Outcomes of pregnancy in women with tetralogy of Fallot

OBJECTIVES: We sought to determine pregnancy outcomes in patients with tetralogy of Fallot (TOF). BACKGROUND: Pregnancy outcomes in patients with TOF are incompletely defined. METHODS: Clinical, hemodynamic, and obstetric data were reviewed for women with TOF and prior pregnancy. RESULTS: Of 72 respondents, 43 (mean age, 26 years) had 112 pregnancies (range, 1 to 5); 82 pregnancies were successful. Eight women had unrepaired TOF at the time of their 20 successful pregnancies. At first assessment (age > or =18 years), six patients had pulmonary hypertension, three had moderate or severe right ventricular (RV) systolic dysfunction, and 13 had severe RV dilation due to pulmonic regurgitation. Sixteen patients had 30 miscarriages (27%) and one term stillbirth. Mean overall birth weight was 3.2 kg (range, 2.1 to 4.2 kg). Unrepaired TOF (p = 0.05) and morphologic pulmonary artery abnormality (p = 0.03) were independently predictive of infant birth weight. Six patients had cardiovascular complications during pregnancy: supraventricular tachycardia in two, heart failure in two, pulmonary embolism in a patient with pulmonary hypertension, and progressive RV dilation in a patient with severe pulmonic regurgitation. Five infants (6%) had congenital anomalies. CONCLUSIONS: Patients with TOF have an increased risk of fetal loss, and their offspring are more likely to have congenital anomalies than offspring in the general population. Adverse maternal events, although rare, may be associated with left ventricular dysfunction, severe pulmonary hypertension, and severe pulmonic regurgitation with RV dysfunction.     

Donor cell expansion is delayed following nonablative in utero transplantation to treat murine mucopolysaccharidosis type VII

To block development of progressive childhood diseases, in utero transplantation (IUTx) requires immediate and significant donor peripheral blood (PB) cell amplification. To date, negligible and nontherapeutic donor PB cell levels have been observed postnatally, except in patients with immunodeficiency diseases. Donor cell fate in utero still is not clear. Ease of identifying and quantifying beta-glucuronidase (GUSB)-expressing donor cells in GUSB-null mucopolysaccharidosis type VII (MPSVII) mouse recipients allowed us to evaluate temporal donor cell engraftment and amplification post-IUTx. Like humans, MPSVII mice are unable to catabolize lysosomal glycosaminoglycans and progressively develop severe storage disease unless they are treated early in life.IUTx recipients were nonablated MPSVII fetuses and genetically stem cell-deficient, and hence myeloablated, W(41)/W(41) MPSVII fetuses. Donor GUSB+ cells were identified and counted in histochemical tissue sections. Quantitative results were confirmed by flow cytometry, enzyme analysis, and histopathology.Whereas GUSB+ cells engraft in most tissues in utero, significant amplification does not occur until the first postnatal week in the nonablated MPSVII hosts. In contrast, genetically myeloablated MPSVII recipients display widely distributed donor cell replacement accompanied by extensive amplification in utero. In both models, storage is alleviated in adult tissues with significant donor cell repopulation.To become therapeutic, IUTx must overcome the limitations of donor cell expansion in the highly competitive fetal environment. Fortunately, nonablative mechanisms to amplify cells in utero are coming on line.     

Swa: a Subdivision

For some time, anomalous serological reactions have been observed when the same anti-Swa sera are tested against red cells from different individuals reported as Sw(a+). A comparative collaborative study using the same collection of Sw(a+) cells and anti-Swa sera was undertaken by 4 reference laboratories, and it was found that Swa represents a heterogeneous group of antigens that can be subdivided into two categories. Both categories, Sw(a+) 700:41 and Sw(a+) 700:-41, were shown to be inherited.     

Circulating markers of oxidative stress and liver fibrosis in Sudanese subjects at risk of schistosomiasis and hepatitis

Epidemiological studies in the developing world are frequently biased by the simultaneous presence of several infectious pathogens. In the present study, we examined the usefulness of circulating markers of oxidative stress and liver fibrosis to investigate the distinct forms of chronic liver inflammations associated with schistosomiasis and viral hepatitis, respectively. The study was performed in a Sudanese population exposed to Schistosoma. Circulating hyaluronic acid (HA) was used as a marker of liver fibrosis; the severity of schistosomiasis was determined by ultrasonic examination; viral hepatitis infection was ascertained by circulating anti-hepatitis antibodies. Serum markers were examined also in Sudanese subjects not exposed to Schistosoma infection and in French control subjects. We found a drastic decrease of lycopene levels in the subjects exposed to schistosomiasis in comparison with non-exposed Sudanese and French control subjects. Retinol, alpha-tocopherol and five carotenoids were unchanged. Lycopene depletion was unlikely to be due to variations of nutritional origin, since the lycopene/beta-carotene ratio was five-fold lower in the population at risk of schistosomiasis than in the other groups. We found that high HA serum levels were associated with severe periportal fibrosis but not with viral infection. Conversely, levels of the oxidized lipid malondialdehyde (MDA) were associated with viral infection but not with the severity of schistosomiasis, even though the two infections had additive effects. We concluded that serum markers are valuable tools for investigating the complex effects of co-existing factors of chronic liver inflammation.     

