Pediatric postmortem CT angiography: validation of vascular access for PMCT angiography in stillbirths, babies and toddlers.

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

COVID-19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection.

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.

Missed opportunities for ovarian salvage in children: an 8-year review of surgically managed ovarian lesions at a tertiary pediatric surgery centre.

INTRODUCTION: The aetiology and management of ovarian pathology in children differs between antenatal and postnatal lesions. However, all lesions may present acutely due to adnexal torsion. In this setting, opportunities to preserve fertility with ovary-sparing surgery (OSS) may be missed. Some studies suggest that pediatric and adolescent gynaecology (PAG) input in care is associated with OSS. METHODS: A retrospective cohort study of children undergoing surgery for ovarian pathology at a tertiary pediatric surgery centre over an 8-year period (2011-2018). Patient factors, lesion characteristics and PAG involvement were examined for association with OSS using multivariate logistic regression. RESULTS: Thirty-five patients with ovarian pathology managed surgically were included. Ten were infants with lesions detected antenatally; all were managed by pediatric surgeons (PS) alone at median age 2 weeks (1 day-25 weeks). Twenty-five patients presented postnatally at median age 11 (0.75-15) years. In total, there were 16 cases of adnexal torsion, each managed primarily by PS. Twelve underwent oophorectomy and six (50%) of these cases had viable ovarian tissue on histology. Furthermore, two infants with large simple cysts were similarly managed by unnecessary oophorectomy based on histology. Overall rate of OSS was 46% and PAG involvement was the only factor associated with ovarian salvage. CONCLUSION: Differences in surgical management between PAGs and PS may be attributable to the different patient populations they serve. We recommend improving the knowledge of PS trainees in OSS approaches for adnexal torsion and large benign lesions.

Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice.

Sleep disturbance is prevalent in cancer with detrimental effects on health outcomes. Sleep problems are seldom identified or addressed in cancer practice. The purpose of this review was to identify the evidence base for the assessment and management of cancer-related sleep disturbance (insomnia and insomnia syndrome) for oncology practice. The search of the health literature included grey literature data sources and empirical databases from June 2004 to June 2012. The evidence was reviewed by a Canadian Sleep Expert Panel, comprised of nurses, psychologists, primary care physicians, oncologists, physicians specialized in sleep disturbances, researchers and guideline methodologists to develop clinical practice recommendations for pan-Canadian use reported in a separate paper. Three clinical practice guidelines and 12 randomized, controlled trials were identified as the main source of evidence. Additional guidelines and systematic reviews were also reviewed for evidence-based recommendations on the assessment and management of insomnia not necessarily in cancer. A need to routinely screen for sleep disturbances was identified and the randomized, controlled trial (RCT) evidence suggests benefits for cognitive behavioural therapy for improving sleep quality in cancer. Sleep disturbance is a prevalent problem in cancer that needs greater recognition in clinical practice and in future research.

Mast cells in the human dura: effects of age and dural bleeding.

BACKGROUND: Animal studies have shown that the dura mater contains mast cells. We investigated the density of mast cells in the human dura mater, and the changes associated with subdural haemorrhage (SDH). METHODS: Samples of the human dura were stained with tryptase antibody and were examined for mast cells. We used control cases with no dural bleeding (n = 9) and cases of fresh (n = 24) and old (n = 18) dural haemorrhage. RESULTS: Mast cells were easily found in dural samples. The mean density in controls (11.05 cells per mm(2)) was less than that in fresh SDH (15.69), which was less than that in old SDH (23.09). CONCLUSIONS: Subdural haemorrhage is associated with an increase in dural mast cell density, and the density increases as the haematoma ages. We hypothesise that dural mast cells may contribute to neurogenic inflammation and the clinical features of subdural haemorrhage.

Developmental changes in human dural innervation.

