Automated glioblastoma patient classification using hypoxia levels measured through magnetic resonance images.

INTRODUCTION: The challenge of treating Glioblastoma (GBM) tumors is due to various mechanisms that make the tumor resistant to radiation therapy. One of these mechanisms is hypoxia, and therefore, determining the level of hypoxia can improve treatment planning and initial evaluation of its effectiveness in GBM. This study aimed to design an intelligent system to classify glioblastoma patients based on hypoxia levels obtained from magnetic resonance images with the help of an artificial neural network (ANN). MATERIAL AND METHOD: MR images and PET measurements were available for this study. MR images were downloaded from the Cancer Imaging Archive (TCIA) database to classify glioblastoma patients based on hypoxia. The images in this database were prepared from 27 patients with glioblastoma on T1W + Gd, T2W-FLAIR, and T2W. Our designed algorithm includes various parts of pre-processing, tumor segmentation, feature extraction from images, and matching these features with quantitative parameters related to hypoxia in PET images. The system's performance is evaluated by categorizing glioblastoma patients based on hypoxia. RESULTS: The results of classification with the artificial neural network (ANN) algorithm were as follows: the highest sensitivity, specificity, and accuracy were obtained at 86.71, 85.99 and 83.17%, respectively. The best specificity was related to the T2W-EDEMA image with the tumor to blood ratio (TBR) as a hypoxia parameter. T1W-NECROSIS image with the TBR parameter also showed the highest sensitivity and accuracy. CONCLUSION: The results of the present study can be used in clinical procedures before treating glioblastoma patients. Among these treatment approaches, we can mention the radiotherapy treatment design and the prescription of effective drugs for the treatment of hypoxic tumors.

Global burden of the COVID-19 associated patient-related delay in emergency healthcare: a panel of systematic review and meta-analyses.

BACKGROUND: Apart from infecting a large number of people around the world and causing the death of many people, the COVID-19 pandemic seems to have changed the healthcare processes of other diseases by changing the allocation of health resources and changing people's access or intention to healthcare systems. OBJECTIVE: To compare the incidence of endpoints marking delayed healthcare seeking in medical emergencies, before and during the pandemic. METHODS: Based on a PICO model, medical emergency conditions that need timely intervention was selected to be evaluated as separate panels. In a systematic literature review, PubMed was quarried for each panel for studies comparing the incidence of various medical emergencies before and during the COVID-19 pandemic. Markers of failure/disruption of treatment due to delayed referral were included in the meta-analysis for each panel. RESULT: There was a statistically significant increased pooled median time of symptom onset to admission of the acute coronary syndrome (ACS) patients; an increased rate of vasospasm of aneurismal subarachnoid hemorrhage; and perforation rate in acute appendicitis; diabetic ketoacidosis presentation rate among Type 1 Diabetes Mellitus patients; and rate of orchiectomy among testicular torsion patients in comparison of pre-COVID-19 with COVID-19 cohorts; while there were no significant changes in the event rate of ruptured ectopic pregnancy and median time of symptom onset to admission in the cerebrovascular accident (CVA) patients. CONCLUSIONS: COVID-19 has largely disrupted the referral of patients for emergency medical care and patient-related delayed care should be addressed as a major health threat.

Prognostic value and optimal threshold of first thyroglobulin in low/intermediate risk DTC.

BACKGROUND: The aim of this study was to define prognostic value and optimal threshold of first thyroglobulin (fTg) measured after thyroidectomy and just before radio-iodine therapy (RIT), in low/intermediate risk patients with differentiated thyroid cancer (DTC). METHODS: This is a retrospective study in 383 patients with DTC who were treated with surgery followed by RIT. Response to treatment was assessed 1 and 2 years after RIT. Odds ratio of different risk factors like age, sex, TNM stage, fTg and Anti-Tg Ab were compared between patients with and without incomplete response 1 and 2 years after treatment. Receiver operating curve analysis was used for definition of optimal fTg cut off for detection of incomplete response. RESULTS: 218 female and 55 male with DTC had negative anti-Tg antibody (mean age: 37.5±14.5 years) and analyzed separately. fTg≥33.5 ng/mL and fTg/TSH ratio of ≥0.36 had the optimal sensitivity and specificity for detection of incomplete response 1 and 2 years after treatment. fTg<33.5 ng/mL had NPV of 98.5% for exclusion of distant metastases. Patients with fTg≥33.5 ng/mL had longer "time to excellent response" (3.6±2.3 vs. 2.0±1.8 yrs) and needed more additional treatments compared to patients with fTg<33.5 ng/mL. Multivariate analysis showed that fTg was the most potent risk factor for prediction of treatment failure 1 and 2 years after RIT. CONCLUSIONS: fTg of ≥33.5 ng/mL was the most important risk factor for prediction of treatment failure after RIT and could be included in decision algorithms regarding intensity of treatments in low/intermediate risk patients with DTC.

