Piloting a prenatal care smartphone application and care navigation intervention at a federally qualified health center.

BACKGROUND: Given that smartphones are widely used among reproductive-age people of all socioeconomic backgrounds, a smartphone application may be a useful supplement to routine prenatal care. OBJECTIVE: This study aimed to describe the implementation of a smartphone app that offers patient education, depression screening, social determinants of health screening, and care coordination as an adjunct to routine prenatal care at a federally qualified health center. We further sought to characterize app engagement and the association of app use with pregnancy outcomes. STUDY DESIGN: The implementation of the smartphone app was a quality improvement initiative in which the app was made available to all people receiving prenatal care at a designated federally qualified health center between December 2020 and December 2021. Individuals who both initiated prenatal care at this site before 28 weeks of gestation and delivered at our institution during the above-defined period were studied retrospectively after obtaining institutional approval. Summary statistics were used to describe app implementation and information regarding social determinants of health and depression screening. Demographics and maternal and neonatal outcomes were compared between app enrollees and patients receiving prenatal care at the same site who were not enrolled in the app. Data were analyzed using the 2-sample t test to compare continuous variables and the chi-square test to compare categorical variables. RESULTS: Overall, 800 patients receiving prenatal care at the federally qualified health center during the identified period were telephonically approached for enrollment in the smartphone app. A total of 613 people (76.6%) were successfully reached, and of those successfully reached, 538 (87.7%) accepted enrollment in the app; 76.6% of app enrollees (n=412) completed at least 1 social determinants of health screen. Of those, 29.1% (n=120) screened positive for at least 1 need. Of those with positive screens, 51.7% (n=62) accepted referral to resources to address the identified need. Furthermore, 81% of app enrollees (n=443) completed at least 1 depression screen. Of those, 13.1% (n=58) screened positive for depression, and 37.9% (n=22) of those with positive screens accepted a referral to behavioral health services. A total of 483 people met the inclusion criteria for retrospective review: 264 were enrolled in the smartphone app and 219 were not. App enrollees were more likely to speak English (79.9% of app group vs 61.6% of the non-app group; P<.0001), identify as Hispanic (52.7% vs 39.7%; P=.02), and be privately insured (24.6% vs 15.5%; P=.005), and less likely to have a social determinants of health-related need (10.0% vs 21.0%; P=.01). There were no significant differences in mode of delivery or maternal and neonatal outcomes between the 2 groups. CONCLUSION: A high proportion of patients receiving care through our federally qualified health center enrolled in and used the smartphone app and its associated care coordination. This could be a useful tool to screen for depression and adverse social determinants of health in underserved communities. Given that individuals of higher-resource backgrounds seem more likely to enroll in smartphone apps, a more targeted approach is needed to help connect patients of lower-resource backgrounds to smartphone apps and the resources that they offer.

Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.

Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.

Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia.

CONTEXT: -The placenta is an important component in understanding the fetal response to intrauterine Zika virus infection, but the pathologic changes in this organ remain largely unknown. Hofbauer cells are fetal-derived macrophages normally present in the chorionic villous stroma. They have been implicated in a variety of physiological and pathologic processes, in particular involving infectious agents. OBJECTIVES: -To characterize the fetal and maternal responses and viral localization in the placenta following Zika virus transmission to an 11 weeks' gestation fetus. The clinical course was notable for prolonged viremia in the mother and extensive neuronal necrosis in the fetus. The fetus was delivered at 21 weeks' gestation after pregnancy termination. DESIGN: -The placenta was evaluated by using immunohistochemistry for inflammatory cells (macrophages/monocytes [Hofbauer cells], B and T lymphocytes) and proliferating cells, and an RNA probe to Zika virus. The fetal brain and the placenta were previously found to be positive for Zika virus RNA by reverse transcription-polymerase chain reaction. RESULTS: -The placenta demonstrated prominently enlarged, hydropic chorionic villi with hyperplasia and focal proliferation of Hofbauer cells. The degree of Hofbauer cell hyperplasia gave an exaggerated immature appearance to the villi. No acute or chronic villitis, villous necrosis, remote necroinflammatory abnormalities, chorioamnionitis, funisitis, or hemorrhages were present. An RNA probe to Zika virus was positive in villous stromal cells, presumably Hofbauer cells. CONCLUSIONS: -Zika virus placental infection induces proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi but does not elicit villous necrosis or a maternal or fetal lymphoplasmacellular or acute inflammatory cell reaction.

Intracardiac tumor causing left-ventricular outflow-tract obstruction in a newborn.

The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left-ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor.

Solid pancreatic pseudopapillary tumor managed laparoscopically in adolescents: a case series and review of the literature.

