Empty sella in somatotropic pituitary adenomas; a series of 23 cases.

Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.

A rare case of aneurysmal bone cyst of the anterior clinoid process in an 18-year-old female mimicking optic neuritis.

BACKGROUND: Aneurysmal bone cyst (ABC) is an uncommon, benign, vascular multicystic bony lesion that most frequently develops in the first two decades of life. The metaphysis of long bones, pelvic, and vertebral column are the most common locations. The precise underlying pathophysiology of ABCs formation remains unclear; however, it is believed that reactive processes subsequent to trauma or vascular disturbance may play an important role. Involvement of the skull base rarely occurs with a prevalence of up to 5% of intracranial ABCs. CASE PRESENTATIONS: An 18-year-old adolescent female with a history of progressive blurred vision since three months ago presented to our office. The brain and orbital MRI demonstrated no abnormal findings. After three months of glucocorticoid treatment with the diagnosis of multiple sclerosis, the visual impairment of the left eye deteriorated abruptly. The patient underwent an MRI and the imaging study demonstrated a well-defined 30 × 22 × 20-mm lesion at the anterior clinoid process with an extension to the optic canal and ethmoid sinus. The patient underwent pterional craniotomy, and the tumor was resected. The histopathological examination was suggestive of ABC. CONCLUSION: ABC and other conditions should be considered in young-age people with an early unilateral decline in vision and imaging studies should be obtained in early stages and during follow-ups.

Integrated bioinformatics approaches and expression assays identified new markers in pituitary adenomas.

Pituitary adenomas (PA) include about one third of primary central nervous tumors in adolescent and young adult. Despite extensive research, the underlying mechanism of PA tumorigenesis is still unknown. In the present study, through bioinformatics analysis of a PA-related dataset downloaded from GEO database, we attempted to identify pair(s) of lncRNA/target mRNA whose expression changes may be involved in the tumorigenesis of PAs. For this end, we evaluated expression of a set of bioinformatically obtained genes in 46 PA tissues against adjacent non-tumor pituitary tissues. The bioinformatics step led to selection of four genes for validation through expression assays. Expression levels of HIF1A and MAPK1 were increased in NFPA tissues (P < 0.0001 and =0.0042, respectively). Expression level of BANCR was significantly decreased in tumor tissues (P < 0.0001). However, expression of STAT3 was not meaningfully different between the two tissue types (P = 0.56). Since there was no significant correlation between MAPK1 and BANCR expressions in either tumor or adjacent normal tissues, the regulatory effect of BANCR on MAPK1 was not confirmed. In conclusion, this study offers information about deregulation of bioinformatically identified genes in PA tumors and indicates that further studies in this field is needed to understand the involved molecular mechanisms.

Vertical triband flag sign for differential diagnosis of Rathke's cleft cyst.

Background: The Rathke cleft cyst (RCC) is a type of cystic growth that is benign, circular, and well-defined with an incidence rate of 4 %. This study aims to identify a useful diagnostic imaging sign that can aid in the differentiation of RCC from other cystic lesions. Methods: We retrospectively analyzed the records of 42 symptomatic RCC patients who were referred to our facility between 2016 and 2023. The data for the study were obtained from our electronic database. All magnetic resonance imaging (MRI) studies were performed using a 1.5-T superconducting magnetic scanner. All patients underwent endonasal transsphenoidal surgical resection. All MRIs were reviewed and evaluated by a neurosurgeon and a neuroradiologist. Results: There were 8 (19 %) males and 34 (81 %) females with a mean age of 37.2-years. Our study identified a distinct imaging characteristic in 38 of the cases, which we have named the "vertical triband flag sign", due to the growth of the cyst developing a specific appearance. The flag sign was mostly observed only in the T1-images (71.5 %), while in four cases the sign was spotted only in T2-images, and in four cases it appeared in both T1 and T2. In 4 cases, the flag sign was not observed in which further investigations revealed that these cases were suprasellar or small sellar RCCs. The dot sign, which is a characteristic finding in RCCs was only observed in one of our cases. Conclusion: Early diagnosis of RCCs may be facilitated by utilizing the vertical triband flag sign.

A bioinformatics-based approach and expression assay for identification of dysregulated genes in pituitary adenoma.