MR Imaging of the Perihepatic Space

The perihepatic space is frequently involved in a spectrum of diseases, including intrahepatic lesions extending to the liver capsule and disease conditions involving adjacent organs extending to the perihepatic space or spreading thanks to the communication from intraperitoneal or extraperitoneal sites through the hepatic ligaments. Lesions resulting from the dissemination of peritoneal processes may also affect the perihepatic space. Here we discuss how to assess the perihepatic origin of a lesion and describe the magnetic resonance imaging (MRI) features of normal structures and fluids that may be abnormally located in the perihepatic space. We then review and illustrate the MRI findings present in cases of perihepatic infectious, tumor-related, and miscellaneous conditions. Finally, we highlight the value of MRI over computed tomography.     

Effect of “Speak Up” educational tools to engage patients in advance care planning in outpatient healthcare settings: A prospective before-after study

BackgroundTools for advance care planning (ACP) are advocated to help ensure patient values guide healthcare decisions. Evaluation of the effect of tools introduced to patients in clinical settings is needed.ObjectiveTo evaluate the effect of the Canadian Speak Up Campaign tools on engagement in advance care planning (ACP), with patients attending outpatient clinics.Patient involvement: Patients were not involved in the problem definition or solution selection in this study but members of the public were involved in development of tools. The measurement of impacts involved patients.MethodsThis was a prospective pre-post study in 15 primary care and two outpatient cancer clinics. The outcome was scores on an Advance Care Planning Engagement Survey measuring Behavior Change Process on 5-point scales and Actions (0?21-point scale) administered before and six weeks after using a tool, with reminders at two or four weeks.Results177 of 220 patients (81%) completed the study (mean 68 years of age, 16% had cancer). Mean Behavior Change Process scores were 2.9 at baseline and 3.5 at follow-up (mean change 0.6, 95% confidence interval 0.5 to 0.7; large effect size of 0.8). Mean Action Measure score was 3.7 at baseline and 4.8 at follow-up (mean change 1.1, 95% confidence interval 0.6–1.5; small effect size of 0.2).Practical valuePublicly available ACP tools may have utility in clinical settings to initiate ACP among patients. More time and motivation may be required to stimulate changes in patient behaviors related to ACP.     

Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys

A blood-stage vaccine based on Plasmodium falciparum merozoite surface protein 3 (MSP3) was tested for efficacy in a primate model. Aotus nancymai monkeys were vaccinated with yeast-expressed MSP3 before a lethal challenge with Plasmodium falciparum parasites. Five of 7 control monkeys had acute infections and required treatment to control parasitemia. Only 1 of 7 monkeys vaccinated with MSP3 required this treatment. The efficacy of the MSP3 vaccination appeared to be comparable to that of MSP1(42), a leading asexual vaccine candidate, in response to which 2 monkeys experienced acute infections. In the MSP3-vaccinated group, protection correlated with prechallenge titers of antibody to MSP3. In the MSP1 and control groups, protection correlated with antibody to MSP3 raised by challenge infection.     

Is shared decision-making vanishing at the end-of-life? A descriptive and qualitative study of advanced cancer patients’ involvement in specific therapies decision-making

Background

Little is known about what is at stake at a subjective level for the oncologists and the advanced cancer patients when they face the question whether to continue, limit or stop specific therapies. We studied (1) the frequency of such questioning, and (2) subjective determinants of the decision-making process from the physicians’ and the patients’ perspectives.

Methods

(1) All hospitalized patients were screened during 1 week in oncology and/or hematology units of five institutions. We included those with advanced cancer for whom a questioning about the pursuit, the limitation or the withholding of specific therapies (QST) was raised. (2) Qualitative design was based on in-depth interviews.

Results

In conventional units, 12.8 % of cancer patients (26 out of 202) were concerned by a QST during the study period. Interviews were conducted with all physicians and 21 advanced cancer patients. The timing of this questioning occurred most frequently as physicians estimated life expectancy between 15 days and 3 months. Faced with the most frequent dilemma (uncertain risk-benefit balance), physicians showed different ways of involving patients. The first two were called the “no choice” models: 1) trying to resolve the dilemma via a technical answer or a “wait-and-see” posture, instead of involving the patients in the questioning and the thinking; and 2), giving a “last minute” choice to the patients, leaving to them the responsibility of the decision. In a third model, they engaged early in shared reflections and dialogue about uncertainties and limits with patients, proxies and care teams. These schematic trends influenced patients’ attitudes towards uncertainty and limits, as they were influenced by these ones. Individual and systemic barriers to a shared questioning were pointed out by physicians and patients.

Conclusions

This study indicate to what extent these difficult decisions are related to physicians’ and patients’ respective and mutually influenced abilities to deal with and share about uncertainties and limits, throughout the disease trajectory. These insights may help physicians, patients and policy makers to enrich their understanding of underestimated and sensitive key issues of the decision-making process.