Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD-0.67 ± 0.12; 1/5 MAD-0.59 ± 0.07; 1/10 MAD-0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels.

Secondary vs. primary pituitary xanthogranulomas: which yellow is more mellow?

Pituitary xanthogranulomatomas (XG) are a rare pathological entity caused by accumulation of lipid laden macrophages and reactive granuloma formation usually triggered by cystic fluid leakage or hemorrhage. Our aim was to compare clinical characteristics and presenting features of patients with secondary etiology of XG and those with no identifiable founding lesion (primary -"pure" XG) in order to gain new insights into this rare pituitary pathology. In a retrospective review of 714 patients operated for sellar masses, at tertiary center, we identified 16 (2.24%) with histologically confirmed diagnosis of pituitary XG over the period of 7 years (2015-2021). Patients were further analyzed according to XG etiology: "pure"- XG (n = 8) with no identifiable founding lesion were compared to those with histological elements of pituitary tumor or cyst - secondary XG (n = 8). We identified 16 patients (11 male), mean age 44.8 ± 22.3 years, diagnosed with pituitary XG. Secondary forms were associated with Ratke's cleft cyst (RCC, n = 2) and pituitary adenoma (PA, n = 6). The most common presenting features in both groups were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Predominance of male sex was noted (males 68.75%, females 31.25%), especially in patients with primary forms. Patients with primary pituitary XG were all males (p = 0.0256) and more frequently affected by panhypopituitarism (87.5% vs. 25%, p = 0.0406) compared to patients with secondary causes. Hyperprolactinemia was noted in pituitary tumor group with secondary etiology only (p = 0.0769). Majority of lesions were solid on magnetic resonance imaging - MRI (81.25%). Distinct clinical phenotype was observed dependent on the etiology of XG.

Plurihormonal Pituitary Neuroendocrine Tumours - A Single Centre Experience.

Introduction. Plurihormonal pituitary neuroendocrine tumours (PitNET)/adenomas are pituitary neuroendocrine tumours composed of monomorphous cell populations expressing anterior pituitary transcription factors and/or hormones belonging to more than one cell lineage. Studies dedicated to plurihormonal tumours are rare and quite heterogenous with their results, bearing in mind changes in diagnostic criteria and inconsistent use of antibodies for anterior pituitary transcription factors in the diagnostic immunohistochemical panel. Material and Methods. We retrospectively analysed all patients surgically treated for PitNETs from 2016 to July 2022 in a tertiary healthcare institution. All tumours previously diagnosed PitNETs with the word "plurihormonal" were re-examined and potentially re-classified, according to 2022 WHO classification of endocrine tumours. Results. Among 721 patients surgically treated for PitNET in 5.5 years period, the diagnosis of plurihormonal PitNET was established in 11 tumours (1.3%). All tumours showed diffuse and intensive positivity for anterior pituitary transcription factors PIT1 and SF1. Clinically, all patients presented with acromegaly. Conclusions. Retrospective studies related to newly defined plurihormonal PitNETs with a reassessment of diagnoses are necessary due to their rarity and ambition to investigate their origin and biological behaviour. The fact that the majority of plurihormonal PitNETs are clinically presented with acromegaly and show simultaneous positivity to PIT1 and SF1 transcription factors deserve special attention and need for further research in larger cohorts of these exceptional tumours.

Incorporating high-resolution climate, remote sensing and topographic data to map annual forest growth in central and eastern Europe.

To enhance our understanding of forest carbon sequestration, climate change mitigation and drought impact on forest ecosystems, the availability of high-resolution annual forest growth maps based on tree-ring width (TRW) would provide a significant advancement to the field. Site-specific characteristics, which can be approximated by high-resolution Earth observation by satellites (EOS), emerge as crucial drivers of forest growth, influencing how climate translates into tree growth. EOS provides information on surface reflectance related to forest characteristics and thus can potentially improve the accuracy of forest growth models based on TRW. Through the modelling of TRW using EOS, climate and topography data, we showed that species-specific models can explain up to 52 % of model variance (Quercus petraea), while combining different species results in relatively poor model performance (R2 = 13 %). The integration of EOS into models based solely on climate and elevation data improved the explained variance by 6 % on average. Leveraging these insights, we successfully generated a map of annual TRW for the year 2021. We employed the area of applicability (AOA) approach to delineate the range in which our models are deemed valid. The calculated AOA for the established forest-type models was 73 % of the study region, indicating robust spatial applicability. Notably, unreliable predictions predominantly occurred in the climate margins of our dataset. In conclusion, our large-scale assessment underscores the efficacy of combining climate, EOS and topographic data to develop robust models for mapping annual TRW. This research not only fills a critical void in the current understanding of forest growth dynamics but also highlights the potential of integrated data sources for comprehensive ecosystem assessments.

