliminated the risk of post-procedural sepsis and, consequently, sepsis-related admission while maintaining a service for prostate cancer diagnosis during the COVID-19 pandemic.

The course of glaucoma during pregnancy: a retrospective case series.

OBJECTIVE: To better understand the course of glaucoma during pregnancy in women with preexisting disease. METHODS: Retrospective case series of 28 eyes of 15 women with glaucoma followed up during pregnancy. Data were analyzed for age, race/ethnicity, medications, glaucoma type, intraocular pressure (IOP), and visual fields before, during, and after pregnancy. RESULTS: In 16 (57.1%) of 28 eyes, IOP was stable during pregnancy, with no progression of visual field loss. In 5 eyes (17.9%), visual field loss progressed during pregnancy, while IOP remained stable or increased. In 5 eyes (17.9%), IOP increased during pregnancy, but there was no progression of visual field loss. In 2 eyes (7.1%), data were inconclusive because of medication noncompliance and preexisting severe visual field loss. Glaucoma medications were used by 13 of 15 patients to control glaucoma during pregnancy. The classes of medications used most frequently were beta-blockers, alpha2-adrenergic agents, cholinergic agents, and topical carbonic anhydrase inhibitors. CONCLUSIONS: The course of glaucoma during pregnancy is variable, and women must be monitored closely during pregnancy. Medications may be necessary to control IOP and to prevent vision loss during pregnancy.

Structural characterization and localization of corticotropin-releasing factor in testis.

To sequence and thereby definitively characterize corticotropin-releasing factor (CRF)-like material from a representative peripheral tissue, CRF was obtained from 76 ovine testes. The novel extraction procedure involved use of an immunoaffinity column to which a high-affinity CRF monoclonal antibody was attached as well as fast protein liquid chromatography. The complete sequence was elucidated by gas-phase sequencing, carboxyamidopeptidase digestion and cyanogen bromide cleavage. Aside from microheterogeneity at position 39, all the other amino acids were identical to ovine hypothalamic CRF. Additionally, in immunohistochemical studies in the rat, CRF was localized to the Leydig cell. These findings along with related observations by ourselves and others are compatible with the hypothesis that CRF plays a significant local role, possibly by paracrine or autocrine mechanisms.

Up-regulation of retinoic acid receptor beta expression in renal cancers in vivo correlates with response to 13-cis-retinoic acid and interferon-alpha-2a.

Retinoic acid receptor-beta (RAR-beta) mRNA is not expressed by retinoid-resistant renal cancer cell lines but is present in retinoid-sensitive SK-RC-06 renal cancer cells and increases following incubation with retinoic acid (RA), suggesting that the antitumor action of RA is mediated through RAR-beta (A. D. Hoffman et al., Clin. Cancer Res., 2: 1077-1082, 2996). To determine whether RAR-beta expression correlates in vivo with major clinical response to patients with renal cell carcinoma (RCC) who were treated with retinoid-based therapy, we used in situ hybridization to analyze RAR-beta expression in tumor specimens obtained from patients who were treated on a clinical trial with 13-cis-RA and IFN-alpha. Thirty-three tissue specimens were analyzed (23 pretreatment and 10 on-treatment). mRNA expression was based on staining intensity, with scores within tumor cells ranging from 0 to 2, where a score of 0 indicated absence of staining, a score of 1 indicated weak staining, and a score of 2 indicated strong staining. RAR-beta expression was present in 22 of 23 (96%) pretreatment and 9 of 10 (90%) on-treatment specimens. Pretreatment levels of expression did not associate with the site of biopsy and did not predict for major clinical response to RA plus IFN-alpha therapy (two-sided Fisher's exact test, P = 0.826). However, an increase in the intensity of RAR-beta mRNA expression was detected in four of five (80%) patients who achieved a major response but in none of the five patients with progressive disease in whom sequential biopsies were available (two-sided Fisher's exact test, P = 0.048). These data show that RAR-beta transcripts increase in tumor cells of RCC patients who clinically respond to retinoid-based therapy. Retinoids that potently induce RAR-beta expression should be evaluated in the treatment of advanced RCC.

Corticotropin-releasing factor levels in the peripheral plasma and hypothalamus of the rat vary in parallel with changes in the pituitary-adrenal axis.

