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1.
AJNR Am J Neuroradiol ; 41(9): 1718-1725, 2020 09.
Article in English | MEDLINE | ID: mdl-32816765

ABSTRACT

BACKGROUND AND PURPOSE: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification. MATERIALS AND METHODS: The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists. RESULTS: Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists. CONCLUSIONS: We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.


Subject(s)
Deep Learning , Image Interpretation, Computer-Assisted/methods , Infratentorial Neoplasms/classification , Infratentorial Neoplasms/diagnostic imaging , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infratentorial Neoplasms/pathology , Magnetic Resonance Imaging/methods , Male , Young Adult
2.
BJOG ; 122(11): 1437-45, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26177561

ABSTRACT

BACKGROUND: Limited epidemiological data on the association between maternal rectovaginal group B Streptococcus (GBS) colonisation and stillbirth makes assessment of antenatal interventions for GBS stillbirth difficult. OBJECTIVES: To systematically review the existing literature and evaluate the incidence of GBS-related stillbirth by region up to March 2015. SEARCH STRATEGY: A systematic review of the published literature was completed using PubMed/MEDLINE, EMBASE, LILACS, and Cochrane Library, with Medical Subject Headings (MeSH) and search terms based upon the Centers for Disease Control and Prevention's (CDC) Active Bacterial Core Surveillance (ABCs) GBS-related stillbirth definition and chorioamnionitis. SELECTION CRITERIA: Studies reporting original data on GBS-related stillbirth occurring ≥20 weeks of gestation, with GBS confirmed by autopsy or by culture from the placenta, amniotic fluid, or other normally sterile site samples from the stillborn. DATA COLLECTION AND ANALYSIS: Descriptive analyses were performed with the absolute GBS-related stillbirth rates and proportion of stillbirths attributed to GBS calculated per study where possible. Differences in stillbirth definitions did not allow for pooled estimates to be calculated. MAIN RESULTS: Seventeen studies reported GBS-related stillbirth rates varying from 0.04 to 0.9 per 1000 births, with the proportion of stillbirths associated with GBS ranging from 0 to 12.1%. Most studies reported data from before the year 2000 and from high-income countries. CONCLUSIONS: The sparsely available epidemiological evidence was not reported consistently, emphasising the importance of standardised stillbirth definitions and diagnostic methods to optimally assess the effectiveness of any future antenatal interventions. Timing of stillbirth, GBS serotype, and global diversity were gaps in the current evidence. TWEETABLE ABSTRACT: Systematic review finds Group B Streptococcus causes up to 12.1% of stillbirths, but more research is needed.


Subject(s)
Pregnancy Complications, Infectious/microbiology , Stillbirth/epidemiology , Streptococcal Infections/epidemiology , Streptococcus agalactiae , Amniotic Fluid/microbiology , Developed Countries , Developing Countries , Female , Humans , Incidence , Placenta/microbiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology
3.
AJNR Am J Neuroradiol ; 35(7): 1433-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24651817

ABSTRACT

BACKGROUND AND PURPOSE: Reduced cerebral perfusion has been observed with elevated intracranial pressure. We hypothesized that arterial spin-labeled CBF can be used as a marker for symptomatic hydrocephalus. MATERIALS AND METHODS: We compared baseline arterial spin-labeled CBF in 19 children (median age, 6.5 years; range, 1-17 years) with new posterior fossa brain tumors and clinical signs of intracranial hypertension with arterial spin-labeled CBF in 16 age-matched controls and 4 patients with posterior fossa tumors without ventriculomegaly or signs of intracranial hypertension. Measurements were recorded in the cerebrum at the vertex, deep gray nuclei, and periventricular white matter and were assessed for a relationship to ventricular size. In 16 symptomatic patients, we compared cerebral perfusion before and after alleviation of hydrocephalus. RESULTS: Patients with uncompensated hydrocephalus had lower arterial spin-labeled CBF than healthy controls for all brain regions interrogated (P < .001). No perfusion difference was seen between asymptomatic patients with posterior fossa tumors and healthy controls (P = 1.000). The median arterial spin-labeled CBF increased after alleviation of obstructive hydrocephalus (P < .002). The distance between the frontal horns inversely correlated with arterial spin-labeled CBF of the cerebrum (P = .036) but not the putamen (P = .156), thalamus (P = .111), or periventricular white matter (P = .121). CONCLUSIONS: Arterial spin-labeled-CBF was reduced in children with uncompensated hydrocephalus and restored after its alleviation. Arterial spin-labeled-CBF perfusion MR imaging may serve a future role in the neurosurgical evaluation of hydrocephalus, as a potential noninvasive method to follow changes of intracranial pressure with time.


