Radiomics Analysis of Contrast-Enhanced Breast MRI for Optimized Modelling of Virtual Prognostic Biomarkers in Breast Cancer.

Objective: Breast cancer clinical stage and nodal status are the most clinically significant drivers of patient management, in combination with other pathological biomarkers, such as estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2) receptor status and tumor grade. Accurate prediction of such parameters can help avoid unnecessary intervention, including unnecessary surgery. The objective was to investigate the role of magnetic resonance imaging (MRI) radiomics for yielding virtual prognostic biomarkers (ER, HER2 expression, tumor grade, molecular subtype, and T-stage). Materials and Methods: Patients with primary invasive breast cancer who underwent dynamic contrast-enhanced (DCE) breast MRI between July 2013 and July 2016 in a single center were retrospectively reviewed. Age, N-stage, grade, ER and HER2 status, and Ki-67 (%) were recorded. DCE images were segmented and Haralick texture features were extracted. The Bootstrap Lasso feature selection method was used to select a small subset of optimal texture features. Classification of the performance of the final model was assessed with the area under the receiver operating characteristic curve (AUC). Results: Median age of patients (n = 209) was 49 (21-79) years. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the model for differentiating N0 vs N1-N3 was: 71%, 79%, 76%, 74%, 75% [AUC = 0.78 (95% confidence interval (CI) 0.72-0.85)], N0-N1 vs N2-N3 was 81%, 59%, 24%, 95%, 62% [AUC = 0.74 (95% CI 0.63-0.85)], distinguishing HER2(+) from HER2(-) was 79%, 48%, 34%, 87%, 56% [AUC = 0.64 (95% CI 0.54-0.73)], high nuclear grade (grade 2-3) vs low grade (grades 1) was 56%, 88%, 96%, 29%, 61% [AUC = 0.71 (95% CI 0.63-0.80)]; and for ER (+) vs ER(-) status the [AUC=0.67 (95% CI 0.59-0.76)]. Radiomics performance in distinguishing triple-negative vs other molecular subtypes was [0.60 (95% CI 0.49-0.71)], and Luminal A [0.66 (95% CI 0.56-0.76)]. Conclusion: Quantitative radiomics using MRI contrast texture shows promise in identifying aggressive high grade, node positive triple negative breast cancer, and correlated well with higher nuclear grades, higher T-stages, and N-positive stages.

Machine Learning Prediction of Lymph Node Metastasis in Breast Cancer: Performance of a Multi-institutional MRI-based 4D Convolutional Neural Network.

Purpose To develop a custom deep convolutional neural network (CNN) for noninvasive prediction of breast cancer nodal metastasis. Materials and Methods This retrospective study included patients with newly diagnosed primary invasive breast cancer with known pathologic (pN) and clinical nodal (cN) status who underwent dynamic contrast-enhanced (DCE) breast MRI at the authors' institution between July 2013 and July 2016. Clinicopathologic data (age, estrogen receptor and human epidermal growth factor 2 status, Ki-67 index, and tumor grade) and cN and pN status were collected. A four-dimensional (4D) CNN model integrating temporal information from dynamic image sets was developed. The convolutional layers learned prognostic image features, which were combined with clinicopathologic measures to predict cN0 versus cN+ and pN0 versus pN+ disease. Performance was assessed with the area under the receiver operating characteristic curve (AUC), with fivefold nested cross-validation. Results Data from 350 female patients (mean age, 51.7 years ± 11.9 [SD]) were analyzed. AUC, sensitivity, and specificity values of the 4D hybrid model were 0.87 (95% CI: 0.83, 0.91), 89% (95% CI: 79%, 93%), and 76% (95% CI: 68%, 88%) for differentiating pN0 versus pN+ and 0.79 (95% CI: 0.76, 0.82), 80% (95% CI: 77%, 84%), and 62% (95% CI: 58%, 67%), respectively, for differentiating cN0 versus cN+. Conclusion The proposed deep learning model using tumor DCE MR images demonstrated high sensitivity in identifying breast cancer lymph node metastasis and shows promise for potential use as a clinical decision support tool. Keywords: MR Imaging, Breast, Breast Cancer, Breast MRI, Machine Learning, Metastasis, Prognostic Prediction Supplemental material is available for this article. Published under a CC BY 4.0 license.

How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Does anxiety, depression, and sleep levels affect the quality of life in patients diagnosed with multiple sclerosis?

