Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

Characterization of the IAA-Producing and -Degrading Pseudomonas Strains Regulating Growth of the Common Duckweed (Lemna minor L.).

The rhizosphere represents a center of complex and dynamic interactions between plants and microbes, resulting in various positive effects on plant growth and development. However, less is known about the effects of indole-3-acetic acid (IAA) on aquatic plants. In this study, we report the characterization of four Pseudomonas strains isolated from the rhizosphere of the common duckweed (Lemna minor) with IAA-degradation and -utilization ability. Our results confirm previous reports on the negative effect of IAA on aquatic plants, contrary to the effect on terrestrial plants. P. putida A3-104/5 demonstrated particularly beneficial traits, as it exhibited not only IAA-degrading and -producing activity but also a positive effect on the doubling time of duckweeds in the presence of IAA, positive chemotaxis in the presence of IAA, increased tolerance to oxidative stress in the presence of IAA and increased biofilm formation related to IAA. Similarly, P. gessardii C31-106/3 significantly shortened the doubling time of duckweeds in the presence of IAA, while having a neutral effect in the absence of IAA. These traits are important in the context of plant-bacteria interactions and highlight the role of IAA as a common metabolite in these interactions, especially in aquatic environments where plants are facing unique challenges compared to their terrestrial counterparts. We conclude that IAA-degrading and -producing strains presented in this study might regulate IAA effects on aquatic plants and confer evolutionary benefits under adverse conditions (e.g., under oxidative stress, excess of IAA or nutrient scarcity).

Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting.

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial-mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment.

Repertoire and abundance of secreted virulence factors shape the pathogenic capacity of Pseudomonas syringae pv. aptata.

Pseudomonas syringae pv. aptata is a member of the sugar beet pathobiome and the causative agent of leaf spot disease. Like many pathogenic bacteria, P. syringae relies on the secretion of toxins, which manipulate host-pathogen interactions, to establish and maintain an infection. This study analyzes the secretome of six pathogenic P. syringae pv. aptata strains with different defined virulence capacities in order to identify common and strain-specific features, and correlate the secretome with disease outcome. All strains show a high type III secretion system (T3SS) and type VI secretion system (T6SS) activity under apoplast-like conditions mimicking the infection. Surprisingly, we found that low pathogenic strains show a higher secretion of most T3SS substrates, whereas a distinct subgroup of four effectors was exclusively secreted in medium and high pathogenic strains. Similarly, we detected two T6SS secretion patterns: while one set of proteins was highly secreted in all strains, another subset consisting of known T6SS substrates and previously uncharacterized proteins was exclusively secreted in medium and high virulence strains. Taken together, our data show that P. syringae pathogenicity is correlated with the repertoire and fine-tuning of effector secretion and indicate distinct strategies for establishing virulence of P. syringae pv. aptata in plants.

Culture-Dependent and Metabarcoding Characterization of the Sugar Beet (Beta vulgaris L.) Microbiome for High-Yield Isolation of Bacteria with Plant Growth-Promoting Traits.

The diversity of plant-associated bacteria is vast and can be determined by 16S rRNA gene metabarcoding. Fewer of them have plant-beneficial properties. To harness their benefits for plants, we must isolate them. This study aimed to check whether 16S rRNA gene metabarcoding has predictive power in identifying the majority of known bacteria with plant-beneficial traits that can be isolated from the sugar beet (Beta vulgaris L.) microbiome. Rhizosphere and phyllosphere samples collected during one season at different stages of plant development were analyzed. Bacteria were isolated on rich unselective media and plant-based media enriched with sugar beet leaves or rhizosphere extracts. The isolates were identified by sequencing the 16S rRNA gene and tested in vitro for their plant-beneficial properties (stimulation of germination; exopolysaccharide, siderophore, and HCN production; phosphate solubilization; and activity against sugar beet pathogens). The highest number of co-occurring beneficial traits was eight, found in isolates of five species: Acinetobacter calcoaceticus, Bacillus australimaris, B. pumilus, Enterobacter ludwiigi, and Pantoea ananatis. These species were not detected by metabarcoding and have not previously been described as plant-beneficial inhabitants of sugar beets. Thus, our findings point out the necessity of a culture-dependent microbiome analysis and advocate for low-nutrient plant-based media for high-yield isolation of plant-beneficial taxa with multiple beneficial traits. A culture-dependent and -independent approach is required for community diversity assessment. Still, isolation on plant-based media is the best approach to select isolates for potential use as biofertilizers and biopesticides in sugar beet cultivation.