Subject(s)
Algorithms , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/etiology , Hydrocephalus/complications , Hydrocephalus/diagnosis , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Angiography/methods , Adolescent , Child , Child, Preschool , Female , Humans , Image Enhancement/methods , Infant , Male , Reproducibility of Results , Sensitivity and Specificity , Spin Labels
4.
AJNR Am J Neuroradiol ; 35(4): 803-7, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24052507

ABSTRACT

BACKGROUND AND PURPOSE: Injury to the dentatothalamic pathway that originates in the cerebellum has been suggested as a mechanism for neurologic complications in children treated for posterior fossa tumors. We hypothesized that time-dependent changes occur in the dentatothalamic pathway. MATERIALS AND METHODS: Diffusion tensor evaluation was performed in 14 children (median age, 4.1 years; age range, 1-20 years) who underwent serial MR imaging at 3T as part of routine follow-up after posterior fossa tumor resection with or without adjuvant therapy. Tensor metrics were obtained in the acute (≤1 week), subacute (1 to <6 months), and chronic (≥6 months) periods after surgery. We evaluated the following dentatothalamic constituents: bilateral dentate nuclei, cerebellar white matter, and superior cerebellar peduncles. Serial dentate nuclei volumes were also obtained and compared with the patient's baseline. RESULTS: The most significant tensor changes to the superior cerebellar peduncles and cerebellar white matter occurred in the subacute period, regardless of the tumor pathology or therapy regimen, with signs of recovery in the chronic period. However, chronic volume loss and reduced mean diffusivity were observed in the dentate nuclei and did not reverse. This atrophy was associated with radiation therapy and symptoms of ataxia. CONCLUSIONS: Longitudinal diffusion MR imaging in children treated for posterior fossa tumors showed time-dependent tensor changes in components of the dentatothalamic pathway that suggest evolution of structural damage with inflammation and recovery of tissue directionality. However, the dentate nuclei did not show tensor or volumetric recovery, suggesting that the injury may be chronic.


Subject(s)
Astrocytoma/surgery , Cerebellar Nuclei/pathology , Diffusion Tensor Imaging , Infratentorial Neoplasms/surgery , Postoperative Complications/pathology , Thalamus/pathology , Adolescent , Child , Child, Preschool , Ependymoma/surgery , Female , Humans , Infant , Longitudinal Studies , Male , Medulloblastoma/surgery , Neural Pathways/pathology , Sensitivity and Specificity , Time Factors , Young Adult
5.
AJNR Am J Neuroradiol ; 35(2): 395-401, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23907239

ABSTRACT

BACKGROUND AND PURPOSE: Pediatric brain tumors have diverse pathologic features, which poses diagnostic challenges. Although perfusion evaluation of adult tumors is well established, hemodynamic properties are not well characterized in children. Our goal was to apply arterial spin-labeling perfusion for various pathologic types of pediatric brain tumors and evaluate the role of arterial spin-labeling in the prediction of tumor grade. MATERIALS AND METHODS: Arterial spin-labeling perfusion of 54 children (mean age, 7.5 years; 33 boys and 21 girls) with treatment-naive brain tumors was retrospectively evaluated. The 3D pseudocontinuous spin-echo arterial spin-labeling technique was acquired at 3T MR imaging. Maximal relative tumor blood flow was obtained by use of the ROI method and was compared with tumor histologic features and grade. RESULTS: Tumors consisted of astrocytic (20), embryonal (11), ependymal (3), mixed neuronal-glial (8), choroid plexus (5), craniopharyngioma (4), and other pathologic types (3). The maximal relative tumor blood flow of high-grade tumors (grades III and IV) was significantly higher than that of low-grade tumors (grades I and II) (P < .001). There was a wider relative tumor blood flow range among high-grade tumors (2.14 ± 1.78) compared with low-grade tumors (0.60 ± 0.29) (P < .001). Across the cohort, relative tumor blood flow did not distinguish individual histology; however, among posterior fossa tumors, relative tumor blood flow was significantly higher for medulloblastoma compared with pilocytic astrocytoma (P = .014). CONCLUSIONS: Characteristic arterial spin-labeling perfusion patterns were seen among diverse pathologic types of brain tumors in children. Arterial spin-labeling perfusion can be used to distinguish high-grade and low-grade tumors.


