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B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting the B-cell receptor pathway and anti-apoptotic proteins alone or in combination have revolutionized the management of CLL, yet combination therapy carries significant toxicity and CLL remains incurable due to residual disease and relapse. Single-molecule inhibitors that can target multiple disease-driving factors are thus an attractive approach to combat both drug resistance and combination-therapy-related toxicities. We demonstrate that SRX3305, a novel small-molecule BTK/PI3K/BRD4 inhibitor that targets three distinctive facets of CLL biology, attenuates CLL cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 also inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals, including stromal cell contact. Furthermore, SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13, which are major chemokines involved in CLL cell homing and retention in microenvironment niches. Importantly, SRX3305 maintains its anti-tumor effects in ibrutinib-resistant CLL cells. Collectively, this study establishes the preclinical efficacy of SRX3305 in CLL, providing significant rationale for its development as a therapeutic agent for CLL and related disorders.

During the COVID-19 pandemic, academic health centers suspended clinical clerkships for students. A need emerged for innovative virtual curricula to continue fostering professional competencies. In March 2020, a multidisciplinary team from the University of Nebraska Medical Center had 2 weeks to create a course on the impact of infectious diseases that addressed the COVID-19 pandemic in real time for upper-level medical and physician assistant students. Content addressing social determinants of health, medical ethics, population health, service learning, health security, and emergency preparedness were interwoven throughout the course to emphasize critical roles during a pandemic. In total, 320 students were invited to complete the survey on knowledge gained and attitudes about the course objectives and materials and 139 responded (response rate 43%). Students documented over 8,000 total hours of service learning; many created nonprofit organizations, aligned their initiatives with health systems efforts, and partnered with community-based organizations. Thematic analysis of qualitative evaluations revealed that learners found the greatest value in the emphasis on social determinants of health, bioethics, and service learning. The use of predeveloped, asynchronous e-modules were widely noted as the least effective aspect of the course. The COVID-19 pandemic introduced substantial challenges in medical education but also provided trainees with an unprecedented opportunity to learn from real-world emergency preparedness and public health responses. The University of Nebraska Medical Center plans to create a health security elective that includes traditional competencies for emergency preparedness and interrogates the social and structural vulnerabilities that drive disproportionately worse outcomes among marginalized communities. With further evaluation, many components of the curriculum could be broadly scaled to meet the increasing need for more public health and health security medical education.

Objective The effect of body habitus for patients who require extracorporeal membrane oxygenation (ECMO) support has not been well-studied and may provide insight into patient survival and outcomes. We sought to determine if there is a correlation of body mass index (BMI) with ECMO outcomes. Methods A retrospective chart review was performed for patients who required any form of ECMO support at our institution between 2012 and 2016. Time variables (overall hospital length of stay, intensive care, and ventilator days), and outcomes variables (ability to wean from ECMO, extubation status, hospital survival, 30-day survival) were studied. Patients were divided into cohorts based on BMI. Descriptive statistics were used to summarize data. Spearman correlation, Fisher's exact test, and independent t-test were used to assess associations. Results A total of 231 patients required ECMO with a mean BMI of 29 (±6.47; BMI range, 17.6-57.9). The mean BMI did not differ based on type of support provided (veno-veno ECMO [VV] vs veno-arterial [VA]). There was no difference between BMI cohorts for length of stay, time in the intensive care unit (ICU), ability to wean from ECMO, hospital survival or 30-day survival. Raw BMI did not predict if or when patients were extubated. Conclusions Neither obesity classification nor BMI as a continuous variable affected any of the outcome variables. Respiratory outcomes including the ability to extubate and to remain ventilator-free were also independent of patient BMI. These data suggest that extremes of body habitus alone should not be used as an exclusion criteria for consideration of ECMO support.