Evaluation of the relationship between inpatient COVID-19 mortality and chest CT severity score.

OBJECTIVES: There is scarce data available on the prognostic application of chest CT. The main purpose of this study was to evaluate the performance of a semi-quantitative CT severity score in identifying the risk of mortality in COVID-19 patients. METHODS: This retrospective cohort study was performed on 262 hospitalized COVID-19 patients. The CT severity score was assessed by two independent radiologists using a method previously used to score the severity of acute respiratory distress syndrome on thin slice lung CT. RESULTS: Multivariate regression analysis showed increasing odds of in-hospital death associated with older age, and the presence of coronary artery disease at the time of admission. The mean CT severity score was 7.5 in the survivor group and 14.5 in the deceased group. Overall, the lower zones were the most frequently affected sites in COVID-19. There was significant difference between the survivor and deceased groups regarding CT severity scores. Multivariate regression analysis showed increasing odds of in-hospital death associated with higher CT severity score at admission. CONCLUSIONS: Our results show that mortality was significantly higher in patients with higher CT severity score even after adjustment for clinical, demographics and laboratory parameters. However, this study is performed retrospectively and needs to be validated in a prospective study.

The burden and predisposing factors of non-communicable diseases in Mashhad University of Medical Sciences personnel: a prospective 15-year organizational cohort study protocol and baseline assessment.

BACKGROUND: The rising burden of premature mortality for Non-Communicable Diseases (NCDs) in developing countries necessitates the institutionalization of a comprehensive surveillance framework to track trends and provide evidence to design, implement, and evaluate preventive strategies. This study aims to conduct an organization-based prospective cohort study on the NCDs and NCD-related secondary outcomes in adult personnel of the Mashhad University of Medical Sciences (MUMS) as main target population. METHODS: This study was designed to recruit 12,000 adults aged between 30 and 70 years for 15 years. Baseline assessment includes a wide range of established NCD risk factors obtaining by face-to-face interview or examination. The questionnaires consist of demographic and socioeconomic characteristics, lifestyle pattern, fuel consumption and pesticide exposures, occupational history and hazards, personal and familial medical history, medication profile, oral hygiene, reproduction history, dietary intake, and psychological conditions. Examinations include body size and composition test, abdominopelvic and thyroid ultrasonography, orthopedic evaluation, pulse wave velocity test, electrocardiography, blood pressure measurement, smell-taste evaluation, spirometry, mammography, and preferred tea temperature assessment. Routine biochemical, cell count, and fecal occult blood tests are also performed, and the biological samples (i.e., blood, urine, hair, and nail) are stored in preserving temperature. Annual telephone interviews and repeated examinations at 5-year intervals are planned to update information on health status and its determinants. RESULTS: A total of 5287 individuals (mean age of 43.9 ± 7.6 and 45.9% male) were included in the study thus far. About 18.5% were nurses and midwives and 44.2% had at least bachelor's degree. Fatty liver (15.4%), thyroid disorders (11.2%), hypertension (8.8%), and diabetes (4.9%) were the most prevalent NCDs. A large proportion of the population had some degree of anxiety (64.2%). Low physical activity (13 ± 22.4 min per day), high calorie intake (3079 ± 1252), and poor pulse-wave velocity (7.2 ± 1.6 m/s) highlight the need for strategies to improve lifestyle behaviors. CONCLUSION: The PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences is the first organizational cohort study in a metropolitan city of Iran aiming to provide a large data repository on the prevalence and risk factors of the NCDs in a developing country for future national and international research cooperation.

Preparation of superparamagnetic iron oxide/doxorubicin loaded chitosan nanoparticles as a promising glioblastoma theranostic tool.

Theranostic nanoparticles (NPs) are promising for opening new windows toward personalized disease management. Using a single particle capable of both diagnosis and drug delivery, is the major benefit of such particles. In the present study, chitosan NPs were used as a dual action carrier for doxorubicin (DOX; chemotherapeutic agent) and superparamagnetic iron oxide nanoparticles (SPIONs; imaging agent). SPIONs and DOX were loaded at different concentrations within poly-l-arginine-chitosan-triphosphate matrix (ACSD) using the ionic gelation method. NPs' size were in the range of 184.33 ± 4.4 nm. Drug release analysis of DOX loaded NPs (NP-DOX) showed burst release at pH 5.5 (as in tumor environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release profile. NP-DOX internalization was confirmed by flowcytometry and fluorescent microscopy. Uptake process results were corroborated by accumulation of drug in the intracellular space. Iron content was evaluated by inductively coupled plasma and prussian blue staining. In vitro magnetic resonance imaging (MRI) showed a decline in T 2 relaxation times by increasing iron concentration. MRI analysis also confirmed uptake of NPs at the optimum concentration in C6 glioma cells. In conclusion, ACSD NPs could be utilized as a promising theranostic formulation for both diagnosis and treatment of glioblastoma.

