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Background: The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother–newborn pairs, although newborns are considered vitK deficient and with sterile gut. Methods: We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). Results: We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother–newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs. [ABSTRACT FROM AUTHOR]

Background: The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother–newborn pairs, although newborns are considered vitK deficient and with sterile gut. Methods: We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). Results: We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother–newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs.

We investigated the presence and ecology of Chirocephalus croaticus (Steuer, 1899) during three successive seasons (spring and autumn 2018, spring 2019) at Lake Petelinje (SW Slovenia). Although the presence (duration, abundance) of this fairy shrimp strongly differs among different seasons and both years, we showed that in a season with favourable conditions (spring 2018) its abundance increases rapidly at the end of the season as the shrimps persist in small pools until the water dries out. The species may appear again during the autumn, however, its abundance and persistence seem to be much lower and shorter than during the spring, respectively. Nevertheless, persistence and abundance may also differ strongly among the two successive spring seasons (less shrimps found during the shorter season of 2019 than in 2018). Larvae appear first, and are most abundant at the beginning of the season, and are followed by adult males (protandry) and females, which become most abundant at the end of the season. Also, larvae seem to be more abundant on exposed bottom (gravel path), while adults are much more abundant in the shelter of a submerged meadow. Ovigerous females had 9-37 cysts (fertilized eggs) in their brood pouch, and the position of differently developed eggs changed during the season; the presence of females without eggs during mid- and at the end of season indicates the production of thin-shelled summer, and thick-shelled winter cysts, respectively. In contrast with the water decrease that is in strongly negative association with the abundance of the fairy shrimps (lake size — abundance: r = − 0.56 , P < 0.001), no other environmental parameters were highly associated (r ⩽ | 0.38 |) with species abundance. Although the local population (one of only two currently known) seems to be in good condition, appropriate conservation action should be taken to prevent the decrease of this population in the future. Résumé: Nous avons étudié la présence et l'écologie de Chirocephalus croaticus (Steuer, 1899) au cours de trois saisons successives (printemps et automne 2018, printemps 2019) dans le Lac Petelinje (SO Slovanie). Bien que la présence (durée, abondance) de cette crevette diffère fortement selon les différentes saisons et les deux années, nous avons montré que dans une saison avec des conditions favorables (printemps 2018) son abondance augmente rapidement à la fin de la saison et que les crevettes persistent dans des flaques d'eau jusqu'à l'assèchement. L'espèce peut apparaitre de nouveau en automne, cependant son abondance semble être plus basse et sa persistance plus courte que pendant le printemps. Néanmoins, persistance et abondance peuvent aussi différer entre deux printemps successifs (moins de crevettes trouvées durant la courte saison de 2019 qu'en 2018). Les larves apparaissent en premier et sont plus abondantes en début de saison, elles sont suivies par des males adultes (protandrie) et les femelles qui deviennent plus abondantes en fin de saison. De plus, les larves semblent être plus abondantes sur des fonds ouverts (graviers), tandis que les adultes sont beaucoup plus abondants dans les abris de prairies submergées. Les femelles ovigères avaient 9-37 cystes (œufs fécondés) dans leur poche incubatrice, et la position des œufs à des stades de développement différents change au cours de la saison ; la présence des femelles sans œufs à la mi-saison et en fin de saison indique la production de cystes d'été à fine enveloppe et de cystes d'hiver à enveloppe épaisse. Alors que la baisse de l'eau est fortement associé négativement avec l'abondance des crevettes (taille du lac — abondance : r = − 0 , 56 , P < 0 , 001), aucun autre facteur environnemental n'a été aussi fortement associé (r ⩽ | 0 , 38 |) avec l'abondance de l'espèce. Bien que la population locale (une ou deux connues actuellement) semble être en bonne condition, une action de conservation appropriée devrait être prise pour éviter la diminution de cette population dans le futur. [ABSTRACT FROM AUTHOR]

