Usage of DNA Fingerprinting Technology to Check Sample Error and Contamination in Molecular Laboratories.

Sample identification error is a severe medical error in clinical molecular diagnostic laboratories, which can lead to reporting the wrong results for the patient involved. Sample contamination can also lead to incorrect test reports. Avoiding sample identification error and sample contamination could be life-saving. Sample switch and sample contamination could happen on laboratory bench works, especially when pipetting into multi-well plates. It is difficult to realize such errors during laboratory bench work. Laboratory staff may not be aware of such an error when it happens. DNA fingerprinting technology can be used to determine sample identity and subsequently identify sample switch and sample contamination in the laboratory. Our laboratory has explored the usage of this technology in our quality control process and successfully established that DNA fingerprinting can be used to monitor sample switch and sample contamination in next-generation sequencing and BCR/ABL1 real-time PCR bench work.

Micronutrient screening, monitoring, and supplementation in pregnancy after bariatric surgery.

We present the case of a woman with a history of biliopancreatic diversion and duodenal switch procedure who developed severe malnourishment requiring total parenteral nutrition during three pregnancies. The widespread use of bariatric surgery, particularly among those of reproductive age, has led to an increase in the number of women who become pregnant following bariatric surgery. There is a paucity of evidence to guide nutritional recommendations for women during pregnancy post bariatric surgery. We review this literature and summarize key published evidence and provide comprehensive recommendations concerning the common challenges in the management of nutrition status during pregnancy. The focus is on the impact of malabsorptive bariatric surgeries on pregnancy outcomes, nutrient deficiencies, recommendations for micro- and macronutrient monitoring and supplementation, and altered glucose metabolism and implications for diabetes screening. Optimizing pregnancy outcomes for individuals following bariatric surgery requires multidisciplinary team management including obstetrical providers, obstetric medicine specialists, and dietitians.

Performance characteristics of the first Food and Drug Administration (FDA)-cleared digital droplet PCR (ddPCR) assay for BCR::ABL1 monitoring in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy that accounts for 15-20% of all cases of leukemia. CML is caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR::ABL1. The amount of BCR::ABL1 transcript RNA is a marker of disease progression and the effectiveness of tyrosine kinase inhibitor (TKI) treatment. This study determined the analytical and clinical performance of a droplet digital PCR based assay (QXDx BCR-ABL %IS Kit; Bio-Rad) for BCR::ABL1 quantification. The test has a limit of detection of MR4.7 (0.002%) and a linear range of MR0.3-4.7 (50-0.002%IS). Reproducibility of results across multiple sites, days, instruments, and users was evaluated using panels made from BCR::ABL1 positive patient samples. Clinical performance of the assay was evaluated on patient samples and compared to an existing FDA-cleared test. The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The assay demonstrated excellent clinical correlation with the comparator test using a Deming regression with a Pearson R of 0.99, slope of 1.037 and intercept of 0.1084. This data establishes that the QXDx™ BCR-ABL %IS Kit is an accurate, precise, and sensitive system for the diagnosis and monitoring of CML.

Canadian Stroke Best Practice Consensus Statement: Acute Stroke Management during pregnancy.

The Canadian Stroke Best Practice Consensus Statement Acute Stroke Management during Pregnancy is the second of a two-part series devoted to stroke in pregnancy. The first part focused on the unique aspects of secondary stroke prevention in a woman with a prior history of stroke who is, or is planning to become, pregnant. This document focuses on the management of a woman who experiences an acute stroke during pregnancy. This consensus statement was developed in recognition of the need for a specifically tailored approach to the management of this group of patients in the absence of any broad-based, stroke-specific guidelines or consensus statements, which do not exist currently. The foundation for the development of this document was the concept that maternal health is vital for fetal well-being; therefore, management decisions should be based first on the confluence of two clinical considerations: (a) decisions that would be made if the patient wasn't pregnant and (b) decisions that would be made if the patient hadn't had a stroke, then nuanced as needed. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include initial emergency management, diagnostic imaging, acute stroke treatment, the management of hemorrhagic stroke, anesthetic management, post stroke management for women with a stroke in pregnancy, intrapartum considerations, and postpartum management. These statements are appropriate for healthcare professionals across all disciplines and system planners to ensure pregnant women who experience a stroke have timely access to both expert neurological and obstetric care.

The Approach to Peripartum Management of Anticoagulation: A Multidisciplinary Survey.

