[Analysis on vaccination willingness and related factors of influenza, pneumonia, and herpes zoster vaccine among people over 50 years old in Minhang district of Shanghai].

Objective: To determine the knowledge of influenza, pneumonia, herpes zoster and related vaccines, willingness to vaccinate under multiple payment scenarios, and corresponding risk factors among people over 50 years old in Minhang District of Shanghai. Methods: A total of 1 672 respondents aged 50-69 from 13 communities/towns in Minhang district of Shanghai were included in this study using a stratified random sampling strategy on December 2020. The knowledge of influenza, pneumonia, herpes zoster and vaccines was investigated using a questionnaire, and the differences in the willingness under multiple payment scenarios were determined using chi-square test. The consistency in the willingness under multiple payment scenarios was compared using Cohen's Kappa and the risk factors of the willingness was determined using ordinal logistic regression. Results: The average age of 1 672 respondents was (60.48±5.96) years old, including 777 (46.47%) males and 895 (53.53%) females. A total of 1 350 subjects (80.74%) had local household registration in Shanghai. The proportion of the willingness to vaccinate for themselves, spouses, and parents under any payment scenario was determined to be 80.6% (influenza vaccine), 81.5% (pneumonia vaccine), and 74.0% (herpes zoster vaccine). The willingness to vaccinate against influenza and pneumonia under multiple payment scenarios remained stable (Kappa value ≥0.6), while that against herpes zoster infection was inconsistent (Kappa value ≤0.35). Logistic regression analysis showed that respondents who had higher knowledge of influenza and influenza vaccine [OR (95%CI): 1.111 (1.054-1.170), 1.182 (1.126-1.240), respectively], aged 50-59 [1.305 (1.085-1.531)] and local household registration in Shanghai [1.372 (1.079-1.721)] had higher willingness to vaccinate against influenza, while males had lower willingness [0.733 (0.551-0.910)]. Respondents who had higher knowledge of pneumonia and pneumonia vaccine [OR (95%CI): 1.837 (1.152-2.517), 2.217 (1.541-2.893), respectively] had higher willingness to receive pneumonia vaccine. Respondents aged 50-59 [1.327 (1.059-1.537)] and with local household registration in Shanghai [2.497 (1.417-4.400)] were more likely to be vaccinated against herpes zoster, while those with middle school degree or below [0.664 (0.396-0.992)] and high school degree [0.559 (0.324-0.964)] were less likely to be vaccinated. Conclusion: Among people aged over 50 years old in Minhang district of Shanghai, the willingness to vaccinate for themselves, spouses, and parents against influenza, pneumonia and herpes zoster infection is quite different under multiple payment scenarios, especially for herpes zoster vaccine.

X-ray-based quantitative osteoporosis imaging at the spine.

Osteoporosis is a metabolic bone disease with a high prevalence that affects the population worldwide, particularly the elderly. It is often due to fractures associated with bone fragility that the diagnosis of osteoporosis becomes clinically evident. However, early diagnosis would be necessary to initiate therapy and to prevent occurrence of further fractures, thus reducing morbidity and mortality. X-ray-based imaging plays a key role for fracture risk assessment and monitoring of osteoporosis. Whereas over decades dual-energy X-ray absorptiometry (DXA) has been the main method used and still reflects the reference standard, another modality reemerges with quantitative computed tomography (QCT) because of its three-dimensional advantages and the opportunistic exploitation of routine CT scans. Against this background, this article intends to review and evaluate recent advances in the field of X-ray-based quantitative imaging of osteoporosis at the spine. First, standard DXA with the recent addition of trabecular bone score (TBS) is presented. Secondly, standard QCT, dual-energy BMD quantification, and opportunistic BMD screening in non-dedicated CT exams are discussed. Lastly, finite element analysis and microstructural parameter analysis are reviewed.

[Component analysis of Ophiocordyceps lanpingensis polysaccharides and study on alleviation of hepatic fibrosis in mice by polysaccharides].