The Influence of Different SARS-CoV-2 Strains on Changes in Maximal Oxygen Consumption, Ventilatory Efficiency and Oxygen Pulse of Elite Athletes.

PURPOSE: The aim of this study was to evaluate the influence of different SARS-CoV-2 strains on the functional capacity of athletes. METHODS: In total, 220 athletes underwent cardiopulmonary exercise testing (CPET) after coronavirus infection and before returning to sports activities. Eighty-eight athletes were infected by the Wuhan virus, and 66 were infected during the Delta and Omicron strain periods of the pandemic. RESULTS: The CPET results showed significantly decreased maximal oxygen consumption, ventilatory efficiency, and oxygen pulse in athletes who were infected with Wuhan and Delta strains compared to athletes who suffered from Omicron virus infection. An early transition from aerobic to anaerobic metabolic pathways for energy production was observed in the Wuhan and Delta groups but not in athletes who were infected with the Omicron strain. There were no differences in the obtained results when Wuhan and Delta virus variants were compared. CONCLUSION: These results suggest that the Wuhan and Delta virus strains had a significantly greater negative impact on the functional abilities of athletes compared to the Omicron virus variant, especially in terms of aerobic capacity and cardiorespiratory function.

Genome Analysis of Two Pseudomonas syringae pv. aptata Strains with Different Virulence Capacity Isolated from Sugar Beet: Features of Successful Pathogenicity in the Phyllosphere Microbiome.

Members of the Pseudomonas syringae species complex are heterogeneous bacteria that are the most abundant bacterial plant pathogens in the plant phyllosphere, with strong abilities to exist on and infect different plant hosts and survive in/outside agroecosystems. In this study, the draft genome sequences of two pathogenic P. syringae pv. aptata strains with different in planta virulence capacities isolated from the phyllosphere of infected sugar beet were analyzed to evaluate putative features of survival strategies and to determine the pathogenic potential of the strains. The draft genomes of P. syringae pv. aptata strains P16 and P21 are 5,974,057 bp and 6,353,752 bp in size, have GC contents of 59.03% and 58.77%, respectively, and contain 3,439 and 3,536 protein-coding sequences, respectively. For both average nucleotide identity and pangenome analysis, P16 and P21 largely clustered with other pv. aptata strains from the same isolation source. We found differences in the repertoire of effectors of the type III secretion system among all 102 selected strains, suggesting that the type III secretion system is a critical factor in the different virulent phenotypes of P. syringae pv. aptata. During genome analysis of the highly virulent strain P21, we discovered genes for T3SS effectors (AvrRpm1, HopAW1, and HopAU1) that were not previously found in genomes of P. syringae pv. aptata. We also identified coding sequences for pantothenate kinase, VapC endonuclease, phospholipase, and pectate lyase in both genomes, which may represent novel effectors of the type III secretion system. IMPORTANCE Genome analysis has an enormous effect on understanding the life strategies of plant pathogens. Comparing similarities with pathogens involved in other epidemics could elucidate the pathogen life cycle when a new outbreak happens. This study represents the first in-depth genome analysis of Pseudomonas syringae pv. aptata, the causative agent of leaf spot disease of sugar beet. Despite the increasing number of disease reports in recent years worldwide, there is still a lack of information about the genomic features, epidemiology, and pathogenic life strategies of this particular pathogen. Our findings provide advances in disease etiology (especially T3SS effector repertoire) and elucidate the role of environmental adaptations required for prevalence in the pathobiome of the sugar beet. From the perspective of the very heterogeneous P. syringae species complex, this type of analysis has specific importance in reporting the characteristics of individual strains.

Savory, Oregano and Thyme Essential Oil Mixture (HerbELICO®) Counteracts Helicobacter pylori.

