Modified hydra bioassay to evaluate the toxicity of multiple mycotoxins and predict the detoxification efficacy of a clay-based sorbent.

Food shortages and a lack of food supply regulation in developing countries often leads to chronic exposure of vulnerable populations to hazardous mixtures of mycotoxins, including aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)). A refined calcium montmorillonite clay [i.e. uniform particle size NovaSil (UPSN)] has been reported to tightly bind these toxins, thereby decreasing bioavailability in humans and animals. Hence, our objectives in the present study were to examine the ability of UPSN to bind mixtures of AFB(1) and FB(1) at gastrointestinally relevant pH in vitro, and to utilize a rapid in vivo bioassay to evaluate AFB(1) and FB(1) toxicity and UPSN efficacy. Isothermal sorption data indicated tight AFB(1) binding to UPSN surfaces at both pH 2.0 and 6.5, but substantially more FB(1) bound at pH 2.0 than 6.5. Site-specific competition occurred between the toxins when exposed to UPSN in combination. Importantly, treatment with UPSN resulted in significant protection to mycotoxin-exposed hydra maintained at pH 6.9-7.0. Hydra were exposed to FB(1), AFB(1) and FB(1) /AFB(1) combinations with and without UPSN. A toxic response over 92 h was rated based on morphology and mortality. Hydra assay results indicated a minimum effective concentration (MEC) of 20 µg ml(-1) for AFB(1), whereas the MEC for FB(1) was not reached. The MEC for co-exposure was 400 µg ml(-1) FB(1) + 10 µg ml(-1) AFB(1). This study demonstrates that UPSN sorbs both mycotoxins tightly at physiologically relevant pH levels, resulting in decreased bioavailability, and that a modified hydra bioassay can be used as an initial screen in vivo to predict efficacy of toxin-binding agents.

Pulmonary Vein Flow Morphology After Transcatheter Mitral Valve Edge-to-Edge Repair as Predictor of Survival.

BACKGROUND: Data on the prognostic factors after mitral valve (MV) transcatheter edge-to-edge repair (TEER; MV-TEER) are limited. Pulsed-wave Doppler interrogation of pulmonary vein flow (PVF) is a convenient method to assess the hemodynamic burden of residual mitral regurgitation (MR), which could be of utility as a predictor of outcomes. METHODS: Patients that underwent MV-TEER between May 2014 and December 2021 at our institution were evaluated. Pulmonary vein flow patterns post-MV-TEER were reviewed on the procedural transesophageal echocardiogram and classified as normal (systolic dominant or codominant) or abnormal (systolic blunting or reversal). The PVF pattern was correlated with all-cause mortality at follow-up. RESULTS: Two-hundred sixty-five patients had diagnostic PVF post-MV-TEER, with 73 (27.5%) categorized as normal and 192 (72.5%) categorized as abnormal. Patients with abnormal PVF morphology were more likely to have atrial fibrillation (70% vs 42%, P < .001) and greater than moderate residual MR (16% vs 3%, P = .01) and had higher mean left atrial pressure (18.1 ± 5.0 vs 15.9 ± 4.2 mm Hg, P = .002) and left atrial V wave (26.6 ± 8.5 vs 21.4 ± 7.3 mm Hg, P < .001) postprocedure. In multivariable analysis, abnormal PVF morphology post-MV-TEER was independently associated with mortality at follow-up (hazard ratio = 1.70; 95% CI, 1.06-2.74; P = .03) after correction for end-stage renal disease, atrial fibrillation, and residual MR. Results were similar in subgroups of patients with moderate or less and those with mild or less residual MR. CONCLUSIONS: Pulmonary vein flow morphology is a simple and objective tool to assess MR severity immediately post-MV-TEER and offers important prognostic information to optimize procedural results. Additional studies are needed to determine whether patients with abnormal PVF pattern post-MV-TEER would benefit from more intensive goal-directed medical therapy postprocedure.