Effectiveness of Eccentric Overload Training in Basketball Players: A Systematic Review.

Several studies have confirmed the efficacy of flywheel eccentric overload training in order to improve or increase muscle volume and strength, as well as several performance-related fitness attributes, but to date, there are no studies that have reviewed the effects of these training methods in basketball. Therefore, the present systematic review aimed to collect the updated information about the influence of flywheel training on performance of basketball players. A search in four electronic databases (PubMed, SCOPUS, Web of Science, and Google Scholar) was conducted up to November 20, 2022. Articles were selected as valid for review if: (i) they were an experimental trial published in English; (ii) participants were basketball players without illnesses or injuries, and (iii) a rotational inertial overload method was used as a performance-dependent variable. A total of 93 articles were found. After filtering procedures, only seven studies were considered in this systematic review. In the selected studies, 203 participants were included, 58 females and 145 males. Focusing on basketball related performance variables, all the studies included the countermovement jump (CMJ), while five included sprinting and a change of direction test (COD). The results showed an improvement in performance-related variables associated with basketball (sprint, CMJ, and COD) through the use of inertial methods. Improvements were reported in professional, semi-professional and amateur players as well as both male and female players. However, given the low number of studies, additional investigations on this topic are warranted before a "clear picture" can be drawn concerning the effects of flywheel eccentric overload training in basketball players.

The effects of early short-term insulin treatment vs. glimepiride on beta cell function in newly diagnosed type 2 diabetes with HbA1c above 9.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a complex metabolic impairment. Beta cell (BC) failure is the most challenging among its pathogenetic mechanisms. Recognizing reversible contributors to BC failure could guide individualized approach to early T2D treatment. The aim of this study was to compare early short-term insulin treatment vs. glimepiride, both added to metformin, on BC function, glycemic and lipid control, during 12-month follow-up. METHODS: Eighty newly diagnosed T2D patients, 30-65 years of age, presenting with HbA1c ≥ 9% were enrolled in the study. They were randomly assigned to single-month initial insulin therapy (INS) added to metformin, or to glimepiride and metformin (OAD) as only treatment. Subjects assigned to initial insulin intervention were thereafter switched to OAD. C-peptide (C-Pep) was analyzed at baseline and 2 hours after standardized test meal (STM). All subjects were STM-retested after 3 and 12 months. HbA1c, serum lipids, BMI, HOMA IR, and HOMA B were assessed over follow-up. RESULTS: HbA1c was lower in INS vs OAD at 3-months: 6.26 ± 0.18% vs 6.78 ± 0.10% (p = 0.016), remaining so by 12 months (p =0.056). BMI-adjusted ΔC-Pep was greater in INS vs. OAD at 3 months (4.60 ± 0.59 vs. 3.21 ± 0.34 m2 /kg; p = 0.044), persisting by 12months (4.57 ± 0.56 vs. 3.04 ± 0.34 m2/kg; p = 0.023). Average ΔC-Pep improvement from recruitment to 3 months was 100.8% in INS,vs. 51.3% in OAD. Prevalence of STM-ΔC-Pep response greater than 2.4 ng/mL had risen 3.2-fold by 12 months in the INS, vs. 2.4-fold only in the OAD group (p = 0.018). DISCUSSION: Early short-term insulin intervention in newly diagnosed T2D improves beta cell function more than glimepiride, both added to metformin, resulting in a superior and longer lasting glycemic and lipid control.

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography.

In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/ß-K6P2W18O62 (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application. The acute intravenous toxicity of single WD-POM doses (1/3, 1/5, and 1/10 MTD), which are at least fifty times higher than the typically used dose (0.015 mmol W kg-1) of tungsten-based contrast agents, was evaluated for 14 days. The results of arterial blood gas analysis, CO-oximetry status, electrolyte and lactate levels for 1/10 MTD group (80% survival rate) indicated the mixed respiratory and metabolic acidosis. The highest deposition of WD-POM (0.6 ppm tungsten) was found in the kidney, followed by liver (0.15 ppm tungsten), for which the histological analysis revealed morphological irregularities, although the renal function parameters (creatinine and BUN levels) were within the physiological range. This study is the first and important step in evaluating side effects of polyoxometalate nanoclusters, which in recent years have shown a large potential as therapeutics and contrast agents.