Initial warfarin dosing and time in therapeutic range (TTR) are poorly characterized for early post-operative left ventricular assist device (LVAD) patients. This study evaluated TTR after LVAD implantation compared between patients receiving low-dose (3 mg) and high-dose (≥3 mg) warfarin. This single-center, retrospective analysis included 234 LVAD patients who received warfarin within 5 days of implantation. The primary outcome was TTR during the 5 days following first international normalized ratio (INR) ≥2 compared between low-dose and high-dose groups. Secondary outcomes were hospital and intensive care unit length of stay, time to first INR ≥2, TTR after first INR ≥2, and reinitiation of parenteral anticoagulation. No difference in TTR was detected between warfarin groups (57.2% vs. 62.7%, P = 0.13). Multivariable analysis did not detect any factors predictive of TTR during the primary outcome timeframe, but age and body mass index were associated with the warfarin dose. The low-dose group received a mean warfarin dose of 1.9 mg (±0.64 mg), and the high dose group received 4.34 mg (±1.38 mg). Cohort TTR during the primary outcome timeframe was 60.5% and 56.5% for hospitalization. The low-dose group had longer intensive care unit length of stay, shorter time to therapeutic INR, and more frequently reinitiated parenteral anticoagulation. Patients with recent LVAD implantation are complex and have diverse warfarin sensitivity factors, which did not allow for optimal warfarin dose detection, although half of all patients received doses between 2.04 mg and 4.33 mg. Individualized dosing should be used, adjusting for patient-specific factors such as age, body mass index, and drug interactions.

Long-term reinfection and mortality rates and clinical outcomes with sufficient subject numbers remain limited for patients undergoing two-stage exchange arthroplasty for chronic periprosthetic knee infections. The purpose of this study was to determine the long-term reinfection, complication, and mortality following reimplantation for two-stage exchange following knee arthroplasty.Retrospective review of 178 patients who underwent two-stage exchange knee arthroplasty for chronic PJI at three large tertiary referral institutions with an average of 6.63-year follow-up from reimplantation from 1990 to 2015. Rates of reinfection, mortality, and all-cause revision were calculated along with the cumulative incidence of reinfection with death as a competing factor. Risk factors for reinfection were determined using Cox multivariate regression analysis.Overall rate of infection eradication was 85.41%, with a mortality rate of 30.33%. Patients with minimum 5-year follow-up (n = 118, average 8.32 years) had an infection eradication rate of 88.98%, with a mortality rate of 33.05%.This is a large series with long-term follow-up evaluating outcomes of two-stage exchange knee arthroplasty resulting in adequate infection eradication and high mortality. Results were maintained at longer follow-up. This technique should be considered in patients with chronic PJI; however, realistic expectations regarding long-term outcomes must be discussed with patients.

INTRODUCTION: Rapid and accurate detection of the novel coronavirus using a nasopharyngeal specimen requires training for professionals who may have limited experience. To respond to the urgent need, an interprofessional team created a just-in-time (JIT) module to provide only what was needed, precisely when needed, and rapidly deployed training sessions to a large group of health professionals. METHODS: In April and May 2020, health professionals from the hospital, ambulatory clinics, and public health attended training. Procedural comfort/knowledge and perception of the training were assessed with pre-survey and post-survey. RESULTS: Comfort level in collecting a nasopharyngeal specimen among participating health professionals increased from 2.89 (n = 338) on the pre-survey to 4.51 (n = 300) on the postsurvey on a 5-point scale. Results revealed a significant difference (P < .01) between pre-post knowledge questions regarding the correct angle and depth of the swab to obtain an adequate sample from the nasopharynx. DISCUSSION: This study demonstrates that a JIT intervention can improve knowledge and comfort regarding the nasopharyngeal swab procedure. In preparation for the prevention and mitigation of future viral outbreaks (ie, coronavirus and influenza), educators should consider creating JIT skills training for health care professionals who may be deployed to assist in mass testing efforts.

OBJECTIVES: To determine the association of the use of the multiplex assay meningitis/encephalitis panel with clinical management of suspected meningitis. METHODS: A cross-sectional study was conducted with children 0 to 18 years of age who received a lumbar puncture within 48 hours of admission for an infectious workup. Patient demographic and presenting information, laboratory studies, and medication administration were collected. The primary measure was length of stay (LOS) with secondary measures: time on antibiotics, time to narrowing antibiotics, and acyclovir doses. LOS and antibiotic times were stratified for outcomes occurring before 36 hours. Logistic regression analysis was used to account for potential confounding factors associated with both the primary and secondary outcomes. A value of P < .05 was considered statistically significant. RESULTS: Meningitis panel use was associated with a higher likelihood of a patient LOS CONCLUSIONS: Use of the meningitis panel was associated with a decreased LOS, time to narrowing of antibiotics, and fewer acyclovir doses. This likely is a result of the rapid turnaround time as compared with cerebrospinal fluid cultures. Additional studies to examine the outcomes related to this change in management are warranted.