Incidence of Severe Adverse Drug Reactions to Ultrasound Enhancement Agents in a Contemporary Echocardiography Practice.

OBJECTIVES: Prior data indicate a very rare risk of serious adverse drug reaction (ADR) to ultrasound enhancement agents (UEAs). We sought to evaluate the frequency of ADR to UEA administration in contemporary practice. METHODS: We retrospectively reviewed 4 US health systems to characterize the frequency and severity of ADR to UEA. Adverse drug reactions were considered severe when cardiopulmonary involvement was present and critical when there was loss of consciousness, loss of pulse, or ST-segment elevation. Rates of isolated back pain and headache were derived from the Mayo Clinic Rochester stress echocardiography database where systematic prospective reporting of ADR was performed. RESULTS: Among 26,539 Definity and 11,579 Lumason administrations in the Mayo Clinic Rochester stress echocardiography database, isolated back pain or headache was more frequent with Definity (0.49% vs 0.04%, P < .0001) but less common with Definity infusion versus bolus (0.08% vs 0.53%, P = .007). Among all sites there were 201,834 Definity and 84,943 Lumason administrations. Severe and critical ADR were more frequent with Lumason than with Definity (0.0848% vs 0.0114% and 0.0330% vs 0.0010%, respectively; P < .001 for each). Among the 3 health systems with >2,000 Lumason administrations, the frequency of severe ADR with Lumason ranged from 0.0755% to 0.1093% and the frequency of critical ADR ranged from 0.0293% to 0.0525%. Severe ADR rates with Definity were stable over time but increased in more recent years with Lumason (P = .02). Patients with an ADR to Lumason since the beginning of 2021 were more likely to have received a COVID-19 vaccination compared with matched controls (88% vs 75%; P = .05) and more likely to have received Moderna than Pfizer-Biotech (71% vs 26%, P < .001). CONCLUSION: Severe and critical ADR, while rare, were more frequent with Lumason, and the frequency has increased in more recent years. Additional work is needed to better understand factors, including associations with recently developed mRNA vaccines, which may be contributing to the increased rates of ADR to UEA since 2021.

Characteristics and Outcomes After Transcatheter Aortic Valve Implantation in Immunocompromised Patients.

Immunocompromised (IC) patients are at greater risk of adverse outcomes from cardiac surgery, and less invasive options for treating severe aortic stenosis among IC patients are often sought. However, despite greater preference for transcatheter aortic valve implantation (TAVI) in this population, there are limited data on outcomes in IC patients. Between January 2015 and December 2019, we studied patients with severe aortic stenosis who underwent TAVI. We defined IC status by the presence of active malignancy and receipt of oncologic treatment, post-organ transplantation-associated immunosuppression, human immunodeficiency virus, chronic steroid use (>5 mg/day), or active autoimmune disorder, and compared characteristics and outcomes of IC patients with those of non-IC patients. Of 173 patients who underwent TAVI, 56 (32%) were IC, 30 (54%) had active malignancy and underwent active treatment, 19 (34%) were IC without malignancy, and 7 (13%) were both IC and had active malignancy. IC patients, compared with non-IC patients, had similar baseline demographics, Society of Thoracic Surgeons risk scores (median 4.3% vs 4.4%), and overall complications (29% vs 26%). There were 37 deaths (16 IC and 21 non-IC) over a median follow-up of 17 months (95% confidence interval [CI] 14 to 20 months), and 1-year survival after TAVI was 84.0% for IC patients and 89.0% for non-IC patients (p = 0.51 by log-rank). After adjusting for Society of Thoracic Surgeons risk scores, IC patients had a nonsignificant trend toward greater risk of death compared with non-IC patients (adjusted hazard ratio 1.48, 95% CI 0.77 to 2.84). IC patients had a significantly smaller risk of cardiac-related death (adjusted hazard ratio 0.21, 95% CI 0.05 to 0.98) but a greater risk of noncardiac-related death (adjusted hazard ratio 4.14, 95% CI 1.71 to 10.0) than non-IC patients. In conclusion, IC patients who underwent TAVI have similar complication rates as non-IC patients, with a nonsignificant trend toward greater mortality, specifically related to noncardiac causes.

