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Dezheng Huo

Publications and source records attributed to Dezheng Huo.

At least 19 recordsLinked to original sources

Development and Validation of a Multimodal Clinical, Pathologic, and Genomic Model for Breast Cancer Recurrence.

PURPOSE: To develop and validate a multimodal recurrence-risk model integrating histology, genomic testing, and clinical variables. METHODS: We developed AI-Path, a whole-slide image biomarker for recurrence prediction trained in CALGB 9344, and validated it in three independent cohorts: TAILORx, a multi-site Chicago cohort, and the MDX-BRCA cohort. We then integrated AI-Path with Oncotype DX Recurrence Score (RS), tumor size, and nodal status into a Cox model, PathClinRS, fit using 60% of cases from TAILORx, with the remaining 40% held out for validation. The primary end point was distant recurrence-free interval. Performance was assessed using Harrell's concordance index (C-index) and Kaplan-Meier analyses. RESULTS: A total of 12,418 patients were included. In TAILORx, AI-Path outperformed RS for distant recurrence (C-index, 0.682 vs 0.647; P = .038), driven by superior prediction of late recurrence (0.656 vs 0.567; P < .001). In node-negative disease, PathClinRS outperformed RSClin in the TAILORx fitting (0.72 vs 0.70; P = .016) and validation sets (0.74 vs 0.70; P = .004). In node-positive disease, PathClinRS outperformed RSClinN+ in Chicago (0.94 vs 0.74; P < .001) and MDX-BRCA (0.71 vs 0.66; P = .004) cohorts. Compared with NATALEE eligibility, PathClinRS identified nearly twice as many high-risk node-negative patients while maintaining a comparable 10-year distant recurrence risk (16.7% vs 16.6% per NATALEE eligibility in TAILORx fitting; 21.0% vs 19.4% in TAILORx validation). PathClinRS identified 68% of intermediate risk premenopausal patients as low-risk with no evidence of chemotherapy benefit, compared to only 36% identified as low risk by standard clinicopathologic criteria. CONCLUSION: Digital histopathology provides prognostic information complementary to genomic assays and has the potential to personalize therapy beyond existing clinicogenomic tools.

Journal Article↗

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates &#x2265;50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article↗

Dietary fatty acids correlate with prostate cancer biopsy grade and volume in Jamaican men.

PURPOSE: Jamaica has the highest incidence of prostate cancer in the world. Dietary fat is associated with prostate cancer. The Omega6 polyunsaturated fatty acids have been shown to stimulate prostate carcinogenesis and the Jamaican diet is rich in linoleic acid. We hypothesized positive correlations between Omega6 polyunsaturated fatty acid, prostate specific antigen and prostate biopsy pathology. MATERIALS AND METHODS: A total of 148 men were enrolled in Kingston, Jamaica. Serum prostate specific antigen and erythrocyte membrane polyunsaturated fatty acids were analyzed. Men with prostate specific antigen 2.6 ng/ml or greater underwent biopsy. Histopathological and statistical analyses were performed on available data. RESULTS: Of the 54 men who underwent biopsy 24 had prostate cancer, 17 had a Gleason score of 7 or greater and 11 had a tumor volume of 50% or greater. There were significant positive correlations between linoleic acid and Gleason score (p = 0.009), and the linoleic acid-to-docosahexaenoic acid (Omega3) ratio and tumor volume (p = 0.03). There was a significant negative correlation between the arachidonic acid (Omega6)-to-docosapentanoic acid (Omega3) ratio and Gleason score (p = 0.04). Statistical correlations between prostate specific antigen and polyunsaturated fatty acids were inconsistent. CONCLUSIONS: The positive correlations between linoleic acid and Gleason score, and the linoleic acid-to-docosahexaenoic acid ratio and tumor volume support studies showing that Omega6 polyunsaturated fatty acids stimulate and Omega3 polyunsaturated fatty acids inhibit prostate cancer growth. The negative correlation between the arachidonic acid-to-docosapentanoic acid ratio and Gleason score supports studies that demonstrate increased metabolism of arachidonic acid in prostate cancer to form carcinogenic metabolites, namely prostaglandin E2. Our findings support the association between dietary fatty acids and prostate cancer, and they warrant further dietary and tissue studies in high risk populations.

