Folate Receptor Alpha Is Preferentially Expressed in the Carcinoma Component of Endometrial Carcinosarcomas: A Potential Target for Adjuvant Therapy.

Carcinosarcomas (CSs) of the endometrium are biphasic malignancies, composed of high-grade carcinomatous and sarcomatous components. Surgical stage and pathologic characteristics are the most important prognostic findings, with a 5-yr survival of 15% to 30% in advance stage disease. Folate receptor alpha (FRA) overexpression has been observed in endometrial carcinomas and not yet studied in CSs. This study evaluates semiquantitative expression of FRA in both carcinomatous and sarcomatous components of CSs on whole tissue sections. Immunohistochemistry for FRA expression was performed and extent and intensity of staining were recorded for each case for both histologic components. A total of 46 cases were stained for FRA. The majority of these (40/46, 87%) showed FRA staining at variable intensity in the carcinomatous component, stronger in serous carcinomas and high-grade endometrioid, while only a small subset of tumors demonstrated weak staining in the sarcomatous component (2/46, 4.35%). CS is known to be associated with poor prognosis and adjuvant therapy is recommended even in low stage disease. Serous and high-grade endometrioid carcinomas are the most common carcinomatous components of CSs and are known to show consistently high FRA expression. Folate plays a role in tumor cell migration and loss of cellular adhesion, which are key steps in epithelial-mesenchymal transition, the process by which CS develops from carcinoma cells. Our study shows expression of FRA in the carcinomatous component of almost all CS cases (87%), further favoring FRA as a target for adjuvant treatment. While expression of FRA in the sarcomatous component was rarely observed, the carcinomatous component being associated with metastatic potential underscores the importance of anti-FRA therapy for systemic disease control.

Comparisons of Depression, Sexual Function, and Quality of Life Between Women With Gynecological Cancers and Race-Matched Healthy Controls.

BACKGROUND: Although higher incidence and mortality of gynecological cancer (GynCa) are documented in black compared with white women, few studies have documented quality of life (QOL) or healthy control comparisons. OBJECTIVE: This study compared depression, sexual function, and QOL between patients with GynCa and race-matched healthy controls. METHODS: Patients with GynCa and healthy controls completed the Patient Health Questionnaire-9, Female Sexual Function Index, and Functional Assessment of Cancer Therapy-General measures at baseline; GynCa patients were assessed again at 6 months post-radiation therapy (RT). RESULTS: Analyses included 84 participants (51% white, 49% black), including 28 GynCa patients and 56 controls with similar marital status. Compared with healthy controls, patients were younger, had a higher body mass index, and had more depression (P = .01); 82% of the patients and 71% of the healthy controls met criteria for sexual dysfunction at baseline (P = .29). Patients pre-RT had greater sexual dysfunction and lower QOL (P = .001) than controls did; patients at 6-month post-RT showed improved sexual function scores compared with pre-RT, with similar results to controls. White GynCa patients reported less sexual desire (P = .02), more pain (P = .05), and lower total Female Sexual Function Index scores (P = .01) than did black GynCa patients. Both black and white GynCa patients reported lower total QOL than their race-matched controls did (P = .07 and P = .002). CONCLUSIONS: Women with GynCa reported more depression and lower QOL than did healthy controls pre-RT. Among GynCa patients, white women had more sexual dysfunction than black women did. IMPLICATIONS FOR PRACTICE: The differences in sexual dysfunction between white and black women with GynCa suggest developing guidelines directing routine sexual assessment and rehabilitation in women treated for GynCa.

Folate Receptor Alpha Expression in Platinum Resistant/Refractory Ovarian Carcinomas and Primary Endocervical Adenocarcinomas.

