Advanced neuroimaging of the trigeminal nerve and the whole brain in trigeminal neuralgia: a systematic review.

ABSTRACT: For trigeminal neuralgia (TN), a major role of imaging is to identify the causes, but recent studies demonstrated structural and microstructural changes in the affected nerve. Moreover, an increasing number of studies have reported central nervous system involvement in TN. In this systematic review, recent quantitative magnetic resonance imaging (MRI) studies of the trigeminal nerve and the brain in patients with TN were compiled, organized, and discussed, particularly emphasizing the possible background mechanisms and the interpretation of the results. A systematic search of quantitative MRI studies of the trigeminal nerve and the brain in patients with TN was conducted using PubMed. We included the studies of the primary TN published during 2013 to 2023, conducted for the assessment of the structural and microstructural analysis of the trigeminal nerve, and the structural, diffusion, and functional MRI analysis of the brain. Quantitative MRI studies of the affected trigeminal nerves and the trigeminal pathway demonstrated structural/microstructural alterations and treatment-related changes, which differentiated responders from nonresponders. Quantitative analysis of the brain revealed changes in the brain areas associated with pain processing/modulation and emotional networks. Studies of the affected nerve demonstrated evidence of demyelination and axonal damage, compatible with pathological findings, and have shown its potential value as a tool to assess treatment outcomes. Quantitative MRI has also revealed the possibility of dynamic microstructural, structural, and functional neuronal plasticity of the brain. Further studies are needed to understand these complex mechanisms of neuronal plasticity and to achieve a consensus on the clinical use of quantitative MRI in TN.

Diagnostic and therapeutic use of oral micronized progesterone in endocrinology.

Progesterone is a natural steroid hormone, while progestins are synthetic molecules. In the female reproductive system, progesterone contributes to the control of luteinizing hormone and follicle-stimulating hormone secretion and their pulsatility, via its receptors on the kisspeptin, neurokinin B, and dynorphin neurons in the hypothalamus. Progesterone together with estradiol controls the cyclic changes of proliferation and decidualization of the endometrium; exerts anti-mitogenic actions on endometrial epithelial cells; regulates normal menstrual bleeding; contributes to fertilization and pregnancy maintenance; participates in the onset of labor. In addition, it exerts numerous effects on other endocrine systems. Micronized progesterone (MP) is natural progesterone with increased bioavailability, due to its pharmacotechnical micronized structure, which makes it an attractive diagnostic and therapeutic tool. This critical literature review aims to summarize and put forward the potential diagnostic and therapeutic uses of MP in the field of endocrinology. During reproductive life, MP is used for diagnostic purposes in the evaluation of primary or secondary amenorrhea as a challenge test. Moreover, it can be prescribed to women presenting with amenorrhea or oligomenorrhea for induction of withdrawal bleeding, in order to time blood-sampling for diagnostic purposes in early follicular phase. Therapeutically, MP, alone or combined with estrogens, is a useful tool in various endocrine disorders including primary amenorrhea, abnormal uterine bleeding due to disordered ovulation, luteal phase deficiency, premenstrual syndrome, polycystic ovary syndrome, secondary amenorrhea [functional hypothalamic amenorrhea, premature ovarian insufficiency], perimenopause and menopause. When administrated per os, acting as a neurosteroid directly or through its metabolites, it exerts beneficial effects on brain function such as alleviation of symptoms of anxiety and depression, asw well as of sleep problems, while it improves working memory in peri- and menopausal women. Micronized progesterone preserves full potential of progesterone activity, without presenting many of the side-effects of progestins. Although it has been associated with more frequent drowsiness and dizziness, it can be well tolerated with nocturnal administration. Because of its better safety profile, especially with regard to metabolic ailments, breast cancer risk and veno-thromboembolism risk, MP is the preferred option for individuals with an increased risk of cardiovascular and metabolic diseases and of all-cause mortality.

Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency.