Ophiocordyceps lanpingensis is mainly used as an ethnic medicine to treat the diseases of liver, kidney and other diseases, but the pharmacological mechanism is not clear yet. In this study, the components and contents of monosaccharides in the O.lanpingensis polysaccharides(OLP) were analyzed. The results showed that the OLP were composed of mannose, glucose, galactose and arabinose, with mass percentages of 19.1%, 21.8%, 21.1%, and 38.0%, respectively. Based on the hepatic fibrosis model induced by CCl_4 in mice, OLP could significantly relieve the inflammation and fibrosis levels of hepatic tissues, reverse the CCl_4-induced increasing levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in mice serum, and recover the functions of liver to a normal state. This study proved that OLP significantly decreased the mRNA expression levels of fibrotic genes, alpha-smooth muscle actin(α-SMA) and collagen type 1(Col-1), as well as the content of hydroxyproline(HYP) in the liver tissues; meanwhile, the contents of antioxidants superoxide dismutase(SOD) and glutathione(GSH) were enhanced and the production of lipid peroxide malondialdehyde(MDA) was reduced. Moreover, OLP inhibited the gene expression levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and nuclear factor kappa B(NF-κB) in the livers of mice. Further study indicated that OLP could restrain the apoptosis of hepatic cells due to the decrease of the apoptosis index and down-regulations of protein expression levels of Bcl-2 associated X protein(Bax), cysteinyl aspartate specific proteinase-3(caspase-3) and cysteinyl aspartate specific proteinase-9(caspase-9), and the promotion of protein expression level of B-cell lymphoma-2(Bcl-2) in livers. To sum up, the mechanism of OLP for alleviating hepatic fibrosis was likely related to the synergy by remitting the oxidative stress of the body, alleviating inflammatory response, anti-apoptosis of hepatic cells, and so on.

Feasibility of opportunistic osteoporosis screening in routine contrast-enhanced multi detector computed tomography (MDCT) using texture analysis.

This study investigated the feasibility of opportunistic osteoporosis screening in routine contrast-enhanced MDCT exams using texture analysis. The results showed an acceptable reproducibility of texture features, and these features could discriminate healthy/osteoporotic fracture cohort with an accuracy of 83%. INTRODUCTION: This aim of this study is to investigate the feasibility of opportunistic osteoporosis screening in routine contrast-enhanced MDCT exams using texture analysis. METHODS: We performed texture analysis at the spine in routine MDCT exams and investigated the effect of intravenous contrast medium (IVCM) (n = 7), slice thickness (n = 7), the long-term reproducibility (n = 9), and the ability to differentiate healthy/osteoporotic fracture cohort (n = 9 age and gender matched pairs). Eight texture features were extracted using gray level co-occurrence matrix (GLCM). The independent sample t test was used to rank the features of healthy/fracture cohort and classification was performed using support vector machine (SVM). RESULTS: The results revealed significant correlations between texture parameters derived from MDCT scans with and without IVCM (r up to 0.91) slice thickness of 1 mm versus 2 and 3 mm (r up to 0.96) and scan-rescan (r up to 0.59). The performance of the SVM classifier was evaluated using 10-fold cross-validation and revealed an average classification accuracy of 83%. CONCLUSIONS: Opportunistic osteoporosis screening at the spine using specific texture parameters (energy, entropy, and homogeneity) and SVM can be performed in routine contrast-enhanced MDCT exams.

Effects of virtual tube current reduction and sparse sampling on MDCT-based femoral BMD measurements.