INTRODUCTION: There is limited published work on the abundant innervation of the human dura mater, its role and responses to injury in humans. The dura not only provides mechanical support for the brain but may also have other functions, including control of the outflow of venous blood from the brain via the dural sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively large size in embryonic life suggests an importance in development; the earliest fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal functions vital to the fetus include the coordination of sucking and swallowing and the protective oxygen-conserving reflexes. Like other parts of the nervous system, the trigeminal undergoes pruning and remodelling throughout development. METHODS: We have investigated changes in the innervation of the human dura with age in 27 individuals aged between 31 weeks of gestation and 60 years of postnatal life. Using immunocytochemistry with antibodies to neurofilament, we have found significant changes in the density of dural innervation with age RESULTS: The density of innervation increased between 31 and 40 weeks of gestation, peaking at term and decreasing in the subsequent 3 months, remaining low until the sixth decade. CONCLUSIONS: Our observations are consistent with animal studies but are, to our knowledge, the first to show age-related changes in the density of innervation in the human dura. They provide new insights into the functions of the human dura during development.

Improvise, Adapt, Overcome: mobile phone LED used as a light source for cystoscopy and resection of posterior urethral valves in a low-cost setting.

We describe use of an improvised light source to perform cystoscopy and PUV resection while working in a resource poor setting. The light emitted from a mobile telephone LED (iPhone 6) was sufficient to perform the procedure and there was an excellent surgical outcome. We hope that this report may prove to be helpful to colleagues working in similar circumstances with limited resources.

Trading treatment toxicity for survival in locally advanced non-small cell lung cancer.

PURPOSE: To determine how patients weigh potential survival benefits against the potential toxicity of different treatment strategies for locally advanced non-small cell lung cancer (NSCLC). Specifically, we were interested in what improvement in survival probability patients would want to have before accepting more toxic therapy. PATIENTS AND METHODS: Fifty-six outpatients who had experienced lung cancer (n = 22) or prostate cancer (n = 34), and 20 clinic nurses and radiation therapy technologists participated. A treatment trade-off interview was conducted with each participant that compared low-dose versus high-dose radiotherapy and high-dose radiotherapy versus combination chemo-radiotherapy. Preferences for treatments were assessed by systematically increasing the hypothetical survival advantage of the more toxic treatment until the person reached his or her threshold for choosing the more toxic treatment. RESULTS: A wide range of thresholds was observed for both groups. The distributions of survival advantage thresholds for lung cancer and prostate cancer patients were not significantly different but were generally lower thresholds than those declared by staff. If the 3-year survival advantage was 10%, 60% of patients and 15% of staff would consider combination therapy over high-dose radiotherapy. Within patients, apparent willingness to consider more toxic treatments was not significantly related to age, sex, education, or preferred role in decision making. The treatment trade-off method had good test-retest reliability. CONCLUSION: There is great interindividual variability in willingness to accept aggressive treatments for locally advanced NSCLC. When choosing NSCLC treatment, each patient should be provided with comprehensive information about the options so that he or she may express his or her preferences should he or she wish to participate in the decision.

Decision analysis in locally advanced non-small-cell lung cancer: is it useful?

PURPOSE: The optimal management of locally advanced non-small-cell lung cancer (NSCLC) has not been established. While combined-modality treatments have been shown to increase the survival of patients with this illness, the appropriate balance between the benefit of increased quantity of life and the quality-of-life costs of the more toxic treatment combinations remains unresolved. Decision analysis has been promoted as useful when medical decisions must be made under conditions of uncertainty. We consider the potential of this method to guide therapy in locally advanced NSCLC. METHODS: We developed two types of decision models that addressed the choice between radiation alone and combined chemotherapy-radiation therapy in locally advanced NSCLC. The models were constructed using the principles of decision analysis. RESULTS: The models successfully replicated results of relevant clinical trials published in the literature. The analyses of both models showed that the treatment decision was sensitive to patients' values, despite significant increases in survival rates. The models clarified a need for further validation of the three fundamental components: structuring the decision, determining the probabilities of events, and assigning utilities to treatment outcomes. CONCLUSION: In the setting of NSCLC, the models suggest that quality-of-life considerations are important in the treatment choice. Further research is required to identify the health states critical to the decision, the probabilities for occurrence of these health states, and valid measures of their utility.