Perinatal inflammation adversely affects health. Therefore, aims of this IRB-approved study are: (1) compare inflammatory compounds within and between maternal and umbilical cord blood samples at the time of delivery, (2) assess relationships between inflammatory compounds in maternal and cord blood with birth characteristics/outcomes, and (3) assess relationships between blood and placental fat-soluble nutrients with blood levels of individual inflammatory compounds.Mother-infant dyads were enrolled (n = 152) for collection of birth data and biological samples of maternal blood, umbilical cord blood, and placental tissue. Nutrient levels included: lutein + zeaxanthin; lycopene; α-, β-carotene; β-cryptoxanthin; retinol; α-, γ-, δ-tocopherol. Inflammatory compounds included: tumor necrosis factor-α, superoxide dismutase, interleukins (IL) 1β, 2, 6, 8, 10.Median inflammatory compound levels were 1.2-2.3 times higher in cord vs. maternal blood, except IL2 (1.3 times lower). Multiple significant correlations existed between maternal vs. infant inflammatory compounds (range of r = 0.22-0.48). While relationships existed with blood nutrient levels, the most significant were identified in placenta where all nutrients (except δ-tocopherol) exhibited relationships with inflammatory compounds. Relationships between anti-inflammatory nutrients and proinflammatory compounds were primarily inverse.Inflammation is strongly correlated between mother-infant dyads. Fat-soluble nutrients have relationships with inflammatory compounds, suggesting nutrition is a modifiable factor.Mother and newborn inflammation status are strongly interrelated. Levels of fat-soluble nutrients in blood, but especially placenta, are associated with blood levels of proinflammatory and anti-inflammatory compounds in both mother and newborn infant. As fat-soluble nutrient levels are associated with blood inflammatory compounds, nutrition is a modifiable factor to modulate inflammation and improve perinatal outcomes.

Very low birth weight (VLBW) infants may be at risk for late-onset circulatory collapse (LCC) where otherwise stable infants develop hypotension resistant to vasoactive agents. The risk factors for LCC development are poorly defined, and it has been theorized that it may be in part due to withdrawal from exogenous prenatal steroids. The goal of this study was to define the clinical characteristics of LCC and investigate its association with antenatal steroid administration.This is a retrospective cohort study of infants born ≤1500 g. LCC was retrospectively diagnosed in infants requiring glucocorticoids for circulatory instability at1 week of life. Demographic and clinical characteristics were compared between groups using Mann-Whitney test.Three hundred and ten infants were included; 19 (6.1%) developed LCC. Infants with LCC were born at a median 4.6 weeks' lower gestation, 509 g lower birth weight than those without LCC. There was no difference in antenatal steroid delivery between the groups.LCC occurs in a distinct subset of VLBW infants, suggesting the need for monitoring in this high-risk population. Antenatal steroids did not significantly increase the risk of LCC development in this study.Late-onset circulatory collapse (LCC) is a life-threatening clinical entity occurring in around 6% in VLBW infants and is likely underdiagnosed in the United States. Targeting specific demographic characteristics such as birth weight (1000 g) and gestational age at birth (26 weeks) may allow for early identification of high-risk infants, allowing close monitoring and prompt treatment of LCC. No significant association was found between antenatal steroid administration and LCC development, suggesting that the theoretical risks of antenatal steroids on the fetal HPA axis does not outweigh the benefits of antenatal steroids in fetal lung maturity. To date, no studies characterizing LCC have originated outside of Asia. Therefore, providing a description of LCC in a U.S.-based cohort will provide insight into both its prevalence and presentation to inform clinicians about this potentially devastating disorder and foster early diagnosis and treatment. This study validates LCC characteristics and prevalence previously outlined by Asian studies in a single-center U.S.-based cohort while also identifying potential risk factors for LCC development. This manuscript will provide education for U.S. physicians about the risk factors and clinical presentation of LCC to facilitate early diagnosis and treatment, potentially decreasing neonatal mortality. With prompt recognition and treatment of LCC, infants may have decreased exposure to vasoactive medications that have significant systemic effects.

