There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a ...retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology.
A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients.
In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients.
Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.
Objectives: The current study evaluates the value of cardiac hybrid imaging (CHI), performed by the fusion of functional and anatomic cardiac images, in the detection of hemodynamically significant ...coronary stenosis in cases with multiple coronary stenosis. Methods: A total of 36 patients (10 female, 26 male) in whom ischemia or infarction was detected on gated myocardial perfusion single photon emission computed tomography (gMPS) and multiple coronary stenosis were concomitantly detected on coronary computed tomography angiography (CCTA) and undergone invasive coronary angiography (ICA) was included in this study. Statistical analyses were performed using SPSS 22 Windows software. McNemar test was applied to show concordance between coronary CT angiography, ICA and CHI in the detection of anatomically or hemodynamically significant stenosis in three major coronary arteries. Comparison results of coronary arteries responsible for perfusion defects on CHI and gMPS are presented as percentages (%). Results: There was total accordance between coronary arteries leading to perfusion defects detected by gMPS and CHI in 50% of patients. It was observed a partial accordance in 36.1% of the patients. Additionally, it was also detected perfusion defects originated from side branches in 25% of the patients. Between results of CCTA and ICA, no statistically significant difference was noted in the detection of anatomically significant stenoses in the left main coronary artery, left anterior descending artery (LAD), left circumflex artery (LCx) and right coronary artery (RCA) (p=1.000, 0.070, 0.549, and 1.000, respectively). In addition, no statistically significant difference was found in the detection of anatomically and hemodynamically significant stenoses in LAD, LCx and RCA by CCTA and CHI (p=0.344, 0.629, and 0.219, respectively). No statistically significant difference was observed in the detection of anatomically and hemodynamically significant stenoses in LAD, LCx and RCA by ICA and CHI (p=0.804, 1.000, and 0.344, respectively). Conclusion: It is possible to detect hemodynamically significant coronary stenosis directly by CHI modality in patients with multiple coronary stenosis, wide perfusion defects. Keywords: Cardiac hybrid imaging, coronary stenosis, myocardial perfusion scintigraphy, coronary CT angiography Amaç: Bu çalismanin amaci, fonksiyonel ve anatomik kardiyak görüntülerin füzyonu ile gerçeklestirilen kardiyak hibrid görüntülemenin (KHG), multipl koroner darliklari ve perfüzyon defektleri olan olgularda, hemodinamik olarak ciddi koroner darliklari saptamadaki katkisini degerlendirmektir. Yöntem: ?alismaya gated miyokard perfüzyon sintigrafisi tek foton emisyonlu bilgisayarli tomografi (gMPS) tetkikinde iskemi veya enfarkt ve koroner bilgisayarli tomografi anjiyografi (KBTA) tetkikinde birden fazla koroner darlik saptanarak girisimsel koroner anjiyografi (GKA) yapilan toplam 36 hasta (10 kadin, 26 erkek) dahil edildi. Anatomik ve fonksiyonel görüntüler CardIQ Fusion yazilimi (GE Healthcare, IL, ABD) ile birlestirildi. Istatistiksel analizler SPSS 22 yazilimi kullanilarak yapildi. ?ç ana koroner arterde anatomik ve hemodinamik olarak ciddi koroner darlik tespitinde, KBTA, GKA ve KHG arasindaki uyumu göstermek için McNemar testi uygulandi. KHG ve gMPS'de perfüzyon defektlerinden sorumlu koroner arterlerin karsilastirildigi sonuçlar yüzde olarak sunuldu. Bulgular: Hastalarin %50'sinde, gMPS ve KHG ile perfüzyon defektlerinden sorumlu oldugu düsünülen koroner arterler arasinda tam bir uyum vardi. Hastalarin %36,1'inde kismi uyum gözlenirken, %13,9'unda ise gMPS ile KHG tamamen uyumsuzdu. Hastalarin %25'inde, KHG sayesinde, perfüzyon defektlerinden koroner yan dallardaki darliklarin sorumlu oldugu saptandi. Sol ana koroner arter, sol ön inen arter, sol sirkumfleks arter ve sag koroner arterde anatomik olarak ciddi darliklarin saptanmasinda; KBTA ve GKA sonuçlari arasinda istatistiksel olarak anlamli bir fark saptanmadi (sirasiyla; p=1,000, 0,070, 0,549 ve 1,000). Ayrica sol ön inen arter, sol sirkumfleks arter ve sag koroner arterde; anatomik ve hemodinamik olarak ciddi darliklarin saptanmasinda, KBTA ve KHG sonuçlari arasinda istatistiksel olarak anlamli fark bulunmadi (sirasiyla; p=0,344, 0,629 ve 0,219). Ayrica sol ön inen arter, sol sirkumfleks arter ve sag koroner arterde; anatomik ve hemodinamik olarak ciddi darliklarin saptanmasinda, GKA ve KHG arasinda istatistiksel olarak anlamli bir fark gözlenmedi (sirasiyla; p=0,804, 1,000 ve 0,344). Sonuç: Multipl koroner darliklari ve genis perfüzyon defektleri olan hastalarda, KHG yöntemi ile iskemiden sorumlu olan, hemodinamik olarak ciddi koroner darliklarin dogrudan tespit edilmesi mümkündür. Anahtar kelimeler: Kardiyak hibrid görüntüleme, koroner stenoz, miyokard perfüzyon sintigrafisi, koroner BT anjiyografi