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary neuroendocrine tumors that are associated with morbidity. The exact pathophysiological process leading to this pathology is not known. Nerve growth factor (NGF) is a neurotropic factor that might be involved in this process. We used bioinformatics tools to analyze expression of genes in NFPA samples. Our analyses led to identification of NGF-related genes, namely ARC, ID1, and SH3GL3 - as well as one long non-coding RNA (lncRNA) called myocardial infarction associated transcript (MIAT). Then, we assessed their expression in NFPAs and their adjacent non-cancerous samples. While expression levels of SH3GL3 and MIAT were different between NFPA samples and control samples, expressions of ARC and ID1 were not meaningfully different between these two groups of specimens. SH3GL3 was over-expressed in NFPA samples compared with control samples (expression ratio (95% CI)= 8.22 (1.51-44.6), P value= 0.03). Similarly, expression of MIAT was higher in NFPAs compared with controls (expression ratio (95% CI)= 7.7 (1.7-33.6), P value= 0.009). Taken together, we validated the bioinformatics results regarding the expression of SH3GL3 and MIAT. This study provides a deeper understanding of the involvement of these genes in the pituitary tumorigenesis.

Importance of Intraoperative Factors in Postoperative Arginine Vasopressin Deficiency After Pituitary Adenoma Surgery.

OBJECTIVE: Pituitary adenoma (PA) is the most frequent tumor in the sellar region. Arginine vasopressin deficiency (AVP-D), formerly known as central diabetes insipidus, is a common complication after pituitary surgeries. In this study, we reviewed patients with PAs after endoscopic transsphenoidal surgery, evaluated the incidence of postoperative AVP-D, and determined associated risk factors. METHODS: We retrospectively studied 520 patients who underwent endoscopic transsphenoidal surgery for PAs and evaluated perioperative risk factors and their associations with postoperative AVP-D. Patients who developed AVP-D were categorized in 3 groups: (1) early AVP-D, (2) transient AVP-D, and (3) permanent AVP-D. RESULTS: Of the 520 patients, 24.8% experienced early AVP-D, and 1.9% (n = 10) had transient AVP-D. Permanent AVP-D was observed in only 6 patients (1.1%). Gross total resection, hormonal remission, pituitary stalk manipulation, and intraoperative cerebrospinal fluid leak were significantly associated with a higher incidence of AVP-D (P = .027, P = .002, P < .001 and P < .001, respectively). All patients who developed permanent AVP-D had somatotroph adenomas. AVP-D was not found to be related with tumor size. The length of hospital stay was prolonged by AVP-D on average by 1.5 days (P = .018). CONCLUSION: The reported incidence of AVP-D has a considerably wide range. A consistent definition and grading for AVP-D will increase consistency and comparability among studies. Nonetheless, most patients experience AVP-D on a temporary basis, and only a few require long-term treatment. Cerebrospinal fluid leak, gross total resection, and hormonal remission were identified as risk factors for postoperative AVP-D. We believe that the intraoperative risk factors play the main role in postoperative AVP-D. The course of surgery and operative findings help us plan selective postoperative patient monitoring and care.

Interaction between SIRT1 and non-coding RNAs in different disorders.

SIRT1 is a member of the sirtuin family functioning in the process of removal of acetyl groups from different proteins. This protein has several biological functions and is involved in the pathogenesis of metabolic diseases, malignancy, aging, neurodegenerative disorders and inflammation. Several long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) have been found to interact with SIRT1. These interactions have been assessed in the contexts of sepsis, cardiomyopathy, heart failure, non-alcoholic fatty liver disease, chronic hepatitis, cardiac fibrosis, myocardial ischemia/reperfusion injury, diabetes, ischemic stroke, immune-related disorders and cancers. Notably, SIRT1-interacting non-coding RNAs have been found to interact with each other. Several circRNA/miRNA and lncRNA/miRNA pairs that interact with SIRT1 have been identified. These axes are potential targets for design of novel therapies for different disorders. In the current review, we summarize the interactions between three classes of non-coding RNAs and SIRT1.

A review on the role of CASC11 in cancers.

The long non-coding RNA (lncRNA) cancer susceptibility 11 (CASC11) is a newly identified lncRNA located on chromosome 8q24.21. The expression of lncRNA CASC11 has been found to be elevated in different cancer types and the prognosis of the tumor is inversely correlated with the high CASC11 expression. Moreover, lncRNA CASC11 has an oncogenic function in cancers. The biological characteristics of the tumors, such as proliferation, migration, invasion, autophagy, and apoptosis can be controlled by this lncRNA. In addition to interacting with miRNAs, proteins, transcription factors, and other molecules, the lncRNA CASC11 modulates signaling pathways including Wnt/ß-catenin and epithelial-mesenchymal transition. In this review, we have summarized studies on the role of lncRNA CASC11 in the carcinogenesis from cell lines, in vivo, and clinical perspectives.