OBJECTIVE: Multiple sclerosis (MS) is a chronic disease characterized by relapses and remissions, causing physical disability and affecting individuals psychosocially. In this study, we aimed to assess anxiety and depression levels, sleep, and quality of life in MS patients. PATIENTS AND METHODS: The study included 66 participants, 30 healthy controls, and 36 patients diagnosed with MS. All participants were administered the Sociodemographic and Clinical Data Form, Multiple Sclerosis Quality of Life Instrument (MSQOL-54), Pittsburgh Sleep Quality Index (PSQI), Expanded Disability Status Scale (EDSS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: The PSQI, EDSS, BDI, and BAI scores of MS patients were found to be significantly higher, while the MSQOL-54 score was considerably lower than the healthy control group (p<0.001). In the patient group, there was a positive correlation between PSQI score and BDI (r=0.599, p<0.001) and BAI (r=0.633, p<0.001), while there was a negative correlation between PSQI and MSQOL-54 (r=0.705, p<0.001) and the duration of MS diagnosis (r=-0.364, p=0.029). A positive correlation was found between the EDSS score and BDI (r=0.401, p=0.015) and the number of hospitalizations (r=0.566, p<0.001). There was a significant negative correlation observed between MSQOL-54 and BDI (r=-0.807, p<0.001) as well as BAI (r=-0.834, p<0.001). There is a significant positive relationship between BDI and BAI (r=0.828, p<0.001). CONCLUSIONS: Our research revealed that individuals diagnosed with multiple sclerosis exhibit elevated levels of anxiety and depression symptoms when compared to a healthy control group. Additionally, they tend to experience lower sleep quality and overall quality of life. The provision of necessary psychiatric interventions to these patients following their diagnosis can enable them to accept the disease and actively participate in treatment, thereby positively impacting their quality of life.

Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer.

Tumor heterogeneity represents a major challenge in breast cancer, being associated with disease progression and treatment resistance. Precision medicine has been extensively applied to dissect tumor heterogeneity and, through a deeper molecular understanding of the disease, to personalize therapeutic strategies. In the last years, technological advances have widely improved the understanding of breast cancer biology and several trials have been developed to translate these new insights into clinical practice, with the ultimate aim of improving patients' outcomes. In the era of molecular oncology, genomics analyses and other methodologies are shaping a new treatment algorithm in breast cancer care. In this manuscript, we review the main steps of precision medicine to predict drug sensitivity in breast cancer from a translational point of view. Genomic developments and their clinical implications are discussed, along with technological advancements that could broaden precision medicine applications. Current achievements are put into perspective to provide an overview of the state-of-art of breast cancer precision oncology as well as to identify future research directions.

A Tale of Two Hospitals: Effect of Access to Care Through a Safety Net Hospital on Adjuvant Therapy, Imaging Compliance and 5-Year Survival Rates Compared to the University Hospital Served by the Same Breast Cancer Clinical Teams.

RATIONALE AND OBJECTIVES: To compare rates of guideline-concordant care, imaging surveillance, recurrence and survival outcomes between a safety-net (SNH) and tertiary-care University Hospital (UH) served by the same breast cancer clinical teams. MATERIALS AND METHODS: 647 women with newly diagnosed breast cancer treated in affiliated SNH and UH between 11.1.2014 and 3.31.2017 were reviewed. Patient demographics, completion of guideline-concordant adjuvant chemotherapy, radiation and hormonal therapy were recorded. Two multivariable logistic regression models were performed to investigate the effect of hospital and race on cancer stage. Kaplan-Meier log-rank and Cox-regression were used to analyze five-year recurrence-free (RFS) and overall survival (OS) between hospitals and races, (p < 0.05 significant). RESULTS: Patients in SNH were younger (mean SNH 53.2 vs UH 57.9, p < 0.001) and had higher rates of cT3/T4 disease (SNH 19% vs UH 5.5%, p < 0.001). Patients in the UH had higher rates of bilateral mastectomy (SNH 17.6% vs UH 40.1% p < 0.001) while there was no difference in the positive surgical margin rate (SNH 5.0% vs UH 7.6%, p = 0.20), completion of adjuvant radiation (SNH 96.9% vs UH 98.7%, p = 0.2) and endocrine therapy (SNH 60.8% vs UH 66.2%, p = 0.20). SNH patients were less compliant with mammography surveillance (SNH 64.1% vs UH 75.1%, p = 0.02) and adjuvant chemotherapy (SNH 79.1% vs UH 96.3%, p < 0.01). RFS was lower in the SNH (SNH 54 months vs UH 57 months, HR 1.90, 95% CI: 1.18-3.94, p = 0.01) while OS was not significantly different (SNH 90.5% vs UH 94.2%, HR 1.78, 95% CI: 0.97-3.26, p = 0.06). CONCLUSION: In patients experiencing health care disparities, having access to guideline-concordant care through SNH resulted in non-inferior OS to those in tertiary-care UH.

