Rejected

The primary objective of this trial (SP1042; NCT02582866) was to assess long-term safety and tolerability of lacosamide monotherapy (200-600 mg/day) in adults with focal (partial-onset) seizures or generalized tonic-clonic seizures (without clear focal origin). This Phase III, long-term, open-label, multicenter, follow-up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double-blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide; 84 (79.2%) completed the trial, and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety-six (90.6%), 64 (60.4%), and 44 (41.5%) patients had ≥12, ≥24, and ≥36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (≥4%) TEAEs were headache (10 [9.4%]), nasopharyngitis (eight [7.5%]), and back pain (five [4.7%]). One (0.9%) patient discontinued due to a TEAE (sudden unexpected death in epilepsy; not considered drug-related), 14 (13.2%) patients reported serious TEAEs, and seven (6.6%) patients reported TEAEs that were considered drug-related. Overall, long-term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.

The COVID-19 pandemic has affected not only the emergency medical system, but also patients' regular ambulatory care, as such decrease in the number of patients visiting outpatient clinics decreased in 2020 than in 2019, or the ban lifting of subsequent visits by telephone for outpatient clinics since March 2020 in lieu of ambulatory care for chronic diseases. In this context, we investigate the impact of the COVID-19 pandemic on ambulatory care at Japanese outpatient clinics for patients with chronic neurological diseases during 2020. We collected data from the administrative claims database (DeSC database) covering more than 1 million individuals. Serial changes in the frequency of subsequent outpatient visits to clinics or hospitals (excluding large hospitals) for chronic ambulatory care of epilepsy, migraine, Parkinson's disease (PD), and Alzheimer's disease (AD) in 2020 were measured. As a result, since April 2020, the monthly outpatient visits for epilepsy, PD, and AD decreased slightly but significantly (approximately 0.90 in relative risk [RR]) but visits for migraine increased (RR = 1.15). Telephone visit was most frequently used in April-May, in less than 5% of monthly outpatient clinic visits for the examined neurological diseases. Outpatient visits for migraine treatment were more likely to be done by telephone than in case of other diseases (adjusted Odds ratio = 2.08). These results suggest that the impact of COVID-19 pandemic on regular ambulatory care for several chronic neurological diseases yielded different effect depending on the disease, in terms of the frequency or type of outpatient visits.

Pituitary adenoma resections comprise a large proportion of intracranial tumor surgeries. This patient population is medically and physiologically complex and requires careful perioperative planning and management on the part of the anesthesiologist. This review will summarize anesthetic considerations for pre, intra, and postoperative management of patients undergoing transsphenoidal pituitary surgery.

We aimed to characterize a large cohort of non-invasive, HPV and p53-independent verruciform lesions, such as "vulvar acanthosis with altered differentiation" (VAAD), "differentiated exophytic vulvar intraepithelial lesion" (DEVIL) and "verruciform lichen simplex chronicus" (vLSC).

Maternal migraine may contribute to mental heath problems in offspring but empirical evidence has been available only for bipolar disorders. Our objective was to examine the association between maternal migraine and the risk of any and specific psychiatric disorders in offspring.

The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety.

Acute Q fever is endemic in Israel, yet the clinical and laboratory picture is poorly defined.

Neuritis of the infrapatellar branch of the saphenous nerve can result from iatrogenic injury, entrapment, bursitis, or patellar dislocation. Currently, there is an unmet clinical need for treating refractory neuritis nonsurgically.

Inflammation is a natural process that occurs in the organism in response to harmful external agents. Despite being considered beneficial, exaggerated cases can cause severe problems for the body. The main inflammatory manifestations are pain, increased temperature, edema, decreased mobility, and quality of life for affected individuals. Diseases such as arthritis, cancer, allergies, infections, arteriosclerosis, neurodegenerative diseases, and metabolic problems are mainly characterized by an exaggerated inflammatory response. Inflammation is related to two categories of substances: pro- and anti-inflammatory mediators. Among the pro-inflammatory mediators is tumor necrosis factor-α (TNF-α). It is associated with immune diseases, cancer, and psychiatric disorders that increase its excretion. Thus, it becomes a target widely used in discovering new anti-inflammatory drugs. In this context, secondary metabolites biosynthesized by plants have been used for thousands of years and continue to be one of the primary sources of new drug scaffolds against inflammatory diseases. To minimize costs related to the drug discovery process, computer-aided drug design (CADD) techniques are broadly explored to increase the chances of success. In this review, the main natural compounds that are derived from alkaloids, flavonoids, terpene, and polyphenols as promising TNF-α inhibitors will be discussed. Finally, we applied a molecular modeling protocol involving all compounds described here, suggesting that their interactions with Tyr59, Tyr119, Tyr151, Leu57, and Gly121 residues are essential for the activity. Such findings may prove useful for research groups worldwide to design new anti-inflammatory TNF-α inhibitors.

A 19-year-old male amateur footballer was referred to our center with complaints of relapsing and remitting pain, swelling, and reduced range of motion of the left knee. History, radiological, and laboratory findings were unrevealing, except for chronic synovitis. On arthroscopy, a 3.3 × 0.3-cm thorn was found embedded in the anteromedial aspect of the anterior cruciate ligament and was carefully removed. The postoperative course was uneventful.