Papers by Daniela Miladinova
Radiologic Clinics of North America, 2004

Arquivos de Gastroenterologia, 2006
RACIONAL: Considerando que o comprometimento linfonodal é o fator determinante no estádio, prognó... more RACIONAL: Considerando que o comprometimento linfonodal é o fator determinante no estádio, prognóstico e, conseqüentemente, na indicação de terapia adjuvante em câncer de cólon, e sendo esta responsável pelo aumento significativo na sobrevida global desses pacientes, os métodos para estádio devem conferir a maior precisão possível para que todos os pacientes com doença linfonodal maligna possam se beneficiar desta terapêutica na sua sobrevida global. O estudo do linfonodo sentinela vem progressivamente sendo mais valorizado no sentido de conferir maior precisão nesse estádio, bem como no prognóstico do câncer de cólon. OBJETIVO: Identificar o linfonodo sentinela e melhor estudar o status linfonodal no câncer de cólon. PACIENTES E MÉTODOS: Foram randomizados prospectivamente 31 pacientes com câncer de cólon em dois grupos: no primeiro, o linfonodo sentinela foi identificado usando-se corante azul patente e no segundo houve adição de colóide radioativo marcado com 99mTecnécio. RESULTA...
Clinical Nuclear Medicine, 2013
We report the use of SPECT/CT in sentinel lymph node biopsy in endometrial cancer. The patient wa... more We report the use of SPECT/CT in sentinel lymph node biopsy in endometrial cancer. The patient was a 54-year-old woman with the diagnosis of endometrial adnenocarcinoma, grade 2. Preoperative MRI and transvaginal ultrasound scans revealed tumor infiltrating more than 50% of the myometrium. The patient was qualified for total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic/paraaortic lymphadenectomy. Before the surgery, 2 cervical injections of the 99m Tc-labeled nanocolloid (0.5 mCi) were administered and the SPECT/CT was performed using a standard dualhead gamma camera and a 6-slice spiral CT component.

Frontiers in Molecular Biosciences
Targeting HER 2 for imaging and therapy in nuclear medicine has been used with a special emphasis... more Targeting HER 2 for imaging and therapy in nuclear medicine has been used with a special emphasis on developing more powerful radiopharmaceuticals. Zirconium-89 plays an essential role in immune PET imaging so was used labeled with anti-HER2 antibody (Trastuzumab and Pertuzumab). Also there were attempts with other PET tracers as Cuprum-64 and Galium-68, as well as SPECT radiopharmaceuticals Indium-111 and Technetium- 99m. Regarding antibody pharmacokinetic that is not quite appropriate for imaging acquisition, several smaller molecules with shorter residence times have been developed. These molecules called nanobody, affibody, minibody do not compromize HER2 receptor affinity and specificity. Excess of Trastuzumab do not block the affinity of labeled affibodies. Silica nanoparticles have been conjugated to anti-HER2 antibodies to enable targeting of HER2 expressing cells with potential of drug delivery carry for antitumor agents and b(beta) or a(alfa) emitting radioisotopes commonl...

Molecular-Guided Surgery: Molecules, Devices, and Applications VII
The staging of solid cancers is critical to the planning of both primary treatment with surgery a... more The staging of solid cancers is critical to the planning of both primary treatment with surgery and adjuvant therapies like chemotherapy; however, staging is not always possible with preoperative information and may require intraoperative evaluation of sentinel lymph nodes to confirm or disaffirm the presence of metastasis. Challenges are presented by standard-of-care sentinel lymph node dissection which must be quick and accurate enough to guide the surgical strategy despite a workflow that stretches from the operating room to the pathology lab; however, a solution is posed by fluorescence-assisted sentinel lymph node dissection which uses fluorescent probes to communicate the location and/or status of sentinel lymph nodes, reducing the complexity of the surgery and/or eliminating the need for rapid pathology. In support of this emerging modality, we have constructed a snapshot hyperspectral imaging system with sensitivity from the far-red to the near-infrared that enables sentinel lymph node dissection with multiple near-infrared fluorophores. We have also developed a spectral unmixing routine for in vivo quantification of the readily available fluorophores indocyanine green and methylene blue that can be extended to emerging fluorophores that actively target tumor cells. Both the imaging system and the unmixing routine have been tested in a clinical setting where they have successfully discriminated two dyes exhibiting different distributions.