INTRODUCTION: Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used. Recently, folate along with its receptor alpha (FRA) has been studied as a potential target in gynecologic malignancy. The objective of this study was to elucidate FRA expression in chemotherapy resistant ovarian cancer and primary EAC. METHODS: FRA expression was evaluated in tissue samples in an epithelial ovarian tumor microarray and 2 study groups: platinum resistant ovarian cancer and primary EAC. Staining intensity was analyzed with a semiquantitative staining algorithm. RESULTS: FRA expression was positive in 32 of 40 (80%) ovarian tumors in the control group. In the platinum resistant ovarian cancer group, FRA was expressed in all 30 samples with moderate to strong staining. None of the EAC samples stained positive for FRA expression. CONCLUSIONS: FRA expression occurs frequently in epithelial ovarian cancer. Our data supports that FRA expressions are maintained after chemotherapy treatment. Folate targeted therapies may be most useful in patients with chemotherapy resistant disease based on high levels of FRA expression in these tumors. There is likely no benefit to folate therapy as an adjuvant treatment in EAC.

Early Detection of Ovarian Cancer using the Risk of Ovarian Cancer Algorithm with Frequent CA125 Testing in Women at Increased Familial Risk - Combined Results from Two Screening Trials.

Purpose: Women at familial/genetic ovarian cancer risk often undergo screening despite unproven efficacy. Research suggests each woman has her own CA125 baseline; significant increases above this level may identify cancers earlier than standard 6- to 12-monthly CA125 > 35 U/mL.Experimental Design: Data from prospective Cancer Genetics Network and Gynecologic Oncology Group trials, which screened 3,692 women (13,080 woman-screening years) with a strong breast/ovarian cancer family history or BRCA1/2 mutations, were combined to assess a novel screening strategy. Specifically, serum CA125 q3 months, evaluated using a risk of ovarian cancer algorithm (ROCA), detected significant increases above each subject's baseline, which triggered transvaginal ultrasound. Specificity and positive predictive value (PPV) were compared with levels derived from general population screening (specificity 90%, PPV 10%), and stage-at-detection was compared with historical high-risk controls.Results: Specificity for ultrasound referral was 92% versus 90% (P = 0.0001), and PPV was 4.6% versus 10% (P > 0.10). Eighteen of 19 malignant ovarian neoplasms [prevalent = 4, incident = 6, risk-reducing salpingo-oophorectomy (RRSO) = 9] were detected via screening or RRSO. Among incident cases (which best reflect long-term screening performance), three of six invasive cancers were early-stage (I/II; 50% vs. 10% historical BRCA1 controls; P = 0.016). Six of nine RRSO-related cases were stage I. ROCA flagged three of six (50%) incident cases before CA125 exceeded 35 U/mL. Eight of nine patients with stages 0/I/II ovarian cancer were alive at last follow-up (median 6 years).Conclusions: For screened women at familial/genetic ovarian cancer risk, ROCA q3 months had better early-stage sensitivity at high specificity, and low yet possibly acceptable PPV compared with CA125 > 35 U/mL q6/q12 months, warranting further larger cohort evaluation. Clin Cancer Res; 23(14); 3628-37. ©2017 AACR.

Use of Unsolicited Patient Observations to Identify Surgeons With Increased Risk for Postoperative Complications.

Importance: Unsolicited patient observations are associated with risk of medical malpractice claims. Because lawsuits may be triggered by an unexpected adverse outcome superimposed on a strained patient-physician relationship, a question remains as to whether behaviors that generate patient dissatisfaction might also contribute to the genesis of adverse outcomes themselves. Objective: To examine whether patients of surgeons with a history of higher numbers of unsolicited patient observations are at greater risk for postoperative complications than patients whose surgeons generate fewer such unsolicited patient observations. Design, Setting, and Participants: This retrospective cohort study used data from 7 academic medical centers participating in the National Surgical Quality Improvement Program and the Vanderbilt Patient Advocacy Reporting System from January 1, 2011, to December 31, 2013. Patients older than 18 years included in the National Surgical Quality Improvement Program who underwent inpatient or outpatient operations at 1 of the participating sites during the study period were included. Patients were excluded if the attending surgeon had less than 24 months of data in the Vanderbilt Patient Advocacy Reporting System preceding the date of the operation. Data analysis was conducted from June 1, 2015, to October 20, 2016. Exposures: Unsolicited patient observations for the patient's surgeon in the 24 months preceding the date of the operation. Main Outcomes and Measures: Postoperative surgical or medical complications as defined by the National Surgical Quality Improvement Program within 30 days of the operation of interest. Results: Among the 32 125 patients in the cohort (13 230 men, 18 895 women; mean [SD] age, 55.8 [15.8] years), 3501 (10.9%) experienced a complication, including 1754 (5.5%) surgical and 2422 (7.5%) medical complications. Prior unsolicited patient observations for a surgeon were significantly associated with the risk of a patient having any complication (odds ratio, 1.0063; 95% CI, 1.0004-1.0123; P = .03), any surgical complication (odds ratio, 1.0104; 95% CI, 1.0022-1.0186; P = .01), any medical complication (odds ratio, 1.0079; 95% CI, 1.0009-1.0148; P = .03), and being readmitted (odds ratio, 1.0088, 95% CI, 1.0024-1.0151; P = .007). The adjusted rate of complications was 13.9% higher for patients whose surgeon was in the highest quartile of unsolicited patient observations compared with patients whose surgeon was in the lowest quartile. Conclusions and Relevance: Patients whose surgeons have large numbers of unsolicited patient observations in the 24 months prior to the patient's operation are at increased risk of surgical and medical complications. Efforts to promote patient safety and address risk of malpractice claims should continue to focus on surgeons' ability to communicate respectfully and effectively with patients and other medical professionals.

