Neonatal outcomes in subgroups of women with preterm prelabor rupture of membranes before 34 weeks

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on short-term neonatal outcome in women with preterm prelabor rupture of membranes before 34 weeks of gestation.

Methods: A prospective observational cohort study including 122 pregnant women with PPROM between 24+0 and 34+0. MIAC was defined as a positive PCR result for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive PCR result for the 16S rRNA gene in the amniotic fluid. HCA was defined according to the Salafia classification. Maternal and short-term neonatal outcomes were evaluated according to the presence or absence of MIAC and/or HCA.

Results: The presence of both MIAC and HCA was observed in 36% (45/122) of women, HCA alone in 34% (41/122) and MIAC in 5% (6/122). A significantly higher incidence of early onset sepsis was observed in newborns born from women with both MIAC and HCA [33% (15/45)] compared with women with HCA alone [12% (5/41)] or MIAC alone [0% (0/6)] or women without MIAC or HCA detected [0% (0/30); p?=?0.001].

Conclusions: The presence of both MIAC and HCA increases the risk of early onset sepsis in pregnancies complicated by preterm prelabor rupture of membranes before 34 weeks of gestation.     

Pulsation of the fetal splenic vein - a potential ultrasound marker of histological chorioamnionitis and funisitis in women with preterm prelabor rupture of membranes

The fetal spleen is involved in the response to intrauterine infection and inflammation. The flow pattern of its vein is not pulsatile in normal conditions. The aim of the study was to determine whether the presence of histological chorioamnionitis and funisitis is associated with a continuous or pulsatile flow pattern in the fetal splenic vein. We performed a prospective study including 79 women with preterm prelabor rupture of membranes. We found a relation between pulsation in the splenic vein and histological chorioamnionitis (likelihood ratio 13.2), as well as funisitis (likelihood ratio 5.7). Ultrasound evaluation of the splenic vein could be a non-invasive tool for the prediction of these inflammatory complications.     

Chromosome study of 85 patients with myelodysplastic syndrome

We studied bone marrow chromosomes in 85 consecutive patients with myelodysplastic syndrome (MDS). Fifty-seven (67%) had a clone with an abnormal karyotype at diagnosis. Eight had secondary MDS, all with abnormal karyotypes. The frequency of abnormal karyotypes in the primary MDS was 64.9%. During subsequent follow-up, five patients acquired chromosome abnormalities; thus, at the end of the study, 72.0% of patients had an abnormal karyotype. The most frequent chromosome abnormalities were 5q-, +8, -7, -5, and -22. Forty patients (i.e., 70% of those with an abnormal karyotype and 47% of the whole group) had one of the karyotype abnormalities associated with secondary MDS or acute nonlymphocytic leukemia; in other words, 5q- or -5, or -7. Of all patients, 21.1% progressed into ANLL. Unfavorable prognostic factors associated with the risk of evolution into ANLL and with shorter overall survival were the presence of greater than 5% of bone marrow blasts, major chromosome abnormalities, and monosomy 7.     

Cervical fluid calreticulin and cathepsin-G in pregnancies complicated by preterm prelabor rupture of membranes

Objective: The study aimed to determine the cervical calreticulin and cathepsin-G concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI).

Methods: Eighty women with singleton pregnancies complicated by PPROM were included in this study. Cervical and amniotic fluids were obtained at the time of admission, and concentrations of calreticulin and cathepsin-G in cervical fluid were determined using ELISA. The MIAC was defined as a positive PCR analysis for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and/or by positivity for the 16S rRNA gene. IAI was defined as amniotic fluid bedside IL-6 concentrations ≥745?pg/mL

Result: Neither women with MIAC nor with IAI had different cervical fluid concentrations of calreticulin (with MIAC: median 18.9?pg/mL vs. without MIAC: median 14.7?pg/mL, p?=?0.28; with IAI: median 14.3?pg/mL vs. without IAI: median 15.6?pg/mL, p?=?0.57;) or of cathepsin-G (with MIAC: median 30.7?pg/mL vs. without MIAC: median 24.7?pg/mL, p?=?0.28; with IAI: median 27.3?pg/mL vs. without IAI: median 25.1?pg/mL, p?=?0.80) than women without those complications. No associations between amniotic fluid IL-6 concentrations, gestational age at sampling, and cervical fluid calreticulin and cathepsin-G concentrations were found.