Infants are at risk of vitamin K deficiency that may lead to vitamin K deficiency bleeding (VKDB). Although many vitamin K prophylactic regimens have been developed throughout the years, still cases of late form VKBD may occur. The introduction of combined prophylactic strategy with prolonged oral prophylaxes after the intramuscular dose at birth has showed a decrease of the late severe VKDB incidence. Nevertheless, there is still lack of consensus about the administration scheme after the first dose at birth. Conclusion: Late form VKBD is not eradicated, and the best prophylactic regimen in term and preterm infants is still an open debate. [ABSTRACT FROM AUTHOR]

• PIVKA-II is increasingly used for the diagnosis and follow-up of HCC. • Biological variation data were generated from 18 European healthy volunteers. • CV A was 2.82% while sex-independent CV I and CV G were 13.35% and 16.05%, respectively. PIVKA-II (DCP) is increasingly used for the diagnosis and the surveillance of hepatocellular carcinoma (HCC) in at-risk populations. However, to date, few data are available concerning the intra- and inter-individual variability of this marker, which makes the interpretation of serial measurements difficult in the context of monitoring. 19 European healthy volunteers (HVs) were taken each week during five consecutive weeks. Samples were analyzed in duplicate on the Lumipulse® analyzer (Fujirebio, Gent, Belgium). Analytical variation (CV A), within-subject biological variation (CV I) and between-subject biological variation (CV G) were calculated using nested ANOVA following normality assessment, outlier exclusion, and homogeneity of variance analysis. No significant difference was observed for the mean values (p = 0.23) between men (mean: 30.66 mAU/mL) and women (mean: 33.90 mAU/mL) subgroups. CV A was 2.82% while sex-independent CV I and CV G were 13.35% and 16.05%, respectively. Taking these values, the calculated reference change value (RCV) and index of individuality were 37.70% and 0.85, respectively. We reported for the first-time biological variation data for PIVKA-II in a cohort of European HVs. We believe that our results can be used to set analytical specification goals as well as to improve the interpretation of serial measurements of PIVKA-II for monitoring purposes. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin K, discovered in the 1930s, is a very important compound for the human body, performing many func- tions. The most well known of them are calcium homeostasis and coagulation. Nowadays it is apparent that many more beneficial multiorgan aspects of vitamin K exist. The aim of the study was to review the properties of vitamin K and to show its potential therapeutic value. Materials and methods: Medline databases (PubMed) and other scientific sources were searched. Results: Vitamin K shows a multifaceted effect on the proper functioning of the human body: preventing coronary vessel calcification, maintains normal blood pressure, has neuroprotective effects, reduces the risk of myocardial infarction, slows the process of osteoclastogenesis, and influences the production of bone reabsorption factors. In addition, vitamin K supplementation has been shown to reduce the risk of hepatocellular carcinoma (HCC) by interfering with tumour cells cycle and inducing their apoptosis. The pro-apoptotic activity of menaquinone is not limited to HCC only, but also to other cancers such as glioblastoma multi-forme, breast cancer or bladder cancer, which reveals the importance of vitamin K in oncology. Possibly, introduction of vitamin K to the therapy may improve malignancy treatment outcomes. Conclusions: Vitamin K derivatives participate in many meta- bolic pathways of the human body. Their multifaceted activity may be used both in prevention of many diseases and in their potential treatments. However, further multicentre studies are necessary to understand better possible therapeutic properties of vitamin K derivatives. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of vitamin K deficiency after intramuscular vitamin K or no treatment in neonates with sepsis on prolonged (>7 days) antibiotic therapy. Study Design: Open label randomized controlled trial. Setting: Level 3 Neonatal Intensive Care Unit (NICU). Participants: Neonates with first episode of sepsis on antibiotics for ≥7 days were included. Neonates with clinical bleeding, vitamin K prior to start of antibiotic therapy (except the birth dose), cholestasis or prenatally diagnosed bleeding disorder were excluded. Intervention: Randomized to receive 1 mg vitamin K (n=41) or no vitamin K (n=39) on the 7th day of antibiotic therapy. Main outcome measure: Vitamin K deficiency defined as Protein Induced by Vitamin K Absence (PIVKA-II) >2 ng/mL after 7 ± 2 days of enrolment. Results: The prevalence of vitamin K deficiency was 100% (n=80) at enrolment and it remained 100% even after 7 ± 2 days of enrolment in both the groups. Conclusion: Neonates receiving prolonged antibiotics have universal biochemical vitamin K deficiency despite vitamin K administration on 7th day of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical value of serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) and alpha-fetoprotein (AFP), alone or in combination, in the diagnosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods A total of 450 patients with HBV infection, who underwent serological tests in the Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, from February 2016 to June 2017, were enrolled in our hospital, including 200 patients with HBV-related HCC (80 surgically treated cases), 143 patients with hepatitis B cirrhosis, 65 patients with severe chronic hepatitis B (CHB), and 42 CHB patients with liver failure. The serum levels of PIVKA-Ⅱ and AFP were compared between the four groups. An analysis of variance was used to compare normally distributed continuous data between multiple groups; the Kruskal-Wallis H test was used to compare non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. A binary stepwise logistic regression was used to obtain a new variable as a combination of PIVKA-Ⅱ and AFP. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUC) of AFP and PIVKA-Ⅱ, alone or in combination, in the diagnosis of HBV-related HCC, and the DeLong test was used for comparison of AUC between these variables. Results The HBV-related HCC patients had significantly higher PIVKA-Ⅱ and AFP levels than other groups (Z=-9.432, -6.369, -2.158, -13.202, -9.609, and -7.584, all P＜0.05). The PIVKA-Ⅱ levels of the patients with severe CHB and CHB patients with liver failure were significantly higher than that of the patients with hepatitis B cirrhosis (Z=-2.977 and -2.308, both P＜0.05). The HBV-related HCC patients showed significant reductions in AFP and PIVKA-Ⅱ levels within 5-7 days after surgical treatment (Z=-96.892 and -76.997, both P＜0.05). In the diagnosis of HBV-related HCC, PIVKA-Ⅱ had 84.0% sensitivity and 86.4% specificity, and AFP had 81.5% sensitivity and 50.4% specificity. The AUCs of AFP, PIVKA-Ⅱ, and a combination of AFP and PIVKA-Ⅱ in the diagnosis of HBV-related HCC were 0.757, 0.905, and 0.912, respectively; there were significant differences in AUC between PIVKA-Ⅱ and AFP (Z=6.048, P＜0.001) and between AFP and a combination of AFP and PIVKA-Ⅱ (Z=7.814, P＜0.001). A combination of AFP and PIVKA-Ⅱ had the highest diagnostic efficiency for HBV-related HCC. Conclusion Serum PIVKA-II has a better diagnostic value for HBV-related HCC than AFP, and a combination of the two can increase the detection rate of HCC and reduce the rate of misdiagnosis. [ABSTRACT FROM AUTHOR]