Imaging Challenges in Diagnosing Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) refers to a heterogeneous group of carcinomas that have more aggressive biologic features, faster growth, and a propensity for early distant metastasis and recurrence compared with other breast cancer subtypes. Due to the aggressiveness and rapid growth of TNBCs, there are specific imaging challenges associated with their timely and accurate diagnosis. TNBCs commonly manifest initially as circumscribed masses and therefore lack the typical features of a primary breast malignancy, such as irregular shape, spiculated margins, and desmoplastic reaction. Given the potential for misinterpretation, review of the multimodality imaging appearances of TNBCs is important for guiding the radiologist in distinguishing TNBCs from benign conditions. Rather than manifesting as a screening-detected cancer, TNBC typically appears clinically as a palpable area of concern that most commonly corresponds to a discrete mass at mammography, US, and MRI. The combination of circumscribed margins and hypoechoic to anechoic echogenicity may lead to TNBC being misinterpreted as a benign fibroadenoma or cyst. Therefore, careful mammographic and sonographic evaluation with US image optimization can help avoid misinterpretation. Radiologists should recognize the characteristics of TNBCs that can mimic benign entities, as well as the subtle features of TNBCs that should raise concern for malignancy and aid in timely and accurate diagnosis. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

The effects of Digoxin use on long-term prognosis in patients with heart failure with reduced ejection fraction.

OBJECTIVE: This study aimed to investigate the effect of digoxin on mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients. Heart failure is a clinical syndrome that requires frequent rehospitalization and has a high mortality. This study aimed to investigate the effect of digoxin on mortality and rehospitalization in patients with heart failure with reduced ejection fraction. PATIENTS AND METHODS: The study included 326 patients with HFrEF that were hospitalized for decompensation between September 2014 and January 2016. The patients were divided into two groups: digoxin users and a control group. The study's endpoints were cardiovascular death and rehospitalization after 24-month long-term follow-ups. RESULTS: Rehospitalization was lower in patients taking digoxin (25% vs. 47%, p = 0.001). The mean age of patients taking digoxin (n: 78) was 63.7 ± 12.4 years, among which 64% were males. The mean age of the control group was 65.4 ± 11.8 years, among which 74% were males. However, there was no difference in mortality between the two groups (34% vs. 45%, p = 0.10). While Kaplan-Meier curves revealed no significant differences between mortality rates in the groups (log-rank p = 0.508), a statistical difference was found between the groups in rehospitalization rates (log-rank p =  0.013). A multiple linear regression analysis revealed that smoking (HR: 1.97, CI: 1.24-3.11, p = 0.004), systolic blood pressure (HR: 0.983, CI: 0.974-0.992, p < 0.001), atrial fibrillation (HR: 2.09, CI: 1.17-3.72, p = 0.012), C-reactive protein (CRP) (HR: 1.009, CI: 1.003-1.015, p = 0.004), beta-blockers (HR: 0.891, CI: 0.799-0.972, p = 0.009), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (HR: 0.778, CI: 0.641-0.956, p < 0.001), mineralocorticoid receptor antagonists (HR: 0.41, CI:0.26-0.65, p < 0.001), and digoxin use (HR: 0.59, CI: 0.43-0.80, p = 0.001) are independent predictors of rehospitalization in patients with HFrEF. CONCLUSIONS: Our results show that digoxin use does not affect mortality in HFrEF patients. However, rehospitalization decreased in patients taking digoxin in HFrEF.

Frontal QRS-T angle in patients with the suspicion of Coronavirus disease 2019 (COVID-19): could it be used as a predictive gravity sign even before the diagnosis by PCR?