Expression pattern of lncRNAs in pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing's syndrome. NFPA carcinogenesis depends on several molecular players. Long non-coding RNAs (lncRNAs) are a class of molecular players whose role in tumorigenesis has just recently been recognized. In the current study, we appraised expressions of 5 lncRNAs, namely FGD5-AS1, ATP6V0E2-AS1, ARHGAP5-AS1, WWC2-AS2 and EPB41L4A-AS1 in NFPAs versus their corresponding non-tumoral samples. Expressions of ATP6V0E2-AS1, EPB41L4A-AS1, FGD5-AS1 and WWC2-AS2 were significantly increased in NFPA samples compared with adjacent non-tumoral samples (P values = 0.037, 0.007, 0.008 and 0.03, respectively). However, expression of ARHGAP5-AS1 was not different between NFPA samples and controls (P value = 0.62). EPB41L4A-AS1 and FGD5-AS1 could discriminate between NFPA samples and adjacent non-tumoral samples (P values = 0.03 and 0.04, respectively). However, the AUC values were not appropriate. There was a significant positive association between age of NFPA patients and invasiveness of NFPA (χ2 = 4.24, P value = 0.039). Moreover, there was a significant positive association between diseases duration and CSF leak (χ2 = 11.4, p value = 0.023). Finally, there was a significant positive association between tumor size and Knosp classification (χ2 = 11.5, p value = 0.02) and invasiveness of NFPA (χ2 = 6.12, p value = 0.04). The current study provides information about dysregulation of lncRNAs in NFPAs and warrants additional studies in this field.

Dysregulation of PVT1 and NEAT1 lncRNAs in pituitary adenomas.

Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.

Upregulation of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in non-functioning pituitary adenoma.

Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94-25.36), 11.22 (4.3-28.8) and 9.33 (4.12-21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.

A review on the role of NDRG1 in different cancers.

NDRG1 is a member of the α/ß hydrolase superfamily that resides in the cytoplasm and participates in the stress responses, hormone response, cell growth, and differentiation. Several studies have pointed to the importance of NDRG1 in the carcinogenesis. This gene has been found to be up-regulated in an array of cancer types such as bladder, esophageal squamous cell carcinoma, endometrial, lung and liver cancers, but being down-regulated in other types of cancers such as colorectal, gastric and ovarian cancers. The current study summarizes the evidence on the role of NDRG1 in the carcinogenic processes in different types of tissues.

Endoscopic versus Microsurgical Resection of Third Ventricle Colloid Cysts: A Single-Center Case Series of 140 Consecutive Patients.

BACKGROUND: Both endoscopic and microsurgery transcortical resection methods are used for colloid cysts of the third ventricle but they have not been compared regarding benefits and pitfalls. METHODS: Data of patients who underwent surgical resection of third ventricle colloid cyst via either endoscopic or microsurgery approach by a single surgeon from 2005 to 2020 were retrospectively collected. After administration of criteria, 140 records were retrieved (60 patients through endoscopic resection and 80 patients by a transcranial microsurgery approach). Clinical and surgical measures were compared between the 2 types of surgery after adjustment for confounders. RESULTS: Length of hospital stay, postoperative meningitis, operation time, cyst size, and baseline comorbidities were similar between two groups. Gross total resection (GTR) was achieved for all patients in the microsurgery group, whereas in the endoscopic group, resection was lower (90% vs. 100%; P = 0.005). Intraoperative hemorrhage occurred in 14 endoscopic patients (23.3%), whereas for the microscopic group, it was zero (P < 0.001). Postoperative shunt was required for 2 patients (one in the endoscopic group and the other in the microscopic group). Two patients had tumor recurrence, both of whom were in the endoscopic group. No mortality was detected in either group. Multivariate analyses were insignificant for confounding effects of clinical and demographic factors in occurrence of worse surgical outcomes (non-GTR and hemorrhage). CONCLUSIONS: In our series, the rate of intraoperative hemorrhage was higher with the endoscopic method and GTR was lower, even after adjustment for other factors. This situation could be caused by technological shortcomings and limited space for resection maneuvers and management of complications.

A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders.

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.

Surgical anatomic findings of sphenoid sinus in 1009 Iranian patients with pituitary adenoma undergoing endoscopic transsphenoidal surgery.

