Evaluation of the AMP SARS-CoV-2 rapid antigen test in a hospital setting.

OBJECTIVES: Quick and inexpensive SARS-CoV-2 screening and frontline testing are in growing demand. Our study aimed to evaluate the performance of the immunochromatographic AMP rapid antigen test (AMP RAT) compared to the gold-standard real-time reverse transcription PCR (rRT-PCR) in a hospital cohort. METHODS: A total of 392 patients, who presented consecutively with COVID-19 symptoms in our emergency department, were included in this retrospective study. Two swabs were collected per patient: a nasopharyngeal for the RAT and a combined naso- and oropharyngeal for the rRT-PCR. A positive rRT-PCR (defined as cycle threshold (Ct) < 40) was found in 94 (24%) patients. RESULTS: In our cohort with a median patient age of 70, overall sensitivity and specificity of the AMP RAT was 69.2% (58.8-78.3, 95% CI) and 99.7% (98.1-100.0, 95% CI), respectively. In patients with a Ct value < 25 and < 30, higher sensitivities of 100.0% (89.4-100.0, 95% CI) and 91.8% (81.9-97.3%, 95% CI) were observed. CONCLUSIONS: The AMP RAT showed a high sensitivity in patients with a Ct value < 25 and < 30 and might be helpful for frontline testing whenever rRT-PCR is not readily available.

Left ventricular hypertrabeculation/noncompaction associated with coronary heart disease and myopathy.

OBJECTIVES: The association of left ventricular hypertrabeculation (LVHT), also known as noncompaction, coronary heart disease, and metabolic myopathy, as presented in the following report, is rare. CASE REPORT: In a 77-yo male with a history of arterial hypertension, coronary heart disease, dilative cardiomyopathy, mitral and tricuspid insufficiency, AV-block III, implantation of a pacemaker, atrial fibrillation, and heart failure, LVHT was detected on transthoracic echocardiography during hospitalization for worsening heart failure. Clinical neurologic investigation, revealing bilateral ptosis, madarosis, absent eyelashes, bilateral hypacusis, sore neck muscles, generally absent deep tendon reflexes, weakness for foot extension, and ataxic stance, and recurrently elevated creatine-kinase with normal troponine, suggested a metabolic myopathy. Autopsy after death from intractable heart failure. 17 months later confirmed severe coronary heart disease and LVHT in the apex. CONCLUSIONS: LVHT may be associated with coronary heart disease and myopathy and may be exclusively located in the left ventricular apex.

Acquired noncompaction associated with coronary heart disease and myopathy.

In a 77-year-old man with a history of arterial hypertension, coronary heart disease, dilative cardiomyopathy, mitral and tricuspid insufficiency, arteriovenous block III, implantation of a pacemaker, atrial fibrillation, and heart failure, left ventricular hypertrabeculation (LVHT) was detected on transthoracic echocardiography during hospitalization for worsening heart failure. Revision of previous echocardiography did not show LVHT in any of the previous investigations why LVHT was interpreted as acquired. The additional presentation with bilateral ptosis, madarosis (absent eyelashes), bilateral hypoacusis, sore neck muscles, absent tendon reflexes, weakness for foot extension, ataxic stance, and recurrently elevated creatine kinase with normal troponin-T suggested a metabolic myopathy. Autopsy after death resulting from intractable heart failure, 17 months later, confirmed severe coronary heart disease and LVHT in the apex. The case confirms that LVHT may be acquired in single cases with neuromuscular disease and may represent an adaptive mechanism of an impaired myocardium.

Mutual associations between malignancy, age, gender, and subsite incidence of colorectal cancer.

BACKGROUND: A cross-sectional study was performed on a cohort of colorectal cancer (CRC) patients to reveal any influence of age, gender, and subsite on grades of malignancy. PATIENTS AND METHODS: Data from histopathological grading according to WHO criteria were pooled into groups of low-grade (well and moderately differentiated) and high-grade (poorly and undifferentiated) cancer and analyzed for associations. RESULTS: In general, women with CRC were significantly older than men (p<0.05). In particular, women with high-grade cancer in the proximal and distal colon had a median age of 75 years and were thus 10-15 years older (p<0.01 and p<0.05, respectively) than their male counterparts. In contrast, high-grade rectal cancer developed in both genders around the early age of 60 years. CONCLUSION: Women are protected from more aggressive cancer in the colon though not in the rectum until well after menopause. This likely reflects the differential sensitivity of the mucosa at these sites against the anticancer effects triggered by activation of estrogen receptor-beta.

Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer.