The primary function of the patient portal is to give patients greater access to their personal health information. Granting patients electronic access allows them to make well-informed health care decisions.This study aimed to identify sociodemographic differences in patient portal use and examine factors affecting patient portal utilization following the final stage of the Meaningful Use program which aimed to promote the use of certified electronic health record (EHR) technology.Survey data from Health Information National Trends Survey (HINTS) 5, cycles 1, 2, and 3 were analyzed. The sample included 8291 completed surveys. Multivariable logistic regression on a selected response for each surveyed question was used to assess the racial and ethnic difference after controlling for age, sex, income, and education.Subjects included English and Spanish speaking adults in the USA.Measures included assessment of patient portal use, patient portal access, understanding health information, usefulness of health records, and privacy and security.After adjusting for age, sex, income, and education, there was a significant association between race/ethnicity and patient portal non-users responding, "no need to use online medical record" as the reason for not using the patient portal (P = 0.005). Among the portal users, there were significant associations between race/ethnicity and health care provider maintaining an EHR (P = 0.006), being offered access to their portal (P 0.001), understanding health information in the portal (P = 0.004), finding the portal useful for health monitoring (P 0.001), reporting concern about unauthorized access (P = 0.017), and keeping information from health care providers (P = 0.012).Race/ethnicity affects perceptions on the need for the patient portal, being offered access to a portal, and the reasons to access information online. Understanding the factors affecting patient portal use can inform future strategies aimed at increasing adoption.

Background/aim Few data are available on the utility of definitive radiation therapy (RT) for pediatric craniopharyngioma. This study sought to evaluate practice patterns and patient outcomes using the Surveillance Epidemiology and End Results database from 2004-2014. Materials and methods Overall survival (OS) was compared between five treatment groups, definitive radiation therapy (RT), gross total resection (GTR), subtotal resection (STR), STR+RT, and observation/biopsy only, using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards modeling determined variables independently associated with OS. Results A total of 373 patients met the study criteria. GTR and definitive RT conferred superior OS than observation/biopsy (p=0.008 and 0.029), but were equivalent to STR+RT (p=0.350 and 0.200). GTR was associated with a higher OS than STR (p=0.027). On multivariate analysis, STR+RT, GTR, and definitive RT were associated with statistically equivalent OS (p=0.990). Conclusion Definitive RT for pediatric craniopharyngioma affords similar outcomes to established modalities of therapy such as GTR and STR+RT.

Background The purpose of this study was to evaluate risk and response-based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. Methods Patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) features were randomized to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported). Those with at least a partial response to VI continued to receive 44 weeks of multi-agent chemotherapy including the assigned VI regimen. UR patients who did not have measurable disease at study entry, did not have a radiographic response after the VI window, or declined VI window therapy received 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ) at weeks 1, 4, 10, 19, and 28. Favorable-risk (FR) patients received 31 weeks of the same multi-agent chemotherapy without VI and TPZ. Results One hundred thirty-six eligible patients were enrolled. For 61 patients not responding to VI, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 17% (95% confidence interval [CI], 8%-29%) and 24% (13%-37%), respectively. For 30 UR patients not treated with VI, the 3-year FFS and OS rates were 21% (8%-37%) and 39% (20%-57%), respectively. FR patients had 3-year FFS and OS rates of 79% (47%-93%) and 84% (50%-96%), respectively. There were no unexpected toxicities. Conclusions Patients with UR RMS at first relapse or disease progression have a poor prognosis when they are treated with this multi-agent therapy, whereas FR patients have a higher chance of being cured with second-line therapy.

Assess patterns of care in the management of craniopharyngioma, especially with respect to the use of radiation therapy (RT) alone (which has been understudied to date) as compared with gross total resection (GTR) and subtotal resection (STR) with adjuvant RT. The epidemiology, treatment modalities, and outcomes of patients with craniopharyngioma were studied using the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2012. Survival was compared between treatment groups using Kaplan-Meier analysis and log-rank tests. In total, 1218 patients with craniopharyngioma were identified, with equal distribution across sex. There were bimodal incidence peaks, one 20 years old or below, and the other between 40 and 65 years. The majority of pediatric tumors with known histology were adamantinomatous type, which did not influence outcomes when adjusting for age (P=0.392). Overall survival/cause-specific death for patients that underwent RT, STR+RT, and GTR were not statistically different (P>0.05). There was improved survival between several modalities: RT only versus STR only (P=0.024), RT only versus observation (P=0.006), STR+RT versus observation (P=0.046), and GTR versus observation (P=0.046). Patients above 65 years old were more likely to undergo observation (P=0.002), with highest proportions of surgery (54%)/RT (21%) in the pediatric population. Multivariable analysis demonstrated that though age was associated with overall survival (P

