Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns.

Introduction: Ficolin-2 is a serum pattern recognition molecule, involved in complement activation via the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum with complications related to premature birth. Methods: 546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method. FCN2 genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method. Findings: Cord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis [OR=2.05, 95% CI (1.24-3.37), p=0.005]. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of FCN2 gene polymorphisms localised to promoter and 3'untranslated regions: for patients born <33 GA: 1471 ng/ml vs. 2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml vs. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml vs. 1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p<0.001). Interestingly, in the neonates born at GA <33, ficolin-2 concentration permitted differentiation of those with/without RDS [AUC=0.712, 95% CI (0.612-0.817), p<0.001] and effective separation of babies with mild RDS from those with moderate/severe form of the disease [AUC=0.807, 95% CI (0.644-0.97), p=0.0002]. Conclusion: Low cord serum ficolin-2 concentration (especially in neonates born at GA <33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care.

Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates.

Single nucleotide polymorphisms (SNPs) localised to the promoter region of the FCN2 gene are known to influence the concentration of ficolin-2 in human serum and therefore potentially have clinical associations. We investigated the relationships between SNPs at positions −986 (A > G), −602 (G > A), −64 (A > C) and −4 (A > G) and clinical complications in 501 preterms. Major alleles at positions −986 and −64 and A/A homozygosity for both polymorphisms were less frequent among babies with very low birthweight (VLBW, ≤1500 g) compared with the reference group (OR = 0.24, p = 0.0029; and OR = 0.49, p = 0.024, respectively for A/A genotypes). A lower frequency of G/G homozygosity at position −4 was associated with gestational age <33 weeks and VLBW (OR = 0.38, p = 0.047; and OR = 0.07, p = 0.0034, respectively). The AGAG haplotype was protective for VLBW (OR = 0.6, p = 0.0369), whilst the GGCA haplotype had the opposite effect (OR = 2.95, p = 0.0249). The latter association was independent of gestational age. The AGAG/GGAA diplotype favoured both shorter gestational age and VLBW (OR = 1.82, p = 0.0234 and OR = 1.95, p = 0.0434, respectively). In contrast, AGAG homozygosity was protective for lower body mass (OR = 0.09, p = 0.0155). Our data demonstrate that some FCN2 variants associated with relatively low ficolin-2 increase the risk of VLBW and suggest that ficolin-2 is an important factor for fetal development/intrauterine growth.

Polymorphisms of the FCN2 Gene 3'UTR Region and Their Clinical Associations in Preterm Newborns.

Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to investigate the association of the FCN2 3'-untranslated region (3'UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3'UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3'UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).

Statins and Colorectal Cancer - A Systematic Review.

OBJECTIVES: Statins act by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase and are an important drug class in the treatment of lipid disorders. They lower cholesterol levels and modulate cardiovascular disease risk in both primary and secondary prevention. In addition, some studies have shown that statins may have an effect on colorectal cancer development and treatment. Our objective is to summarize published studies on the effect of statins on colorectal carcinogenesis. METHODS: A systematic review of the PubMed and Cochrane databases was performed to identify studies published between April 2010 and April 2018 that investigated the association between statin use and colorectal cancer incidence, mortality, and treatment. RESULTS: Overall, 126 articles were identified with our search strategy. Based on the eligibility criteria, 69 studies were excluded from the review process. In vitro and animal studies have shown a potential chemopreventive effect of statins and their efficacy in adjuvant therapy of colorectal cancer. The anticarcinogenic effect on cancer risk in human studies was heterogeneous. Some studies reported better overall and cancer specific survival rates in patients using statins before and during colorectal cancer treatment. Statins also show a potential role in chemoprevention of colorectal cancer in patients with inflammatory bowel disease. CONCLUSIONS: Accumulating evidence suggests that statins may have a role in colorectal cancer prevention and treatment. Further studies are necessary to define the associations between individual statin characteristics, their doses and colorectal cancer.

Metformin and Colorectal Cancer - A Systematic Review.

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. The development of preventive strategies in CRC has been the subject of much research. Multiple studies have shown an association between diabetes and CRC. In addition to its glucose-lowering properties, metformin might have an additional role in the prevention and treatment of CRC. OUR OBJECTIVE: was to summarize findings on role of metformin in colorectal cancer. METHODS: We conducted a systematic review of the PubMed and Cochrane databases from January 2005 to December 2017 in search for studies on the association between metformin and CRC. RESULTS: Of the total of 189 studies identified by the search, we excluded 123 studies and reviewed the remaining 66 studies on cell lines, animals, patients with diabetes, and healthy subjects. In vitro and animal studies have shown a protective effect of metformin use on the incidence of CRC and amplification of the therapeutic effects of CRC chemotherapy. Studies on patients with type 2 diabetes treated with metformin analyzed data on total of 146 496 patients. The results of those studies on the role of metformin in CRC suggest risk reduction and potential applications within therapeutic regimens, although some of those are conflicting. CONCLUSION: Further studies are warranted to define the role of metformin in both prevention and treatment of CRC.

Multiple multiparity is a negative prognostic factor for endometrial cancer in Poland.

BACKGROUND: Nulliparity is one of the most important reproductive risk factors for endometrial cancer. It is still discussed whether multiparity implies a more favorable course of the disease and higher overall survival rates. The aim of the study was to analyze the effect of parity on the overall survival of endometrial cancer patients in Poland. MATERIAL AND METHOD: A retrospective analysis of parity on survival rates was performed in 810 women treated surgically for endometrial cancer in a single referential center of gynecological oncology. RESULTS: Higher parity was shown to be associated with significantly lower survival rates (p=0.03). Parity turned out to be an independent prognostic factor of survival (HR 1.9). Multiple multiparous women were older at the time of surgery, more often presented with deep myometrial infiltration and with involvement of the cervical stroma and had higher clinical stages of the cancer (only according to FIGO 1988 classification). The group of multiple multiparous women was characterized by significantly lower recurrence rates. Multiple multiparous women significantly more often presented with lower educational level, more often were diagnosed with comorbidities and a history of other malignancies, while breast cancer and colon cancer were of lesser evidence in multiple multiparous endometrial cancer patients. CONCLUSION: Multiparity turns out to be an unfavorable prognostic factor of survival in Polish women. Unfavorable prognosis in endometrial cancer patients in this group is associated with interactions between risk factors and negative prognostic factors, i.e. the conditions of tumor growth, rather than with the nulliparity itself.

Nutrition and pregnancy after bariatric surgery.

Obesity is an escalating problem in all age groups and it is observed to be more common in females than males. About 25% of women meet the criteria of obesity and one-third of them are in the reproductive age. Because morbid obesity requiring surgical treatment is observed with increasing frequency, surgeons and gynecologists are undergoing new challenges. It is not only a matter of women's health and their quality of life but also proper development of the fetus, which should be a concern during bariatric treatment. Therefore complex perinatal care has to be provided for morbid obesity patients. The paper reviews pregnancy and fertility issues in bariatric surgery patients.