Fifty percent of the world's population is infected with Helicobacter pylori, which can trigger many gastrointestinal disorders. H. pylori eradication therapy consists of two to three antimicrobial medicinal products, but they exhibit limited efficacy and may cause adverse side effects. Alternative therapies are urgent. It was assumed that an essential oil mixture, obtained from species from genera Satureja L., Origanum L. and Thymus L. and called the HerbELICO® essential oil mixture, could be useful in H. pylori infection treatment. HerbELICO® was analyzed by GC-MS and assessed in vitro against twenty H. pylori clinical strains isolated from patients of different geographical origins and with different antimicrobial medicinal products resistance profiles, and for its ability to penetrate the artificial mucin barrier. A customer case study included 15 users of HerbELICO®liquid/HerbELICO®solid dietary supplements (capsulated HerbELICO® mixture in liquid/solid form). Carvacrol and thymol were the most dominant compounds (47.44% and 11.62%, respectively), together with p-cymene (13.35%) and γ-terpinene (18.20%). The minimum concentration required to inhibit in vitro H. pylori growth by HerbELICO® was 4-5% (v/v); 10 min exposure to HerbELICO® was enough to kill off the examined H. pylori strains, while HerbELICO® was able to penetrate through mucin. A high eradication rate (up to 90%) and acceptance by consumers was observed.

Genotyping-driven diversity assessment of biocontrol potent Bacillus spp. strain collection as a potential method for the development of strain-specific biomarkers.

Bacillus species are among the most researched and frequently applied biocontrol agents. To estimate their potential as environmentally friendly microbial-based products, reliable and rapid plant colonization monitoring methods are essential. We evaluated repetitive element-based (rep) and Random Amplified Polymorphic DNA (RAPD) PCR (Polymerase Chain Reaction) genotyping in a diversity assessment of 251 strains from bulk soil, straw, and manure samples across Serbia, highlighting their discriminative force and the presence of unique bands. RAPD 272, OPG 5, and (GTG)5 primers were most potent in revealing the high diversity of a sizable environmental Bacillus spp. collection. RAPD 272 also amplified a unique band for a proven biocontrol strain, opening the possibility of Sequence Characterized Amplified Region (SCAR) marker design. That will enable colonization studies using the SCAR marker for its specific detection. This study provides a guide for primer selection for diversity and monitoring studies of environmental Bacillus spp. isolates.

In situ detection of the genotoxic potential as one of the lines of evidence in the weight-of-evidence approach-the Joint Danube Survey 4 Case Study.

Environmental studies which aim to assess the ecological impact of chemical and other types of pollution should employ a complex weight-of-evidence approach with multiple lines of evidence (LoEs). This study focused on in situ genotoxicological methods such as the comet and micronucleus assays and randomly amplified polymorphic DNA analysis as one of the multiple LoEs (LoE3) on the fish species Alburnus alburnus (bleak) as a bioindicator. The study was carried out within the Joint Danube Survey 4 (JDS4) at nine sites in the Danube River Basin in the Republic of Serbia. Out of nine sampling sites, two were situated at the Tisa, Sava, and Velika Morava rivers, and three sites were at the Danube River. The three additionally employed LoEs were: SumTUwater calculated based on the monitoring data in the database of the Serbian Environmental Protection Agency (SEPA) (LoE1); in vitro analyses of JDS4 water extracts employing genotoxicological methods (LoE2); assessment of the ecological status/potential by SEPA and indication of the ecological status for the sites performed within the JDS4 (LoE4). The analyzed biomarker responses in the bleak were integrated into the unique integrated biomarker response index which was used to rank the sites. The highest pollution pressure was recorded at JDS4 39 and JDS4 36, while the lowest was at JDS4 35. The impact of pollution was confirmed at three sites, JDS4 33, 40, and 41, by all four LoEs. At other sampling sites, a difference was observed regarding the pollution depending on the employed LoEs. This indicates the importance of implementing a comprehensive weight-of-evidence approach to ensure the impact of pollution is not overlooked when using only one LoE as is often the case in environmental studies.