Effects of Eccentric-Oriented Strength Training on Return to Sport Criteria in Late-Stage Anterior Cruciate Ligament (ACL)-Reconstructed Professional Team Sport Players.

Background and Objectives: An effective post-injury training program is essential to regain performance and fulfill criteria for return to sport for team sport athletes following anterior cruciate ligament (ACL) reconstruction. The aim of this study was to compare the effects of 6 weeks of eccentric-oriented strength training vs. traditional strength training during the late-stage ACL-rehab phase on leg strength and vertical and horizontal jumping performance in professional team sport athletes. Materials and Methods: Twenty-two subjects (14 males, 8 females, age 19.9 ± 4.4 years, mass 77.4 ± 15.6 kg, height 182.4 ± 11.7 cm) (mean ± SD) with a unilateral reconstructed ACL (BTB graft) were included in the study. All participants enrolled in the same rehabilitation protocol prior to the training study. Players were randomly assigned to an experimental (ECC: n = 11, age 21.8 ± 4.6 years, mass 82.7 ± 16.6 kg, height 185.4 ± 12.2 cm), and a control group (CON: n = 11, age 19.1 ± 2.1 years, mass 76.6 ± 16.5 kg, height 182.5 ± 10.2 cm). Both groups underwent an equivolumed rehabilitation program, with the only difference being in strength training, which consisted of flywheel training vs. traditional strength training for the experimental and control groups, respectively. Testing was organized before and after the 6-week training programs and included isometric semi-squat tests (ISOSI-injured and ISOSU-uninjured legs), vertical jump tests (CMJ), single-leg vertical jump tests (SLJI-injured and SLJU-uninjured legs), single-leg hop tests (SLHI-injured and SLHU-uninjured legs), and triple hop tests (TLHI-injured and TLHU-uninjured legs). In addition, limb symmetry indexes were calculated for the isometric semi-squat (ISOSLSI) test, the single-leg vertical jump (SLJLSI), and the hop (SLHLSI) tests, as well as the triple-leg hop (THLLSI) test. Results: Main effects of time across training were observed for all dependent variables (posttest > pretest, p < 0.05). Significant group-by-time interactions were found for ISOSU (p < 0.05, ES = 2.51, very large), ISOSI (p < 0.05, ES = 1.78, large), CMJ (p < 0.05, ES = 2.23, very large), SLJI (p < 0.05, ES = 1.48, large), SLHI (p < 0.05, ES = 1.83, large), and TLHI (p < 0.05, ES = 1.83, large). Conclusions: This study suggests that eccentric-oriented strength training in late-stage ACL recovery, undertaken twice or three times weekly for 6 weeks, results in better outcomes than traditional strength training in leg strength, vertical jump ability, and single and triple hop tests with injured legs in professional team sport athletes. It seems that flywheel strength training can be recommended in late-stage ACL recovery for professional team sport athletes in order to regain recommended performance outcome levels faster.

Toward a better understanding of angiosperm xylogenesis: a new method for a cellular approach.

The kinetics of wood formation in angiosperms are largely unknown because their complex xylem anatomy precludes using the radial position of vessels and fibers to infer their time of differentiation. We analyzed xylogenesis in ring-porous ash (Fraxinus angustifolia) and diffuse-porous beech (Fagus sylvatica) over 1 yr and proposed a novel procedure to assess the period of vessel and fiber enlargement using a referential radial file (RRF). Our approach captured the dynamics of wood formation and provided a robust estimation of the kinetics of vessel and fiber enlargement. In beech, fibers and vessels had a similar duration of enlargement, decreasing from 14 to 5 d between April and July. In ash, wide vessels formed in April enlarged at a rate of 27 × 103 µm2 d-1 , requiring half the time of contemporary fibers (6 vs 12 d), and less time than the narrower vessels (14 d) formed in May. These findings reveal distinct cell-type-dependent mechanisms for differentiation in diffuse-porous and ring-porous trees, enhancing our understanding of angiosperm wood cell kinetics. Our approach presents an effective method for investigating angiosperm wood formation and provides a more accurate representation of vessel and fiber morphogenesis in wood formation models.

