Antenatal factors modulate hearing screen failure risk in preterm infants.

OBJECTIVE: The objective of this study was to characterise the effects of antenatal inflammatory factors and maternal therapies on neonatal hearing screen outcomes in very low birthweight infants. METHODS: We conducted a retrospective study of a cohort of infants <33 weeks' gestational age and <1501 g birth weight prospectively enrolled between 1999 and 2003 for whom placental pathology, cord blood interleukin (IL) 6, IL-1ß, tumour necrosis factor-α and neonatal hearing screen results were available. RESULTS: Of 289 infants with documented hearing screen results, 244 (84%) passed and 45 (16%) failed the hearing screen (unilateral, N=25 (56%); bilateral, N=20 (44%)). In the final logistic model, the fetal inflammatory response syndrome defined as the presence of fetal vasculitis and/or cord serum IL-6>18.2 pg/mL was the factor with greatest risk for hearing screen failure (OR 3.62, 95% CI 1.38 to 9.5). A patent ductus arteriosus treated with indomethacin significantly increased the risk (OR 3.3, 95% CI 1.3 to 8.26), while combined maternal steroid and magnesium sulfate exposure (0.37, 95% CI 0.11 to 0.81) reduced the risk for hearing screen failure. CONCLUSIONS: Intrauterine infection with a fetal inflammatory response is a risk factor for neonatal hearing loss while maternal therapies significantly reduced the risk of neonatal hearing loss in very low birthweight infants.

A study of gata3 and phox2b expression in tumors of the autonomic nervous system.

Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.

Recurrent myxoid liposarcoma of the buccal mucosa in a young boy: a case report and review of the literature.

Liposarcomas are uncommon in the pediatric population. We present the case of a boy who had experienced multiple recurrences of liposarcoma in the buccal space before he reached the age of 13 years. We also provide a review of the literature and a discussion of adjuvant therapy, which are important to understanding the nature of this disease.

NICU admission hypothermia, chorioamnionitis, and cytokines.

OBJECTIVE: To determine whether neonatal intensive care unit (NICU) admission hypothermia is associated with an intrauterine inflammatory response. METHODS: We analyzed a cohort of 309 very low birthweight infants to determine relationships between admission hypothermia, chorioamnionitis, and serum and cerebrospinal fluid (CSF) interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. RESULTS: Admission hypothermia <36°C occurred in 72% of patients <26 weeks and 44% of patients ≥26 weeks gestational age. NICU admission hypothermia was not associated with histologic chorioamnionitis or with elevated serum cytokine concentrations. CSF IL-6 concentrations ≥6.3 pg/mL were associated with admission hypothermia in infants <26 weeks' gestation. Clinical chorioamnionitis was associated with a lower risk of admission hypothermia, while cesarean section delivery was associated with increased risk. CONCLUSIONS: NICU admission hypothermia is common among preterm infants and is not associated with the fetal inflammatory response syndrome. Hypothermia is less common in the setting of clinical chorioamnionitis and more common in cesarean section deliveries, identifying two groups in whom extra attention to appropriate thermoregulation is warranted.

Necrotizing enterocolitis is associated with ureaplasma colonization in preterm infants.

The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants <33 wk gestation is associated with an increased risk for necrotizing enterocolitis (NEC). One or more tracheal or nasopharyngeal aspirates for Ureaplasma culture and PCR were obtained during the first week of life from 368 infants <33 wk gestation enrolled from 1999 to 2003 or from 2007 to 2009. NEC Bell stage ≥ 2 was confirmed by radiological criteria, and pathology, if available. Cord serum samples were analyzed for IL-6 and IL-1ß concentrations, and placentas were reviewed for histological chorioamnionitis in the first cohort. NEC was confirmed in 29 of 368 (7.9%) of the combined cohorts. The incidence of NEC was 2.2-fold higher in Ureaplasma-positive (12.3%) than Ureaplasma-negative (5.5%) infants <33 wk (OR, 2.43; 95% CI, 1.13-5.2; p = 0.023) and 3.3-fold higher in Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤ 28 wk (OR, 3.67; 95% CI, 1.36-9.93; p = 0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1ß concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses.

