Reliable Pregnancy Testing Before Intravenous Cyclophosphamide: A Quality Improvement Study.

BACKGROUND AND OBJECTIVE: Cyclophosphamide is a teratogenic medication used in the treatment of adolescents with autoimmune disorders. This adolescent population is sexually active, does not receive adequate contraceptive care, and is at risk for unintended pregnancy. We undertook a quality improvement initiative to improve rates of pregnancy screening before intravenous cyclophosphamide administration in our adolescent girl patients. METHODS: Data were collected from the electronic medical record. The primary outcome was completion of a urine pregnancy test before intravenous cyclophosphamide infusion in girls aged 12 to 21 years between July 2011 and June 2015. Data were reviewed quarterly and an iterative quality improvement approach was used. Interventions included staff education, electronic order set updates, and a Maintenance of Certification project. Interrupted time series analysis and multivariable mixed effects logistic regression were used to evaluate trends over time and to adjust for potential confounders. RESULTS: Thirty girls received 153 cyclophosphamide infusions during the study. Pregnancy testing before medication administration increased from 25% to 100% by study completion. Infusions in the last time period were significantly more likely to be accompanied by a pregnancy test versus those in the first time period (odds ratio: 17.7; 95% confidence interval [CI]: 3.1-101.6) after adjustment for patient age, managing service, infusion setting, and insurance type. CONCLUSIONS: Our institution achieved a significant increase in standard pregnancy screening in adolescent girls receiving intravenous cyclophosphamide. The interventions most valuable in increasing screening rates were updating electronic order sets, educating staff, and physician engagement in the Maintenance of Certification program.

Demographic factors determining termination of pregnancy following the detection of lethal fetal malignancy.

OBJECTIVE: To identify demographic and clinical variables differentiating pregnant Polish women who decided to terminate the pregnancy in the case of lethal fetal malformation from those who preferred to continue the pregnancy in such a situation. STUDY DESIGN: Cross-sectional study. RESULTS: The group of women who decided to abort contained a higher fraction of multiparas than the group of patients who chose to continue their pregnancies, and was characterized by significantly lower mean gestational age at diagnosis of lethal fetal malformation. The only demographic variable approaching statistical significance was the presence of siblings, which was significantly more frequent amongst women who decided to terminate the pregnancy. CONCLUSIONS: As the decision-making process on pregnancy termination is multimodal, pregnant women require particular support in the case of detecting lethal malformation in their fetuses.

Bone deformities and skeletal malformations in the Roman Imperial Age.

This paper describes some cases of individuals affected by skeletal deformities resulting in "freak" appearance. The skeletal remains were found during large archaeological excavations in the Roman territory, carried out by the Special Superintendence to the Archeological Heritage of Rome in the last years, dated back to the Imperial Age. The first cases reported are referred to two growth disorders with opposite effects: a case of dwarfism and another of gigantism. The former concerns a young man from the Collatina necropolis with very short and malformed limbs, which allowed a diagnosis of acondroplasic dwarfism, a rare congenital disorder that limits height below 130 cm. The latter case comes from the necropolis of Torre Serpentana in Fidenae, and is instead referred to a young person of very high stature, about 204 cm, suffering from Gigantism, a rare condition which in this case seems to have been linked to a hormonal dysfunction due to a pituitary adenoma. A third case regards a joint disease affecting the vertebral column and causing severe deformities. The skeleton was found in the Collatina necropolis and belongs to an old woman, suffering from ankylosing spondylitis. Finally, the last and very peculiar case is related to an individual recovered in the necropolis of Castel Malnome. The skeletal remains belong to an adult man with a complete fusion of the temporo-mandibular joint, which compromised mastication and caused severe deformation of the maxillofacial complex. These cases are described in detail together with the possible implications that these deformities could have on in the social context.

Heteropagus (parasitic) twins: a review.

Heteropagus, or "parasitic," twins are asymmetric conjoined twins in which the tissues of a severely defective twin (parasite) are dependent on the cardiovascular system of the other, largely intact twin (autosite) for survival. The estimated incidence of heteropagus twins is approximately 1 per 1 million live births. Isolated case reports comprise most of published work on this rare congenital anomaly. In the past, review articles have focused narrowly on one particular anatomical subtype of parasitic twin and/or on the anatomicopathology observed. Here, we present the epidemiology, proposed pathoembryogenic origins, anatomical abnormalities, management, and outcomes of the wide array of heteropagus twins described in the English language literature.

Essaying the mechanical hypothesis: Descartes, La Forge, and Malebranche on the formation of birthmarks.

This essay examines the determination by Cartesians to explain the maternal imagination's alleged role in the formation of birthmarks and the changing notion of monstrosity. Cartesians saw the formation of birthmarks as a challenge through which to demonstrate the heuristic capacity of mechanism. Descartes claimed to be able to explain the transmission of a perception from the mother's imagination to the fetus' skin without having recourse to the little pictures postulated by his contemporaries. La Forge offered a detailed account stating that the failure to explain the maternal imagination's impressions would cast doubt on mechanism. Whereas both characterized the birthmark as a deformation or monstrosity in miniature, Malebranche attributed a role to the maternal imagination in fashioning family likenesses. However, he also charged the mother's imagination with the transmission of original sin.

Acardiac twin presenting as fetus amorphous with an attenuated umbilical cord.

Acardiac anomaly sequence is a rare malformation cluster occurring in the setting of monozygotic monochorionic twin pregnancies. In addition to an absent heart (acardia), variable degrees of somatic developmental disruption are present. We describe an extreme example of what we believe to be acardiac twinning, with almost complete absence of gross tissue organization but recognizable microscopic evidence of body-axis establishment and organ formation. The case is also notable for the absence of a grossly identifiable umbilical cord, with attachment to the placental vasculature by 2 vessels invested by amnion but without Wharton's jelly. We discuss the controversy regarding the requirement of an umbilical cord in the definition of acardiac twin and distinguish this case from placental teratoma.

Fetus amorphous acardious: report of a rare case and differential diagnosis from placental teratoma with review of the literature.

Fetus amorphous acardious is a rare fetal malformation, lacking a functional heart and bearing no resemblance to human embryos. The main differential diagnosis is with placental teratoma and is based on the degree of skeletal organization and umbilical cord formation. A 27-year old woman delivered a healthy newborn at 37 weeks' gestation. An amorphous mass, covered with healthy looking skin, was connected to the placenta with a short pendicle. X-ray examination of the mass revealed the presence of vertebral column associated with ribs and pelvic bones. Histopathologic examination demonstrated the presence of spinal tube inside the vertebral column. Microscopy of the pedicle was consistent with umbilical cord. Various other tissues were also discovered, such as adipose tissue, gastric and large.

Lumbosacral parasitic rachipagus twin.

A rare case of a newborn girl presenting with a mass representing an aborted parasitic twin attached to the back in the midline over the lumbosacral region (parasitic rachipagus) is reported. Rudimentary digits were attached to the mass, and in one area, the overlying skin resembled scrotal skin. A depression resembling an anal dimple was also present on the surface of the mass. Investigations showed a well-developed long bone and other small bones within the parasite, and sacral spina bifida in the autosite. Successful surgical excision of the parasitic mass was performed. A review of the literature pertaining to parasitic rachipagus twinning is presented.

Epignathus: always a simple teratoma? Report of an exceptional case with two additional fetiforme bodies.

We report on a case of a fetal epignathus combined with two fetus-like structures resembling acardius acranius. The anomaly was detected at 23 weeks of gestation and led to termination of pregnancy at 24 weeks. This is the first description of epignathus with parasitic fetuses detected prenatally. It shows that the boundary between fetal teratoma and multiple pregnancy in special cases may be difficult to define.

Chorangiopagus parasiticus twins.

Chorangiopagus parasiticus twins (CAPP) occur due to asymmetric abnormality of monozygous, twinning. It is the commonest form of asymmetric twinning, occurring in 1% of monozygous twins. The asymmetric twin survives by parasitizing the more normally developed co-twin by connecting with the chorionic circulation, hence, chorangiopagus parasiticus. CAPP twin is a markedly edematous foetus with relatively well-developed legs, incomplete pelvis and lower spine. The body cavity contains some incomplete abdominal viscera but usually no thoracic organs. The upper portion of the twin consists of edematous cystic tissue. This parasitic perfused twin has no placental vascular connection and its cord vessels are conjoint with those of the parasitized pump twin on the surface of the placenta or somewhere along the cord. This malformation can be identified by ultrasound as early as 12 weeks gestation.

Treatment of acardiac twinning.

BACKGROUND: The twin reversed-arterial-perfusion sequence is a complication of monochorionic twin pregnancies characterized by the hemodynamic dependence of a "recipient" twin from a "pump" twin. The recipient twin exhibits lethal abnormalities including acardia and acephaly. The pump twin has a mortality rate of 50% as a result of high-output heart failure. CASE: The blood supply to an acardiac-acephalus twin was interrupted at 24 weeks' gestation using endoscopic laser coagulation. The co-twin was delivered at 35 weeks and had an uneventful neonatal course following correction of a persistent patent ductus arteriosus. Review of the literature reveals 22 cases of acardiac twinning treated with invasive procedures, seven of them using endoscopic laser coagulation. Pump twin mortality with fetal surgery was 13.6% in comparison with 50% mortality with expectant management (P < .001). CONCLUSION: Fetal surgery is the best available treatment for acardiac twinning. Endoscopic laser coagulation at or before 24 weeks and endoscopic or sonographic guided umbilical cord ligation after this gestational age seem to be the best treatments for this condition.

Severe brain and limb defects with possible autosomal recessive inheritance: a series of six cases and review of the literature.

Six fetuses with normal chromosomes were found to have severe craniofacial, limb, and visceral malformations during the second trimester of pregnancy. Two of these fetuses were monozygotic twins while a third one had a healthy dizygotic twin brother. A case with familial recurrence was also observed. Autopsy and skeletal radiographs suggested several diagnoses such as neural tube defect with limb defects or XK aprosencephaly. The development of these severe conditions in monozygotic twins and familial recurrence emphasize the difficulties of genetic counseling in such situations. These cases may suggest autosomal recessive inheritance.

Epigastric heteropagus.

Incomplete parasitic twinning with the parasite attached at the host's epigastrium is extremely rare. We report a case of epigastric parasitic twinning where the parasite with a well-developed pelvis and lower limbs had accessory pelvic organs and was attached to the host above an omphalocele. The parasite was excised and the omphalocele managed conservatively by mercurochrome application. A review of the four previously reported cases is presented along with a discussion of the possible etiopathogenesis and nomenclature of this condition.

Treatment of acardiac-acephalus twin gestations by hysterotomy and selective delivery.

The acardius syndrome is a rare complication of monozygotic twin pregnancies, occurring once in 35,000 births. The outcome is invariably fatal for the acardiac twin and for 50-75% of the normal twins. We present a surgical approach to the treatment of this problem involving hysterotomy and selective delivery of the acardiac twin, which we have used in five cases. In the first case, placental abruption shortly after the procedure led to fetal death. The next two cases resulted in cesarean delivery of the remaining healthy singleton at 35 weeks' gestation. The fourth and fifth cases were delivered at 27 and 28 weeks' gestation, respectively, the first because of preterm rupture of membranes 2 weeks after the procedure and the second because of partial placental abruption 8 weeks after surgery; both of these infants are now doing well. There were no residual maternal complications. We conclude that hysterotomy has direct applicability in the management of these high-risk pregnancies.

Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe "boomerang dysplasia"?

The authors report a case of lethal neonatal dwarfism characterized by striking micromelia, fused rudimentary and supernumerary digits, large, soft head, pronounced hypertelorism, protruding eyes set laterally, enormous omphalocele and severe deficiency of tubular bone and spine ossification. Histologic examination showed lack of ossification of the cartilaginous anlage of many tubular bones. The cartilage had irregularly distributed chondrocytes. The matrix contained hypocellular and degenerated areas with scattered large chondrocytes. In a few bones a very disorganized growth cartilage was present. The case is similar to that described by Piepkorn et al. (1977) and may represent a severe form of "boomerang dysplasia" (Kozlowski et al., 1981; Tenconi et al., 1983; Kozlowski et al., 1985; Winship et al., 1990).

Iniencephaly with cyclopis (a case report).

Iniencephaly is a rare neural tube defect. We report a rare association of iniencephaly with cyclopia, probably the third such report in the literature.

Syndromology: an updated conceptual overview. VIII. Deformations and disruptions.

A deformation is an abnormal form or position of the body caused by nondisruptive mechanical forces. Clubfoot, congenital hip dislocation, and infantile mandibular asymmetry (not based on mandibular malformation) serve as examples. The musculoskeletal system is involved in almost all deformations. Various disturbances of intrauterine movement are the usual causes and commonly occur during the fetal period. Causes may be mechanical or malformational. The former includes first pregnancies, small maternal size, uterine malformations and tumors, and amnionic rupture leading to oligohydramnios. Malformational causes usually involve the urogenital system and the central nervous system. A disruption is a morphologic defect of an organ, part of an organ, or a larger region of the body resulting from a breakdown of, or interference with, an originally normal developmental process. Amnionic band disruptions with digital amputations serve as an example. The most recent studies of disruptions and their suggested mechanisms are discussed. Finally, the interrelationships between malformations, deformations, and disruptions are explained.

Electron-microscopic studies on the pathogenesis of exencephaly and cranioschisis induced in the rat after neural tube closure: role of the neuroepithelium and choroid plexus.

Exencephaly was induced in Wistar rat fetuses by the administration of a single dose of cyclophosphamide (15 mg/kg) in saline, after neural tube closure. The neuroepithelium (NE) and the choroid plexus were studied electron-microscopically in sections taken from a few hours after treatment to day 19 of gestation. The reduction in polyribosomes and condensation of the nucleus and cytoplasm were followed by cell death and fragmentation in the NE. Such cellular debris were phagocytosed and digested by the apparently normal neuroblasts. Cell proliferation was inhibited. The progressive loss of cells and lack of neuropil arborisation resulted in the expansion of the extracellular space and reduced intercellular contacts. The internal and external limiting membranes became weak. The vascular endothelium was attenuated. There were no obvious discontinuities of endothelium, but clusters of extravascular red blood cells, particularly in the vicinity of capillaries, in the cavitations in the NE and in the ventricular lumen were prominent by day 15. Subsequently, the cavities in the NE frankly communicated with the ventricle internally and subcutaneous blebs externally. The choroid plexus of exencephalic embryos was more extensive than that of the age-matched controls. Hydropic vacuoles, dense bodies, distended mitochondria, clusters of vesicles in basal cytoplasm and lakes of monoparticulate glycogen progressively increased in the plexus cells. Pericapillary oedema was obvious in the core of the plexus. These observations suggest that, in addition to cell death and reduced cell proliferation, haemorrhage, oedema and enhanced cerebrospinal fluid production contribute to reopening of the closed neural tube in this model.