Subject(s)
Algorithms , Brain Neoplasms/pathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Angiography/methods , Adolescent , Child , Child, Preschool , Female , Humans , Image Enhancement/methods , Infant , Male , Reproducibility of Results , Sensitivity and Specificity , Spin Labels
6.
J Anim Sci ; 91(8): 3899-908, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23908163

ABSTRACT

The objective of this study was to test the hypothesis that feed additives such as chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract would improve nutrient digestibility when included in an equine diet. Horses (Quarter Horse geldings 4.5 to 16 yr of age; mean BW 522 kg ± 46 kg) were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) commercially available sources of the aforementioned additives followed by a 14-d collection period of feces and urine. Chelated sources of Cu, Zn, Mn and Co were utilized versus sulfated forms, at a 100% replacement rate. No significant differences among apparent the digestibility of DM, ADF, or NDF (P= 0.665, P = 0.866, P = 0.747, respectively) were detected between dietary treatments. Likewise, no differences in apparent digestibility of Cu (P = 0.724), Zn (P = 0.256), Mn (P = 0.888), Co (P = 0.71), or Se (P = 0.588) were observed. No differences were observed in serum Cu, Mn, or Co concentrations between ADD and CTRL at acclimation or collection time points (P > 0.05). While no difference in serum Zn concentrations were observed between ADD and CTRL groups at acclimation (P > 0.05), they were statistically higher at the collection time period for horses consuming CTRL (P < 0.0001). Whole blood Se concentration was greater in the CTRL group versus the ADD group both at acclimation (P = 0.041) and collection (P = 0.005) time periods. In reference to time, serum Cu concentrations increased (P = 0.012) for animals consuming CTRL, but not ADD (P > 0.05). Serum Zn concentrations of horses consuming both ADD (P = 0.021) and CTRL (P < 0.0001) increased over time from acclimation to collection time points. No time differences (P > 0.05) were observed in serum Mn concentrations. Serum Co concentrations increased over time in horses consuming both ADD (P = 0.001) and CTRL (P = 0.021). From acclimation to collection, whole blood Se concentration increased for horses consuming CTRL (P = 0.01) but not for ADD (P > 0.05). The results of this study indicate no effect on nutrient digestibility due to the inclusion of chelated minerals, organic Se, yeast culture, direct-fed microbials, and Yucca schidigera extract for horses at maintenance.


Subject(s)
Horses/blood , Horses/physiology , Selenium/pharmacology , Trace Elements/pharmacology , Yeasts , Yucca/chemistry , Animals , Cross-Over Studies , Digestion/physiology , Male , Nutritive Value , Plant Extracts/chemistry , Plant Extracts/pharmacology
7.
J Anim Sci ; 91(8): 3909-16, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23881677

ABSTRACT

The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P > 0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P > 0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P < 0.003). Differences due to diet were found for selenium fecal (P < 0.0001) and urine (P < 0.0001) excretions, with decreased concentrations found for horses consuming organic selenium yeast (ADD). In contrast, fecal K (%) was greater (P = 0.0421) for horses consuming ADD, whereas concentrations of fecal solids, total N, ammonia N, P, total ammonia, and fecal output did not differ between dietary treatments (P > 0.05). In feces stockpiled to simulate a crude composting method, no differences (P > 0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P < 0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.