Introduction Pancreatic neuroendocrine tumors are rare. Treatment includes aggressive local management of the primary lesion and metastases, and systemic somatostatin. This is the first report of an isolated metachronous metastasis to the adrenal gland from a pancreatic neuroendocrine tumor that presented 90 months after the primary tumor. Presentation of case The patient presented as a 53yo man with a left upper quadrant mass and synchronous metastases to the spleen and liver (pancreatic neuroendocrine tumor T4N0M1, Stage IV), which were resected (CD56-, synaptophysin+, chromogranin+, Ki-67 < 1%). Over the next 90 months, he underwent five procedures to treat hepatic recurrences (2 liver resections and 3 percutaneous radiofrequency ablations). Serum PIVKA levels were elevated prior to treatment of four of six lesions and returned to baseline after therapy. He presents now, asymptomatic, with a right adrenal mass found on routine imaging and no other lesions. Serum PIVKA was elevated to 44 mg/dL. The adrenal gland was resected and shown to be a metastasis (CD56+, synaptophysin+, chromogranin+, Ki-67 15–20%). Discussion This patient’s clinical course reflects aggressive local therapy of the primary lesion and multiple metastatic lesions to three organs (liver, spleen, adrenal) over nearly eight years. The utility of serum PIVKA levels in patients with pancreatic neuroendocrine tumors is not previously reported and needs further investigation. Conclusion This patient has a pancreatic neuroendocrine tumor with metastases to the spleen, liver and adrenal gland and elevated PIVKA levels with recurrent disease. These unique clinical features add to the diversity of clinical presentation of these rare tumors. [ABSTRACT FROM AUTHOR]

Ob suši se Pivka pojavi med Prestrankom in Rakitnikom, pri Zagorju pa je podzemna kraška voda deset metrov pod dolinskim dnom presihajoče reke Pivke. Visoke vode se prelivajo na površje in napolnijo strugo reke Pivke, ki v takšnih razmerah teče površinsko od Zagorja do ponora v Postojnsko jamo. Ko se gladina podzemne vode dvigne, so poplavljene tudi plitve kraške kotanje – uvale in pojavi se več kot 15 presihajočih jezer. Ključne besede: kraško presihajoče jezero, uvala, Pivka, Slovenija. At dry season the Pivka river appears between Prestranek and Rakitnik while near Zagorje the underground karst waters are about ten meters below the valley bottom of periodical Pivka river. High waters pour over the surface and fill stream valley of the Pivka river, which runs continually from Zagorje to the ponor of Postojnska jama. When the level of the underground water increases, also shallow karst hollows – uvalas are fl ooded and changed into more than 15 periodical karst lakes.

The article discusses relief evolution in the catchment area of the highest situated permanent spring of the Pivka river – the Pivšce karst spring near the village Zagorje. The discussed landscape, which lies on the southernmost edge of the Upper Pivka valley, shows several geomorphological particularities, which are the result of different geomorphogenetic processes in the past. The basic characteristics of the present relief were shaped in the Pliocene when also the original valley of the Pivka river was formed. The region was more profoundly transformed by Pleistocene processes, which strongly altered the surface. Apart from karstic relief forms, there are several small dry stream channels on the land surface, which were carved by torrents. The two most distinctive relief features are the karst polje situated between the villages Koritnice, Bač and Knežak, which is covered with rubble and gravel-like clastic sediments, and the dry valley of the former Pivka river lying southwest from Koritnice.

Hepatic vitamin K-dependent proteins (e.g., Factors II, VII, IX and X) form part of the clotting cascade. Factor II (FII)/Prothrombin incorporates 10 Glu residues on the N-terminal region that are γ-carboxylated to Gla residues by the action of γ-glutamyl carboxylase to confer biological activity. Vitamin K is also required for the normal function of Matrix Gla Protein (MGP)-one of several non- clotting-related extra-hepatic vitamin K-dependent proteins. MGP is known to have protective action against vascular calcification-indeed it is a powerful tissue-bound inhibitory mechanism and can be found in blood vessel walls. The mature protein is also dependent on activation by γ-glutamyl carboxylase enzyme to convert Glu residues in its amino acid sequence to Gla. This reaction can only take place when the enzyme is activated in the presence of vitamin K. It is of great potential interest to investigate whether subtle deficiencies of vitamin K may, through its effect on the action of MGP, be a contributing factor to vascular calcification in CKD patients, in whom CV disease is greatly accelerated and in whom vascular calcification is not only common, but progresses aggressively, and is something for which as yet there is no clinically applicable remedy. [ABSTRACT FROM AUTHOR]

Background: As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD). Objectives: To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns. Methods: A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 μg/die of vitamin K (G I), 12 μg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life. Results: G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 ( p = 0.001) and from 2.3 to 3.5 ( p < 0.001). No significant changes were found in GI. PT showed no significant changes among groups. Conclusions: PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 μg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk. [ABSTRACT FROM AUTHOR]