Purpose Patients with metastatic rhabdomyosarcoma (RMS), except those younger than 10 years with embryonal RMS, have an estimated long-term event-free survival (EFS) of less than 20%. The main goal of this study was to improve outcome of patients with metastatic RMS by dose intensification with interval compression, use of the most active agents determined in phase II window studies, and use of irinotecan as a radiation sensitizer. Patients and Methods Patients with metastatic RMS received 54 weeks of therapy: blocks of therapy with vincristine/irinotecan (weeks 1 to 6, 20 to 25, and 47 to 52), interval compression with vincristine/doxorubicin/cyclophosphamide alternating with etoposide/ifosfamide (weeks 7 to 19 and 26 to 34), and vincristine/dactinomycin/cyclophosphamide (weeks 38 to 46). Radiation therapy occurred at weeks 20 to 25 (primary) but was also permitted at weeks 1 to 6 (for intracranial or paraspinal extension) and weeks 47 to 52 (for extensive metastatic sites). Results One hundred nine eligible patients were enrolled, with a median follow-up of surviving patients of 3.8 years (3-year EFS for all patients, 38% [95% CI, 29% to 48%]; survival, 56% [95% CI, 46% to 66%]). Patients with one or no Oberlin risk factor (age > 10 years or < 1 year, unfavorable primary site of disease, ≥ three metastatic sites, and bone or bone marrow involvement) had a 3-year EFS of 69% (95% CI, 52% to 82%); high-risk patients with two or more risk factors had a 3-year EFS of 20% (95% CI, 11% to 30%). Toxicity was similar to that on prior RMS studies. Conclusion Patients with metastatic RMS with one or no Oberlin risk factor had an improved 3-year EFS of 69% on ARST0431 compared with an historical cohort from pooled European and US studies; those with two or more risk factors have a dismal prognosis, and new approaches are needed for this very-high-risk group.

Purpose The Soft Tissue Sarcoma Committee of the Children's Oncology Group has conducted five upfront window trials in patients with newly diagnosed metastatic rhabdomyosarcoma to identify promising new treatment agents. Patients and Methods This pooled analysis identified a total of 420 patients (115 from Intergroup Rhabdomyosarcoma Study III [IRS-III] and 305 from the five window trials). We assessed window therapy response rate, failure-free survival (FFS), and overall survival (OS). Results Response rates (complete + partial response) assessed at week 6 of window therapy ranged from 41% to 55% and did not predict FFS (P = .073) or OS (P = .31). FFS was influenced by trial (P = .048); patients enrolled onto IRS-III and the ifosfamide/etoposide and ifosfamide/doxorubicin trials fared best. When grouped and compared with topoisomerase I poison trials, ifosfamide/topoisomerase II inhibitor trials had superior FFS (P = .013). However, there was no difference in survival. Conclusion Upfront phase II window trials can efficiently provide robust estimates of activity for new agents and combinations in newly diagnosed patients with high-risk rhabdomyosarcoma. Our data indicate that, for some phase II window trials, the risk of treatment failure may be increased but that the trend towards lower survival for some of the window trials compared with IRS-III is not statistically significant. Window nonresponders did not suffer worse FFS or OS than patients who responded to window therapy. Finally, these results provide a rationale for incorporating ifosfamide, etoposide, doxorubicin, and topoisomerase I poisons in future trials of high-risk metastatic rhabdomyosarcoma.

Purpose To determine the antitumor activity and toxicity of topotecan given immediately after cyclophosphamide as window therapy, then in combination with conventional agents in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma (RMS). Patients and Methods Sixty-one patients younger than 21 years with newly diagnosed metastatic RMS or undifferentiated sarcoma were assigned window therapy (weeks 0 to 6) with topotecan (0.75 mg/m2 daily × 5 every 21 days) immediately after cyclophosphamide (250 mg/m2 daily × 5 every 21 days; TC). We continued to give these agents in combination with vincristine (VTC) to patients who showed objective improvement, partial response (PR), or complete response (CR) to TC and alternated courses of VTC with vincristine, dactinomycin and cyclophosphamide (VAC) during weeks 6 to 41 (VTC/VAC). Those who showed no response or progressive disease after TC received only VAC. All patients received radiotherapy to sites of unresected disease (weeks 15 to 21). Results The overall response rate (CR + PR) to TC was 47% (95% CI, 35% to 60%). Tumor size ≤ 5 cm was associated with early response. Myelosuppression was the primary toxicity to TC. Overall 3-year disease-free survival and survival were estimated to be 10% (95% CI, 2% to 19%) and 20% (95% CI, 8% to 32%), respectively. Toxicity profiles for patients who received VTC/VAC or VAC alone were comparable. Conclusion Topotecan after cyclophosphamide is a combination that is active against newly diagnosed RMS, with an acceptable toxicity profile. Disease-free survival and overall survival, however, remain disappointing for children with metastatic RMS at diagnosis.

