Wpływ zapalenia tarczycy Hashimoto, stężenia TSH oraz dodatniego wyniku obecności przeciwciał przeciwtarczycowych na występowanie zróżnicowanego raka tarczycy

  Introduction: The relationship between Hashimoto’s thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. Material and methods: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. Results: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716–1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403–3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. Conclusions: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT. (Endokrynol Pol 2016; 67 (1): 48–53)    Wstęp: Związek pomiędzy zapaleniem tarczycy Hashimoto (HT) i rakiem tarczycy (TC) jest uważany za kontrowersyjny. Podczas gdy większość badań nad operacjami dokumentuje wysoką częstotliwość występowania guzów wśród pacjentów z HT, badania cytologiczne tego nie potwierdzają. Rola autoprzeciwciał w częstotliwości występowania guzów nie jest do końca jasna. Materiał i metody: Wśród pacjentów, u których stwierdzono guzki tarczycy przeprowadzono jednoośrodkowe, retrospektywne badanie obserwacyjne poprzez aspiracyjną cytologię cienkoigłową (FNAC) pod kontrolą USG oraz operacyjnie, jeśli takie było wskazanie. Stężenia tyreotropiny (TSH) oraz przeciwciał przeciwtarczycowych zmierzono podczas przeprowadzania FNAC. Wyniki: Z 4947 pacjentów, u 599 (12,1%) zdiagnozowano HT. Zły/podejrzany wynik cytologii stwierdzono u 14,2% pacjentów z HT oraz u 15,2% innych pacjentów. Iloraz szans (OR) dla guza przy HT wynosił 0,921 (0,716–1,183, p = 0,51). Z 1603 pacjentów, których poddano operacji, zróżnicowanego raka tarczycy wykryto u 29,5% pacjentów z HT i u 15,2% innych pacjentów (OR 2,33; 95% CI; 1,403–3,854, p < 0,001). Niski poziom TSH (< 0,4 mIU/l) obniża wskaźnik występowania guza w całej populacji pacjentów, zarówno gdy bierze się pod uwagę wyniki cytologiczne, jak i operacyjne. Nie zostało to potwierdzone w podgrupie, u której zdiagnozowano HT. Nie zaobserwowano związku pomiędzy autoprzeciwciałami przeciw peroksydazie tarczycowej (ATP) lub tyreoglobulinie (ATG) i wskaźnikiem występowania guzów. Wnioski: Nie zaobserwowano cytologicznego związku pomiędzy HT i rakiem tarczycy; dodatni związek w seriach histologicznych spowodowany był stronniczością selekcji. Niskie stężenie TSH obniżył ryzyko TC u pacjentów z wolem guzkowym, lecz nie zostało to udowodnione u pacjentów z HT. (Endokrynol Pol 2016; 67 (1): 48–53)

Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Background To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). Methodology/Principal Finding A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty-six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. Conclusion A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected

Maternal Serum C-Reactive Protein in Women with Preterm Prelabor Rupture of Membranes

Objective This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation. Methods This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification. Results Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection. Conclusion CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages

Intra-amniotic inflammatory response in subgroups of women with preterm prelabor rupture of the membranes.

BACKGROUND: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the magnitude of intra-amniotic inflammatory response in preterm prelabor rupture of membranes (PPROM). METHODOLOGY/PRINCIPAL FINDING: A prospective cohort study was performed in 107 women with PPROM between 23.0 and 36.6 weeks of gestational age. Twenty-six proteins were assayed by multiple immunoassay in amniotic fluid. The policy for PPROM in Czech Republic is active, and 90% of the women were delivered within 96 hours of membrane rupture. Histopathological placental findings were evaluated based on the Salafia classification. Data were analyzed in four subgroups of population according to the presence of MIAC and/or HCA. Results were stratified by gestational age at PPROM (< or ≥ 34.0 weeks). The rates of MIAC and HCA were 44% and 57%, respectively. Regardless of gestational age at PPROM, intra-amniotic inflammatory response was higher when MIAC and HCA were both present. There were no differences in the intra-amniotic inflammatory response between women with MIAC or HCA alone and women without infection. CONCLUSION: A higher intra-amniotic inflammatory response was identified when both HCA and MIAC were detected

Oligohydramnios in women with preterm prelabor rupture of membranes and adverse pregnancy and neonatal outcomes.