Vitamins D and K are lipid-phase nutrients that are pleiotropic - endowed with versatile homeostatic capacities at the organ, tissue, and cellular levels. Their metabolic and physiologic roles overlap considerably, as evidenced in the bone and cardiovascular systems. Vitamin D3 (cholecalciferol, D3) is the prehormone for the vitamin D endocrine system. Vitamin D3 undergoes initial enzymatic conversion to 25-hydroxyvitamin D (25D, calcidiol), then to the seco-steroid hormone lalpha, 25-dihydroxyvitamin D (1,25D, calcitriol). Beyond its endocrine roles in calcium homeostasis, 1,25D likely has autocrine, paracrine, and intracrine effects. At least 17 tissues likely synthesize 1,25D, and 35 carry the vitamin D receptor (VDR). Vitamin D functional deficiency is widespread in human populations. Vitamin K, (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-4, menatetrenone). Menadione ("vitamin K3") has minimal K activity. Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically re-reduced. Warfarin inhibits this vitamin K reduction, necessitating K supplementation during anticoagulation therapy. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, facilitate bone mineralization, inhibit vessel wall calcification, support endothelial integrity, are involved in cell growth control and tissue renewal, and have numerous other effects. This review updates vitamin D and K skeletal and cardiovascular benefits and evidence for their synergy of action. [ABSTRACT FROM AUTHOR]

Copyright of Contributions to Contemporary History / Prispevki za Novejšo Zgodovino is the property of Prispevki za Novejso Zgodovino and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses relief evolution in the catchment area of the highest situated permanent spring of the Pivka river - the Pivšce karst spring near the village Zagorje. The discussed landscape, which lies on the southernmost edge of the Upper Pivka valley, shows several geomorphological particularities, which are the result of different geomorphogenetic processes in the past. The basic characteristics of the present relief were shaped in the Pliocene when also the original valley of the Pivka river was formed. The region was more profoundly transformed by Pleistocene processes, which strongly altered the surface. Apart from karstic relief forms, there are several small dry stream channels on the land surface, which were carved by torrents. The two most distinctive relief features are the karst polje situated between the villages Koritnice, Bač and Knežak, which is covered with rubble and gravel-like clastic sediments, and the dry valley of the former Pivka river lying southwest from Koritnice. [ABSTRACT FROM AUTHOR]

Prispevek obravnava razvoj površja v povirnem zaledju najvišje ležečega stalnega izvira reke Pivke, kraškega izvira Pivšce pri Zagorju. Obravnavana pokrajina na skrajnem južnem robu Zgornje Pivke izkazuje številne geomorfološke posebnosti, ki so rezultat različnih geomorfogenetskih procesov v preteklosti. Osnovne poteze današnjega površja so bile začrtane v času pliocena, ko se je tudi izoblikovala prvotna dolina Pivke. Pokrajino so izraziteje preoblikovali pleistocenski procesi, ki so površju dali poseben pečat. Poleg kraških reliefnih oblik, so v reliefu prisotne številne manjše suhe struge nekdanjih hudourniških tokov. V površju izstopata kraško polje med Koritnicami, Knežakom in Bačem, ki je nasuto z gruščnato-prodnatim drobirjem ter suha dolina nekdanje Pivke jugovzhodno od Koritnic. [ABSTRACT FROM AUTHOR]

Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants. [ABSTRACT FROM AUTHOR]

Copyright of Kronika is the property of Kronika, Casopis za Slovensko Krajevno Zgodovino and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Alpha-fetoprotein (AFP) has long been used as an effective biomarker for hepatocellular carcinoma (HCC) screening; however, not all HCC patients can be detected with an elevated AFP level, especially in early HCC patients. Protein Induced by vitamin K absence or antagonist-II (PIVKA-II) is another serum biomarker linked to HCC; however, sensitivity and specificity remain controversial and data in Chinese groups is even rarer., Objectives: To evaluate the performance of PIVKA-II alone and combined with AFP in HCC screening in Chinese population., Patients and Methods: This retrospective study enrolled 150 HCC patients in Southwest Hospital, of which 16 patients were excluded due to lack of basic information. A total of 347 patients with hepatitis B, 105 with non-HCC cancers and 53 healthy people were enrolled as controls. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively., Results: The sensitivity and specificity of PIVKA-II were 74.6% and 67.8% at a cutoff of 40 mAU/mL and 64.2% and 89.7% at a cutoff of 200 mAU/mL. The sensitivity and specificity of AFP were 76.7% and 65.0% at a cutoff of 20 ng/mL and 60.4% and 88.9% at a cutoff of 195.23 ng/mL. The combination of two markers had a sensitivity and specificity of 91.1% and 41.0%, respectively. The area under the receiving operating curve (AUROC) for PIVKA-II (0.756, 95% confidence interval, CI: 0.695 - 0.816) was less than the AUROC for AFP (0.823, 95% CI: 0.780 - 0.865), and in combination, the AUROC increased to 0.843 (95% CI: 0.801 - 0.885)., Conclusions: PIVKA-II was as efficient as AFP when used as a single marker for HCC screening and the combination of two biomarkers gave a better performance.