This study investigates the impact of tube current reduction and sparse sampling on femoral bone mineral density (BMD) measurements derived from multi-detector computed tomography (MDCT). The application of sparse sampling led to robust and clinically acceptable BMD measurements. In contrast, BMD measurements derived from MDCT with virtually reduced tube currents showed a considerable increase when compared to original data. INTRODUCTION: The study aims to evaluate the effects of radiation dose reduction by using virtual reduction of tube current or sparse sampling combined with standard filtered back projection (FBP) and statistical iterative reconstruction (SIR) on femoral bone mineral density (BMD) measurements derived from multi-detector computed tomography (MDCT). METHODS: In routine MDCT scans of 41 subjects (65.9% men; age 69.3 ± 10.1 years), reduced radiation doses were simulated by lowering tube currents and applying sparse sampling (50, 25, and 10% of the original tube current and projections, respectively). Images were reconstructed using FBP and SIR. BMD values were assessed in the femoral neck and compared between the different dose levels, numbers of projections, and image reconstruction approaches. RESULTS: Compared to full-dose MDCT, virtual lowering of the tube current by applying our simulation algorithm resulted in increases in BMD values for both FBP (up to a relative change of 32.5%) and SIR (up to a relative change of 32.3%). In contrast, the application of sparse sampling with a reduction down to 10% of projections showed robust BMD values, with clinically acceptable relative changes of up to 0.5% (FBP) and 0.7% (SIR). CONCLUSIONS: Our simulations, which still require clinical validation, indicate that reductions down to ultra-low tube currents have a significant impact on MDCT-based femoral BMD measurements. In contrast, the application of sparse-sampled MDCT seems a promising future clinical option that may enable a significant reduction of the radiation dose without considerable changes of BMD values.

Use of Mother-Child Screws in the Treatment of Coronoid Fractures in Terrible Triad Injury of the Elbow.

PURPOSE OF THE STUDY This study aims to analyze the clinical and radiographic outcomes of a consecutive series of 18 patients with terrible triad injury. The coronoid fractures of these patients were repaired using Mother-Child screw (MCS). MATERIAL AND METHODS Twelve men and six women (mean age: 47.2 years) with terrible triad injury of the elbow were followed up for a mean of 17.6 months (range: 13-42 months). Surgical treatment consisted of open reduction and internal fixation of coronoid fractures with MCS, radial head fracture with MCS (Mason type II, n = 10), or mini-plate (Mason type III, n = 3). Furthermore, all underwent lateral collateral ligament repair (n = 9, 100%), and in cases of persistent instability, medial collateral ligament repair was performed (n = 3, 33%). RESULTS At last follow-up, average arc of ulnohumeral motion was 130° (range: 65° to 150°), average arc of forearm rotation was 148° (range: 100°-160°), mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 7.1 (range: 0-28.5), and mean Mayo Elbow Performance Score (MEPS) was 92 (range: 70-100). According to the Mayo Elbow Performance Index (MEPI), 10 patients were excellent in, seven patients were good, and one patient was fair. All patients had a stable elbow. No secondary coronoid fragment dislocation or implant failures was reported. Fracture healing was observed in all patients. CONCLUSIONS This study shows that coronoid fracture treatment with MCS may be a new, effective and easy therapeutic option in terrible triad injury. Key words:terrible triad of the elbow, coronoid process, radial head, functional outcome.

[The understanding of Epstein-Barr virus associated lymphoproliferative disorder].

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases. According to this concept, EBV+ LPD should not include infectious mononucleosis (IM) and severe acute EBV infection (EBV+ hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+ lymphomas (such as extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma, and Hodgkin lymphoma, etc.) either. EBV+ LPD should currently include: (1) EBV+ B cell-LPD: lymphomatoid granulomatosis, EBV + immunodeficiency related LPD, chronic active EBV infection-B cell type, senile EBV+ LPD, etc. (2) EBV+ T/NK cell-LPD: CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc. In addition, EBV+ LPD is classified, based on the disease process, pathological and molecular data, as 3 grades: grade1, hyperplasia (polymorphic lesions with polyclonal cells); grade 2, borderline (polymorphic lesions with clonality); grade 3, neoplasm (monomorphic lesions with clonality). There are overlaps between EBV+ LPD and typical hyperplasia, as well as EBV+ LPD and typical lymphomas. However, the most important tasks are clinical vigilance, early identification of potential severe complications, and treating the patients in a timely manner to avoid serious complications, as well as the active treatment to save lives when the complications happened.

Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients.