Factors affecting match running performance in elite soccer: Analysis of UEFA Champions League matches.

This study aimed to examine the independent effect of different match-related factors on match running performance (MRP) in elite soccer. Players' MRPs (n = 244) were collected during UEFA Champions League (UCL) group stage matches in the 2020-21 season. All MRP data were collected by the semi-automatic optical system InStat Fitness (InStat Limited, Limerick, Republic of Ireland). Match-related factors included match outcome, team quality, match location, opponent quality and difference in team quality, while MRP included cumulative and relative measures of total distance (TD and R-TD), low-intensity running (LIR and R-LIR) (≤ 4 m/s), moderate-intensity running (MIR and R-MIR) (4-5.5 m/s) and high-intensity running (HIR and R-HIR) (≥ 5.5 m/s). Linear mixed models were used to examine the collective effect of match-related factors on MRPs when controlling for between-player, between-playing position and between-team variation. The main findings were that match outcome was associated with reduced HIR (d = -0.38, p = 0.04), match location was associated with increased TD, R-TD, LIR and R-LIR (d = 0.54-0.87, all p < 0.01), while team quality, opponent quality and difference in team quality were not associated with MRP. These results show that (i) winning UCL matches was not strongly influenced by players' physical performance, (ii) away UCL matches were characterized by a slower match pace and greater match volume, and (iii) players' physical performance was similar irrespective of playing either in or against high- or low-quality teams. The findings from this study may help soccer coaches to ensure optimal physical preparation of players in elite soccer.

Sap flow and growth response of Norway spruce under long-term partial rainfall exclusion at low altitude.

Introduction: Under ongoing climate change, more frequent and severe drought periods accompanied by heat waves are expected in the future. Under these conditions, the tree's survival is conditioned by fast recovery of functions after drought release. Therefore, in the presented study, we evaluated the effect of long-term water reduction in soil on tree water use and growth dynamics of Norway spruce. Methods: The experiment was conducted in two young Norway spruce plots located on suboptimal sites at a low altitude of 440 m a.s.l. In the first plot (PE), 25% of precipitation throughfall was excluded since 2007, and the second one represented the control treatment with ambient conditions (PC). Tree sap flow, stem radial increment, and tree water deficit were monitored in two consecutive growing seasons: 2015-2016, with contrasting hydro-climatic conditions. Results: Trees in both treatments showed relatively isohydric behavior reflected in a strong reduction of sap flow under the exceptional drought of 2015. Nevertheless, trees from PE treatment reduced sap flow faster than PC under decreasing soil water potential, exhibiting faster stomatal response. This led to a significantly lower sap flow of PE, compared to PC in 2015. The maximal sap flow rates were also lower for PE treatment, compared to PC. Both treatments experienced minimal radial growth during the 2015 drought and subsequent recovery of radial growth under the more the humid year of 2016. However, treatments did not differ significantly in stem radial increments within respective years. Discussion: Precipitation exclusion treatment, therefore, led to water loss adjustment, but did not affect growth response to intense drought and growth recovery in the year after drought.

Networking the forest infrastructure towards near real-time monitoring - A white paper.

Forests account for nearly 90 % of the world's terrestrial biomass in the form of carbon and they support 80 % of the global biodiversity. To understand the underlying forest dynamics, we need a long-term but also relatively high-frequency, networked monitoring system, as traditionally used in meteorology or hydrology. While there are numerous existing forest monitoring sites, particularly in temperate regions, the resulting data streams are rarely connected and do not provide information promptly, which hampers real-time assessments of forest responses to extreme climate events. The technology to build a better global forest monitoring network now exists. This white paper addresses the key structural components needed to achieve a novel meta-network. We propose to complement - rather than replace or unify - the existing heterogeneous infrastructure with standardized, quality-assured linking methods and interacting data processing centers to create an integrated forest monitoring network. These automated (research topic-dependent) linking methods in atmosphere, biosphere, and pedosphere play a key role in scaling site-specific results and processing them in a timely manner. To ensure broad participation from existing monitoring sites and to establish new sites, these linking methods must be as informative, reliable, affordable, and maintainable as possible, and should be supplemented by near real-time remote sensing data. The proposed novel meta-network will enable the detection of emergent patterns that would not be visible from isolated analyses of individual sites. In addition, the near real-time availability of data will facilitate predictions of current forest conditions (nowcasts), which are urgently needed for research and decision making in the face of rapid climate change. We call for international and interdisciplinary efforts in this direction.