Aged↗

Therapy-related myelodysplastic syndrome: morphologic subclassification may not be clinically relevant.

In practice, cases of therapy-related myelodysplastic syndrome (t-MDS) are often classified according to morphologic schemes used for de novo MDS. However, there are few data addressing the appropriateness of such classification. We studied 155 patients with therapy-related acute myeloid leukemia (t-AML)/t-MDS to determine whether subclassification by the World Health Organization (WHO) criteria for de novo MDS provides prognostic information in t-MDS. In addition, we assessed whether cytogenetic stratification by the International Prognostic Scoring System (IPSS) guidelines or karyotypic complexity was prognostically important. We found no differences in median survival times among patients classified into the different WHO subgroup of MDS or according to their bone marrow blast percentage; our results indicate a uniformly poor outcome in t-MDS regardless of morphologic classification. However, significant survival differences correlated with cytogenetic stratification according to IPSS guidelines and/or karyotypic complexity. We found only a borderline difference in median survival of patients with an initial t-MDS diagnosis compared with patients with an initial t-AML diagnosis.

Acute Disease↗

Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis.

BACKGROUND & AIMS: Aminosalicylates have been suggested as chemopreventive agents for colorectal cancer (CRC) in ulcerative colitis (UC). We studied the effect of aminosalicylate use on dysplasia and CRC risk in chronic UC. METHODS: UC patients with dysplasia or CRC were matched with controls by disease duration, extent, and age at diagnosis. The total amount of aminosalicylates over the duration of the disease and the mean daily amount of drug was calculated. Conditional logistic regression was used to examine the relationship of aminosalicylates to the risk of neoplasia; potential confounders were controlled in a multivariable model. RESULTS: Twenty-six cases (8 CRC, 18 dysplasia) were matched with 96 controls. Cases and controls were similar in age (median, 43 vs 42.5 y), age at diagnosis of UC (median, 29.5 vs 30.5 y), duration of UC (median, 11.5 vs 9 y), and extent of disease (58% pancolitis), sex, family history of UC, history of primary sclerosing cholangitis, and smoking history. Cases were more likely to have a family history of CRC than controls (27% of cases, 9% of controls, P = .036). Conditional logistic regression adjusted for disease duration, age at diagnosis, and family history of CRC showed that aminosalicylate use of 1.2 g/day or more was associated with a 72% reduction in the odds of dysplasia/CRC (odds ratio, 0.28; 95% confidence interval, 0.09-0.85). As the total dose of aminosalicylates increased, the odds of dysplasia/CRC decreased (P = .056). CONCLUSIONS: This case-control study shows a significant risk reduction of dysplasia and CRC in UC patients exposed to aminosalicylate therapy.

Adult↗

Role of single nucleotide polymorphisms of cytokine genes in spontaneous preterm delivery.

Intra-amniotic infections are implicated in spontaneous preterm delivery (PTD). Certain genetic polymorphisms are associated with increased production of proinflammatory and/or decreased production of anti-inflammatory cytokines, thereby possibly promoting PTD. We determined the relationship between maternal and fetal cytokine gene polymorphisms with occurrence and severity of spontaneous PTD (PTD after spontaneous-onset preterm labor and/or preterm prelabor rupture of membranes) and their association with intrauterine inflammation and infection. DNA from buccal brushings of 80 preterm (gestation < 35 weeks) and 80 matched term mother-infant pairs was assayed for tumor necrosis factor alpha (TNF-alpha [-308G/A]), interferon-gamma (IFN-gamma [+874A/T]), interleukin-6 (IL-6 [-174C/G]), interleukin-10 (IL-10 [-1082G/A, -819C/T, -592C/A]), and transforming growth factor beta1 (TGF-beta1 [T/Ccodon10,G/Ccodon25]) by using polymerase chain reaction (PCR) with sequence-specific primers. The presence of histologic chorioamnionitis was determined for PTDs. Conditioned on maternal IFN-gamma genotypes, fetal high IFN-gamma producing allele (IFN-gamma[+874T]) was associated with spontaneous PTD (odds ratio = 2.3 [1.2-4.4]). Among preterm deliveries, maternal low TGF-beta1 (TGF-beta1 [codon10C]) producing genotypes correlated negatively with gestation. Fetal TNF-alpha (-308G) was significantly associated with histologic chorioamnionitis. Underlying genitourinary infections and/or inflammation were significantly associated with maternal and fetal IL-6 (-174G), fetal TNF-alpha (-308GG), and fetal IL-10 (-1082A). We conclude that certain fetal and maternal cytokine gene polymorphisms may be associated with occurrence and/or severity of spontaneous PTD and with intrauterine inflammation and infection.