Clinical utility of postchemoradiation endoscopic brush cytology and biopsy in predicting residual esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma generally carries a poor prognosis. Treatment with combination chemoradiation (CRT) followed by esophagectomy is becoming common. A pathologic complete response is uncommon but predicts improved survival. Identifying the subset of patients with residual carcinoma has potential management implications. Post-CRT endoscopic brush cytology and biopsy may detect residual tumor; however, the accuracy and clinical value of these methods remain unclear. METHODS: Sixty-seven patients with esophageal adenocarcinoma who underwent preoperative CRT and post-CRT endoscopic brush cytology and biopsy followed by esophagectomy were identified. By using esophagectomy histology as the gold standard, the performance of cytology and biopsy was evaluated in diagnosing residual carcinoma. Two pathologists independently reviewed all false-negative and false-positive cases and resolved disagreements by consensus. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cytology for diagnosing residual carcinoma were 26%, 95%, 92%, 35%, and 45%, respectively. For biopsy, these rates were 13%, 90%, 75%, 31%, and 36%, respectively. Sampling error accounted for false-negative diagnoses in approximately 66% of cytology analyses and 98% of biopsy analyses. Approximately 33% of false-negative cytology analyses and 1 false-negative biopsy analysis were caused by the under-recognition of tumor cells. Major diagnostic pitfalls included obscuring acute inflammation, necrosis, tumor cells that mimicked benign cells with radiation/reactive atypia, and the under recognition of mucin-containing adenocarcinoma cells. CONCLUSIONS: Brush cytology and biopsy were specific but not sensitive methods for predicting residual cancer after CRT. However, cytology was superior. The current results indicated that brush cytology can be used alone to diagnose residual esophageal carcinoma, and awareness of specific diagnostic pitfalls will help pathologists improve its accuracy.

Combined cardiac sympathetic excitation and vagal impairment in patients with non-organic erectile dysfunction.

OBJECTIVE: Patients with non-organic erectile dysfunction (ED) frequently present with syndromes involving systemic sympathovagal dysfunction. The linkage of ED to cardiac autonomic regulation is not well understood. METHODS: Forty-four men with non-organic ED and 38 healthy age-matched control subjects with ages ranging from 40 years to 69 years were recruited. These two groups were divided into three distinct age categories at 10-year intervals. Patients were divided into three different severity categories, among whom 35 patients received a two-month oral treatment of trazodone. Power spectral analysis of successive R-R intervals (RR) was performed to evaluate the variance (variance of RR-interval values), the high-frequency power (HF), and the ratio of low-frequency power to HF (LF/HF) of their heart rate variability (HRV). RESULTS: Patients exhibited a significantly lower variance and HF, but a higher LF/HF compared to the control group across all age categories. The changes in variance and HF were severity dependent. In addition, all the HRV parameters of the patients with a satisfactory response after treatment have significantly improved. CONCLUSION: The results indicate that patients with non-organic ED had significant cardiac sympathetic hyperactivity and severity-dependent cardiac vagal impairment. SIGNIFICANCE: Non-organic ED may be accompanied by an abnormality in cardiac autonomic regulation.

Cytologic findings and differential diagnosis in hepatic Epithelioid hemangioendothelioma: a case report.

BACKGROUND: Epithelioid hemangioendothelioma is a rare tumor of vascular origin with nonspecific clinical and radiologic presentation. Cytologic findings described in the few case reports are variable. CASE: We describe a rare case of unifocal, hepatic hemangioendothelioma in a 47-year-old woman; a broad differential diagnosis of malignant neoplasm was considered during on-site evaluation of fine needle aspiration (FNA); diagnosis was made on subsequent core biopsy. To better describe the cytologic findings, FNA was performed on the resected tumor. The cytologic feature of this tumor, comparison with histol ogy findings and the differential diag nosis are discussed in detail. CONCLUSION: A correct diagnosis of hepatic epithelioid hemangioendothelioma can be rendered in cytology when an adequate specimen is obtained. The smears are characterized by a discohesive population of atypical cells in a clean background, fragments of metachromatic stroma, scattered benign hepatocytes and bile duct epithelium. The atypical cells are polygonal with abundant, dense cytoplasm and occasional tailing. On careful review, a few cells with a sharp, punched out intracytoplasmic lumen can be seen. The nuclei are round to reniform, with fine chromatin and occasionally prominent nucleoli. Sharply defined intranuclear cytoplasmic inclusions are seen in many cells, better appreciated in Papanicolaou-stained smears.