Subject(s)
Horses/physiology , Selenium/pharmacology , Trace Elements/pharmacology , Yeasts , Yucca/chemistry , Animals , Cross-Over Studies , Digestion/physiology , Environment , Feces/chemistry , Male , Nitrogen/chemistry , Nitrogen/metabolism , Nutritive Value , Phosphorus/chemistry , Phosphorus/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Potassium/chemistry , Potassium/metabolism
8.
J Neurooncol ; 113(3): 479-83, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23673514

ABSTRACT

Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.


Subject(s)
Brain Neoplasms/pathology , Diffusion Magnetic Resonance Imaging , Optic Nerve Glioma/pathology , Brain Neoplasms/mortality , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Infant , Male , Optic Nerve Glioma/mortality , Prognosis , Survival Rate
9.
J Perinatol ; 33(1): 52-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22499081

ABSTRACT

OBJECTIVE: To characterize true coagulase-negative Staphylococcus (CoNS) infections in infants receiving neonatal intensive care. STUDY DESIGN: Retrospective cohort study of neonatal intensive care unit (NICU) infants with clinical sepsis and CoNS isolated from ≥ 2 blood cultures (BCs) or one BC and a sterile site (proved infection) or CoNS isolated from one BC and deemed significant after blinded data review (probable infection). RESULT: In all, 98% of 40 proved and 96% of 55 probable infections occurred in infants with birth weight (BW) <2000 g and gestation <34 weeks. Total central lines (CLs) placed, but not CL duration or presence in situ, predicted proved (odds ratio (OR) 3.5, 95% confidence interval (CI) 1.4 to 8.3; P=0.005) and probable infection (OR 2.7, 95% CI 1.3 to 5.6; P=0.007) by multivariate analysis as did lethargy and gastric residuals. CONCLUSION: True CoNS infection is unlikely in infants with BW >2000 g and gestation >34 weeks. Total CL required for care, lethargy and gastric residuals predicted true CoNS infection.


Subject(s)
Bacteremia/diagnosis , Bacteremia/microbiology , Catheterization, Central Venous , Coagulase/metabolism , Cross Infection/diagnosis , Cross Infection/microbiology , Culture Media , Equipment Contamination , Infant, Extremely Low Birth Weight , Infant, Low Birth Weight , Intensive Care Units, Neonatal , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcus/enzymology , Bacteremia/epidemiology , Cross Infection/epidemiology , Cross-Sectional Studies , Diagnosis, Differential , Female , Humans , Infant, Newborn , Male , Recurrence , Retrospective Studies , Risk Factors , Staphylococcal Infections/epidemiology
10.
AJNR Am J Neuroradiol ; 34(5): 1056-61, S1, 2013 May.
Article in English | MEDLINE | ID: mdl-23124635

ABSTRACT

BACKGROUND AND PURPOSE: Chordoma and chondrosarcoma of the skull base are rare tumors with overlapping presentations and anatomic imaging features but different prognoses. We hypothesized that these tumors might be distinguished by using diffusion-weighted MR imaging. MATERIALS AND METHODS: We retrospectively reviewed 19 patients with pathologically confirmed chordoma or chondrosarcoma who underwent both conventional and diffusion-weighted MR imaging. Differences in distributions of ADC were assessed by the Kruskal-Wallis test. Associations between histopathologic diagnosis and conventional MR imaging features (T2 signal intensity, contrast enhancement, and tumor location) were assessed with the Fisher exact test. RESULTS: Chondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10(-6) mm(2)/s) and was significantly different from classic chordoma (1474 ± 117 × 10(-6) mm(2)/s) and poorly differentiated chordoma (875 ± 100 × 10(-6) mm(2)/s) (P < .001). Poorly differentiated chordoma was characterized by low T2 signal intensity (P = .001), but other conventional MR imaging features of enhancement and/or lesion location did not reliably distinguish these tumor types. CONCLUSIONS: Diffusion-weighted MR imaging may be useful in assessing clival tumors, particularly in differentiating chordoma from chondrosarcoma. A prospective study of a larger cohort will be required to determine the value of ADC in predicting histopathologic diagnosis.


Subject(s)
Algorithms , Chondrosarcoma/pathology , Chordoma/pathology , Diffusion Magnetic Resonance Imaging/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Skull Base Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
11.
Colorectal Dis ; 14(2): e31-47, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21848897

ABSTRACT

AIM: A systematic review of treatment guidelines for metastatic colorectal cancer (mCRC) was performed to assess recommendations for monoclonal antibody therapy in these guidelines. METHOD: Relevant papers were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of reference lists; and by searching the Internet. RESULTS: A total of 57 relevant guidelines were identified, 32 through electronic database searches and 25 through the website searches. The majority of guidelines were published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany (three), Australia (two), Spain (two) and Italy (one). In addition, eight European and three international guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European and US guidelines recommend combination chemotherapy with the addition of a monoclonal antibody for the first-line treatment of mCRC. Second-line treatment depends on the first-line regimen used. For chemoresistant mCRC, cetuximab or panitumumab are recommended as monotherapy in patients with wild-type KRAS tumours. CONCLUSION: The study indicates that recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC, and that treatment guidelines should be updated in a timely manner to reflect the most recently available data.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Immunologic Factors/therapeutic use , Practice Guidelines as Topic , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Cetuximab , Humans , Panitumumab
12.
J Perinatol ; 29(4): 320-2, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19325554

ABSTRACT

Micafungin is an echinocandin-class antifungal agent licensed for treatment of invasive disease in adults. The optimal dosing regimens have not been established for infants. We describe a premature infant who developed hepatitis and cholestasis during micafungin therapy initiated for protracted candidemia. Practitioners should be aware of this potential adverse effect if using micafungin in young patients.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antifungal Agents/adverse effects , Candidiasis/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Echinocandins/adverse effects , Fungemia/drug therapy , Infant, Premature, Diseases/drug therapy , Lipopeptides/adverse effects , Alanine Transaminase/blood , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Antifungal Agents/administration & dosage , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/diagnosis , Cholestasis/chemically induced , Cholestasis/diagnosis , Dose-Response Relationship, Drug , Drug Therapy, Combination , Echinocandins/administration & dosage , Female , Humans , Infant , Infant, Newborn , Lipopeptides/administration & dosage , Liver Function Tests , Micafungin
13.
J Cardiovasc Surg (Torino) ; 49(5): 591-608, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18670377

ABSTRACT

Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal dysfunction and secondary hypertension, and is associated with adverse cardiovascular events and increased mortality. The natural history of ARAS is characterized by anatomic disease progression and/or renal dysfunction in only a minority of patients. Medical therapy for ARAS is directed primarily toward blood pressure control and cardiovascular risk factor reduction. Renal artery revascularization is an additional treatment option for ARAS associated with ischemic nephropathy or severe, poorly controlled hypertension despite aggressive medical therapy. Unfortunately, the benefits associated with revascularization versus medical therapy alone remain unproven. Renal artery revascularization may be accomplished through open surgical revascularization or angioplasty and stenting. Although surgical renal revascularization is associated with more durable results and relatively lower risk for postoperative renal function decline, the increased risk of death or major complications associated with this management approach limit its use in patients with significant comorbidities. Renal artery angioplasty and stenting is being utilized with increasing frequency but is of uncertain benefit and is associated with rates of post-intervention renal function improvement and deterioration that are approximately equal. Renal function outcomes associated with angioplasty and stenting may be improved through a selective treatment approach and utilization of distal embolic protection. Renal artery revascularization represents the only treatment alternative for patients unresponsive to medical management, and is therefore the ''treatment of choice'' in this select group. Results of ongoing randomized trials are eagerly anticipated and may provide useful guidance for future management of ARAS.