WHAT IS KNOWN AND OBJECTIVE: The dofetilide label recommends using actual body weight (ABW) to calculate the Cockcroft-Gault creatinine clearance (CrCl) for the determination of the initial dose; however, few studies have attempted to evaluate this dosing recommendation in overweight and obese patients. We evaluated whether the current dofetilide dosing recommendation based on ABW is appropriate in overweight and obese patients. METHODS: This is a retrospective cohort study conducted at two large academic medical centres in the United States on overweight and obese patients (body mass index ≥ 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. RESULTS AND DISCUSSION: Of the 132 patients included in the study, 29 (22·0%) were in the different-dose group and 40 (30·3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37·9% vs. 28·2%; P = 0·31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2·54; 95% confidence interval 1·05-6·15). WHAT IS NEW AND CONCLUSION: Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients.

Core stability exercise is as effective as task-oriented motor training in improving motor proficiency in children with developmental coordination disorder: a randomized controlled pilot study.

OBJECTIVE: To compare the effectiveness of a core stability program with a task-oriented motor training program in improving motor proficiency in children with developmental coordination disorder (DCD). DESIGN: Randomized controlled pilot trial. SETTING: Outpatient unit in a hospital. PARTICIPANTS: Twenty-two children diagnosed with DCD aged 6-9 years were randomly allocated to the core stability program or the task-oriented motor program. INTERVENTION: Both groups underwent their respective face-to-face training session once per week for eight consecutive weeks. They were also instructed to carry out home exercises on a daily basis during the intervention period. MAIN MEASURES: Short Form of the Bruininks-Oseretsky Test of Motor Proficiency (Second Edition) and Sensory Organization Test at pre- and post-intervention. RESULTS: Intention-to-treat analysis revealed no significant between-group difference in the change of motor proficiency standard score (P=0.717), and composite equilibrium score derived from the Sensory Organization Test (P=0.100). Further analysis showed significant improvement in motor proficiency in both the core stability (mean change (SD)=6.3(5.4); p=0.008) and task-oriented training groups (mean change(SD)=5.1(4.0); P=0.007). The composite equilibrium score was significantly increased in the task-oriented training group (mean change (SD)=6.0(5.5); P=0.009), but not in the core stability group (mean change(SD) =0.0(9.6); P=0.812). In the task-oriented training group, compliance with the home program was positively correlated with change in motor proficiency (ρ=0.680, P=0.030) and composite equilibrium score (ρ=0.638, P=0.047). CONCLUSION: The core stability exercise program is as effective as task-oriented training in improving motor proficiency among children with DCD.

Clinicopathological characteristics and outcome of patients with small cell neuroendocrine carcinoma of the uterine cervix: case series and literature review.

OBJECTIVE: To analyze the clinicopathological data of 13 cases of small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix who received treatment at this medical institutions over the past five years with patient survival as the primary endpoint. MATERIALS AND METHODS: The clinicopathologic data of 13 cases were reviewed. Immunohistochemistry was performed using antibodies against synaptophysin and chromogranin A and Ki-67. Survival was analyzed using the Kaplan-Meier method and log-rank tests. RESULTS: The median age of these patients was 37 years (range 21-62). Immunohistochemistry showed that the positive rate of synaptophysin and chromogranin A was 100% (13/13) and 69.23% (9/13), respectively. The median survival of patients with early-Stage I-II SCNEC of the uterine cervix (17.5 months) was significantly higher than that of patients with advanced stage SCNEC of the uterine cervix (four months) (p < 0.05). There was no local recurrence in all 13 patients. Five patients died of distant metastasis in less than six months. CONCLUSION: SCNEC of the uterine cervix is a highly-malignant disease and early-stage patients showed significantly longer survival compared to late-stage patients. Early diagnosis and prompt combination treatment may improve the outcome of patients with SCNEC of the uterine cervix.

Does airway integrated nasal packing after septal surgery improve body oxygenation?