Adult↗

The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma.

Despite considerable efforts to improve early detection of ovarian cancer, the majority of women at time of diagnosis will have metastatic disease. Understanding and targeting the molecular underpinnings of metastasis continues to be the principal challenge in the clinical management of ovarian cancer. Whereas the multistep process of metastasis development has been well established in both clinical and experimental models, the molecular factors and signaling pathways involved in successful colonization of a secondary site by disseminated cancer cells are not well defined. We have previously identified mitogen-activated protein kinase (MAPK) kinase 4/c-Jun NH2-terminal kinase (JNK)-activating kinase (MKK4/JNKK1/SEK1, hereafter referred to as MKK4) as a metastasis suppressor protein in ovarian carcinoma. In this study, we elucidate key mechanisms of MKK4-mediated metastasis suppression. Through the use of a kinase-inactive mutant, we show that MKK4 kinase activity is essential for metastasis suppression and prolongation of animal survival. Because MKK4 can activate either of two MAPKs, p38 or JNK, we expressed MKK6 or MKK7, specific activators of these MAPKs, respectively, to delineate which MAPK signaling module was involved in MKK4-mediated metastasis suppression. We observed that MKK6 expression suppressed metastatic colonization whereas MKK7 had no effect. Our finding that MKK4 and MKK6 both suppress metastasis points to the p38 pathway as an important regulatory pathway for metastatic colonization in ovarian cancer.

Animals↗

Zoledronic acid initiated during the first year of androgen deprivation therapy increases bone mineral density in patients with prostate cancer.

PURPOSE: Androgen deprivation therapy in patients with prostate cancer is associated with bone loss and an increased risk of fractures. Zoledronic acid protects against bone mineral density loss when initiated concurrently with androgen deprivation therapy. We evaluated the effect of zoledronic acid initiated subsequent to androgen deprivation therapy on bone mineral density and biochemical markers of bone turnover. MATERIALS AND METHODS: Patients with prostate cancer without bone metastases who had received androgen deprivation therapy for 12 months or less were randomized to 4 mg zoledronic acid or placebo intravenously every 3 months for 1 year. Patients were stratified according to androgen deprivation therapy duration (less than 6 vs 6 to 12 months). The primary end point was the change in femoral neck and lumbar spine bone mineral density in the 2 groups. The secondary end point was the change in serum bone specific alkaline phosphatase and urine N-telopeptide levels. Total hip bone mineral density was also measured. RESULTS: The 120 patients with prostate cancer received zoledronic acid (61) or placebo (59). Compared with placebo, zoledronic acid increased femoral neck, total hip and lumbar spine bone mineral density yearly by 3.6% (p = 0.0004), 3.8% (p <0.0001) and 6.7% (p <0.0001), respectively. The effects of zoledronic acid on bone mineral density at these 3 sites were not differentiated according to androgen deprivation therapy duration. Additionally, mean bone specific alkaline phosphatase and N-telopeptide levels were decreased in the zoledronic acid group (each p <0.0001) and were increased in the placebo group (p <0.0001 and p = 0.004, respectively). CONCLUSIONS: Zoledronic acid increased bone mineral density and suppressed bone turnover markers in patients with prostate cancer without bone metastases when initiated during year 1 of androgen deprivation therapy.

