Rejected

As the most commonly used endocrine therapy regimen for patients with hormone receptor-positive (HR+) breast cancer (BC) at present, aromatase inhibitors (AIs) reduce the risk of localized and distant recurrence, contralateral BC and secondary cancer, and prolong disease-free survival. Clinical data show that poor adherence during AI treatment is mainly attributed to muscle and joint pain, fatigue, anxiety, depression and sleep disturbances during treatment. The rapid decline of estrogen caused by AIs in a short period of time enhances sympathetic activity, activates T cells in the body, produces inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-17A, and promotes the occurrence of inflammation and bone loss. This article reviewed the mechanism of poor dependence on AIs in BC patients from the neuro-immuno-endocrine (NIE) perspective and provided clues for clinical intervention against poor adherence.

Topiramate is an anticonvulsant from sulfamate-substituted monosaccharides that is increasingly used to treat migraines. Serious topiramate intoxications have been described. Unfortunately, indications for and the effect of interventions, including hemodialysis, in severe intoxications seem expert-based and lack empirical evidence. We aim to review the literature on topiramate intoxication cases and to describe the first topiramate intoxication with toxicokinetic data following treatment with hemodialysis.

Kimura's disease (KD) is a rare chronic inflammatory condition of unknown aetiology. It is a benign disease that might mimic a neoplastic process. It primarily affects the head and neck region, presenting as deep subcutaneous masses, and is often accompanied by triad regional lymphadenopathy, salivary gland involvement, and high serum immunoglobulin (IgE) levels. Here, we report the second documented case of KD in Palestine diagnosed in a 28-year-old male patient who presented with lymphadenopathy and increased serum immunoglobulin and (IgE and IgG) associated with intermittent abdominal pain, generalised fatigue, hepatomegaly, cardiomyopathy, reactive airway disease, peripheral vasculopathy, peripheral neuropathy, and focal segmental glomerulosclerosis. The patient was managed with steroids and an immunosuppressant (Azathioprine) with a moderate response for two years. In 2021, treatment with Mycophenolate Mofetil was initiated, which was more effective than Azathioprine.

As the discussion of first-line anagrelide treatment is ongoing, we aimed to prospectively examine the efficacy and safety of anagrelide in cytoreduction therapy-naïve high risk essential thrombocythemia (ET) patients in Korea. Seventy patients from 12 centers were treated with anagrelide monotherapy for up to 8 weeks, followed up until 24 months. At week 8, 50.0% of the patients were able to achieve platelet < 600 x 10/L, and by 12 months, 55/70 (78.6%) patients stayed on anagrelide, and 40.0% patients showed platelet normalization. 14 patients required additional hydroxyurea (HU) for cytoreduction. The median daily dose of needed HU was 500mg (range 250mg – 1500mg). The efficacy was independent of the somatic mutation status. There were 4 thromboembolic events and 7 bleeding events during the follow-up period. The most common adverse events associated with anagrelide use were headache, followed by palpitation/chest discomfort, edema and generalized weakness/fatigue. 7 patients wished to discontinue anagrelide treatment due to adverse events (3 due to headache; 2 due to edema; 1 due to palpitation and 1 due to skin eruption). All in all, first-line anagrelide treatment showed a favorable response with tolerable safety profiles regardless of somatic mutation status.

Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies.

A 66-year-old man developed multiple erosions and pain in the lips and mouth, fever, and black stools. There was persistent bleeding from the lip erosions. When he was admitted to our hospital, his white blood cell count increased to 53,420/µl with 3% eosinophils, and hemoglobin decreased to 3.1 g/dl. Bone marrow biopsy revealed an elevated eosinophil level (24.0%) with markedly toxic granules. Gastrointestinal endoscopy revealed multiple ulcers and erosions in the pharynx, esophagus, stomach, and colon. Histopathological diagnosis indicated nonspecific inflammation with poor infiltration of eosinophils. Bone marrow FISH test was positive for 4q12 deletion (FIP1L1::PDGFRA), leading to the diagnosis of FIP1L1::PDGFRA-positive chronic eosinophilic leukemia. Following initiation of oral administration of imatinib 100 mg/day, the number of eosinophils decreased rapidly, and normalized 2 days after the start of imatinib. The mucosal lesions showed significant improvement and were diagnosed as leukemia-associated lesions. Based on the clinical course of our patient, multiple oral cavity and gastrointestinal ulcers could be the initial presentation in this leukemia.

Endometriosis is a complex and potentially debilitating condition that has major impact on quality of life. There is emerging evidence that biological compounds found in garlic () may be effective for attenuating endometrial pain. Suggested mechanisms for efficacy include modulation of inflammation and potent antioxidant effects. Aged-garlic-extract (AGE) is a centuries old process describing ethanolic extracts of garlic bulbs for 12-20 months. The AGE formulation realised contains a complex array of stabilised biologics with significant immunomodulatory effects relevant to inflammatory conditions. This perspective article puts forward a hypothesis that AGE should be considered as a prophylactic to manage endometrial pain.

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Advances in spinal cord stimulator (SCS) technology and increasing prevalence of magnetic resonance imaging (MRI) diagnostic testing require empirical evidence describing the presence of MRI-related SCS adverse events related to off-label use of imaging. MRI safety recommendations vary based on the type of stimulator used with scant availability regarding adverse events associated with off-label MRI use. The aim of this case series is to describe the type and frequency of adverse events associated with off-label MRI use in patients with implanted SCSs.

We report the introduction of a novel single-port laparoscopic-assisted trans-scrotal hernia sac ligation (LAT-HSL) technique for the treatment of inguinal hernias in pediatric males. In this article, we describe the LAT-HSL technique and the outcomes.