BACKGROUND: Solid pancreatic pseudopapillary tumors make up 1%-3% of all pancreatic tumors, occur predominantly in females, and usually present in the third and fourth decades of life. Less frequently, these tumors may present in children. Complete surgical excision is the treatment of choice with excellent outcomes. Usage of a laparoscopic approach has become more common for adult patients. However, the laparoscopic approach is not routinely used in the pediatric population. MATERIALS AND METHODS: A literature review was performed noting 13 documented cases of solid pancreatic pseudopapillary tumors resected laparoscopically in children. We report our case series of three children with a solid pancreatic pseudopapillary tumor treated through a minimally invasive approach. RESULTS: In the literature, most patients had the tumor in the body or distal pancreas. The most common complication was pancreatic fistula, which was managed with total parenteral nutrition. In addition, there were reports of recurrence after biopsy of the tumor. In our case series 2 of the 3 patients received a splenectomy because of the proximity of the tumor to the spleen. There were no intraoperative or postoperative complications. Follow-up length from 13 to 36 months revealed no evidence of recurrence. CONCLUSIONS: In the pediatric population, solid pancreatic pseudopapillary tumors located in the body or tail of the pancreas can be managed with a laparoscopic distal pancreatectomy.

Hemangioendothelioma: a rare case of a primary intracardiac tumor.

Kaposiform hemangioendothelioma (KH) is a rare tumor of vascular origin that commonly affects the cutaneous tissues of the extremities. It can, however, affect the abdomen, thorax, head, or neck. Compared with juvenile hemangiomas, which tend to regress, KH tumors are locally aggressive and usually persist. Associated morbidity and mortality rates range from 12 to 30 % and typically are related to either compressive effects on surrounding vital structures or effects of the Kasabach-Merritt phenomenon [10, 11, 13]. To our knowledge, this report is the first to describe KH presenting as a primary intracardiac tumor.

Identification of a novel, recurrent SLC44A1-PRKCA fusion in papillary glioneuronal tumor.

Mixed neuronal-glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)-based positional cloning strategy revealed SLC44A1, a member of the choline transporter-like protein family, and PRKCA, a protein kinase C family member of serine/threonine-specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1-PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual-color breakpoint-spanning probe set custom-designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1-PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT-PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.

Placental weight and neurologic outcome in the infant: a review.

OBJECTIVE: To review the agreement of published standards on placental weights (PW) and fetal-placental (F/P) ratios, examine factors contributing to PW and ask whether aberrant placental weight is associated with adverse neurologic outcome. METHODS: We conducted a literature search for standards of PW, F/P ratio and the relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy. We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven studies compared mean and extreme percentile bounds between 35 and 42 weeks of gestation. Nine publications examined PW and neurologic outcome. RESULTS: Untrimmed placentas were heavier by 131-193 g. F/P ratios differed by 0.2-2.34 between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior to weighing had minimal effect on weight. Gender and race had negligible affect. Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries. There were no consistent associations of aberrant PW and neurologic outcome. CONCLUSIONS: Reference standards of recent studies on trimmed placentas were largely in agreement. Current findings relating aberrant PW and adverse neurologic outcome are inconclusive. Further study of the relationship between placental weight and neonatal encephalopathy or cerebral palsy is warranted, in representative populations using within-study controls.

Benign sacrococcygeal neoplasm arising at birth from a giant congenital melanocytic nevus.

Giant congenital melanocytic nevi (CMN) are considered to be premalignant with the highest risk for conversion to melanoma. Solid tumors within giant CMN presenting at birth are relatively unusual, and a variety of malignancies have been reported within these masses. However, the frequency of malignancy in these tumors is unknown. We report the unusual case of a female neonate who was born with 2 large, perianal masses within a giant CMN over her trunk. We resected the larger of the 2 masses because of discomfort and bleeding. The mass consisted of an outgrowth of melanocytes with benign characteristics. The smaller of the 2 masses was managed expectantly and has subsequently decreased in size. We propose that pathologically benign masses within giant CMNs may not require immediate resection. We will discuss the management and pathologic findings of this case and review the literature regarding management of CMN-associated neoplasms arising at birth.

Closed-chest transthoracic magnetic resonance imaging-guided ventricular septal defect closure in swine.

