Role of demographics in non-invasive testing for colorectal cancer screening: do targeted cut-off values improve detection?

BACKGROUND: Fecal immunochemical test (FIT) is a yearly alternative colorectal screening modality for average risk individuals unwilling or unable to undergo invasive colorectal cancer (CRC) screening due to cost and accessibility. This study aims to determine whether FIT should be interpreted within the context of patient demographics and medical history. METHODS: Patients >50 years old who had a FIT followed by colonoscopy within 1 year were analyzed based on age, race, BMI, social and medical comorbidities. False positive (FP) and false negative (FN) FIT results within each patient demographic and medical history variable were determined by comparing with the gold standard of colonoscopy using Chi-square analysis. RESULTS: 1025 patients were reviewed. 21.8% of FIT results were positive. Factors which differed in positive FIT rates were age (p=0.003), smoking (p<0.001), alcohol (p=0.001), and hypertension (p<0.001). The difference in rates of FP and FN FIT outcomes among each variable underwent further sub-analysis. The FP was 66.8% and the FN rate was 12.8%. Higher FN outcomes were noted in those above 70, males and smokers, though the result was only statistically significant for males (p=0.009). Females were observed to have higher FP rates (p=0.019). CONCLUSIONS: Females had higher FP FIT rates compared to males, indicating that sex may influence FIT outcomes and should be accounted for when interpreting FIT results. This information can be utilized to identify populations at higher risk of FP or FN FIT results to target CRC screening. Additionally, recalculating the FP and FN rates for each variable may help determine new FIT targets.

Cell therapy strategies for COVID-19: Current approaches and potential applications.

Coronavirus disease 2019 (COVID-19) continues to burden society worldwide. Despite most patients having a mild course, severe presentations have limited treatment options. COVID-19 manifestations extend beyond the lungs and may affect the cardiovascular, nervous, and other organ systems. Current treatments are nonspecific and do not address potential long-term consequences such as pulmonary fibrosis, demyelination, and ischemic organ damage. Cell therapies offer great potential in treating severe COVID-19 presentations due to their customizability and regenerative function. This review summarizes COVID-19 pathogenesis, respective areas where cell therapies have potential, and the ongoing 89 cell therapy trials in COVID-19 as of 1 January 2021.

Low yield of head CT in cirrhotic patients presenting with hepatic encephalopathy.

GOALS AND BACKGROUND: The utility of routine head CT (HCT) in hepatic encephalopathy (HE) evaluation is unclear. We investigated HCT yield in detecting acute intracranial abnormalities in cirrhotic patients presenting with HE. STUDY: Retrospective review of cirrhotic patient encounters with HE between 2016 and 2018 at Beaumont Health, in Michigan was performed. A low-risk (LR) indication for HCT was defined as altered mental status (AMS), which included dizziness and generalised weakness. A high-risk (HR) indication was defined as trauma/fall, syncope, focal neurological deficits (FNDs) or headache. Descriptive statistics and univariate/multivariate analyses by logistic regression were performed using SPSS to identify HCT abnormality correlates. RESULTS: Five hundred twenty unique encounters were reviewed. Mean age was 63.4 (12.1) years, 162 (37.5%) had alcoholic cirrhosis and median Model for End-Stage Liver Disease (MELD)-score was 17 (13-23). LR indication was reported in 408 (78.5%) patients and FNDs reported in 24 (4.6%) patients. Only 13 (2.5%) patients were found to have an acute intracranial pathology (seven haemorrhagic stroke, two ischaemic stroke, four subdural haematoma). Aspirin use prior to presentation (aOR 4.6, 95% CI 1.1 to 19.2), and HR indication (aOR 7.3, 95% CI 2.3 to 23.8) were independent correlates of acute intracranial pathology on HCT. Age, sex, MELD-score, haemoglobin, platelet count, race and cirrhosis aetiology did not correlate with HCT abnormalities. Number needed to screen to identify one acute pathology was 14 in HR indications versus 82 for LR indications. CONCLUSION: Routine HCTs in cirrhotic patients presenting with HE with AMS in the absence of history of trauma, headache, syncope, FNDs or aspirin use is of low diagnostic yield.

Hypercalcemia of Malignancy and Acute Pancreatitis.