OBJECTIVE: This study sought to determine whether there is practice variation in the treatment and prevention of acute venous thromboembolism (VTE) in pregnant patients, potentially to prioritize future studies. BACKGROUND: The risk of VTE during pregnancy is five-fold that of the non-pregnant state. Guidance is often lacking for the treatment and prophylaxis of VTE because there are few RCTs. METHODS: The study used a cross-sectional study design using a self-administered electronic questionnaire consisting of 11 case scenarios that were sent to hematologists, maternal-fetal medicine specialists, obstetricians and gynaecologists, and internal medicine specialists across Canada. RESULTS: A total of 254 participants responded to the survey and 193 (76%) completed the survey, 158 of whom indicated that they were involved in the decision to anticoagulate these patients. Anticoagulation of patients with superficial venous thrombosis during pregnancy, monitoring of low-molecular-weight heparin antepartum, and discontinuation of this agent at the time of delivery were the scenarios associated with the largest variability of responses. For the management of acute VTE antepartum, most participants favoured a once-daily regimen, although internists more so than obstetrics and gynaecology physicians (94.7% vs. 73.7%). Cesarean section was not perceived to be a procedure with a marked increased risk of thrombosis to warrant thromboprophylaxis because most physicians elected not to offer thromboprophylaxis for this scenario. However, obesity and severe preeclampsia with Cesarean section led to the predominant use of thromboprophylaxis, at 80.0% and 68.4%, respectively. CONCLUSION: Prospective studies addressing peripartum management where significant discrepancies exist are warranted.

Pregnancy outcomes following single and repeat liver transplantation: An international 2-center cohort.

Due to advances in obstetric and transplant medicine, women with a history of liver transplantation can have successful pregnancies. However, data on pregnancy outcomes is still limited, especially for women who have had a repeat liver transplant following graft rejection. This retrospective study compares pregnancy outcomes in women with single and repeat liver transplants managed at 2 tertiary hospitals in Toronto, Canada and Leuven, Belgium. We identified 41 pregnancies in 28 transplanted women, 6 of whom conceived following a second liver transplant after the first was rejected. Mean maternal age at delivery was 30 ± 7 years, and transplant-to-pregnancy interval was 8.5 ± 5.1 years. All women had normal liver function upon conception. Immunosuppressants included tacrolimus ± azathioprine (n = 26), cyclosporine (n = 4), and prednisone with immunosuppressants (n = 11). There were no maternal deaths. Maternal complications included hypertensive disorders of pregnancy (n = 10), deterioration in renal function (n = 6), gestational diabetes (n = 4), graft deterioration (n = 2), and anemia requiring blood transfusion (n = 1). Fetal/neonatal adverse outcomes included 2 miscarriages, 3 stillbirths, 1 neonatal death, 5 small-for-gestational-age infants, and 1 minor congenital anomaly. Mean gestational age at delivery was 36.7 ± 4.2 weeks. There were 14 (38.9%) preterm births. Outcomes in women with a second transplant were similar to those with a single transplant, except for a higher incidence of hypertensive disorders. In conclusion, with appropriate multidisciplinary care, stable graft function at pregnancy onset, and adherence to immunosuppressive regimens, women with single and repeat liver transplants have low rates of graft complications but remain at increased risk for pregnancy complications. Immunosuppressants and high-dose glucocorticoids can be safely used for maintenance of graft function and management of graft deterioration in pregnancy. Liver Transplantation 24 769-778 2018 AASLD.

Thromboembolism following cesarean section: a retrospective study.

OBJECTIVES: As thromboembolism (TE) continues to be one of the principal causes of death in obstetrical patients and as the postpartum period is associated with the highest risk for TE, we sought to determine the risk factors associated with TE following cesarean section (CS). METHODS: A retrospective analysis of patients who had CS at a large tertiary referral center was conducted. Patients were identified through hospital medical records and were contacted approximately 1 year following their CS. Medical records and a questionnaire were used to identify features that were potentially associated with TE. Univariate analysis was used to determine the risk associated with these characteristics. RESULTS: A total of 2206 patients had a CS, of which 1377 (62%) participated. Of the respondents, 137 patients received heparin (94% received a prophylactic dose, 6% received a therapeutic dose) and the remainder, 1233 patients, did not receive heparin. Seven patients (0.5%) developed a TE and 86% developed a TE within 7 days of CS. The odds ratio (OR) for TE for women with hypertension prior to pregnancy compared to patients who did not receive anticoagulation was 21.28 [95% confidence interval (CI) 4.64-90.13] and for patients who had varicose veins with superficial thrombophlebitis when compared to patients who had received heparin postpartum was 21.01 (95% CI 1.55-288.24). DISCUSSION: Hypertension and the presence of varicose veins were associated with TE following CS. Larger cohort analyses are required to confirm these associations so that risk scores incorporating these characteristics may accurately predict the occurrence of TE.

