Imaging Features of Triple N Negative Breast Cancers – Mammography, Ultrasound and Magnetic Resonance Imaging

Breast cancer (BC) is a highly heterogeneous disease. Aim was to evaluate imaging features of triple negative breast cancers (TNBC) in comparison to non-TNBC. We reviewed data of 30 patients who had been diagnosed as having TNBC and 37 patients with non-TNBC (control group) using criteria described for mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) in Breast Imaging-Reporting and Data System (BI-RADS) lexicon for image interpretation. Age of patients, size of tumor, multifocality, histological type, tumor grade and status of lymph nodes were reviewed. TNBC were more often histological grade 3 and had significantly more positive lymph nodes at the time of diagnosis on pathology reports. On MMG, US and MRI TNBC mostly appeared as regularly shaped masses. On US as hypoechogenic masses with no posterior acoustic features and on MRI as masses with rim type of enhancement, fast wash-in and plateau type of curves. Most frequent category reported after MMG and US was BI RADS 4, and after MRI BI RADS 5. In conclusion, our study confirmed higher histological grade of TNBC, as well as more frequent lymph node involvement in comparation to the non-TNBC. TNBC showed tendency to affect younger women and to be larger than non-TNBC. Although, they most often presented as a mass on mammography and sonography, in a significant number of cases they remained miscategorized, due to the benign imaging features. All cases are recognized on MRI where they appear as rim enhancing masses

Vrućica nepoznata uzroka u pasa: 50 slučajeva

Although in veterinary medicine the term “Fever of unknown origin” (FUO) is still liberally used for any febrile patient where no diagnosis has been set after routine diagnostics, the term “true FUO” should be assigned to those cases in which no aetiology is found after extensive diagnostics. The aim of this study was to investigate the occurrence of FUO in dogs, to research the structure of the FUO population, as well as to explore clinical signs and their duration, and the prior treatment and incidence of different diagnoses and their outcomes. Also, this study was conducted in order to explore the amount of diagnostic procedures (with their effectiveness) required to reach a final diagnosis with the intention of helping design and prioritize diagnostics of FUO in dogs in Croatia. Final diagnosis was reached in 94% (47/50) of dogs with a total of 626 diagnostic procedures used. Immune-mediated diseases occurred most frequently (56%), followed by infectious diseases (24%), neoplastic diseases (10%) and congenital diseases (4%), with only 6% of “true FUO”. Body temperature ranged between 39.6 °C and 42.0 °C. The most common symptoms were nonspecific (anorexia and lethargy in 88%, pain in 78%, and gait disorders in 60%). The most frequent test performed was hematology while hemoculture was performed the least. Cytology and/or pathohistology were the most effective tests in achieving the final diagnosis (76.32%). The duration of clinical signs before the diagnosis/ proper treatment was 4-1825 days. The outcome was favorable in 62%, unfavorable in 32% and unknown in 6%.Premda termin vrućica nepoznatog uzroka (VNU) u veterinarskoj medicini još uvijek nema točno određenu definiciju ni kriterije klasifikacije, te se vrlo često liberalno upotrebljava u febrilnih pacijenata u kojih nije postavljena egzaktna dijagnoza nakon rutinske dijagnostičke obrade, VNU bi trebalo rezervirati za one pacijente u kojih ni nakon opsežne dijagnostike nije otkriven uzrok, tj. postavljena konačna dijagnoza. Ciljevi ovog istraživanja bili su istražiti pojavnost VNU-a kao i različitih dijagnoza u pasa s vrućicom, kliničke simptome i njihovo trajanje do postavljanja dijagnoze i početka ciljanog liječenja, te ishode liječenja, odnosno bolesti. Također, svrha ovog istraživanja bila je istražiti prosječan broj dijagnostičkih postupaka (i njihovu učinkovitost) potrebnih za postavljanje konačne dijagnoze, s ciljem kreiranja dijagnostičkog plana u pasa s VNU-om u Hrvatskoj. U 94 % pasa (47/50) postavljena je konačna dijagnoza pomoću ukupno 626 dijagnostičkih postupaka. Najčešće su bile zastupljene imunosno posredovane bolesti (56 %), zatim infekcijske (24 %), neoplastične (10 %) i kongenitalne (4 %), dok je pravi VNU bio zastupljen u samo 6 % slučajeva. Tjelesna temperatura kretala se od 39,6 do 42,0 °C. Najčešći su klinički znakovi bili nespecifični (gubitak apetita i letargija u 88 %, bolnost u 78 % te poremećaji kretanja u 60 % slučajeva). Najčešći je dijagnostički postupak bila hematološka pretraga, a najrjeđi hemokultura. Citološka i/ili patohistološka pretraga pokazale su se najučinkovitijima u postavljanju konačne dijagnoze (76,32 %). Trajanje simptoma do postavljanja dijagnoze, odnosno početka adekvatnog liječenja iznosilo je od 4 do 1825 dana. Ishod je u 62 % pasa bio povoljan, u 32 % nepovoljan, dok je u 6 % ostao nepoznat