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has been an ongoing global public health concern, causing serious challenges in diagnosing the disease timely. We investigated the value of the frontal QRS-T (fQRS-T) angle in patients visiting the emergency department with the suspicion of COVID-19. PATIENTS AND METHODS: A hundred and thirty-seven patients with the complaint of dyspnea were evaluated retrospectively. The patients with a history of coronary artery disease, heart failure, pulmonary disease, hypertension, diabetes mellitus, or using any medication such as heart rate controllers or antiarrhythmic drugs were excluded from the study. The angle between frontal QRS- and T-wave axis was defined as the fQRS-T angle, and the patients were divided into two groups based on the fQRS-T angle (group 1, <90° and group 2, ≥90°). Demographic, clinical, electrocardiographic data and rRT-PCR results were compared between the groups. RESULTS: The mean value of the fQRS-T angle of all participants was 45.26°. There was no significant difference between the groups according to the demographic and clinical data. Subjects with wider fQRS-T angle (group 2) had higher heart rates (p = 0.018), higher corrected QT values (p = 0.017), and higher QRS axis (p = 0.001). The patients in group 2 had a higher number of positive COVID-19 rRT-PCR test results compared to subjects with the normal fQRS-T angle (p = 0.002). In multivariate regression analysis, fQRS-T angle (p = 0.027, OR: 1.013, 95% CI: 1.001-1.024) was found as an independent variable affecting the PCR test results. CONCLUSIONS: Prompt diagnosis, initiating preventive and protective measures in an early stage of COVID-19 are crucial. In suspected COVID-19 infection, the use of faster-resulting tests and diagnostic tools for COVID-19 allows patients to be diagnosed and treated in a timely manner for recovery, thereby optimizing patient management. Therefore, the fQRS-T angle can be used in patients with dyspnea as a part of diagnostic scores of COVID-19, even before the rRT-PCR test results and overt disease.

Radial Scars Without Atypia Diagnosed at Percutaneous Core Needle Breast Biopsy: Support for Imaging Surveillance.

Objective: Radial scar (RS) is a low-risk breast lesion that can be associated with or mimic malignancy. Management guidelines remain controversial for patients with RS without atypia on core needle biopsy (CNB). The aim was to evaluate the upgrade rate of these lesions and factors associated with malignancy risk and excision rate to more definitively guide management. Materials and Methods: In this retrospective study, 123 patients with RS without atypia, diagnosed with CNB between January 2008 to December 2014 who were either referred for surgical excision or followed-up with imaging, were reviewed. The differences in clinical presentation, imaging features, and biopsy technique among the benign RS patients and those upgraded, as well as the excised versus the observed patients were compared. Results: Of 123 RS reviewed, 93 cases of RS without atypia as the highest-grade lesion in the ipsilateral breast and with either 24-month imaging follow-up or surgical correlation were included. Seventy-four (79.6%) lesions were surgically excised and 19 (20.4%) were followed-up for at least 24 months. A single upgrade to malignancy (1%) and 15 upgrades to high-risk lesions (16%) were found. There was no association of any upgraded lesion with presenting symptoms or imaging features. The use of vacuum-assistance and larger biopsy needles, along with obtaining a higher number of samples, was associated with fewer upgrades and lower surgical excision rates. Conclusion: The upgrade rate of RS without atypia in our population was low, regardless of the imaging features and biopsy technique utilized. Close imaging surveillance is an acceptable alternative to surgical excision in these patients.

Outcome of Imaging and Biopsy of BI-RADS Category 3 Lesions: Follow-Up Compliance, Biopsy, and Malignancy Rates in a Large Patient Cohort.

