Safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth.

The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. This is the first observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V)) in pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy. Women were offered a course of LACTIN-V at 14 weeks gestation for five consecutive days followed by weekly administration for six weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks' gestation and at delivery for assessment of adverse events, compliance and tolerability. Participants completed a questionnaire to gauge experience and acceptability. In total, 73 women were recruited, of whom eight withdrew, leaving a final cohort size of 61. Self-reported compliance to the course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was judged to be unrelated to LACTIN-V. No serious adverse events occurred. One mild adverse event led to study withdrawal. Thirty-one women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) found the schedule of use difficult to remember. The rate of PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2,190 women at similar background PTB risk. With satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and accepted in pregnancy, with high tolerability. Further studies are needed to assess colonisation of Lactobacillus crispatus CTV-05 and clinical efficacy.

The effect of different ß-blockers on vascular graft nitric oxide levels: comparison of nebivolol versus metoprolol.

OBJECTIVES: The aim of this study was to investigate the effects of the vasodilating ß-blocker nebivolol and the cardioselective ß-blocker metoprolol on nitric oxide (NO) levels at vascular graft endothelium and vasa vasorum compared to controls in patients undergoing coronary artery bypass graft surgery. METHODS: This was a prospective study. Fifty-five patients were divided into three groups: nebivolol group (group N, n = 23), metoprolol group (group M, n = 16), and control group (group A, n = 16). Group N received nebivolol 5 mg once daily, and group M received metoprolol 50 mg once daily for 15 days in the preoperative period. Control patients did not use ß-blocker therapy. Tissue samples of both left internal mammary artery (LIMA) and saphenous vein grafts were investigated for NO activity using immunohistochemical methods. RESULTS: Demographic characteristics and risk factors were similar between groups. We observed the highest NO activity in group N in both endothelial and vasa vasorum samples of LIMA and saphenous veins. NO activity of metoprolol group was similar to controls. CONCLUSIONS: According to our results, we think that nebivolol may be safer and preferable in order to diminish graft spasm in patients undergoing coronary artery bypass graft surgery due to the NO-mediated vasodilating effect.

Is there a potential role for serum cardiac troponin I as a marker for myocardial dysfunction in pediatric patients receiving anthracycline-based therapy? A pilot study.

Serum cardiac troponin I (cTnI) levels have been reported to have high specificity and sensitivity to acute myocardial infarction and coronary ischemic syndromes in adult patients. Our goal was to evaluate the usefulness of serum cTnI in the early diagnosis of cardiac injury from anthracyclines, and to compare these values with echocardiographic findings of cardiac dysfunction. In this prospective study, children being treated on several Children's Cancer Group protocols underwent measurement of shortening fraction (SF), ejection fraction (EF), and serum cTnI levels prior to anthracycline therapy. Sequential serum cTnI levels were then measured along with regularly scheduled echocardiograms with progressively increasing doses of anthracyclines. Fifteen children with median age of 5.75 years (range, 15 months to 15.5 years) at diagnosis were evaluated. Anthracycline doses ranged from 11.72 mg/kg (in patients < 3 years of age) to 375 mg/m2. All but one patient had normal cTnI levels. His level measured at 1.7 ng/ml after 315 mg/m2, but was normal on follow-up testing. Initial SF ranged from 32 to 48%, and EF from 60 to 80%. On follow-up, SF and EF ranged from 30 to 41% and 55 to 70%, respectively. Both SF and EF were significantly lower (p < 0.001) as compared to the initial values. Despite this, all patients remained clinically asymptomatic from the cardiac standpoint. We did not observe elevations of serum cTnI levels in clinically asymptomatic children who received anthracycline therapy up to doses of 375 mg/m2. Does this mean that cardiac injury has not occurred? The possibility of assay sensitivity and the timing of serum sampling and echocardiograms may be important. In addition, larger sample size or longer follow-up may be helpful to determine if higher doses or symptomatic patients potentially have elevations in cTnI levels.

Unilateral retinoblastoma with acquired monosomy 7 and secondary acute myelomonocytic leukemia.

Patients with a nongenetic form of retinoblastoma are not particularly at high risk of developing second malignant neoplasms. We report here a case of treatment-related leukemia (secondary leukemia) with acquired monosomy 7, in a child with unilateral retinoblastoma.

Monozygotic twins with congenital acute lymphoblastic leukemia (ALL) and t(4;11)(q21;q23).

Congenital acute lymphoblastic leukemia (CALL) is a rare disorder and is frequently associated with t(4;11)(q21;q23). To our knowledge this is the first case report of monozygous twins with CALL and t(4;11)(q21;q23).

Successful treatment of disseminated central nervous system malignant rhabdoid tumor.

PURPOSE: Malignant rhabdoid tumor (MRT) of the central nervous system (CNS) is pathologically identical to MRT of the kidney. CNS MRTs have the clinicopathological behavior of a high-grade intracranial sarcoma, and the children have a very poor prognosis. We report on three cases of primary CNS MRT with a review and summary of the pediatric literature with respect to demographic features and multidisciplinary management. PATIENTS AND METHODS: The 18 cases reviewed had a male to female ratio of 1.0 and an extremely young median age of 32 months. Our three cases of CNS MRT were treated with surgery, chemotherapy, radiotherapy, and triple intrathecal (TIT) chemotherapy similar to the Intergroup Rhabdomyosarcoma Study III guidelines for parameningeal primary tumors with intracranial extension. RESULTS: The three patients described in this report are surviving with no evidence of disease at 5 years, 2 years, and 9 months from diagnosis. Before these three cases, only four of 16 reported patients were known to have survived. One unique case in our report involved disease in the cerebral cortex, sinuses, and orbit with metastases to the subarachnoid space. This metastatic MRT responded to treatment with TIT, multiagent chemotherapy and cranial-spinal radiation after partial resection of only the cortical portion of the MRT. CONCLUSIONS: Disseminated CNS MRTs can be treated using multidisciplinary management with an approach similar to that used to treat rhabdomyosarcoma.