BACKGROUND: Airway integrated nasal packing reportedly improves body oxygenation after septal surgery. This randomized controlled study examined the effect of airway integrated nasal packing on oxygen saturation. METHODS: Eighty patients with septal deviation and hypertrophic turbinate were randomly divided into two groups: Group 1 patients were postoperatively packed with airway integrated Nasopore, and Group 2 patients were postoperatively packed with Nasopore without airway integration. The haemodynamic parameters and SpO2 (oxyhemoglobin saturation levels when measured using pulse oximetry) were sequentially checked. Nasal pain sensations were recorded using a visual analog scale. RESULTS: SpO2 was not significantly different between Groups 1 and 2. Nasal pain levels were significantly higher in Group 1 than in Group 2 at both 4 (p = 0.034) and 6 (p = 0.001) hours postoperatively. There were no significant differences between the two groups in the incidences of septal haematoma, perforation, or bleeding, or in sequentially checked heart rate, mean blood pressure, or respiration rate. CONCLUSION: It was not evident that integrated airways improved the reduction of SpO2. However, Group 1 patients, with integrated airways, had more pain than did Group 2 patients, without integrated airways. EVIDENCE LEVEL: 1b.

Typing study of human semen DIA3 by isoelectric focusing--distribution in the Wuhan population, China.

Human semen DIA3 typing was studied by isoelectric focusing on ultra-thin-layer polyacrylamide gel which resulted in a simpler and more definite separation of the products of DIA3 alleles than hitherto. In 198 semen samples collected from unrelated Chinese males four different phenotypes were observed. The DIA3 allele frequencies were calculated: DIA 3(1) = 0.7727, DIA 3(2) = 0.2172, DIA 3(3) = 0.0101. The results of the stability study of 12 laboratory-prepared semen stains stored at room temperature suggested that DIA3 in seminal strains is a relatively stable genetic marker. Our gene frequencies have been compared to those reported in other populations.

[Genetic polymorphism of STR loci D19S253 and D8S1179 for Han population in Wuhan].

OBJECTIVE: This article reports a population genetic study on two short tandem repeat loci, D19S253 and D8S1179, in a sample of unrelated Chinese individuals(n=225-233) living in Wuhan. METHODS: PCR and PAGE. RESULTS: Nine alleles were identified for the two loci, the ranges of fragment size were 209bp-241bp and 174bp-206bp respectively. The genotypes distributions of D19S253 and D8S1179 were in accordance with Hardy-Weinberg equilibrium. Family studies confirmed Mendelian inheritance of alleles. No mutation was detected in 100 meiosis for the two STR loci studied. The observed heterozygosities of D19S253 and D8S1179 were 0.8089 and 0.8712. The polymorphism information content(PIC) in Chinese was calculated as 0.7754 for D19S253 and 0.8258 for D8S1179. The power of discrimination(PD) and mean exclusion chance(MEC) were 0.9309 and 0.6133 for D19S253 and 0.9515 and 0.6874 for D8S1179 respectively. The combined PD and cumulative chance of exclusion were calculated as 0. 9966 and 0.8791. CONCLUSION: The results demonstrate that the combined use of the two polymorphic systems provides a high power of discrimination and power of exclusion for use in forensic identification and paternity testing.

[Classification and treatment of torsades de pointes (TdP): a report of 11 cases].

A clinical analysis of 11 cases with TdP was reported. These patients were divided into two groups: 9 cases with long QT syndrome and 2 with normal QT interval. All of the patients suffered from coronary heart disease with various concomitant ailments, such as pulmonary heart disease (1 case), atrioventricular block (5 cases with complete or type II second degree AV block), hypokalemia (7 cases). In one case the TdP was caused by aminodarone administration. The principle of treatment included removing the inducing causes, treating the primary diseases and interrupting TdP. All patients who had hypokalemia were treated with potassium chloride. 7 of 9 cases showed effective response to treatment with magnesium sulfate. The patients with long QT syndrome failed to respond with MgSO4. Severe bradycardia should be treated with isoprenaline. Only one patient had pacing therapy and another received electric conversion. According to our experience, for patients of TdP with long QT syndrome class Ia and III antiarrhythmic agents were contraindicated, but those with normal QT interval can take these drugs.

Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group.