Nasu-Hakola disease as suspected cause for bone disease and dementia.

Progressive dementia in conjunction with multiple bone fractures in a previously healthy young man led to the investigation of the underlying cause. The differential diagnoses (most importantly hypoparathyroidism) were limited given basal ganglia calcifications on the brain computed tomographic scan. Electronic search of the key words basal ganglia calcification, osteoporosis, and dementia revealed a rare condition termed Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. This very rare and potentially fatal genetic disease is characterized by pathological fractures, multiple lytic bone lesions, and presenile dementia. We report an Iranian patient with this disease and a review of the literature.

Applying chemical shift images (in-phase/opposed phased) for differentiating low-grade from high-grade glioma and comparison with magnetic resonance spectroscopy.

BACKGROUND: Grading gliomas is essential for treatment decisions and patient prognosis. In this study we evaluated the in-phase and out-of-phase sequences for distinguishing high-grade (HGG) from low-grade glioma (LGG) and the correlation with magnetic resonance spectroscopy (MRS) results. METHODS: This observational study comprised patients with brain tumors referred to our center for brain MRS. The gold standard for diagnosis was based on the World Health Organization (WHO) glioma classification. A standard tumor protocol was accomplished using a 1.5­T MRS scanner. Before contrast medium administration, extra in- and out-phase sequences were acquired. Three 20-30-mm2 oval regions of interest (ROIs) were placed in the solid component and the signal loss ratio (SLR) was calculated with the following formula: SLR tumor = (SI In phase - SI Opposed phase) / SI In phase Correlations and comparisons between groups were made using the Pearson, chi-square and, independent samples t tests. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance. Statistical significance was set at p < 0.05. RESULTS: In total, 20 patients were included in the LGG and 13 were included in the HGG group. The mean SLR in the HGG and LGG groups was 3.66 ± 2.12 and 1.63 ± 1.86, respectively (p = 0.01). There was a statistically significant correlation between lipid lactate (0.48, p = 0.004) and free lipid (0.44, p = 0.009) concentrations on MRS with SLR. CONCLUSIONS: The SLR is a simple, rapid, and noninvasive marker for differentiating between LGG and HGG. There is a significant correlation with both the concentration and presence of free lipid and lipid-lactate peaks in MRS.

The accuracy of non-contrast brain CT scan in predicting the presence of a vascular etiology in patients with primary intracranial hemorrhage.

Spontaneous intraparenchymal cerebral hemorrhages (SIPH) account for 10-15% of acute strokes. Sorting these patients according to the risk of harboring an underlying vascular etiology may help selecting the patients who would mostly benefit from Multidetector CT Angiography (MDCTA). The aim of this study was to evaluate the accuracy of Non-Contrast brain CT (NCCT) in predicting possible vascular etiologies in patients with SIPH. In this retrospective study, we evaluated the NCCT of 334 patients who presented with SIPH from March 2017 to March 2021 and we looked for vascular etiologies in the CTA which was performed for these patients. We used NCCT criteria to predict the presence of any vascular etiologies in SIPH patients and proposed a scoring system based on these criteria which might predict the risk of vascular ICH (VICH score). Out of 334 evaluated patients, 9.3% had an underlying vascular etiology. Independent predictors of the vascular etiology included: age < 46 years, no history of hypertension and coagulation disorders, lobar hemorrhages, and presence of significant perilesional edema. We used these criteria and NCCT classification to create a practical scoring system to predict the risk of vascular ICH (VICH). In our study, VICH score ≥ 4 had 51.6% sensitivity and 96.4% specificity for predicting a positive MDCTA as the maximum optimal cut-off point. The VICH score seemed to be successful in predicting vascular etiologies in this retrospective cohort of 334 patients. This scoring system can be used to select patients if there are limited resources to perform CT angiography.

Neglected alkaptonuric patient presented with low back pain and radiculopathy: A case report.

