Report of 5146 Cases of Coronavirus Disease 2019-Related Mortality From Cook County, Illinois Causes of Death, Demographics, and Comorbidities.

ABSTRACT: A cross-sectional study used 5216 laboratory-confirmed coronavirus disease 2019 (severe acute respiratory syndrome coronavirus 2)-related mortality cases in Cook County of Illinois. The data set included each case's demographic data, manner of death, and comorbidities. The age ranged from 0 to 108 years, with a median of 73.5 years. There were few mortality cases in the age group younger than 30 years, and the incidence of fatal infection increased with age. We demonstrated an increased incidence of mortality in males compared with females (P < 0.01). The urban population had a higher incidence of fatal infection than the suburban population (P < 0.01). We found a significant increase (P < 0.01) in the incidence of fatal coronavirus disease 2019 (severe acute respiratory syndrome coronavirus 2) infection in African American males compared with background frequencies. Latino population demonstrated younger ages at death compared with the non-Latino population. Obesity and hypertension significantly predict fatal outcomes in the younger age group. In comparison, dementia and hypertensive and arteriosclerotic cardiovascular disease are significant predictive factors in the older age group. In a large data set, we demonstrated that the demographical distribution of the population and comorbidities is associated with the risk of fatal complications and death.

Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

INTRODUCTION: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.

Use of stimulants, over-the-counter and prescription drugs among Danish pregnant women.

Using self-reports and blood samples from 225 unselected Danish first trimester pregnant women, the purpose of this study was to assess their use of stimulants, for example caffeine and nicotine as well as over-the-counter (OTC) and prescription drugs. According to self-reported information, 24% had used prescription drugs and 48% had used OTC drugs mainly acetaminophen (42%), 9.3% were habitual smokers, 44% stated a daily use of caffeinated beverages, and 1.3% used illegal drugs. Ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-HR-TOFMS) analysis was performed on corresponding blood samples applying golden standards for use of UPLC-HR-TOFMS in forensic medicine. Traces of prescription drugs were detected in 5.3% of the samples and 8.9% contained OTC drugs (acetaminophen 7.1%). Traces of smoking were identified in 8.0%, caffeine in 83% and illegal drugs in 0.9%. These results indicate a substantial use of OTC drugs and caffeine among Danish pregnant women. Blood analysis indicated that many women could be unaware of their caffeine intake. As common substances may be associated with adverse pregnancy outcomes, healthcare professionals should inquire about such habits during pregnancy. The results also underline the need for more research into the molecular effects of such drugs on placental function and foetal development.

Use of alternative medicine, ginger and licorice among Danish pregnant women - a prospective cohort study.

BACKGROUND: The use of alternative medicines and dietary supplements is constantly changing, as are dietary habits. One example of this phenomenon is the current popularity of ginger products as an everyday health boost. Ginger and licorice has also been shown to ameliorate nausea a common complaint in early pregnancy. Alternative medicines are often regarded as safe. However, they might affect fetal development, such as through alterations of hormone metabolism and cytochrome P450 function. Health care professionals may be unaware of the supplementation habits of pregnant women, which may allow adverse exposures to go unnoticed, especially if the rates of use in pregnancy are not known. We therefore investigated the use of alternative medicines and licorice among pregnant Danish women. METHODS: A total of 225 pregnant women were included in a prospective cohort when attending the national prenatal screening program at gestational weeks 10-16. Participants were asked to complete a questionnaire regarding their socio-economic status and lifestyle habits, including their intake of alternative medicine and licorice. RESULTS: We found that 22.7% of women reported taking alternative medicines, with 14.7% reporting daily consumption. Ginger supplements were consumed by 11.1%, mainly as health boost and 87.1% reported consumption of licorice. Regular or daily licorice consumption was reported by 38.2 and 7.1%, respectively. Notably, the use of licorice was reflected by an increase in blood pressure of the pregnant women. CONCLUSIONS: The use of licorice and alternative medicines appears to be common in pregnant Danish women, supporting the need for further investigations into the safety of alternative medicine use during pregnancy and the importance of up-to-date personalized counseling regarding popular health trends and lifestyle habits.

Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition.

Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition.

Prevalence of xenobiotic substances in first-trimester blood samples from Danish pregnant women: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence of xenobiotic substances, such as caffeine, nicotine and illicit drugs (eg, cannabis and cocaine), in blood samples from first-trimester Danish pregnant women unaware of the screening. DESIGN: A cross-sectional study examined 436 anonymised residual blood samples obtained during 2014 as part of the nationwide prenatal first-trimester screening programme. The samples were analysed by ultra performance liquid chromatography with high-resolution time-of-flight mass spectrometry. SETTING: An antenatal clinic in a Danish city with 62 000 inhabitants, where >95% of pregnant women joined the screening programme. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence and patterns of caffeine, nicotine, medication and illicit drug intake during the first trimester of pregnancy. RESULTS: The prevalence of prescription and over-the-counter drug detection was 17.9%, including acetaminophen (8.9%) and antidepressants (3.0%), of which citalopram (0.9%) was the most frequent. The prevalence of illegal drugs, indicators of smoking (nicotine/cotinine) and caffeine was 0.9%, 9.9%, and 76.4%, respectively. Only 17.4% of women had no substance identified in their sample. CONCLUSIONS: This study emphasises the need for further translational studies investigating lifestyle habits during pregnancy, as well as the underlying molecular mechanisms through which xenobiotic substances may affect placental function and fetal development.

Manner of Death Certification After Significant Emotional Stress: An Inter-Rater Variability Study and Review of the Literature.

Not commonly seen, the risk of sudden death after significant emotional stress has been reported since antiquity and incorporated into folk wisdom, reflected by phrases such as "scared to death" and "broken heart." A typical "victim" suffers from significant and often life-threatening natural diseases, making determination of the manner of death complicated, and at times controversial. The present study is designed to assess inter-rater variability and nonuniformity and controversy seen in manner of death certification in certain cases of death with significant stress involved in the circumstances of death. Members of the National Association of Medical Examiner (NAME) were surveyed to assess differences in manner of death certification for eight sudden unexpected death scenarios in middle-aged men and women with underlying cardiac disease after significant stressful events including: being chased down a lonely road followed by a verbal confrontation, a roll-over motor vehicle collision (MVC) without injuries, a fall from a wheelchair in a MVC, an alleged armed robbery, an involuntary commitment, an arrest by police, sexual intercourse, and a severe panic attack with breathing problems. In all cases, the autopsy examination revealed hypertensive and arteriosclerotic cardiovascular disease. In all cases, natural diseases were identified as significant contributing condtions, including emphysema in six cases and diabetes mellitus in three. Eighty-six responses were collected. The results show wide inter-rater variability, ranging from very good to poor (Kappa ranges from 0.16 to 0.94). One hundred fifty-five comments were collected. Most of the comments addressed more than one topic and were followed by discussions, open questions, and responders' experiences with previous cases and legal proceedings. Our data show that cases of sudden death after significant stress have almost complete agreement in four cases and very high inter-rater variability in the other four. We propose that a detailed analysis of each case and an algorithmic approach could improve the predictability of the outcomes of death investigations for the legal system and for families.

DNA and RNA analysis of blood and muscle from bodies with variable postmortem intervals.

The breakdown of DNA and RNA in decomposing human tissue represents a major obstacle for postmortem forensic molecular analysis. This study investigated the feasibility of performing PCR-based molecular analysis of blood and muscle tissue from 45 autopsy cases with defined postmortem intervals ranging from one to more than 14 days. It was not possible to collect blood from 38 % of the autopsy cases due to severe coagulation and hemolysis, whereas muscle tissue was available for all cases. PCR-amplifiable DNA could be extracted from 96 % of the frozen muscle specimens and from 93 % of the formalin fixed and paraffin embedded (FFPE) muscle specimens. A quality assessment of muscle-derived DNA showed increased fragmentation with advancing body decomposition and generally more fragmentation in DNA from FFPE tissue than in DNA from frozen tissue. It was possible to amplify 1,000 basepair (bp) DNA fragments from all samples with postmortem intervals below 3 days whereas 400-600 bp long fragments typically could be amplified from the most decomposed muscle specimens. RNA was less stable than DNA in postmortem muscle tissue, yet selected mRNA molecules could be detected by reverse-transcriptase PCR in all samples up to 3 days after death. We conclude that analysis of DNA from bodies with a wide postmortem interval range is usually possible whereas the consistency of RNA analyses decreases considerably 3 days postmortem. We showed that muscle tissue is a highly usable source of DNA and RNA for postmortem forensic molecular analysis as well as for retrospective research projects based on archived FFPE specimens.

Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma.

Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18, is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin embedded (FFPE) sections of cervical cancer.Tissue blocks from 35 cases of in situ or invasive cervical squamous cell carcinoma and surrogate FFPE sections containing the cell lines HeLa and SiHa were tested for HPV 16 and HPV18 by conventional PCR using type specific primers, and for the housekeeping gene beta-actin. Using HPV 16 E7 primers, PCR products with the expected length were detected in 18 of 35 of FFPE sections (51%). HPV 18 E7 specific sequences were detected in 3 of 35 FFPE sections (9%).In our experience, the PCR technique is a robust, simple and sensitive way of type specific detection of HPV16 and HPV18 genes in FFPE tissue. That makes this technique applicable to routine practices of HPV detection.

HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens.

Published studies have reported widely variable incidence of HER2/neu (c-erbB-2) protein expression and HER2/neu (c-erbB-2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde-fixed paraffin-embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her-2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia.

p16 as a diagnostic marker of cervical neoplasia: a tissue microarray study of 796 archival specimens.

BACKGROUND: To evaluate the usefulness of this biomarker in the diagnosis of cases of cervical neoplasia we studied the immunohistochemical expression of p16INK4a in a large series of archival cervical biopsies arranged into tissue microarray format. METHODS: TMAs were constructed with tissue cores from archival formalin fixed, paraffin-embedded donor tissues from 796 patients, and included cases of cervical intraepithelial neoplasia (CIN)1 (n = 249), CIN2 (n = 233), CIN3 (n = 181), and invasive cervical carcinoma (n = 133). p16INK4a expression was scored using two different protocols: 1) positive vs negative p16INK4a staining; 2) a semi-quantitative immunohistochemical score (0 to 8 points) according to the intensity of staining and the proportion of stained cells RESULTS: p16INK4A expression was not seen in normal cervix tissue, but was found with increasing frequency in the sequence: CIN1 (180/249; 72.3%) - CIN2 (212/233; 91.0%) - CIN3 (178/181; 98.3%) - invasive carcinoma (131/133; 98.5%). Using semi-quantitative scoring, all normal cervical samples had low scores (from 0 to 2 points), whilst the number of specimens with high scores was proportional to the degree of cervical dysplasia or the presence of invasive carcinoma. CONCLUSION: Immunohistochemical analysis of p16INK4a expression is a useful diagnostic tool. Expression is related to the degree of histological dysplasia, suggesting that it may have prognostic and predicative value in the management of cervical neoplasia.

Squamous cell carcinoma of the nasal vestibule 1993-2002: a nationwide retrospective study from DAHANCA.

BACKGROUND: A retrospective nationwide study of cancer of the nasal vestibule was conducted to evaluate classification systems and prognostic factors for treatment outcome. METHODS: Patients treated between 1993 and 2002 at head and neck oncology centers in Denmark were included. RESULTS: The 5-year results were locoregional control 67%, overall survival 50%, cancer-specific survival 74%. Cancer-specific survival according to Wang classification was 83%, 63%, and 39% for T1, T2, T3, respectively (p < .000). Regarding T1 tumors, 5-year locoregional control for surgery, surgery + radiotherapy (RT), or RT was 94%, 87%, or 61%, respectively (p < .000). Fifty-four Gray in 18 fractions was found comparable with 66 Gy in 33 fractions regarding T1 tumors. CONCLUSION: This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach.