Workload Measurement in Subspecialty Placental Pathology in Canada.

BACKGROUND: Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind. METHODS: In 2016, a Pan-Canadian Pediatric-Perinatal Pathology Workload Committee (PCPPPWC) was organized to adapt the L4E System to assess Pediatric-Perinatal Pathology workload. Four working groups were formed. The Placental Pathology Working Group was tasked to develop a scheme for fair valuation of placental specimens signed out by subspecialists in the context of the L4E System. Previous experience, informal time and motion studies, a survey of Canadian Pediatric-Perinatal Pathologists, and interviews of Pathologists' Assistants (PA) informed the development of such scheme. RESULTS: A workload measurement scheme with average L4E workload values for examination and reporting of singleton and multiple gestation placentas was proposed. The proposal was approved by the Canadian Association of Pathologist - Association canadienne des pathologistes Workload and Human Resources Committee for adoption into the L4E System. CONCLUSION: The development of a workload measurement model for placental specimens provides an average and fair valuation of these specimen types, enabling its use for resource planning and workload distribution.

Reproducibility and validity of a food frequency questionnaire in assessing dietary intakes of low-income Caucasian postpartum women living in Sheffield, United Kingdom.

The aim of this study was to examine the reproducibility and validity of a semi-quantitative food frequency questionnaire (FFQ) for assessing dietary intakes of low-income, Caucasian, English-speaking, postpartum women living in Sheffield, United Kingdom. Data was obtained from a cross-sectional sample of the 'Healthy Start' study; a population-based survey of mothers and infants. Participants completed two FFQs at 4 and 8 weeks postpartum. Measures from 24-hour dietary recalls (24HDRs) were collected at 4, 6, 8 and 12 weeks postpartum. In the reproducibility study, crude Pearson's correlation coefficients ranged from 0.40 (riboflavin) to 0.73 (thiamine), mean value 0.54. In the validation study, crude Pearson correlation coefficients between the FFQ and the measures from the 24HDRs ranged from 0.10 (B12) to 0.55 (manganese), mean value 0.34. Energy-adjustments and corrections for attenuation had no significant effect on the strength of the correlation both observed in the reproducibility and validity study. On average, 68% of the participants were classified correctly, and 3% were misclassified into the extreme opposite quintile of the distribution. The authors conclude that the questionnaire performed well for the majority of nutrients examined and that is a valid tool for ranking individuals according to nutrient distribution.

Parental views on tissue banking in pediatric oncology patients.

PURPOSE: Research using banked tissue is key to advancing risk-stratification and treatment of children with cancer. Knowledge of parental attitudes to ethical issues arising in tissue banking is very limited but essential in obtaining respectful consent. METHODS: One hundred parents of consecutively diagnosed children with cancer were offered a validated 34-item questionnaire. RESULTS: Respondents (n = 54) included 10 of 16 parents of deceased children. The majority (89%; n = 48) would agree to have tissue sent anywhere in the world but prefer pediatric aims (69%). Most (98%; n = 53) would permit genetic research, if it might improve the child's health, and 76% (n = 41) would permit it, even if no impact was anticipated. A minority (41%) would not allow painful, strictly research procedures, while 15% would regardless of the child's dissent. Just over half (54%; n = 29) wish to renew consent if stored tissue is used for another purpose. Most (98%) believe their child should confirm consent by the age of majority, but only 71% believe the mature child should be able to withdraw consent. A minority (n = 40; 74%) claim few or no rights to research profits; 83% believe these should be used to fund childhood cancer research. CONCLUSIONS: Parents are very supportive of tissue research, including genetic research. A majority of parents would prefer restricting research to pediatric conditions, and to be informed of results, even if of uncertain significance. These findings may assist Institutional Review Boards in assessing parentally perceived risks of research, and researchers in providing consent elements that support parents and adolescents in making fully informed choices.

Are the benefits of the 'Healthy Start' food support scheme sustained at three months postpartum? Results from the Sheffield 'before and after' study.