Adenocarcinoma↗

Do patients with inflammatory bowel disease want genetic testing?

BACKGROUND: Inflammatory bowel disease (IBD) is a complex genetic disorder characterized by nonmendelian inheritance, incomplete penetrance, and disease susceptibility but not disease certainty. Genotype and phenotype associations are described, but the level of interest of patients with IBD in genetic testing for themselves or at-risk family members remains unknown. Thus, the goal of this study was to assess the interest of patients with IBD in genetic testing and their willingness to accept the uncertainty inherent in complex genetics. MATERIALS AND METHODS: Consecutive outpatients with IBD were recruited to complete a 57-item self-administered survey. The survey included a layperson explanation of the limits of IBD genetics. A 5-point Likert scale was used to determine willingness to undergo genetic testing to determine diagnosis, prognosis, and treatment; to help their family; and to advance medical knowledge. The IBD Questionnaire, a validated measure of the health status attitudes of patients with IBD, was used. To determine limits of patient interest in testing family members, the standard reference gamble paradigm was used. Patients were presented with situations for the genetic test with various levels of certainty in 10% decrements starting with 100%. They indicated the lowest degree of certainty that they would accept to test their family member. RESULTS: One hundred fourteen patients (mean age 38.4 years; 48.2% women) completed the survey. Of these 114, 71.9% (82) had Crohn's disease. Among the patients who answered questions on self-willingness, 76.8% (86 of 112) would undergo testing for diagnostic confirmation, 81.3% (91 of 112) for prognostic value, 88.4% (99 of 112) for therapeutic decision making, and 85.0% (96 of 113) for advancement of medical knowledge. We found that 28.1% of patients (32 of 114) had a first-degree relative with IBD. Those patients with a first-degree relative with IBD were more willing to undergo genetic testing than those without a first-degree relative with IBD (raw score on self-willingness 4.62 vs 4.36; P=0.026). There was no significant association between patients' health status and their willingness to undergo genetic testing (IBD Questionnaire score and raw score on self-willingness; Spearman's correlation coefficient -0.06; P=0.51). We also found that 88.6% of patients (93 of 105) indicated an interest in testing family members if the test provided absolute certainty of future disease. The average lowest level of certainty these patients were willing to accept was 42.2%. CONCLUSIONS: Despite the complexity of IBD genetics, most patients with IBD are interested in testing and willing to accept a variable degree of uncertainty about the results. An important minority of patients does not wish to be tested. Future work should better identify the reasons for these different attitudes. This information should be factored into plans for widespread clinical testing.

Adult↗

Planned post-chemoradiation neck dissection: significance of radiation dose.

OBJECTIVE: The increasing prominence of multimodality therapy for patients with advanced head and neck cancer reflects its high survival and functional preservation rates. We report the pathologic data on patients undergoing neck dissection (ND) after induction chemotherapy followed by concomitant chemoradiotherapy (IC-CRT) in three similar protocols utilizing decreasing doses of radiation therapy. MATERIALS AND METHODS: The databases of 221 patients who underwent IC-CRT between 1999 and 2002 were reviewed. Based on posttreatment residual or pretreatment N2a or greater neck disease, 73 patients without pretreatment neck surgery were eligible for analysis (1 N1, 3 N2a, 26 N2b, 20 N2c, 23 N3). Three additional subgroups were also analyzed with respect to outcome: Undissected patients with less than N2 disease, patients who had neck surgery prior to IC-CRT, and patients with N2a or greater neck disease who did not have post-IC-CRT ND. STUDY DESIGN: Retrospective analysis. RESULTS: Sixty-seven patients underwent unilateral or bilateral selective neck dissection. Six patients had modified or radical ND. There were no wound healing complications. Pathologic analysis revealed viable cancer in 15 of 73 patients (20.5%): 1 had N1, 3 had N2b, 4 had N2c, and 7 had N3 neck disease. The incidence of viable cancer in the neck dissection specimen increased as radiation dose decreased. Complete response induction chemotherapy predicted negative pathology (P = .003). In the subgroup analysis, patients who had pretreatment surgery had a lower risk of dying from the primary cancer CONCLUSIONS: 1) The incidence of positive pathology after IC-CRT increases as radiation dose decreases. 2) Selective neck dissection after CRT has been demonstrated to be feasible and safe; the complication rate of ND after IC-CRT is acceptably low. 3) There is viable posttreatment cancer in 20.5% of patients, indicating necessity of ND in these patients.