OBJECTIVES: To identify biopsy rates and indications for BI-RADS 3 lesions in a large cohort of patients and compare with follow-up compliance and malignancy outcomes. METHODS: We retrospectively reviewed all BI-RADS category-3 lesions seen on mammography and/or ultrasound between 2013 and 2015. Patient age, lesion size, follow-up rates at 6-, 12-, and 24-months were collected. Biopsy timing, indication, and outcomes (malignant vs benign) were recorded using at least 2-year follow-up or biopsy pathology as endpoint. RESULTS: Of 2319 BI-RADS 3 lesions in 2075 women analyzed, biopsy was performed in 173 (7.5%). Most biopsies were performed upfront (99, 57.2%), followed by at 6 (44, 25.4%), 12 (21, 12.1%), and 24-month follow-up (9, 5.2%; P < .001). Palpable (P < .001) and larger (median 1.4 vs 1.0 cm, P < .001) lesions in women <40 years (15.2% vs 4.8%, P < .001) were more likely to undergo biopsy. Most biopsies were prompted by patient/physician desire (64.5%, P < .001). Of 783 lesions with available endpoint, 5 (0.6%) were cancer. All cancers were identified either at presentation (in 0-5 months, n = 1) or 6-month follow-up (in 5-9 months, n = 4) with biopsy prompted by either morphology change (n = 3) or lesion growth (n = 2). Of the 1855 lesions which were expected for follow up, only 310 (16.7%) underwent all follow-ups, while 482 (26.1%) had two, 489 (26.5%) one, and 565 (30.6%) had no follow-up. CONCLUSIONS: In our cohort, BI-RADS category 3 lesions had significantly higher biopsy rates compared with the small malignancy rate, all of which were identified at baseline or first follow-up. Overall patient follow-up compliance low. Imaging follow-up, especially at first 6-month time point, should be encouraged in BI-RADS 3 lesions, instead of upfront biopsies.

Pregnancy management and outcome after uterus transplantation.

Uterus transplantation is a novel approach in women whose uterus is absent or severely abnormal. However, it is still an experimental procedure that poses risks to both mother and baby. To date, 32 live births after uterus transplantation have been reported in peer-reviewed journals, with several maternal, fetal and neonatal complications. The most common complications were preterm delivery, hypertensive disorders and placenta previa. Four patients experienced episodes of transplant rejection during pregnancy. The appropriate management of complicated and non-complicated pregnancies following uterus transplantation is still unresolved. In this review, obstetric outcomes after uterus transplantation and optimal management during pregnancy are discussed in light of the available data. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Determination of mTOR signal pathway in MMTV-TGFα mice ovary at different ages.

Transforming growth factor alpha (TGFα), a member of the epidermal growth factor (EGF) family, regulates cell proliferation, differentiation, and development, and involves follicular development and viability. In ovaries, TGFα is shown localized in granulosa cells (GCs) of primary follicles, theca cells (TCs) of pre-antral, antral and pre-ovulatory follicles. TGFα overexpression in mouse mammary tumor virus (MMTV-TGFα) transgenic mice causes mammary tumor after 50 weeks. However, follicular development and preservation of the ovarian follicle reserve-mediating follicle stimulating hormone (FSH) response are unknown. Mammalian target of rapamycin (mTOR) is a key regulator for cell proliferation, growth, differentiation, and apoptosis, and important for ovarian folliculogenesis and oocyte maturation. The study aim determines TGFα overexpression during folliculogenesis via mTOR signaling pathway in ovaries from 10-, 18-, 50-, and 82-week-old MMTV-TGFα mice. Histological analysis was performed, along with western blot for mTOR, p-mTOR, P70S6K, PCNA, and Caspase-3, and quantitative RNA (qRT-PCR) for mTOR and P70S6K. Developing follicles number decreased and atretic follicles number increased with aging in MMTV-TGFα mice ovary. Ovaries at 18 and 82 weeks had decreased PCNA and increased Caspase-3 protein expression levels as compared to 10-week ovaries. Protein expression levels of mTOR and p-mTOR decreased gradually from ovaries at 10-18 weeks, increased at 50 weeks and decreased again at 82 weeks. These results indicate that TGFα may be one regulator of healthy follicular development and affect mTOR signaling pathway during ovarian aging. Thus, over-expression of TGFα might lead to reduced ovarian reserve and premature ovarian insufficiency.

The impact of Coronavirus disease 2019 (COVID-19) on urinalysis parameters.