The Clinical Benefit of Percutaneous Transhepatic Biliary Drainage for Malignant Biliary Tract Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) is a decompression procedure for malignant proximal biliary obstruction. In this research, over a six-year period, 89 patients underwent PTBD procedure for jaundice caused by malignant disease to restart chemotherapy or for palliative intent. Clinical outcomes after PTBD procedure in the two groups of patients, according to the adequate bilirubin decline (ABD) needed for subsequent chemotherapy, are presented in this paper. Survival and logistic regression were plotted and compared using Kaplan−Meier survival multivariate analysis with a long-range test. Results were processed by MEDCALC software. In the series, 58.4% (52/89) of patients were in good performance status (ECOG 0/1), and PTBD was performed with the intention to (re)start chemotherapy. The normalization of the bilirubin level was seen in 23.0% (12/52), but only 15.4% (8/52) received chemotherapy. The median survival time after PTBD was 9 weeks. In patients with ABD that received chemotherapy, the median survival time was 64 weeks, with 30-day mortality of 27.7%, and 6.4% of death within 7 days. The best outcome was in patients with good performance status (ECOG 0−1), low bilirubin (<120 µmol/L) and LDH (<300 µmol/L) levels and elevated leukocytes at the time of the procedures. PTBD is considered in ABD patients who are candidates for chemotherapy.

Genetic Diversity of Orobanche cumana Populations in Serbia.

In this study, we report genetic characterization of Orobanche cumana, the causal agent of sunflower wilting in Serbia. The genetic diversity of this parasitic plant in Serbia was not studied before. Random amplified polymorphic DNA (RAPD) markers and partial rbcL gene sequences analysis were used to characterize the O. cumana populations at the molecular level. While phylogenetic analyses of RAPD-PCR amplicons were performed using unweighted pair-group Method analyses, rbcL gene sequences were analyzed using neigbor joining method and minimum spanning tree. Molecular analyses of RAPD-PCR analysis revealed high genetic diversity of O. cumana populations which indicated high adaptive potential of this parasitic weed in Serbia. Further analyses of rbcL gene using minimum spanning tree revealed clear differences among diverse sections of Orobanche genus. Although this molecular marker lacked the resolution to display intrapopulation diversity it could be a useful tool for understanding the evolution of this parasitic plant. Our results suggested that O. cumana has great genetic potential which can lead to differentiation of more virulent races which is important for determining crop breeding strategies for their control.

COVID-19 vaccines and cancer patients: acceptance, attitudes and safety.

PURPOSE: Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines. METHODS: The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records. RESULTS: During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported. CONCLUSION: We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.

Influence of Higenamine on Exercise Performance of Recreational Female Athletes: A Randomized Double-Blinded Placebo-Controlled Trial.

The aim of this study was to determine the ergogenic effects and the safety profile of a one-component higenamine supplement in female recreational athletes. Twelve recreational female basketball players (age 29-41 years, oxygen consumption (VO2max) > 30 ml⋅kg-1⋅min-1, with training > 5 h wk-1) were randomized either to the higenamine group, or to the placebo group for 3 weeks. In order to determine ergogenic effects and safety profile of higenamine administration, we assessed the following variables before and after 3 weeks of supplementation: anthropometric parameters, resting metabolic rate (RMR), exercise testing variables, serum free fatty acids (FFAs), blood pressure, enzyme activity, urea, lipid profile, and complete blood count. There were no differences between groups in anthropometric parameters, including basal metabolic rate (BMR), RMR and body fat [p = 0.706 (Cohen's d 0.223), p = 0.169 (Cohen's d 0.857), and p = 0.223 (Cohen's d 0.750), respectively], FFAs [0.43 ± 0.03 vs. 0.54 ± 0.23, p = 0.206 (Cohen's d 0.540)], neither significant differences in cardiopulmonary parameters after the intervention period. Furthermore, all measured outcome variables in the safety assessment were not significant, with values remaining stable during the intervention period for participants in both groups. This is the first study to document the effects and the safety profile of higenamine-based dietary supplements at a specified dose in female recreational athletes. Our data indicate that 21-day of supplementation with 75 mg higenamine would not result in improving cardiopulmonary exercise fitness and weight loss in female recreational athletes. Moreover, supplementation with 75 mg higenamine is safe and well-tolerated in younger recreational female athletes.