OBJECTIVE: The most common surgical technique for the management of pituitary adenomas is the endoscopic endonasal transsphenoidal approach (EEA). preoperative neuroimaging along with detecting surgical landmarks of the sphenoid sinus during surgery is important for making a successful operation. METHOD: This study includes 1009 patients with pituitary adenomas who underwent EEA between 2013 and 2020. We evaluated the anatomical features of the sphenoid sinus through a panel of items obtained from imaging and intra-operative findings. RESULTS: Our result includes 57.38% nonfunctional, 8.42% cushing, 12.39% prolactinoma, and 21.8% acromegaly patients who had undergone endoscopic endonasal transsphenoidal surgery. The mean age of the patients was 45 with a male to female ratio of 1.2:1. Sellar sphenoid type was the most common (91.8%) with only 12% symmetrical inter sphenoid septa, Internal carotid artery dehiscence was found in 1.7% of the cases. Apoplexy was present in 6.3% of patients, which was found more prevalent in nonfunctional adenomas (9.67%, Odds ratio: 4.85, 95% CI 2.24-11.79) and further investigation revealed a significant association between apoplexy and sphenoid mucosal edema and hemorrhage (Odds ratio: 43.0, 95% CI 22.50-84.26), and between apoplexy and cystic lesions (OR = 4.14, 95% CI 1.87-8.45, P-value < 0.0001). Acromegaly is associated with the increased number of lateral recces (Odds ratio: 11.41, 95% CI 7.54-17.52), septation of the sphenoid sinus (Marginal mean: 3.92, 95% CI 3.69-4.14), edematous sinonasal mucosa (Odds ratio: 6.7; 95% CI 4.46-10.08), and higher bony (OR: 4.81, 95% CI 2.60-8.97, P-value < 0.001) and cavernous (OR: 1.7, 95% CI 1.13-2.46, P-value < 0.01) invasion. CONCLUSION: The present study provides anatomical data about the sphenoid sinus and its adjacent vital structures with adenomal specific changes that are necessary to prevent complications during endoscopic advanced transsphenoidal surgery.

National and subnational burden of brain and central nervous system cancers in Iran, 1990-2019: Results from the global burden of disease study 2019.

INTRODUCTION: Central nervous system cancers (CNS cancers) impose a significant burden upon healthcare systems worldwide. Currently, the lack of a comprehensive study to assess various epidemiological indexes of CNS cancers on national and subnational scales in Iran can hamper healthcare planning and resource allocation in this regard. This study aims to fill this gap by providing estimates of CNS cancer epidemiological measures on national and subnational levels in Iran from 1990 to 2019. MATERIALS AND METHODS: This study is a part of Global Burden of Disease (GBD) 2019 that contains epidemiological measures including prevalence, incidence, mortality, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) of CNS cancers. Age standardization was utilized for comparing different provinces. RESULTS: In 2019, 5811 (95% Uncertainty Interval: 2942-7046) national new cases and 3494 (1751-4173) deaths due to CNS cancers were reported. National age-standardized incidence (ASIR), deaths (ASDR), and DALYs rates were 7.3 (3.7-8.8), 4.6 (2.3-5.5), and 156.4 (82.0-187.0) per 100,000 in 2019, respectively. Subnational results revealed that ASDR and ASIR have increased in the past 30 years in all provinces. Although incidence rates have increased in all age groups and genders since 1990, death rates have remained the same for most age groups and genders except for young patients aged under 15, where a decrease in mortality and YLLs can be observed. CONCLUSION: The incidence, deaths, and DALYs of CNS cancers increased at national and subnational levels. These findings should be considered for planning and resource allocation.

The Sensorineural Hearing Loss Related to a Rare Infratentorial Developmental Venous Angioma: A Case Report and Review of Literature.

BACKGROUND: Developmental venous anomaly (DVA) is a benign venous abnormality draining normal brain parenchyma. It is mostly asymptomatic; however, rare complications such as hemorrhage may lead to symptomatic conditions. Headache and seizure are the most common symptoms. Hearing loss is an extremely rare presentation of DVA. To our knowledge, only five cases of DVA, presenting with hearing loss, had been reported so far. CASE PRESENTATION: We report the case of a 27-year-old woman who presented with a sensorineural hearing loss followed by facial paresis. Magnetic resonance imaging (MRI) and computed tomography (CT) angiography revealed hematoma with adjacent converging veins showing a typical "caput medusa" sign in the left middle cerebellar peduncle, in favor of DVA. Due to the compression effect of hematoma, she underwent surgery. Hearing loss and facial paresis improved significantly during the postoperative follow-up. CONCLUSION: Although DVA is mostly benign and asymptomatic, complications such as hemorrhage rarely occur. Hearing loss is an extremely rare presentation that can be attributable to the compression effect on the cranial nerve VII to VIII complex. In the case of compression effect or progression of symptoms, surgical intervention is necessary. A good clinical outcome could be expected postoperatively.