Late postpartum eclampsia: report of two cases managed by uterine curettage and review of the literature.

The purpose of this study was describe two patients with rapid recovery of refractory late postpartum eclampsia (LPPE) following uterine curettage, and to evaluate the literature about supportive evidence for such a management in LPPE. A detailed literature search was performed focusing on studies reporting the clinical presentation, laboratory workup, imaging, and management of LPPE. Mean reported onset of LPPE was on postpartum day 7.0 +/- 2.9. Only 35.3% had a history of preeclampsia: these had earlier onset of seizures compared with the subjects without history of preeclampsia (4.3 +/- 1.4 versus 7.6 +/- 2.9 days; p < 0.005). Onset of seizure was correlated with systolic blood pressure (Pearson's r = 0.34; p < 0.05). Major associated symptoms were headaches (71.4%), visual changes (46.0%), and nausea/vomiting (22.2%); 67.5% of patients were proteinuric. The remaining laboratory tests were usually normal. Among the patients with a normal head computed tomography, magnetic resonance imaging identified additional abnormalities in 53.8% (seven of 13). A total of 69.7% of patients developed multiple seizure episodes, some of these occurred while the patient was receiving magnesium sulfate treatment; 82.5% of patients underwent magnesium therapy and approximately half of those patients required multiple antiseizure drugs. The number of seizures was only correlated with the diastolic blood pressure (Pearson's r = 0.52; p < 0.01). Even remote from delivery, headaches, visual change, and nausea/vomiting are important symptoms of LPPE. Hypertension and/or proteinuria are important diagnostic findings. LPPE is often characterized by refractory seizures and controlling the diastolic blood pressure is important. Patients presented in our case report showed no seizures after uterine curettage. This potential useful management for LPPE requires additional investigation.

Extra-oral plasmablastic lymphoma: report of a case and review of literature.

Plasmablastic lymphoma (PBL) of the oral cavity is classified as one subtype of diffuse large B-cell lymphoma that is most commonly seen in patients with human immunodeficiency virus infection. We report a rare case of PBL in the anal canal of a 33-year-old man with human immunodeficiency virus infection. The lymphoma cells were positive for CD138 and weakly positive for CD79a. In addition, these cells were also positive for CD10. The neoplastic cells were positive for Epstein-Barr virus and negative for human herpes virus 8. Review of the English medical literature revealed many more cases of extra-oral PBL. We propose that the term plasmablastic lymphoma of the oral cavity in World Health Organization classification be revised to simply plasmablastic lymphoma, which would include both oral and extra-oral PBLs, and the term to define the primary site of the lymphoma (ie, oral cavity) be dropped from the terminology used in World Health Organization classification.

Disordered pulmonary myofibroblast distribution and elastin expression in preterm infants with Ureaplasma urealyticum pneumonitis.

Respiratory colonization of preterm infants with Ureaplasma urealyticum is a significant risk factor for bronchopulmonary dysplasia, a chronic lung disease characterized by arrest of alveolar development, variable interstitial fibrosis, and disordered elastic fibers in the distal airspaces. As indicated in previous studies, moderate to severe fibrosis is a hallmark of pathology in the Ureaplasma-infected preterm lung. To further characterize the preterm lung's response to Ureaplasma, lung specimens from 4 gestational controls (GC), 12 other pneumonia and 5 Ureaplasma-infected infants were analyzed by immunohistochemistry for alpha-smooth muscle actin (alphaSMA) and transforming growth factor beta1 (TGFbeta1), Hart's elastin staining, and in situ hybridization for tropoelastin (TE) expression. Cells positive for alphaSMA were observed in thickened, extensive bundles surrounding terminal airspaces in Ureaplasma and other pneumonia cases compared to individual myofibroblasts in GC. The myofibroblast pattern correlated with the severity of fibrosis, but not duration of ventilation. Transforming growth factor beta1 immunostaining was primarily localized to alveolar macrophages and was increased in Ureaplasma more than in other pneumonia cases. Elastic fibers and TE-expressing cells were spatially limited to emerging septal tips in GC. In pneumonia cases, increased deposition of elastic fibers was observed surrounding terminal airspaces, but TE expression was similar to GC. In Ureaplasma specimens, accumulation of elastic fibers correlated with duration of ventilation, and TE expression was extensive throughout the walls of terminal airspaces. These findings suggest that Ureaplasma is associated with alveolar macrophage TGFbeta1 immunostaining and myofibroblast proliferation contributing to abnormal septation, interstitial fibrosis, and a prolonged and strong elastogenic response in the preterm lung.

Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants.

Recent evidence strongly implicates the inflammatory response to intrauterine infection in the pathogenesis of neonatal brain and lung injury. We hypothesized that lung and brain injury in preterm infants occurs during a common developmental window of vulnerability as the result of an inflammatory response in different compartments. To determine whether inflammatory markers in these compartments are associated with bronchopulmonary dysplasia (BPD) or cranial ultrasound (CUS) abnormalities in infants <33 wk gestation age (GA) and <1501 g birth weight, we analyzed placental pathology and serum and cerebrospinal fluid (CSF) IL-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations in 276 infants. Logistic regressions were performed stratified by GA. Histologic chorioamnionitis was significantly associated with BPD in infants /=17 pg/mL was associated with an abnormal CUS in infants >28 wk GA (OR 3.36, p = 0.023) but not /=6.5 pg/mL and TNF-alpha >/=3 pg/mL were associated with abnormal CUS in infants /=28 wk GA. These data suggest that in infants

Congenital fibrosarcoma with metastasis in a fetus.

It is well known that congenital or infantile fibrosarcoma has a much less aggressive behavior than fibrosarcoma in adults, and it rarely metastasizes. We report a case of congenital fibrosarcoma in a 26-wk-old fetus, the diagnosis of which was made by an in utero needle core biopsy. Metastatic tumors were identified at autopsy when the pregnancy was terminated 3 wk later. English literature of metastatic congenital fibrosarcoma was also reviewed.

The value of autopsy in pediatric cardiology and cardiovascular surgery.

Autopsy has been considered extremely helpful in determining the accuracy of the premorbid diagnosis. With recent advances in diagnostic imaging, the value of the autopsy has been called into question. The aim of this study was to assess the value of the pediatric autopsy in the current era of advanced diagnostic technology and sophisticated surgical intervention for congenital heart disease (CHD) and also to determine the autopsy's potential impact on clinical management. We compared the data from the postmortem examination of 29 children with CHD with the data obtained before death and evaluated for the accuracy of the diagnosis of the cardiac anatomy as well as the cause of death. The diagnosis of the anatomy was confirmed in 13 cases (45%), additional cardiovascular abnormalities with potential clinical impact were found in 11 cases (38%), and additional abnormalities without clinical impact were found in 5 cases (17%). The cause of death was confirmed in 15 cases (52%), determined by autopsy in 12 cases (41%), and uncertain in 2 cases (7%). We conclude that the pediatric autopsy continues to provide clinically relevant information with a potential impact on patient management and to reveal unexpected causes of death in a significant proportion of patients with CHD.

Choledochal cysts and multilocular cysts of the pancreas.

Choledochal cyst is a rare congenital anomaly of the biliary system that may be associated with other abnormalities of the hepatobiliary tract. We report a case of an 11-year-old boy in whom the preoperative evaluation revealed a choledochal cyst and intraoperative cholangiopancreatography showed a cystic mass in the pancreas. Examination of the choledocho-pancreatico-duodenectomy specimen showed a multilocular cyst in the pancreas in addition to a segmental dilation of the common bile duct. The findings in our case adds pancreatic cyst to the spectrum of abnormalities associated with choledochal cyst and may also support the theory that choledochal cyst is the predominant abnormality in a widespread spectrum of the pancreatobiliary duct dysplasia.

Mycobacterium avium complex-associated cholecystitis in an HIV-infected woman.