Early results examining nutritional behaviour of Caucasian, English-speaking, postpartum women living in Sheffield, who were beneficiaries or eligible for the Welfare Food Scheme (WFS) or the Healthy Start (HS) scheme, suggested significant between-groups differences. The aim of this study was to examine whether differences observed at 4 weeks postpartum were sustained over time. Eighty-six WFS and 64 HS participants were recruited at baseline and, thereafter, 53 WFS and 33 HS participants at week 8, and 47 WFS and 39 HS participants at week 12. Dietary intakes were assessed by an interviewer-administered, semi-quantified food frequency questionnaire. At 4 weeks, HS women had higher energy intakes compared to WFS women, (9.7 MJ and 8.1 MJ, respectively). Differences were also sustained at 8 weeks, (8.8 MJ and 7.2 MJ) and 12 weeks (9.4 MJ and 7.6 MJ) for the HS and WFS participants, respectively. Within-groups, energy and most of nutrient intakes did not change appreciably over time. Consumption of fruit and vegetables at baseline, were significantly higher (P = 0.023) for participants under the HS scheme (3.4 portions) compared to WFS participants (2.7 portions). Differences were sustained over time as HS women reported consuming 4.1 and 3.7 portions/day respectively at 8 and 12 weeks, as opposed to 2.8 and 2.7 portions/day reported by WFS women. The study findings provided evidence of the potential effectiveness of the HS scheme in a population subgroup at risk of dietary deficiencies. Early findings could provide a useful snapshot of the diet of such mobile population and should be further exploited.

Effect of the introduction of 'Healthy Start' on dietary behaviour during and after pregnancy: early results from the 'before and after' Sheffield study.

The aim of the study was to examine the effect of the introduction of a new food-support benefit 'Healthy Start' (HS) on dietary intakes and eating patterns of low-income, Caucasian, pregnant and postpartum women living in Sheffield (UK). A before-and-after study comparing nutritional behaviour of participants, who were beneficiaries or eligible for the Welfare Food Scheme (WFS) (phase 1) or HS (phase 2), was conducted. Dietary intakes and eating patterns were assessed using a validated semi-quantified FFQ. In phase 1, 176 WFS subjects (ninety pregnant and eighty-six postpartum) were recruited and in phase 2, there were 160 HS subjects (ninety-six pregnant and sixty-four postpartum). The results suggested that pregnant and postpartum HS women significantly increased their daily intakes of energy, Fe, Ca, folate and vitamin C compared with the WFS women. Observed differences remained significant after controlling for potential confounding effects of known factors, i.e. education and age. HS women were more likely to meet the recommended nutrient intakes for Fe, folate, Ca and vitamin C. HS women ate significantly more mean portions of fruit and vegetables per d (P = 0.004 and P = 0.023) respectively. None of the HS recipients was receiving HS vitamin supplements. The present study showed that pregnant and postpartum HS women increased their food consumption, and a higher proportion of them than the earlier WFS scheme met the recommended intakes for Ca, folate, Fe and vitamin C.

Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma.

We describe 2 cases of malignant melanotic epithelioid renal neoplasms bearing TFE3 gene fusions. Both neoplasms occurred in children (an 11-y-old boy and a 12-y-old girl), and presented with disseminated metastatic disease including mediastinal and mesenteric adenopathy. Both neoplasms featured sheets of epithelioid cells with clear to finely granular eosinophilic cytoplasm set in a branching capillary vasculature. The neoplastic cells contained variable amounts of finely brown pigment confirmed to be melanin by histochemical stains. By immunohistochemistry, the neoplastic cells labeled for melanocytic markers HMB45 and Melan A, but not for S100 protein, MiTF, or any epithelial marker (cytokeratins, epithelial membrane antigen), renal tubular marker (CD10, PAX8, PAX2, RCC Marker) or muscle marker (actin, desmin). Both neoplasms demonstrated nuclear labeling for TFE3 protein by immunohistochemistry, and the presence of TFE3 gene fusions was confirmed by TFE3 fluorescence in situ hybridization analysis. These distinctive neoplasms combine morphologic features of perivascular epithelioid cell neoplasms (PEComas), Xp11 translocation carcinoma, and melanoma, though the phenotype most closely approaches PEComa. These neoplasms represent the first documented examples in which TFE3 gene fusions coexist with melanin production, and their identification raises the possibility that TFE3 gene fusions may underlie an aggressive subset of lesions currently classified as PEComa in young patients.

Carboxypeptidase A5 identifies a novel mast cell lineage in the zebrafish providing new insight into mast cell fate determination.