Gonadotropin-releasing hormone (GnRH) deficiency (GD) is a disorder characterized by absent or delayed puberty, with largely unknown genetic causes. The purpose of this study was to obtain and exploit gene expression profiles of GnRH neurons during development to unveil novel biological mechanisms and genetic determinants underlying GD. Here, we combined bioinformatic analyses of immortalized and primary embryonic GnRH neuron transcriptomes with exome sequencing from GD patients to identify candidate genes implicated in the pathogenesis of GD. Among differentially expressed and filtered transcripts, we found loss-of-function (LoF) variants of the autism-linked neuroligin 3 (NLGN3) gene in two unrelated patients co-presenting with GD and neurodevelopmental traits. We demonstrated that NLGN3 is upregulated in maturing GnRH neurons and that NLGN3 wild-type, but not mutant, protein promotes neuritogenesis when overexpressed in developing GnRH cells. Our data represent proof of principle that this complementary approach can identify new candidate GD genes and demonstrate that LoF NLGN3 variants can contribute to GD. This novel genotype-phenotype correlation implies common genetic mechanisms underlying neurodevelopmental disorders, such as GD and autistic spectrum disorder.

Disease Burden and Treatment Preferences Amongst Postmenopausal Women with Severe Osteoporosis in Greece.

Objective: The objectives of this study were to elicit self-reported health status, quantify osteoporosis-related burden, and understand preferences for treatment attributes among postmenopausal women with severe osteoporosis in Greece. Methods: Postmenopausal women with self-reported severe osteoporosis, defined as having suffered at least one osteoporotic fracture and reporting a T-score of ≤-2.5, were asked to evaluate their health status, osteoporosis management, and disease-related physical, emotional, and financial burden. Participants were also asked to rate a series of treatment attributes and state their preference for unlabeled anabolic treatments, based on scenarios describing key treatment characteristics. Results: Approximately one third (31%) of the 186 participants who responded to the survey in full had been living with severe osteoporosis for more than 10 years. Three quarters of participants (72%) considered their overall quality of life (QoL) to be worse than it had been 10 years prior, and the vast majority (89%) attributed this deterioration to osteoporosis. Direct, out of pocket, disease-related costs of at least €100 per month were reported by 86% of participants. Patients attached the greatest value to a treatment that would decrease probability of future fractures, followed by increase in bone density, safety, and mode and frequency of administration. When asked to select their preferred treatment scenario between two anabolic treatments, 70% of participants opted for the scenario that shared treatment characteristics with romosozumab over a scenario that shared treatment characteristics with teriparatide. Conclusion: Our study revealed that osteoporosis placed a considerable burden on QoL for postmenopausal women with severe osteoporosis in Greece. Patients reported valuing treatment efficacy, measured through reduction in future fractures and increase in bone density, and safety, as key treatment attributes.

The effect of positron emission tomography/computed tomography in axillary surgery approach after neoadjuvant treatment in breast cancer

SUMMARY OBJECTIVE: The aim of this study was to determine the role of positron emission tomography/computed tomography in the decision to perform axillary surgery by comparing positron emission tomography/computed tomography findings with pathology consistency after neoadjuvant chemotherapy. METHODS: Patients who were diagnosed for T1-4, cN1/2 breast cancer receiving neoadjuvant chemotherapy in our clinic between January 2016 and February 2021 were evaluated. Clinical and radiological responses, axillary surgery, and histopathological results after neoadjuvant chemotherapy were evaluated. RESULTS: Axillary involvement was not detected in positron emission tomography/computed tomography after neoadjuvant chemotherapy in 140 (60.6%) of 231 node-positive patients. In total, 88 (62.8%) of these patients underwent sentinel lymph node biopsy, and axillary lymph node dissection was performed in 29 (33%) of these patients upon detection of 1 or 2 positive lymph nodes. The other 52 (37.1%) patients underwent direct axillary lymph node dissection, and no metastatic lymph nodes were detected in 33 (63.4%) patients. No metastatic lymph node was found pathologically in a total of 92 patients without involvement in positron emission tomography/computed tomography, and the negative predictive value was calculated as 65.7%. Axillary lymph node dissection was performed in 91 (39.4%) patients with axillary involvement in positron emission tomography/computed tomography after neoadjuvant chemotherapy. Metastatic lymph nodes were found pathologically in 83 of these patients, and the positive predictive value was calculated as 91.2%. CONCLUSION: Positron emission tomography/computed tomography was found to be useful in the evaluation of clinical response, but it was not sufficient enough to predict a complete pathological response. When planning axillary surgery, axillary lymph node dissection should not be decided only with a positive positron emission tomography/computed tomography. Other radiological images should also be evaluated, and a positive sentinel lymph node biopsy should be the determinant of axillary lymph node dissection.

