Rejected

This is an updated version of the original Cochrane Review published in 2008 and updated in 2013. Epilepsy is a common neurological condition which affects up to 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have focal epilepsy. Vigabatrin is an antiepileptic drug licensed for use in drug-resistant epilepsy.

Nonsteroidal anti-inflammatory drugs (NSAIDS) are increasingly important alternatives to opioids for analgesia during hospitalization as health systems implement opioid-minimization initiatives. Increasing NSAID use may increase AKI rates, particularly in patients with predisposing risk factors. Inconclusive data in outpatient populations suggests that NSAID nephrotoxicity is magnified by renin-angiotensin system inhibitors (RAS-I). No studies have tested this in hospitalized patients.

There is no knowledge about the effects of kinesio taping (KT) on the radial nerve in lateral epicondylitis.

The need for improved medications for the treatment of epilepsy and chronic pain is essential. Epileptic patients typically take multiple antiseizure drugs without complete seizure freedom and chronic pain is not fully managed with current medications. A positive allosteric modulator (PAM) of α2/3-containing GABA receptors (5-(8-ethynyl-6-(pyridin-2-yl)-4-benzo[]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81 () is a lead compound in a series of imidazodiazepines. We previously reported that KRM-II-81 produces broad-based anticonvulsant and antinociceptive efficacy in rodent models and provides a wider margin over motoric side effects than that of other GABA receptor PAMs. The present series of experiments was designed to fill key missing gaps in prior preclinical studies assessing whether KRM-II-81 could be further differentiated from non-selective GABA receptor PAMs using the anticonvulsant diazepam (DZP) as a comparator. In multiple chemical seizure provocation models in mice, KRM-II-81 was either equally or more efficacious than that of DZP. Most strikingly, KRM-II-81 but not DZP blocked the development of seizure sensitivity to the chemoconvulsants cocaine and pentylenetetrazol in seizure kindling models. This antiepileptogenic effect is considered the holy grail of antiepileptic treatment suggesting the slowing disease progression. These and predecessor data have placed KRM-II-81 into consideration for clinical development requiring the manufacture of kilogram amounts of GMP material. We describe here a novel synthetic route amenable to kilogram quantity production. The new biological and chemical data provide key steps forward in the development of KRM-II-81 () as an improved treatment option for patients suffering from epilepsy.

Mucosal melanoma is a rare variant of melanoma representing around 1% of total cases of melanoma diagnosed. The usual sites of mucosal involvement are the sino-nasal passages, the oral cavity, and less commonly the upper gastrointestinal (GI) tract. It also has been reported to occur in vulvovaginal and anorectal mucosa.  We present a rare case of mucosal melanoma that presented as recurrent epistaxis, headache, and sinus pressure. CT maxillofacial imaging revealed a large mass right nasal cavity. This was biopsied by ENT and shown to be mucosal melanoma. This was treated with palliative radiation followed by immunotherapy with nivolumab.  Along with details of the case, we also discuss current treatment options with a focus on the role of immunotherapy and its efficacy in cases of head and neck mucosal melanoma. Our review of literature supports use of combination immunotherapy (including both nivolumab and ipilimumab) as it shows greater efficacy than either therapy alone. When combined with radiation therapy (RT) the overall response rate is improved and RT induces an abscopal effect; where benefits of RT are also seen at nonirradiated locations.  In our patient, the use of radiation was essentially palliative as the patient was deemed to not be a surgical candidate. We discuss in our literature review the optimum timing of radiation in relation to definitive surgery or immunotherapy.

Clerodendranthus spicatus, popularly known as "kidney tea" in China, is consumed traditionally as a functional food for treatment of renal inflammation, dysuria, and gout. We evaluated the effects of C. spicatus on gout by assessing activities of anti-hyperuricemia, anti-gouty arthritis, and analgesia in vivo, and the results indicated that the ethyl acetate fraction shows potential activities. Subsequent phytochemical investigation of this fraction led to the isolation of 32 compounds consisting of 20 diterpenoids (including the new orthosiphonones E and F), 2 triterpenoids, 6 flavonoids, 2 lignanoids, and 2 phenolic acid derivatives. Pharmacological investigation of the pure compounds in cellular model of hyperuricemia indicated that 12 compounds could promote the excretion of uric acid at 10 μg/mL, and compounds 3, 4, 5, and 21 had better effects than benzbromarone, a famous uricosuric drug. Furthermore, compounds 4, 6, 7, 9, 14, 15, 23, 26, and 31 showed significant anti-gouty arthritis activity in monosodium urate (MSU)-induced joint swelling at the dose of 50 mg/kg, while compounds 4, 5, 7, 9, and 26 exhibited significant inhibition of pain induced by acetic acid. Our findings provided scientific justification to support the traditional application of "kidney tea" for treating gout and suggested its good application prospects in the future.

Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of anti-fibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents. Raw data for this study are available through ProteomeXchange with identifier PXD020601.

There is debate regarding the timing of procedural sedation and analgesia (PSA) in relation to fasting status. Point-of-care ultrasound (POCUS) provides the ability to measure gastric content and is being used as a surrogate for aspiration risk in anesthesia. We sought to evaluate the gastric content of pediatric emergency department (PED) patients undergoing PSA using POCUS.

Please see the Author Video associated with this article. A multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) has recently been described. To evaluate imaging findings of MIS-C associated with COVID-19. Imaging studies and medical records of sixteen patients (0-20 years) admitted with MIS-C were retrospectively reviewed. Thoracic imaging studies were evaluated for parenchymal, mediastinal and hilar, and cardiovascular abnormalities. Abdominal imaging studies were evaluated for abnormalities of solid viscera, hollow viscera, peritoneum, as well as the mesentery and retroperitoneum. Studies were reviewed independently by two radiologists, and disagreements were resolved by a third, senior radiologist. Sixteen patients were included (10 male and 6 female; 20 months – 20 years). All 16 patients presented with fever. Other presenting signs and symptoms included: vomiting (12; 75%), abdominal pain (11; 69%), rash (10;62.5%), conjunctivitis (8;50%), diarrhea (7;44%), headache (6;37.5%), and sore throat (5;31%). Shortness of breath and cough were each present in one patient. Chest radiograph demonstrated cardiomegaly (10; 62.5%), congestive heart failure or pulmonary edema (9; 56%), atelectasis (9; 56%), pleural effusions (7; 44%), adult respiratory distress syndrome (2; 12.5%) and pneumonia (1; 6%). Absolute interobserver agreement was 69-100%. Eight patients (50%) were evaluated for PE (6 [75%] by CT angiography [CTA] and 2 [25%] by ventilation/perfusion scintigraphy). In 2 (25%), CTA demonstrated a segmental PE. Abdominal imaging findings (US and CT) included small volume ascites (6; 38%), hepatomegaly (6; 38%), echogenic kidneys (5; 31%), bowel wall thickening (3; 19%), gallbladder wall thickening (3; 19%), mesenteric lymphadenopathy (2; 13%), splenomegaly (1; 6%), and bladder wall thickening (1; 6%). The frequencies of findings based on all the reviewed modalities were: cardiomegaly (12; 75%), pleural effusion (10; 63%) and atelectasis (10; 63%). 15 patients (94%) were discharged home (length of hospital stay 3-20 days). There were no mortalities. MIS-C associated with COVID-19 is characterized predominantly by cardiovascular abnormalities, though also solid visceral organ, gallbladder, and bowel abnormalities as well as ascites, reflecting a multisystemic inflammatory process. The constellation of imaging findings in the setting of COVID-19 may alert pediatric radiologists to the diagnosis of MIS-C prior to rapid deterioration of patients.