There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon cancer, we evaluated clock gene and estrogen receptor (ER) alpha/beta expression in colon cancer cells of primary colorectal tumors and adjacent normal colon mucosa (NM) by real-time RT-PCR. Analysis of gene expression in G(2) and G(3) colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G(2): 0.52-fold; P = n.s. and G(3): 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G(2) tumors as compared with NM (female: 0.38-fold; P = 0.004 vs. male: 0.73-fold; P = n.s.). Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G(2) and G(3) tumors (G(2): 0.32-fold; P = 0.003 and 0.27; P = 0.001). No significant gender specific differences of ER-beta reduction in tumors were observed. A significant correlation between the decrease of Per1 and ER-beta in colorectal tumors (r = 0.61; P < 0.001) was found. No changes in gene expression were detected for ER-alpha and Per2. Our data demonstrate a correlated decrease of Per1 and ER-beta in colorectal tumors, mediated probably by epigenetic mechanisms. The observed gender differences in the expression of CLOCK and Per1 in G(2) tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis.

Regulation of genes of the circadian clock in human colon cancer: reduced period-1 and dihydropyrimidine dehydrogenase transcription correlates in high-grade tumors.

Expression of dihydropyrimidine dehydrogenase (DPD) displays a regular daily oscillation in nonmalignant cells. In colorectal cancer cells, the expression of this 5-fluorouracil-metabolizing enzyme is decreased, but the reason remains unclear. In this study, we analyzed by real-time reverse transcription-PCR (RT-PCR) the expression of DPD and of members of the cellular oscillation machinery, period 1 (Per1), period 2 (Per2), and CLOCK, in primary colorectal tumors and normal colon mucosa derived from the same patients. Analysis of tumors according to differentiation grade revealed a 0.46-fold (P = 0.005) decrease for DPD mRNA and a 0.49-fold (P = 0.004) decrease for Per1 mRNA in undifferentiated (G3) tumors compared with paired normal mucosa. In this tumor cohort, the correlation between DPD and Per1 levels was r = 0.64, P < 0.01. In moderately differentiated (G2) colon carcinomas, reduction of DPD and Per1 mRNA levels did not reach significance, but a significant correlation between the respective mRNA levels was detectable (r = 0.54; P < 0.05). The decrease and correlation of DPD and Per1 mRNA levels were even more pronounced in female (G3) patients (DPD: female, 0.35-fold, P < 0.001 versus male, 0.58-fold, P < 0.05; and Per1: female, 0.47-fold, P < 0.01 versus male, 0.52-fold, P < 0.01). The highly significant correlation of DPD mRNA with Per1 mRNA expression suggests control of DPD transcription by the endogenous cellular clock, which is more pronounced in women. Our results also revealed a disturbed transcription of Per1 during tumor progression, which might be the cause for disrupted daily oscillation of DPD in undifferentiated colon carcinoma cells.

25-hydroxyvitamin D3-1alpha-hydroxylase expression in normal and malignant human colon.

1,25-dihydroxyvitamin D(3) has anti-mitotic, pro-differentiating, and pro-apoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D(3)-synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high- to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D(3) could prevent intestinal tumor formation and progression.

Molecular and functional characterization of the extracellular calcium-sensing receptor in human colon cancer cells.

Presence of a functional extracellular calcium-sensing receptor (CaR) is of particular relevance for the growth-inhibitory action of Ca2+ on human colon carcinoma cells. In order to detect CaR gene alterations that may have occurred during the tumorigenic process, we applied Southern blot, DNA sequence, and RT-PCR analysis to DNA from normal human colon mucosa and from cancerous lesions of different grading, as well as from primary cultured and established colonic carcinoma cell lines (e.g., Caco-2). No evidence was obtained for mutations or other sequence alterations in the CaR gene in any of the colon carcinoma cells analyzed. Only a differential expression of two splice variants of the CaR gene, which are generated by usage of different promoters in the 5'-untranslated region, was detected in colon carcinomas of different grade. From Western blot analysis a tendency towards lower CaR protein levels in carcinoma cells in parallel with tumor progression became apparent. Activation of the CaR by extracellular Ca2+ or by specific receptor agonists resulted in substantial growth inhibition in Caco-2 cells. Activation of the CaR was transduced into inhibition of phospholipase A2-mediated arachidonic acid formation, but also into increased production of cAMP and IP3. This provides evidence for a cell type-specific function of the CaR in human colonocytes. We conclude that neoplastic colon epithelial cells can respond to antimitogenic signals generated by activation of the CaR as long as they express sufficient amounts of the CaR protein. This provides a rationale for the use of calcium in chemoprevention of colon tumor development.