Adult↗

Cessation of injection drug use and change in injection frequency: the Chicago Needle Exchange Evaluation Study.

AIMS: To examine the effect of a needle exchange program (NEP) on incidence of injection cessation and change in injection frequency; to explore predictors for injection cessation and change in injection frequency; and to assess whether injection quitters transitioned to non-injected drug use. DESIGN AND SETTING: Between 1997 and 2002, 901 injection drug users (IDUs) were recruited from an NEP program or an area with no NEP in Chicago, Illinois, interviewed for drug use behaviors, tested for HIV and followed for three annual visits. All participants were exposed to prevention services targeting HIV and drug abuse. MEASUREMENTS: Injection cessation was defined as no injection drug use since the last interview, and changes in the number of injections in a typical month were examined. FINDINGS: Sixteen per cent of study participants reported stopping injection for a median duration of 16 months, and most of them also ceased rather than initiated the use of non-injected drugs. Those who continued injecting reduced their injection frequency by 12% per year, on average. Independent predictors of injection cessation were infrequent injection at baseline, younger age and injecting with others. NEP use was not associated with injection cessation and change in injection frequency. CONCLUSION: These results did not support the hypothesis that NEP use influences the frequency of injection over time. One-sixth of IDUs stopped injection for more than 1 year, providing a substantial window for relapse prevention interventions.

Adolescent↗

Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer.

BACKGROUND: Despite the general acceptance of gemcitabine/cisplatin in metastatic bladder cancer, its role and tolerability in the adjuvant setting, in which renal insufficiency is common, is unclear. PATIENTS AND METHODS: A total of 39 patients with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2) were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical cystectomy. All toxicities were evaluated by the National Cancer Institute Common Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53, and p16. RESULTS: Thirty-five patients (90%) completed 4 cycles of chemotherapy. Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients (36%) experienced grade 3 nonhematologic toxicity. The median increase in creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70 months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after completion of therapy. Twelve patients (31%) died, including 11 (28%) with recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16 alterations. In an exploratory analysis, altered expression of p53, p16, and pRB was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No association between altered p53 and disease-free or overall survival was detected, but altered p16 and pRB expression was associated with better outcome (P < or = 0.001). CONCLUSION: Gemcitabine/cisplatin with amifostine is tolerated in the adjuvant setting for patients with locally advanced bladder cancer. The favorable prognostic value of altered p16 and pRB raises the hypothesis of a relative beneficial effect of chemotherapy in this population but needs verification in other studies.

Adult↗

Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN. EXPERIMENTAL DESIGN: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy. RESULTS: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively). CONCLUSIONS: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.

Adult↗

Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma.

While most osteosarcoma patients have metastatic or micrometastatic lesions, less than 15% of them have clinically detectable metastatic diseases at presentation. To identify potential markers that may predict osteosarcoma metastasis, we analyzed the expression of S100A6 in 50 osteosarcoma cases and found that 84% of the analyzed specimens stained positive for S100A6. There is a trend towards decreased clinically evident metastasis with increased S100A6 staining. Overexpression of S100A6 in osteosarcoma cells decreases cell motility and anchorage independent growth on collagen gels. Our findings provide evidence that, while S100A6 is commonly overexpressed in human osteosarcoma, loss of its expression correlates with a metastatic phenotype.

Adolescent↗

Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.