OBJECTIVE: To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). METHODS: Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. RESULTS: In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122-748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8-146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1-27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = -0.34; p = 0.003). CONCLUSION: The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications

Umbilical cord blood IL-6 as predictor of early-onset neonatal sepsis in women with preterm prelabour rupture of membranes.

OBJECTIVE: To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM). DESIGN: Prospective cohort study. SETTING: Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM. POPULATION: 176 women with PPROM between 23+0-36+6 weeks of gestation. METHODS: Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics. MAIN OUTCOME MEASURES: Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM. RESULTS: The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9-734.8) vs 5.2 (0.1-801-4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p = 0.004). CONCLUSION: Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not

Prediction model for the presence of microbial invasion of the amniotic cavity and histological chorioamnionitis in PPROM below/above 32 weeks of gestation using extreme CRP values.

<p>Prediction model for the presence of microbial invasion of the amniotic cavity and histological chorioamnionitis in PPROM below/above 32 weeks of gestation using extreme CRP values.</p

Microorganisms identified in the amniotic fluid.

<p>Microorganisms identified in the amniotic fluid.</p

Cervical human papillomavirus infection in women with preterm prelabor rupture of membranes.

OBJECTIVE:To evaluate the association between cervical human papillomavirus (HPV) infection at the time of admission and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI) in women with preterm prelabor rupture of membranes (PPROM) and to determine the association between cervical HPV infection and short-term neonatal morbidity. METHODS:One hundred women with singleton pregnancies complicated by PPROM between the gestational ages of 24+0 and 36+6 weeks were included in the study. The presence of HPV DNA was evaluated in scraped cervical cells using polymerase chain reaction (PCR). Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS:The rate of cervical HPV infection in women with PPROM was 24%. The rates of MIAC and IAI were not different between women with cervical HPV infection and those without cervical HPV infection [MIAC: with HPV: 21% (5/24) vs. without HPV: 22% (17/76), p = 1.00; IAI: with HPV: 21% (5/24) vs. without HPV: 18% (14/76), p = 0.77]. There were no differences in the selected aspects of short-term neonatal morbidity between women with and without cervical HPV infection. CONCLUSIONS:In women with PPROM, the presence of cervical HPV infection at the time of admission is not related to a higher risk of intra-amniotic infection-related and inflammatory complications or worse short-term neonatal outcomes

Amniotic fluid cathelicidin in PPROM pregnancies: from proteomic discovery to assessing its potential in inflammatory complications diagnosis.

BACKGROUND: Preterm prelabor rupture of membranes (PPROM) complicated by microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA) significantly impacts perinatal morbidity. Unfortunately, no well-established tool for identifying PPROM patients threatened by these disorders is available. METHODOLOGY/PRINCIPAL FINDINGS: We performed an unbiased exploratory analysis of amniotic fluid proteome changes due to MIAC and HCA. From among the top five proteins that showed the most profound and significant change, we sought to confirm results concerning cathelicidin (P49913, CAMP_HUMAN), since an ELISA kit was readily available for this protein. In our exploratory proteomic study, cathelicidin showed a ∼6-fold higher concentration in PPROM patients with confirmed MIAC and HCA. We verified significantly higher levels of cathelicidin in exploratory samples (women without both MIAC and HCA: median 1.4 ng/ml; women with both conditions confirmed: median 3.6 ng/ml; p = 0.0003). A prospective replication cohort was used for independent validation and for assessment of cathelicidin potential to stratify women with MIAC leading to HCA from women in whom at least one of these conditions was ruled out. We confirmed the association of higher amniotic fluid cathelicidin levels with MIAC leading to HCA (the presence of both MIAC and HCA: median 3.1 ng/ml; other women: median 1.4 ng/ml; p<0.0001). A cathelicidin concentration of 4.0 ng/ml was found to be the best cut-off point for identifying PPROM women with both MIAC and HCA. When tested on the validation cohort, a sensitivity of 48%, a specificity of 90%, a likelihood ratio of 5.0, and an area under receiver-operating characteristic curve of 71% were achieved for identification of women with MIAC leading to HCA. CONCLUSIONS: Our multi-stage study suggests cathelicidin as a candidate marker that should be considered for a panel of amniotic fluid proteins permitting identification of PPROM women with MIAC leading to HCA