Canadian stroke best practice consensus statement: Secondary stroke prevention during pregnancy.

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.

Anemia in Pregnancy: A Pragmatic Approach.

IMPORTANCE: Anemia is common in pregnancy, ranging from 5.4% in developed countries to more than 80% in developing countries. Anemia in pregnancy has been associated with prematurity, low birth weight, and adverse pregnancy outcomes. OBJECTIVE: This review uses clinical vignettes to illustrate the clinical presentations, approach to diagnosis, maternal and fetal implications, and treatment for the common etiologies of anemia in pregnancy. EVIDENCE ACQUISITION: Literature review. RESULTS: Normal physiological changes in pregnancy result in alterations of hematological parameters particularly in a reduction of hemoglobin (Hb) concentration. Consequently, the Hb used to define anemia in pregnancy is lower than in nonpregnant patients. As there is an increased requirement of iron in pregnancy, it is not unexpected that iron deficiency remains the most common cause of anemia and warrants a preemptive approach to prevent a further reduction in Hb. The syndromes associated with microangiopathic hemolytic anemia may pose a diagnostic challenge, as there are several potential etiologies that may be difficult to differentiate, and microangiopathic hemolytic anemia can be associated with significant maternal and fetal morbidity andmortality. Anemia secondary to sickle cell disease and autoimmune hemolytic anemiamerit special attention because there are risks secondary to red blood cell transfusion and risks to withholding transfusion. CONCLUSIONS: Anemia in pregnancy is potentially associated with maternal and fetal adverse outcomes. Providing evidence-based care is essential to achieving the best pregnancy outcomes.

Long-term Risk of a Seizure Disorder After Eclampsia.

OBJECTIVE: To evaluate the incidence rate and relative risk of a seizure disorder after eclampsia. METHODS: We evaluated 1,565,733 births in a retrospective data linkage cohort study in Ontario, Canada, from April 1, 2002, to March 31, 2014. We included females aged 15-50 years and excluded patients with epilepsy, conditions predisposing to seizure, and those who died within 30 days of the delivery discharge date. The exposure was defined as a hypertensive disorder of pregnancy, namely 1) eclampsia, 2) preeclampsia, or 3) gestational hypertension. The referent was an unaffected pregnancy. The primary outcome was the risk of seizure disorder starting 31 days after a hospital birth discharge. Risk was expressed as an incidence rate and a hazard ratio (HR) with 95% CI. The predefined study hypothesis was that women with eclampsia would have an increased risk of future seizure disorder. RESULTS: There were 1,615 (0.10%) pregnancies exclusively affected by eclampsia, 17,264 (1.1%) with preeclampsia, 60,863 (3.9%) with gestational hypertension, and 1,485,991 (94.9%) unaffected. A future seizure disorder was significantly more likely after a pregnancy with eclampsia (4.58/10,000 person-years) than a pregnancy without a hypertensive disorder of pregnancy (0.72/10,000 person-years; crude HR 6.09, 95% CI 2.73-13.60). The adjusted HR was minimally attenuated from 6.09 to 5.42 (95% CI 2.42-12.12) after multivariable adjustment for confounders at the index birth as well as adjusting for traumatic brain injury, stroke, cerebral tumor, aneurysm or hemorrhage, and multiple sclerosis. The risk of seizure disorder was doubled in pregnancies affected by preeclampsia (adjusted HR 1.96, 95% CI 1.21-3.17), but not by gestational hypertension (adjusted HR 1.01, 95% CI 0.71-1.43). CONCLUSION: Women with eclampsia should be reassured that, although the relative risk of a seizure disorder is higher than unaffected women, the absolute risk is extremely low (approximately one seizure/2,200 person-years).

Pheochromocytoma in a Pregnant Woman With Prior Traumatic Aortic Injury.

BACKGROUND: Pheochromocytoma, a catecholamine-producing tumor seldom encountered in pregnancy, is often heralded by nonspecific symptoms and undue mortality with delayed diagnosis. The presence of an aortic pseudoaneurysm poses a management challenge given the risk of aortic rupture amplified by hypertensive events. CASE: A 30-year-old woman, gravida 3 para 1, presented at 23 6/7 weeks of gestation with vomiting, chest pain, and severe hypertension. Investigation revealed adrenal pheochromocytoma and pseudoaneurysm at the site of a previous aortic injury. Prazosin and phenoxybenzamine achieved α-blockade with subsequent addition of labetalol for ß-blockade. Concerns for aortic dissection led to endovascular aortic repair at 30 2/7 weeks of gestation. A female neonate was delivered by urgent cesarean delivery for persistent postprocedure fetal bradycardia. An adrenalectomy followed with near-immediate symptom resolution. Mother and neonate remain well. CONCLUSION: The case underscores the necessity of a meticulous approach to hypertension management and the pivotal role of diligent multidisciplinary collaboration to achieve a safe outcome.