Obuzeto-prisilni poremećaj

U radu su prikazane najnovije spoznaje o epidemiologiji, dijagnostici i liječenje obuzeto-prisilnog poremećaja (OPP). Prikazani rezultati pokazuju da je OPP znatno češći no što se ranije mislilo, a dijagnostika je obogaćena nizom novih neuroslikovnih istraživanja što pobuđuju nadu u bolje poznavanje etiologije poremećaja. Dat je pregled genetskih istraživanja, kao i načini liječenja poremećaja, kako psihofarmakološki, psihoterapijski tako i transkranijskom magnetskom stimulacijom, dubokom stimulacijom mozga i neurokirurškim metodama

Use of bendamustin instead of carmustin in autologous stem cell transplantation conditioning – toxicity and infectious complications comparison

Unatrag nekoliko godina u hematologiji i onkologiji globalno sve češći problem postaje prikladna opskrba „starijim i manje zanimljivim“ kemoterapeuticima. Zbog povremene nestašice karmustina, jednog od osnovnih kemoterapeutika pri kondicioniranju prije autologne transplantacije krvotvornih matičnih stanica (ATK S) u oboljelih od limfoma, u našem se centru od 2016. godine on zamjenjuje bendamustinom. U ovom radu retrospektivno analiziramo tijek ATK S-a u 41 bolesnika koji su primili bendamustin u sklopu protokola BeEA M te ga uspoređujemo s tijekom ATK S-a u 40 bolesnika koji su primili karmustin u sklopu protokola BEA M. Medijan oporavka vrijednosti neutrofila (> 0,5 × 109/l) u skupini koja je primila bendamustin iznosio je 11 dana, dok je u skupini kondicioniranoj karmustinom iznosio 10 dana. Medijan oporavka vrijednosti trombocita (> 20 × 109/l) bio je duži kod skupine koja je primala bendamustin (16 prema 13 dana) te su ti bolesnici bili duže ovisni o transfuzijama eritrocita (7 prema 5 dana). Infektivne komplikacije nisu bile češće nakon primjene bendamustina, ali smo nakon primjene karmustina imali veću pojavu mukozitisa II. – III. stupnja (35% prema 12%). Nakon primjene bendamustina zabilježen je jedan slučaj nefrotoksičnosti i kardiotoksičnosti terapije, dok kod primjene karmustina te komplikacije nisu zabilježene. Pri upotrebi bendamustina kod kondicioniranja u naših bolesnika u ovom trenutku nije utvrđena znatnija hematološka toksičnost u odnosu prema karmustinu, ali su prisutni dulji period oporavka vrijednosti trombocita te niža incidencija mukozitisa.Inadequate supply of „old and less interesting“ chemotherapeutic agents is becoming a global issue in hemato-oncology today. In 2016 we were faced with occasional carmustin shortage, one of the most commonly used in autologous transplant conditioning regimens for lymphoma in our centre, so we decided to use bendamustin instead. We performed a retrospective analysis of 41 patients treated at our centre who had received bendamustin within BeEA M protocol and compared them with 40 patients who had received carmustin within BEA M protocol. Both protocols were used as conditioning protocols before autologous stem cell transplantation. Neutrophil recovery median following transplantation (AN C>0,5x109/l) was 11 days in the bendamustin group in comparison to 10 days in the carmustin group.Platelets recovery median following transplantation (PLT>20x109/l) was longer in the bendamustin group (16 vs.13 days) as was blood transfusion dependency (7 vs. 5 days). Infectious complications were not more frequent after bendamustin, but grade II–III mucositis was more frequent in patients who received carmustin (35% vs.12%). Following bendamustin we had one reported case of nephrotoxicity and cardiac toxicity, not reported with carmustin. Bendamustin has shown similar hematologic toxicity compared to carmustin but a longer platelet recovery period and a lower mucositis incidence

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Exploring Association of Breast Pain, Pregnancy, and Body Mass Index with Breast Tissue Elasticity in Healthy Women: Glandular and Fat Differences