Mycobacterium avium complex (MAC) is commonly associated with fever, fatigue, nausea, diarrhea, and cytopenias related to invasion of the intestine and bone marrow. Infection and clinical disease has been reported in other organs as well. We report the first case of cholecystitis associated with MAC infection of the gallbladder.

Discrepancy in pathologic diagnosis of placental lesions.

CONTEXT: Placentas are routinely examined by surgical pathologists, but peer review of placental diagnosis is rarely performed. OBJECTIVE: To determine the frequency of discrepant placental diagnosis between general surgical pathologists and a pediatric pathologist. DESIGN: One hundred fourteen placentas from infants with intrauterine growth restriction (IUGR) and 170 placentas from infants appropriate for gestational age (AGA) were reviewed for 10 lesion types using standardized criteria. The review diagnosis was compared with original reports. RESULTS: The review identified 333 lesions, 168 in the IUGR group and 165 in AGA group. Discrepant diagnosis occurred in 137 lesions (41.1%). There was no significant difference in the frequency of discrepant diagnosis between the IUGR (44.7%) and AGA groups (37.6%) (P >.05). Most discrepancies (92.7%) were due to underdiagnosis (identified on review but not mentioned in original diagnosis), but a few (7.3%) were due to misdiagnosis (mentioned in original report but disagreed on review). The common underdiagnoses with their corresponding rates were as follows: hemorrhagic endovasculitis (84.6%), fetal thrombotic vasculopathy (75%), massive perivillous fibrin deposition (68.4%), maternal floor infarction (66.7%), retroplacental hemorrhage (60.6%), intervillous thrombus (57.1%), decidual angiopathy (33.3%), placental infarction (25.4%), acute chorioamnionitis (22.7%), and chronic villitis (21.7%). Misdiagnosis was found in 10 cases: 5 cases of infarction (review diagnosis was perivillous fibrin deposits in 4, intervillous thrombus in 1), 3 cases of acute chorioamnionitis, and 2 cases of decidual angiopathy. Among the 8 general surgical pathologists involved, the frequency of discrepant diagnosis ranged from 31.5% to 58.6% (P >.05). The intraobserver discrepancy rate for the reviewer was 4.8%, significantly lower than the discrepancy rate for the 8 general surgical pathologists. CONCLUSION: It is common for general surgical pathologists not to recognize placental lesions, which may have clinical significance. Awareness of this deficiency, standardization of diagnostic criteria, and increased knowledge in placental pathology may improve the quality of diagnosis in this area.

Lung pathology in premature infants with Ureaplasma urealyticum infection.

Respiratory tract colonization with Ureaplasma urealyticum in preterm infants has been associated with a higher incidence of pneumonia, severe respiratory failure, bronchopulmonary dysplasia (BPD), and death. In this report, we characterize the lung pathology and expression of tumor necrosis factor-alpha (TNF-alpha) associated with U. urealyticum pneumonia in very low-birth weight infants (VLBW; < or =1500 g). Lung pathology of archived autopsy specimens was retrospectively reviewed in three groups of VLBW infants: 5 gestational controls who died from nonpulmonary causes, 13 infants with pneumonia who were culture and/or PCR negative for U. urealyticum, and 5 infants with pulmonary disease and positive for U. urealyticum by tracheal aspirate and/or lung tissue culture or polymerase chain reaction (PCR). Presence and extent of alveolar macrophages and neutrophils, as well as interstitial lymphocytic infiltration and fibrosis were evaluated. PCR was performed on formalin-fixed, paraffin-embedded lung sections. Additional sections were immunostained for TNF-alpha. The peripheral total white blood cell counts and absolute neutrophil counts were three-fold higher in infants with U. urealyticum pneumonia than cell counts in infants infected with other organisms. There was a trend toward a predominance of neutrophils in alveoli of non- Ureaplasma pneumonia infants, but a trend toward a predominance of alveolar macrophages in U. urealyticum-infected infants. The most striking finding was the presence of increased interstitial fibrosis in all Ureaplasma-infected infants. TNF-alpha immunoreactive cell density was very low in the gestational controls, but increased in both pneumonia groups. We conclude that persistent lung U. urealyticum infection may contribute to chronic inflammation and early fibrosis in the preterm lung.