Impressive evidence has emerged indicating that immunoassayable and bioassayable CRF, which is immunoneutralizable, is present not only in the hypothalamus but in many peripheral tissues as well. Using highly specific and sensitive RIAs and immunoaffinity chromatography to investigate whether this extrabrain CRF circulates in the rat, we found low but clearly measurable levels in peripheral plasma (mean, 11.4 +/- 0.8 pg/ml). Immunological findings were corroborated by fast protein liquid chromatography, which resolves peptides by both hydrophobicity and ionic charge. With this approach the major immunoreactive peak was eluted at the position of synthetic rat CRF standard. To assess whether levels of peripheral plasma CRF-like immunoreactivity (CRF-LI) vary in parallel with those of hypothalamic CRF-LI, we performed studies with low and high dose dexamethasone administration and withdrawal, adrenalectomy, and hypophysectomy. Seven days after oral administration of dexamethasone, there was a decrement in the levels of peripheral plasma and hypothalamic CRF-LI. Depending on the dose, recovery was also found 7 days after cessation of the treatment. After either adrenalectomy or hypophysectomy, there were increments in the levels of CRF-LI in both peripheral plasma and hypothalamus. Thus, concentrations of CRF-LI in the peripheral plasma and in the hypothalamus vary in parallel in response to alterations in the pituitary-adrenal axis.

Interleukin 1 beta mediates stress-induced immunosuppression via corticotropin-releasing factor.

Intracerebroventricular (icv) infusion of human interleukin 1 beta (IL-1) into intact and adrenalectomized rats impairs immune function. Using antibody to IL-1 as well as an inhibitor of IL-1 action, we sought to determine if endogenous IL-1 in the central nervous system has a physiological role in mediating the immunosuppressive effects of stress. Compared with freely moving controls, rats given intermittent electric shock to the tail for 40 min exhibited a fall in T lymphocyte proliferation and natural killer (NK) cell cytotoxicity of 33% and 38%, respectively; however, when pretreated with icv human IL-1 monoclonal antibody, which significantly crossreacts with rat IL-1, the decrement was attenuated to 14.6% and 15%, respectively. When rats were pretreated with icv alpha-MSH, which blocks many IL-1 effects, shock-induced suppression of 42% in both T lymphocyte proliferation and NK cytotoxicity were blunted to 33% and 31%, respectively. Similar results were found in adrenalectomized rats. These findings suggest that endogenous IL-1 is a physiologically relevant mediator of the immune response to stress. As IL-1 has been reported to release CRF, which we have shown always plays a significant role in stress-induced immunomodulation, we then assessed the relationship of IL-1 and CRF in immunosuppression. Infusion of icv IL-1 caused a decrease of 35% in T lymphocyte proliferation and 34% in NK activity, but pretreatment with CRF antibody icv attenuated IL-1 suppression of T lymphocyte proliferation and NK activity to 10% and 8%, respectively. Comparable results were observed in adrenalectomized rats. These findings suggest that CRF antibody is able to block the immunosuppressive effects of IL-1. To further examine the interaction of CRF in mediating stress-induced immunosuppression, we found that animals pretreated with icv CRF antibody, shocked and then given icv IL-1, had a decrement in T lymphocyte proliferation and NK cytotoxicity of 24% and 21%, respectively, demonstrating that the immunosuppressive effect of icv IL-1 is blocked when central CRF has been neutralized by prior administration of icv CRF antibody. In contrast, animals pretreated with icv IL-1 antibody, shocked and then given icv CRF, had decrements of 38% and 40%, respectively, showing that icv CRF does act even when central IL-1 has been neutralized by prior administration of icv IL-1 antibody. Thus, we conclude there is a sequential relationship between two of the known mediators of stress-induced immunosuppression, with release of central IL-1 followed by that of CRF.

Corticotropin-releasing factor modulates the immune response to stress in the rat.

We examined the role of CRF, a key mediator of the endocrine response to stress, in modulating immunosuppression during the subacute stress of intermittent electrical shock over 1 h. Administration of shock to intact rats resulted in a 74% decrement in T-lymphocyte proliferation and a 59% decrease in natural killer cytotoxicity. Similar suppression of these two parameters of immune function in response to shock was noted in adrenalectomized rats as well. The immunosuppressive effects of this shock were significantly and comparably blunted when both intact and adrenalectomized animals were pretreated 1) iv with either a highly potent polyclonal CRF antibody or a specific CRF antagonist or 2) intracerebroventricularly with either a high affinity monoclonal antibody to CRF or a specific CRF antagonist. An immunomodulatory role for CRF is further supported by the findings that administration of exogenous CRF, either iv (10 micrograms/animal) or intracerebroventricularly (1 microgram/animal), resulted in significant decrements in lymphocyte proliferation and natural killer cytotoxicity, similar to those seen with the stress paradigm. Our observations indicate that CRF plays a significant role in modulating the immune response to subacute stress, largely by adrenal-independent mechanisms.

Sensitivity of adipocyte basal and insulin-stimulated hexose transport to the membrane lipid structure.