The human guanylate-binding protein 1 (hGBP1) is a large GTP-binding protein belonging to the dynamin family, a common feature of which is nucleotide-dependent assembly to homotypic oligomers. ...Assembly leads to stimulation of GTPase activity, which, in the case of dynamin, is responsible for scission of vesicles from membranes. By yeast two-hybrid and biochemical experiments we addressed intermolecular interactions between all subdomains of hGBP1 and identified the C-terminal subdomain, alpha12/13, as a new interaction site for self-assembly. alpha12/13 represents a stable subdomain of hGBP1, as shown by CD spectroscopy. In addition to contacts between GTPase domains leading to dimer formation, the interaction between two alpha12/13 subdomains, in the course of GTP hydrolysis, results in tetramer formation of the protein. With the help of CD spectroscopy we showed coiled-coil formation of two alpha12/13 subdomains and concentration-dependent measurements allow estimating a value for the dissociation constant of 7.3μm. We suggest GTP hydrolysis-driven release of the alpha12/13 subdomain, making it available for coiled-coil formation. Furthermore, we can demonstrate the biological relevance of hGBP1 tetramer formation in living cells by chemical cross-link experiments. Structured digital abstract * andby() * andby(View Interaction:,) * withby(View Interaction:,,) PUBLICATION ABSTRACT
This study aims to examine bone mineral density (BMD) and osteoporosis in older adults with dementia compared to those with a normal cognitive status and to evaluate the type, severity, and duration ...of dementia.
Between May 2013 and May 2017, a total of 363 participants aged ≥65 years (136 males, 227 females; mean age 78.4±5.4 years; range 66 to 99 years) with and without Alzheimer's disease (AD), vascular dementia (VaD), or mixed dementia (AD-VaD) were included in this single-center, prospective, cross-sectional study. The dementia group included 93 patients with dementia and the control group included 270 age- and sex-matched healthy individuals. We used dual-energy X-ray absorptiometry (DXA) to measure BMD of the lumbar spine, total hip, and femoral neck.
Controlled for age and sex, demented and non-demented participants had a similar BMD (g/cm
) at lumbar spine F (1, 358):0.83, p=363, but lower BMD values of total hip F (1, 359):10.26, p=0.001 and femoral neck F (1, 359):15.21, p<0.001 in the patients with dementia. Adjusted percentage of osteoporosis and low bone mass based on total hip and femoral neck T-scores were also significantly higher in the patient group. The mean BMD values, frequency of osteoporosis, and low bone mass did not significantly differ according to the subtype of dementia, sex, and disease duration or severity.
Our study results show that demented elders have a lower BMD and higher frequency of osteoporosis at the hip, but not at the lumbar spine, irrespective of sex and type of dementia. Based on these results, we can speculate that not only AD, but also VaD and AD-VaD may be associated with bone loss at the hip.
Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumor. A great majority of the cases live a disease-free life with quite favorable prognosis. There are lots of variants of PTC ...and a few of them exhibit aggressive behaviour. Typical example is the tall cell variant (TCV). Patients experience a greater incidence of recurrence, nodal and extranodal metastases, tumor associated mortality than other variants of PTC. Studies related to TCV almost always compared it with its patient population of PTC according to risk factors and clinicopathologic features. The aim of this study is to evaluate the risk factors in metastatic/recurrent TCV.
This is a retrospective cohort study of 1813 patients with differentiated thyroid carcinoma treated with radioiodine between 1992 and 2011. 56 of these patients are TCV. 34 of them developed metastasis/recurrence and 22 lived a disease-free life during the 23-year follow-up. We evaluated the risk factors in these metastatic and nonmetastatic subgroups.
We found tumor size, preablation thyroglobulin level, vascular invasion, preablation central and lateral cervical lymph node metastasis, preablation lung metastasis and stage independent risk factors. However age, preablation thyroglobulin level and stage appeared together as striking factors impacting metastasis in multivariate analysis.
Higher ablation doses up to 250-300 mCi should be administered to TCV patients having advanced stage (III,IV), pretty high preablation thyroglobulin level (over 400 ng/ml) and older age (over 52 years) especially with large tumor size (over 3.5 cm) and initial cervical lymph node metastasis.