Mast cells (MCs) play critical roles in allergy and inflammation, yet their development remains controversial due to limitations posed by traditional animal models. The zebrafish provides a highly efficient system for studying vertebrate hematopoiesis. We have identified zebrafish MCs in the gill and intestine, which resemble their mammalian counterparts both structurally and functionally. Carboxypeptidase A5 (cpa5), a MC-specific enzyme, is expressed in zebrafish blood cells beginning at 24 hours post fertilization (hpf). At 28 hpf, colocalization is observed with pu.1, mpo, l-plastin, and lysozyme C, but not fms or cepbalpha, identifying these early MCs as a distinct myeloid population arising from a common granulocyte/monocyte progenitor. Morpholino "knock-down" studies demonstrate that transcription factors gata-2 and pu.1, but not gata-1 or fog-1, are necessary for early MC development. These studies validate the zebrafish as an in vivo tool for studying MC ontogeny and function with future capacity for modeling human MC diseases.

Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials.

The objective of the study was to study the effects of continuous subcutaneous insulin infusion (CSII) vs multiple-dose insulin (MDI) therapy on glycemic control and pregnancy outcome in diabetic women. Randomized, controlled trials comparing CSII vs MDI in pregnant diabetic women were included after an electronic database search. Studies were rated for quality independently by 2 reviewers in accordance with the Quality of Reporting of Metaanalyses statement. Summary weighted mean difference and odds ratio were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death. Six randomized clinical trials met the inclusion criteria. Pregnancy outcomes and glycemic control were not significantly different among treatment groups. Higher number of ketoacidotic episodes and diabetic retinopathy found in the CSII group did not reach statistical significance. This systematic review does not show any advantage or disadvantage of using CSII over MDI in pregnant diabetic women. Large multicenter, randomized, controlled trials addressing the quality of life/cost effectiveness are required.

Congenital placental-cerebral adhesion: an unusual case of amniotic band sequence. Case report.

Amniotic band sequence is a disruption sequence having a broad spectrum of clinical manifestations ranging from partial amputations to major craniofacial and limb-body wall defects. Most reported cases of placental-cerebral adhesion pertain to patients with severe craniofacial defects who were either stillborn or who died a few hours after birth. The authors present a case of a male infant born with a placental-cerebral adhesion through a cranial defect. This adhesion was separated at birth, and duraplasty and primary scalp closure were performed. A detailed examination of the placenta revealed the presence of multiple amniotic bands. The case demonstrates that survival and normal early post-natal development are possible if the condition is treated promptly.

Validation of a food-frequency questionnaire for use in pregnancy.

OBJECTIVES: As a part of an ongoing project to develop a nutritional screening tool, we evaluated the performance of a semi-quantitative food-frequency questionnaire (FFQ) in terms of validity in a Sheffield Caucasian pregnant population using two different statistical approaches--the correlation coefficient and the limits of agreement (LOA). The FFQ was designed specifically for pregnant women and previously used in a large-scale study. DESIGN: A validation study. SETTING: A community-based field study of a general population of pregnant women booked for their first antenatal appointment at the Jessop Wing, Royal Hallamshire Hospital, Sheffield, UK. SUBJECTS: One hundred and twenty-three women of different socio-economic status, aged between 17 and 43 years, provided complete dietary data. RESULTS: The validity of the FFQ was tested against a series of two 24-hour recalls. As expected, the intakes of all examined nutrients, except for iodine, carotene, vitamin E, biotin, vitamin C and alcohol, were higher when determined by the FFQ than when determined by 24-hour recall. Pearson's correlation coefficient between the two methods ranged from 0.19 (added sugar, zinc) to 0.47 (Englyst fibre). The LOA were broader for some of the nutrients, e.g. protein, Southgate fibre and alcohol, and an increasing lack of agreement between the two methods was identified with higher dietary intakes. CONCLUSIONS: The FFQ gave useful estimates of the nutrient intakes of Caucasian pregnant women and appears to be a valid tool for categorising pregnant women according to dietary intake. The FFQ performed well for most nutrients and had acceptable agreement with the 24-hour recall.

C-Kit-positive metastatic malignant pigmented clear-cell epithelioid tumor arising from the kidney in a child without tuberous sclerosis.

We report the first pediatric case of malignant pigmented epithelioid clear-cell tumor arising from kidney; the lesion occurred in a 12-year-old girl without tuberous sclerosis. The tumor was widely metastatic to the retroperitoneum and chest, and the patient died of the disease 9 months after diagnosis, despite active chemotherapy. Pigmented epithelioid clear-cell tumor of the kidney is a rare variant of epithelioid angiomyolipoma and a member of the family of perivascular epithelioid cell tumors (PEComas). The tumor demonstrated overlapping features between clear-cell sugar tumor and epithelioid variant of angiomyolipoma. Tumor cells were positive for HMB-45 expression, negative for any evidence of muscular differentiation, and contained melanin pigment and premelanosomes in the cytoplasm. Diffuse C-Kit (CD117) positivity was identified throughout the tumor. This is the first report of C-Kit-positive malignant PEComas.