A series of anesthetic alcohols inhibited basal and insulin-stimulated 2-deoxy-D-[1-14C]glucose transport in adipocytes over total alcohol concentration ranges that cause local anesthesia of rat sciatic nerve. The relative potencies of the inhibition caused by the alcohols increased in the following order: methanol less than ethanol less than propanol less than butanol less than benzyl alcohol less than hexanol less than octanol. The inhibition was reversible and correlated well with the known partitioning of the alcohols into lipids of biological membranes. Adipocyte membranes were labeled with the 5-nitroxide stearate spin probe to investigate the effects of the alcohols on the dynamic structure of membrane lipids of the adipocyte. The alcohols increased the membrane "fluidity", and the relative concentration dependence of the effects closely paralleled that noted from methanol to octanol in transport studies. Alcohols from methanol to hexanol caused inhibition of hexose transport at molar potencies comparable to that observed for membrane disordering. This suggests that hydrophobic regions of the transporter and its lipid environment are perturbed by a comparable mechanism for each alcohol. The cholesterol-complexing polyene antibiotic filipin inhibited hexose transport and influenced the mobility of lipid domains sampled with the nitroxide cholestane, cholesterol-like spin probe. The data are consistent with the concept that the membrane structural/functional effects are mediated by formation of 1:1 cholesterol:filipin complexes. Alcohols and filipin inhibited inherent transporter activity and perturbed the membrane lipid structure without dramatically diminishing transport stimulation by insulin above basal. The specific organization of membrane lipids (particularly cholesterol) may provide an essential environment for optimal transport system activity.

The outflow tract in pigmentary glaucoma: a light and electron microscopic study.

Buttons obtained by trephination from both eyes of a 44-year-old myopic man with pigmentary glaucoma were studied by light and electron microscopy. Although clinically both eyes exhibited heavy pigmentation of the trabecular meshwork in the whole circumference, microscopically the trabecular meshwork of the left eye contained more pigment granules than that of the right eye, which appeared relatively acellular with collapse of the trabecular sheets. In both eyes endothelial cells covering the trabecular sheets were filled with pigment and showed various stages of degeneration. The intertrabecular spaces contained free pigment granules as well as cell debris. These observations suggest that plugging of the trabecular spaces by pigment and cell debris together with fragmentation and collapse of trabecular sheets contribute to the decrease in the facility of outflow that occurs in pigmentary glaucoma.

Iris nodules in essential iris atrophy.

Seven cases are reported, believed to be the first in the literature, in which iris nodules are verified in the complete spectrum of essential iris atrophies. This feature appears late in the course of the disease as small yellow nodules that progressively increase in number and gradually become dark brown. The differential diagnosis of multiple iris nodules includes neurofibromatosis, melanomas, inflammatory nodules, and developmental anomalies such as iridocorneal dysgenesis.

Acetazolamide dosage forms in the treatment of glaucoma.

Patients with chronic glaucoma had a carefully scheduled series of intraocular pressure measurements before and after taking acetazolamide for one week at the following dosages: none, 500 mg of sustained-release capsules once a day, 500 mg of capsules twice a day, and 250 mg of tablets four times a day. A capsule taken once a day, which is better tolerated than one taken twice a day by some patients, offers a substantial pressure-lowering effect that lasts at least 23 hours, although the magnitude of the pressure lowering is less than with higher dosages. One capsule twice a day appears to be as effective in the regulation of IOP as one tablet four times a day. The 45% reduction in outflow pressure is achieved with an acetazolamide serum concentration in the range of 15 to 20 micrograms/mL.

Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels.

Rapid intraoperative choroidal effusion and flattening of the anterior chamber occurred during glaucoma filtering surgery in four young patients with prominent episcleral vessels, elevated episcleral venous pressure, and advanced open-angle glaucoma. Two of these four patients had Sturge-Weber syndrome. Intraoperative release of suprachoroidal fluid (SCF) through a posterior sclerotomy facilitated reformation of the anterior chamber and repositioning of the iris and ciliary body. Posterior sclerostomy performed prior to opening the anterior chamber minimized the above-mentioned untoward series of events. Analysis of SCF and serum demonstrated considerable differences in total protein and individual immunoglobulin levels; this appears to be a manifestation of molecular sieving at the level of the choriocapillaris. Choroidal detachment and postoperative serous retinal detachment are manifestation of this phenomenon.

The effect of anterior chamber depth on endothelial cell count after filtration surgery.

Eighteen patients undergoing glaucoma filtration surgery underwent specular microscopic examination 1 day prior to surgery and 4 to 6 months after surgery. Patients were evaluated postoperatively for the presence of iridocorneal or lenticular-corneal touch, anterior chamber depth, and inflammation. Ten eyes that maintained their anterior chamber following glaucoma filtration surgery did not have a significant decrease in corneal endothelial cell density. However, eight eyes that developed a shallow anterior chamber with iridocorneal touch had a mean (+/- SD) decrease of 265 +/- 185 cells (12.4%) peripherally and 250 +/- 243 cells (11.6%) centrally in corneal endothelial cell count. None of the patients with iridocorneal touch developed corneal edema after a mean follow-up of 44.4 +/- 18.0 months. Iridocorneal touch after glaucoma filtration surgery is associated with loss of endothelial cells yet appears to be well tolerated by the cornea.