Clinical, Serological, and Immunological Characteristics of Greek Patients with Polymyalgia Rheumatica and/or Giant Cell Arteritis: A Research Protocol.

Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) are chronic inflammatory disorders that usually affect older people. Although the aetiology of these diseases remains unknown, genetic, environmental, and immune factors have been implicated. Specific cytokines such as the IL-6, IL-1ß, IL-12, IL-17, and interferon -γ seem to play an essential role. The diagnosis of the disease is usually based on clinical manifestations and the use of histology or imaging, while disease monitoring is based on physical examination, laboratory, and imaging findings. However, there is the unmet need in identifying possible biomarkers that could help the diagnosis and the monitoring as well. The present study aims to investigate the epidemiological, clinical, and immunological characteristics of PMR and/or GCA patients in the region of northwest Greece and to evaluate the role of specific molecules associated with the pathogenesis of the diseases, giving evidence to possible future biomarkers.

An Uncommon Case of Dulaglutide-Related Morbilliform Drug Eruption.

Dulaglutide is a once-weekly injectable glucagon-like peptide-1 (GLP-1) receptor agonist that has shown a durable glycemic efficacy as well as beneficial effects on body weight and major adverse cardiovascular events (MACE) outcomes, making it an important option for the treatment of type 2 diabetes. Common side effects of dulaglutide include nausea, diarrhea, and abdominal distension, and these are usually mild to moderate in severity and tend to diminish over time. Morbilliform drug eruptions to dulaglutide are very rare, with only one case reported until now. We report another case of dulaglutide-morbilliform drug eruption to alert the attending physicians that dulaglutide-related adverse skin reactions should be kept in mind as generalized use of dulaglutide and other GLP-1 receptor agonists are expected to remain in widespread clinical use in the future.

Y-shaped RNA secondary structure of a noncoding region in the genomic RNA of tick-borne encephalitis virus affects pathogenicity.

Tick-borne encephalitis virus (TBEV) is a zoonotic virus that causes encephalitis in humans. Various deletions have been reported in a variable region of the 3' untranslated region of the TBEV genome. This study analyzed the role of a Y-shaped secondary structure in the pathogenicity of TBEV by using reverse genetics. Deletion of the structure increased the mortality rate of virus-infected mice but did not affect the virus multiplication in cultured cells and organs. The results indicate that the secondary structure is involved in the regulation of TBEV pathogenesis.

Impact of spexin on metabolic diseases and inflammation: An updated minireview.