Defining the Role of Point-of-Care Ultrasound in Cardiovascular Disease.

Echocardiography is the foundation for diagnostic cardiac testing, allowing for direct identification and management of various conditions. Point-of-care ultrasound (POCUS) has emerged as an invaluable tool for bedside diagnosis and management. The objective of this review is to address the current use and clinical applicability of POCUS to identify, triage, and manage a wide spectrum of cardiac conditions. POCUS can change diagnosis and management decisions of various cardiovascular conditions in a range of settings. In the outpatient setting, it is used to risk stratify and diagnose a variety of medical conditions. In the emergency department (ED) and critical care settings, it is used to guide triage and critical care interventions. Furthermore, the skills needed to perform POCUS can be taught to noncardiologists in a way that is retained and allows identification of normal and grossly abnormal cardiac findings. Various curricula have been developed that teach residents and advanced learners how to appropriately employ point-of-care ultrasound. In conclusion, POCUS can be a useful adjunct to the physical exam, particularly in critical care applications.

Disruption of the diaphragm by blunt trauma: new dimensions of diagnosis.

Early diagnosis of diaphragmatic defects after blunt trauma is difficult. Multiple co-existing injuries complicate the accurate detection of lacerations of the diaphragm. Roentgenographic evaluation and a "high index of suspicion" have proven to be inefficient and inaccurate, since the average reported time for diagnosis is three and one-half years. Modified peritoneal lavage with intercostal water seal tubes in the pleural spaces is an added dimension of diagnosis. Earlier detection of diaphragmatic defects should become possible by this method.

Legal issues in sharing the benefits of biodiversity prospecting.

The National Cancer Institute (NCI) is the US Government's principal agency for research on the prevention, diagnosis and treatment of cancer. A critical component of the Institute's mission is the identification and development of new and promising treatments for cancer and AIDS. For many years these efforts have included a program to investigate natural products for potential new therapeutic agents. In 1986, with the advent of new screening techniques, the National Cancer Institute stepped up its exploration of natural products and began world-wide collections of plants in tropical and subtropical regions. In recognition of the principles of the Biodiversity Treaty, NCI appreciates that continued access to the natural products of these countries depends on the Institute's ability to recognize the contributions of these source countries and their indigenous peoples, and to provide them adequate incentives to conserve their natural resources for the purposes of drug discovery. Accomplishing this goal presented several legal issues for the National Cancer Institute. As an agency of the US government, the NCI has an adjunct statutory mission to facilitate the transfer of technology developed through the Institute's programs into the private sector for further development and commercialization, and NCI operates under a national policy to use the patent system to transfer Federally supported research to the private domestic sector. Reliance on patent law may limit the Institute's ability to recognize the rights of source countries and their indigenous people and provide compensation for their contributions. However, other legal instruments, such as contracts, can serve as interim measures to provide compensation to source countries and indigenous populations. The National Cancer Institute's Letter of Collection agreement (LOC, formerly the "Letter of Intent'), is an example of an alternative means that "fills-in the gaps' created by patent law and through which source countries may share in the benefits of natural product development.

Worse outcomes among uninsured general surgery patients: does the need for an emergency operation explain these disparities?