OBJECTIVES: The aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure. BACKGROUND: Surgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity. METHODS: Percutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter. Under real-time MRI guidance, a direct transthoracic vascular access sheath was introduced through the chest into the heart along a trajectory suitable for VSD access and closure. Through this transthoracic sheath, muscular VSDs were occluded using a commercial nitinol device. Finally, the right ventricular free wall was closed using a commercial collagen plug intended for arterial closure. RESULTS: Anterior, posterior, and mid-muscular VSDs (6.8 ± 1.8 mm) were created. VSDs were closed successfully in all animals. The transthoracic access sheath was displaced in 2, both fatal. Thereafter, we tested an intracameral retention sheath to prevent this complication. Right ventricular access ports were closed successfully in all, and after as many as 30 days, healed successfully. CONCLUSIONS: Real-time MRI guidance allowed closed-chest transthoracic perventricular muscular VSD closure in a clinically meaningful animal model. Once applied to patients, this approach may avoid traditional surgical, percutaneous, or open-chest transcatheter ("hybrid") risks.

Novel SCN1A mutation in a proband with malignant migrating partial seizures of infancy.

OBJECTIVE: To characterize a novel SCN1A mutation in a proband with malignant migrating partial seizures of infancy. DESIGN: Genomic DNA was isolated from blood and submitted for commercial testing. The identified missense mutation was confirmed in brain DNA obtained at autopsy. Genomic DNA from the brain of the proband was analyzed by comparative genome hybridization, and the coding exons of SCN9A were amplified. Quantitation studies of the mutant transcript were performed. SETTING: Children's National Medical Center and Yale University School of Medicine. PROBAND: A full-term female infant who experienced seizure onset at age 10 weeks, with progression of hemiclonic, apneic, and multifocal migrating partial seizures leading to recurrent status epilepticus and death at age 9 months. MAIN OUTCOME MEASURES: Electroencephalographic and magnetic resonance imaging results, quantitative RNA expression, and secondary mutation test results. RESULTS: The heterozygous missense mutation c.C5006C>A was identified by sequencing genomic DNA from blood and was confirmed in brain DNA. The resulting amino acid substitution p.A1669E alters an evolutionarily conserved residue in an intracellular linker of domain 4 of the SCN1A sodium channel protein Na(v)1.1. The mutant transcript is found to be expressed at levels comparable to the wild-type allele in brain RNA. No variation in copy number was detected in the chromosome region 2q24 containing SCN1A or elsewhere in the genome. No mutations were detected in the linked sodium channel gene SCN9A, which has been reported to act as a modifier of SCN1A mutations. CONCLUSION: This report expands the spectrum of SCN1A epileptic channelopathies to include malignant migrating partial seizures of infancy.

Multiple papillary fibroelastomas of the heart.

We report the case of a 41-year-old woman who presented with extensive papillary fibroelastomas of the heart after multiple previous surgical procedures for hypertrophic cardiomyopathy. This case is significant because of the locally aggressive nature of the cardiac papillary fibroelastoma.

Castleman disease: surgical cure in pediatric patients.

Castleman disease is a rare disorder characterized by lymphoid hyperplasia which rarely manifests in children. We present 2 cases which highlight both histologic variants of this disease, and provide suggestions regarding workup and treatment with the goal of making practitioners aware of Castleman disease in the differential diagnosis of a child presenting with vague symptoms.

Effects of hemoglobin C and S traits on the results of 14 commercial glycated hemoglobin assays.

Glycated hemoglobin is widely used in the management of diabetes mellitus. At least 300,000 Americans with diabetes mellitus have the hemoglobin (Hb) C or S trait. The accuracy of HbA1c methods can be adversely affected by the presence of these traits. We evaluated the effects of HbC and HbS traits on the results of 14 commercial HbA1c methods that use boronate affinity, enzymatic, immunoassay, and ion exchange methods. Whole blood samples from people homozygous for HbA or heterozygous for HbC or HbS were analyzed for HbA1c. Results for each sample type were compared with those from the CLC 330 comparative method (Primus Diagnostics, Kansas City, MO). After correcting for calibration bias by comparing results from the homozygous HbA group, method bias attributable to the presence of HbC or HbS trait was evaluated with a clinically significant difference being more than 10% (ie, 0.6% at 6% HbA1c). One immunoassay method exhibited clinically significant differences owing to the presence of HbC and HbS traits.

Evaluation of the BiliChek being used on hyperbilirubinemic newborns undergoing home phototherapy.