Journal of Biomedical Optics
Significance: Near-infrared fluorescence image-guided surgery is often thought of as a spectral i... more Significance: Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important. Aim: Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff. Approach: In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer. We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making. Conclusions: These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.

Journal of Clinical Ultrasound
ObjectiveTo analyze the ultrasound (US) characteristics and fine needle biopsy (FNAB) of thyroid ... more ObjectiveTo analyze the ultrasound (US) characteristics and fine needle biopsy (FNAB) of thyroid carcinomas (TCs) prior to surgery and compare with postoperative histopathology and to determine FNAB sensitivity and specificity.Material and MethodsRetrospective analysis of the US data during 1999–2015 was performed, as well as analysis of FNAB results and using histopathology report as “gold standard” the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this method was evaluated.ResultsData revealed that tumors >51 mm were declining by 50% in the period 2011–2015 compared to 2005–2010 or by 18% 2011–2015 compared to 1999–2004 and significant increase was detected in diagnosis of multicentric tumors. The analysis revealed that FNAB has sensitivity = 65.7% CI (0.59% ‐ 0.71%) and specificity = 50% CI (0.43%–0.56%), PPV = 56.9% and NPV = 59.2%.ConclusionWe found increasing detection of smaller TCs, as well as more frequent detection of m...

Journal of Morphological Sciences
Amiodarone, an antiarrhythmic drug with 37% iodine of its weight, is often used for treatment of ... more Amiodarone, an antiarrhythmic drug with 37% iodine of its weight, is often used for treatment of severe cardiac arrhythmias. Enormous iodine content and structural similarity to thyroxine leads to thyroid dysfunction in 14-18% of patients. A 64-year-old man presented at our department with signs of thyrotoxicosis for further work up. He reported taking amiodarone for treatment of atrial fibrillation for two years. The patient denied any thyroid dysfunctions in the past. Full thyroid examination revealed elevated FT4 and suppressed TSH, with undetectable level of thyroid antibodies, increased iodine urinary concentration and normal thyroid ultrasound features. Although the above mentioned was indicative for amiodarone-induced thyrotoxicosis (AIT) type 2, 99mTc-pertechnetate scan showed normal thyroid uptake, highly unusual for iodine contamination and destructive thyroiditis. We presumed that this was a mixed form of AIT. Amiodarone administration was stopped and the patient was put on antithyroid drug therapy with thiamazole. During the follow up period he became clinically and biochemically euthyroid and thiamazole was discontinued. Thyroid screening should be performed in all patients undergoing amiodarone treatment. The presented case highlights the challenge of differentiation and management of a form of AIT with mixed features of both types.

Journal of Pediatric Endocrinology and Metabolism
Objectives Many studies have shown that socio-economic status (SES) contributes to health inequal... more Objectives Many studies have shown that socio-economic status (SES) contributes to health inequalities, with nutrition as one of the major risk factors. Iodine intake entirely depends on external sources, and deficiencies are known to be more prevalent in lower social groups, especially in countries with limited access to iodized salt. This study aimed to determine the influence of SES on iodine status and iodine availability from household salt in North Macedonia. Methods Using cluster sampling, 1,200 children were recruited, and 1,191 children participated (response rate: 99.2%). Iodine status was assessed through urinary iodine concentration (UIC), and iodine availability through iodine content in household salt requested from participants. SES was assessed using standardized Family Affluence Score (FAS). Results No statistically significant correlation was found between FAS and iodine in salt. Median regression revealed no significant associations of middle vs. low FAS (β=0.00; ...

Journal of B.U.ON. : official journal of the Balkan Union of Oncology, Sep 9, 2019
Purpose: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, par... more Purpose: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and<br> the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference.<br> Methods: Cancer prevention and treatment strategies were discussed according to existing international guidelines.<br> The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/m...

Insulin resistance together with obesity, hypertension and dyslipidemia is part of the cluster th... more Insulin resistance together with obesity, hypertension and dyslipidemia is part of the cluster that represents the metabolic syndrome. The impaired insulin sensitivity has been reported to be linked with obesity; however the importance of the fat distribution has also been emphasized in the development of this disorder. The aim of our study was to determine to association of serum insulin and insulin resistance assessed by HOMA with anthropometric parameters in obese and overweight women. Also the correlation of insulin and insulin resistance (HOMA-IR) with the subcutaneous and visceral abdominal fat was evaluated. The study included 41 overweight and obese women, aged 20- 60 years. The anthropometric parameters like body mass index (BMI), waist, hip and thigh circumference were measured with standard methods. Abdominal subcutaneous fat tissue (SFT) and visceral fat tissue (VFT) were determined by ultrasonography. Insulin values were measured with radioimmunoassay and the insulin re...

