Kernicterus Spectrum Disorders Diagnostic Toolkit: validation using retrospective chart review.

BACKGROUND: Kernicterus Spectrum Disorders (KSDs) result from hyperbilirubinemia-induced brain injury. We developed a Toolkit (KSD-TK) to predict the likelihood of KSDs. This study aims to validate the KSD-TK by comparing it to clinical diagnoses made by the Kernicterus Clinic in the Division of Neurology. METHODS: Through retrospective chart review, we completed a KSD-TK for 37 patients evaluated between 2011 and 2019 using highest bilirubin, newborn risk factors, neonatal exam, follow-up exam, auditory testing, tooth enamel, and MRI brain results. KSD-TK results were compared to the clinical diagnoses given by a kernicterus expert (SS). RESULTS: Of 37 patients, 29 were clinically diagnosed with kernicterus, including 14/14 with KSD-TK scored as "definite", 14/15 "probable", and 1/2 with "possible" kernicterus. None of 6 patients with KSD-TK "not kernicterus" were clinically diagnosed with kernicterus. Combining KSD-TK "definite" and "probable", the KSD-TK has 96.6% sensitivity and 87.5% specificity. Each KSD-TK component had high sensitivity, but only three had specificity ≥0.75: auditory neuropathy spectrum disorder, abnormal movements and/or tone on follow-up exam, and abnormal globus pallidus and/or subthalamic nucleus on MRI. CONCLUSION: The KSD-TK is a promising screening tool for patients at risk for kernicterus. IMPACT: This study provides validation of a Kernicterus Spectrum Disorders (KSDs) Toolkit. The toolkit provides screening criteria for predicting KSD diagnosis. Scores of definite or probable have high sensitivity and specificity for KSDs. Abnormal auditory processing, exam, and MRI were most specific for KSDs.

The Influence of Lifestyle Factors on the Burden of Pediatric Migraine.

There is a gap in patient education and coaching of lifestyle factors related to pediatric migraine, which nurses are in a unique position to fill in order to provide comprehensive care to these patients. In order to help fill this gap, we conducted a targeted review of studies examining migraine and lifestyle factors in children and adolescents. Studies older than 2010, studies examining adults above the age of 18, studies not available in the English language, and secondary sources were excluded from the review. A final sample of 42 studies was included in this review. Lifestyle factors including stress, sleep, obesity, and diet were identified as playing a significant role in increasing the frequency, severity, and duration of migraine attacks in pediatric patients. Based on these findings, a framework is discussed for practical applications of this knowledge by nursing staff working in primary and specialty care clinics.

Efficient Green Synthesis, Anticancer Activity, and Molecular Docking Studies of Indolemethanes Using a Bioglycerol-Based Carbon Sulfonic Acid Catalyst.

Indolemethane derivatives are significant molecules in the study of N-heterocyclic chemistry. Herein, we designed and developed a highly efficient green synthesis of indolemethane compounds using a recyclable biodegradable glycerol-based carbon solid acid catalyst under solvent-free conditions at room temperature for 5 min with excellent yields. The synthesized compounds were subjected to cytotoxic activity against prostate (DU145), hepatocellular carcinoma (HepG2), and melanoma (B16) cell lines. The highest cytotoxicity effects were found with 1k (1.09 µM) and 1c (2.02 µM) against DU145, followed by 1a, 1d, 1f, 1n, and 1m between 5.10 and 8.18 µM concentrations. The anticancer activity is validated using molecular docking simulations, and comparing binding energies with the standard drug doxorubicin suggests that the title compounds are well fitted into the active site pocket of the target molecules..

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A PATIENT WITH FREQUENT MIGRAINE WITH AURA: A CASE REPORT.

BACKGROUND/PURPOSE: To explore the possible relationship between Paracentral Acute Middle Maculopathy (PAMM) and migraine. Paracentral acute middle maculopathy is a recently described clinical and optical coherence tomography entity involving infarction of the inner nuclear layer secondary to deep retinal capillary ischemia. It presents as a painless paracentral scotoma and often results in permanent visual deficits. Migraine, especially migraine with aura, has been shown to cause structural changes in the retinal microvasculature and to be a risk factor for retinal ischemia. METHODS: A case report and review of the literature. RESULTS: A 39-year-old woman with migraine with visual aura presented with a discrete, monocular, painless "buffalo-shaped" paracentral scotoma, which started during a period of frequent typical visual auras. Her exam and optical coherence tomography were consistent with PAMM. CONCLUSION: We propose that migraine is a risk factor for the development of PAMM. The changes in retinal microvasculature in migraine may increase a patient's susceptibility to retinal ischemia. Other risk factors for retinal ischemia, including diabetes, hypertension, hyperlipidemia, sickle cell disease, and orbital trauma, have been shown to be associated with PAMM. Further research should be conducted to determine whether there is a definite relationship between migraine and PAMM.

Hypocaloric home parenteral nutrition and nutrition parameters in patients following bariatric surgery.