BACKGROUND: Creatinine elevation and changes in urinalyse parameters may be seen due to acute kidney injury during COVID-19. In the present study, we aimed to investigate the changes in urinalysis of COVID-19 patients with normal kidney function. METHODS: The data of COVID-19 patients with normal renal functions were retrospectively analyzed. Urinalysis parameters of these patients were recorded. The patients were divided into three groups as mild, moderate and severe with respect to the clinical course of the disease. It was examined whether the urine analysis values in the groups were different from normal reference values and whether these values were different between the groups. In addition, possible relationship between the urinalysis parameters and the clinical severity of the disease was investigated. RESULTS: There are three groups; mild (N.=40), moderate (N.=38) and severe (N.=42). Mean age were significantly higher in the severe group, while gender distribution of the groups was similar (P=0.033, P=0.091) Creatinine values of all patients were normal. There were 6.7% glucose positivity, 13.4% protein positivity, 5.8% urobilinogen positivity and 7.5% ketone positivity in urine dipstick analysis and these changes were all significantly higher than the reference values (P=0.008, P<0.0001, P=0.016, P=0.016). Pyuria and hematuria were detected in 8.3% and 9.2%, respectively. The urinalysis parameters and urine microscopy findings were not affected by the severity of the disease. CONCLUSIONS: Glycosuria, proteinuria, pyuria and hematuria may occur during COVID-19 disease, regardless of comorbidity and renal dysfunction. However, these urine parameters were not correlated with the severity of the disease.

The magnetic resonance imaging assessment of optic nerve sheath diameter in pediatric acute liver failure patients.

OBJECTIVE: To evaluate the diagnostic value of optic nerve sheath diameter (ONSD) using brain MRI in the pretransplantation period in the pediatric acute liver failure patients, and correlate the ONSD with clinical grade of hepatic encephalopathy (HE) and MRI findings. PATIENTS AND METHODS: Forty acute liver failure patients and 40 control group patients were retrospectively analyzed. The high signal intensities in T2W (T2-weighted image), FLAIR (Fluid Attenuated Inversion Recovery) and DWI (diffusion-weighted imaging) sequences were evaluated and ONSD was measured. The patients were grouped first into 5 according to their West Haven score, and HE grade 0 and grade 1 were accepted as low grade HE, HE grade 2, 3 and 4 were accepted as high grade HE. The patients were grouped to 2 according to the MRI findings as low grade and high grade MRI group. RESULTS: The mean value of ONSD was 6.0 ± 1.80 and 4.94 ± 1.27 in the all patients and in the control group, respectively. There was statistically significant difference between both the ONSD and the low grade-high grade HE groups (p=0.01), and between the ONSD and the low grade-high grade MRI groups (p<0.001). CONCLUSIONS: Although high ONSD values do not make the diagnosis of cerebral edema, it may cause suspicion in the early period. MRI can be helpful in the diagnoses of increased intracranial pressure like ultrasound. Our study is the first study to compare ONSD and MRI findings in addition to HE grades. The widespread use of MRI in children in recent years may help determine the normal range of ONSD values.

Chronic appendicitis: the process from pre-diagnosis to pathology.

OBJECTIVE: Chronic appendicitis (CA) is a rare medical condition. CA is characterized by a less severe and almost continuous abdominal pain. It has a clinical picture lasting longer than 1-2 days and extending over weeks, months, even years. The exact etiology of CA is unclear. Certain resources have reported it as the cause of partial obstruction in the lumen of the appendix. PATIENTS AND METHODS: Our study was carried out with the approval of the Clinical Research Ethics Committee. A retrospective analysis was performed between August 2018 and March 2020. RESULTS: It was determined that 207 appendectomies were performed during the retrospective scan period. The data of 182 of these patients could be accessed fully and we could get answers to the criteria we thought. Only 8 of the patients screened were likely to be diagnosed with chronic appendicitis in the preoperative period. CA was found in 1 of the 8 patients (12.5%) who underwent surgery after a preliminary diagnosis of CA. Two patients were reported as malignant (25%), 3 patients (37.5%) as reactive lymphoid hyperplasia, and 1 patient as peri appendicitis (12.5%). Bleeding and congestion were reported in the last patient (12.5%). CONCLUSIONS: The diagnosis of chronic appendicitis is made by pathological examination. It may not always be possible to consider "chronic appendicitis" as a preliminary diagnosis. This should still be kept in mind. In our opinion, it is a bit difficult to make a preliminary diagnosis of chronic appendicitis and make a surgical decision. We believe that controlled and prospective studies can shed more light on chronic appendicitis.

Effects of two types of energy restriction on methylation levels of adiponectin receptor 1 and leptin receptor overlapping transcript in a mouse mammary tumour virus-transforming growth factor-α breast cancer mouse model.