The Pulmonary Edema Preeclampsia Evaluation (PEPE) Study.

BACKGROUND: Women with preeclampsia may develop pulmonary edema, but the reasons for this are largely unknown. METHODS: We performed a case-control study of women with preeclampsia at two major obstetrical centres in Toronto, ON, between 2005 and 2012. Cases (n = 28) were women with preeclampsia who had pulmonary edema on a chest CT or plain X-ray during the index delivery hospitalization. Control subjects (n = 64) were those with preeclampsia but no diagnosis of pulmonary edema or heart failure in the index hospitalization for delivery. Study variables were abstracted from each woman's paper chart and electronic medical record. Multivariable logistic regression with backward elimination was used to select a final set of significant predictors. RESULTS: Approximately one half of the cases of pulmonary edema occurred antepartum. Each 10 × 10(9)/L reduction in platelet count (OR 1.32; 95% CI 1.06 to 1.65) or 10 µmol/ L increase in peak serum uric acid concentration (OR 1.19; 95% CI 1.06 to 1.34) was significantly associated with pulmonary edema, as was receiving magnesium sulphate (OR 10.42; 95% CI 1.39 to 78.22). Multiparity (OR 0.03; 95% CI 0.004 to 0.29) and each 500 mL increase in the volume of intravenous crystalloids received (OR 0.60; 95% CI 0.37 to 0.98) were associated with a lower risk of pulmonary edema. CONCLUSION: We identified several preliminary risk factors for pulmonary edema in women with preeclampsia. Additional work is needed to better understand the role of these and other factors predicting the development of pulmonary edema in women with preeclampsia.

Contexte : Les femmes qui présentent une prééclampsie peuvent en venir à connaître un œdème pulmonaire; toutefois, les raisons pouvant expliquer cette situation demeurent largement inconnues. Méthodes : Nous avons mené, entre 2005 et 2012, une étude cas-témoins auprès de femmes présentant une prééclampsie au sein de deux centres majeurs offrant des services d'obstétrique à Toronto (Ont.). Les « cas ¼ (n = 28) étaient représentés par les femmes présentant une prééclampsie chez qui la présence d'un œdème pulmonaire avait été révélée par tomodensitographie thoracique ou par radiographie régulière au cours de l'hospitalisation dans le cadre de la grossesse probante. Les « témoins ¼ (n = 64) étaient représentés par les femmes présentant une prééclampsie qui n'avaient toutefois pas reçu un diagnostic d'œdème pulmonaire ou d'insuffisance cardiaque au cours de l'hospitalisation dans le cadre de la grossesse probante. Les variables à l'étude ont été résumées à partir du dossier papier et du dossier médical électronique de chacune des femmes. Une régression logistique multivariée (s'accompagnant d'une élimination descendante) a été utilisée aux fins de la sélection d'un ensemble final de facteurs prédictifs significatifs. Résultats : Près de la moitié des cas d'œdème pulmonaire se sont manifestés pendant la période antepartum. Tant chacune des baisses de 10 × 109/l de la numération plaquettaire (RC, 1,32; IC à 95 %, 1,06 - 1,65) que chacune des hausses de 10 µmol/l du pic de concentration sérique en acide urique (RC, 1,19; IC à 95 %, 1,06 - 1,34) ont été associées de façon significative à l'œdème pulmonaire, tout comme le fait de recevoir du sulfate de magnésium (RC, 10,42; IC à 95 %, 1,39 - 78,22). La multiparité (RC, 0,03; IC à 95 %, 0,004 - 0,29) et chaque hausse de 500 ml du volume de cristalloïdes administrés par intraveineuse (RC, 0,60; IC à 95 %, 0,37 - 0,98) ont été associées à un risque moindre d'œdème pulmonaire. Conclusion : Nous avons identifié plusieurs facteurs de risque préliminaires en ce qui concerne l'œdème pulmonaire chez les femmes présentant une prééclampsie. D'autres études s'avèrent requises pour nous permettre de mieux comprendre le rôle de ces facteurs et celui d'autres facteurs pour ce qui est de la prévision de l'apparition d'un œdème pulmonaire chez les femmes qui présentent une prééclampsie.