Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Variation assessment of deformable registration in stereotactic radiosurgery.

INTRODUCTION: The regular functions of CT-MRI registration include delineation of targets and organs-at-risk (OARs) in radiosurgery planning. The question of whether deformable image registration (DIR) could be applied to stereotactic radiosurgery (SRS) in its place remains a subject of debate. METHODS: This study collected data regarding 16 patients who had undergone single-fraction SRS treatment. All lesions were located close to the brainstem. CT and MRI two image sets were registered by both rigid image registration (RIR) and DIR algorithms. The contours of the OARs were drawn individually on the rigid and deformable CT-MRI image sets by qualified radiation oncologists and dosimetrists. The evaluation metrics included volume overlapping (VO), Dice similarity coefficient (DSC), and dose. The modified demons deformable algorithm (VARIAN SmartAdapt) was used for evaluation in this study. RESULTS: The mean range of VO for OARs was 0.84 ± 0.08, and DSC was 0.82 ± 0.07. The maximum average volume difference was at normal brain (17.18 ± 14.48 cm3) and the second highest was at brainstem (2.26 cm3 ± 1.18). Pearson correlation testing showed that all DIRs' OAR volumes were linearly and significantly correlated with RIRs' volume (0.679-0.992, two tailed, P << 0.001). The 100% dose was prescribed at gross tumor volume (GTV). The average maximum percent dose difference was observed in brainstem (26.54% ± 27.027), and the average mean dose difference has found at same organ (1.6% ± 1.66). CONCLUSION: The change in image-registration method definitely produces dose variance, and is significantly more what depending on the target location. The volume size of OARs, however, was not statistical significantly correlated with dose variance.

Preferential depletion of gut CD4-expressing iNKT cells contributes to systemic immune activation in HIV-1 infection.

Chronic inappropriate immune activation is the central defect-driving loss of CD4(+) T helper cells and progression to AIDS in persons with HIV-1 infection, but the mechanisms remain controversial. We examined key regulatory invariant receptor natural killer T (iNKT) cells in the gut, the largest reservoir of lymphocytes and a key arena of HIV-1 pathogenesis. In healthy control persons, the anti-inflammatory CD4(+) iNKT-cell subset predominated over the pro-inflammatory CD4(-) iNKT-cell subset in the gut, but not in the blood, compartment. HIV-1 infection resulted in a preferential loss of this anti-inflammatory CD4(+) iNKT-cell subset within the gut. The degree of loss of the CD4(+) iNKT-cell subset in the gut, but not in the blood, correlated to the systemic immune activation and exhaustion that have been linked to disease progression. These results suggest a potentially important contribution of gut iNKT-cell imbalance in determining the systemic immune activation that is the hallmark of HIV-1 pathogenesis.

MO-A-BRB-01: Non-Coplanar Rotational Therapy by Using High Efficient Unflattened Beams.

The rapid dose fall-off from treatment target to the adjacent critical organs has been the Holy Grail for radiotherapy treatment planning. The modern treatment delivery technologies to address such goal include volumetric modulated rotational therapy, non-coplanar EVIRT beams and the use of unflattened beams to reduce the penumbra area. In this lecture, the integration of above techniques will be presented to achieve the goal of a sharp gradient dose around the target and also the discussion of middle to low dose volumes. Use of volumetric modulated rotational therapy by multiple non-coplanar arcs is an idea treatment modality to focus the high dose in the target area while spreading the low dose to even larger volume to reduce the middle range dose to surrounding critical organs. This is especially important for SBRT treatment plans since the fraction dose is much higher than the traditional fraction schema. The challenges we face today are 1. the gantry-couch (patient) collision issue for non-coplanar beam angles, 2. the treatment delivery efficiency due to multiple arc rotations and 3. the massive inverse optimization computation for multiple rotational arcs can be resource intensive and time consuming for treatment plan systems. It might not be easy to resolve all the challenges at one time. However, the high efficient unflattened beam can certainly improve the delivery speed by reducing the beam- on time and this, again, is essential to SBRT patients with high fractional dose. In this lecture, the non-coplanar rotational therapy treatment planning techniques will be presented and be evaluated by using comformality index, gradient index as well as dose volume histogram comparison. The differences in treatment delivery time will be tabulated and compared. At the end, the high-medium-low dose volumes will be illustrated with radiobiological models for the philosophy of sun tanned versus sun burned. LEARNING OBJECTIVES: 1. Understand treatment plan and dose gradient advantages of using non- coplanar rotational therapy 2. Understand potential delivery efficiency by using unflattened beams for multiple non-coplanar rotational beams 3. Understand sun tanned versus sun burned: the low dose volume and integrated dose.