An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.

Isocarboxazid and placebo were evaluated in 130 anxious depressives. Drug was superior to placebo on depression, anxiety, interpersonal sensitivity, and global measures, and on symptoms of hostility, anxiety, obsessiveness, and psychological-cognitive components of depression. There were no significant differences between treatment effects on psychomotor and typical vegetative symptoms. Isocarboxazid was more effective than placebo in major, but not in minor, depression. It was significantly more effective in depression classified as endogenous depression or melancholia by various diagnostic criteria. Drug was more effective than placebo in atypical depression with vegetative reversal and in Brief Psychiatric Rating Scale (BPRS)-derived profiles of anxious and hostile depression; there were no drug-placebo differences in atypical depression without vegetative reversal, or in BPRS retarded and agitated/excited depression. Interpersonal sensitivity emerged as an important drug-responsive dimension.

Psychotropic drugs on general medical and surgical wards of a teaching hospital.

We examined the prescribing habits for psychotropic drugs of internists, surgeons, and gynecologists on their inpatient wards in a teaching hospital. Data were gathered from patients' charts and pharmacy records. In a six-week period, 9% of all admissions received such a drug. The male:female ratio and black:white ratios were studied; the maximum incidence of receiving these medications was in the 50- to 60-year age group. Minor tranquilizers were prescribed most frequently, followed, respectively, by major tranquilizers, barbiturates, and antidepressants. Less than half the available drugs were used, but drugs of differernt groups were often used interchangeably in an unsystematic fashion, and there was little evidence as to how effective a drug had been. It also seemed that depression was often overlooked or insufficiently treated.

The boundary of social phobia. Exploring the threshold.

BACKGROUND: Individuals with subthreshold social phobia (SSP) in the community are characterized relative to nonphobic, healthy controls (C), and diagnosed social phobics (SP). METHODS: Data from 1488 subjects from the Duke University Epidemiological Catchment Area Study were examined. Bivariate and multivariate methods were used to compare the SSP, SP, and C groups on 10 sets of variables. RESULTS: Compared with C respondents, SSP respondents were more likely to be female and unmarried and to report less income and education. The SSP respondents were also more likely to report work attendance problems, poor grades in school, symptoms of conduct disturbance, impaired subjective social support, lack of self-confidence, lack of a close friend, use of psychotropic drugs in past year, and a greater number of life changes, chronic medical problems, and mental health visits within the past 6 months. In a multivariate logistic regression model with group membership as the dependent variable, compared with C respondents, SSP respondents were more likely to be female, to have less education, and to report more indicators of poor school performance and symptoms of adolescent conduct disturbance. In contrast, in a similar but separate multivariate model, compared with SP respondents, SSP respondents met the criteria for fewer DSM-III psychiatric disorders and were less likely to report impaired instrumental support. CONCLUSION: Social phobia adversely affects over 10% of the population. Previous epidemiologic catchment area-based prevalence estimates have probably been unrealistically low.

Platelet monoamine oxidase activity and the classification of depression.

An attempt was made to compare platelet monoamine oxidase (MAO) activity in descriptively based types of nonbipolar depression. Platelet MAO activity was significantly higher in depression secondary to chronic anxiety, compared with primary unipolar depression and depression secondary to borderline personality, and in women compared with men. No significant differences were observed between endogenous-nonendogenous, delusional-nondelusional, psychomotor states, or different age groups.

Atypical depression.

The term atypical depression generally indicates either depression accompanied by severe anxiety (type A) or by atypical vegetative symptoms, ie, increased appetite, weight, sleep, or libido (type V). Early age at onset, predominance in women, outpatient status, mild intensity, rarity of attempted suicide, nonbipolarity, nonendogenicity, and minimal psychomotor change are common to both types. Some types of bipolar depression may be considered as atypical if accompanied by reversed vegetative change. Monoamine oxidase inhibitors are more effective than placebo in treating atypical depression, but their reported superiority to tricyclic antidepressants awaits confirmation, for which the development of appropriate operational criteria would be helpful. Atypical depression is a term that covers several types of depressive disorder and can, for the most part, be better defined using the standard nomenclature.

