Visual Outcome for Children with Optic Pathway Gliomas Treated with Systemic Chemotherapy.

Purpose: This study aims to report visual acuity outcomes for patients with optic pathway gliomas (OPG) treated with systemic chemotherapy and analyze the associated factors. Patients and Methods: A retrospective study of 29 children with OPG treated with chemotherapy at King Hussein Cancer Center (KHCC), Amman, Jordan, between May/2005 and August/2020. Details on patient demographics, tumor location, systemic chemotherapy, and progression of disease were extracted from medical records. Results: Fifty-four eyes of twenty-nine patients were included in this study with a follow-up range from 2 to 17 years. Sixteen patients (55%) had a history of neurofibromatosis-1 (NF1). Most of the eyes (31, 57%) had visual acuity ranges in the moderate or better group. The age group ≥5 years at diagnosis, those with hydrocephalus, and patients with non-NF1 presented the worst visual acuity ranges from severe or worse; the p-value was 0.043, 0.0320, and 0.0054, respectively. Following treatment with systemic chemotherapy, visual acuity improved in 5 (17%) patients, remained the same in 23 (79%) patients, and only one patient (3%) had vision deterioration. Of the five patients who showed vision improvement, only one had radiological regression of the tumor. Parallel to this, three (10%) patients showed tumor progression in the final magnetic resonance image (MRI) findings without affecting the final vision. Conclusion: Children older than 5 years at diagnosis, in sporadic OPG, and those with hydrocephalus had the worst vision at presentation. Treatment with systemic chemotherapy prevented further deterioration of vision, and following treatment with systemic chemotherapy, most of the patients had the same vision; this stability indicates that vision at diagnosis is an important predictor for the final visual outcome.

Trends in Hospital Admissions Due to Neoplasms in England and Wales between 1999 and 2019: An Ecological Study.

Objectives: This study aimed to investigate the trends in neoplasm-related hospital admissions (NRHA) in England and Wales between 1999 and 2019. Methods: This is an ecological study using publicly available data taken from the two main medical databases in England and Wales; the Hospital Episode Statistics database in England and the Patient Episode Database in Wales. Hospital admissions data were collected for the period between April 1999 and March 2019. Results: A total of 35,704,781 NRHA were reported during the study period. Females contributed to 50.8% of NRHA. The NRHA rate among males increased by 50.0% [from 26.62 (95% CI 26.55−26.68) in 1999 to 39.93 (95% CI 39.86−40.00) in 2019 per 1000 persons, trend test, p < 0.001]. The NRHA rate among females increased by 44.1% [from 27.25 (95% CI 27.18−27.31) in 1999 to 39.25 (95% CI 39.18−39.32) in 2019 per 1000 persons, trend test, p < 0.001]. Overall, the rate of NRHA rose by 46.2% [from 26.93 (95% CI 26.89−26.98) in 1999 to 39.39 (95% CI 39.34−39.44) in 2019 per 1000 persons, trend test, p < 0.001]. Conclusion: Hospital admission rates due to neoplasms increased between 1999 and 2019. Our study demonstrates a variation in NRHA influenced by age and gender. Further observational studies are needed to identify other factors associated with increased hospital admissions among patients with different types of neoplasms.

The first reported case of CDH3-related hypotrichosis with juvenile macular dystrophy from Jordan: a case report.

BACKGROUND: Pathogenic variants in the Cadherin 3 (CDH3) gene are responsible for the occurrence of Hypotrichosis with Juvenile Macular Dystrophy (HJMD) and Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy Syndrome (EEMS), both of which are rare autosomal recessive disorders characterized by hypotrichosis and progressive macular dystrophy. The CDH3 gene encodes for P-cadherin, a calcium-binding protein that is essential for cell-cell adhesion, which is expressed in the retinal pigment epithelial cells and hair follicles. MATERIALS AND METHODS: Fundus examination of both eyes was done in addition to clinical investigation. Genomic DNA was extracted from a whole-blood sample and whole-exome sequencing (WES) was performed to identify the underlying etiology.All identified variants were evaluated for their pathogenicity and causality. RESULTS: We present the first case of HJMD in a 23-year-old female patient from Jordan. The patient presented to our ophthalmology clinic with poor vision in both eyes. Gross examination revealed sparse scalp hair along with macular dystrophy on fundus exam in both eyes. HJMD was suspected and whole-exome sequencing (WES) confirmed the diagnosis with the identification of a homozygous frameshift deletion (p.Gly277AlafsTer20) localised in exon 7 of the CDH3 gene. CONCLUSION: Blindness due to progressive macular degeneration is a common manifestation in numerous syndromic recessive disorders such as HJMD. Ophthalmologists should consider the importance of systemic manifestations and genetic testing for the confirmation of diagnosis.