Margins for cervical and vulvar cancer.

Surgery is the primary treatment for vulvar cancer as well as early-stage carcinoma of the cervix. This article reviews the significance of margin status after surgery on overall survival, need for further surgical intervention, and role for possible adjuvant therapy. It summarizes the abundant literature on margin status in vulvar cancer and highlights the need for further investigation on the prognostic significance of margins in cervical cancer. In addition, it reviews other important operative considerations.

Successful treatment of an adolescent with locally advanced cervicovaginal clear cell adenocarcinoma using definitive chemotherapy and radiotherapy.

Pediatric cervicovaginal clear cell adenocarcinoma (CCA) is rare but continues to occur in the postdiethylstilbestrol era. Ideal management is unclear. We report a case of locally advanced, node-negative CCA in a 14-year-old girl without a history of diethylstilbestrol exposure. The patient's disease was FIGO stage IIIA, involving the cervix, vagina, and parametrium. She was treated with concurrent cisplatin and external beam radiation, followed by interstitial low-dose rate brachytherapy. The patient has no evidence of disease after 2 years of follow-up. These findings support the use of definitive chemoradiation as a treatment option for adolescents with locally advanced CCA.

Is the incidence of heparin-induced thrombocytopenia affected by the increased use of heparin for VTE prophylaxis?

BACKGROUND: The increased exposure to heparin products for thromboprophylaxis against VTE in hospitalized patients raises concerns for an increase in the incidence of heparin-induced thrombocytopenia(HIT). METHODS: We analyzed, among 90,875 patients exposed to heparin products between 2005 and 2009, the number of hematologic consultations for thrombocytopenia, requests for heparin induced antibodies by enzyme-linked immunosorbent assay, and cases given a diagnosis of HIT by the hematology consult service. RESULTS: We observed that despite a doubling in the number of patients receiving pharmacoprophylaxis with heparin, there was no significant increase in the number of consultations for thrombocytopenia,the number of requests for HIT tests, the number of positive HIT test results, or the number of HIT diagnoses. The number of cases of HIT was low and represented < 0.1% of patients exposed to heparin. CONCLUSIONS: We conclude that concerns about HIT should not be a limiting factor for the systematic implementation of heparin-based VTE prophylaxis.

Methicillin-resistant Staphylococcus aureus colonization in a pediatric intensive care unit: risk factors.