BACKGROUND: Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual presentation of a lumbar disc herniation occurring in a patient with AKU warranting surgical intervention. CASE DESCRIPTION: A 28-year-old male presented with 1 year of low back pain. The lumbar magnetic resonance imaging showed an extruded disc at the L4-L5 level accompanied extensive disc space narrowing and osteophyte formation. At surgery, the interspinous ligaments, facet joints, and disc herniation were black. In addition, the postoperative re-examination revealed a black discoloration of the nasal and ear cartilage. Finally, the diagnosis of AKU was confirmed when the urine specimen was positive for HGA. CONCLUSION: Rarely, younger patients with AKU who develop excess black deposits of HGA in connective tissues (i.e., ochronosis) may present with lumbar disc herniations and spondylosis.

Decreased Pulmonary Artery Bifurcation Angle: A Novel Imaging Criterion for the Diagnosis of Chronic Pulmonary Thromboembolism.

Background: Chronic pulmonary thromboembolism (CTEPH) is an unusual complication of acute pulmonary embolism (PE), which is now considered to be treatable. In modern multi-detector scanners, a detailed evaluation of pulmonary artery geometry is currently possible. This study aimed to evaluate the changes in pulmonary artery bifurcation angle (PABA) in the follow-up computed tomography angiography (CTA) of patients with acute PE. Methods: In this cross-sectional study, the records of two tertiary-level academic hospitals were gathered from 2012 to 2019. Pulmonary artery (PA) bifurcation angle and diameter were measured. Chi square test, independent samples t test, Mann-Whitney, and Pearson's tests were employed to compare data. To evaluate the cut-off point, we utilized receiver operating characteristic (ROC) curve analysis. The accuracy, sensitivity, and specificity of pulmonary artery bifurcation angle changes were calculated. A P value <0.05 was considered to be significant. Results: Forty-six patients were included in the study. No significant differences were found between patients with and without CTEPH, and PABA in the dimeters of PA trunk, right PA, and left PA in the first CTA images (P values of 0.151, 0.142, 0.891, and 0.483, respectively), while in the secondary CTA, the mean PABA was significantly smaller in patients with CTEPH (P=0.011). In the receiver operating characteristic (ROC) analysis, delta angle revealed an area under the curve of 0.745 and an optimal cutoff of 0, leading to a sensitivity of 64%, specificity of 87%, and accuracy of 76% for diagnosing CTEPH. Conclusion: We showed a significant decrease in PABA in patients developing CTEPH. This parameter can be easily measured in lung CTA.

Evaluating anemia on non-contrast thoracic computed tomography.

Anemia is a major global disease burden factor linked to an adverse impact on overall prognosis and negatively affects the quality of life. There are some suggested findings for anemia on non-contrast chest CT, like relatively dense interventricular septum (septal sign) or fairly dense aortic wall (aortic ring sign). The measured attenuation value is a reproducible physical density measurement, readily obtainable from a standard CT examination. There is no reliable cut-off for blood attenuation to suggest anemia on the non-contrast chest CT. In the current study, we evaluated subjective and objective criteria' diagnostic accuracy for diagnosing anemia on unenhanced thoracic CT. This study is approved by Mashhad University of Medical Sciences. The patients admitted in the internal medicine ward of our hospital from June 2019 to March 2020 for whom a non-contrast chest CT was acquired for any non-traumatic medical indication, were enrolled in this retrospective study. For the subjective assessment, the radiologists were asked to record the presence or absence of the "aortic ring sign" and "interventricular septum sign". For the objective evaluations, blood density was measured at various anatomic locations. A total of 325 patients were included in this study. There was a significant correlation between blood attenuation in all measured segments and Hb level (0.78 (R2: 0.61), p = 0.000). Findings revealed that considering the aortic arch threshold value as 20 HU is the best diagnostic performance for detecting severe anemia. Subjective analysis revealed that the aortic ring sign was more sensitive (82.5%) than the interventricular septum sign (32%) in detecting anemia, whereas the latter character was more specific (87% and 99.2%, respectively). The results suggest that it is possible to detect anemia from an unenhanced chest CT scan. Both objective and subjective criteria show promising sensitivity and specificity.

Temporal changes of lung computed tomography findings pulmonary COVID-19 infection.

