Search

Carboxymethyl starches are added to food products for thickening or tablet binding/filling purposes. Although they lack toxicity, their synthesis creates the chemical byproduct diglycolic acid (DGA), which is difficult to eliminate and whose toxicity is in question. A rare case of an accidental direct exposure to extremely high concentrations of DGA in a person revealed that DGA has the potential to be toxic to several organs, with the kidneys and liver being the most affected organs. Given that DGA is present in our food supply as a chemical byproduct of carboxymethyl starch food additives, we sought to perform in vitro testing of its potential hepatotoxicity to help complement a recent in vivo rat acute dose-response study that also tested for the potential hepatotoxic effects of daily DGA ingestion by oral gavage over a period of 28 days. Using the HepG2/C3A cellular in vitro model, we tested how escalating doses of DGA exposure over 24 h could induce hepatotoxicity. Both in vitro and in vivo testing systems revealed that DGA is indeed a hepatotoxin once a certain exposure threshold is reached. The concordance of these models highlights the utility of in vitro testing to support and help predict in vivo findings., (Published by Elsevier Ltd.)

Purpose: Studies suggest that subclinical hypothyroidism (SCH) is related to cardiovascular mortality (CVM). We explored the role of microalbuminuria (MIA) as a predictor of long-term CVM in population with and without SCH with normal kidney function., Materials and Methods: We examined the National Health and Nutrition Education Survey - III database (n = 6,812). Individuals younger than 40 years, thyroid-stimulating hormone levels ≥20 and ≤0.35mIU/L, estimated glomerular filtration rate <60mL/minute/1.73m 2 and urine albumin-to-creatinine ratio of >250mg/g in men and >355mg/g in women were excluded. SCH was defined as thyroid-stimulating hormone levels between 5 and 19.99mIU/L and serum T4 levels between 5 and 12µg/dL. MIA was defined as urine albumin-to-creatinine ratio of 17-250mg/g in men and 25-355mg/g in women. Patients were categorized into the following 4 groups: (1) no SCH or MIA, (2) MIA, but no SCH, (3) SCH, but no MIA and (4) both SCH and MIA., Results: Prevalence of MIA in the subclinical hypothyroid cohort was 21% compared to 16.4% in those without SCH (P = 0.03). SCH was a significant independent predictor of MIA (n = 6,812), after adjusting for traditional risk factors (unadjusted odds ratio = 1.75; 95% CI: 1.24-2.48; P = 0.002 and adjusted odds ratio = 1.83; 95% CI: 1.2-2.79; P = 0.006). MIA was a significant independent predictor of long-term all-cause (adjusted hazard ratio = 1.7, 95% CI: 1.24-2.33) and CVM (adjusted hazard ratio = 1.72, 95% CI: 1.07-2.76) in subclinical hypothyroid individuals., Conclusions: In a cohort of subclinical hypothyroid individuals, the presence of MIA predicts increased risk of CVM as compared to nonmicroalbuminurics with SCH. Further randomized trials are needed to assess the benefits of treating microalbuminuric subclinical hypothyroid individuals and impact on CVM., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1). Interestingly, in vitro KIM-1 levels also correlated with in vivo KIM-1 levels in urine collected from rats treated with DGA by daily oral gavage. The use of in vitro and in vivo models towards understanding the effectiveness of an established in vitro system to predict in vivo outcomes would be particularly useful in rapidly screening compounds that are suspected to be unsafe to consumers. The merit of the HK-2 cell model in predicting human toxicity and accelerating the process of food toxicant screening would be especially important for regulatory purposes. Overall, our study not only revealed the value of HK-2 in vitro cell model for nephrotoxicity evaluation, but also uncovered some of the mechanistic aspects of the human proximal tubule injury that DGA may cause.