Breast sonoelastography is a relatively novel ultrasound (US) method that enables estimation of tissue stiffness to estimate the elasticity of normal breast tissue and seek to correlate it with well-known breast cancer risk factors. Two hundred women of different age were included in the study and completed a questionnaire about personal, familiar, and reproductive history. Glandular and fatty tissue elasticity in all breast quadrants was measured by shear wave elastography (SWE). Mean elastographic values of breast tissue were calculated and compared to personal history risk factors. Elasticity of normal glandular tissue (66.4 kilopascals (kPa)) was higher than fatty tissue (26.1 kPa) in all breast quadrants and in both breasts. Lower outer quadrant (LOQ) had the lowest elasticity values of both parenchyma and fat. Higher elasticity values of breast tissue were confirmed in the left breast than in the right breast. Glandular and fat tissue elasticity negatively correlated with body mass index (BMI). Women with mastodynia had higher glandular elastographic values compared to subjects without breast pain. Nuliparity was also associated with higher elasticity of glandular breast tissue. The results of this study are promising and could, over time, contribute to a better understanding of glandular breast tissue elasticity as a potential risk factor for breast cancer

Elastic Modulus and Elasticity Ratio of Malignant Breast Lesions with Shear Wave Ultrasound Elastography: Variations with Different Region of Interest and Lesion Size

Shear wave elastography (SWE) is a type of ultrasound elastography with which the elastic properties of breast tissues can be quantitatively assessed. The purpose of this study was to determine the impact of different regions of interest (ROI) and lesion size on the performance of SWE in differentiating malignant breast lesions. The study included 150 female patients with histopathologically confirmed malignant breast lesions. Minimal (Emin), mean (Emean), maximal (Emax) elastic modulus and elasticity ratio (e-ratio) values were measured using a circular ROI size of 2, 4 and 6 mm diameters and the lesions were divided into large (diameter ≥ 15 mm) and small (diameter < 15 mm). Highest Emin, Emean and e-ratio values and lowest variability were observed when using the 2 mm ROI. Emax values did not differ between different ROI sizes. Larger lesions had significantly higher Emean and Emax values, but there was no difference in e-ratio values between lesions of different sizes. In conclusion, when measuring the Emin, Emean and e-ratio of malignant breast lesions using SWE the smallest possible ROI size should be used regardless of lesion size. ROI size has no impact on Emax values while lesion size has no impact on e-ratio values

Models of Drug Induced Liver Injury (DILI) - Current Issues and Future Perspectives

BACKGROUND: Drug-induced Liver Injury (DILI) is an important cause of acute liver failure cases in the United States, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. METHODS: A structured search of bibliographic databases - Web of Science Core Collection, Scopus and Medline for peer-reviewed articles on models of DILI was performed. The reference lists of relevant studies was prepared and a citation search for the included studies was carried out. In addition, the characteristics of screened studies were described. RESULTS: One hundred and six articles about the existing knowledge of appropriate models to study DILI in vitro and in vivo with special focus on hepatic cell models, variations of 3D co-cultures, animal models, databases and predictive modeling and translational biomarkers developed to understand the mechanisms and pathophysiology of DILI are described. CONCLUSION: Besides descriptions of current applications of existing modeling systems, associated advantages and limitations of each modeling system and future directions for research development are discussed as well

Implementation of Elastography Score and Strain Ratio in Combination with B-mode Ultrasound Avoids Unnecessary Biopsies of Breast Lesions

The aim of this study was to evaluate whether the combination of B-mode ultrasound, elastography score (ES) and strain ratio (SR) improves diagnostic performance with respect to breast lesions. One hundred thirty lesions were prospectively evaluated by B-mode ultrasound and strain elastography, followed by fine-needle aspiration cytology/biopsy in 117 woman who were scheduled for regular breast BUS. The median ES (4.5 vs. 2.9, p , 0.001) and SR (4.9 vs. 2.3, p , 0.001) were significantly higher for malignant than for benign lesions. A sensitivity of 90.5% and specificity of 93.2% for the ES (cutoff point53.8) and a sensitivity of 87.5% and specificity of 87.6% for the SR (cutoff point53.5) were obtained. Elastography combined with B-mode ultrasound improved the specificity, accuracy and positive predictive value. Receiver operating characteristic curves yielded a higher value for the combined technique for diagnosis of breast lesions. Routine use of such a diagnostic algorithm could reduce the number of unnecessary biopsies