BACKGROUND: We hypothesize that lack of access to care results in propensity toward emergent operative management and may be an important factor in worse outcomes for the uninsured population. The objective of this study is to investigate a possible link to worse outcomes in patients without insurance who undergo an emergent operation. METHODS: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) 2005-2011 dataset. Patients who underwent biliary, hernia, and colorectal operations were evaluated. Multivariate analyses were performed to assess the associations between insurance status, urgency of operation, and outcome. Covariates of age, sex, race, and comorbidities were controlled. RESULTS: The uninsured group had greatest odds ratios of undergoing emergent operative management in biliary (OR 2.43), colorectal (3.54), and hernia (3.95) operations, P < .001. Emergent operation was most likely in the 25- to 34-year age bracket, black and Hispanic patients, men, and patients with at least one comorbidity. Postoperative complications in emergencies, however, were appreciated most frequently in the populations with government coverage. CONCLUSION: Although the uninsured more frequently underwent emergent operations, patients with coverage through the government had more complications in most categories investigated. Young patients also carried significant risk of emergent operations with increased complication rates. Patients with government insurance tended toward worse outcomes, suggesting disparity for programs such as Medicaid. Disparity related to payor status implies need for policy revisions for equivalent health care access.

Socioeconomic disparity in inpatient mortality after traumatic injury in adults.

BACKGROUND: Prior studies have demonstrated that race and insurance status predict inpatient trauma mortality, but have been limited by their inability to adjust for direct measures of socioeconomic status (SES) and comorbidities. Our study aimed to identify whether a relationship exists between SES and inpatient trauma mortality after adjusting for known confounders. METHODS: Trauma patients aged 18-65 years with an Injury Severity Scores (ISS) of ≥9 were identified using the 2003-2009 Nationwide Inpatient Sample. Median household income (MHI) by zip code, available by quartiles, was used to measure SES. Multiple logistic regression analyses were performed to determine odds of inpatient mortality by MHI quartile, adjusting for ISS, type of injury, comorbidities, and patient demographics. RESULTS: In all, 267,621 patients met inclusion criteria. Patients in lower wealth quartiles had significantly greater unadjusted inpatient mortality compared with the wealthiest quartile. Adjusted odds of death were also higher compared with the wealthiest quartile for Q1 (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.06-1.20), Q2 (OR, 1.09; 95% CI, 1.02-1.17), and Q3 (OR, 1.11; 95% CI, 1.04-1.19). CONCLUSION: MHI predicts inpatient mortality after adult trauma, even after adjusting for race, insurance status, and comorbidities. Efforts to mitigate trauma disparities should address SES as an independent predictor of outcomes.

Increased complications after appendectomy in patients with cerebral palsy: are special needs patients at risk for disparities in outcomes?

BACKGROUND: Cerebral palsy (CP) is a nonprogressive neurologic disorder. Anecdotal evidence suggests there are worse outcomes in this population after common operative procedures like appendectomy. This study aims to classify whether there are relevant disparities in postoperative outcomes in CP versus non-CP patients after open or laparoscopic appendectomy. METHODS: Hospital discharge data from the 2003-2009 weighted Nationwide Inpatient Sample were used. Unadjusted and adjusted multiple logistic regression were used to assess postoperative complications, as well as inpatient mortality, average duration of hospital stay, and cost. RESULTS: Approximately 1,250 patients with CP met the inclusion criteria. After adjusted analysis, CP patients displayed significantly greater odds of the following postoperative complications: Sepsis/organ failure, operation-related infection, pneumonia, urinary tract infection, and acute respiratory distress syndrome. Patients with CP also had a greater cost and in-hospital stay after appendectomy. CONCLUSION: Patients with CP have greater adjusted odds of complications after open or laparoscopic appendectomy. The mechanisms that led to these disparities need to be studied and may include difficulties in patient assessment and communication. Additional education of healthcare providers to improve recognition of symptoms and care for patients with disabilities may be more immediately helpful in decreasing disparities in outcomes.

Concurrent ivermectin and Solanum spp. toxicosis in a herd of horses.