Relationship between socio-descriptive characteristics, burnout syndrome, and quality of life of employees.

Introduction: Burnout syndrome develops as a consequence of chronic stress among employees. The study objective was to examine what socio-descriptive characteristics of employees might be associated with the appearance of the occupational burnout and to evaluate the relationship between job burnout and the quality of life among security employees of the professional private security sector in Central Serbia. Methods: A multicenter cross-sectional questionnaire-based study was performed. A multivariate logistic regression analysis and ANOVA post choc test was applied. Results: A total of 353 respondents (330 male and 23 female) participated in the study. Female sex and older age were associated with a higher risk of total burnout and the development of emotional exhaustion while male sex, higher education, and managerial position were associated with higher personal achievement and lower risk of total burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of employees. A significant negative correlation was found between total burnout and the Physical Health Composite Score (PHC) score with a correlation coefficient (rs) of -0.265 (95%CI from -0.361 to -0.163); between total burnout and the and Mental Health Composite Score (MHC) score with a rs of -0.391 (95%CI from -0.480 to -0.301); and between total burnout and TQL score with a rs of -0.351 (95%CI from -0.445 to -0.258). Conclusion: Female sex and older age were associated with a higher risk of total burnout and the development of EE while a managerial position and higher education were protective factors in relation to the development of burnout. Male sex, marital union, two or more children, and direct contact with clients were significantly associated with a lower quality of life of the employees. Shift work significantly reduced the total quality of life, while managerial positions increased the quality of life.

The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies.

The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.

Chloroquine Attenuates Oxidative Stress in Gentamicin-Induced Nephrotoxicity in Rats.

The wider application of gentamicin is limited by potential adverse effects (nephrotoxicity and ototoxicity). The goal of our study was to investigate the effects of chloroquine on biochemical and oxidative stress parameters in gentamicin-induced nephrotoxicity in rats. Animals were randomly divided into 1 of 5 groups. First was Sham group (0.9% NaCl) (n = 8); second group received gentamicin (n = 8); while third (n = 8), fourth (n = 8) and fifth group (n = 8) received gentamicin and chloroquine in a dose of 0.3, 1 and 3 mg/kg, respectively. The urea and creatinine levels were significantly lower in chloroquine treated groups in doses of 0.3 mg/kg and 1 mg/kg (P < 0.001). Total oxidant status and the oxidative stress index showed significantly lower values in all chloroquine treated groups (P < 0.001; P < 0.005). Malondialdehyde was lower in chloroquine treatment in doses of 0.3 mg/kg (P < 0.005) and 3 mg/kg (P < 0.05). Chloroquine treatment markedly reduced the level of superoxide dismutase in doses of 1 mg/kg (P < 0.01) and 3 mg/kg (P < 0.05). Our study showed that chloroquine attenuates gentamicin-induced nephrotoxicity in rats regarding biochemical and oxidative stress parameters.

Influence of stathmin 1 (STMN1) expression on neoangiogenesis in colorectal adenocarcinoma.

Stathmin1 is a microtubular regulatory protein. The expression disorders of this protein result in significant changes in cell migration, invasion, adhesion and colony formation in many malignant tumors. The aim of our research was to investigate the effects of Stathmin1 expression on neoangiogenesis in colorectal adenocarcinoma. Biopsy material that was obtained by the resection of colorectal carcinoma was used. The experimental group consisted of operative biopsies of colorectal cancer (n = 72), and the control group (n = 72) consisted of biopsies of adjacent non-tumor colon tissue. The biopsy material was taken from an operative preparation submitted to the Department of Pathology. After histopathological treatment, classical Hematoxylin- Eosin and immunohistochemical ABC methods with anti-Stathmin1, anti-VEGF and anti CD105 antibodies were applied on 4 µm thick sections. High expression of Stathmin1 is associated with severe (91.9%) and moderate (8.1%) expression of VEGF in a significantly high number of cases. This relation is defined by a highly significant correlation coefficient (r = 0.768; p = 0.000). High expression of Stathmin1 is associated with a high microvascular density index (mvdIDX) in a significant number of cases (73.0%) while low expression of Stathmin1 is in relation with low mvdIDX in a significant 73.7% of cases. This relationship is also defined by a highly significant correlation coefficient (r = 0.566; p = 0.000). ROC analysis showed that the sensitivity for Stathmin1 was 97.4% and the specificity was 91.4%. Based on Stathmin1 expression, it is possible to differentiate patients with increased risk for metastatic disease. The highly significant association of Stathmin1 expression with VEGF expression and microvascular density (MVD) suggests that Stathmin1 may be a serious candidate for therapeutic target.