Cytochrome 4Z1 Expression is Associated with Unfavorable Survival in Triple-Negative Breast Cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. MATERIALS AND METHODS: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. RESULTS: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). CONCLUSION: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1-targeted treatments.

Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study.

BACKGROUND: Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. OBJECTIVE: The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme's relationship with several clinicopathological features. METHODS: Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. RESULTS: CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). CONCLUSIONS: The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.

Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer.

BACKGROUND: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. METHODS: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme's relationship to several clinicopathological features and survival was explored. RESULTS: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). CONCLUSIONS: CYP4Z1 expression is associated with cervical cancer patients' survival and may serve as an independent predictor of poor prognosis in cervical cancer patients.

Glypican-1 Overexpression in Different Types of Breast Cancers.

PURPOSE: Treatment of metastatic breast cancer patients is challenging and remains a major underlying cause of female mortality. Understanding molecular alterations in tumor development is critical to identify novel biomarkers and targets for cancer diagnosis and therapy. One of the aberrant cancer expressions gaining recent research interest is glypican-1. Several studies reported strong glypican-1 expression in various types of human cancers. However, none of these investigated glypican-1 expression in a large cohort of breast cancer histopathological subtypes. PATIENTS AND METHODS: Immunohistochemistry was used to assess glypican-1 expression in 220 breast cancer patients and its relation to demographic and clinical features, as well as important prognostic immunohistochemical markers for breast cancer. RESULTS: Intense glypican-1 expression was recognized in all breast cancer histopathological subtypes. Normal, healthy breast tissue displayed a heterogeneous low expression (20%). Importantly, a strong differential in glypican-1 expression was determined between normal and malignant breast tissues. Moreover, there was a significantly high rate of glypican-1 expression in advanced grades of breast cancer patients and larger tumor sizes. Unfortunately, the glypican-1 expression demonstrated no obvious relationship with the expression of various biomarkers in breast cancer. CONCLUSION: This study may establish glypican-1 as a promising new therapeutic target for the development of therapy in breast cancer.

Polimorfismos de la metilenotetrahidrofolato reductasa C677T como factor de riesgo para el síndrome de ovario poliquístico en una muestra de mujeres jordanas / Methylenetetrahydrofolate Reductase C677T Polymorphisms as a Risk Factor for Polycystic Ovarian Syndrome in a Sample of Jordanian Women

Antecedentes: el síndrome de ovario poliquístico (SOP) es un trastorno endocrino reproductivo común, se puede identificar por hiperandrogenismo, oligomenorrea o anovulación y ovarios poliquísticos en la ecografía. Los polimorfismos de la metilentetrahidrofolato reductasa (MTHFR) C677T asociados con la hiperhomocisteinemia se encuentran entre los factores de riesgo del síndrome de ovario poliquístico. Objetivo: El presente estudio de casos y controles tiene como objetivo explorar la relación entre los polimorfismos C677T de la metilenotetrahidrofolato reductasa (MTHFR) como factor de riesgo y el síndrome de ovario poliquístico entre los pacientes jordanos que padecen esta enfermedad. Métodos: Se inscribieron en el estudio 306 sujetos (146 pacientes con SOP y 160 sujetos sanos como grupo de control). Se extrajo ADN de una muestra de sangre venosa extraída de cada participante para analizar los polimorfismos de MTHFR C677T utilizando la reacción en cadena de la polimerasa (PCR) en combinación con digestión con enzima de restricción (PCRRFLP). Posteriormente, los productos de PCR-RFLP se digirieron con la enzima HinfI, luego se sometieron a electroforesis en un gel de agarosa al 2%, se tiñeron y se examinaron bajo luz ultravioleta. Los niveles de homocisteína en plasma se analizaron utilizando el método ELISA. Resultados: Se observó una diferencia significativa en los niveles plasmáticos de homocisteína entre los pacientes con SOP frente a los sujetos de control y entre los diferentes polimorfismos de los pacientes con SOP. No se detectaron diferencias significativas en la distribución y frecuencia alélica de los polimorfismos MTHFR C677T en pacientes con SOP en comparación con los controles. El genotipo 677 / TT y el alelo T se asociaron con un aumento de 1,54 y 1,46 veces en la susceptibilidad al síndrome de ovario poliquístico. Conclusión: El estudio ha demostrado que el polimorfismo MTHFR T677T y el alelo T son posibles factores de riesgo de SOP entre las mujeres jordanas y pueden desempeñar un papel en la patogenia de la enfermedad