Focal Myocarditis after Mild COVID-19 Infection in Athletes.

COVID-19 infection in athletes usually has a milder course, but in the case of complications, myocarditis and even sudden cardiac death may occur. We examined an athlete who felt symptoms upon returning to training after asymptomatic COVID-19 infection. Physical, laboratory, and echocardiography findings were normal. The cardiopulmonary exercise test was interrupted at submaximal effort due to severe dyspnea in the presence of reduced functional capacity in comparison to previous tests. Cardiac magnetic resonance (CMR) detected the focal myocarditis. After three months of recovery, CMR still revealed the presence of focal myocarditis and the persistence of decreased functional capacity. This case raises the question of screening athletes even after asymptomatic forms of COVID-19 infection.

Immunotherapy in the treatment of lymphoma.

Relapsed or refractory non-Hodgkin's lymphomas, especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases. Patients who do not respond to initial therapy or experience relapse are treated with salvage regimens, and if eligible for aggressive therapy, treatment is continued with high-dose chemotherapy and autologous stem cell transplantation. Current therapy options can cure substantial numbers of patients, however for some it is still an uncurable disease. Numerous new drugs and cell therapies are being investigated for the treatment of relapsed or refractory lymphomas. Different types of immunotherapy options have shown promising results, and some have already become the standard of care. Here, we review immunotherapy options for the treatment of lymphoma and discuss the results, positions, practical aspects, and future directions of different drugs and cellular therapies for the treatment of this disease.

Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases.

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a "gold standard". RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the "gold standard", it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

Cognitive impairment and structural brain damage in multiple system atrophy-parkinsonian variant.

In this multiparametric, cross-sectional study, we aimed to investigate cognitive impairment and brain structural changes in patients with multiple system atrophy (MSA)-parkinsonian variant (MSA-p). Twenty-six MSA-p patients and 19 controls underwent clinical and neuropsychological evaluation and 1.5 T brain MRI scan. Cortical thickness measures and volumes of deep grey matter structures were obtained. A regression analysis correlated MRI metrics with clinical features in MSA-p patients. Almost 46% of MSA-p patients showed a mild cognitive impairment involving mainly attentive-executive and memory domains. Apathy and depression were found in half of MSA-p patients. MSA-p patients showed significant cortical thinning of fronto-temporal-parietal regions and atrophy of periaqueductal grey matter, left cerebellar hemisphere, left pallidum and bilateral putamen, compared to controls. Cortical thinning in temporal regions correlated with global cognitive status and memory impairment. Grey matter cerebellar atrophy correlated with motor deficits. MSA-p patients showed a multidomain cognitive impairment with a prominent cortical damage in anterior more than posterior brain regions and grey matter volume reduction in subcortical structures. Cortical and subcortical structural changes might lead to cognitive dysfunction in MSA-p.

Cyclin D1 and p57 expression in relation to clinicopathological characteristics and overall survival in patients with renal cell carcinoma.

PURPOSE: There is a need for identifying molecular prognostic biomarkers to better predict clinical outcomes in patients with renal cell carcinoma (RCC). This study investigated the pattern of cyclin D1 and p57 expression in RCC patients and evaluated their relation with clinicopathological characteristics and overall survival (OS). METHODS: Immunohistochemistry was applied to paraffin-embedded tissue sections of 74 RCC patients. Two cut-off groups were defined by the fraction of positive cells as follows: ≤10% and >10% positive cells for cyclin D1, and ≤5% and >5% positive cells for p57. RESULTS: Cyclin D1 expression in >10% of positive cells was observed mostly in the clear cell RCC, while p57 expression in ≤5% of positive cells was found in 86% of chromophobe RCC specimens. The higher expression of cyclin D1 and lower expression of p57 were more frequent in grade I-II tumors. OS was associated with unfavorable clinicopathological characteristics. However, cyclin D1/p57 expression did not influence the survival rates. CONCLUSION: Although cyclin D1 and p57 expression did not affect survival rates in RCC patients, proper validation and establishment of the qualitative cut-off point are needed for these tumors.