Preliminary evaluation of a coping strategy enhancement method of preparation for labour.

OBJECTIVES: To compare the use and effects of enhanced pre-existing coping strategies with the use and effects of coping strategies usually taught in National Health Service (NHS) antenatal education on women's experience of pain and emotions during labour. DESIGN: A between-group comparison of women who chose to attend NHS antenatal education where courses of preparation were randomly assigned to include either a new method of coping strategy enhancement (CSE) or standard taught coping strategies. SETTING: Two large maternity units in one city in the North of England. PARTICIPANTS: 20 women participated in antenatal classes incorporating the CSE method and 21 women participated in antenatal classes incorporating the standard approach to developing coping strategies for labour. FINDINGS: Women who attended CSE classes used enhanced coping strategies for a larger proportion of their labour than women who attended standard classes who used taught coping strategies. Birth companions were more involved in women's use of enhanced than taught strategies. Self-efficacy for use of coping strategies and subsequent experiences of pain and emotions during labour were equivalent between groups. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: An approach based on enhancing pre-existing coping strategies was associated with greater coping strategy use and involvement from the birth companion, and provided benefits to women's overall experience of labour at least equivalent to that associated with standard preparation. Further research should explore this novel approach in larger groups, and for women who may choose not to attend group antenatal preparation.

The crucial role of tumour specimen handling in childhood cancer outcomes.

The significant advances achieved in the care of children with cancer have been the result of carefully conducted clinical trials in international cooperative group settings. Specialized biological testing of tumour specimens is now an essential component of risk and treatment assignment for many childhood cancers. Thus, the appropriate collection and handling of tumour specimens is crucial to maintaining and further advancing the excellent outcomes that we have achieved. We recommend that all children with a strongly suspected malignancy, or cases in which the situation is unclear, be discussed with a paediatric oncologist before obtaining a tumour specimen. When a tumour is discovered incidentally at surgery, we recommend that the tumour be placed in a saline-soaked gauze and a paediatric pathologist or oncologist contacted immediately. Further progress in understanding and treating childhood cancer is intimately linked to basic studies of biology, translational research and determining the role of biological markers in risk stratification. Early and careful collaboration between front-line physicians and tertiary care oncology specialists is essential to the continuing success of treatment of children with cancer.

The range of coping strategies women use to manage pain and anxiety prior to and during first experience of labour.

OBJECTIVES: To investigate whether nulliparous women, during pregnancy, can identify their own pre-existing coping strategies for managing pain and anxiety and whether the range of coping strategies used in Labour by women who do not attend antenatal classes can be described. DESIGN: Qualitative semi-structured interviews. SETTING: Two large maternity units in a city in the North of England. PARTICIPANTS: Twenty-three nulliparous women were interviewed during their third trimester of pregnancy (prior to any antenatal class attendance) regarding strategies used to cope with previous experiences of pain and anxiety. A separate sample of 20 women, who had not attended any form of antenatal education, were interviewed within 72h of their first experience of labour regarding the coping strategies used to manage pain and anxiety during labour. FINDINGS: Template Analysis was used to code data from transcribed interviews. The findings indicate that as women approach their first experience of labour they can identify coping strategies that they have employed to manage pain and anxiety in their past. Equally women who have not attended antenatal classes use a wide range of strategies in labour. The range of identified coping strategies is described and comprises thoughts and behaviours with positive and negative consequences. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: It is possible to help nulliparous women to identify, in pregnancy, a range of strategies that they have previously employed to manage pain and anxiety. This range reflects the coping strategies that women may potentially use in labour to manage pain and anxiety. Women may benefit from assistance in pregnancy to develop strategies for labour that are based on knowledge of their own coping repertoire, which includes enhancing positive strategies and finding alternatives to negative strategies.

Selected coping strategies in labor: an investigation of women's experiences.

BACKGROUND: Antenatal education classes offer women information about labor and birth and ways of coping with pain and emotional distress. The purpose of this paper was to describe women's experiences of using, starting, and discontinuing three coping strategies in labor that were taught in antenatal education classes. METHODS: An exploratory research design was used in which 121 women were interviewed within 72 hours of the birth of their first child. Information was obtained on why women initiated and discontinued their use of three coping strategies (breathing technique, postural changes, relaxation technique) and the reported effects of use. RESULTS: The effects of the coping strategies investigated varied widely among participants. Common aspects of care, changes of environment, and use of pharmacological pain relief affected women's discontinuation of coping strategies. CONCLUSIONS: The implications of study findings for clinical practice include the need for caregivers to provide women with accurate information about the effects of coping strategies and to be alert to aspects of care that may disrupt women's use of strategies.