Conclusions: Cervical fluid calreticulin and cathepsin-G concentrations did not reflect the presence of MIAC or IAI in women with PPROM.     

Periodontal disease and intra-amniotic complications in women with preterm prelabor rupture of membranes

Objective: Periodontal disease is frequently suggested as a possible causal factor for preterm delivery. The link between periodontal disease and preterm delivery is a possible translocation of periopathogenic bacteria to the placenta and amniotic fluid as well as a systemic response to this chronic inflammatory disease. However, there is a lack of information on whether there is an association between clinical periodontal status in women with preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). Therefore, the main aim of this study was to evaluate the incidence and severity of periodontal disease in women with PPROM. The secondary aim was to characterize an association between periodontal status and the presence of intra-amniotic PPROM complications (MIAC and/or IAI).

Materials and methods: Seventy-eight women with PPROM at gestational ages between 24?+?0 and 36?+?6 weeks were included in this study. The samples of amniotic fluid were obtained at admission via transabdominal amniocentesis, and amniotic fluid interleukin (IL)-6 concentrations were determined using a point-of-care test. All women had a full-mouth recording to determine the periodontal and oral hygiene status. Probing pocket depth and clinical attachment loss were measured at four sites on each fully erupted tooth.

Results: In total, 45% (35/78) of women with PPROM had periodontal disease. Mild, moderate, and severe periodontal disease was present in 19% (15/78), 19% (15/78), and 6% (5/78) of women, respectively. The presence of MIAC and IAI was found in 28% (22/78) and 26% (20/78) of women, respectively. Periopathogenic bacteria (2?×?Streptococcus intermedius and 1?×?Fusobacterium nucleatum) was found in the amniotic fluid of 4% (3/78) of women. There were no differences in periodontal status between women with MIAC and/or IAI and women without these intra-amniotic complications.

Conclusions: The presence of MIAC and IAI was not related to the periodontal status of women with PPROM.     

Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Methods: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6?>?11?pg/mL.

Result: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1?pg/mL versus without MIAC: median 5.8; p?<?0.0001; with IAI: median 32.9?pg/mL, versus without IAI: median 5.8; p?<?0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4?pg/mL) and rates of FIRS (78% and 67%).

Conclusions: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC.     

Amniotic fluid clusterin in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate clusterin concentrations in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of the microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred thirty-six women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid clusterin concentrations were assessed by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥745?pg/mL. Microbial-associated IAI was characterized as the presence of both MIAC and IAI.

Result: Women with MIAC, IAI and microbial-associated IAI had lower amniotic fluid clusterin concentrations than women without these complications (with MIAC: median 1314?ng/mL versus without MIAC: median 1633?ng/mL, p?=?0.003; with IAI: median 1281?ng/mL versus without IAI: median 1575?ng/mL, p?=?0.04; with microbial associated-IAI: median 1220?ng/mL versus without microbial-associated IAI: median 1575?pg/mL; p?=?0.008). A week negative correlation between amniotic fluid clusterin concentrations and gestational age at sampling was revealed (rho=??0.30; p?=?0.0005).

Conclusions: The presence of MIAC, IAI and microbial-associated IAI was characterized by lower amniotic fluid clusterin concentrations in pregnancies complicated by PPROM.     

Dendritic Cell-based Immunotherapy for the Treatment of Hematological Malignancies

Dendritic cells (DCs) are professional antigen-presenting cells and are frequently used in current immunotherapy protocols. The administration of DCs loaded with tumor-associated proteins or peptides results in the induction of immune responses against different types of malignant cells. Methods for large-scale generation of DCs in a sufficient quality and quantity have permitted their use in clinical experiments. DC-based vaccines have already shown promise in follicular non-Hodgkin's lymphoma, and to some extent, in other hematological malignancies. Several strategies have been developed to boost their potency as a new and relatively non-toxic treatment modality. Our review focuses on clinical trials using DCs in the treatment of hematologic malignancies and on recent studies of the immunophenotype, development, and maturation of DCs may have an important impact on designing DC-based antitumor vaccines.