BACKGROUND: Surgical intervention is considered an acceptable treatment for morbid obesity. Complications following bariatric surgery procedures (BSPs) may necessitate home parenteral nutrition (HPN). No studies have been published on patients receiving HPN following BSP complications. The study aim was to determine if hypocaloric HPN has an effect on body mass index (BMI), albumin, and HPN complications. METHODS: A historic cohort of patients was identified from a clinical database. Obese patients (BMI ≥35 kg/m(2)) who underwent BSP and received HPN for an anastomotic leak/fistula or bowel obstruction were included. Comparisons for start and end of therapy were made for calorie and protein intake, BMI, white blood cell count, and serum albumin level. Readmissions and metabolic and infectious complications were recorded. Obese patients received hypocaloric feeds to promote weight loss and protein for wound healing. RESULTS: Twenty-three patients were included for an average study length of 1.5 months. Patients received an average of 1.2 g of protein and a median of 13.6 kcal per kg actual body weight (ABW) per day. BMI decreased by 7.1% ± 5.2%, from a median of 39.8 to 37.1, and serum albumin increased by 12.5%, from 2.8 ± 0.5 to 3.2 ± 0.6 g/dL. Readmissions occurred in 52.2% of patients with 40.0% of complications related to HPN. CONCLUSIONS: Hypocaloric HPN is efficacious in maintaining adequate nutrition while allowing for weight loss in morbidly obese patients following complications of bariatric surgery. Frequency of HPN complications was comparable to those reported in the literature.

Species difference in the in vitro and in vivo metabolism of amtolmetin guacil.

Tolmetin (TMT, CAS 26171-23-3) is a non-steroidal anti-inflammatory drug (NSAID) indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis. As TMT causes gastro-intestinal side effects like other NSAIDs, its nonacidic prodrug amtolmetin guacil (AMG, CAS 87344-06-7) was synthesized. AMG has similar NSAID properties like TMT with additional gastroprotective property. The aim of this study was to investigate whether TMT and AMG are differentially metabolised in rat and human plasma (fresh and acidified) and liver microsomes. TMT was found to be stable in all the matrices tested viz., rat and human plasma (fresh and acidified) and liver microsomes. AMG was found to be stable only in acidified rat and human plasma. On the contrary, in fresh human plasma and human liver microsomes AMG was rapidly converted to two metabolites, which were subsequently identified as MED5 and MED5 methyl ester, without yielding any intact TMT. However, in rat fresh plasma and liver microsomes, AMG formed MED5 (predominant) and TMT. To corroborate the in vitro findings, in vivo pharmacokinetics (PK) studies were done following separate dosing of AMG in both rats and humans. In rats, the PK data substantiated that following oral administration of AMG it will be converted to TMT resulting in similar PK parameters observed for TMT when it was administered alone. In humans, however, AMG yields low levels of TMT which substantes the in vitro results. Levels of AMG were not detectable in the plasma. These results confirm the species differences in the in vitro and in vivo metabolism and disposition of AMG. More research work to further explore and understand AMG metabolism in humans is required.

Intestinal failure management at the Cleveland Clinic.

The Cleveland Clinic institutional guidelines for the management of intestinal failure, including long-term or home parenteral nutrition and related complications, intestinal rehabilitation, and small bowel transplantation, were reviewed. PubMed was searched for relevant articles. The search was performed in November 2008; keywords used were home parenteral nutrition, short bowel syndrome, intestinal rehabilitation, and small-bowel transplantation. Randomized, prospective, observational, retrospective reviews and case report articles that contained relevant data for long-term parenteral nutrition, intestinal rehabilitation, and intestinal transplantation were selected. Researchers reviewed 67 selected articles that met our inclusion criteria. Our institution data registries for intestinal rehabilitation and home parenteral nutrition were also reviewed for relevant data. The survival of tens of thousands of children and adults with complicated gastrointestinal problems has been possible because of parenteral nutrition. In selected patients, a program of intestinal rehabilitation may avoid the need for long-term parenteral nutrition.

Vaccines in development to prevent and treat atherosclerotic disease.

Coronary heart disease (CHD) remains the leading cause of death in the United States. Immune mechanisms have been recently proposed to play an important role in the development of atherosclerotic plaques in CHD. Heat shock proteins and oxidized low-density lipoprotein are proinflammatory substances that have been shown to have an important role in the pathogenesis of atherosclerosis, and are now targets for clinical vaccine development. In addition, a vaccine has been developed to inhibit cholesteryl ester transfer protein. It is now recognized that many medications used to combat plaque development and rupture have significant anti-inflammatory effects and these effects are critical for drug efficacy. The influenza vaccine is associated with an atheroprotective effect. In addition, a nicotine vaccine, an antiangiotensin vaccine, and an anti-obesity vaccine may play a therapeutic role in modifying known risk factors for the development of atherosclerosis and its complications. This article reviews these vaccines as possible additions to the armamentarium of atheroprotective treatment modalities.