Subcutaneous and Intraosseous Fat Necrosis Associated with Chronic Pancreatitis.

Background: Extra-abdominal manifestations of fat necrosis, like subcutaneous fat necrosis, polyarthritis, and polyserositis may appear with an occurrence rate of about 0.8%, wherein intraosseous fat necrosis is a more rare complication of pancreatitis, with few reports in English literature. Case report: A 34-year-old male with a 15-year-history of alcohol abuse was hospitalized several times in the last few years because of attacks of relapsed chronic pancreatitis. After the last attack, pancreatitis came in a stable state ("burned out") with no symptoms and signs of the disease. The patient had been free of symptoms for 28 months since the last admission when he came with sub-febrile temperature, huge pain, swelling, and erythema in the area of the left lateral malleolar region with propagation in the foot. Blood biochemistry was normal. Conventional radiography showed multiple sites of osteolysis in the left calcaneus. Images on multislice computed tomography (MSCT) with 3D reconstruction revealed hypodense focuses that corresponded to osteonecrosis areas and bone marrow edema in the left calcaneus. Conclusions: The possibility of intraosseous fat necrosis should be considered in situations of unexplained polyarthritis or panniculitis, particularly in individuals with alcohol abuse or pancreatic disease.

Isolated Spleen Metastases of Endometrial Cancer: A Case Report.

BACKGROUND: Isolated splenic metastases from endometrial cancer, which is a relatively common malignancy, are extremely rare findings; to date, only 14 cases have been reported in the literature. CASE SUMMARY: We report a patient with isolated splenic metastases of endometrial cancer 3 years after radical surgery of the primary tumor. The patient was successfully treated by splenectomy and six cycles of paclitaxel. Fifty months after splenectomy, she was alive and well, and with no evidence of disease. CONCLUSION: Isolated spleen metastasis of endometrial cancer is very rare. Radical surgery and adjuvant therapy may offer excellent long-term survival.

The sellar region as presenting theater for hematologic malignancies-A 17-year single-center experience.

Hematological neoplastic mass lesions of the sellar region are rare. We identified five cases of hematological malignancy with first presentation in the sellar region from our departmental database of 1,405 patients (0.36%) with sellar lesions diagnosed over the 17-year period (2005-2021). All patients were females (mean age 55.2 ± 3.4 years). One patient had multiple myeloma (MM), one patient had acute myeloid leukemia (AML), while three other patients had lymphoma (intravascular lymphoma (IVL, n = 1) or non-Hodgkin's lymphoma (NHL, n = 2). Most patients presented with ophthalmoplegia, and one patient with diabetes insipidus (DI), with short duration of symptoms (median 30 days). All patients had an elevated erythrocyte sedimentation rate and altered blood count, while patients with lymphoma had elevated lactate dehydrogenase (LDH). Sellar mass was demonstrated in three patients while the patient with IVL had an empty sella and in the AML patient posterior lobe T1W hyperintensity was lost. Two patients (IVL and NHL) presented with multiple anterior pituitary deficiencies and one patient (AML) had DI. All patients were treated with chemotherapy. Two patients responded well to treatment (one had reversed hypopituitarism), while three patients died. Differential diagnosis of sellar-parasellar pathology should include suspicion of hematological malignancy, particularly in patients with short duration of nonspecific symptoms, neurological signs (ophthalmoplegia), blood count alterations and LDH elevation, pituitary dysfunction and imaging features atypical for pituitary adenoma. Early diagnosis is crucial for timely initiation of hematological treatment aimed at inducing disease remission and partial or full recovery of pituitary function.

Pituitary tumors and the risk of other malignancies: is the relationship coincidental or causal?

Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushing's disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors - obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.