Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing.

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7hi versus IRF7lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7lo children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms (p = 0.011) and nearly three times as long for cough (p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold (p = 0.018), and time to recurrence was shorter (p = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes.

Management and survival of patients with FIGO high-risk gestational trophoblastic neoplasia: the U.K. experience, 1995-2010.

OBJECTIVE: To present survival rates of high-risk gestational trophoblastic neoplasia (GTN) (FIGO score > 7) patients treated between 1995 and 2010 in the U.K. Death due to GTN is largely confined to patients with high-risk disease. In the U.K. a national system ensures that all patients are treated at only 2 specialist centers: Charing Cross Hospital (CXH) in London and Weston Park Hospital (WPH) in Sheffield. STUDY DESIGN: A total of 196 high-risk patients were identified using the CXH and WPH GTN databases, based on the risk score at the time of presentation. RESULTS: In all, 140 CXH and 56 WPH high-risk patients were treated with EMA/CO (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine) and MEA (methotrexate, etoposide, actinomycin D), respectively. The FIGO score at presentation ranged from 6-23. Eight patients (7from WPH and 1 from CXH) who were treated prior to 2002 as high-risk based on their pre-2002 scoring scored a 6 using FIGO 2002. Two (1%) patients died within 4 weeks of starting treatment (early death), 12 (6%) relapsed, and 9 patients subsequently died due to drug resistance. The overall survival was 94%, with a median follow-up of 4.69 years. CONCLUSION: In the context of a national trophoblastic disease service, patients with high-risk GTN have an excellent prognosis with EMA/CO or MEA.

A conservative approach in persistent low-level elevation of serum beta-human chorionic gonadotropin following chemotherapy for gestational trophoblastic neoplasia.

OBJECTIVE: To question whether patients with persistent low-level elevation of beta-human chorionic gonadotropin (beta-hCG) following chemotherapy for gestational trophoblastic neoplasia can be managed conservatively. STUDY DESIGN: A retrospective study of all patients requiring chemotherapy for gestational trophoblastic neoplasia (GTN), treated in Sheffield from 1994 to 2007, evaluating those for whom a clinical decision was made to stop chemotherapy when the serum beta-hCG level remained elevated. RESULTS: Of the 350 patients requiring chemotherapy, 17 had persistently elevated beta-hCG at the time chemotherapy was stopped. The range of elevation was 4-43 IU/L (mean, 7.5) and duration 3-32 weeks (mean, 10.7). In 16 patients, beta-hCG became undetectable and further treatment was not required; in only 1 patient did the level suddenly become elevated (from 12 to 77 IU/L after 3 months), requiring further and curative chemotherapy. CONCLUSION: These results suggest that a conservative but watchful approach can be taken for persistent low-level elevation (up to 40 IU/L) of serum beta-hCG following chemotherapy.

Low-risk gestational trophoblastic neoplasia: evaluating the need for initial inpatient treatment during low-dose methotrexate chemotherapy.

OBJECTIVE: To evaluate the need for initial inpatient treatment for patients being treated with low-dose intramuscular methotrexate for low-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Clinical notes of all patients treated with low-dose intramuscular methotrexate for low-risk GTN were analyzed and side effects noted. RESULTS: There were no episodes of increased uterine bleeding requiring extra medical intervention. There were 7 cases of chest pain; none required a change from methotrexate chemotherapy. CONCLUSION: Patients being treated with low-dose intramuscular methotrexate for low-risk GTN do not need to be treated routinely in the hospital for their first treatment cycle.

Persistent gestational trophoblastic neoplasia after partial hydatidiform mole incidence and outcome.

OBJECTIVE: To report the Sheffield experience with persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform mole (PHM) and to review worldwide experience. METHODS: All PHMs registered at the Sheffield Trophoblast Centre between 1991 and 2004 were included in this retrospective study. Any case of PHM leading to persistent GTN was reviewed centrally by an expert gynecologic pathologist. Clinical features, treatment and outcome were recorded. RESULTS: During the 14-year study period 3189 PHMs were registered. Forty-one developed persistent GTN. Central histopathology review confirmed PHM in only 14 cases (0.91% of all those registered). Twelve scored low and 2 high risk according to International Federation of Gynecology and Obstetrics 2000 criteria. During the same period, 271 cases of persistent GTN originally registered as complete hydatidiform mole were reviewed; 3 were found to be PHMs (2 low, 1 high risk). In all, 15 of 17 persistent PHMs required chemotherapy. CONCLUSION: Persistent GTN requiring chemotherapy can occasionally occur after PHM; surveillance of all cases continues to be recommended.

Twin mole and viable fetus: The case for misdiagnosis.

OBJECTIVE: To report the Sheffield Trophoblast Centre experience of twin molar gestations and review this in the light of international experience. CASE: Thirty patients with possible twin molar gestations were registered from 1986 to 2004 (during which period 7,200 cases of mole were seen). The accuracy of suspected clinical and histologic diagnoses was investigated. RESULTS: In 10 cases twin mole/fetus had been suspected clinically but not confirmed when products of conception were examined. In 3 of these cases the pregnancy had been therapeutically terminated because of clinical (ultrasound) suspicion of coexisting molar pregnancy. In the 19 cases where twin mole/fetus was suspected, central histopathology review was possible in 14 cases. Only 7 were confirmed. In 2 further cases twin molar gestation was diagnosed on specimens referred for central review as partial mole singleton pregnancies. For confirmed cases the pregnancy outcome was term delivery in 5 cases and miscarriage in 4. CONCLUSION: Clinical and histopathologic diagnosis of twin molar pregnancies is inaccurate in many suspected cases; therefore, a second (expert) opinion should be sought. When the diagnosis is accurate, maternal and fetal complications are common. However, in suspected cases the pregnancy may be allowed to proceed, with caution, if the mother wishes.