Background: Polycystic ovary syndrome (PCOS) is a common endocrine reproductive disorder, it can be identified by hyperandrogenism, oligomenorrhea or anovulation and polycystic ovaries on ultrasound. Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphisms associated with hyperhomocysteinemia are among the risk factors for PCOS. Objective: The present case control study aims to explore the relationship between Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphisms as a risk factor and PCOS among Jordanian patients suffering from this disease. Methods: 306 subjects (146 PCOS patients and 160 healthy subjects as a control group) were enrolled in the study. DNA was extracted from venous blood sample withdrawn from each participant for analyzing MTHFR C677T polymorphisms using Polymerase Chain Reaction (PCR) in combination with restriction enzyme fragment length polymorphism (PCR-RFLP). Later, PCR-RFLP products were digested with hinfI enzyme, then, electrophoresed on a 2% agarose gel, stained and examined under UV light. Plasma homocysteine levels were assayed using ELISA method. Results: A significant difference was observed in plasma homocysteine levels among PCOS patients versus the control subjects and in between the different polymorphisms of PCOS patients. No significant difference was detected in the distribution and allelic frequency of MTHFR C677T polymorphisms in PCOS patients compared to the controls. 677/TT genotype and T allele were associated with 1.54 and 1.46 folds increase in the susceptibility for PCOS. Conclusion: The study has shown that MTHFR T677T polymorphism and T allele are possible risk factors for PCOS among Jordanian women and may play a role in the pathogenesis of the disease.

¿Existe una asociación entre polimorfismos de inserción/supresión - 2549 en la región promotora del gen que codifica la vegfa como factor de riesgo y el descargo espontáneo idiopático recurrente en una muestra de mujeres jordanas? / Is there an association between - 2549 Insertion/ Deletion Polymorphisms in the Promotor Region of the Gene Encoding for VEGFA as a Risk Factor and the Idiopathic Recurrent Spontaneous Miscarriage in a sample of Jordanian Women?

Antecedentes: al menos el 50% de los casos de aborto espontáneo recurrente son etiológicamente idiopáticos. Recientemente se han propuesto varios polimorfismos genéticos como factores de riesgo de susceptibilidad a la pérdida del embarazo. Objetivo: El objetivo del presente estudio de casos y controles es establecer la asociación entre los polimorfismos funcionales −2549 I / D en la región promotora del gen del factor de crecimiento endotelial vascular A (VEGFA) y el aborto espontáneo recurrente idiopático (IRSM) en una muestra de las mujeres jordanas. Sujetos y métodos: Se reclutaron 328 sujetos, 103 y 98 mujeres con IRSM primario y secundario, respectivamente, se seleccionaron 127 mujeres normales como grupo de control. Se aisló ADN genómico de una muestra de sangre extraída de cada participante, luego, se genotipificaron los polimorfismos I / D -2549 del gen VEGFA mediante la reacción en cadena de la polimerasa (PCR). Resultados: Los resultados obtenidos revelaron que el polimorfismo ID y el alelo D de VEGFA -2549 polimorfismos I / D tienen las frecuencias más altas en pacientes IRSM tanto primario como secundario, sin diferencia significativa entre los tres grupos en cuanto a polimorfismos y frecuencias alélicas, pacientes con DD + ID Los modelos genéticos tienen una asociación positiva con un alto riesgo de IRSM versus el modelo II, y los pacientes con alelo D son más propensos a tener IRSM que los que tienen el alelo I, no hay diferencia significativa en la asociación de polimorfismos VEGFA -2549 I / D con IRSM en los tres modelos genéticos de los pacientes con IRSM primario y secundario. Conclusión: los pacientes con modelo genético ID de polimorfismos I / D -2549 en la región promotora del gen VEGFA y el alelo D tienen mayor riesgo de IRSM

Background: At least 50% of the cases of recurrent spontaneous miscarriage are aetiologically idiopathic. Recently various genetic polymorphisms have been proposed as susceptibility risk factors for pregnancy loss. Objective: The aim of the present case control study is to establish the association between the functional −2549 I/D polymorphisms in the promoter region of the vascular endothelial growth factor A (VEGFA) gene and idiopathic recurrent spontaneous miscarriage (IRSM) in a sample of Jordanian women. Subjects and methods: 328 subjects were recruited, 103 and 98 women with primary and secondary IRSM, respectively, 127 normal women were selected as a control group. Genomic DNA was isolated from a blood sample withdrawn from each participant, then, -2549 I/D polymorphisms of VEGFA gene were genotyped by Polymerase Chain Reaction (PCR). Results: The obtained results revealed that ID polymorphism and D allele of VEGFA -2549 I/D polymorphisms have the highest frequencies in both primary and secondary IRSM patients, no significant difference between the three groups regarding polymorphisms and allele frequencies, patients with DD+ID genetic models have positive association with high risk of IRSM versus II model, and patients with D allele are more liable to have IRSM than those having I allele, no significant difference in the association of VEGFA -2549 I/D polymorphisms with IRSM in the three genetic models of the primary and secondary IRSM patients. Conclusion: patients with ID genetic model of -2549 I/D polymorphisms in the VEGFA gene's promotor region and D allele have higher risk for IRSM.