The association of sexual assault and attempted suicide within the community.

BACKGROUND: Lifetime community rates of attempted suicide were compared between those who reported a history of sexual assault and a control group without such a history. METHODS: The 2918 respondents in the Duke University Epidemiological Catchment Area Study were placed into groups with reported sexual assault (n = 67) and those with no known history of such (n = 2851). Multivariate and bivariate procedures were used to examine the relation between sexual assault and attempted suicide. RESULTS: Subjects reporting a history of sexual assault were more likely to be female, younger, and to report higher rates of lifetime suicide attempt and post-traumatic stress symptoms; no differences were found in the number of chronic medical disorders, major depression, substance abuse or substance dependence, or panic attacks. Nine (14.9%) of the 67 index group subjects reported a suicide attempt, 4 of whom reported their first sexual assault as occurring before age 16 years. A sexual assault history was associated with increased prevalence of lifetime suicide attempt after controlling for sex, age, education, posttraumatic stress symptoms, and psychiatric disorder. Findings were similar in the female-only subsample (n = 1778). For women, the odds of attempting suicide was 3 to 4 times greater when the first reported sexual assault occurred prior to age 16 years compared with age 16 years or older. CONCLUSIONS: Sexual assault is associated with an increased lifetime rate of attempted suicide. In women, a history of sexual trauma before age 16 years is a particularly strong correlate of attempted suicide.

Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported. METHODS: Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings. RESULTS: Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%). CONCLUSION: The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD.

Acquisition of quality gamma-ray spectra with HPGe spectrometers.

We propose practices to optimize the quality of acquired gamma-ray spectra at a radioanalytical laboratory and to assist in the identification of extraneous spectral peaks including those from limitations in the physical setup, electronics, and counting conditions. This paper offers visible comparisons of high-quality spectra with those of inferior quality. We demonstrate the impacts on gamma-ray spectra taken with germanium (HPGe) detectors due to detector size, shape and energy resolution, background radiation, high-energy beta- or beta+ decay in the sample, beta(-)-, beta(+)- and gamma-ray backscatter, pole-zero cancellation, pulse pileup, coincidence summing, and unwanted sources of radiation.

Generalized anxiety disorder: neurobiological and pharmacotherapeutic perspectives.

The concept of generalized anxiety has evolved over many years, from initial descriptions of "anxiety neurosis" to recognition of generalized anxiety disorder (GAD) as a clinical entity included in the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980. Since 1980, the definition of GAD has undergone further change, with modifications in the salience of autonomic and panic like symptoms, duration, and allowance of comorbidity. The importance of these historical considerations lies in the fact that most of our current knowledge about GAD rests on outdated definitions, including most of the literature pertaining to treatment. Indeed, we cannot be sure that the DSM-III definition of GAD bears resemblance to the current concept, and these differences may have profound implications for findings from research. The following two-part report comprises i) a review of the basic neurobiology of GAD, with reference to serotonergic, noradrenergic, neuroendocrine, autonomic imaging, and other systems; and ii) an overview of the current status of pharmacotherapy for GAD.

Diagnostic utility of the dexamethasone suppression test.

This article discusses the current controversy surrounding the diagnostic utility of the Dexamethasone Suppression Test, addresses the questions raised by the recent editorial by Ross in this journal, discusses the general principles behind the development of tests, and estimates their diagnostic utility. This discussion aims to clarify some aspects of the controversy. It presents an operational analysis of the Dexamethasone Suppression Test as utilized at a state hospital. This operational analysis shows that the test may be useful in distinguishing schizophrenia from psychotic depression, and mania from schizophrenia. Furthermore, it shows that the test is not useful as a screening test. These results are compared with those obtained by other investigators. The authors further show how test results can be used rationally by clinicians by so-called threshold analysis. Clinical data from a state hospital are used to illustrate this.