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.

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.

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.

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.

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.