PRILOZI, 2021
Wound healing is a dynamic and physiological process for restoring the normal architecture and fu... more Wound healing is a dynamic and physiological process for restoring the normal architecture and functionality of damaged tissue. Platelet-rich plasma (PRP) is an autologous whole blood product that contains a large number of platelets in a small volume of plasma with complete set of coagulation factors, which are in physiological concentrations. PRP has haemostatic, adhesive properties and acts supraphysiologically in the process of wound healing and osteogenesis. Platelets play a very important role in the wound healing process by providing growth factors that enhance the rate and quality of wound healing by many different mechanisms. The aim of this review is to describe: the biology of platelets and their role in the wound healing process, the terminology of platelet rich products, PRP preparation, activation and concentration of PRP, as well as the use of PRP in plastic surgery.
Science Translational Medicine, 2021
A color/near-infrared camera inspired by the mantis shrimp visual system enables tumor detection ... more A color/near-infrared camera inspired by the mantis shrimp visual system enables tumor detection and lymph node mapping during cancer surgery.
European Journal of Nuclear Medicine and Molecular Imaging, 2021

Open Access Macedonian Journal of Medical Sciences, 2020
OBJECTIVE: Our goal was to evaluate the analytical performance of the novel immunoassay platform ... more OBJECTIVE: Our goal was to evaluate the analytical performance of the novel immunoassay platform and to compare the agreement between thyroid-stimulating hormone (TSH) and FT4 results, obtained by novel and currently used platform. MATERIALS AND METHODS: Both immunoassay platforms, current Immulite 2000 and novel Maglumi 800, are based on chemiluminecsence immunoassay method. Analytical performance was evaluated by the use of serum pools and commercial quality control samples. The comparison study was carried out with 80 serum samples. Obtained results were analyzed by descriptive statistics, Mann–Whitney U-test, and Paired t-test. Method comparison was performed with Passing-Bablok regression analysis and Bland-Altman plots. RESULTS: TSH Maglumi 800 showed better within-run precision for both concentration ranges (1.7–2.8 CV%) in comparison to Immulite 2000 (4.4–5.7 CV%). FT4 Maglumi 800 imprecision was higher compared with Immulite 2000 FT4 in both within-run (3.5–3.9 CV% vs. 4.9–...

Journal of Endocrinological Investigation, 2020
Purpose North Macedonia is historically iodine deficient, but due to the longstanding and effecti... more Purpose North Macedonia is historically iodine deficient, but due to the longstanding and effective preventive measures, it has been considered iodine replete since 2003. The aim of the recent national survey was to re-evaluate iodine status and to measure thyroid volume (TVol) by ultrasound in schoolchildren as a representative of the general population. Methods A stratified probability proportionate to size cluster sampling was used to obtain a representative national sample of school children aged 7–10 years between the 28th of March and 4th of October 2016. Thyroid volume (TVol) was measured using ultrasonography in 1188 children. All TVol measurements were done by a single operator and their medians were compared with an international reference standard. Results Significant positive correlation was found between Tvol and age, height, weight, body surface area (BSA), body mass index (BMI) in both girls and boys ( p < 0.001), but not between TVol and urinary ioidine concentration (UIC). The most important predictors for Tvol in all children were age, height, weight, BMI, and BSA ( all p < 0.001). In multivariate regression, independent predictors for TVol were only BSA ( p < 0.001) and age ( p = 0.004) after being adjusted for sex, BMI, and UIC ( R 2 = 0.291). The 97th percentile of Tvol in our survey was generally higher than in the reference study and goiter prevalence of 18.3% in boys and 15.6% in girls was found compared to the international standard. Conclusion In our survey, Tvol of schoolchildren was larger than in the international reference study, although iodine nutritional status of the country has been considered sufficient for many years. In countries and regions with long and effective, well-documented iodine prophylaxis, the optimal way to have realistic normative TVol would be to create their TVol reference limits. Therefore, the provided data for TVol measured in our survey could be proposed as the national reference TVol for schoolchildren aged 7–10 years.
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Papers by Daniela Miladinova