BACKGROUND: Both methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae have become significant causes of disease, both in health care and community settings. OBJECTIVES: All patients admitted to our pediatric intensive care unit (PICU) currently had a rapid test for methicillin-resistant Staphylococcus aureus (MRSA) performed as per hospital guidelines. This study looked at risk factors for colonization. METHODS: Nasal swabs were tested for MRSA on all admissions to the PICU from May 2008 to September 2009 using polymerase chain reaction as per hospital guidelines. All patients enrolled were placed in either a MRSA-positive or a MRSA-negative group, which were compared with each other. Risk factors were assessed from a questionnaire and the resident history. RESULTS: The prevalence of MRSA colonization in our study was 4.5%. Six hundred sixty-six patients were negative for MRSA, and 31 were positive. Patients in the MRSA colonization group were younger, more likely had family (household members) employed in medicine, and were more likely hospitalized or had undergone surgery within the previous 12 months. Prolonged neonatal intensive care unit stay (>1 week) was associated with MRSA colonization (P < .001). CONCLUSION: The percentage of patients positive for MRSA admitted to a PICU is low. Recent exposure to the health care system, especially a stay in the neonatal intensive care unit, is associated with an increased risk of colonization.

Age-group differences in human papillomavirus types and cofactors for cervical intraepithelial neoplasia 3 among women referred to colposcopy.

BACKGROUND: Recommendations for high-risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged <30. Here, we assess age-group differences in HPV types and other risk factors for cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) versus CIN0-2 in women from four colposcopy clinics. METHODS: Women ages 18 to 69 (n = 1,658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was done on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group. RESULTS: After 2 years of follow-up, we identified 178 CIN3+, 1,305 CIN0-2, and 175 indeterminate outcomes. Nonvaccine HR-HPV types were only associated with CIN3+ among women ≥ 30 (RR = 2.3, 95% CI: 1.5-3.4; <30: RR = 0.9). Among all HR-HPV-positive women, adjusting for age, significant cofactors for CIN3+ included current smoking (RR = 1.5), former smoking (RR = 1.8), regular Pap screening (RR = 0.7), current regular condom use (RR = 0.5), and parity ≥ 5 (RR = 1.6, P(trend) for increasing parity = 0.07). However, the parity association differed by age group (≥ 30: RR = 1.8, P(trend) = 0.008; <30: RR = 0.9; P(trend) =.55). CONCLUSION: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection. IMPACT: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups.

Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status.

Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women).

Haemophilus influenzae type B meningitis in a previously healthy child.

Vaccines have proven successful in virtually eradicating certain infectious diseases that typically attack the pediatric population. Since 1988, when the conjugate vaccine was introduced, the incidence of invasive Haemophilus influenzae type B disease was reduced dramatically. However, immunization rates have decreased in certain parts of the country because of a combination of vaccine shortage and widespread parental perception that vaccines are harmful. We present the case of a previous healthy child, who ultimately succumbed to H. influenzae type B meningitis where multiple factors were likely responsible for his acquisition of the disease.

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study.

PURPOSE: This study evaluated efficacy of single-agent trastuzumab against advanced or recurrent HER2-positive endometrial carcinoma (EC), and explored predictors for HER2 amplification. PATIENTS AND METHODS: Eligible patients had measurable stage III, IV, or recurrent EC. There was no limit on prior therapy although total prior doxorubicin dose was limited to 320 mg/m(2). Tumors were required to have HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (FISH HER2/CEP 17 ratio >2.0). Trastuzumab was administered intravenously at a dose of 4 mg/kg in week 1, then 2 mg/kg weekly until disease progression. The primary endpoint was tumor response. RESULTS: Of the 286 tumors centrally screened by LabCorp, 33 (11.5%) were HER2-amplified. Three of 8 clear (38%) cell carcinomas and 7 of 25 serous carcinomas (28%) screened exhibited HER2 amplification compared with 7% (2/29) of endometrioid adenocarcinomas. HER2 overexpression was correlated with HER2 amplification (r=0.459; p<0.0001). Thirty-four women were enrolled; 1 was excluded (refused treatment); and 18 had tumors with known HER2 amplification. No major tumor responses were observed. Twelve women experienced stable disease, 18 had increasing disease, and 3 were indeterminate for tumor response. Neither HER2 overexpression nor HER2 amplification appeared to be associated with progression-free survival or overall survival. CONCLUSION: Trastuzumab as a single agent did not demonstrate activity against endometrial carcinomas with HER2 overexpression or HER2 amplification, although full planned accrual of women with HER2 amplified tumors was not achieved due to slow recruitment. Serous and clear cell endometrial carcinomas appear to be more likely to demonstrate HER2 amplification.