BACKGROUND: Representatives from a herd of horses with acute onset of neurologic signs after administration of ivermectin presented for evaluation and treatment. OBJECTIVES: Describe clinical signs of horses intoxicated by ingestion of Solanum sp. and administered ivermectin. ANIMALS: Six of 11 affected unrelated horses presented for evaluation and treatment. The remaining 5 affected horses were treated at the farm. Four additional horses, housed separately, were unaffected. METHODS: Case series is presented. Serum ivermectin concentrations were evaluated in the 6 hospitalized horses. The remnants of the tubes of ivermectin paste were analyzed for ivermectin concentration. The hay fed to the affected horses was analyzed for the presence of toxic plants. RESULTS: Serum ivermectin concentrations were higher than expected, given the dosage of ivermectin administered. The ivermectin concentration remaining in the administration tubes did not exceed specifications. The hay was heavily contaminated by 2 Solanum species. All horses returned to normal neurologic function with supportive care. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses might exhibit signs of ivermectin toxicity after appropriate dosing of the drug if they concurrently consume toxic plants of the Solanum family.

Intravenous iron-dextran therapy in the treatment of anemia occurring in surgical, gynecologic and obstetric patients.

An infusion of iron-dextran diluted in 1,000 milliliters of physiologic saline solution was given to 51 patients. The average hemoglobin response was 1.9 grams per deciliter per week. Mean corpuscular volume, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin deficits also were corrected. There were no allergic reactions. This is an extremely reliable and safe method of replenishing depleted iron in patients.

Antidepressants in the management of cancer pain.

Most patients who have been diagnosed with cancer will experience pain at some point during the course of their disease. Often, opioid analgesics are not enough to completely alleviate the patient's pain and the selection of appropriate adjunct analgesic agents is critical. This article reviews the mechanisms of action and analgesic effects of several classes of antidepressants to enable the clinician to select the appropriate agent for the patient.

Novel antibiotic resistance transfer in Bacteroides.

Resistance to tetracycline and lincosamide antibiotics was transferred en bloc from a strain of Bacteroides fragilis (V503) to a plasmidless strain of Bacteroides uniformis (V528) during in vitro filter matings. Resistance transfer was detected at frequencies of 10(-5) to 10(-6) drug-resistant progeny per input donor cell and was dependent on cell-to-cell contact of donors and recipients. Transfer was insensitive to DNase and was not mediated by chloroform- or filter-sterilized donor broth cultures. A determinant for resistance to cefoxitin in V503 was not transferred in this system. V503 contained a 3.7 x 10(6)-dalton plasmid (pVA503). Drug-resistant progeny of V503 x V528 matings usually contained pVA503, but up to 20% of the total progeny of such crosses were plasmid free. Filter blot DNA hybridization studies (Southern method) confirmed that pVA503 was not integrated into the host chromosome of the plasmidless progeny. Drug-resistant progeny from V503 x V528 matings (with or without pVA503) conjugally transferred clindamycin resistance an tetracycline resistance to a suitable recipient strain. None of the drug resistance determinants of V503 were affected by treatment with standard plasmid curing regimens, and methods designed to detect very large plasmid molecules failed to suggest the involvement of extrachromosomal DNA in this resistance transfer system. The well-characterized Bacteroides R plasmid, pBF4 (conferring clindamycin resistance), was found to share hybridizing sequences with bulk cellular V503 DNA when examined by filter blot hybridization. Similarly sized sequences were found in drug-resistant progeny recovered from matings. Neither of the two pBF4 derivatives carrying deletions that abolished clindamycin resistance hybridized with V503 DNA.

Problem-based learning in a health sciences librarianship course.

Problem-based learning (PBL) has been adopted by many medical schools in North America. Because problem solving, information seeking, and lifelong learning skills are central to the PBL curriculum, health sciences librarians have been actively involved in the PBL process at these medical schools. The introduction of PBL in a library and information science curriculum may be appropriate to consider at this time. PBL techniques have been incorporated into a health sciences librarianship course at the School of Library and Information Science (LIS) at the University of Wisconsin-Milwaukee to explore the use of this method in an advanced Library and Information Science course. After completion of the course, the use of PBL has been evaluated by the students and the instructor. The modified PBL course design is presented and the perceptions of the students and the instructor are discussed.