Spexin (SPX) is a 14 amino acid length peptide hormone which was discovered using bioinformatic tools. It is extensively expressed in central and peripheral tissues and secreted into circulation in response to metabolic stress. Recent studies revealed that SPX acts as a multifunctional peptide in various metabolic processes such as body weight, food intake, energy balance, glucose and lipid metabolism, lipid storage, salt-water balance, and arterial blood pressure. Endogenous SPX is sensitive to metabolic changes, and circulating levels of SPX have been shown to be reduced in chronic diseases such as obesity, diabetes, and insulin resistance. Moreover, in fish and rodent models, systemic SPX treatment has positive effects on metabolism including reduced food intake, fat mass, lipid accumulation, and inflammation, improved insulin sensitivity, energy expenditure, and organ functions which are underlying mechanisms in diseases. Taken together, these findings suggest that SPX is a potential drug target for the development of new pharmacological strategies to cure metabolic diseases. This review focuses on metabolo-protective properties of SPX and discusses novel insights into the biology and mechanism of SPX in the pathogenesis of diabetes, obesity, non-alcoholic fatty liver disease, metabolic syndrome, polycystic ovary syndrome, cardiovascular diseases, and kidney diseases, which are considerable global health problems.

Novel pediatric granulomatosis with polyangiitis with a marked bloody pericardial effusion and bloody stool: a case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis involving the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries that affects all age groups. No pediatric case with a bloody pericardial effusion resulting in cardiac tamponade and co-existing hematochezia has been reported. CASE PRESENTATION: A 14-year-old boy was referred for evaluation of prolonged fever, chest pain, and intermittent hematochezia. Diagnostic imaging showed a prominent pericardial effusion. Immediately after admission, his systolic blood pressure decreased. Emergent pericardiocentesis resulted in aspiration of a massive amount of bloody pericardial fluid. This was diagnosed as cardiac tamponade because his blood pressure recovered immediately after the drainage. The patient had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level on serological examination. Head MRI showed thickening of nasal and sinusoidal mucosa and a cystic mass in the left sphenoid sinus. After ruling out malignancy based on the cytology of the effusion, chest MRI, and gallium scintigraphy, total colonoscopy showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments. Biopsy specimens of aphthous lesions confirmed necrotizing granulomatous inflammation. A diagnosis of GPA was made based on these findings, and oral prednisolone (PSL) and azathioprine were started. The hematochezia disappeared rapidly, and no recurrence of pericardial effusion was seen after PSL tapering was completed. The PR3-ANCA level decreased into the normal range immediately after the initial therapy. CONCLUSIONS: Pericarditis is a common cardiac complication of GPA, but there have been no reports of resultant cardiac tamponade. This is the first case of pediatric GPA with cardiac and gastrointestinal complications preceding the common symptoms such as respiratory or renal symptoms. A case of pediatric GPA with hematochezia is also extremely rare. In conclusion, serial measurement of ANCA levels is important in patients with persistent fever and bloody stool, such as in inflammatory bowel disease, to make the diagnosis of a vasculitic syndrome.

Prevalence of morphometric vertebral fractures in osteoporotic patients in Greece: the Vertebral Integrity Assessment (VERTINAS) study.

Our purpose was to assess the prevalence of morphometric vertebral fractures (VFs) in osteoporotic patients in our country. We found that 25.4% of patients had sustained a VF, and the majority of them (76.6%) were undiagnosed prior to inclusion in this study. INTRODUCTION: We assessed the prevalence of morphometric vertebral fractures (VFs) in osteoporotic patients in our country. METHODS: Patients were recruited via announcements by the national media, their attending physicians or the National patients' Society. Inclusion criteria were (1) age > 50 years, (2) postmenopausal status > 2 years (women), (3) > 1-year use of medication for osteoporosis and (4) lack of radiological vertebral assessment for > 1 year. Exclusion criteria were (1) bone metabolic diseases other than osteoporosis, (2) patients with secondary osteoporosis, (3) patients with inability to stand/walk, (4) previous high-energy VFs. All patients performed lateral X-rays of the thoracic and lumbar spine that were evaluated separately both by certified radiologists on site as well as 3 consultant orthopaedic surgeons remotely through a specifically designed web database system. The Genant semi-quantitative method was used for the classification and grading of VFs and statistical analysis of the results was performed. RESULTS: One thousand six hundred fifty-two patients (1516 female, 70.02 ± 8.28 years; 136 male, 74.78 ± 8.25 years) were included in the final analysis. The prevalence of VFs was 25.4%, 76.6% of fractured patients were previously undiagnosed, and of these 39.9% had > 1 VFs. The most common fracture was T12, most fractures were found to be mild (grade 1) across all age groups, and patients 70-79 years and > 80 years were found to have a statistically significantly higher number of fractures than younger patients (p < 0.001). CONCLUSIONS: Our results of the high prevalence of morphometric VFs emphasise the need for baseline assessment of vertebral fragility in patients receiving treatment for osteoporosis, as well as follow-up radiographs at specified time periods while on therapy.