Acute myelogenous leukemia and glycogen storage disease 1b.

Glycogen storage disease 1b (GSD 1b) is caused by a deficiency of glucose-6-phosphate translocase and the intracellular accumulation of glycogen. The disease presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, as well as neutropenia causing increased susceptibility to pyogenic infections. We present a case of a young woman with GSD 1b who developed acute myelogenous leukemia while on long-term granulocyte colony-stimulating factor therapy. The presence of two rare diseases in a single patient raises suspicion that GSD 1b and acute myelogenous leukemia are linked. Surveillance for acute myelogenous leukemia should become part of the long-term follow-up for GSD 1b.

Association between Breus' mole and partial hydatidiform mole: chance or can hydropic villi precipitate placental massive subchorionic thrombosis?

Breus' mole (massive subchorionic hematoma) is a rare entity most often found in the placentae of macerated stillborn fetuses. Previously considered to represent a postmortem event, recent evidence suggests that it occurs prior to fetal demise. A 23-week gestation male neonate was delivered of a 23-year-old gravida 3, para 2 woman and survived for 49 min. An autopsy with chromosomal studies resulted in a diagnosis of triploidy. Placental examination showed the presence of both Breus' mole and also partial hydatidiform mole. DNA samples extracted from portions of the fresh hematoma and from the fetal spleen were compared using molecular techniques. PCR analysis showed the presence of Y chromosome specific DNA in the placental clot, but a semiquantitative Southern blot demonstrated that roughly 85% of the clot DNA was of maternal origin. These findings suggest that Breus' mole represents primarily maternal thrombosis rather than fetal hemorrhage. We hypothesize that the partial mole could have contributed to the formation of the Breus' mole as some of the hydropic villi may have focally obstructed the maternal venous return from the intervillus space causing sluggish flow and promoting thrombosis. A review of the literature on Breus' mole shows that the majority of reported cases have not included cytogenetic findings. However, several authors have reported an association with triploidy and other chromosomal anomalies characterized by scattered placental hydropic villi. Thus, we suggest that obstruction of maternal venous return by hydropic villi may have played a contributory role in some of these other reported cases.

T-cell/periodic acid-Schiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection.

Distinguishing between tubulitis and tubulointerstitial mononuclear cell infiltrates and determining the severity of tubulitis are critical components of diagnosing and grading renal allograft rejection using the 1993 Banff schema, the revised 1997 Banff schema, or the Cooperative Clinical Trials in Transplantation grading system. We describe a novel staining method, the T-PAS stain (CD3 and periodic acid-Schiff), which removes some of the subjectivity in the evaluation of tubulointerstitial infiltrates in renal allograft biopsies. The method simply combines two routine stains, immunoperoxidase staining for T cells (CD3) and periodic acid-Schiff (PAS) staining for tubular basement membrane, on the same section.

Eosinophilic/T-cell chorionic vasculitis.

Chorionic vasculitis is the hallmark of a fetal response in chorioamnionitis. There are five highly characteristic findings: (1) leukocyte migration is not concentric but rather radiates toward the infected amniotic fluid; (2) the infiltrate is primarily neutrophils; (3) multiple chorionic vessels, first veins and then arteries, are usually involved; (4) the infiltrate never extends into the vasculature of stem villi; and (5) it is rare in the absence of chorioamnionitis (or its precursors). Here we describe a new form of chorionic vasculitis characterized by an infiltrate composed primarily of eosinophils and CD3+ T lymphocytes that very focally involves a single chorionic vessel (artery or vein), that radiates away from the amniotic fluid (i.e., toward the intervillous spaces), and that may extend into the stem villous vasculature; this lesion occurs in the absence of any evidence of chorioamnionitis. During the past 7+ years, using accepted placental review criteria, we have examined 7104 placentas and identified 14 cases of eosinophilic/T-cell chorionic vasculitis (or related lesions). Although the frequency of diagnosis in the placentas examined was 0.197%, its true incidence cannot be estimated because of its very focal nature and the limited nature of placental disk sampling. Its etiology and significance are unknown, but it may represent a focal immune-mediated vasculitis.