The aim of this study was to determine the prognostic value of systemic inflammatory indices as factors for postoperative complications and survival in patients with advanced stages of p16-negative ...head and neck squamous cell carcinoma undergoing free-flap reconstruction.
This was a retrospective cohort study. The primary predictor variables were inflammatory markers such as neutrophil, lymphocyte, monocyte, and platelet count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, lymphocyte-monocyte ratio, derived NLR, systemic immune-inflammatory index, and systemic inflammatory marker index (SIM). Multivariate regression analyses were used to measure the associations between systemic inflammatory indices and overall and disease-free survival as a primary outcome and occurrence of postoperative complications as a secondary outcome measure.
The sample was composed of 69 male (76.67%) and 21 female (23.33%) patients, with an average age of 61.15 ± 9.79 years. The median follow-up time was 24 months, and 73 of 91 (66.43%) patients were alive during the median follow-up.
Overall disease survival correlated with systemic immune-inflammation (P = .022, cutoff >1,005.3, sensitivity 67.1%, and specificity 70.6%) and SIM (P = .0001, cutoff >4.05, sensitivity 90.4%, and specificity 41.2%), preoperative platelets (P = .036, cutoff <194, sensitivity 28.8%, and specificity 94.1%), and postoperative lymphocytes (P = .012, cutoff <0.6, sensitivity 38%, and specificity 76.5%), whereas increased SIM (P = .042, cutoff >4.05, sensitivity 91.3%, and specificity 38.1%), NLR (P = .031, cutoff >13.2, sensitivity 56.9%, and specificity 60%), and preoperative platelets (P = .006, cutoff <244, sensitivity 52.3%, and specificity 76%) were associated with adverse disease-free survival. The cumulative postoperative complication rate was 34.5%, of which 13.3% accounted for major complications, whereas derived NLR (P = .013, degrees of freedom 1, χ2 test 6.161, cutoff >2.3) and postoperative lymphocytes (P = .009, DF 1, χ2 test 6.756, cutoff <1) correlated with occurrence of complications.
Inflammatory indices as measures of inflammation-related systemic dysfunction may be associated with adverse survival in patients with head and neck squamous cell carcinoma and occurrence of postoperative complications and with specific cutoff values.
Necrotizing enterocolitis (NEC) of infants is a devastating disease that is both difficult to treat and to effectively predict its development. Its occurrence and progression are associated with a ...plethora of possible causes. That is why, in recent years, many studies were made with the intent of finding efficient new ways of treatment and prevention. Some of those were designed to study and isolate specific factors found in maternal milk and others were more focused on testing synthetic molecules or natural remedies. The etiology of NEC and its epidemiology followed by a characterization of the pathology and pathogenesis, as well as symptomatology, clinical, radiological, and biochemical methods of detection. New possible treatment methods and techniques are briefly described: insulin-like growth factor, human milk oligosaccharides, epidermal growth factor family, transforming growth factor β, an enzyme – alkaline phosphatase, vitamin A, trefoil factor family, branch chain fatty acids, erythropoietin, oxygen, and ozone. Particular emphasis is given to the role of maternal milk as a source of many of biochemical factors in prevention and even treatment of NEC. Further investigations are needed to decrease the incidence and severity as well as to improve the chances of NEC patients.
All immunoglobulin G molecules carry N-glycans, which modulate their biological activity. Changes in N-glycosylation of IgG associate with various diseases and affect the activity of therapeutic ...antibodies and intravenous immunoglobulins. We have developed a novel 96-well protein G monolithic plate and used it to rapidly isolate IgG from plasma of 2298 individuals from three isolated human populations. N-glycans were released by PNGase F, labeled with 2-aminobenzamide and analyzed by hydrophilic interaction chromatography with fluorescence detection. The majority of the structural features of the IgG glycome were consistent with previous studies, but sialylation was somewhat higher than reported previously. Sialylation was particularly prominent in core fucosylated glycans containing two galactose residues and bisecting GlcNAc where median sialylation level was nearly 80%. Very high variability between individuals was observed, approximately three times higher than in the total plasma glycome. For example, neutral IgG glycans without core fucose varied between 1.3 and 19%, a difference that significantly affects the effector functions of natural antibodies, predisposing or protecting individuals from particular diseases. Heritability of IgG glycans was generally between 30 and 50%. The individual's age was associated with a significant decrease in galactose and increase of bisecting GlcNAc, whereas other functional elements of IgG glycosylation did not change much with age. Gender was not an important predictor for any IgG glycan. An important observation is that competition between glycosyltransferases, which occurs in vitro, did not appear to be relevant in vivo, indicating that the final glycan structures are not a simple result of competing enzymatic activities, but a carefully regulated outcome designed to meet the prevailing physiological needs.