The role of adiponectin and leptin signalling pathways has been suggested to play important roles in the protective effects of energy restriction (ER) on mammary tumour (MT) development. To study the effects of ER on the methylation levels in adiponectin receptor 1 (AdipoR1) and leptin receptor overlapping transcript (Leprot) genes using the pyrosequencing method in mammary fat pad tissue, mouse mammary tumour virus-transforming growth factor-α (MMTV-TGF-α) female mice were randomly assigned to ad libitum (AL), chronic ER (CER, 15 % ER) or intermittent ER (3 weeks AL and 1 week 60 % ER in cyclic periods) groups at 10 weeks of age until 82 weeks of age. The methylation levels of AdipoR1 in the CER group were higher than those in the AL group at week 49/50 (P < 0·05), while the levels of methylation for AdipoR1 and Leprot genes were similar among the other groups. Also, the methylation levels at CpG2 and CpG3 regions of the promoter region of the AdipoR1 gene in the CER group were three times higher (P < 0·05), while CpG1 island of Leprot methylation was significantly lower compared with the other groups (P < 0·05). Adiponectin and leptin gene expression levels were consistent with the methylation levels. We also observed a change with ageing in methylation levels of these genes. These results indicate that different types of ER modify methylation levels of AdipoR1 and Leprot in different ways and CER had a more significant effect on methylation levels of both genes. Epigenetic regulation of these genes may play important roles in the preventive effects of ER against MT development and ageing processes.

Performance of a clinical and imaging-based multivariate model as decision support tool to help save unnecessary surgeries for high-risk breast lesions.

PURPOSE: To investigate the performance of an imaging and biopsy parameters-based multivariate model in decreasing unnecessary surgeries for high-risk breast lesions. METHODS: In an IRB-approved study, we retrospectively reviewed all high-risk lesions (HRL) identified at imaging-guided biopsy in our institution between July 1, 2014-July 1, 2017. Lesions were categorized high-risk-I (HR-I = atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ and atypical papillary lesion) and II (HR-II = Flat epithelial atypia, radial scar, benign papilloma). Patient risk factors, lesion features, detection and biopsy modality, excision and cancer upgrade rates were collected. Reference standard for upgrade was either excision or at least 2-year imaging follow-up. Multiple logistic regression analysis was performed to develop a multivariate model using HRL type, lesion and biopsy needle size for surgical cancer upgrade with performance assessed using ROC analysis. RESULTS: Of 699 HRL in 652 patients, 525(75%) had reference standard available, and 48/525(9.1%) showed cancer at surgical excision. Excision (84.5% vs 51.1%) and upgrade (17.6%vs1.8%) rates were higher in HR-I compared to HR-II (p < 0.01). In HR-I, small needle size < 12G vs ≥ 12G [32.1% vs 13.2%, p < 0.01] and less cores [< 6 vs ≥ 6, 28.6%vs13.7%, p = 0.01] were significantly associated with higher cancer upgrades. Our multivariate model had an AUC = 0.87, saving 28.1% of benign surgeries with 100% sensitivity, based on HRL subtype, lesion size(mm, continuous), needle size (< 12G vs ≥ 12G) and biopsy modality (US vs MRI vs stereotactic) CONCLUSION: Our multivariate model using lesion size, needle size and patient age had a high diagnostic performance in decreasing unnecessary surgeries and shows promise as a decision support tool.

Psycho-social impact of malocclusion in adolescents in Kosovo.

OBJECTIVE: To assess the psychosocial impact of malocclusion, establish its association with the severity of malocclusion and determine the effects of gender and age in such association. BASIC RESEARCH DESIGN: Cross-sectional study. METHODS: 400 adolescents aged between 12-15 years were randomly selected. Each participant was examined for malocclusion and categorized according to Index of Orthodontic Treatment Need (IOTN) and Dental Aesthetic Index (DAI). The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) was used to assess the psychosocial impact of malocclusion. RESULTS: Significant differences were noted between PIDAQ subscales, and grades of malocclusion assessed by IOTN and DAI (p⟨0.05). Gender differences were noted in Dental Self Confidence (DSC), Social Impact (SI) and Psychological Impact (PI) for the same severity of malocclusion (p⟨0.05). IOTN-DHC predicted the total and subscales of PIDAQ scores. Gender and age were the independent predictive variables of the relationship between the PIDAQ scores and the IOTN-DHC grades for the DSC and AC subscales. Gender independently predicted psychological impact. CONCLUSION: Severity of malocclusion, gender and age were related to impacts on the psychosocial wellbeing of participants. Overall, females and older participants experienced worse psychosocial impact.