The presentation of acute pulmonary thromboembolism (PE) can be highly variable resulting in diagnostic challenges and management difficulties. Current guidelines suggest that therapy must be adjusted based on the severity of PE presentation. Systemic thrombolysis is the standard therapy for acute massive PE; however, systemic thrombolysis carries an estimated 20% risk of major hemorrhage, including a 3% to 5% risk of hemorrhagic stroke. There are data supporting the use of catheter-directed therapy (CDT) in massive and submassive PE, but past studies have limited its use to patients in whom systemic thrombolysis has either failed or was contraindicated. There is a paucity of data comparing the efficacy of CDT compared to systemic thrombolysis in different risk groups. This review will summarize the available data on the techniques and indications and outcomes of CDT for acute PE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Catheter related thrombosis (CRT) is a commonly encountered entity fraught with substantial risk for mortality secondary to various complications including pulmonary embolism (PE), tricuspid regurgitation, endocarditis, right sided heart failure, and cardiogenic and septic shock. CRT carries a mortality rate of 18% in hemodialysis patients and more than 40% in nonhemodialysis patients. Management strategies include systemic anticoagulation, systemic thrombolysis, surgical evacuation, and percutaneous retrieval with no established guidelines. Ultrasound assisted catheter directed thrombolysis emerges as promising modality with a relatively lower risk of hemorrhage compared to systemic thrombolysis. We report a case of a 75-year-old man with dialysis catheter related thrombosis without PE for which ultrasound assisted catheter directed thrombolysis was used successfully as an alternative therapy.

The Impella LP 2.5 (Abiomed, Danvers, MA) has been a tool of use for high risk coronary procedures and for cardiogenic shock. As with any invasive or intracardiac device, improper placement can result in disastrous complications. Hemolytic anemia secondary to Impella implantation is one of the documented complications. However, cases of severe hemolytic anemia are rare in the literature. Proven imaging modalities like ultrasound need to be used to guide proper placement. We present a case of device induced severe hemolysis due to Impella insertion and the need to use ultrasound guidance to avoid such an unnecessary complication.

The use of interatrial septal occluder devices is an efficacious and less invasive alternative to open heart surgery for the repair of atrial septal defects. These devices present significant risks including thrombus formation on the device and subsequent thromboembolic events. We present a case of a woman who presented with stroke-like symptoms five years after PFO closure. The patient was subsequently found to have a thrombus on the occluder device. Our case highlights the risk of such thrombolic phenomenon and the risk associated with the device structure as a nidus for such a complication.

We describe a patient with a recent chest tube insertion leading to atrial fibrillation with rapid ventricular rate that led to multiple inappropriate internal cardiac defibrillator (ICD) shocks. This is the first reported case of this occurring in a patient with an ICD leading to inappropriate shocks. Our elderly patient with emphysema presented with a spontaneous pneumothorax and developed rapid atrial fibrillation following emergency tube thoracostomy. The patient had a single lead ICD and received multiple inappropriate shocks for the rapid ventricular rate in the therapy zone. Although medical treatment helped stabilize the patient, resolution of the atrial fibrillation occurred only after the chest tube was removed. In a patient with a chest tube or other intrathoracic catheters, maintaining a high index of suspicion that chest tube insertions can cause secondary life threatening cardiovascular complications needs to be considered. In such patients, removal of the device proves to be the most prudent treatment action.

Chromatin remodeling and activation of transcription are important aspects of gene regulation, but these often go awry in disease progression, including during colon cancer development. We investigated the status of global histone acetylation (by measuring H3, H4 acetylation of lysine residues, which also occur over large regions of chromatin including coding regions and non-promoter sequences) and expression of histone deacetylase 2 (HDAC2) in colorectal cancer (CRC) tissue microarrays using immunohistochemical staining. Specifically, HDAC2 and the acetylation of histones H4K12 and H3K18 were evaluated in 134 colonic adenomas, 55 moderate to well differentiated carcinomas, and 4 poorly differentiated carcinomas compared to matched normal tissue. In addition, the correlation between expression of these epigenetic biomarkers and various clinicopathological factors including, age, location, and stage of the disease were analyzed. HDAC2 nuclear expression was detected at high levels in 81.9%, 62.1%, and 53.1% of CRC, adenomas, and normal tissue, respectively (P = 0.002). The corresponding nuclear global expression levels in moderate to well differentiated tumors for H4K12 and H3K18 acetylation were increased while these levels were decreased in poorly differentiated tumors (P = 0.02). HDAC2 expression was correlated significantly with progression of adenoma to carcinoma (P = 0.002), with a discriminative power of 0.74, when comparing cancer and non-cancer cases. These results suggest HDAC2 expression is significantly associated with CRC progression.