On the Fourth Intergroup Rhabdomyosarcoma study, older children experienced excessive neurotoxicity, whereas younger children had increased myelosuppression. The purpose of this study was to determine whether the same pattern of toxicity was seen on the successor study when use of growth factor was required and dosing of chemotherapy was different by performing a retrospective cohort analysis on patients treated on Children's Oncology Group protocol D9803. Toxicity data were analyzed by stratifying children into 4 age groups. The frequency of grade 3/4 neurotoxicity, myelosuppression, infection, and mucositis was predicted for each age group. The cumulative doses of vincristine and cyclophosphamide administered were measured as percent of protocol-prescribed dose. Adolescents (aged 15+) were more likely to experience neurotoxicity compared with younger patients (odds ratio, 3.6; P

The majority of intermediate risk Rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999-2005) who had Group III tumors of the bladder dome, extremity, or trunk (thorax, abdomen, pelvis) were candidates for DPE at week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease (NED) 36 Gy, microscopic residual (MR) 41.4 Gy, and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity, and 74 trunk). Seventy-three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose [43/73 received 36 Gy, 19/73 received 41.4 Gy]. The local 5-year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS-IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk), and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone.

The sinonasal computer tomography (CT) scan is frequently used to help confirm the diagnosis of rhinosinusitis. However, little data exist correlating patient symptoms with CT findings.Immediately preceding CT of the sinuses, 94 subjects without evidence of trauma, nasal tumors, or previous sinus surgery completed the Rhinosinusitis Outcome Measure 31 symptom questionnaire and were asked to locate areas of facial pain or pressure. CT scans were graded according to the Lund-MacKay system, and agger nasi and ethmoid bulla cells were measured. Data from CT scans and symptom/pain questionnaire responses were analyzed for significant correlations.No correlation was identified when comparing total Lund-MacKay scores, opacification of individual sinuses, and size of the agger nasi and ethmoid bulla cells with the Rhinosinusitis Outcome Measure 31 subset scores and areas of facial pain or pressure.The sinus CT scan is a necessary tool for preoperative planning; however, it should not be used to predict symptoms or to localize areas responsible for facial pain or pressure.

Purpose: To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV). Patients and Methods: Patients with metastatic RMS were treated with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin, and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of metastatic disease were correlated with those end points. Results: One hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly influenced by histology (47% for embryonal v 34% for all others, P = .026) and increasing number of metastatic sites (P = .028). By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P = .007 and .006, respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year FFS of 40% and OS of 47%. Conclusion: Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m2 of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m2, dactinomycin 1.5 mg/m2, and cyclophosphamide 2.2 g/m2 (VAC) and vincristine 1.5 mg/m2, topotecan 0.75 mg/m2 daily × 5, and cyclophosphamide 250 mg/m2 daily × 5. Patients who did not respond to topotecan received continuation therapy with VAC alone. RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival. CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

BACKGROUND:Several anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. The recently approved valganciclovir is the most commonly used and most expensive drug for CMV prevention. The safety and efficacy data have been drawn from a single trial. We hypothesized that valganciclovir may not be as safe as nor more effective than other therapies for CMV prevention. METHODS:All experimental and analytical studies that compared valganciclovir with other therapies for prevention of CMV infection after SOT were selected. Based on meta-analytic and multivariate regression methodologies we critically analyzed all available evidence. FINDINGS:Nine studies were included (N = 1,831). In trials comparing valganciclovir with ganciclovir, the risk for CMV disease is 0.98 (95% Confidence Interval (95%CI) 0.67 to 1.43; P = 0.92; I(2) = 0%). Valganciclovir was significantly associated with the risk of absolute neutropenia (