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p

Dose effects of guide wires for catheter-based intravascular brachytherapy.

PURPOSE: Guide wires with high torquability and steerability are commonly used to navigate through a tortuous and/or branching arterial tree in a catheter-based intravascular brachytherapy procedure. The dosimetric effects due to the presence of metallic guide wires have not been addressed. This work investigates these dose effects for the three most commonly used beta and gamma sources (90Sr, 32P, and 192Ir). METHODS AND MATERIALS: The EGS4 Monte Carlo codes were used to calculate the dose distributions for the 90Sr(NOVOSTE), 32P (Guidant), and 192Ir (BEST Ind.) with and without a guide wire in place. Energy spectra for particles exiting the sources were calculated from the full phase-space data obtained from the Monte Carlo simulations of the source constructions. Guide wires of various thicknesses and compositions were studied. RESULTS: The dose perturbations due to the presence of guide wires were found to be far more significant for the 90Sr/90Y and 32P beta sources than those for the 192Ir gamma source. Because of the attenuation by the guide wires, a dose reduction of up to 60% behind a guide wire was observed for the beta sources, whereas the dose perturbation was found to be negligible for the gamma source. For a beta source, the dose perturbations depend on the thickness and the material of the guide wire. When the region behind a guide wire is part of an intravascular brachytherapy target, the presence of the guide wire results in a significant underdosing for beta sources. The underdosed region can extend a few mm behind the guide wire and up to 1 mm in other directions. CONCLUSION: Significant dose perturbations by the presence of a metallic guide wire have been found in catheter-based intravascular brachytherapy using beta sources. The dose effects should be considered in the dose prescription and/or in analyzing the treatment outcome for beta sources. Such precautions are not necessary if using a gamma source.

Monte Carlo dose verification for intensity-modulated arc therapy.

Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan. Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-Ill computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

Research fundamentals: choosing an appropriate journal, manuscript preparation, and interactions with editors.

This article, the last in a series on research methodology prepared by the Research Committee of the Society for Academic Emergency Medicine (SAEM), describes the process of journal selection, manuscript preparation, manuscript submission, and responding to editorial and reviewer comments. Methods for completing each step of this process are described. Following these methods will increase the chance of publishing one's work in the highest-quality and most appropriate journal.

Dynamic wedge versus physical wedge: a Monte Carlo study.

The purpose of this study is to analyze the characteristics of dynamic wedges (DW) and to compare DW to physical wedges (PW) in terms of their differences in affecting beam spectra, energy fluence, angular distribution, contaminated electrons, and dose distributions. The EGS4/BEAM Monte Carlo codes were used to simulate the exact geometry of a 6 MV beam and to calculate 3-D dose distributions in phantom. The DW was simulated in accordance with the segmented treatment tables (STT). The percentage depth dose curves and beam profiles for PW, DW, and open fields were measured and used to verify the Monte Carlo simulations. The Monte Carlo results were found to agree within 2% with the measurements performed using film and ionizing chambers in a water phantom. The present EGS4 calculation reveals that the effects of a DW on beam spectral and angular distributions, as well as electron contamination, are much less significant than those for a PW. For the 6 MV photon beam, a 45 degrees PW can result in a 30% increase in mean photon energy due to the effect of beam hardening. It can also introduce a 5% dose reduction in the build-up region due to the reduction of contaminated electrons by the PW. Neither this mean-energy increase nor such dose reduction is found for a DW. Compared to a DW, a PW alters the photon-beam spectrum significantly. The dosimetric differences between a DW and a PW are significant and clearly affect the clinical use of these beams. The data presented may be useful for DW commissioning.

Dosimetric characteristics of dynamic wedged fields: a Monte Carlo study.

We have developed a Monte Carlo (MC) technique using the EGS4/BEAM system to calculate dosimetric characteristics of dynamic wedges (DW) for photon beam radiotherapy. The simulation of DW was accomplished by weighting the history numbers of the electrons, which are incident on the target in accordance with the segmented treatment table. Calculations were performed for DW with wedge angles ranging from 15 degrees to 60 degrees as well as for open fields with different field sizes for both degrees 6 and 18 MV beams. The MC-calculated percentage depth dose (PDD) and beam profiles agreed with the measurements within +/- 2% (of the dose maximum along the beam axis) or +/- 2 mm in high dose gradient region. The DW slightly affects energy spectra of photons and contaminating electrons. These slight changes have no significant effects on PDD as compared to the open field. The MC-calculated dynamic wedge factors agree with the measurements within +/- 2%. The MC method enables us to provide more detailed beam characteristics for DW fields than a measurement method. This beam characteristic includes photon energy spectra, mean energy, spectra of contaminating electrons and effects of moving jaw on off-axis beam quality. These data are potentially important for treatment planning involving dynamic wedges.

Riboflavin transport by isolated perfused rabbit renal proximal tubules.

Rabbit renal proximal tubular transport of riboflavin (RF) was examined by using the in vitro isolated tubule perfusion technique. We found that proximal tubules actively reabsorbed (J(lb)) and secreted (J(bl)) RF. At 0.1 microM RF concentration, J(bl) was significantly higher than J(lb), resulting in a net secretion. This net secretion of RF was decreased at 0.01 microM RF concentration and increased at 1 microM RF concentration. Both J(lb) and J(bl) were inhibited by lowering temperature or by adding iodoacetate, a metabolic inhibitor, and lumichrome, an RF analog, suggesting the involvement of carrier-mediated transport mechanisms. J(bl) was inhibited by probenecid, an anion transport inhibitor, and by para-aminohippuric acid, an organic anion, suggesting the relevance of RF secretion to renal organic anion transport. J(bl) was also inhibited by alkaline pH (8.0) and by the calmodulin inhibitor trifluoperazine, indicating the influence of pH and Ca(2+)/calmodulin-dependent pathway on RF secretion. Finally, we found that addition of chlorpromazine, a phenothiazine derivative, inhibited both J(lb) and J(bl), raising the concern about the nutritional status in patients receiving such a type of medication.

Lower limb skeletal muscle mass: development of dual-energy X-ray absorptiometry prediction model.

Although magnetic resonance imaging (MRI) can accurately measure lower limb skeletal muscle (SM) mass, this method is complex and costly. A potential practical alternative is to estimate lower limb SM with dual-energy X-ray absorptiometry (DXA). The aim of the present study was to develop and validate DXA-SM prediction equations. Identical landmarks (i.e., inferior border of the ischial tuberosity) were selected for separating lower limb from trunk. Lower limb SM was measured by MRI, and lower limb fat-free soft tissue was measured by DXA. A total of 207 adults (104 men and 103 women) were evaluated [age 43 +/- 16 (SD) yr, body mass index (BMI) 24.6 +/- 3.7 kg/m(2)]. Strong correlations were observed between lower limb SM and lower limb fat-free soft tissue (R(2) = 0.89, P < 0.001); age and BMI were small but significant SM predictor variables. In the cross-validation sample, the differences between MRI-measured and DXA-predicted SM mass were small (-0.006 +/- 1.07 and -0.016 +/- 1.05 kg) for two different proposed prediction equations, one with fat-free soft tissue and the other with added age and BMI as predictor variables. DXA-measured lower limb fat-free soft tissue, along with other easily acquired measures, can be used to reliably predict lower limb skeletal muscle mass.

Differential change in cardiac baroreflex sensitivity estimated by sequence and spectral analysis during etomidate anesthesia.

Spontaneous baroreflex sensitivity, high-frequency gain, (0.15-0.35 Hz), and mid-frequency gain (0.07-0.14 Hz) are noninvasive measures of cardiac baroreflex function derived by spontaneous sequence and cross-spectral analysis. To demonstrate the difference between these baroreflex estimates, 14 patients received etomidate (0.3 mg/kg bolus and 0.9 mg/kg/h infusion), lidocaine (60 mg), and vecuronium (0.1 mg/kg) by intravenous injection. The authors found that spontaneous baroreflex sensitivity and high-frequency gain were decreased (p <0.05) after etomidate anesthesia, whereas mid-frequency gain was maintained. Spontaneous baroreflex sensitivity, high-frequency gain, and mid-frequency gain, although compared simultaneously, did not change in a parallel manner. In another 5 patients, who received normal saline only, measures were unchanged. The authors conclude that spontaneous baroreflex sensitivity, high-frequency gain, and mid-frequency gain are not interchangeable. Experimental results on baroreflex control depend on the parameter selected.

A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine.

OBJECTIVE: Adulterants, contaminants, and diluents are all examples of additives to street drugs. Some of these additives may be pharmacologically active; however, it is unusual for them to cause toxic side effects. In the spring of 1995, a new form of heroin appeared in New York City, spreading to other East Coast cities, that was adulterated with scopolamine. It caused severe anticholinergic toxicity in heroin users with patients often presenting to emergency departments in great numbers. This is a report of the demographics and clinical characteristics of the epidemic. METHODS: A combination of prospective and retrospective data collection from the New York City, New Jersey, Delaware Valley, and Maryland Poison Centers. The primary measurements were age, sex, route of drug use, vital signs, signs and symptoms, disposition, and treatment. RESULTS: Of the 370 cases reported to the participating poison centers, 129 were excluded from the final analysis because of insufficient data. Of the patients who used this product, 55% presented with signs and symptoms of heroin toxicity but then became severely agitated with anticholinergic symptoms when naloxone was used to reverse respiratory depression. Nasal insufflation was the route of administration in 34% of the cases. Seizures were rare (3%). Ninety percent required admission, and half were admitted to a critical care unit. CONCLUSIONS: Adulteration of street drugs can lead to toxic epidemics. Poison centers are essential for identification of these trends and are the primary source of information on diagnosis and treatment.