CONTEXT: Newborns are often screened prior to discharge for hyperbilirubinemia. Transcutaneous bilirubin analyzers, such as the BiliChek, are promoted as screening tools, but it is unclear whether they also function well as monitoring devices. Newborns on home phototherapy require frequent determinations of serum bilirubin levels to monitor therapy effects. A transcutaneous bilirubin analyzer would be helpful to limit blood draws and enhance staff efficiency. We evaluated the accuracy of the BiliChek analyzer in this setting. OBJECTIVE: Is the BiliChek sufficiently accurate to monitor the effectiveness of home phototherapy and establish when to terminate therapy? DESIGN: Paired serum bilirubin results and results from the BiliChek were obtained from newborns on home phototherapy during daily home health care visits. RESULTS: The BiliChek demonstrates a negative bias (mean bias, -1.71 mg/dL; 95% confidence interval, -1.89 to -1.52 mg/dL) compared with serum bilirubin values. This bias worsens as the serum bilirubin level rises. If a value of 14 mg/dL or less obtained using the BiliChek had been used as the cutoff for termination of phototherapy, 45% of newborns would have had therapy terminated prematurely. If, knowing the negative bias of the BiliChek, the cutoff for termination of therapy was set at less than or equal to 11 mg/dL, then 29% of newborns would have had therapy terminated prematurely. CONCLUSIONS: The values obtained using the BiliChek, compared to serum bilirubin values, have a negative bias that worsens at the higher bilirubin levels expected in newborns at home on phototherapy. The BiliChek does not provide sufficient accuracy to be utilized to monitor newborns on home phototherapy or to ascertain when to discontinue such therapy.

Loss of the PTCH1 gene locus in cardiac fibroma.

BACKGROUND: Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. METHODS: Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome. RESULTS: Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal. CONCLUSION: These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.

Intracranial leptomeningeal metastasis from thymic carcinoma: case report and review.

BACKGROUND: Thymic carcinoma is an uncommon malignant tumor of the anterior mediastinum. Meningeal metastasis from this type of neoplasm is extraordinarily rare and the prognosis is abysmal. CASE DESCRIPTION: This article presents the case of a 45-year-old man with known metastatic thymic carcinoma who presented with intractable headaches. An MRI scan was highly suggestive of a meningioma, and it was initially suspected that this patient had 2 primary tumors. Surgical resection of the mass both demonstrated a metastatic thymic lesion and ameliorated the patient's quality of life. CONCLUSION: The authors report a case of intracranial meningeal metastasis from a lymphoepithelioma-like poorly differentiated metastatic thymic carcinoma, which was treated by resection and WBRT. A review of the current literature revealed no other cases of this uncommon alhistologic subtype of thymic carcinoma metastatic to the cranium. The incidence, histologic classification of subtypes, and treatment are discussed. This case also illustrates the importance of maintaining a high degree of suspicion for a metastasis in patients with known primary malignancy who present with an MRI highly suspicious for meningioma.

Impaired conditioned fear and enhanced long-term potentiation in Fmr2 knock-out mice.

FRAXE mental retardation results from expansion and methylation of a CCG trinucleotide repeat located in exon 1 of the X-linked FMR2 gene, which results in transcriptional silencing. The product of FMR2 is a member of a family of proteins rich in serine and proline, members of which have been associated with transcriptional activation. We have developed a murine Fmr2 gene knock-out model by replacing a fragment containing parts of exon 1 and intron 1 with the Escherichia coli lacZ gene, placing lacZ under control of the Fmr2 promoter. Expression of lacZ in the knock-out animals indicates that Fmr2 is expressed in several tissues, including brain, bone, cartilage, hair follicles, lung, tongue, tendons, salivary glands, and major blood vessels. In the CNS, Fmr2 expression begins at the time that cells in the neuroepithelium differentiate into neuroblasts. Mice lacking Fmr2 showed a delay-dependent conditioned fear impairment. Long-term potentiation (LTP) was found to be enhanced in hippocampal slices of Fmr2 knock-out compared with wild-type littermates. To our knowledge, this mouse knock-out is the first example of an animal model of human mental retardation with impaired learning and memory performance and increased LTP. Thus, although a number of studies have suggested that diminished LTP is associated with memory impairment, our data suggest that increased LTP may be a mechanism that leads to impaired cognitive processing as well.

Epstein-Barr virus-associated smooth muscle tumors in ataxia-telangiectasia: a case report and review.

Chromosomal breakage syndromes, including ataxia-telangiectasia (AT), are autosomal recessive disorders in which DNA repair mechanisms are defective resulting in chromosomal instability. Affected individuals are at high risk for developing malignancy because of the widespread resulting cellular effects. One such effect, severe immunosuppression, can permit virally mediated neoplasms to manifest, similar to those seen in acquired immunodeficiency syndrome (AIDS), congenital immune deficiency syndromes, and posttransplant populations. Epstein-Barr virus (EBV) is a common viral agent known to be associated with lymphoid, epithelial, and smooth muscle malignancies in such patients. Although smooth muscle tumors have been reported in patients with AT, their association with EBV has not been evaluated. We present a case of EBV-associated laryngeal leiomyosarcoma and jejunal cellular leiomyoma in a child with AT. This case suggests that the development of neoplasia in patients with chromosomal breakage syndromes may be related to the immunosuppressive consequences of these diseases, and searching for infectious causes (such as EBV) is important.