Arachnoid prolapse in endoscopic transsphenoidal surgery of pituitary adenoma, technical note.

PURPOSE: An arachnoid prolapse after endoscopic transsphenoidal surgery for a pituitary adenoma is an uncommon, but important, phenomenon which should be managed. We have evaluated the efficacy of a new simple technique to correct the prolapsed arachnoid following endoscopic surgery of pituitary adenomas. METHODS: A total of 1352 patients with pituitary adenomas, 24-76 years old, who underwent full endoscopic transsphenoidal surgeries between February 2014 and February 2019 in Erfan and Loghman Hakim hospitals. 46 patients with arachnoid prolapse participated in this study and41 patients completed the study. Arachnoid prolapse was repaired by bipolar cauterization with either autologous fat grafts (36 patients) or without autologous fat grafts (5patients). RESULTS: Of 41 patients who completed the study, all except one, had large adenomas with significant suprasellar extension and enlarged diaphragma sellae. All patients had arachnoid prolapse at the end of the tumor removal stage and 13 patients had very minor intraoperative CSF leakage. Prolapsed arachnoid was repaired using a bipolar cautery with or without the autologous fat graft. During the postoperative follow-up period, none of the patient experienced early or delayed postoperative CSF leakage, meningitis, visual deterioration, delayed epistaxis, cranial nerve palsy, recurrence, or death. CONCLUSION: Bipolar cauterization is a safe, effective technique to repair a suprasellar arachnoid prolapse during reconstruction of the sellar floor following endoscopic transsphenoidal pituitary surgery.

Epidemiology of Brain and Other Central Nervous System Cancers in the North Africa and Middle East Region: A Systematic Analysis of the Global Burden of Disease Study 1990-2019.

OBJECTIVE: To present estimates of prevalence and incidence of and contributors to central nervous system (CNS) cancers, death, years of life lost, years lived with disability, and disability-adjusted life years from 1990 to 2019 in North Africa and the Middle East. METHODS: Primary measures were retrieved from Global Burden of Disease 2019. Contribution of various factors to observed incidence and mortality changes was investigated with decomposition and age-period-cohort analyses. RESULTS: In 2019, 27,529 (95% uncertainty interval [UI]: 18,554-32,579; percent change compared with 1990: +152.5%) new CNS cancers and 17,773 (95% UI:12,096-20,936; percent change compared with 1990: +111.5%) deaths occurred. Meanwhile, 71.0% increase led to 71,6271 (95% UI: 493,932-848,226) disability-adjusted life years in 2019 with a halved years of life lost/years lived with disability ratio of 66.3% (proxy of worse care quality). Altogether, 97,195 (95% UI: 64,216-115,621; percent change compared with 1990: +280.5%) patients with prevalent cases were alive in 2019. All decomposed indices, including aging, cause-specific incidence, and population growth, contributed substantially to increased incidence of CNS cancers. Moreover, age brackets, study period (1990-2019), and 5-year cohorts all demonstrated positive effects, while age had a mixed influence in different age groups. Palestine harbored the highest age-standardized disability-adjusted life years rate in 2019 (232.0 [95% UI: 175.6-279.5]), while Tunisia had the lowest (41.8 [95% UI: 27.6-57.1] per 100,000). The greatest burden increase was found in Saudi Arabia (32.3%). CONCLUSIONS: The burden of CNS cancers is rising in North Africa and the Middle East, with major heterogeneities among countries. Improved early detection and health care access across countries are required to bridge inequalities and address the rising burden of CNS malignancies.

Interplay between programmed death-ligand 1 and non-coding RNAs.

Programmed death-ligand 1 (PD-L1) is a transmembrane protein with essential roles in the suppression of adaptive immune responses. As an immune checkpoint molecule, PD-L1 can be exploited by cancer cells to evade the anti-tumor attacks initiated by the immune system. Thus, blockade of the PD1/PD-L1 axis can eliminate the suppressive signals and release the antitumor immune responses. Identification of the underlying mechanisms of modulation of the activity of the PD1/PD-L1 axis would facilitate the design of more efficacious therapeutic options and better assignment of patients for each option. Recent studies have confirmed the interactions between miRNAs/lncRNAs/circ-RNAs and the PD1/PD-L1 axis. In the current review, we give a summary of interactions between these transcripts and PD-L1 in the context of cancer. We also overview the consequences of these interactions in the determination of the response of patients to anti-cancer drugs.