Telemedicine in the emergency department: a randomized controlled trial.

Emergency physicians and nurses were trained in telemedicine techniques in two emergency departments, one rural (low volume) and one suburban (high volume). Fifteen patient complaints were selected as appropriate for the study. Of 122 patients who met the inclusion criteria, 104 (85%) consented to participate. They were randomized to control and experimental groups. The suburban emergency physician diagnosed and treated the control patients. Experimental patients presenting to the high-volume emergency department were evaluated and treated by the telemedicine nurse in person and the rural emergency physician via the telemedicine link. Immediately before discharge all telemedicine patients were re-evaluated by the suburban emergency physician. Data collected on each patient included: diagnosis; treatment; 72 h return visits; need for additional care; and satisfaction of patient, physicians and nurses. There were no significant differences (P > 0.05) for occurrence of 72 h return visits, need for additional care or overall patient satisfaction. The average patient throughput time (from admission to discharge) was 106 min for the telemedicine group and 117 min for the control group. Telemedicine was a satisfactory technique for the chosen group of patients in the emergency department and was acceptable to the participants.

Chloride dependency of renal brush-border membrane phosphate transport.

In our present study, we examined the effect of Cl(-) on rabbit renal brush-border membrane (BBM) phosphate (P(i)) uptake. It was found that the Na(+)-dependent BBM (32)P uptake was significantly inhibited by Cl(-) replacement in the uptake solution with other anions, or by Cl(-) transport inhibitors, including DIDS, SITS, diphenylamine-2-carboxylate (DPC), niflumic acid (NF), and 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB). Intravesicular formate or Cl(-) increased BBM (36)Cl(-) uptake but did not affect BBM (32)P uptake. BBM (22)Na(+) uptake was lowered by Cl(-) replacement in the uptake solution but not by Cl(-) transport inhibitors. Changes in transmembrane electrical potential altered BBM (36)Cl(-) and (32)P uptake in directions consistent with a net inward movement of negative and positive charges, respectively. However, the Cl(-)-dependent BBM P(i) uptake was not affected by changes in transmembrane electrical potential. Finally, a similar Cl(-) dependency of P(i) uptake was also found with BBM derived from rat and mouse kidneys. In summary, our study showed that a component of Na(+)-dependent P(i) uptake was also Cl(-) dependent in rabbit, rat, and mouse renal BBM. The mechanism underlying this Cl(-) dependency remains to be identified.

Expression and prognostic significance of proliferating cell nuclear antigen and Ki-67 in malignant ovarian germ cell tumors.

BACKGROUND: Both proliferating cell nuclear antigen (PCNA) and Ki-67 are proliferative markers known to correlate with the cell proliferative state. The aim of this study was to evaluate the usefulness of PCNA and Ki-67 immunoreactivity in the assessment of clinicopathologic features and prognosis in patients with malignant ovarian germ cell tumors. METHODS: Thirty-one patients with surgically resected malignant ovarian germ cell tumors were investigated. The clinicopathologic features and survival data of these patients were recorded. Immunohistochemical staining with monoclonal antibodies (PC 10 for PCNA, and MIB-1 for Ki-67) were performed on paraffin embedded tissue from each patient. The correlation of the immunoreactivity of these two markers with the clinicopathologic features and prognosis were studied. RESULTS: All of the tumors were positive for PCNA and Ki-67, but the intensity of expression varied widely. The immunoreactivity in each tumor was also heterogeneous. The scoring of PCNA and Ki-67 was determined by a semiquantitative method. Both advanced tumor stage (stages III and IV) and high PCNA score (scores 3 and 4) indicated a poorer prognosis for survival than did early stage (stages I and II) and a low PCNA score (scores 1 and 2) (p = 0.017 and p = 0.008, respectively). In addition, the proportion of tumor relapse and tumor-induced death was more accurately predicted by PCNA and Ki-67 scoring than by tumor staging (chi 2 = 0.3159, chi 2 = 0.7186 and chi 2 = 1.9689, respectively). CONCLUSIONS: PCNA and Ki-67 proliferative markers appear promising to differentiate patients into low- and high-risk groups. In the presence of a high PCNA or Ki-67 score, aggressive postoperative chemotherapy is warranted, even if the disease is in a very early stage.