Lymphadenectomy for patients with cervical cancer: is it of value?

INTRODUCTION: Discovery of positive lymph nodes (LNs) in patients with cervix cancer is important prognostically, may direct adjuvant therapy, and may have therapeutic benefit. The purpose of this Surveillance Epidemiology and End Results (SEER) analysis was to assess the value of lymphadenectomy (LND) in patients with cervical cancer. METHODS: The 17-registry SEER database was searched for patients treated for cervical cancer between 1988 and 1998. Observed survival (OS) and expected survival (ES) were reported with a minimum of 5-year follow-up. Chi-square analysis and log-rank test were used to compare OS and ES. RESULTS: Between 1988 and 1998, 4,059 of 12,882 patients underwent LND for cervical cancer and were registered. By stage, 2,653 of 7,621 stage I, 341 of 2,042 stage II, 814 of 1,986 stage III, 251 of 1,233 stage IV, and 28 of 226 stage IVA patients underwent LND. Of these, 778 stage III and 210 stage IV patients had a +LN. Patients who underwent LND had improved OS (P = 0.001). OS was significantly increased for each stage after LND. OS increased based on number of nodes resected. OS increased up to 15 nodes resected (P = 0.01). CONCLUSION: This SEER analysis of 12,882 patients suggests that LND benefited patients with cervical cancer and OS was improved.

Proteomics-based approach to elucidate the mechanism of antitumor effect of curcumin in cervical cancer.

Cervical cancer is the second leading cause of cancer death for women in the world. A potential target for preventing and treating cervical cancer is cyclooxygenase-2 (cox-2). Curcumin is an anti-inflammatory agent that is known to have anti-cox-2 activity. In this study we examined the expression of cox-2 in cervical cancer and its precursors by immunohistochemistry. The effect of curcumin in inhibiting cervical cancer cells was determined via 2-dimensional gel electrophoresis, data analysis, and ingenuity pathway analysis. No significant differences in the expression of cox-2 in squamous cell carcinoma, and carcinoma in situ were observed. However, there was a statistically significant difference in the expression of cox-2 in adenocarcinoma in comparison to normal (p value=0.01) and squamous cell carcinoma (p value=0.02) tissues. Proteins associated with cancer and cell cycle were significantly altered in cultured cells. Curcumin may have antitumor effect in cervical cancer.

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

PURPOSE: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. METHODS AND MATERIALS: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. RESULTS: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). CONCLUSION: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.

Hypoalbuminemia in critically ill children.

OBJECTIVE: To evaluate whether hypoalbuminemia on admission is a predictor of adverse outcome in critically ill children. DESIGN: Retrospective medical record review. SETTING: A 14-bed medical and surgical pediatric intensive care unit (PICU). PARTICIPANTS: All patients admitted to the PICU from January 1, 1998, through December 31, 2000, under the care of the PICU team or trauma service and whose albumin level was measured were potential subjects. One hundred fifty-five patients were divided into 4 groups on the basis of age and appropriate albumin level for that age group. The groups of hypoalbuminemic patients were combined (hypoalbuminemia group) and compared with the combined group of patients with albumin levels above the reference cutoff (normal albumin level group). EXPOSURE: Serum albumin level. MAIN OUTCOME MEASURES: Length of PICU and hospital stays, receipt and length of ventilatory support, survival, pediatric risk of mortality score, mortality risk, and number of organ failures. RESULTS: Controlling for mortality risk, the hypoalbuminemia group had a longer average stay in the PICU (8.08 vs 4.41 days; 95% confidence interval [CI] for difference, 1.02-6.32) and the hospital (11.36 vs 6.63 days; 95% CI for difference, 1.31-8.16) than did the normal albumin level group. The hypoalbuminemia group had a lower survival rate (odds ratio, 0.10; 95% CI, 0.02-0.46) and a higher number of organ failures (1.38 vs 0.65; 95% CI for difference, 0.40-1.04). CONCLUSION: Admission hypoalbuminemia is a significant marker of morbidity and mortality in critically ill children.

Evaluation of RNA markers for early detection of cervical neoplasia in exfoliated cervical cells.

Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (C(t)) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators.