Rejected

Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres in 15 countries. Sequential patients were included. We identified 444 patients, with median follow up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV patients. Our data represents the largest real-world study of MPN patients age <25 years at diagnosis). Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

Prescribed opioid doses > 100 mg oral morphine equivalent (OME) and/or co-prescribing of sedating psychoactive medications increase the risk of unintentional fatal overdose. We describe general practice encounters where opioids are prescribed and examine high-risk opioid prescribing.

α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.

Multisystem Inflammatory Syndrome in Children associated with COVID-19 infection attracted attention because some features overlapped with Kawasaki disease. And due to these overlapping features with Kawasaki disease, it has become difficult to diagnose both disorders. Therefore, this study focused on the differences between the patients diagnosed with MIS-C after COVID-19 and Kawasaki patients analyzed, particularly during the pre-pandemic period. In this way, it is aimed to reduce the dilemmas experienced in Diagnosis. In this descriptive study, 98 patients diagnosed with MIS-C throughout the pandemic were compared to 37 patients diagnosed with Kawasaki Disease during the pre-pandemic period.The patients in the MIS-C group were older children and clinically suffered from more headaches, vomiting, diarrhea, abdominal pain, and chest pain than Kawasaki patients. Signs of shock such as hypotension and tachycardia were more remarkable. Also, myocarditis and mitral regurgitation were detected at a higher rate in the MIS-C group. Besides, in the laboratory, lymphopenia, hypoalbuminemia, and creatinine elevation were more apparent.In conclusion, our present study findings support that although the MIS-C and Kawasaki share common features, they present with different clinical and laboratory features. And these differences are thought to be supportive in treatment and patient management.

Topiramate has multiple pharmacological mechanisms that are efficient in treating epilepsy and migraine. Ginger has been established to have gingerols and shogaols that cause migraine relief. Moreover, Topiramate has many off-label uses. Thus, it was necessary to explore the possible neurotoxicity of Topiramate and the role of ginger oil in attenuating the Topiramate neurotoxicity. Male albino mice were orally gavaged with Topiramate, ginger oil (400 mg/kg), and Topiramate plus ginger oil with the same pattern for 28 days. Oxidative stress markers, acetylcholinesterase (AchE), gamma-aminobutyric acid (GABA), and tumor necrosis factor-alpha (TNF-α) were examined. Histopathological examination, immunohistochemical glial fibrillary acidic protein (GFAP), and Bax expression analysis were detected. The GABAAR subunits, Gabra1, Gabra3, and Gabra5 expression, were assessed by RT-qPCR. The investigation showed that Topiramate raised oxidative stress markers levels, neurotransmitters, TNF-α, and diminished glutathione (GSH). In addition, Topiramate exhibited various neuropathological alterations, strong Bax, and GFAP immune-reactivity in the cerebral cortex. At the same time, the results indicated that ginger oil had no neurotoxicity. The effect of Topiramate plus ginger oil alleviated the changes induced by Topiramate in the tested parameters. Both Topiramate and ginger oil upregulated the mRNA expression of gabra1 and gabra3, while their interaction markedly downregulated them. Therefore, it could be concluded that the Topiramate overdose could cause neurotoxicity, but the interaction with ginger oil may reduce Topiramate-induced neurotoxicity and should be taken in parallel.

Chronic pain after breast cancer surgery is affecting up to 60% of patients, causing significant morbidity to patients. Lately, fat grafting has been applied as a therapy for chronic neuropathic pain.

The purpose of this review is to present a brief background on chronic subdural hematomas (cSDH), middle meningeal artery (MMA) embolization, and its role in decreasing recurrence of cSDH. A review of the most up-to-date literature should demonstrate the efficacy of this procedure.

Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities, including sensory, motor, and visceral activities, through cholinergic signaling. Cholinergic signaling plays an important role in pancreatic exocrine secretion. A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors, participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis, and can also inhibit the progression of pancreatic cancer. However, cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors, but enhances the proliferation and invasion of pancreatic tumor cells. This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.

A woman in her early 30s in the 11 2/7 week of pregnancy was admitted with severe abdominal pain and emesis. One year prior, the patient had undergone hysteroscopic adhesiolysis to treat Asherman syndrome resulting from a prior pregnancy. Examination of the patient revealed a haemoperitoneum and an intact intrauterine pregnancy. Laparoscopic adhesiolysis and haemostasis was performed and the patient was transferred to the intensive care unit. Subsequent examination due to persistent abdominal pain revealed an occult iatrogenic perforation of the uterus and placenta percreta with spontaneous uterine rupture. Although treatment for placenta percreta has generally been hysterectomy, in this case, the rupture and perforation sites were resected, representing successful fertility preserving management for this oft-overlooked pregnancy complication.