BACKGROUND: Chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia in premature infants are associated with abnormal neurodevelopmental outcomes. In a previous randomized, controlled, single-center trial of premature infants with the respiratory distress syndrome, inhaled nitric oxide decreased the risk of death or chronic lung disease as well as severe intraventricular hemorrhage and periventricular leukomalacia. We hypothesized that infants treated with inhaled nitric oxide would also have improved neurodevelopmental outcomes. METHODS: We conducted a prospective, longitudinal follow-up study of premature infants who had received inhaled nitric oxide or placebo to investigate neurodevelopmental outcomes at two years of corrected age. Neurologic examination, neurodevelopmental assessment, and anthropometric measurements were made by examiners who were unaware of the children's original treatment assignment. RESULTS: A total of 138 children (82 percent of survivors) were evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24 percent) had abnormal neurodevelopmental outcomes, defined as either disability (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no disability, but one score of less than 70 on the Bayley Scales of Infant Development II), as compared with 31 of 68 children (46 percent) in the placebo group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87; P=0.01). This effect persisted after adjustment for birth weight and sex, as well as for the presence or absence of chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia. The improvement in neurodevelopmental outcome in the group given inhaled nitric oxide was primarily due to a 47 percent decrease in the risk of cognitive impairment (defined by a score of less than 70 on the Bayley Mental Developmental Index) (P=0.03). CONCLUSIONS: Premature infants treated with inhaled nitric oxide have improved neurodevelopmental outcomes at two years of age.

Administration, Inhalation↗

Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection.

BACKGROUND: Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. METHODS: C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (> or =50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. RESULTS: PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P< or =0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. CONCLUSION: Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

Biopsy↗

Changes in the sharing of drug injection equipment among street-recruited injection drug users in Chicago, Illinois, 1994--1996.

This study examines changes in the multi-person use of drug injection paraphernalia during the mid-1990s, a time of increasing awareness of HIV transmission modes and availability of prevention programs. Beginning in 1994, 794 street-recruited injection drug users in Chicago were interviewed and followed at 6 and 12 months postbaseline. Random-effects, pattern-mixture logistic regression models were used to determine correlates of five injection-equipment sharing practices, while accounting for repeated measurement and study attrition. At baseline, 45.7% of participants reported receptive syringe sharing in the previous 6 months. Syringe-mediated sharing was reported by 28.7% of participants and the sharing of cookers (65.1%), cotton filters (55.7%), and rinse water (46.9%) was common. During follow-up, the proportion of all sharing behaviors decreased significantly, especially receptive syringe sharing. Participation in a syringe exchange program was associated with reductions in receptive syringe sharing and syringe-mediated sharing, but not the sharing of cookers.

Adolescent↗

Preoperative clinic visits reduce operating room cancellations and delays.

BACKGROUND: Anesthesiologist-directed preoperative medicine clinics are used to prepare patients for the administration of anesthesia and surgery. Studies have shown that such a clinic reduces preoperative testing and consults, but few studies have examined the impact of the clinic on the day of surgery. The authors tested whether a visit to an anesthesia preoperative medicine clinic (APMC) would reduce day-of-surgery case cancellations and/or case delays. METHODS: The authors conducted a retrospective chart review of all surgical cases during a 6-month period at the University of Chicago Hospitals. Case cancellations and rates of first-start case delay over the 6-month period were cross-referenced with a database of APMC attendees in both the general operating rooms and the same-day surgery suite. The impact of a clinic visit on case cancellation and delay in both sites were analyzed separately. RESULTS: A total of 6,524 eligible cases were included. In the same-day surgery suite, 98 of 1,164 (8.4%) APMC-evaluated patients were cancelled, as compared with 366 of 2,252 (16.2%) in the non-APMC group (P < 0.001). In the general operating rooms, 87 of 1,631 (5.3%) APMC-evaluated patients were cancelled, as compared with 192 of 1,477 (13.0%) patients without a clinic visit (P < 0.001). For both operating areas, APMC patients had a significantly earlier room entry time than patients not evaluated in the APMC. CONCLUSIONS: An evaluation in the APMC can significantly impact case cancellations and delays on the day of surgery.

Adult↗