OBJECTIVES: Hypercalcemia of malignancy confers a poor prognosis. This systematic review evaluated published cases of hypercalcemia of malignancy presenting with acute pancreatitis (AP), in terms of clinical presentation and outcomes. METHODS: A comprehensive review of PubMed and Embase until March 18, 2020, was conducted. Studies were included if they reported on patients with hypercalcemia of malignancy and AP with attempts to exclude other etiologies of hypercalcemia and AP. Two independent reviewers selected and appraised studies using the Murad tool. RESULTS: Thirty-seven cases were identified. Mean (standard deviation) age was 44.8 (2.46) years. Mean (standard deviation) presenting corrected calcium was 14.5 (0.46) mg/dL. Parathyroid carcinoma (21.6%) and multiple myeloma (21.6%) were the most common malignancies. Cases were classified as severe (37.8%), mild (21.6%), and moderately severe (18.9%), whereas 21.6% did not report severity. Necrotizing pancreatitis developed in 21.6% of cases. Most cases were treated with intravenous hydration and bisphosphonates or calcitonin/calcitonin analogues. Mortality was 32.4% during the same presentation of AP. Among mortality cases, 10 of 12 had severe AP, and 5 of 12 had necrotizing pancreatitis. Degree of hypercalcemia did not influence mortality. CONCLUSION: Acute pancreatitis associated with hypercalcemia of malignancy is rare. One in 3 patients with this presentation may not survive AP.

Cholestatic Hepatitis in Graves' Disease: A Diagnostic Challenge.

Cholestatic hepatitis is a rare presentation of thyrotoxicosis potentially confused as an adverse effect of antithyroid therapy. We report a 37-year-old man with cholestatic hepatitis as an initial presentation of Graves' disease. Diagnostic evaluation demonstrated (i) elevated transaminases and alkaline phosphatase (R-factor value: 2.6), and marked cholestasis (total bilirubin: 17.3 mg/dL, direct bilirubin: 9.4 mg/dL); (ii) negative hepatitis, viral, and autoimmune serologies; (iii) normal magnetic resonance cholangiopancreatography; (iv) liver biopsy with marked cholestasis and no fibrosis; (v) thyroid-stimulating hormone <0.01, fT4 (free thyroxine): 1.5, fT4 (free triiodothyronine): 4.3 and positive thyroid-stimulating immunoglobulins. Radioiodine uptake scan confirmed Graves' disease. Clinical resolution was achieved with propranolol, prednisone, methimazole, and thyroidectomy.

Multiple liver abscesses caused by S treptococcus intermedius bacteremia in the setting of a routine dental cleaning.

Streptococcus intermedius is a Gram-positive cocci, normally found in the oral cavity and gastrointestinal tract. It has been associated with deep-seated purulent abscesses commonly in the brain or liver in immunocompromised patients. Here, we discuss the case of a 21-year-old immunocompetent patient that presented with septic shock in the setting of multiple pyogenic liver abscesses with positive blood cultures for S. intermedius The patient had a dental cleaning 3 months prior to admission. The abscesses resolved with ultrasound guided drainage and antibiotic therapy.

Early life stress increases testosterone and corticosterone and alters stress physiology in zebra finches.

Early life stress has enduring effects on behavior and physiology. However, the effects on hormones and stress physiology remain poorly understood. In the present study, parents of zebra finches of both sexes were exposed to an increased foraging paradigm from 3 to 33days post hatching. Plasma and brains were collected from chicks at 3 developmental time points: post hatching days 25, 60 and adulthood. Plasma was assayed for testosterone (T), estradiol (E2), and corticosterone (CORT). The paraventricular nucleus of the hypothalamus was assessed for corticotrophin releasing factor (CRH) and glucocorticoid receptor (GR) expression. As expected, body mass was lower in nutritionally stressed animals compared to controls at multiple ages. Nutritionally stressed animals overall had higher levels of CORT than did control and this was particularly apparent in females at post hatching day 25. Nutritionally stressed animals also had a higher number of cells expressing CRH and GR in the paraventricular nucleus of the hypothalamus than did controls. There was an interaction, such that both measures were higher in control animals at PHD 25, but higher in NS animals by adulthood. Females, regardless of treatment, had higher circulating CORT and a higher number of cells expressing CRH than did males. Nutritionally stressed animals also had higher levels of T than did control animals, and this difference was greatest for males at post hatching day 60. There were no effects of nutritional stress on E2. These findings suggest that nutritional stress during development has long-lasting effects on testosterone and stress physiology.