Knowledge and awareness of the general population and healthcare providers about retinoblastoma: It is time to know the glow.

Retinoblastoma is the most frequent primary intraocular tumour in childhood. Early detection of retinoblastoma is the key to successful management with a higher chance of survival. This study aims to assess the knowledge of the general population and healthcare providers about retinoblastoma in term of presentation, risk factors, timing for diagnosis, and complications. A cross-sectional study using an online survey was conducted in three Arab countries (Jordan, Saudi Arabia, and Iraq) between 28 August and 16 September 2020. The questionnaire tool was constructed based on an extensive literature review to explore the study's aim and objectives. Logistic regression was used to identify predictors of better knowledge about retinoblastoma. A total of 3676 participants were involved in the study (Jordan = 2654, Saudi Arabia = 604, and Iraq = 418). The average retinoblastoma knowledge score for the whole study population was 6.25 (SD = 4.12) out of 21, representing 29.8% (out of the maximum possible total score). Participants aged above 50 years old, married individuals, those with a secondary education level, those who work as professionals in industry, those who have more than four children, and those who reported that they were not in direct contact with a large number of children were less likely to be knowledgeable about retinoblastoma presentation, risk factors, the timing for diagnosis, and complications (P < .05). Early detection is the cornerstone for decreasing morbidity and mortality among children with retinoblastoma. However, the awareness and knowledge about retinoblastoma are very limited in our study population. Efforts should be directed at increasing awareness of both the general population and healthcare providers regarding retinoblastoma. Policymakers are responsible for improving knowledge and awareness about retinoblastoma to facilitate early detection of the disease by conducting awareness campaigns in addition to improve screening skills of healthcare providers and providing them with proper screening and diagnostic tools.

Screening of cytochrome 4Z1 expression in human non-neoplastic, pre-neoplastic and neoplastic tissues.

BACKGROUND: Cytochromes P450 (CYPs) constitute an enzyme family involved in the oxidative metabolism of a wide variety of endogenous and exogenous compounds, including anti-cancer drugs and carcinogens. Unlike other human CYPs, CYP4Z1 is highly expressed in human breast carcinoma and is associated with poor prognosis. As a result, CYP4Z1 was hypothesised to be a potential biomarker or drug target for the discovery and development of promising anti-cancer therapies. MATERIALS AND METHODS: CYP4Z1 expression was immunohistochemically studied in a set of 100 different human tissues, including normal, benign, malignant and metastatic tissues, which originated from 27 anatomical sites. As a tumour model for CYP4Z1 expression, a panel of different breast cancers was evaluated for CYP4Z1 expression and its relation to histopathological features and prognostic immunohistochemical markers. RESULTS: The immunohistochemical results revealed that CYP4Z1 was expressed in only one (4.3%) of the normal tissues from the mammary glands, while the expression of the enzyme was positive in 1 (11%), 12 (19%) and 2 (40%) of the benign, malignant and metastatic tissues, respectively. Interestingly, several tumour entities showed prominent expressions of CYP4Z1, including carcinomas of adrenal cortex, squamous cells of oesophagus, lung and cervix, as well as seminoma, astrocytoma, melanoma and lastly endometrial adenocarcinoma. In breast cancers, CYP4Z1 was expressed in 82% of the cases. Its expression was significantly associated with the pathology of tumour, histological grade and status of lymph node metastasis. Importantly, it was also significantly associated with the expressions of Her2, P53 and Ki-67. CONCLUSION: These findings greatly support future plans for the use of CYP4Z1 as a biomarker or target for anti-cancer drugs. However, large-scale validation studies are needed to better delineate the potential use of CYP4Z1 for therapeutic purposes.

Clinical and Sonographic Evaluation of Postmenopausal Bleeding (PMB) Followed by Diagnostic and/or Therapeutic Hysteroscopy and Guided Biopsy in Jordanian Hospitals.

Background and Objectives: The goal of this study was to evaluate the clinical sonographic evaluation of postmenopausal bleeding (PMB) followed by diagnostic and/or therapeutic hysteroscopy and guided biopsy in Jordanian hospitals. Materials and Methods: A retrospective multi-centric study was performed in hospitals in Al-Karak and Amman from 2014-2016. The study recruited 189 cases to evaluate the aetiology of postmenopausal bleeding. Atrophic endometrium was observed as a major cause of postmenopausal bleeding according to histopathology. The cases were also distributed according to parity in which nulliparous patients were observed. Results: Hysteroscopy was observed to be effective for the diagnosis of postmenopausal bleeding. Conclusion: There is a need to assess more approaches for the diagnosis of postmenopausal bleeding among women.