PURPOSE: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage leukemia (MLL) gene rearrangements, is only 30% to 40%. Relapse has been the major source of treatment failure for these patients. The parallel Children's Cancer Group (CCG) 1953 and Pediatric Oncology Group (POG) 9407 studies were designed to test the hypothesis that more intensive therapy, including dose intensification of chemotherapy, and hematopoietic stem-cell transplantation (HSCT) would improve the outcome for this group of patients. PATIENTS AND METHODS: One hundred eighty-nine infants (CCG 1953, n = 115; POG 9407, n = 74) were enrolled between October 1996 and August 2000. For infants with the MLL gene rearrangement and an appropriate donor, HSCT was the preferred treatment on CCG 1953 and investigator option on POG 9407 after completion of the second phase of therapy. Fifty-three infants underwent HSCT. RESULTS: The 5-year EFS rate was 48.8% (95% CI, 33.9% to 63.7%) in patients who received HSCT and 48.7% (95% CI, 33.8% to 63.6%) in patients treated with chemotherapy alone (P = .60). Transplantation outcomes were not affected by the preparatory regimen or donor source. CONCLUSION: Our data suggest that routine use of HSCT for infants with MLL-rearranged ALL is not indicated. However, limited by small numbers, this study should not be considered the definitive answer to this question.

Young adults with acute lymphoblastic leukemia have an excellent outcome with chemotherapy alone and benefit from intensive postinduction treatment: a report from the children's oncology group.

PURPOSE: Patients 16 to 21 years of age with acute lymphoblastic leukemia (ALL) have an inferior outcome compared with younger children, leading some medical oncologists to advocate allogeneic stem-cell transplantation in first remission for these patients. We examined outcome for young adults with ALL enrolled onto the Children's Cancer Group (CCG) 1961 study between 1996 and 2002. PATIENTS AND METHODS: CCG 1961 entered patients with ALL 1 to 21 years of age with initial WBC count > or = 50,000/microL and/or age > or = 10 years. Randomly assigned therapies evaluated the impact of postinduction treatment intensification on outcome. We examined outcome and prognostic factors for 262 young adults with ALL. RESULTS: Five-year event-free and overall survival rates for young adult patients are 71.5% (SE, 3.6%) and 77.5% (SE, 3.3%), respectively. Rapid responder patients (< 25% bone marrow blasts on day 7) randomly assigned to augmented therapy had 5-year event-free survival of 81.8% (SE, 7%), as compared with 66.8% (SE, 6.7%) for patients receiving standard therapy (P = .07). One versus two interim maintenance and delayed intensification courses had no significant impact on event-free survival. WBC count more than 50,000/microL was an adverse prognostic factor. CONCLUSION: Young adult patients with ALL showing a rapid response to induction chemotherapy benefit from early intensive postinduction therapy but do not benefit from a second interim maintenance and delayed intensification phase. Given the excellent outcome with this chemotherapy, there seems to be no role for the routine use of allogeneic stem-cell transplantation in first remission for young adults with ALL.

Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with "higher risk" acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 x 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/mm3 or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P < .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.

Simultaneous analysis of steady-state intracellular pH and cell morphology by automated laser scanning cytometry.

BACKGROUND: Cytosolic pH (pHi) changes are critical in cellular response to diverse stimuli, including cell survival and death signaling. The potential drawback in flow-based analysis is the inability to simultaneously visualize the cells during pHi measurements. Here, the suitability of laser scanning cytometer (LSC) in pHi measurement was investigated. AIM: Using the two extensively reported pH-sensitive fluorescent probes, 2,7-bis(2-Carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and 5-(and-6)-carboxy SNARF-1 acetoxymethyl ester, we evaluated the potential of automated LSC as a platform for simultaneous determination of pHi and cell morphology. The effect of a variety of buffer systems-commonly employed for pHi measurements-on cell morphology before pH clamping with the ionophore, nigericin, was also assessed. METHODS: Measurement of cytosolic pH was performed using pH-sensitive fluorescent probes BCECF-AM and SNARF-1. pH clamping was carried out using nigericin and samples were analyzed on the LSC or CyAn ADP Flow Cytometer. RESULTS: The pHi clamping conditions were optimized as 140 mM potassium and 10 microM nigericin. The suitable buffers used for pH clamping: 140 mM KCl, 1 mM MgCl2, 2 mM CaCl(2).2H2O, 5 mM glucose, 20 mM MES and 140 mM KCl, 1 mM MgCl2, 2 mM CaCl(2).2H2O, 5 mM glucose, and 20 mM Tris. Results obtained with the LSC strongly correlated with those obtained by flow cytometry. CONCLUSION: We report here that LSC is an excellent and highly reproducible platform for pHi determination, and provides the added advantage of simultaneous imaging of cells before, during, and after pH measurements.

Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children's Oncology Group study CCG-1952.

PURPOSE: The event-free survival (EFS) of children with standard-risk acute lymphoblastic leukemia (SR-ALL) is now more than 80%. However, prognosis after relapse continues to be poor. We examined postrelapse outcomes of children initially treated on the Children's Cancer Group CCG-1952 study. PATIENTS AND METHODS: We evaluated outcomes after bone marrow (BM) relapse and isolated extramedullary (EM) relapse for 347 patients with SR-ALL (WBC < 50,000/microL; age, 1 to 9 years). The prognostic significance of several factors for EFS after relapse (EFS2) was assessed by Cox regression analysis. Stem-cell transplant (SCT) was compared with chemotherapy as salvage treatment. RESULTS: The mean +/- SE times to isolated central nervous system relapse, BM relapse, and isolated testicular relapse were 23 +/- 1 months (range, 1 to 88 months), 36 +/- 1 months (range, 2 to 79 months), and 40 +/- 2 months (range, 16 to 64 months), respectively. The estimated percent +/- SE 3-year EFS2 and overall survival rates after BM relapse were 37% +/- 4% and 46% +/- 4%, respectively, and rates after isolated EM relapse were 57% +/- 5% and 71% +/- 5%, respectively. By multivariate analysis, we found the duration of first remission to be the most significant predictor of EFS2 for either BM relapse or isolated EM relapse. Outcome was equivalent with SCT or chemotherapy after early or late relapse of SR-ALL at any site. CONCLUSION: Duration of first remission remains the most significant predictor of outcome after either BM or isolated EM relapse of SR-ALL. Prognosis after early BM relapse remains poor and is not improved with SCT in this cohort.

Intravenous 6-mercaptopurine decreases salvage after relapse in childhood acute lymphoblastic leukemia: a report from the Children's Cancer Group study CCG 1922.

PURPOSE: To compare outcomes of patients with NCI standard risk acute lymphoblastic leukemia (ALL) who relapsed after being randomized to receive either oral or intravenous 6-mercaptopurine (6MP) in the Children's Cancer Group study CCG 1922. PATIENTS AND METHODS: CCG 1922 accrued patients from March 1993 to August 1995. A total of 1,060 patients were randomly assigned to four treatment groups: oral 6MP plus prednisone (OP), intravenous 6MP plus prednisone (IP), oral 6MP plus dexamethasone (OD), and intravenous 6MP plus dexamethasone (ID). During the 2nd through 4th month of therapy groups OP and OD were treated with 75 mg/m(2)/day of oral 6MP for 70 days and groups IP and ID with 1,000 mg/m(2)/week of intravenous 6MP over 10 hr for 11 doses. All patients received a single delayed intensification and all received oral 6MP in maintenance. RESULTS: Patients randomized to oral 6MP had significantly better 5-year overall survival (96 +/- 1% vs. 92 +/- 1%; P = 0.008). There was, however, no statistically significant difference in the event-free survival (EFS). Of the 179 patients who relapsed, 84 had a second or later event and 68 have died. Forty of the 84 second events were a death. Survival after relapse was significantly greater for patients randomized to oral 6MP during consolidation than those receiving intravenous 6MP (P = 0.002, log rank test) with 4-year survival post-relapse of 67 +/- 6% vs. 48 +/- 6%. The steroid randomization had no influence on outcome. Post-relapse therapy details are not available and if different between groups may have influenced the outcome. CONCLUSION: Treatment with intravenous 6MP during a brief period of total therapy had a significant negative impact on the prognosis in childhood ALL even though oral 6MP was used during maintenance.