OBJECTIVES: COVID-19 infection demonstrates characteristic findings in chest CT. The optimal timing of repeated CT scans still needs to be clarified, and the optimal time to assess imaging clearance in COVID-19 is still unknown. It is crucial to have a roadmap of the imaging course of COVID-19 pneumonia to develop guidelines for prompt diagnosis of pulmonary complications, especially fibrosis, at the earliest stage. PURPOSE: To assess the temporal changes of chest CT findings in patients with COVID-19 pneumonia and evaluate the rate of a complete resolution and determine the patients are at excessive risk for residual parenchymal abnormalities. MATERIALS AND METHODS: This retrospective observational study included 48 patients with real-time polymerase chain reaction-confirmed COVID-19 who were admitted to three academic hospitals. These patients underwent at least one initial chest CT before or after admission and at least one follow-up CT scan four weeks or more after the onset of the symptoms. All chest CTs were categorized according to time of performance into four groups, including the first week, second week, third-fourth week, and more than 28 days. Lung involvement was categorized as predominantly alveolar (ground-glass opacity and consolidation), organizing pneumonia, and reticular patterns. The severity of involvement was also evaluated by the reader. RESULTS: Forty-eight patients and a total of 130 chest CT scans were evaluated. The alveolar pattern showed a gradual decrease in frequency from 91% in the first week to 9% after the fourth week of the disease but the organizing pneumonia pattern gradually increased with disease progression and the frequency of reticular pattern increased significantly after third week. Complete resolution of CT findings was seen in 17 patients (13.1%) and was significantly more prevalent in patients of younger age (p value<0.001) and with lower initial CT severity scores (p value=0.048). CT severity scores in the second week were significantly higher in ICU admitted patients (p value=0.003). CONCLUSION: There are temporal patterns of lung abnormalities in patients with COVID-19 pneumonia. The predominant CT pattern was alveolar infiltrate in the first and second weeks of the disease, replaced with an organizing pneumonia pattern in the third and fourth weeks. Progression of lung involvement was correlated with ICU admission due to the highest CT severity score in the second and third weeks of presentation but not in the first week in patients who were admitted at ICU. Complete CT resolution was significantly more common in patients of younger age and lower initial CT severity scores.

Launching Awake Craniotomy Technique in a Resource-Limited Center: New Insights into the Patient Experience, Costs, and Long-Term Outcomes and a Narrative Review of the Literature.

BACKGROUND: Awake craniotomy (AC) with brain mapping is a standard surgical technique for the excision of lesions located in eloquent areas. We aimed to assess the clinical challenges, patient experience, costs, and long-term outcomes of AC in a resource-limited setting. METHODS: In this cross-sectional study, electronic documents of 12 patients who underwent AC with functional brain mapping were prospectively collected from August 2017 to October 2020. Patient characteristics, surgical specifications, hospitalization period, intraoperative and postoperative events, functional outcome, patients' satisfaction, costs, and survivals were collected and analyzed. RESULTS: Twelve patients with a median age of 42.5 (interquartile range, 13.5) were enrolled, of whom 8 were male (66.7%), and 9 (75%) were harboring grade 2 glioma. Of the patients, 8.34%, 33.34%, and 58.33% had partial, subtotal, and gross total excision of the tumors, respectively. The intraoperative seizure was the only complication and occurred in 2 cases (16.67%). At 1 year follow-up, none of the patients experienced any neurologic deficit. Eleven patients (91.6%) had a satisfactory opinion about reappearing in the AC. At 38 months follow-up, mortality was 8% for AC group and 25% among the historically matched controls who had surgery under general anesthesia (P = 0.27). Most costs belonged to the neurosurgery team (43%), and the overall expenses were reduced by 13% compared with a putatively well-equipped setting in our country. CONCLUSIONS: In carefully selected individuals, AC with brain mapping for excision of gliomas could be a safe, effective, and affordable strategy in a resource-limited setting and can be successfully performed with satisfactory outcomes.

Evaluation of Normal Renal Size and its Influencing Factors: A Cross-Sectional Study on the Adult Population of Mashhad.

Background: The normal range of kidney size is a controversial issue among different populations given to its impressibility by multiple factors, therefore, this study aimed to provide valid reference ranges for kidney dimensions in the adult population of Mashhad. Also, we assessed the association of kidney size characteristics with some personal predisposing factors. Methods: This cross-sectional study was conducted on 938 healthy individuals. Ultrasound measurement, physical examination, and laboratory analysis were performed. Demographic, dietary, and anthropometric data were obtained. The variables were categorized into 5 groups each, and data analysis were performed using the following statistical tests: Pearson correlation test, variance analysis, t-test, and chi-square test. A value of p<0.05 was considered statistically significant. Results: Weight had the most association with kidney size followed to a lesser extent by height and age. Even after adjustment for other confounding variables, weight remained as an independent factor, while this effect was resolved for height and age. Also, all values for renal function, body bio-impedance, blood pressure components, and water intake were notably correlated with kidney size. Conclusion: This study determined the normal kidney size in healthy adults. We also declared the normal range of kidney size is a dynamic concept and should be assessed for each individual separately according to their personal determinative factors.