Objective: Primary testicular lymphoma (PTL) is a form of extra-nodal lymphoma originating from the testicles. Currently, positron emission tomography (PET) with glucose analogue ...18F-fluorodeoxyglucose (18F-FDG) is the most popular and widely used modality for evaluating tumor metabolism, and PTL usually displays increased 18F-FDG uptake. Despite the rapid increase in clinical applications of FDG PET/ computed tomography (CT), its role in PTL has neither been clearly defined nor reviewed systematically. This study reviews the usefulness and limitation of FDG PET/CT in the diagnosis and treatment of PTL. Methods: This study included 12 patients with PTL between 2004 and 2015. We retrospectively examined PET/CT results along with patient outcome. The maximum standardized uptake value (SUV.sub.max) was calculated. Results: The mean overall survival (OS) and disease-free survival (DFS) was 44.5 months and 35.5 months, respectively. The mean SUV.sub.max was identified as 18.5 in recurrent/metastatic group. The 1-year and 3-year OS was 94% and 69%, while the 1-year and 2-year DFS was 93.5% and 56%, respectively. Conclusion: FDG PET/CT is very helpful in both staging and evaluating treatment response. Although it is not a perfect tool in the initial diagnosis, it might aid in the differential diagnosis of challenging testicular tumors. Pre-treatment and post-treatment FDG uptake values may also have a prognostic value in patients with PTL. Keywords: Primary testicular lymphoma, SUV.sub.max, FDG PET/CT Amac: Primer testis lenfomasi (PTL) testis kaynakli bir ekstranodal lenfomadir. .sup.18F-florodeoksiglukoz (.sup.18F-FDG) pozitron emisyon tomografisi/bilgisayarli tomografi (PET/BT) tumor metabolizmasini degerlendirmede yaygin olarak kullanilmaktadir ve PTL yuksek FDG tutulumu gosterir. FDG PET/BT'nin klinik uygulamalarinin gun gectikce artmasina ragmen, PTL'deki rolu tam olarak tanimlanmamis ve sistematize edilmemistir. Bu calisma FDG PET/BT'nin PTL tani ve tedavisindeki yararlilik ve kisitlamalarini arastirmaktadir. Yontem: Calisma 2004-2015 yillari arasinda 12 PTL hastasini icermektedir. Olgularin geriye donuk olarak FDG PET/BT sonuclari ve gidisatlari incelenmistir. Maksimum standart tutulum degeri (SUV.sub.maks) hesaplandi. Bulgular: Ortalama toplam sagkalim (OS) ve hastaliksiz sagkalim (DFS) sirasiyla 44,5 ay ve 35,5 ay idi. Ortalama SUV.sub.maks rekurrent/metastatik grupta 18,5 idi. OS 1. yilda %94, 3. yilda %69; DFS 1. yilda %93,5, 2. yilda %56 idi. Sonuc: FDG PET/BT evreleme ve tedaviye yanit takibinde cok faydalidir. Testis tumorlerinin ayirici tanisinin zor oldugu olgularda yararli olabilir. Fakat ilk tanida iyi bir yontem degildir. Tedavi oncesi veya sonrasi FDG tutulum degerleri prognostik bir onem tasiyabilir. Anahtar kelimeler: Primer testis lenfomasi, SUV.sub.maks, FDG PET/BT
We show for the first time that bisphenol A (10) has the capacity to interact directly with K-Ras and that Rheb weakly binds to bisphenol A (10) and 4,4′-biphenol derivatives. We have characterized ...these interactions at atomic resolution suggesting that these compounds sterically interfere with the Sos-mediated nucleotide exchange in H- and K-Ras. We show that 4,4′-biphenol (5) selectively inhibits Rheb signaling and induces cell death suggesting that this compound might be a novel candidate for treatment of tuberous sclerosis-mediated tumor growth. Our results propose a new mode of action for bisphenol A (10) that advocates a reduced exposure to this compound in our environment. Our data may lay the foundation for the future design of GTPase-selective antagonists with higher affinity to benefit of the treatment of cancer because K-Ras inhibition is regarded to be a promising strategy with a potential therapeutic window for targeting Sos in Ras-driven tumors.
Tall cell variant (TCV), an aggressive form of papillary thyroid carcinoma (PTC), frequently presents with extrathyroidal disease and recurrence. The aim of this study was to evaluate the ...clinicopathologic features and outcomes of patients with TCV by comparing them with a larger group of patients with classic variant of papillary thyroid carcinoma (cPTC).
A total of 2500 patients with differentiated thyroid carcinoma were treated and monitored during a 23-year period (1992-2015). Of them, 2250 (90%) had PTC and 235 (9.5%) had follicular thyroid carcinoma. Of the 2250 patients, 862 (38.3%) and 70 (3.1%) had cPTC and TCV, respectively. Cases of TCV and cPTC of PTC were compared on the basis of risk factors.
Patients with TCV were significantly older compared with cPTC patients (P<0.001). Tumor size was significantly bigger (P=0.01) and preablation thyroglobulin level was significantly higher (P<0.001) in TCV patients than in cPTC patients. The incidence of capsule invasion, extrathyroidal extension, and vascular invasion was significantly higher in TCV (P=0.003, <0.001, and 0.011, respectively). The incidence of initial lymph node metastasis was significantly higher in TCV (P<0.001). Patients with TCV were mostly at an advanced stage compared with patients with cPTC (P<0.001). Development of local or distant metastasis during the follow-up was significantly higher in TCV than in cPTC. Sex and multifocality were not statistically significant.
TCV has a higher incidence of local or distant metastasis and mortality rate. Thus, it must be treated with the highest possible I ablation doses and followed up carefully.