Adropin and spexin hormones regulate the systemic inflammation in adenine-induced chronic kidney failure in rat.

Chronic kidney disease is one of the major global health problems. Chronic renal failure is stimulated by many cytokines and chemokines. Adropin and spexin (SPX) are peptides hormones. These peptides could affect inflammatory conditions, but this is unclear. Due to the limited information, we planned to investigate the impact of adropin and SPX hormones on systemic inflammation in adenine induced chronic kidney failure rat model. Chronic kidney failure was induced by administering adenine hemisulfate. Renal functions were measured by an autoanalyzer. Granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, tumor necrosis factor-alpha, Eotaxin, growth-regulated oncogene-alpha, IP-10, monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1α, MIP-2, and RANTES levels were determined by Luminex. We observed an increase in 24-h urine volume and serum creatinine. Blood urea nitrogen (BUN) and urine protein levels were also significantly higher in the chronic kidney failure (CKF) group. Urine protein and 24-h urine volume were reduced with adropin and SPX treatments. Furthermore, G-CSF, IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-17A, and GRO-α significantly increased by CKF induction; however, these cytokines and chemokines significantly decreased by adropin treatment in the CKF group. Furthermore, adropin increased IP-10, MCP-1, MIP-1α, and MIP-2 levels. In addition, SPX treatment had a more limited effect, decreasing only G-CSF, IFN-γ, and IL-5 levels. The combined adropin + SPX treatment significantly reduced G-CSF, IFN-γ, IL-4, IL-5, IL-12, and IL-17A. Furthermore, IP-10, MCP-1, MCP-3, and MIP-2 were significantly increased by these combined treatments. Our findings indicate that renal functions and inflammatory response were modulated by adropin and SPX peptides. These peptides may have protective effects on systemic inflammation and renal failure progression.

Delivery of Financial Navigation Services Within National Cancer Institute-Designated Cancer Centers.

Background: Cancer centers have a responsibility to help patients manage the costs of their cancer treatment. This article describes the availability of financial navigation services within the National Cancer Institute (NCI)-designated cancer centers. Methods: Data were obtained from the NCI Survey of Financial Navigation Services and Research, an online survey administered to NCI-designated cancer centers from July to September 2019. Of the 62 eligible centers, 57 completed all or most of the survey, for a response rate of 90.5%. Results: Nearly all cancer centers reported providing help with applications for pharmaceutical assistance programs and medical discounts (96.5%), health insurance coverage (91.2%), assistance with nonmedical costs (96.5%), and help understanding medical bills and out-of-pocket costs (85.9%). Although other services were common, in some cases they were only available to certain patients. These services included direct financial assistance with medical and nonmedical costs and referrals to outside organizations for financial assistance. The least common services included medical debt management (63.2%), detailed discussions about the cost of treatment (54.4%), and guidance about legal protections (50.1%). Providing treatment cost transparency to patients was reported as a common challenge: 71.9% of centers agreed or strongly agreed that it is difficult to determine how much a cancer patient's treatment will cost, and 70.2% of oncologists are reluctant to discuss financial issues with patients. Conclusions: Cancer centers provide many financial services and resources. However, there remains a need to build additional capacity to deliver comprehensive financial navigation services and to understand the extent to which patients are referred and helped by these services.

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin.

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1ß, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFß1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1ß, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFß1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.