Protein glycosylation affects nearly all molecular interactions at the cell surface and in the intercellular space. Many of the physiological variations which are part of homeostatic mechanisms ...influence glycosylation. However, a comprehensive overview of changes in glycosylation caused by aging and common lifestyle parameters is still lacking. After analyzing N-glycans in the plasma of 1914 individuals from the Croatian islands of Vis and Korčula, we performed a comprehensive analysis of the dependence of different glycosylation features (position of fucose, level of galactosylation, sialylation and branching) on aging, smoking, body fat and plasma lipid status. A number of statistically significant associations were observed. Glycosylation changes with aging were especially evident in females, mostly in association with the transition from pre-menopausal to post-menopausal age. Levels of core-fucosylated, non-galactosylated, digalactosylated and disialylated biantennary glycans were shown to be mainly age dependent, but the level of branching and higher levels of galactosylation were found to correlate with lipid status. For the majority of glycans which we analyzed, all examined parameters explained up to 5% of the variance. The only notable exception were non-galactosylated glycans where 20% of the variance was explained mostly by age and blood pressure. In general, only a small fraction of the variability in glycan levels observed in a population was explained by age and other measured parameters, indicating that even in the absence of a genetic template, glycan levels are mostly determined by genetic background and/or specific pathophysiological processes.
Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein ...function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
After performing hydrophilic interaction and weak anion exchange high-performance liquid chromatography to analyze N-glycans in the plasma of 1991 people, we identified several individuals that ...differed significantly from the "normal" profile of N-glycans. By performing consensus scoring of pairwise distances between vectors containing measured glycan values, we formed six groups of individuals with specific glyco-phenotypes. Some aberrations from the normal plasma protein patterns were found to be associated with clinical conditions (such as renal problems in people with increased monosialylated biantennary glycans, A2G2S1), while other substantial changes in N-glycan structure, such as the near complete absence of neutral glycans or antennary fucosylated tri- and tetraantennary glycans, were not associated with any observed adverse health outcomes. These results demonstrate the existence of specific altered glyco-phenotypes in some individuals and indicate that in some cases they might represent risk factors for the development of specific diseases.
Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the ...absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.
Purpose
For patients at high-risk of developing hepatocellular carcinoma (HCC), biannual ultrasound surveillance has long been recommended, in order to detect the tumor in the early, potentially ...curative stages. However, globally reported HCC surveillance rates vary greatly, ranging from as low as 1.7 to as high as 80%. Our aim was to assess the utilization of surveillance with biannual ultrasound in high-risk Croatian patients and to identify the factors that impact the implementation of the recommended protocol.
Methods
This retrospective study included 145 newly diagnosed HCC patients in the period from January 2010 to September 2015. We identified low-risk and high-risk patients. The latter were further subdivided into the regular biannual ultrasound surveillance group and the non-surveillance group. The groups were compared according to demographic characteristics and BCLC stage at the time of HCC diagnosis.
Results
Among 145 patients, 80 patients were classified as high-risk according to EASL criteria. During the relevant period, 28.7% underwent regular surveillance, while 71.25% did not. Younger patients were more likely to undergo surveillance (OR 0.935 CI 0.874–0.999;
p
= 0.05). The patients who underwent regular surveillance had a higher chance of being diagnosed at a curative stage (BCLC 0 or A) (OR 3.701 CI 1.279–10.710;
p
< 0.05).Gender was not a predictor of participation in the regular surveillance protocol. Among the high-risk patients who did not undergo regular surveillance, 56.1% were not aware of the chronic liver disease prior to the HCC diagnosis.
Conclusion
HCC surveillance is still underutilized in high-risk Croatian patients despite its obvious benefits possibly due to the untimely diagnosis of the chronic liver disease.
Introduction:
We present a case of an extensive endometriosis involving left paracolpium and left parametrium, rectovaginal septum, urinary bladder, left interiliac region between artery and vein, ...left ureter and rectum, presenting as dysmenorrhoea, alternating bouts of diarrhea and constipation and hydronephrosis.
Methods:
Laparoscopic surgery made by a multidisciplinary team consist of gynecologic, abdominal surgeon and urologist.
Results:
Successfully managed deep infiltrated endometriosis.
Conclusion:
The aim of this report is to demonstrate benefit of one-stage, minimally invasive radical surgical procedure performed in a tertiary referral center. To the best of our knowledge, this report presents an extremely complex case because we successfully managed deep infiltrating endometriosis in three different organ systems at the same time, using minimally invasive nerve-sparing technique. A case with the same constellation has not been published yet since reported cases of extrapelvic endometriosis chiefly address one organ system involvement.
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