Subject(s)
Arteriosclerosis/complications , Renal Artery Obstruction/etiology , Renal Artery Obstruction/surgery , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Arteriosclerosis/physiopathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Renal Artery Obstruction/physiopathology
14.
J Cardiovasc Surg (Torino) ; 48(4): 443-53, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17653004

ABSTRACT

Atherosclerotic renovascular disease is an increasingly recognized cause of both renal function impairment and hypertension, and its presence is associated with increased cardiovascular mortality and dialysis dependence. Although surgical renal revascularization is associated with the most favorable reported renal function outcomes, the significant perioperative mortality and complication rates have resulted in a shift to renal artery percutaneous transluminal angioplasty and stenting (RA-PTAS) as the most frequently performed method of revascularization. Renal function outcomes following RA-PTAS are less favorable, with patients experiencing functional improvement and deterioration with approximately equal frequency in reported series. Distal atheroembolization is thought to occur during RA-PTAS and has been suggested as a potential cause of the disparate renal function outcomes. Distal embolic protection devices primarily used and evaluated in the coronary and cerebrovascular circulations have also been successfully employed during RA-PTAS. Initial clinical results following RA-PTAS with distal embolic protection have been promising, with high rates of technical success, renal function outcomes that approximate those reported with open surgical revascularization, and maintenance of relatively low death and complication rates. Further investigation with controlled comparison groups is warranted before routine use of distal embolic protection can be uniformly endorsed.


Subject(s)
Angioplasty/methods , Embolism/prevention & control , Endarterectomy , Renal Artery Obstruction/therapy , Angioplasty/adverse effects , Angioplasty/instrumentation , Embolism/etiology , Humans , Treatment Outcome
15.
Arch Dis Child ; 88(5): 375-8, 2003 May.
Article in English | MEDLINE | ID: mdl-12716700

ABSTRACT

Linkage of bacterial capsular polysaccharides to proteins to create conjugate vaccines has had a dramatic impact on the health of children. Although unconjugated polysaccharides are poorly immunogenic in infants and some older children and adults, their covalent coupling with proteins stimulates T cell dependent antigenic recognition that profoundly enhances immunogenicity. In the decade since the introduction and widespread use of Haemophilus influenzae type b polysaccharide conjugate vaccines in the United States, invasive H influenzae infections have become a rarity in childhood. Similarly, the conjugation of polysaccharides of Streptococcus pneumoniae to a derivative of diphtheria toxoid and the addition of pneumococcal conjugate vaccine to infant immunisation schedules carries with it promise for a similar decline in the incidence of invasive pneumococcal disease in paediatric patients.


Subject(s)
Bacterial Capsules/immunology , Streptococcal Infections/prevention & control , Streptococcal Vaccines/therapeutic use , Streptococcus agalactiae/immunology , Adult , Antibodies, Bacterial/immunology , Child , Clinical Trials as Topic , Dose-Response Relationship, Immunologic , Female , Haemophilus Infections/prevention & control , Haemophilus influenzae type b/immunology , Humans , Immunization/methods , Infant , Licensure , Male , Pneumococcal Vaccines , Serotyping , Streptococcal Vaccines/immunology , Streptococcus pneumoniae/immunology , Tetanus Toxoid/immunology , Vaccines, Conjugate/therapeutic use
17.
Pediatr Infect Dis J ; 20(10): 1007-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11642620

ABSTRACT

Although infectious complications of nephrotic syndrome are common, group B Streptococcus is a rare pathogen in these patients. We present a 4-year-old child with nephrotic syndrome who developed group B streptococcal cellulitis and bacteremia, an association not previously discussed in the literature, and review the factors that predispose patients with nephrotic syndrome to infection.


Subject(s)
Abdominal Muscles/microbiology , Cellulitis/diagnosis , Cellulitis/microbiology , Nephrotic Syndrome/complications , Streptococcal Infections/diagnosis , Streptococcus agalactiae/isolation & purification , Child, Preschool , Diagnosis, Differential , Glucocorticoids/therapeutic use , Humans , Male , Nephrotic Syndrome/drug therapy , Prednisone/therapeutic use , Streptococcal Infections/microbiology , Treatment Outcome
18.
Mol Genet Metab ; 73(3): 259-67, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11461193