Background: A significant proportion of hemodialysis patients have functional, but modifiable, vitamin K deficiency., Objective: To determine the correlates of poor vitamin K status in hemodialysis patients., Design: Cross-sectional study., Setting: Hemodialysis units at Kingston General Hospital and its satellite centres, Ontario, Canada., Patients: Patients undergoing outpatient hemodialysis for end-stage kidney disease., Measurements: Serum concentrations of phylloquinone, undercarboxylated prothrombin, also known as protein induced by vitamin K absence or antagonism - factor II (PIVKA-II), and the percentage of undercarboxylated osteocalcin (%ucOC)., Methods: Vitamin K status was determined in fasting blood samples of hemodialysis patients. Bivariate relationships were examined using parametric and non-parametric statistics as appropriate. Multivariable linear regression models were applied to identify predictors of vitamin K status., Results: Among 44 HD patients, criteria for subclinical vitamin K deficiency were met in 13.6% (phylloquinone < 0.4 nmol/L), 51% (%ucOC > 20%) and 90.9% (PIVKA-II > 2.0 nmol/L) of subjects. Phylloquinone levels were positively associated with total cholesterol, triglyceride levels and non-smoking status. Higher %ucOC was associated with increased calcium-phosphate product. Increased PIVKA-II levels were observed with advancing age, reduced dialysis adequacy, lower HDL and a history of coronary artery disease. There were no associations found among the individual biomarkers of vitamin K status. In a multi-variable model, triglycerides were the only significant predictor of phylloquinone levels, while increasing phosphate and decreasing PTH were independent predictors of %ucOC. PIVKA-II levels increased by 0.54 nmol/L for every 10-year increase in age., Limitations: Observational study; small sample size., Conclusions: A significant proportion of HD patients met criteria for subclinical vitamin K deficiency. Of the biomarkers measured, PIVKA-II may be superior given its independence of renal function or dyslipidemia, both of which may confound the other vitamin K biomarkers. Studies in patients with ESKD linking biomarkers of vitamin K status to important patient outcomes, including cardiovascular disease, nutritional status and mortality, are required in order to determine the optimal biomarker for evaluating vitamin K status in this particular population.

Background: The prognosis in advanced hepatocellular carcinoma (HCC) with multiple intrahepatic metastases is extremely poor. Combination therapy with subcutaneous interferon (IFN) alfa and intraarterial 5-fluorouracil was reported to be effective against such advanced HCC. We describe results of debulking surgery followed by combination therapy with IFN alfa and 5-FU for massive HCC with multiple intrahepatic metastases., Methods: In 27 HCC patients with massive tumors and multiple intrahepatic metastases, we performed combination therapy with IFN alfa and 5-FU after maximal liver tumor resection., Results: Mean patient age was 63.3 years. Including intrahepatic metastases, tumors numbered 5 or more in 17 patients (63%). Portal or hepatic vein branches were invaded in 22 (81%). The mean maximum tumor diameter was 102 mm. Among 24 patients whose results were analyzed, an objective response by residual intrahepatic metastases was observed in 13 (54%; complete response in 12, and partial response in 1). Overall 1-, 3-, and 5-year survival was 73.2%, 38.7%, and 38.7%, respectively; 1-, 3-, and 5-year progression-free rates were 38.2%, 22.3%, and 22.3%., Conclusions: Debulking surgery followed by IFN alfa and 5-FU combination chemotherapy offers possibility of long-term survival despite massive HCC with multiple intrahepatic metastases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)