ABSTRACT

The effect of hyperglycemia upon susceptibility to bacterial infection in diabetes mellitus is incompletely elucidated. The present experiments assessed the effect of hyperglycemia upon neutrophil-mediated phagocytosis of type III group B Streptococcus (GBS). Type III GBS was chosen for study because the incidence of invasive GBS disease is substantially increased in type 2 diabetic compared with nondiabetic subjects. The hypothesis tested was that severe hyperglycemia would alter neutrophil metabolism by diverting NADPH from superoxide production into the aldose reductase-dependent polyol pathway that converts glucose into sorbitol and thus would impair opsonophagocytosis (OP) of type III GBS. Neutrophils from 10 adults with type 2 diabetes had no intrinsic phagocytic defect under baseline glycemic conditions. After equilibration in 60 or 120 mM glucose or in 60 mM choline chloride, OP activity was reduced significantly (P < or = 0.03). Neutrophil superoxide production correlated with glucose concentration and also was significantly reduced during hyperglycemia (P < 0.05). Addition of III GBS capsular polysaccharide-specific IgG in a sufficient concentration supported efficient OP, even during hyperglycemia. Alrestatin, an aldose reductase inhibitor, increased superoxide production and significantly improved OP of type III GBS (P = 0.03). Thus, diversion of NADPH into the polyol pathway is one mechanism by which OP of GBS III is impaired during hyperglycemia, and this effect is mitigated when levels of capsular polysaccharide-specific IgG are sufficient.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Neutrophils/metabolism , Streptococcus agalactiae/metabolism , Superoxides/metabolism , Adult , Aged , Aldehyde Reductase/antagonists & inhibitors , Blood Glucose/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Humans , Hyperglycemia/metabolism , Immunoglobulin G/metabolism , Isoquinolines/pharmacology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Phagocytosis , Time Factors
19.
Pediatr Infect Dis J ; 20(4): 371-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11332660

ABSTRACT

BACKGROUND: Mucous membrane colonization with group B streptococci (GBS) frequently persists in infants after treatment of invasive infection and may be associated with recurrent disease. OBJECTIVE: To determine the frequency with which GBS colonization persists at mucous membrane sites after treatment of invasive early or late onset infection and to determine the efficacy of oral rifampin in eradicating colonization in these infants and their mothers. METHODS: Cultures for isolation of GBS were obtained from infants and their mothers after completion of the infant's parenteral therapy, 1 week later when rifampin therapy was initiated and at approximately 1 and 4 weeks after completion of rifampin therapy. Rifampin was administered (10-mg/kg dose; maximum, 600 mg) twice daily for 4 days. RESULTS: Ten of 21 infants (48%) and 13 (65%) of their 20 mothers were colonized with GBS at throat or rectal (infant) or vaginal, rectal or breast milk (mother) sites before rifampin was initiated. One week or less after rifampin treatment, 7 (70%) infants and 4 (31%) mothers remained colonized with GBS. At study completion 6 infants and 7 mothers had GBS colonization. Persistent colonization was not related to GBS serotype, to initial rifampin minimal inhibitory concentration or to the development of rifampin resistant strains. CONCLUSIONS: Rifampin treatment for four days utilized as a single agent after completion of parenteral therapy failed to reliably eradicate GBS colonization in infants.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Rifampin/therapeutic use , Streptococcal Infections/drug therapy , Streptococcus agalactiae/drug effects , Anti-Bacterial Agents/pharmacology , Humans , Infant, Newborn , Microbial Sensitivity Tests , Mucous Membrane/microbiology , Rifampin/pharmacology , Streptococcus agalactiae/isolation & purification , Treatment Failure
20.
Ann Surg ; 233(1): 51-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11141225

ABSTRACT

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.


Subject(s)
Breast Neoplasms/pathology , Lymphatic Metastasis/pathology , Radiopharmaceuticals , Rosaniline Dyes , Sentinel Lymph Node Biopsy/methods , Technetium Tc 99m Sulfur Colloid , Adult , Aged , Aged, 80 and over , Analysis of Variance , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , False Negative Reactions , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Radionuclide Imaging
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